|
Welcome to my compendium website
on Liver Enzymes.
This site will give you a lot of information
helpful to learn about your liver. My liver is not
doing what it should. I am on my 2nd round of a bout with cancer. It
started as a tumor in my parotid gland. ( Read details at
www.IamFightingCancer.com )
6
months ago I developed a significant cough. Finally after a couple of months it
was determined that my Parotid Gland tumor that was gone had metastiszed
showing up in my left lung. After a chemo scheduled every 3 weeks it was
re-scheduled to a weekly infusion to lessen the side effects.
One of the side effects was
depression for which I was prescribed a prescription of the generic sertraline,
50 mg. which is better known as Zoloft. It was determined that my blood tests
showed that my liver enzymes were 10 times what they should be. WOW. One
of the possible causes was the DOCETAIL chemotherapy. Dr. G. stopped the
chemo but continued on with the herceptin for HER2 Another blood test was taken.
Now the bad count in the blood had not improved but had gotten worse than
before. YUK. WHAT IS CAUSING MY LIVER TO PRODUCE TOO MANY ENZYMES.
The new experiment would be to
cut off the only pill I am taking which would be the Zoloft or Sertraline,
50 mg. A week later blood test showed that the enzyme count was down but
the count was still bad enough to prevent any type of serving of the standard
chemo. Dr. G felt it was the Zoloft because cutting it down improve the liver
function. Today1-25-07 I will take the Herceptin infusion and not any chemo for
2 more weeks to see if the blood will return to more reasonable level. As I
research more about the causes of liver damage for my own use, I
will document them below to better enhance your personal awareness of the
problem.
I will research Zoloft further to see what sides effects the manufacture
indicates could happen. Do you have any experience with Zoloft? If
so please e-mail me
People the peace
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If after you
scan to the bottom of this very large webpage and can't find the
information
you are looking for try another Google search here.
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Contact information for
this Website:
Brian Nelson
Webpage
Marketing Consultant
31 Gessner Rd. Houston, TX 77024
01/24/2007 10:57 PM -0600
713-467-3025 Fax 713-467-3192 Click:
E-mail me |
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ud
01/24/2007 10:57 PM -0600
Bookmark
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Misspelled words used to find this page 1 of 3.
Page Title, Keywords Description Metas,
BB |
Liver
The liver is an
organ in some
animals,
including
mammals (and therefore humans),
birds, and
reptiles.
It plays a major role in
metabolism and has a number of
functions in the body including
glycogen
storage,
plasma protein synthesis, and drug detoxification. This organ also is
the largest
gland in the
human body. It produces
bile, which
is important in
digestion. It performs and regulates a wide variety of high-volume
biochemical reactions requiring specialized
tissues. Medical terms related to the liver often start in hepato-
or hepatic from the
Greek word for liver, hepar.
Anatomy
Posterior and inferior surfaces
The adult human liver normally weighs between 1.3
- 3.0
kilograms, and it is a soft, pinkish-brown "boomerang
shaped" organ. It is the second
largest organ (the largest organ being the
skin) and the
largest gland within the human body.
It is located on the right side of the upper
abdomen body
diaphragm. The liver lies on the right of the stomach and makes a kind
of bed for the
gallbladder (which stores
bile).
Flow of blood
The
splenic vein, joining with the
superior mesenteric vein to form the
portal vein, brings venous
blood from
the spleen,
pancreas,
small intestine, and
large intestine, so that the liver can process the
nutrients and byproducts of food digestion.
The
hepatic veins drain directly into the
inferior vena cava.
The
hepatic artery is generally a branch from the
celiac trunk, although occasionally some or all of the blood can be
from other branches such as the
superior mesenteric artery.
Approximately ⅔ of the blood flow to the liver is
from the portal venous system, and ⅓ is from the hepatic artery.
Flow of bile
The
bile produced
in the liver is collected in
bile canaliculi, which merge to form bile ducts.
These eventually drain into the right and left
hepatic ducts, which in turn merge to form the
common hepatic duct. The
cystic duct (from the
gallbladder) joins with the
common hepatic duct to form the
common bile duct.
Bile can either drain directly into the
duodenum
via the
common bile duct or be temporarily stored in the
gallbladder via the cystic duct. The
common bile duct and the
pancreatic duct enter the
duodenum
together at the
ampulla of Vater.
The branchings of the
bile
ducts resemble those of a tree, and indeed the term "biliary
tree" is commonly used in this setting.
Regeneration
The liver is among the few internal human organs
capable of natural
regeneration of lost
tissue; as little as 25% of remaining liver can regenerate into a
whole liver again.
This is predominantly due to the
hepatocytes acting as unipotential
stem
cells (i.e. a single
hepatocyte can divide into two
hepatocyte daughter cells). There is also some evidence of
bipotential
stem
cells, called
oval cells, which can differentiate into either
hepatocytes or
cholangiocytes (cells that line the
bile
ducts).
Peritoneal ligaments
Apart from a patch where it connects to the
diaphragm, the liver is covered entirely by
visceral
peritoneum, a thin, double-layered
membrane that reduces
friction
against other organs. The
peritoneum folds back on itself to form the
falciform ligament and the
right and
left triangular ligaments.
These "ligaments"
are in no way related to the true
anatomic ligaments in
joints,
and have essentially no functional importance, but they are easily
recognizable surface landmarks.
Lobes
Traditional gross anatomy divided the
liver into four
lobes based on surface features.
The
falciform ligament is visible on the front (anterior
side) of the liver. This divides the liver into a
left anatomical lobe, and a
right anatomical lobe.
If the liver is flipped over, to look at it from
behind (the
visceral
surface), there are two additional lobes between the right and left. These
are the
caudate lobe (the more
superior),
and below this the
quadrate lobe.
From behind, the lobes are divided up by the
ligamentum venosum and
ligamentum teres (anything left of these is the left lobe), the
transverse fissure (or
porta hepatis) divides the
caudate
from the
quadrate lobe, and the right
sagittal fossa, which the
inferior vena cava runs over, separates these two lobes from the right
lobe.
Modern (Functional) anatomy
For purposes such as advanced liver surgery, it
is crucial to understand the fundamental importance of the liver on the
blood supply and biliary drainage system. The central area where the
common bile duct,
portal vein, and
hepatic artery enter the liver is the
hilum or "porta
hepatis". The duct, vein, and artery divide into left and right
branches, and the portions of the liver supplied by these branches
constitute the functional left and right lobes.
The functional lobes are separated by a plane
joining the gallbladder fossa to the inferior vena cava. This separates
the liver into the true right and left lobes. The middle hepatic vein also
demarcates the true right and left lobes. The right lobe is further
divided into an
anterior
and
posterior segment by the right hepatic vein. The left lobe is divided
into the
medial and
lateral
segments by the left hepatic vein. The fissure for the
ligamentum teres (the ligamentum teres becomes the falciform ligament)
also separates the medial and lateral segmants. The medial segment is what
used to be called the
quadrate lobe. In the widely used Couinaud or "French" system, the
functional lobes are further divided into a total of eight subsegments
based on a transverse plane through the bifurcation of the main portal
vein. The
caudate lobe is a separate structure which receives blood flow from
both the right- and left-sided vascular branches.[2][3]
The subsegments corresponding to the anatomical lobes are as follows:
| Segment* |
Couinaud segments |
| Caudate |
1 |
| Lateral |
2, 3 |
| Medial |
4a, 4b |
| Right |
5, 6, 7, 8 |
- or lobe in the Caudate's case.
Each number in the list corresponds to one in the
table.
- Caudate
- Superior subsegment of the lateral segment
- Inferior subsegment of the lateral segment
-
- Superior subsegment of the medial segment
- Inferior subsegment of the medial segment
- Inferior subsegment of the anterior segment
- Inferior subsegment of the posterior segment
- Superior subsegment of the posterior segment
- Superior subsegment of the anterior segment
Physiology
The various functions of the liver are carried
out by the liver cells or
hepatocytes.
- The liver produces and excretes
bile
required for emulsifying fats. Some of the bile drains directly into the
duodenum, and some is stored in the
gallbladder.
- The liver performs several roles in
carbohydrate
metabolism:
- The liver also performs several roles in
lipid
metabolism:
- The liver produces
coagulation factors
I
(fibrinogen),
II
(prothrombin),
V,
VII,
IX,
X
and
XI, as well as
protein C,
protein S and
antithrombin.
- The liver breaks down
hemoglobin, creating
metabolites that are added to
bile as
pigment (bilirubin
and
biliverdin).
- The liver breaks down
toxic
substances and most medicinal products in a process called
drug metabolism. This sometimes results in
toxication, when the metabolite is more toxic than its precursor.
- The liver converts
ammonia
to urea.
- The liver stores a multitude of substances,
including glucose in the form of glycogen,
vitamin B12,
iron, and
copper.
- In the first trimester
fetus,
the liver is the main site of
red blood cell production. By the 32nd week of gestation, the
bone marrow has almost completely taken over that task.
- The liver is responsible for immunological
effects- the reticuloendothelial system of the liver contains many
immunologically active cells, acting as a 'sieve' for antigens carried
to it via the portal system.
Currently, there is no artificial organ or device
capable of emulating all the functions of the liver. Some functions can be
emulated by
liver dialysis, an experimental treatment for
liver failure.
Diseases of the liver
Many diseases of the liver are accompanied by
jaundice
caused by increased levels of
bilirubin in the system. The bilirubin results from the breakup of the
hemoglobin of dead
red blood cells; normally, the liver removes bilirubin from the blood
and excretes it through bile.
-
Hepatitis, inflammation of the liver, caused mainly by various
viruses
but also by some poisons, autoimmunity or hereditary conditions.
-
Cirrhosis is the formation of fibrous tissue in the liver, replacing
dead liver cells. The death of the liver cells can for example be caused
by viral hepatitis,
alcoholism or contact with other liver-toxic chemicals.
-
Hemochromatosis, a hereditary disease causing the accumulation of
iron in the
body, eventually leading to liver damage.
-
Cancer
of the liver (primary
hepatocellular carcinoma or
cholangiocarcinoma and metastatic cancers, usually from other parts
of the
gastrointestinal tract).
-
Wilson's disease, a
hereditary disease which causes the body to retain
copper.
-
Primary sclerosing cholangitis, an
inflammatory disease of the
bile
duct, autoimmune in nature.
-
Primary biliary cirrhosis, autoimmune disease of small bile ducts
-
Budd-Chiari syndrome, obstruction of the hepatic vein.
-
Gilbert's syndrome, a genetic disorder of bilirubin metabolism,
found in about 5% of the population.
-
Glycogen storage disease type II,The build-up of glycogen causes
progressive muscle weakness (myopathy) throughout the body and affects
various body tissues, particularly in the heart, skeletal muscles, liver
and nervous system.
There are also many pediatric liver disease,
including
biliary atresia,
alpha-1 antitrypsin deficiency,
alagille syndrome, and
progressive familial intrahepatic cholestasis, to name but a few.
A number of
liver function tests are available to test the proper function of the
liver. These test for the presence of enzymes in blood that are normally
most abundant in liver tissue, metabolites or products.
Liver transplantation
-
Human liver transplant was first performed by
Thomas Starzl in USA and Roy Calne in England in 1963 and 1965
respectively.
Liver transplantation is the only option for those with irreversible
liver failure. Most transplants are done for chronic liver diseases
leading to
cirrhosis, such as chronic hepatitis C, alcoholism, autoimmune
hepatitis, and many others. Less commonly, liver transplantation is done
for
fulminant hepatic failure, in which liver failure occurs over days to
weeks.
Liver
allografts for
transplant usually come from non-living donors who have died from
fatal brain injury.
Living donor liver transplantation is a technique in which a portion
of a living person's liver is removed and used to replace the entire liver
of the recipient. This was first performed in
1989 for
pediatric liver transplantation. Only 20% of an adult's liver (Couinaud
segments 2 and 3) is needed to serve as a liver allograft for an infant or
small child.
More recently, adult-to-adult liver
transplantation has been done using the donor's right hepatic lobe which
amounts to 60% of the liver. Due to the ability of the liver to
regenerate, both the donor and recipient end up with normal liver
function if all goes well. This procedure is more controversial as it
entails performing a much larger operation on the donor, and indeed there
have been at least 2 donor deaths out of the first several hundred cases.
A recent publication has addressed the problem of donor mortality, and at
least 14 cases have been found.[4]
The risk of postoperative complications (and death) is far greater in
right sided hepatectomy than left sided operations
Development
The liver develops as an
endodermal outpocketing of the
foregut called
the hepatic diverticulum. Its initial blood supply is primarily
from the
vitelline veins that drain blood from the
yolk sac.
The superior part of the hepatic diverticulum gives rise to the
hepatocytes and bile ducts, while the inferior part becomes the
gallbladder and its associated cystic duct.
Fetal blood supply
In the growing fetus, a major source of blood to
the liver is the
umbilical vein which supplies nutrients to the growing fetus. The
umbilical vein enters the abdomen at the umbilicus, and passes upward
along the free margin of the
falciform ligament of the liver to the inferior surface of the liver.
There it joins with the left branch of the portal vein. The
ductus venosus carries blood from the left portal vein to the left
hepatic vein and thence to the
inferior vena cava, allowing placental blood to bypass the liver.
In the fetus, the liver is developing throughout
normal gestation, and does not perform the normal filtration of the infant
liver. The liver does not perform digestive processes because the fetus
does not consume meals directly, but receives nourishment from the mother
via the
placenta. The fetal liver releases some blood stem cells that migrate
to the fetal
thymus, so initially the
lymphocytes, called
T-cells,
are created from fetal liver stem cells. Once the fetus is delivered, the
formation of blood stem cells in infants shifts to the red
bone marrow.
After birth, the umbilical vein and ductus
venosus are completely obliterated two to five days postpartum; the former
becomes the
ligamentum teres and the latter becomes the
ligamentum venosum. In the disease state of
cirrhosis and
portal hypertension, the umbilical vein can open up again.
|
Liver function tests
Liver function tests (LFTs or LFs), which include
liver enzymes, are groups of
clinical biochemistry laboratory blood assays designed to give information
about the state of a patient's
liver. Most
liver diseases cause only mild symptoms initially, while it is vital that
these diseases be detected early. Hepatic involvement in some diseases can be
of crucial importance. This testing is performed by a
Medical technologist on a patient's serum or plasma which is collected by
a
phlebotomist.
Standard liver panel
Total Protein (TP)
The liver produces most of the
plasma
proteins in the body making a measure of the amount of protein in the
blood useful. Reference range (60-80 g/L).
Albumin (Alb)
Albumin is
a protein made specifically by the liver, and can be measured cheaply and
easily. It is the main constituent of total protein; the remaining fraction is
called
globulin (including e.g. the
immunoglobulins). Albumin levels are decreased in chronic liver disease,
such as
cirrhosis. It is also decreased in
nephrotic syndrome, where it is lost through the urine. Poor
nutrition
or states of protein catabolism may also lead to hypoalbuminaemia. The
half-life
of albumin is approximately 20 days. Albumin is not considered to be an
especially useful marker of liver synthetic function, coagulation factors (see
below) are much more sensitive. The reference range is 30-50 g/L. (3.0-5.0 g/dL)
Alanine transaminase (ALT)
Alanine transaminase (ALT), also called Serum Glutamic Pyruvic
Transaminase (SGPT) or Alanine aminotransferase (ALAT) is an
enzyme
present in
hepatocytes (liver cells). When a cell is damaged, it leaks this enzyme
into the blood, where it is measured. ALT rises dramatically in acute liver
damage, such as
viral hepatitis or
paracetamol (acetaminophen) overdose. Elevations are often measured in
multiples of the upper limit of normal (ULN). The reference range is 15-45 U/L
in most laboratories.
Aspartate transaminase (AST)
Aspartate transaminase (AST) also called Serum Glutamic Oxaloacetic
Transaminase (SGOT) or aspartate aminotransferase (ASAT) is similar to ALT in
that it is another enzyme associated with liver parenchymal cells. It is
raised in acute liver damage, but is also present in red cells, and cardiac
and skeletal muscle and is therefore not specific to the liver. The ratio of
AST to ALT is sometimes useful in differentiating between causes of liver
damage:
In resource-poor settings, the AST is more frequently
available than the ALT, because it is a cheaper assay.
