Valproic acid (
VPA) is a
chemical compoundA chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
that has found clinical use as an
anticonvulsantThe anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers. The goal of an anticonvulsant is to suppress the rapid and...
and
mood-stabilizingA mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, which is not the same as "feeling good one minute and then bad the next."-Uses:...
drugA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
, primarily in the treatment of
epilepsyEpilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures...
,
bipolar disorderBipolar disorder, also known as manic depressive disorder, manic depression or bipolar affective disorder, is a serious mental disorder that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated mood clinically referred to as mania or, if...
, and less commonly major depression. It is also used to treat migraine
headacheIn medicine a headache or cephalalgia is a symptom of a number of different conditions of the head. Some of the causes are benign while others are medical emergencies.There are a number of different classification systems for headaches...
s and
schizophreniaSchizophrenia , from the Greek roots skhizein and phrēn, phren- is a psychiatric diagnosis that describes a mental disorder characterized by abnormalities in the perception or expression of reality...
. It is marketed under the brand names
Depakote,
Depakote ER,
Depakene,
Depacon,
Stavzor.
Related drugs include the sodium salts
sodium valproateSodium valproate or valproate sodium is the sodium salt of valproic acid and is an anticonvulsant used in the treatment of epilepsy and bipolar disorder, as well as other psychiatric conditions requiring the administration of a mood stabilizer...
, used as an anticonvulsant, and a combined formulation,
valproate semisodiumValproate semisodium or divalproex sodium consists of a compound of sodium valproate and valproic acid in a 1:1 molar relationship in an enteric coated form. It is used in the UK, Canada, and U.S. for the treatment of the manic episodes of bipolar disorder...
, used as a mood stabilizer and additionally in the U.S. also as an anticonvulsant.
History
Valproic acid (by its official name
2-propylvaleric acid) was first synthesized in 1882 by Burton as an
analogueIn chemistry, structural analogs , also known as chemical analogs or simply analogs, are compounds in which one or more atoms, functional groups, or substructures have been replaced with different atoms, groups, or substructures...
of
valeric acidValeric acid, or pentanoic