Alkaline phosphatase (ALP)
Alkaline phosphatase (ALP) is an enzyme in the cells lining the
biliary ducts of the liver. ALP levels in plasma will rise with large bile
duct obstruction, intrahepatic
cholestasis or infiltrative diseases of the liver. ALP is also present in
bone and
placental
tissue, so it is higher in growing children (as their bones are being
remodelled). The reference range is usually 30-120 U/L.
Total bilirubin (TBIL)
Bilirubin
is a breakdown product of
heme (a part of
haemoglobin in red blood cells). The liver is responsible for clearing the
blood of bilirubin. It does this by the following mechanism: bilirubin is
taken up into
hepatocytes, conjugated (modified to make it water-soluble), and
secreted into the
bile, which is excreted into the intestine.
Liver function tests typically measure Total
bilirubin (TBIL) and Direct bilirubin (a.k.a. conjugated bilirubin,
CB). Indirect bilirubin (a.k.a. unconjugated bilirubin, UCB) is
obtained by subtracting direct bilirubin from total bilirubin.
Increased total bilirubin causes jaundice, and can
signal a number of problems:
1. Increased bilirubin production. This can be
due to a number of causes, including hemolytic anemias and internal
hemorrhage.
2. Problems with the liver, which are reflected as
deficiencies in bilirubin metabolism (e.g. reduced hepatocyte uptake,
impaired conjugation of bilirubin, and reduced hepatocyte secretion of
bilirubin). Some examples would be cirrhosis and viral hepatitis.
3. Obstruction of the bile ducts, reflected as
deficiencies in bilirubin excretion. (Obstruction can be located either
within the liver or outside the liver.)
The diagnosis is narrowed down further by looking at
the levels of direct bilirubin. If direct (i.e. conjugated) bilirubin is
normal, then the problem is an excess of unconjugated bilirubin, and the
location of the problem is upstream of bilirubin excretion. Anemia, viral
hepatitis, or cirrhosis can be suspected. If direct bilirubin is elevated,
then the liver is conjugating bilirubin normally, but is not able to excrete
it. Bile duct obstruction by gallstones or cancer should be suspected.
:
Gamma glutamyl transpeptidase (GGT)
Although reasonably specific to the liver and a more
sensitive marker for cholestatic damage than ALP,
Gamma glutamyl transpeptidase (GGT) may be elevated with even minor,
sub-clinical levels of liver dysfunction. It can also be helpful in
identifying the cause of an isolated elevation in ALP. GGT is raised in
alcohol toxicity (acute and chronic).
5' nucleotidase (5'NTD)
5'NTD is another test specific for cholestasis or
damage to the intra or extrahepatic biliary system, and in some laboratories,
is used as a substitute for GGT for ascertaining whether an elevated ALP is of
biliary or extra-biliary origin.
Coagulation tests (e.g. INR)
The liver is responsible for the production of
coagulation factors. The
international normalized ratio (INR) measures the speed of a particular
pathway of coagulation, comparing it to normal. If the INR is increased, it
means it is taking longer than usual for blood to clot. The INR will only be
increased if the liver is so damaged that synthesis of
vitamin K-dependent
coagulation factors has been impaired: it is not a sensitive measure of liver
function.
It is very important to normalize the INR before
operating on people with liver problems (usually by transfusion with blood
plasma containing the deficient factors) as they could bleed excessively.
Serum
glucose
(BG, Glu)
The liver's ability to produce glucose (gluconeogenesis)
is usually the last function to be lost in the setting of fulminant liver
failure.
|
Liver function tests
From Wikipedia, the free
encyclopedia
Liver function tests (LFTs or LFs), which include
liver enzymes, are groups of
clinical biochemistry laboratory blood assays designed to give information
about the state of a patient's
liver. Most
liver diseases cause only mild symptoms initially, while it is vital that
these diseases be detected early. Hepatic involvement in some diseases can be
of crucial importance. This testing is performed by a
Medical technologist on a patient's serum or plasma which is collected by
a
phlebotomist.
Standard liver panel
Total Protein (TP)
The liver produces most of the
plasma
proteins in the body making a measure of the amount of protein in the
blood useful. Reference range (60-80 g/L).
Albumin (Alb)
Albumin is
a protein made specifically by the liver, and can be measured cheaply and
easily. It is the main constituent of total protein; the remaining fraction is
called
globulin (including e.g. the
immunoglobulins). Albumin levels are decreased in chronic liver disease,
such as
cirrhosis. It is also decreased in
nephrotic syndrome, where it is lost through the urine. Poor
nutrition
or states of protein catabolism may also lead to hypoalbuminaemia. The
half-life
of albumin is approximately 20 days. Albumin is not considered to be an
especially useful marker of liver synthetic function, coagulation factors (see
below) are much more sensitive. The reference range is 30-50 g/L. (3.0-5.0 g/dL)
Alanine transaminase (ALT)
Alanine transaminase (ALT), also called Serum Glutamic Pyruvic
Transaminase (SGPT) or Alanine aminotransferase (ALAT) is an
enzyme
present in
hepatocytes (liver cells). When a cell is damaged, it leaks this enzyme
into the blood, where it is measured. ALT rises dramatically in acute liver
damage, such as
viral hepatitis or
paracetamol (acetaminophen) overdose. Elevations are often measured in
multiples of the upper limit of normal (ULN). The reference range is 15-45 U/L
in most laboratories.
Aspartate transaminase (AST)
Aspartate transaminase (AST) also called Serum Glutamic Oxaloacetic
Transaminase (SGOT) or aspartate aminotransferase (ASAT) is similar to ALT in
that it is another enzyme associated with liver parenchymal cells. It is
raised in acute liver damage, but is also present in red cells, and cardiac
and skeletal muscle and is therefore not specific to the liver. The ratio of
AST to ALT is sometimes useful in differentiating between causes of liver
damage:
In resource-poor settings, the AST is more frequently
available than the ALT, because it is a cheaper assay.
Alkaline phosphatase (ALP)
Alkaline phosphatase (ALP) is an enzyme in the cells lining the
biliary ducts of the liver. ALP levels in plasma will rise with large bile
duct obstruction, intrahepatic
cholestasis or infiltrative diseases of the liver. ALP is also present in
bone and
placental
tissue, so it is higher in growing children (as their bones are being
remodelled). The reference range is usually 30-120 U/L.
Total bilirubin (TBIL)
Bilirubin
is a breakdown product of
heme (a part of
haemoglobin in red blood cells). The liver is responsible for clearing the
blood of bilirubin. It does this by the following mechanism: bilirubin is
taken up into
hepatocytes, conjugated (modified to make it water-soluble), and
secreted into the
bile, which is excreted into the intestine.
Liver function tests typically measure Total
bilirubin (TBIL) and Direct bilirubin (a.k.a. conjugated bilirubin,
CB). Indirect bilirubin (a.k.a. unconjugated bilirubin, UCB) is
obtained by subtracting direct bilirubin from total bilirubin.
Increased total bilirubin causes jaundice, and can
signal a number of problems:
1. Increased bilirubin production. This can be
due to a number of causes, including hemolytic anemias and internal
hemorrhage.
2. Problems with the liver, which are reflected as
deficiencies in bilirubin metabolism (e.g. reduced hepatocyte uptake,
impaired conjugation of bilirubin, and reduced hepatocyte secretion of
bilirubin). Some examples would be cirrhosis and viral hepatitis.
3. Obstruction of the bile ducts, reflected as
deficiencies in bilirubin excretion. (Obstruction can be located either
within the liver or outside the liver.)
The diagnosis is narrowed down further by looking at
the levels of direct bilirubin. If direct (i.e. conjugated) bilirubin is
normal, then the problem is an excess of unconjugated bilirubin, and the
location of the problem is upstream of bilirubin excretion. Anemia, viral
hepatitis, or cirrhosis can be suspected. If direct bilirubin is elevated,
then the liver is conjugating bilirubin normally, but is not able to excrete
it. Bile duct obstruction by gallstones or cancer should be suspected.
Other tests commonly requested
alongside LFTs:
Gamma glutamyl transpeptidase
(GGT)
Although reasonably specific to the liver and a more
sensitive marker for cholestatic damage than ALP,
Gamma glutamyl transpeptidase (GGT) may be elevated with even minor,
sub-clinical levels of liver dysfunction. It can also be helpful in
identifying the cause of an isolated elevation in ALP. GGT is raised in
alcohol toxicity (acute and chronic).
5' nucleotidase (5'NTD)
5'NTD is another test specific for cholestasis or
damage to the intra or extrahepatic biliary system, and in some laboratories,
is used as a substitute for GGT for ascertaining whether an elevated ALP is of
biliary or extra-biliary origin.
Coagulation tests (e.g. INR)
The liver is responsible for the production of
coagulation factors. The
international normalized ratio (INR) measures the speed of a particular
pathway of coagulation, comparing it to normal. If the INR is increased, it
means it is taking longer than usual for blood to clot. The INR will only be
increased if the liver is so damaged that synthesis of
vitamin K-dependent
coagulation factors has been impaired: it is not a sensitive measure of liver
function.
It is very important to normalize the INR before
operating on people with liver problems (usually by transfusion with blood
plasma containing the deficient factors) as they could bleed excessively.
Serum
glucose
(BG, Glu)
The liver's ability to produce glucose (gluconeogenesis)
is usually the last function to be lost in the setting of fulminant liver
failure.
|
HELLP syndrome
From Wikipedia, the free encyclopedia
HELLP syndrome is a life-threatening complication of
pre-eclampsia. Both conditions occur during the latter stages of
pregnancy,
or sometimes after
childbirth.
HELLP
is an abbreviation of the main findings:
Signs and symptoms
Often, a patient who develops HELLP syndrome has already been followed
up for
pregnancy-induced hypertension (gestational hypertension), or is
suspected to develop
pre-eclampsia (high blood pressure and
proteinuria). Up to 8% of all cases present after delivery.
There is gradual but marked onset of
headaches
(30%), blurred vision,
malaise
(90%), nausea/vomiting
(30%), "band pain" around the upper
abdomen
(65%) and tingling in the extremities.
Oedema may
occur but its absence does not exclude HELLP syndrome.
Arterial hypertension is a diagnostic requirement, but may be mild.
Rupture of the liver capsule and a resultant
hematoma
may occur. If the patient gets a
seizure or
coma, the
condition has progressed into full-blown
eclampsia.
Patients who present symptoms of HELLP can be misdiagnosed in the early
stages, increasing the risk of liver failure and morbidity (Padden, 1999).
Diagnosis
In a patient with possible HELLP syndrome, a batch of
blood
tests is performed: a
full blood count,
liver
enzymes,
renal function and
electrolytes and
coagulation studies. Often,
fibrin
degradation products (FDPs) are determined, which can be elevated.
Lactate dehydrogenase is a marker of hemolysis and is elevated (>600
U/liter).
Proteinuria is present but can be mild.
Classification
The
platelet count has been found to be moderately predictive of severity:
under 50 million/L is class I (severe), between 50 and 100 is class II
(moderately severe) and >100 is class III (mild). This system is termed the
Mississippi classification (Martin et al 1990).
Pathophysiology
The exact cause of HELLP is unknown, but general activation of the
coagulation cascade is considered the main underlying problem. Fibrin forms
crosslinked networks in the small
blood
vessels. This leads to a
microangiopathic hemolytic anemia: the mesh causes destruction of
red blood cells as if they were being forced through a strainer.
Additionally,
platelets are consumed. As the
liver appears
to be the main site of this process, downstream liver cells suffer
ischemia,
leading to periportal necrosis. Other organs can be similarly affected. HELLP
syndrome leads to a variant form of
disseminated intravascular coagulation (DIC), leading to paradoxical
bleeding,
which can make emergency surgery a serious challenge.
Treatment
The only effective treatment is delivery of the baby, preferably by
cesarean section. Several medications have been investigated for the
treatment of HELLP syndrome, but evidence is conflicting as to whether
magnesium sulfate decreases the risk of seizures and progress to eclampsia.
The DIC is treated with
fresh frozen plasma to replenish the coagulation proteins, and the
anemia may
require
blood transfusion. In mild cases,
corticosteroids and
antihypertensives (labetalol,
hydralazine,
nifedipine) may be sufficient. Intravenous fluids are generally required.
Epidemiology
Its incidence is reported as 0.2-0.6% of all pregnancies. Of women with
(pre)eclampsia, 4-12% also develop signs of a "superimposed" HELLP syndrome.
Mortality is 7-35% and perinatal mortality of the child may be up to 40%.
HELLP usually begins after the third trimester, and usually in Caucasian women
over the age of 25. (Padden, 1999.) Rarely, cases have been reported as early
as 23 weeks gestation.
History
HELLP syndrome was identified as a distinct clinical entity (as opposed
to severe preeclampsia) by Dr Louis Weinstein in 1982.
|
|
HELLP syndrome
HELLP syndrome is a life-threatening complication of
pre-eclampsia. Both conditions occur during the latter stages of
pregnancy, or sometimes after
childbirth.
HELLP is an abbreviation of the main findings:
Signs and symptoms
Often, a patient who develops HELLP syndrome has already been followed
up for
pregnancy-induced hypertension (gestational hypertension), or
is suspected to develop
pre-eclampsia (high blood pressure and
proteinuria). Up to 8% of all cases present after delivery.
There is gradual but marked onset of
headaches (30%), blurred vision,
malaise (90%),
nausea/vomiting (30%), "band pain" around the upper
abdomen (65%) and tingling in the extremities.
Oedema may occur but its absence does not exclude HELLP syndrome.
Arterial hypertension is a diagnostic requirement, but may be mild.
Rupture of the liver capsule and a resultant
hematoma may occur. If the patient gets a
seizure or
coma, the condition has progressed into full-blown
eclampsia.
Patients who present symptoms of HELLP can be misdiagnosed in the early
stages, increasing the risk of liver failure and morbidity (Padden, 1999).
Diagnosis
In a patient with possible HELLP syndrome, a batch of
blood tests is performed: a
full blood count,
liver enzymes,
renal function and
electrolytes and
coagulation studies. Often,
fibrin degradation products (FDPs) are determined, which can be
elevated.
Lactate dehydrogenase is a marker of hemolysis and is elevated (>600
U/liter).
Proteinuria is present but can be mild.
Classification
The
platelet count has been found to be moderately predictive of severity:
under 50 million/L is class I (severe), between 50 and 100 is class II
(moderately severe) and >100 is class III (mild). This system is termed
the Mississippi classification (Martin et al 1990).
Pathophysiology
The exact cause of HELLP is unknown, but general activation of the
coagulation cascade is considered the main underlying problem. Fibrin
forms crosslinked networks in the small
blood vessels. This leads to a
microangiopathic hemolytic anemia: the mesh causes destruction of
red blood cells as if they were being forced through a strainer.
Additionally,
platelets are consumed. As the
liver appears to be the main site of this process, downstream liver
cells suffer
ischemia, leading to periportal necrosis. Other organs can be
similarly affected. HELLP syndrome leads to a variant form of
disseminated intravascular coagulation (DIC), leading to paradoxical
bleeding, which can make emergency surgery a serious challenge.
Treatment
The only effective treatment is delivery of the baby, preferably by
cesarean section. Several medications have been investigated for the
treatment of HELLP syndrome, but evidence is conflicting as to whether
magnesium sulfate decreases the risk of seizures and progress to
eclampsia. The DIC is treated with
fresh frozen plasma to replenish the coagulation proteins, and the
anemia may require
blood transfusion. In mild cases,
corticosteroids and
antihypertensives (labetalol,
hydralazine,
nifedipine) may be sufficient. Intravenous fluids are generally
required.
Epidemiology
Its incidence is reported as 0.2-0.6% of all pregnancies. Of women with
(pre)eclampsia, 4-12% also develop signs of a "superimposed" HELLP
syndrome. Mortality is 7-35% and perinatal mortality of the child may be
up to 40%. HELLP usually begins after the third trimester, and usually in
Caucasian women over the age of 25. (Padden, 1999.) Rarely, cases have
been reported as early as 23 weeks gestation.
History
HELLP syndrome was identified as a distinct clinical entity (as opposed
to severe preeclampsia) by Dr Louis Weinstein in 1982.
|
|
Liver function tests
Liver function tests (LFTs or LFs), which include
liver enzymes, are groups of
clinical biochemistry laboratory blood assays designed to give
information about the state of a patient's
liver. Most liver diseases cause only mild symptoms initially, while
it is vital that these diseases be detected early. Hepatic involvement in
some diseases can be of crucial importance. This testing is performed by a
Medical technologist on a patient's serum or plasma which is collected
by a
phlebotomist.
Standard liver panel
Total Protein (TP)
The liver produces most of the
plasma
proteins in the body making a measure of the amount of protein in the
blood useful. Reference range (60-80 g/L).
Albumin (Alb)
Albumin is a protein made specifically by the liver, and can be
measured cheaply and easily. It is the main constituent of total protein;
the remaining fraction is called
globulin (including e.g. the
immunoglobulins). Albumin levels are decreased in chronic liver
disease, such as
cirrhosis. It is also decreased in
nephrotic syndrome, where it is lost through the urine. Poor
nutrition or states of protein catabolism may also lead to
hypoalbuminaemia. The
half-life of albumin is approximately 20 days. Albumin is not
considered to be an especially useful marker of liver synthetic function,
coagulation factors (see below) are much more sensitive. The reference
range is 30-50 g/L. (3.0-5.0 g/dL)
Alanine transaminase (ALT)
Alanine transaminase (ALT), also called Serum Glutamic Pyruvic
Transaminase (SGPT) or Alanine aminotransferrase (ALAT) is an
enzyme present in
hepatocytes (liver cells). When a cell is damaged, it leaks this
enzyme into the blood, where it is measured. ALT rises dramatically in
acute liver damage, such as
viral hepatitis or
paracetamol (acetaminophen) overdose. Elevations are often measured in
multiples of the upper limit of normal (ULN). The reference range is 15-45
U/L in most laboratories.
Aspartate transaminase (AST)
Aspartate transaminase (AST) also called Serum Glutamic Oxaloacetic
Transaminase (SGOT) or aspartate aminotransferase (ASAT) is similar to ALT
in that it is another enzyme associated with liver parenchymal cells. It
is raised in acute liver damage, but is also present in red cells, and
cardiac and skeletal muscle and is therefore not specific to the liver.
The ratio of AST to ALT is sometimes useful in differentiating between
causes of liver damage:
In resource-poor settings, the AST is more
frequently available than the ALT, because it is a cheaper assay.
Alkaline phosphatase (ALP)
Alkaline phosphatase (ALP) is an enzyme in the cells lining the
biliary ducts of the liver. ALP levels in plasma will rise with large
bile duct obstruction, intrahepatic
cholestasis or infiltrative diseases of the liver. ALP is also present
in
bone and
placental tissue, so it is higher in growing children (as their bones
are being remodelled). The reference range is usually 30-120 U/L.
Total bilirubin (TBIL)
Bilirubin is a breakdown product of
heme (a part of
hemoglobin in red blood cells). The liver is responsible for clearing
the blood of bilirubin. It does this by the following mechanism: bilirubin
is taken up into
hepatocytes, conjugated (modified to make it water-soluble),
and secreted into the
bile, which is excreted into the intestine.
Liver function tests typically measure Total
bilirubin (TBIL) and Direct bilirubin (a.k.a. conjugated
bilirubin, CB). Indirect bilirubin (a.k.a. unconjugated bilirubin,
UCB) is obtained by subtracting direct bilirubin from total bilirubin.
Increased total bilirubin causes jaundice, and
can signal a number of problems:
1. Increased bilirubin production. This
can be due to a number of causes, including hemolytic anemias and internal
hemorrhage.
2. Problems with the liver, which are reflected
as deficiencies in bilirubin metabolism (e.g. reduced hepatocyte
uptake, impaired conjugation of bilirubin, and reduced hepatocyte
secretion of bilirubin). Some examples would be cirrhosis and viral
hepatitis.
3. Obstruction of the bile ducts, reflected as
deficiencies in bilirubin excretion. (Obstruction can be located
either within the liver or outside the liver.)
The diagnosis is narrowed down further by looking
at the levels of direct bilirubin. If direct (i.e. conjugated) bilirubin
is normal, then the problem is an excess of unconjugated bilirubin, and
the location of the problem is upstream of bilirubin excretion. Anemia,
viral hepatitis, or cirrhosis can be suspected. If direct bilirubin is
elevated, then the liver is conjugating bilirubin normally, but is not
able to excrete it. Bile duct obstruction by gallstones or cancer should
be suspected.
Other tests commonly requested alongside
LFTs:
Gamma glutamyl transpeptidase (GGT)
Although reasonably specific to the liver and a
more sensitive marker for cholestatic damage than ALP,
Gamma glutamyl transpeptidase (GGT) may be elevated with even minor,
sub-clinical levels of liver dysfunction. It can also be helpful in
identifying the cause of an isolated elevation in ALP. GGT is raised in
alcohol toxicity (acute and chronic).
5' nucleotidase (5'NTD)
5'NTD is another test specific for cholestasis or
damage to the intra or extrahepatic biliary system, and in some
laboratories, is used as a substitute for GGT for ascertaining whether an
elevated ALP is of biliary or extra-biliary origin.
Coagulation tests (e.g. INR)
The liver is responsible for the production of
coagulation factors. The
international normalized ratio (INR) measures the speed of a
particular pathway of coagulation, comparing it to normal. If the INR is
increased, it means it is taking longer than usual for blood to clot. The
INR will only be increased if the liver is so damaged that synthesis of
vitamin K-dependent coagulation factors has been impaired: it is not a
sensitive measure of liver function.
It is very important to normalize the INR before
operating on people with liver problems (usually by transfusion with blood
plasma containing the deficient factors) as they could bleed excessively.
Serum
glucose (BG, Glu)
The liver's ability to produce glucose (gluconeogenesis)
is usually the last function to be lost in the setting of fulminant liver
failure.
This entry is from Wikipedia, the
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professional editors (see
full disclaimer)
|
SIDE EFFECTS OF ZOLOFT
During its premarketing assessment,
multiple doses of ZOLOFT were
administered to over 4000 adult
subjects as of February 18, 2000. The conditions and duration of
exposure to ZOLOFT varied
greatly, and included (in overlapping categories)
clinical
pharmacology studies,
open and double-blind studies,
uncontrolled and controlled studies,
inpatient and
outpatient studies,
fixed-dose and titration studies, and studies for
multiple indications,
including major depressive disorder, OCD,
panic disorder, PTSD, PMDD and
social anxiety disorder.
Untoward events associated with this
exposure were recorded by
clinical investigators using
terminology of their own
choosing. Consequently, it is not possible to provide a meaningful estimate
of the proportion of individuals experiencing adverse events without first
grouping similar types of
untoward events into a smaller
number of standardized event categories.
In the tabulations that follow, a World Health
Organization dictionary of terminology has been used to classify reported
adverse events. The frequencies presented, therefore, represent the
proportion of the over 4000 adult
individuals exposed to multiple
doses of ZOLOFT who experienced a treatment-emergent adverse event of the
type cited on at least one
occasion while receiving ZOLOFT. An
event was considered treatment-emergent if it occurred for the first
time or worsened while receiving
therapy following
baseline evaluation. It is
important to emphasize that events reported during
therapy were not necessarily
caused by it.
The prescriber should be aware that the figures in
the tables and tabulations cannot be used to predict the
incidence of
side effects in the course of
usual medical
practice where
patient characteristics and
other factors differ from those that prevailed in the
clinical trials. Similarly,
the cited frequencies cannot be compared with figures obtained from other
clinical investigations
involving different treatments, uses, and investigators. The cited figures,
however, do provide the prescribing
physician with some
basis for estimating the
relative contribution of drug and
nondrug factors to the side
effect incidence
rate in the
population studied.
Incidence in Placebo-Controlled Trials¾Table 1
enumerates the most common treatment-emergent adverse events associated with
the use of ZOLOFT (incidence of at least 5% for ZOLOFT and at least twice
that for placebo within at
least one of the indications) for the
treatment of adult patients
with major depressive disorder/other*, OCD,
panic disorder, PTSD, PMDD and
social anxiety
disorder in
placebo-controlled clinical
trials. Most patients in major depressive disorder/other*, OCD,
panic disorder, PTSD and social
anxiety disorder studies
received doses of 50 to 200 mg/day. Patients in the PMDD study with daily
dosing throughout the menstrual
cycle received doses of 50 to 150 mg/day, and in the PMDD study with
dosing during the luteal
phase of the menstrual
cycle received doses of 50 to
100 mg/day. Table 2 enumerates treatment-emergent adverse events that
occurred in 2% or more of adult
patients treated with ZOLOFT and with
incidence greater than
placebo who participated in
controlled clinical trials comparing ZOLOFT with
placebo in the
treatment of major
depressive disorder/other*, OCD,
panic disorder, PTSD, PMDD and social
anxiety disorder. Table 2
provides combined data for the pool
of studies that are provided separately by indication in Table 1.
TABLE 1
MOST COMMON TREATMENT-EMERGENT ADVERSE EVENTS:
INCIDENCE IN PLACEBO-CONTROLLED CLINICAL TRIALS
| |
Percentage of Patients Reporting Event
|
| |
Major Depressive
Disorder/Other*
|
OCD
|
Panic
Disorder
|
PTSD
|
|
Body System/Adverse Event
|
ZOLOFT
(N=861)
|
Placebo
(N=853)
|
ZOLOFT
(N=533)
|
Placebo
(N=373)
|
ZOLOFT
(N=430)
|
Placebo
(N=275)
|
ZOLOFT
(N=374)
|
Placebo
(N=376)
|
|
Autonomic Nervous System
Disorders
|
|
|
|
|
|
|
|
|
|
Ejaculation Failure(1)
|
7
|
<1
|
17
|
2
|
19
|
1
|
11
|
1
|
|
Mouth Dry
|
16
|
9
|
14
|
9
|
15
|
10
|
11
|
6
|
|
Sweating Increased
|
8
|
3
|
6
|
1
|
5
|
1
|
4
|
2
|
|
Centr. & Periph. Nerv. System
Disorders
|
|
|
|
|
|
|
|
|
|
Somnolence
|
13
|
6
|
15
|
8
|
15
|
9
|
13
|
9
|
|
Tremor
|
11
|
3
|
8
|
1
|
5
|
1
|
5
|
1
|
|
Dizziness
|
12
|
7
|
17
|
9
|
10
|
10
|
8
|
5
|
|
General
|
|
|
|
|
|
|
|
|
|
Fatigue
|
11
|
8
|
14
|
10
|
11
|
6
|
10
|
5
|
|
Pain
|
1
|
2
|
3
|
1
|
3
|
3
|
4
|
6
|
|
Malaise
|
<1
|
1
|
1
|
1
|
7
|
14
|
10
|
10
|
|
Gastrointestinal Disorders
|
|
|
|
|
|
|
|
|
|
Abdominal Pain
|
2
|
2
|
5
|
5
|
6
|
7
|
6
|
5
|
|
Anorexia
|
3
|
2
|
11
|
2
|
7
|
2
|
8
|
2
|
|
Constipation
|
8
|
6
|
6
|
4
|
7
|
3
|
3
|
3
|
|
Diarrhea/Loose Stools
|
18
|
9
|
24
|
10
|
20
|
9
|
24
|
15
|
|
Dyspepsia
|
6
|
3
|
10
|
4
|
10
|
8
|
6
|
6
|
|
Nausea
|
26
|
12
|
30
|
11
|
29
|
18
|
21
|
11
|
|
Psychiatric Disorders
|
|
|
|
|
|
|
|
|
|
Agitation
|
6
|
4
|
6
|
3
|
6
|
2
|
5
|
5
|
|
Insomnia
|
16
|
9
|
28
|
12
|
25
|
18
|
20
|
11
|
|
Libido Decreased
|
1
|
<1
|
11
|
2
|
7
|
1
|
7
|
2
|
| |
PMDD
Daily
Dosing
|
PMDD
Luteal Phase
Dosing(2)
|
|
|
| Body System/Adverse Event |
ZOLOFT
(N=121)
|
Placebo
(N=122)
|
ZOLOFT
(N=136)
|
Placebo
(N=127)
|
ZOLOFT
(N=344)
|
Placebo
(N=268)
|
|
|
|
Autonomic Nervous System
Disorders
|
|
|
|
|
|
|
|
|
|
Ejaculation Failure(1)
|
N/A
|
N/A
|
N/A
|
N/A
|
14
|
-
|
|
|
|
Mouth Dry
|
6
|
3
|
10
|
3
|
12
|
4
|
|
|
|
Sweating Increased
|
6
|
<1
|
3
|
0
|
11
|
2
|
|
|
|
Centr. & Periph. Nerv. System
Disorders
|
|
|
|
|
|
|
|
|
|
Somnolence
|
7
|
<1
|
2
|
0
|
9
|
6
|
|
|
|
Tremor
|
2
|
0
|
<1
|
<1
|
9
|
3
|
|
|
|
Dizziness
|
6
|
3
|
7
|
5
|
14
|
6
|
|
|
|
General
|
|
|
|
|
|
|
|
|
|
Fatigue
|
16
|
7
|
10
|
<1
|
12
|
6
|
|
|
|
Pain
|
6
|
<1
|
3
|
2
|
1
|
3
|
|
|
|
Malaise
|
9
|
5
|
7
|
5
|
8
|
3
|
|
|
|
Gastrointestinal Disorders
|
|
|
|
|
|
|
|
|
|
Abdominal Pain
|
7
|
<1
|
3
|
3
|
5
|
5
|
|
|
|
Anorexia
|
3
|
2
|
5
|
0
|
6
|
3
|
|
|
|
Constipation
|
2
|
3
|
1
|
2
|
5
|
3
|
|
|
|
Diarrhea/Loose Stools
|
13
|
3
|
13
|
7
|
21
|
8
|
|
|
|
Dyspepsia
|
7
|
2
|
7
|
3
|
13
|
5
|
|
|
|
Nausea
|
23
|
9
|
13
|
3
|
22
|
8
|
|
|
|
Psychiatric Disorders
|
|
|
|
|
|
|
|
|
|
Agitation
|
2
|
<1
|
1
|
0
|
4
|
2
|
|
|
|
Insomnia
|
17
|
11
|
12
|
10
|
25
|
10
|
|
|
|
Libido Decreased
|
11
|
2
|
4
|
2
|
9
|
3
|
|
|
(1)Primarily
ejaculatory delay.
Denominator used was for male
patients only (N=271 ZOLOFT major depressive disorder/other*; N=271
placebo major depressive
disorder/other*; N=296 ZOLOFT OCD; N=219
placebo OCD; N=216 ZOLOFT
panic disorder; N=134
placebo
panic disorder; N=130 ZOLOFT
PTSD; N=149 placebo PTSD; No
male patients in PMDD studies; N=205 ZOLOFT social
anxiety disorder; N=153
placebo social anxiety
disorder).
*Major depressive
disorder and other
premarketing controlled trials.
(2)The
luteal
phase and daily dosing PMDD
trials were not designed for making direct comparisons between the two
dosing regimens. Therefore, a comparison between the two dosing regimens of
the PMDD trials of incidence
rates shown in Table 1 should be avoided.
TABLE 2
TREATMENT-EMERGENT ADVERSE EVENTS: INCIDENCE IN
PLACEBO-CONTROLLED CLINICAL TRIALS Percentage of Patients Reporting Event
Major Depressive Disorder/Other*, OCD, Panic Disorder, PTSD, PMDD and Social
Anxiety Disorder combined
|
Body System/Adverse Event**
|
ZOLOFT
(N=2799)
|
Placebo
(N=2394)
|
|
Autonomic Nervous System Disorders
|
|
|
|
Ejaculation Failure(1)
|
14
|
1
|
|
Mouth Dry
|
14
|
8
|
|
Sweating Increased
|
7
|
2
|
|
Centr. & Periph. Nerv. System Disorders
|
|
|
|
Somnolence
|
13
|
7
|
|
Dizziness
|
12
|
7
|
|
Headache
|
25
|
23
|
|
Paresthesia
|
2
|
1
|
|
Tremor
|
8
|
2
|
|
Disorders of Skin and Appendages
|
|
|
|
Rash
|
3
|
2
|
|
Gastrointestinal Disorders
|
|
|
|
Anorexia
|
6
|
2
|
|
Constipation
|
6
|
4
|
|
Diarrhea/Loose Stools
|
20
|
10
|
|
Dyspepsia
|
8
|
4
|
|
Nausea
|
25
|
11
|
|
Vomiting
|
4
|
2
|
|
General
|
|
|
|
Fatigue
|
12
|
7
|
|
Psychiatric Disorders
|
|
|
|
Agitation
|
5
|
3
|
|
Anxiety
|
4
|
3
|
|
Insomnia
|
21
|
11
|
|
Libido Decreased
|
6
|
2
|
|
Nervousness
|
5
|
4
|
|
Special Senses
|
|
|
|
Vision Abnormal
|
3
|
2
|
(1)Primarily
ejaculatory delay.
Denominator used was for male
patients only (N=1118 ZOLOFT; N=926 placebo).
*Major depressive
disorder and other
premarketing controlled trials.
**Included are events reported by at least 2% of
patients taking ZOLOFT except the following events, which had an
incidence on
placebo greater than or equal
to ZOLOFT: abdominal pain,
back pain, flatulence, malaise,
pain, pharyngitis, respiratory
disorder, upper respiratory
tract infection.
Associated with Discontinuation in Placebo-Controlled
Clinical
Trials
Table 3 lists the adverse events associated with
discontinuation of ZOLOFTÒ
(sertraline hydrochloride)
treatment (incidence at least twice that for placebo and at least 1% for
ZOLOFT in clinical trials) in
major depressive disorder/other*, OCD,
panic disorder, PTSD, PMDD and
social anxiety disorder.
TABLE 3
MOST COMMON ADVERSE EVENTS ASSOCIATED WITH
DISCONTINUATION IN PLACEBO-CONTROLLED CLINICAL TRIALS
|
Adverse
Event
|
Major Depressive
Disorder/Other*,
OCD, Panic
Disorder, PTSD,
PMDD and Social Anxiety Disorder combined
(N=2799)
|
Major
Depressive
Disorder/
Other*
(N=861)
|
OCD
(N=533)
|
Panic
Disorder
(N=430)
|
PTSD
(N=374)
|
PMDD
Daily
Dosing
(N=121)
|
PMDD
Luteal
Phase
Dosing
(N=136)
|
Social
Anxiety
Disorder
(N=344)
|
|
Abdominal
Pain
|
¾
|
¾
|
¾
|
¾
|
¾
|
¾
|
¾
|
1%
|
|
Agitation
|
¾
|
1%
|
¾
|
2%
|
¾
|
¾
|
¾
|
¾
|
|
Anxiety
|
¾
|
¾
|
¾
|
¾
|
¾
|
¾
|
¾
|
2%
|
|
Diarrhea/
Loose Stools
|
2%
|
2%
|
2%
|
1%
|
¾
|
2%
|
¾
|
¾
|
|
Dizziness
|
¾
|
¾
|
1%
|
¾
|
¾
|
¾
|
¾
|
¾
|
|
Dry Mouth
|
¾
|
1%
|
¾
|
¾
|
¾
|
¾
|
¾
|
¾
|
|
Dyspepsia
|
¾
|
¾
|
¾
|
1%
|
¾
|
¾
|
¾
|
¾
|
|
Ejaculation
Failure(1)
|
1%
|
1%
|
1%
|
2%
|
¾
|
N/A
|
N/A
|
2%
|
|
Fatigue
|
¾
|
¾
|
¾
|
¾
|
¾
|
¾
|
¾
|
2%
|
|
Headache
|
1%
|
2%
|
¾
|
¾
|
1%
|
¾
|
¾
|
2%
|
|
Hot Flushes
|
¾
|
¾
|
¾
|
¾
|
¾
|
¾
|
1%
|
¾
|
|
Insomnia
|
2%
|
1%
|
3%
|
2%
|
¾
|
¾
|
1%
|
3%
|
|
Nausea
|
3%
|
4%
|
3%
|
3%
|
2%
|
2%
|
1%
|
2%
|
|
Nervousness
|
¾
|
¾
|
¾
|
¾
|
¾
|
2%
|
¾
|
¾
|
|
Palpitation
|
¾
|
¾
|
¾
|
¾
|
¾
|
¾
|
1%
|
¾
|
|
Somnolence
|
1%
|
1%
|
2%
|
2%
|
¾
|
¾
|
¾
|
¾
|
|
Tremor
|
¾
|
2%
|
¾
|
¾
|
¾
|
¾
|
¾
|
¾
|
(1)Primarily
ejaculatory delay.
Denominator used was for male
patients only (N=271 major depressive disorder/other*; N=296 OCD; N=216
panic disorder; N=130 PTSD; No
male patients in PMDD studies;
N=205 social anxiety
disorder).
*Major depressive
disorder and other
premarketing controlled trials.
Male and Female Sexual Dysfunction with SSRIs
Although changes in
sexual desire,
sexual
performance and
sexual satisfaction often occur
as manifestations of a
psychiatric disorder, they may also be a
consequence of
pharmacologic treatment. In
particular, some evidence
suggests that selective
serotonin reuptake inhibitors (SSRIs) can
cause such untoward
sexual experiences. Reliable
estimates of the incidence
and severity of untoward experiences involving
sexual desire,
performance and
satisfaction are difficult to obtain, however, in part because patients and
physicians may be reluctant to discuss them. Accordingly, estimates of the
incidence of untoward sexual
experience and
performance cited in
product labeling, are likely
to underestimate their actual
incidence.
Table 4 below displays the
incidence of
sexual
side effects reported by at least
2% of patients taking ZOLOFT in placebo-controlled trials.
TABLE 4
|
Adverse Event
|
ZOLOFT
|
Placebo
|
|
Ejaculation failure* (primarily delayed
ejaculation)
|
14%
|
1%
|
|
Decreased libido**
|
6%
|
1%
|
*Denominator used was for
male patients only (N=1118
ZOLOFT; N=926 placebo)
**Denominator used was for
male and
female patients (N=2799 ZOLOFT;
N=2394 placebo)
There are no adequate and well-controlled studies
examining sexual dysfunction
with sertraline treatment.
Priapism has been reported with all SSRIs.
While it is difficult to know the precise
risk of
sexual
dysfunction associated
with the use of SSRIs, physicians should routinely inquire about such
possible side effects.
Other Adverse Events in Pediatric Patients¾In over
600 pediatric patients
treated with ZOLOFT, the overall
profile of adverse events was generally similar to that seen in
adult studies. However, the
following adverse events, from controlled trials, not appearing in Tables 1
and 2, were reported at an
incidence of at least 2% and occurred at a
rate of at least twice the
placebo
rate (N=281 patients treated with
ZOLOFT): fever, hyperkinesia,
urinary incontinence, aggressive reaction, sinusitis,
epistaxis and purpura.
Other Events Observed During the Premarketing
Evaluation of ZOLOFTÒ
(sertraline hydrochloride)¾Following is a list of treatment-emergent adverse
events reported during premarketing assessment of ZOLOFT in
clinical trials (over 4000
adult subjects) except those
already listed in the previous tables or elsewhere in labeling.
In the tabulations that follow, a World Health
Organization dictionary of terminology has been used to classify reported
adverse events. The frequencies presented, therefore, represent the
proportion of the over 4000 adult
individuals exposed to multiple
doses of ZOLOFT who experienced an event of the
type cited on at least one
occasion while receiving ZOLOFT. All events are included except those
already listed in the previous tables or elsewhere in
labeling and those reported
in terms so general as to be uninformative and those for which a causal
relationship to ZOLOFT treatment
seemed remote. It is important to emphasize that although the events
reported occurred during
treatment with ZOLOFT, they were not necessarily caused by it.
Events are further categorized by
body
system and listed in
order of decreasing
frequency according to the
following definitions: frequent adverse events are those occurring on one or
more occasions in at least 1/100 patients; infrequent adverse events are
those occurring in 1/100 to 1/1000 patients; rare events are those occurring
in fewer than 1/1000 patients. Events of major clinical importance are also
described in the
PRECAUTIONS
section.
Autonomic Nervous System Disorders¾Frequent:
impotence; Infrequent: flushing, increased saliva,
cold clammy skin, mydriasis;
Rare: pallor, glaucoma, priapism, vasodilation.
Body as a Whole¾General Disorders¾Rare:
allergic reaction, allergy.
Cardiovascular¾Frequent: palpitations,
chest pain; Infrequent:
hypertension, tachycardia,
postural dizziness, postural
hypotension, periorbital
edema, peripheral edema,
hypotension, peripheral ischemia, syncope, edema, dependent edema; Rare:
precordial
chest pain,
substernal
chest pain, aggravated
hypertension, myocardial
infarction, cerebrovascular disorder.
Central and Peripheral Nervous System Disorders¾Frequent:
hypertonia, hypoesthesia; Infrequent: twitching, confusion,
hyperkinesia, vertigo, ataxia, migraine,
abnormal coordination,
hyperesthesia, leg cramps,
abnormal gait, nystagmus,
hypokinesia; Rare: dysphonia, coma, dyskinesia, hypotonia, ptosis,
choreoathetosis, hyporeflexia.
Disorders of Skin and Appendages¾Infrequent:
pruritus, acne, urticaria, alopecia, dry skin, erythematous rash,
photosensitivity reaction,
maculopapular rash; Rare:
follicular rash, eczema,
dermatitis, contact
dermatitis, bullous eruption,
hypertrichosis, skin
discoloration, pustular rash.
Endocrine Disorders¾Rare: exophthalmos,
gynecomastia.
Gastrointestinal Disorders¾Frequent:
appetite increased; Infrequent: dysphagia,
tooth
caries aggravated, eructation,
esophagitis, gastroenteritis; Rare: melena, glossitis, gum
hyperplasia, hiccup, stomatitis, tenesmus, colitis, diverticulitis, fecal
incontinence, gastritis, rectum
hemorrhage, hemorrhagic
peptic ulcer, proctitis,
ulcerative stomatitis, tongue
edema, tongue ulceration.
General¾Frequent:
back pain, asthenia, malaise,
weight increase; Infrequent:
fever, rigors, generalized edema; Rare: face edema,
aphthous stomatitis.
Hearing and Vestibular Disorders¾Rare:
hyperacusis, labyrinthine
disorder.
Hematopoietic and Lymphatic¾Rare: anemia,
anterior
chamber
eye hemorrhage.
Liver and Biliary System Disorders¾Rare:
abnormal hepatic function.
Metabolic and Nutritional Disorders¾Infrequent:
thirst; Rare: hypoglycemia,
hypoglycemia reaction.
Musculoskeletal System Disorders¾Frequent:
myalgia; Infrequent: arthralgia, dystonia, arthrosis,
muscle cramps,
muscle weakness.
Psychiatric Disorders¾Frequent: yawning,
other male
sexual dysfunction, other
female
sexual dysfunction;
Infrequent: depression, amnesia, paroniria, teeth-grinding, emotional
lability, apathy, abnormal
dreams, euphoria, paranoid
reaction, hallucination, aggressive reaction, aggravated depression,
delusions; Rare:
withdrawal syndrome, suicide ideation,
libido increased, somnambulism,
illusion.
Reproductive¾Infrequent: menstrual disorder,
dysmenorrhea,
intermenstrual bleeding,
vaginal hemorrhage, amenorrhea, leukorrhea; Rare:
female
breast pain, menorrhagia,
balanoposthitis, breast enlargement, atrophic vaginitis,
acute
female mastitis.
Respiratory System Disorders¾Frequent:
rhinitis; Infrequent: coughing, dyspnea, upper
respiratory
tract infection, epistaxis,
bronchospasm, sinusitis; Rare: hyperventilation, bradypnea, stridor,
apnea, bronchitis, hemoptysis, hypoventilation, laryngismus, laryngitis.
Special Senses¾Frequent: tinnitus;
Infrequent: conjunctivitis, earache,
eye pain,
abnormal accommodation;
Rare: xerophthalmia, photophobia, diplopia,
abnormal lacrimation, scotoma,
visual
field defect.
Urinary System Disorders¾Infrequent:
micturition frequency,
polyuria, urinary retention,
dysuria, nocturia, urinary incontinence; Rare: cystitis, oliguria,
pyelonephritis, hematuria, renal pain, strangury.
Laboratory Tests¾In man, asymptomatic elevations in
serum transaminases (SGOT [or
AST] and SGPT [or ALT]) have been
reported infrequently (approximately 0.8%) in
association with ZOLOFTÒ
(sertraline hydrochloride) administration. These
hepatic
enzyme elevations usually
occurred within the first 1 to 9 weeks of
drug
treatment and promptly
diminished upon drug
discontinuation.
ZOLOFT
therapy was associated with small
mean increases in total cholesterol (approximately 3%) and
triglycerides
(approximately 5%), and a small mean
decrease in serum
uric
acid (approximately 7%) of no
apparent
clinical importance.
The safety
profile observed with ZOLOFT
treatment in patients with
major depressive disorder, OCD,
panic disorder, PTSD, PMDD and social
anxiety
disorder is similar.
Other Events Observed During the Postmarketing
Evaluation of ZOLOFT¾Reports of adverse events temporally associated with
ZOLOFT that have been received since market introduction, that are not
listed above and that may have no causal relationship with the drug, include
the following: acute
renal failure, anaphylactoid
reaction, angioedema, blindness,
optic neuritis, cataract, increased coagulation times, bradycardia, AV
block, atrial arrhythmias,
QT-interval prolongation,
ventricular tachycardia
(including torsade de pointes-type arrhythmias), hypothyroidism,
agranulocytosis, aplastic anemia
and pancytopenia, leukopenia, thrombocytopenia, lupus-like syndrome,
serum sickness, hyperglycemia,
galactorrhea, hyperprolactinemia,
neuroleptic
malignant syndrome-like
events, extrapyramidal
symptoms, oculogyric crisis,
serotonin syndrome, psychosis,
pulmonary hypertension,
severe skin reactions, which
potentially can be fatal, such as Stevens-Johnson syndrome, vasculitis,
photosensitivity and
other severe cutaneous
disorders, rare reports of pancreatitis, and
liver events—clinical
features (which in the
majority of cases appeared to be
reversible with
discontinuation of ZOLOFT) occurring in one or more patients include:
elevated enzymes, increased bilirubin, hepatomegaly, hepatitis, jaundice,
abdominal pain, vomiting,
liver
failure and death.
DRUG ABUSE AND DEPENDENCE
Controlled Substance Class¾ZOLOFTÒ
(sertraline hydrochloride) is not a controlled substance.
Physical and Psychological Dependence¾In a
placebo-controlled, double-blind, randomized study of the comparative abuse
liability of ZOLOFT,
alprazolam, and d-amphetamine in humans, ZOLOFT did not produce the
positive
subjective effects
indicative of abuse potential,
such as euphoria or
drug liking, that were observed
with the other two drugs. Premarketing
clinical
experience with ZOLOFT did
not reveal any tendency for a withdrawal
syndrome or any drug-seeking
behavior. In
animal studies ZOLOFT does not
demonstrate stimulant or
barbiturate-like (depressant) abuse
potential. As with any CNS active
drug, however, physicians should carefully evaluate patients for history of
drug
abuse and follow such patients
closely, observing them for signs of ZOLOFT misuse or
abuse (e.g.,
development of tolerance,
incrementation of dose, drug-seeking behavior).
DRUG INTERACTIONS
Potential Effects of Coadministration of Drugs
Highly Bound to Plasma Proteins¾Because sertraline is tightly
bound to
plasma protein, the
administration of
ZOLOFTÒ (sertraline
hydrochloride) to a patient
taking another drug which is
tightly bound to
protein (e.g., warfarin,
digitoxin) may cause a
shift in
plasma concentrations
potentially resulting in an adverse effect. Conversely, adverse effects may
result from displacement
of protein
bound ZOLOFT by other tightly
bound drugs.
In a study comparing
prothrombin
time
AUC (0-120 hr) following dosing
with warfarin (0.75 mg/kg) before and after 21 days of dosing with either
ZOLOFT (50-200 mg/day) or placebo, there was a
mean increase in
prothrombin
time of 8% relative to
baseline for ZOLOFT compared
to a 1% decrease for placebo
(p<0.02). The normalization
of prothrombin
time for the ZOLOFT
group was delayed compared to
the placebo group. The
clinical significance of this
change is unknown. Accordingly,
prothrombin
time should be carefully
monitored when ZOLOFT therapy
is initiated or stopped.
Cimetidine¾In a study assessing disposition of
ZOLOFT (100 mg) on the second of 8 days of
cimetidine
administration (800
mg daily), there were
significant increases in
ZOLOFT mean
AUC (50%), Cmax (24%) and
half-life (26%) compared to
the placebo group. The
clinical significance of
these changes is unknown.
CNS Active Drugs¾In a study comparing the
disposition of
intravenously administered
diazepam before and after 21 days of dosing with either ZOLOFT (50 to
200 mg/day escalating dose) or placebo, there was a 32% decrease relative to
baseline in
diazepam
clearance for the ZOLOFT
group compared to a 19% decrease
relative to baseline for the
placebo group (p<0.03). There
was a 23% increase in Tmax for desmethyldiazepam in the ZOLOFT
group compared to a 20% decrease
in the placebo
group (p<0.03). The
clinical significance of
these changes is unknown.
In a placebo-controlled trial in
normal volunteers, the
administration of two
doses of ZOLOFT did not significantly alter steady-state
lithium levels or the
renal
clearance of lithium.
Nonetheless, at this time, it is recommended that
plasma
lithium levels be monitored
following initiation of ZOLOFT
therapy with appropriate
adjustments to the lithium
dose.
In a controlled study of a single
dose (2 mg) of pimozide, 200
mg sertraline (q.d.)
co-administration to steady state
was associated with a mean
increase in pimozide AUC and Cmax
of about 40%, but was not associated with any changes in EKG. Since the
highest recommended pimozide dose
(10 mg) has not been evaluated in combination with sertraline, the
effect on QT
interval and
PK parameters at doses higher than
2 mg at this
time are not known. While the
mechanism of this
interaction is unknown, due to the narrow
therapeutic
index of pimozide and due to the
interaction noted at a low dose
of pimozide, concomitant
administration of ZOLOFT and pimozide should be contraindicated (see
CONTRAINDICATIONS).
The risk
of using ZOLOFT in combination with other
CNS active drugs has not been
systematically evaluated. Consequently, caution is advised if the
concomitant administration
of ZOLOFT and such drugs is required.
There is limited controlled
experience regarding the
optimal timing of switching from other drugs effective in the
treatment of major
depressive disorder, obsessive-compulsive disorder,
panic disorder, posttraumatic
stress disorder,
premenstrual dysphoric
disorder and social
anxiety
disorder to ZOLOFT. Care and
prudent medical judgment
should be exercised when switching, particularly from long-acting agents.
The duration of an
appropriate washout
period which should intervene
before switching from one selective
serotonin reuptake
inhibitor (SSRI) to another
has not been established.
Monoamine Oxidase Inhibitors¾See
CONTRAINDICATIONS and
WARNINGS.
Drugs Metabolized by P450 3A4¾In three separate
in vivo interaction studies, sertraline was co-administered with
cytochrome P450 3A4
substrates, terfenadine, carbamazepine, or cisapride under steady-state
conditions. The results of these studies indicated that sertraline did not
increase plasma concentrations
of terfenadine, carbamazepine, or cisapride. These data indicate that
sertraline’s extent of
inhibition of P450 3A4 activity is not likely to be of
clinical significance.
Results of the interaction study with
cisapride indicate that
sertraline 200 mg (q.d.) induces
the metabolism of cisapride
(cisapride AUC and Cmax were
reduced by about 35%).
Drugs Metabolized by P450 2D6¾Many
drugs effective in the treatment
of major depressive disorder, e.g., the SSRIs, including sertraline, and
most tricyclic
antidepressant drugs effective in the treatment of major depressive
disorder inhibit the
biochemical
activity of the
drug metabolizing
isozyme
cytochrome P450 2D6 (debrisoquin
hydroxylase), and, thus, may increase the
plasma concentrations of
co-administered drugs that are metabolized by P450 2D6. The drugs for which
this potential interaction
is of greatest concern are those metabolized primarily by 2D6 and which have
a narrow therapeutic
index, e.g., the tricyclic
antidepressant drugs effective in the
treatment of major
depressive disorder and the
Type 1C antiarrhythmics propafenone and flecainide. The extent to which this
interaction is an important
clinical problem depends on the extent of the
inhibition of P450 2D6 by
the antidepressant and
the therapeutic index of the
co-administered drug. There is
variability among the drugs effective in the
treatment of major
depressive disorder in the
extent of clinically important 2D6 inhibition, and in fact sertraline at
lower doses has a less prominent inhibitory
effect on 2D6 than some others
in the class. Nevertheless, even sertraline has the
potential for clinically
important 2D6 inhibition. Consequently, concomitant use of a
drug metabolized by P450 2D6 with
ZOLOFT may require lower doses than usually prescribed for the other drug.
Furthermore, whenever ZOLOFT is withdrawn from co-therapy, an increased
dose of the co-administered
drug may be required (see
Tricyclic Antidepressant Drugs Effective in the Treatment of Major
Depressive Disorder under
PRECAUTIONS).
Sumatriptan¾There have been rare postmarketing
reports describing patients with weakness, hyperreflexia, and incoordination
following the use of a selective
serotonin reuptake inhibitor
(SSRI) and sumatriptan. If
concomitant treatment
with sumatriptan and an SSRI (e.g., citalopram, fluoxetine, fluvoxamine,
paroxetine, sertraline) is clinically warranted,
appropriate observation of
the patient is advised.
Tricyclic Antidepressant Drugs Effective in the
Treatment of Major Depressive Disorder (TCAs)¾The
extent to which SSRI¾TCA interactions may pose
clinical problems
will depend on the
degree of inhibition and the
pharmacokinetics of
the SSRI involved. Nevertheless, caution is indicated in the
co-administration of TCAs with ZOLOFT, because sertraline may inhibit TCA
metabolism. Plasma TCA concentrations may
need to be monitored, and the
dose of TCA may
need to be reduced, if a TCA is
co-administered with ZOLOFT (see Drugs Metabolized by P450 2D6 under
PRECAUTIONS).
Hypoglycemic Drugs¾In a placebo-controlled trial in
normal volunteers,
administration of
ZOLOFT for 22 days (including 200 mg/day for the final 13 days) caused a
statistically significant
16% decrease from baseline in
the clearance of
tolbutamide following an
intravenous 1000
mg dose. ZOLOFT
administration did not
noticeably change either the plasma
protein binding or the apparent
volume of
distribution of
tolbutamide, suggesting that the decreased
clearance was due to a
change in the metabolism of
the drug. The clinical
significance of this decrease in
tolbutamide
clearance is unknown.
Atenolol¾ZOLOFT (100 mg) when administered to 10
healthy
male subjects had no
effect on the beta-adrenergic
blocking ability of atenolol.
Digoxin¾In a placebo-controlled trial in
normal volunteers,
administration of
ZOLOFT for 17 days (including 200 mg/day for the last 10 days) did not
change serum
digoxin levels or
digoxin
renal clearance.
Microsomal Enzyme Induction¾Preclinical studies
have shown ZOLOFT to induce
hepatic microsomal enzymes. In
clinical studies, ZOLOFT was shown to induce
hepatic enzymes minimally as
determined by a small (5%) but statistically
significant decrease in
antipyrine half-life following
administration of 200
mg/day for 21 days. This small change in antipyrine
half-life reflects a
clinically insignificant change in
hepatic metabolism.
Drugs That Interfere With Hemostasis (Non-selective
NSAIDs, Aspirin, Warfarin, etc.)
Serotonin
release by platelets plays an important
role in hemostasis.
Epidemiological studies of the case-control and
cohort design that have
demonstrated an association between the use of psychotropic drugs that
interfere with serotonin
reuptake and the occurrence of upper
gastrointestinal
bleeding have also shown that
concurrent use of a non-selective
NSAID (i.e., NSAIDs that inhibit both cyclooxygenase isoenzymes, COX 1
and 2) or aspirin potentiated
the risk of bleeding. Thus,
patients should be cautioned about the use of such drugs concurrently with
ZOLOFT.
Electroconvulsive Therapy¾There are no
clinical studies establishing
the risks or benefits of the combined use of electroconvulsive
therapy (ECT) and ZOLOFT.
Alcohol¾Although ZOLOFT did not potentiate the
cognitive and psychomotor
effects of alcohol in
experiments with normal subjects, the
concomitant use of ZOLOFT
and alcohol is not
recommended.
|
Drug monograph
Contents
ZOLOFT Pfizer
Sertraline HCI
Use:
SSRI. Depression: Patients > 18 years of age: Initially, 50 mg once daily;
increase dosage gradually, if needed, at 1-week intervals. Maximum: 200
mg/day. Maintenance: lowest effective dose.
Panic disorder: 25 mg once daily and increase, if
necessary, by 50 mg increments at intervals of no less than 1 week, to a
maximum of 200 mg/day.
Obsessive-compulsive disorder (OCD): Initially, 50
mg/day. Thereafter, increase the dosage, if necessary, by 50 mg increments,
over several weeks or months, to a maximum of 200 mg/day.
Zoloft's effectiveness for more than 12 weeks of
therapy in panic disorder and OCD not yet established.
Contraindications:
Not to be use with an MAOI or within 14 days of starting or discontinuing
MAOI therapy. Concomitant use with pimozide.
Precautions:
Pregnancy, lactation, patients< 18 years of age. Seizure disorders, a
history of drug abuse, renal or hepatic impairment. Activation of
mania/hypomania, suicidal tendency, concomitant illnesses that could affect
metabolism or hemodynamic responses. Rare reports of altered platelet
function; hyponatremia, possibly due to the syndrome of inappropriate
antidiuretic hormone secretion.
Side effects:
Nausea, diarrhea/loose stools, dyspepsia, male sexual dysfunction (primarily
ejaculatory delay), insomnia, somnolence, tremor, increased sweating, dry
mouth, dizziness.
Interactions:
See Contraindications. Use cautiously with CNS-active drugs; serotonergic
drugs, such as fenfluramine, should not be used with sertraline.
Hypoglycemic agents, drugs highly bound to plasma proteins, cimetidine (may
decrease clearance of sertraline). Warfarin (monitor PT). St. John's Wort
(increase in undesirable effects).
Patient tips:
Full therapeutic effect may be delayed until 4 or more weeks of treatment.
Take capsules with food once daily, preferably with evening meal or
breakfast. May cause dizziness (NB driving). Restrict alcohol intake.
Supplied:
25 mg, 50 mg, 100mg capsules.
to top
Antidepressant
The antidepressant effect of sertraline is presumed
to be linked to its ability to inhibit the neuronal reuptake of serotonin.
It has only very weak effects on norepinephrine and dopamine neuronal
reuptake. At clinical doses, sertraline blocks the uptake of serotonin into
human platelets.
Like most clinically effective antidepressants,
sertraline downregulates brain norepinephrine and serotonin receptors in
animals. In receptor binding studies, sertraline has no significant affinity
for adrenergic (alpha(1), alpha(2) and beta), cholinergic, GABA,
dopaminergic, histaminergic, serotonergic (5-HT1A, 5-HT1B, 5-HT2) or
benzodiazepine binding sites.
In placebo-controlled studies in normal volunteers,
sertraline did not cause sedation and did not interfere with psychomotor
performance.
Pharmacokinetics:
Following multiple oral once-daily doses of 200 mg, the mean peak plasma
concentration (C(max)) of sertraline is 0.19 mcg/mL occurring between 6 to 8
hours post-dose. The area under the plasma concentration time is 2.8 mg
hr/L. For desmethylsertraline, C(max) is 0.14 mcg/mL, the half-life 65 hours
and the area under the curve 2.3 mg hr/L. Following single or multiple oral
once-daily doses of 50 to 400 mg/day the average terminal elimination
half-life is approximately 26 hours. Linear dose proportionality has been
demonstrated over the clinical dose range of 50 to 200 mg/day.
Food appears to increase the bioavailability by
about 40%: it is recommended that sertraline be administered with meals.
Sertraline is extensively metabolized to N-desmethylsertraline,
which shows negligible pharmacological activity. Both sertraline and N-desmethylsertraline
undergo oxidative deamination and subsequent reduction, hydroxylation and
glucuronide conjugation. Biliary excretion of metabolites is significant.
Approximately 98% of sertraline is plasma protein
bound. The interactions between sertraline and other highly protein bound
drugs have not been fully evaluated (see Precautions).
The pharmacokinetics of sertraline itself appear to
be similar in young and elderly subjects. Plasma levels of N-desmethylsertraline
show a 3-fold elevation in the elderly following multiple dosing, however,
the clinical significance of this observation is not known.
Liver and Renal Disease:
The pharmacokinetics of sertraline in patients with significant hepatic or
renal dysfunction have not been determined.
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For the symptomatic relief of depressive illness.
However, the antidepressant action of sertraline in hospitalized depressed
patients has not been adequately studied.
A placebo-controlled European study carried out
over 44 weeks, in patients who were responders to sertraline has indicated
that sertraline may be useful in continuation treatment, suppressing
reemergence of depressive symptoms.
However, because of methodological limitations,
these findings on continuation treatment have to be considered tentative at
this time.
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Patients with known hypersensitivity to the drug.
No clinical data are available on the effects of
the combined use of sertraline and MAO inhibitors; therefore, sertraline
should not be administered together with MAO inhibitors. At least 14 days
should elapse between the discontinuation of an MAO inhibitor and the
initiation of treatment with sertraline, as well as between the
discontinuation of sertraline and the initiation of treatment with an MAO
inhibitor. Administration at shorter intervals may increase the risk of
serious events.
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None.
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Activation of
Mania/Hypomania:
During clinical testing in depressed patients, hypomania or mania occurred
in approximately 0.6% of sertraline-treated patients. Activation of
mania/hypomania has also been reported in a small proportion of patients
with Major Affective Disorder treated with other marketed antidepressants.
Seizure:
Sertraline has not been evaluated in patients with seizure disorders. These
patients were excluded from clinical studies during the product's premarket
testing. Accordingly, sertraline should be introduced with care in epileptic
patients.
Suicide:
The possibility of a suicide attempt is inherent in depression and may
persist until significant remission occurs. Therefore, high risk patients
should be closely supervised throughout therapy and consideration should be
given to the possible need for hospitalization. In order to minimize the
opportunity for overdosage, prescriptions for sertraline should be written
for the smallest quantity of drug consistent with good patient management.
Occupational Hazards:
Any psychoactive drug may impair judgment, thinking, or motor skills, and
patients should be advised to avoid driving a car or operating hazardous
machinery until they are reasonably certain that the drug treatment does not
affect them adversely.
Patients with Concomitant
Illness:
General:
Clinical experience with sertraline in patients with certain concomitant
systemic illnesses is limited. Caution is advisable in using sertraline in
patients with diseases or conditions that could affect metabolism or
hemodynamic responses.
Cardiac Disease:
Sertraline has not been evaluated or used to any appreciable extent in
patients with a recent history of myocardial infarction or unstable heart
disease.
The electrocardiograms of 598 patients who received
sertraline were compared in a blinded fashion to the electrocardiograms of
244 placebo patients and 206 amitriptyline patients. The data indicate that
sertraline is not associated with the development of significant ECG
abnormalities.
Effect on Blood Pressure:
The frequency of clinically noticeable changes (+/-15 to 20 mm Hg) in blood
pressure in placebo controlled studies was similar for patients being
treated with sertraline or placebo (see Table I).
----------------------------------------------------------------------
Table I
Percentage of Patients with Noticeable Changes in Blood Pressure
----------------------------------------------------------------------
Change Numbers and % of Patients
Relative to Numbers Tested with Specified Change
Parameter Baseline Sertraline Placebo Sertraline Placebo
----------------------------------------------------------------------
Standing increase 703 358 13 1.8% 3 0.8%
Systolic BP decrease 31 4.4% 16 4.5%
Standing increase 703 358 20 2.8% 13 3.6%
Diastolic BP decrease 28 4.0% 12 3.4%
Supine increase 706 362 15 2.1% 6 1.7%
Systolic BP decrease 19 2.7% 7 1.9%
Supine increase 706 362 16 2.3% 7 1.9%
Diastolic BP decrease 18 2.5% 4 1.1%
----------------------------------------------------------------------
Hepatic Dysfunction:
Sertraline is extensively metabolized by the liver. The pharmacokinetics and
therapeutic efficacy of sertraline have not been studied in patients with
significant hepatic dysfunction. Accordingly, it should be used with caution
in such patients.
Renal Dysfunction:
Sertraline is extensively metabolized and excretion of unchanged drug in the
urine is a minor route of elimination. The pharmacokinetics of sertraline
have not been studied in patients with renal impairment and, until adequate
numbers of patients with mild, moderate or severe renal impairment have been
evaluated during chronic treatment with sertraline, it should be used with
caution in such patients.
Carcinogenesis:
In carcinogenicity studies in CD-1 mice, sertraline at doses up to 40 mg/kg
produces a dose related increase in the incidence of liver adenomas in male
mice. Liver adenomas have a very variable rate of spontaneous occurrence in
the CD-1 mouse. The clinical significance of these findings is unknown.
Pregnancy and Lactation:
The safety of sertraline during pregnancy and lactation has not been
established and therefore, it should not be used in women of childbearing
potential or nursing mothers, unless, in the opinion of the physician, the
potential benefits to the patient outweigh the possible hazards to the
fetus.
Labor and Delivery:
The effect of sertraline on labor and delivery in humans is unknown.
Children:
The safety and effectiveness of sertraline in children below the age of 18
have not been established.
Geriatrics:
462 elderly patients (>=65 years) have participated in multiple dose
therapeutic studies with sertraline. The pattern of adverse reactions in the
elderly was comparable to that in younger patients.
Drug Interactions:
Co-Administration of Drugs Highly Bound to Plasma Proteins:
Because sertraline is highly bound to plasma proteins, the co-administration
of other highly bound drugs such as warfarin or digitoxin may cause a shift
in plasma concentrations potentially resulting in adverse effects. At this
time, the effect of sertraline on the anticoagulant activity of warfarin is
unknown. Accordingly, prothrombin time should be carefully monitored when
sertraline therapy is initiated or discontinued. Conversely, adverse effects
may result from displacement of protein bound sertraline by other tightly
bound drugs.
CNS Active Drugs:
The risk of using sertraline in combination with other CNS active drugs has
not been systematically evaluated. Consequently, caution is advised if the
concomitant administration of sertraline and such drugs is required.
Co-administration with tryptophan may lead to a
high incidence of serotonin-associated side effects. There is no experience
with the concomitant use of sertraline and tryptophan in depressed patients.
In placebo-controlled trials in normal volunteers,
the combined administration of lithium and sertraline did not alter the
pharmacokinetics of sertraline. There is, however, no clinical experience
with sertraline in lithium treated patients. Therefore, it is recommended
that plasma lithium levels be monitored following initiation of sertraline
therapy, so that appropriate adjustments to the lithium dose may be made if
necessary. Co-administration with lithium may lead to a high incidence of
serotonin-associated side effects.
Electroconvulsive
Therapy:
There are no clinical studies with the combined use of electroconvulsive
therapy (ECT) and sertraline.
Alcohol:
Although sertraline did not potentiate the cognitive and psychomotor effects
of alcohol in experiments with normal subjects, the concomitant use of
sertraline and alcohol in depressed patients has not been studied and is not
recommended.
Hypoglycemic Drugs:
There are no controlled clinical trials with sertraline in diabetic patients
treated with insulin or oral hypoglycemic drugs.
In a placebo-controlled trial in normal volunteers,
the administration of sertraline for 22 days (dose was 200 mg/day for the
final 13 days), caused a statistically significant 16% decrease in the
clearance of tolbutamide following an i.v. dose of 1000 mg.
Hypoglycemia requiring dextrose infusion was
observed in one patient treated with sertraline, glibenclamide, haloperidol,
bisacodyl, ASA and flucloxacillin. The causal relationship to sertraline
treatment was not firmly established. Nevertheless, close monitoring of
glycemia in patients treated with sertraline and oral hypoglycemic drugs or
insulin is recommended.
Beta Blockers:
There is no experience with the use of sertraline in hypertensive patients
controlled by beta-blockers. In a placebo-controlled crossover study in
normal volunteers, the effect of sertraline on the beta-adrenergic blocking
activity of atenolol was assessed. The mean CD25's (the doses of
isoproterenol required to increase heart rate by 25 bpm, the chronotropic
dose 25 or CD25) and the average decreases in heart rate seen with atenolol
during exercise test were not statistically different in the sertraline
versus the placebo group. These data suggest that sertraline does not alter
the beta-blocking action of atenolol.
Cimetidine:
In a placebo-controlled crossover study in normal volunteers, the potential
of cimetidine to alter the disposition of a single 100 mg dose of sertraline
was assessed. The mean sertraline C(max) and AUC were significantly higher
in the cimetidine-treated group, as were the mean desmethylsertraline T(max)
and AUC. These data suggest that concomitant administration of cimetidine
may inhibit the metabolism of sertraline and its metabolite,
desmethylsertraline, and may result in a decrease in the clearance and first
pass metabolism of sertraline, with a possible increase in drug-related side
effects.
Microsomal Enzyme
Induction:
Sertraline was shown to induce hepatic enzymes as determined by the decrease
of the antipyrine half-life. This degree of induction reflects a clinically
insignificant change in hepatic metabolism.
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In clinical development programs, sertraline has
been evaluated in 1902 subjects with depression. The most commonly observed
adverse events associated with the use of sertraline were: gastrointestinal
complaints, including nausea, diarrhea/loose stools and dyspepsia; male
sexual dysfunction (primarily ejaculatory delay); insomnia and somnolence;
tremor; increased sweating and dry mouth; and dizziness. In the fixed dose
placebo controlled study, the overall incidence of side effects was dose
related with a majority occurring in the patients treated with 200 mg dose.
The discontinuation rate due to adverse events was
15% in 2710 subjects who received sertraline in premarketing multiple dose
clinical trials. The more common events (reported by at least 1% of
subjects) associated with discontinuation included agitation, insomnia, male
sexual dysfunction (primarily ejaculatory delay), somnolence, dizziness,
headache, tremor, anorexia, diarrhea/loose stools, nausea and fatigue.
Incidence in Controlled
Clinical Trials:
Table II enumerates adverse events that occurred at a frequency of 1% or
more among sertraline patients who participated in controlled trials
comparing titrated sertraline with placebo.
-----------------------------------------------------------------
Table II
Treatment-Emergent Adverse Experience Incidence in
Placebo-Controlled Clinical Trials*
-----------------------------------------------------------------
Percent of Patients Reporting
Zoloft Placebo Difference
Adverse Experience (N=861) (N=853) Percentage
Autonomic Nervous System Disorders
Mouth Dry 16.3 9.3 7.0
Sweating Increased 8.4 2.9 5.5
Cardiovascular
Palpitations 3.5 1.6 1.9
Chest Pain 1.0 1.6 -0.6
Central and Peripheral Nervous System Disorders
Headache 20.3 19.0 1.3
Dizziness 11.7 6.7 5.0
Tremor 10.7 2.7 8.0
Paresthesia 2.0 1.8 0.2
Hypoesthesia 1.7 0.6 1.1
Twitching 1.4 0.1 1.3
Hypertonia 1.3 0.4 0.9
Disorders of Skin and Appendages
Rash 2.1 1.5 0.6
Gastrointestinal Disorders
Nausea 26.1 11.8 14.3
Diarrhea/Loose Stools 17.7 9.3 8.4
Constipation 8.4 6.3 2.1
Dyspepsia 6.0 2.8 3.2
Vomiting 3.8 1.8 2.0
Flatulence 3.3 2.5 0.8
Anorexia 2.8 1.6 1.2
Abdominal Pain 2.4 2.2 0.2
Appetite Increased 1.3 0.9 0.4
General
Fatigue 10.6 8.1 2.5
Hot Flushes 2.2 0.5 1.7
Fever 1.6 0.6 1.0
Back Pain 1.5 0.9 0.6
Metabolic and Nutritional Disorders
Thirst 1.4 0.9 0.5
Musculo-Skeletal System Disorders
Myalgia 1.7 1.5 0.2
Psychiatric Disorders
Insomnia 16.4 8.8 7.6
Sexual Dysfunction-
Male (1) 15.5 2.2 13.3
Somnolence 13.4 5.9 7.5
Agitation 5.6 4.0 1.6
Nervousness 3.4 1.9 1.5
Anxiety 2.6 1.3 1.3
Yawning 1.9 0.2 1.7
Sexual Dysfunction-
Female (2) 1.7 0.2 1.5
Concentration Impaired 1.3 0.5 0.8
Reproduction
Menstrual Disorder (2) 1.0 0.5 0.5
Respiratory System Disorders
Rhinitis 2.0 1.5 0.5
Pharyngitis 1.2 0.9 0.3
pecial Senses
Vision Abnormal 4.2 2.1 2.1
Tinnitus 1.4 1.1 0.3
Taste Perversion 1.2 0.7 0.5
Urinary System Disorders
Micturition Frequency 2.0 1.2 0.8
Micturition Disorder 1.4 0.5 0.9
-----------------------------------------------------------------
*Events reported by at least 1% of patients treated with
Zoloft are included.
(1)% based on male patients only: 271 Zoloft and 271 placebo
patients. Male sexual dysfunction can be broken down into
the categories of decreased libido, impotence and ejaculatory
delay. In this data set, the percentages of males in the
Zoloft group with these complaints are 4.8%, 4.8% and 8.9%,
respectively. It should be noted that since some Zoloft
patients reported more than one category of male sexual
dysfunction, the incidence of each category of male sexual
dysfunction combined is larger than the incidence for the
general category of male sexual dysfunction, in which each
patient is counted only once.
(2)% based on female patient only: 590 Zoloft and 582 placebo
patients.
-----------------------------------------------------------------
Other events observed during the premarketing
evaluation of sertraline:
During its premarketing assessment, multiple doses of sertraline were
administered to 2710 subjects. The conditions and duration of exposure to
sertraline varied greatly, and included (in overlapping categories) clinical
pharmacology studies, open and double-blind studies, uncontrolled and
controlled studies, inpatient and outpatient studies, fixed-dose and
titration studies, and studies for indications other than depression.
Untoward events associated with this exposure were recorded by clinical
investigators using terminology of their own choosing. Consequently, it is
not possible to provide a meaningful estimate of the proportion of
individuals experiencing adverse events without first grouping similar types
of untoward events into a smaller number of standardized event categories.
All events are included except those already listed
in Table II or in the Precautions section, and those reported in terms so
general as to be uninformative. It is important to emphasize that although
the events reported occurred during treatment with sertraline, they were not
necessarily caused by it.
Autonomic Nervous System
Disorders:
Infrequent: Flushing, mydriasis, increased saliva, cold clammy skin. Rare:
Pallor.
Cardiovascular:
Infrequent: Postural dizziness, hypertension, hypotension, postural
hypotension, edema, dependent edema, periorbital edema, peripheral edema,
peripheral ischemia, syncope, tachycardia. Rare: Precordial chest pain,
substernal chest pain, aggravated hypertension, myocardial infarction,
varicose veins.
Central and Peripheral
Nervous System Disorders:
Frequent: Confusion. Infrequent: Ataxia, abnormal coordination, abnormal
gait, hyperesthesia, hyperkinesia, hypokinesia, migraine, nystagmus,
vertigo. Rare: Local anesthesia, coma, convulsions, dyskinesia, dysphonia,
hyporeflexia, hypotonia, ptosis.
Disorders of Skin and
Appendages:
Infrequent: Acne, alopecia, pruritus, erythematous rash, maculopapular rash,
dry skin. Rare: Bullous eruption, dermatitis, erythema multiforme, abnormal
hair texture, hypertrichosis, photosensitivity reaction, follicular rash,
skin discoloration, abnormal skin odor, urticaria.
Endocrine Disorders:
Rare: Exophthalmos, gynecomastia.
Gastrointestinal
Disorders:
Infrequent: Dysphagia, eructation. Rare: Diverticulitis, fecal incontinence,
gastritis, gastroenteritis, glossitis, gum hyperplasia, hemorrhoids, hiccup,
melena, hemorrhagic peptic ulcer, proctitis, stomatitis, ulcerative
stomatitis, tenesmus, tongue edema, tongue ulceration.
General:
Frequent: Asthenia. Infrequent: Malaise, generalized edema, rigors, weight
decrease, weight increase. Rare: Enlarged abdomen, halitosis, otitis media,
aphthous stomatitis.
Hematopoietic and
Lymphatic:
Infrequent: Lymphadenopathy, purpura. Rare: Anemia, anterior chamber eye
hemorrhage.
Metabolic and Nutritional
Disorders:
Rare: Dehydration, hypercholesterolemia, hypoglycemia.
Musculo-Skeletal System
Disorders:
Infrequent: Arthralgia, arthrosis, dystonia, muscle cramps, muscle weakness.
Rare: Hernia.
Psychiatric Disorders:
Infrequent: Abnormal dreams, aggressive reaction, amnesia, apathy, delusion,
depersonalization, depression, aggravated depression, emotional lability,
euphoria, hallucination, neurosis, paranoid reaction, suicide attempt
(including suicidal ideation), teeth-grinding, abnormal thinking. Rare:
Hysteria, somnambulism withdrawal syndrome.
Reproductive:
Infrequent: Dysmenorrhea (2), intermenstrual bleeding (2). Rare: Amenorrhea
(2), balanoposthitis (1), breast enlargement (2), female breast pain (2),
leukorrhea (2), menorrhagia (2), atrophic vaginitis (2).
(1) - % based on male subjects only: 1005
(2) - % based on female subjects only: 1705
Respiratory System
Disorders:
Infrequent: Bronchospasm, coughing, dyspnea, epistaxis. Rare: Bradypnea,
hyperventilation, sinusitis, stridor.
Special Senses:
Infrequent: Abnormal accommodation, conjunctivitis, diplopia, earache, eye
pain, xerophthalmia. Rare: Abnormal lacrimation, photophobia, visual field
defect.
Urinary System Disorders:
Infrequent: Dysuria, face edema, nocturia, polyuria, urinary incontinence.
Rare: Oliguria, renal pain, urinary retention.
Laboratory Tests:
In man, asymptomatic elevations in serum hepatic transaminases [AST (SGOT)
and ALT (SGPT)] to a value >=3 times the upper limit of normal have been
reported infrequently (approximately 0.6% and 1.1%, respectively) in
association with sertraline administration. The proportion of patients
having these elevations was greater in the sertraline group than in the
placebo group. These hepatic enzyme elevations usually occurred within the
first 1 to 9 weeks of drug treatment and promptly diminished upon drug
discontinuation.
Sertraline therapy was associated with small mean
increases in total cholesterol (approximately 3%) and triglycerides
(approximately 5%), and a small mean decrease in serum uric acid
(approximately 7%) of no apparent clinical importance.
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Symptoms and Treatment:
Human Experience:
There have been 3 cases of sertraline overdosage (approximately 4 to 10
times the maximum recommended daily dose). These 3 patients recovered
completely without the need for specific therapy.
Management of Overdoses:
Establish and maintain an airway, insure adequate oxygenation and
ventilation. Activated charcoal, which may be used with sorbitol, may be as
or more effective than emesis or lavage, and should be considered in
treating overdose.
Cardiac and vital signs monitoring are recommended
along with general symptomatic and supportive measures.
There are no specific antidotes for sertraline.
Due to the large volume of distribution of
sertraline, forced diuresis, dialysis, hemoperfusion, and exchange
transfusion are unlikely to be of benefit.
In managing overdose, the possibility of multiple
drug involvement must be considered.
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The administration should be initiated at 50 mg
daily and increased gradually if needed, noting carefully the clinical
response and any evidence of intolerance. It should be kept in mind that
there may be a lag in therapeutic response. Increasing the dosage rapidly
does not normally shorten this latent period and may increase the incidence
of side effects.
Initial Treatment:
As no clear dose-response relationship has been demonstrated, a dose of 50
mg/day is recommended as the initial dose. A gradual increase in dosage may
be considered if no clinical improvement is observed. Based on
pharmacokinetic parameters, steady-state sertraline plasma levels are
achieved after approximately 1 week of once daily dosing; accordingly, dose
changes, if necessary, should be made at intervals of at least 1 week. Doses
should not exceed a maximum of 200 mg/day.
As with other antidepressants, the full
antidepressant effect may be delayed until 4 weeks of treatment or longer.
Sertraline should be administered with food once
daily preferably with the evening meal, or, if administration in the
morining is desired, with breakfast.
As with many other medications, sertraline should
be used with caution in patients with renal and/or hepatic impairment (see
Precautions).
Maintenance:
When a satisfactory clinical response has been obtained, the dosage should
be reduced (within the 50 to 200 mg range) to the minimum that will maintain
relief of symptoms.
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50 mg:
Each white and yellow capsule contains: Sertraline HCl 50 mg. Nonmedicinal
ingredients: Cornstarch; lactose, anhydrous; magnesium stearate; sodium
lauryl sulfate. Capsule shells contain gelatin, silicon dioxide, sodium
lauryl sulfate, methyl and propylparabens, titanium dioxide, dye D & C
Yellow #10, and dye FD & C Yellow #6. Tartrazine-free. White high density
polyethylene botles of 100 and 250.
100 mg:
Each orange capsule contains: Sertraline HCl 100 mg. Nonmedicinal
ingredients: Cornstarch; lactose, anhydrous; magnesium stearate; sodium
lauryl sulfate. Capsule shells contain gelatin, silicon dioxide, sodium
lauryl sulfate, methyl- and propylparabens, titanium dioxide, dye D&C Yellow
#10 and dye FD&C Red #40. Tartrazine-free. White high density polyethylene
bottles of 100.
Store at controlled room temperature between 15 and
30°C.
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|
Zoloft
Generic Name: sertraline (SER tra leen)
What is the most important information I should
know about Zoloft?
You may have an increased risk of suicidal
thoughts or behavior at the start of treatment with an antidepressant
medication, especially if you are under 18 years old. Talk with your doctor
about this risk. While you are taking Zoloft you will need to be monitored for
worsening
symptoms of depression and/or suicidal thoughts during the first weeks of
treatment, or whenever your dose is changed. In addition to you watching for
changes in your own symptoms, your family or other caregivers should be alert to
changes in your mood or symptoms. Your doctor will need to check you at regular
visits for at least the first 12 weeks of treatment.
Contact your doctor promptly if you have any of the
following side effects, especially if they are new symptoms or if they get
worse: mood changes, anxiety, panic attacks, trouble sleeping, irritability,
agitation, aggressiveness, severe restlessness, mania (mental and/or physical
hyperactivity), thoughts of suicide or hurting yourself. Do not take Zoloft
together with pimozide (Orap), or a monoamine oxidase inhibitor (MAOI) such as
isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl,
Emsam), or tranylcypromine (Parnate). You must wait at least 14 days after
stopping an MAOI before you can take Zoloft. After you stop taking Zoloft, you
must wait at least 14 days before you start taking an MAOI. SSRI antidepressants
may cause serious or life-threatening lung problems in newborn babies whose
mothers take the medication during pregnancy. However, you may have a relapse of
depression if you stop taking your antidepressant during pregnancy. If you are
planning a pregnancy, or if you
become pregnant while taking Zoloft, do not stop taking the medication
without first talking to your doctor.
What is Zoloft?
Zoloft is an antidepressant in a group of drugs
called
selective serotonin reuptake inhibitors (SSRIs). Zoloft affects chemicals
in the brain that may become unbalanced and cause depression, panic, anxiety, or
obsessive-compulsive symptoms.
Zoloft is used to treat depression,
obsessive-compulsive disorder,
panic disorder, anxiety disorders, post-traumatic stress disorder (PTSD),
and premenstrual dysphoric disorder (PMDD).
Zoloft may also be used for purposes other than
those listed in this medication guide.
What should I discuss with my healthcare
provider before taking Zoloft?
You may have an increased risk of suicidal
thoughts or behavior at the start of treatment with an
antidepressant medication, especially if you are under 18 years old. Talk
with your doctor about this risk. While you are taking Zoloft you will need to
be monitored for worsening symptoms of depression and/or suicidal thoughts
during the first weeks of treatment, or whenever your dose is changed. In
addition to you watching for changes in your own symptoms, your family or other
caregivers should be alert to changes in your mood or symptoms. Your doctor will
need to check you at regular visits for at least the first 12 weeks.
Do not use Zoloft if you are using pimozide (Orap), or
an MAO inhibitor such as isocarboxazid (Marplan), tranylcypromine (Parnate),
phenelzine (Nardil), rasagiline (Azilect), or selegiline (Eldepryl, Emsam).
Serious and sometimes fatal reactions can occur when these medicines are taken
with Zoloft. You must wait at least 14 days after stopping an MAO inhibitor
before you can take Zoloft. After you stop taking Zoloft, you must wait at least
14 days before you start taking an MAOI.
Before taking Zoloft, tell your doctor if you
have:
If you have any of these conditions, you may
not be able to use Zoloft, or you may need a dosage adjustment or special tests.
FDA pregnancy category C. SSRI antidepressants may
cause serious or life-threatening lung problems in
newborn babies whose mothers take the medication during pregnancy.
However, you may have a relapse of depression if you stop taking your
antidepressant during pregnancy. If you are planning a pregnancy, or if you
become pregnant while taking Zoloft, do not stop taking the medication without
first talking to your doctor. It is not known whether Zoloft passes into breast
milk or if it could harm a nursing baby. Do not use this medication without
telling your doctor if you are breast-feeding a baby.
How should I take Zoloft?
Take this medication exactly as it was
prescribed for you. Do not take the medication in larger amounts, or take it for
longer than recommended by your doctor. Your doctor may occasionally change your
dose to make sure you get the best results from the medication.
Take each tablet with water.
Zoloft may be taken with or without food.
Try to take the medicine at the same time each
day. Follow the directions on your prescription label.
The oral liquid form of this medicine must be
diluted before you take it. To be sure you get the correct dose, measure the
liquid with medicine dropper provided, not with a regular table spoon. Mix the
dose with 4 ounces (one-half cup) of water, ginger ale, lemon/lime soda,
lemonade, or orange juice. Do not use any other liquids to dilute the medicine.
Stir this mixture and drink all of it right away. To make sure you get the
entire dose, add a little more water to the same glass, swirl gently and drink
right away.
It may take 4 weeks or longer before you start feeling
better. Do not stop using Zoloft without first talking to your doctor. You may
have unpleasant side effects if you stop taking this medication suddenly. Store
Zoloft at room temperature away from moisture and heat.
What happens if I miss a dose of Zoloft?
Take the missed dose as soon as you remember.
However, if it is almost time for the next regularly scheduled dose, skip the
missed dose and take the next one as directed. Do not take extra medicine to
make up the missed dose.
What happens if I overdose with Zoloft?
Seek emergency medical attention if you think you have
taken too much of this medication. Symptoms of a Zoloft overdose may include
dizziness, drowsiness, nausea, vomiting, rapid heartbeat, agitation, tremor,
confusion, seizures, and coma.
What should I avoid while taking Zoloft?
Avoid drinking alcohol, which can increase some of the
side effects of Zoloft.
Do not take the liquid form of Zoloft if you
are taking disulfiram (Antabuse). Liquid Zoloft may contain alcohol and you
could have a severe reaction to the disulfiram.
Avoid using other medicines that make you
sleepy (such as cold medicine,
pain medication, muscle relaxers, medicine for seizures, other medication
for depression or anxiety). They can add to sleepiness caused by Zoloft.
Zoloft can cause side effects that may impair your
thinking or reactions. Be careful if you drive or do anything that requires you
to be awake and alert.
What are the possible side effects of Zoloft?
Get emergency medical help if you have any of these
signs of an
allergic reaction: skin rash or hives; difficulty breathing; swelling of
your face, lips, tongue, or throat. Contact your doctor promptly if you have any
of the following side effects, especially if they are new symptoms or if they
get worse: mood changes, anxiety, panic attacks, trouble sleeping, irritability,
agitation, aggressiveness, severe restlessness, mania (mental and/or physical
hyperactivity), thoughts of suicide or hurting yourself.
Call your doctor at once if you have any of
these serious side effects:
- seizure (convulsions);
-
tremors, shivering, muscle stiffness or
twitching;
-
problems with balance or coordination; or
-
agitation, confusion, sweating, fast
heartbeat.
Other less serious side effects are more likely
to occur, such as:
-
feeling nervous, restless, or unable to sit
still;
-
drowsiness, dizziness, weakness;
- sleep problems (insomnia);
-
nausea, diarrhea, dry mouth, or changes in
appetite or weight; or
-
decreased sex drive, impotence, or difficulty
having an orgasm.
Side effects other than those listed here may
also occur. Talk to your doctor about any side effect that seems unusual or that
is especially bothersome.
What other drugs will affect Zoloft?
Talk to your doctor before taking any medicine
for pain, arthritis, fever, or swelling. This includes aspirin, ibuprofen
(Advil, Motrin), naproxen (Aleve, Naprosyn), diclofenac (Voltaren), indomethacin,
piroxicam (Feldene), nabumetone (Relafen), etodolac (Lodine), and others. Taking
any of these drugs with Zoloft may cause you to bruise or bleed easily.
Before taking Zoloft, tell your doctor if you
are using any of the following medicines:
-
tramadol (Ultram, Ultram ER, Ultracet);
- digitoxin (Crystodigin);
-
phenytoin (Dilantin), valproate (Depacon,
Depakene);
- lithium (Lithobid, Eskalith);
-
a
blood thinner such as warfarin (Coumadin);
-
any other antidepressants such as
amitriptyline (Elavil), citalopram (Celexa), escitalopram (Lexapro),
fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), imipramine (Tofranil),
nortriptyline (Pamelor), or paroxetine (Paxil);
-
almotriptan (Axert), frovatriptan (Frova),
sumatriptan (Imitrex), naratriptan (Amerge), rizatriptan (Maxalt), or
zolmitriptan (Zomig); or
-
heart rhythm medication such as flecainide (Tambocor), propafenone (Rhythmol),
and others.
If you are using any of these drugs, you may
not be able to use Zoloft, or you may need dosage adjustments or special tests
during treatment.
There may be other drugs not listed that can
affect Zoloft. Tell your doctor about all the prescription and over-the-counter
medications you use. This includes vitamins, minerals, herbal products, and
drugs prescribed by other doctors. Do not start using a new medication without
telling your doctor.
Where can I get more information on Zoloft?
- Your pharmacist has additional information
about Zoloft written for health professionals that you may read.
What does my medication look like?
Sertraline is available with a prescription
under the brand name Zoloft. Other brand or generic formulations may also be
available. Ask your pharmacist any questions you have about this medication,
especially if it is new to you.
-
Zoloft 25 mg-capsule-shaped, green,
film-coated, scored tablets
-
Zoloft 50 mg--capsule-shaped, light-blue,
film-coated, scored tablets
-
Zoloft 100 mg--capsule-shaped, light-yellow,
film-coated, scored tablets
-
Zoloft Oral Concentrate 20 mg/mL-clear,
colorless solution with a menthol scent
|
Sertraline
From Wikipedia, the free
encyclopedia
"Lustral" redirects here. For the electronic music
band, see
Lustral (band).
Sertraline hydrochloride (also labeled under numerous
brand names: Zoloft, Sertralin, Lustral, Apo-Sertral, Asentra, Gladem, Serlift,
Stimuloton, Xydep, Serlain, Concorz) is a popular orally administered
antidepressant of the
selective serotonin reuptake inhibitor (SSRI) type. It was first approved
by the
Food and Drug Administration (FDA) in 1991.
[edit]
Invention
The invention of Sertraline has been attributed to
two scientists at Pfizer: Steve Werner and Billy Dzomba. At the time, the
notion that the neurotransmitter serotonin and depression might be linked was
a fairly new concept. Together, Werner and Dzomba explored a variety of
potential anti-depressant compounds and, within the space of one year,
developed Sertraline.[1]
[edit]
Indications
[edit]
Approved
Sertraline is used medically mainly to treat the
symptoms of
depression and
anxiety. It
is also prescribed for the treatment of
obsessive-compulsive disorder (OCD),[2]
post-traumatic stress disorder (PTSD),[3]
premenstrual dysphoric disorder (PMDD),[4]
panic disorder (PD)[5]
and
social phobia/social anxiety disorder.[6]
[edit]
Unapproved, off-label, and investigational
Sertraline can also be used in the treatment of
general anxiety disorder,[7]
binge eating disorder,[8]
and
premature ejaculation.[9]
There is also evidence that sertraline may be
effective in the treatment of refractory
neurocardiogenic syncope in children and
adolescents.[10]
A study has shown that sertraline is an effective
treatment for impulsive aggressive behavior in
personality disordered patients.[11]
[edit]
Side effects
Sertraline can have adverse effects, including: sleep
disorder (both
insomnia
and increased sleep time),
asthenia,
gastrointestinal complaints, tremors, weight gain, confusion, dizziness,
anorgasmia, nausea/vomiting,
bruxism,
mild
depersonalization, and decreased
libido.
Sertraline, like all of the other
SSRI drugs, can
increase anxiety and depression symptoms in the first few days/week of use.
These side effects generally go away as the body adjusts chemicals to adjust
to the drug. Sertraline can induce
mania or
hypomania
in around 0.5% of patients. It has also been known to cause minor weight loss.
It is
contraindicated in individuals taking
monoamine oxidase inhibitors (MAOIs) or undergoing
electroconvulsive therapy. Patients are advised to stop taking MAOIs for
at least 14 days before beginning a course of sertraline.[12]
Until 2003, sertraline was only approved for use in
adults ages 18 and over; that year it was approved by the FDA for use in
treating children ages 6 to 17 with extreme obsessive compulsive disorder. In
June 2004,
Britain banned Zoloft's use by minors and in
February 2005, Pfizer was forced to change Zoloft's labeling to include
information regarding increased incidences of suicidal behavior and depression
in adolescent users of the drug. According to mentalhealth.com, Zoloft is not
currently recommended or advised for use in individuals under the age of 18.
After these changes, multiple incidences and at least one medical study showed
an increased suicide risk in seniors who were taking Zoloft. In response to
these findings, the FDA released a public health warning. This warning
indicates that anyone currently using Zoloft for any reason has a greater
chance of exhibiting
suicidal thoughts or behaviors regardless of age. This warning is
questionable, however, due to the types of illnesses Zoloft is used to treat,
it is impossible to determine if these tendencies are a side effect of the
drug or the illness the drug is meant to treat.
Zoloft has long been seen as the best option for
breastfeeding mothers who wish to continue breastfeeding and be able to
take their antidepressants. Despite its apparent safety and effectiveness
during the breastfeeding period, recent studies and consumer complaints have
seen a need to alter Zoloft's labeling regarding use during the third
trimester of pregnancy. Though there are no
teratogenic effects associated with Zoloft, there is reason to be
concerned about its effects on infants who were exposed to sertraline during
the third trimester in utero. It seems that Zoloft use in late pregnancy
significantly increases the potential need for hospitalization and breathing
assistance in the newborn period and has also been shown to cause an increased
risk of neonatal death. In light of this increased risk it is still being used
due to the greater potential risk of a seriously depressed mother to herself
and her fetus. Like all other medications, Zoloft's use must be decided only
after carefully weighing out all potential risks and benefits.
Although SSRI anti-depressants may cause problems in
newborn babies whose mothers took Zoloft during pregnancy, the ceasing of
Zoloft consumption during pregnancy may cause a relapse of depression. If you
are planning on becoming pregnant, or are currently pregnant and are taking
Zoloft, do not stop taking this medication. Consult your physician first.[13]
According to the manufacturer's website, "if
depression is left untreated, the risk of childhood suicide increases about 12
times, according to federal figures".[14]
Sertraline and other SSRIs have been shown to cause
sexual side effects in up to 98% of both males and females taking them.[15]
Sometimes, the sexual side effects last months, years, or permanently after
the drug has been withdrawn. This disorder is known as
Post SSRI Sexual Dysfunction.
[edit]
Distribution
This drug has been heavily prescribed in the United
States. According to one source, more than 115 million prescriptions for
Sertraline had been written in the U.S. by
February 2000.[16]
The world over, $3.5 billion worth of Zoloft was sold in 2005.[17]
[edit]
Formulations
Zoloft logo
Sertraline is manufactured by
Pfizer and
sold as Zoloft in the United States as small green 25 mg
tablets, blue 50 mg tablets, and yellow 100 mg tablets (Generic 100 mg
sertraline tablets are also yellow), each of which is scored to allow easy
halving.
In the UK, the brand name is Lustral and is available
in white 50 mg or 100 mg scored tablets, according to the
British National Formulary (BNF). Elsewhere in the
EU the brand name is Zoloft, available in white 50 mg or 100 mg scored
tablets. In Australia, only the 50 mg and 100 mg strengths are available, both
as white tablets.
Sertraline is an odorless, white, sparingly soluble
crystalline solid. The minimum effective dose is usually 50 mg per day (it can
be still effective at 25 mg or 37.5 mg), but lower doses may be used in the
initial weeks of treatment to acclimate the patient's body, especially the
liver, to the drug and to minimize the severity of any side effects. Patients
who do not experience relief of symptoms at 50 mg a day may have their dose
increased, up to 200 mg a day.
Drug maker Pfizer Inc. confirmed that its subsidiary
Greenstone Ltd. is prepared to release a generic version of the antidepressant
Zoloft to compete with generic drug makers, who can release their own versions
after the drug's patent expires.
The patent for this brand-name drug expired in
June 2006.[18]
The drug is now available in generic form in the United States. The generic
version of the drug is being produced by Greenstone Ltd.(a Pfizer Inc.
subsidiary) and Israeli drug maker
Teva Pharmaceutical Industries Ltd.[19]
In Scandinavia a generic drug called Sertralin, manufactured by
HEXAL, is available. The price differences between Zoloft and Sertraline
are as much as 1.50 dollars
per pill.[citation
needed] In
India, this
drug is sold under the name
Zosert.
[edit]
Green technology
In 2002, Pfizer, inc. received an award from the U.S.
Environmental Protection Agency, specifically in relation to the
manufacture of sertraline. According to the EPA, Pfizer introduced methods of
production that reduced necessary inputs of raw materials and allowed for a
reduction of toxic waste. These new methods have been described as more
energy-efficient, permitting the company to multiply sertraline production
two-fold. Further, the application of this new process is purportedly safer
for workers.[20]
[edit]
Precautions
-
Liver
impairment can affect the
elimination of this drug from the body. If someone with liver impairment
is treated with sertraline, lower or less frequent dosage should be used.
- Patients should limit their
alcohol
intake while on sertraline (or any antidepressant). Because the liver is
doubly taxed with processing both substances (in addition to any other drugs
the patient may be taking), alcohol remains in the bloodstream longer, so
the effects of alcohol may be more strongly and quickly felt by people
taking sertraline or other antidepressants. Heavy alcohol consumpution while
on any SSRI can
damage liver cells much quicker than those off of the drugs.
- According to some studies
grapefruit juice might interfere with the metabolisation of sertraline,
increasing its concentration in the blood.
- People 80 years or older should be started on 25 mg
initial dose.
[edit]
Dopamine
Sertraline appears to also be a minor
dopamine
reuptake inhibitor (see
Dopamine reuptake inhibitor). Dopamine is responsible for the 'feel good'
feeling in the brain. While this generally will leave the user of the drug
feeling great, it is not the intent of the drug. Interestingly, since
activities like smoking
cigarettes increases
dopamine
levels in the brain, some smokers actually have increased cravings while on
SSRI drugs. There
are numerous studies on this.
[1]
[edit]
Controversy
In
June 2003,
Britain
banned sertraline's use for patients under 18 years of age after studies
showed a link to increasing suicidal rates. Similar concern has prevailed in
the United States, where only the anti-depressant
fluoxetine (another
SSRI) was
officially banned by the FDA for the treatment of depression in minors.
However, because the antidepressant-suicide link is correlational, scientists
do not know whether the increased suicide risk for people taking
antidepressants occurs because the drugs make people suicidal, whether suicide
occurs because the drugs un-depress the people enough to motivate the energy
required to commit suicide (a popular theory), whether people statistically
more likely to commit suicide are over-represented among takers of Zoloft, or
because of a fourth, unknown factor.
The brand-name form of setraline, Zoloft, was widely
advertised to consumers as "correcting a chemical imbalance", a claim not
found in the FDA-approved product labeling. Hundreds of millions of dollars
were spent promoting Zoloft this way while it was still on-patent. Some have
argued that this advertising may lead consumers to believe that they must take
Zoloft to recover when in fact they may benefit from other non-medical
treatments such as psychotherapy or exercise.[21][22]
In the case of Hawkins v The Commonwealth (an
Australian court case from the state of New South Wales), Zoloft was described
as an important factor in Hawkins murder (through strangling) of his wife.
Hawkins had been depressed, was prescribed 50 mg of Zoloft a day and on his
first day of treatment took 250 mgs. He claimed on the night of the murder
that he couldn't sleep, was agitated and claimed he had hallucinations during
the attack on his wife. As a result of this case Zoloft received a large
amount of negative publicity, with questions being raised about its impact on
behaviour. [23]
[edit]
Discontinuation Syndrome
-
Zoloft, along with other
SSRIs, has been
associated with a "cessation syndrome." This syndrome has both
somatic and
psychological elements, although SSRIs fall short of being classified as
addictive.
This non-addictive classification stems from the fact persons given the drug
will not seek it out in ever-increasing quantities. Although Zoloft is defined
as non-habit forming, the existence of
SSRI discontinuation syndrome often necessitates a gradual tapering of
one's prescribed dose when seeking to stop SSRI therapy. The prescription
insert for Zoloft describes the potential side effects SSRI discontinuation as
follows:
"During marketing of Zoloft and other
SSRIs and
SNRIs
(Serotonin and Norepinephrine Reuptake Inhibitors), there have been
spontaneous reports of adverse events occurring upon discontinuation of
these drugs, particularly when abrupt, including the following: dysphoric
mood, irritability, agitation, dizziness, sensory disturbances (e.g.
paresthesias such as electric shock sensations), anxiety, confusion,
headache, lethargy, emotional lability, insomnia, and hypomania. While these
events are generally self-limiting, there have been reports of serious
discontinuation symptoms."[24]
|
Sertraline
(ser' tra leen)
  |
| Studies have shown that children and teenagers who
take antidepressants ('mood elevators') such as sertraline may be more
likely to think about harming or killing themselves or to plan or try to do
so than children who do not take antidepressants.If your child's doctor has
prescribed sertraline for your child, you should watch his or her behavior
very carefully, especially at the beginning of treatment and any time his or
her dose is increased or decreased. Your child may develop serious symptoms
very suddenly, so it is important to pay attention to his or her behavior
every day. Call your child's doctor right away if he or she experiences any
of these symptoms: new or worsening depression; thinking about harming or
killing him- or herself or planning or trying to do so; extreme worry;
agitation; panic attacks; difficulty falling asleep or staying asleep;
irritability; aggressive behavior; acting without thinking; severe
restlessness; frenzied, abnormal excitement; or any other sudden or unusual
changes in behavior.Your child's doctor will want to see your child often
while he or she is taking sertraline, especially at the beginning of his or
her treatment. Your child's doctor may also want to speak with you or your
child by telephone from time to time. Be sure that your child keeps all
appointments for office visits or telephone conversations with his or her
doctor.Your child's doctor or pharmacist will give you the manufacturer's
patient information sheet (medication guide) when your child begins
treatment with sertraline. Read the information carefully and ask your
child's doctor or pharmacist if you have any questions. You also can obtain
the Medication Guide from the FDA website: http://www.fda.gov/cder/drug/antidepressants/MG_template.pdf.Talk
to your child's doctor about the risks of giving sertraline to your child. |
Why is this medication prescribed?Return to
top
Sertraline is used to treat depression,
obsessive-compulsive disorder (bothersome thoughts that won't go away and the
need to perform certain actions over and over), panic attacks (sudden,
unexpected attacks of extreme fear and worry about these attacks), posttraumatic
stress disorder (disturbing psychological symptoms that develop after a
frightening experience), and social anxiety disorder (extreme fear of
interacting with others or performing in front of others that interferes with
normal life). It is also used to relieve the symptoms of premenstrual dysphoric
disorder, including mood swings, irritability, bloating, and breast tenderness.
Sertraline is in a class of antidepressants called selective serotonin reuptake
inhibitors (SSRIs). It works by increasing the amounts of serotonin, a natural
substance in the brain that helps maintain mental balance.
How should this medicine be used?Return to
top
Sertraline comes as a tablet and a concentrate (liquid)
to take by mouth. It is usually taken once daily in the morning or evening. To
treat premenstrual dysphoric disorder, sertraline is taken once a day, either
every day of the month or on certain days of the month. To help you remember to
take sertraline, take it around the same time every day. Follow the directions
on your prescription label carefully, and ask your doctor or pharmacist to
explain any part you do not understand. Take sertraline exactly as directed. Do
not take more or less of it or take it more often than prescribed by your
doctor.
Sertraline concentrate must be diluted before use.
Immediately before taking it, use the provided dropper to remove the amount of
concentrate your doctor has directed you to take. Mix the concentrate with 4
ounces (1/2 cup) of water, ginger ale, lemon or lime soda, lemonade, or orange
juice. Do not mix the concentrate with any liquids other than the ones listed.
Drink immediately.
Your doctor may start you on a low dose of sertraline and
gradually increase your dose, not more than once a week.
It may take a few weeks or longer before you feel the
full benefit of sertraline. Continue to take sertraline even if you feel well.
Do not stop taking sertraline without talking to your doctor.
Other uses for this medicineReturn to top
Sertraline is also used sometimes to treat headaches and
sexual problems. Talk to your doctor about the possible risks of using this
medication for your condition.
This medication may be prescribed for other uses; ask
your doctor or pharmacist for more information.
What special precautions should I follow?Return
to top
Before taking sertraline,
- tell your doctor and pharmacist if you are allergic to sertraline or
any other medications. Before taking sertraline liquid concentrate, tell your
doctor if you are allergic to latex.
- do not take sertraline if you are taking monoamine oxidase (MAO)
inhibitors, including phenelzine (Nardil) and tranylcypromine (Parnate), or
have stopped taking them within the past 2 weeks, or if you are taking
pimozide (Orap).
- do not take disulfiram (Antabuse) while taking sertraline concentrate.
- tell your doctor and pharmacist what other prescription and
nonprescription medications, vitamins, nutritional supplements, and herbal
products you are taking or plan to take. Be sure to mention any of the
following: anticoagulants ('blood thinners') such as warfarin (Coumadin);
antidepressants (mood elevators) such as amitriptyline (Elavil), amoxapine (Asendin),
clomipramine (Anafranil), desipramine (Norpramin), doxepin (Adapin, Sinequan),
imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil),
and trimipramine (Surmontil); aspirin and other nonsteroidal anti-inflammatory
medications (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve,
Naprosyn); cimetidine (Tagamet); diazepam (Valium); digoxin (Lanoxin); lithium
(Eskalith, Lithobid); medications for anxiety, mental illness, Parkinson's
disease, and seizures; medications for irregular heartbeat such as flecainide
(Tambocor) and propafenone (Rythmol); oral medications for diabetes such as
tolbutamide (Orinase); medications for migraine headaches such as almotriptan
(Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge),
rizatriptan (Maxalt), sumatriptan (Imitrex), and zolmitriptan (Zomig);
sedatives; sleeping pills; and tranquilizers. Your doctor may need to change
the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you or anyone in your family has or has ever had
depression, bipolar disorder (mood that changes from depressed to abnormally
excited), or mania (frenzied, abnormally excited mood), or if you or anyone in
your family has thought about or attempted suicide. Also tell your doctor if
you have recently had a heart attack and if you have or have ever had seizures
or liver or heart disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are
breast-feeding. If you become pregnant while taking sertraline, call your
doctor.
- you should know that sertraline may make you drowsy. Do not drive a car
or operate machinery until you know how this medication affects you.
- ask your doctor about the safe use of alcoholic beverages while you are
taking sertraline.
- you should know that your mental health may change in unexpected ways,
especially at the beginning of your treatment and at any time your dose is
increased or decreased. These changes may occur at any time if you have
depression or other mental illness, whether or not you are taking sertraline
or any other medication. You, your family, or your caregiver should call your
doctor right away if you experience any of the following symptoms: new or
worsening depression; thinking about harming or killing yourself or planning
or trying to do so; extreme worry; agitation; panic attacks; difficulty
falling or staying asleep; irritability; aggressive behavior; acting without
thinking; severe restlessness; and frenzied abnormal excitement. Be sure that
your family or caregiver knows which symptoms may be serious so they can call
the doctor when you are unable to seek treatment on your own.
What special dietary instructions should I follow?Return
to top
Unless your doctor tells you otherwise, continue your
normal diet.
What should I do if I forget a dose?Return to
top
Take the missed dose as soon as you remember it. However,
if it is almost time for the next dose, skip the missed dose and continue your
regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?Return
to top
Sertraline may cause side effects. Tell your doctor if
any of these symptoms are severe or do not go away:
- upset stomach
- diarrhea
- constipation
- vomiting
- dry mouth
- gas or bloating
- loss of appetite
- weight changes
- drowsiness
- dizziness
- excessive tiredness
- headache
- pain, burning, or tingling in the hands or feet
- excitement
- nervousness
- shaking hands that you cannot control
- difficulty falling asleep or staying asleep
- sore throat
- changes in sex drive or ability
- excessive sweating
Some side effects can be serious. The
following symptoms are uncommon, but if you experience any of them or those
listed in the IMPORTANT WARNING section, call your doctor immediately:
- blurred vision
- seizure
- abnormal bleeding or bruising
- seeing things or hearing voices that do not exist (hallucinating)
Sertraline may cause other side
effects. Call your doctor if you have any unusual problems while taking this
medication.
What storage conditions are needed for this medicine?Return
to top
Keep this medication in the container it came in, tightly
closed, and out of reach of children. Store it at room temperature and away from
excess heat and moisture (not in the bathroom). Throw away any medication that
is outdated or no longer needed. Talk to your pharmacist about the proper
disposal of your medication.
In case of emergency/overdoseReturn to top
In case of overdose, call your local poison control
center at 1-800-222-1222. If the victim has collapsed or is not breathing, call
local emergency services at 911.
Symptoms of overdose may include:
- hair loss
- changes in sex drive or ability
- drowsiness
- excessive tiredness
- difficulty falling asleep or staying asleep
- diarrhea
- vomiting
- rapid pounding or irregular heartbeat
- upset stomach
- dizziness
- excitement
- shaking hands that you cannot control
- seizures
- hearing voices or seeing things that do not exist (hallucinating)
- unconsciousness
- fainting
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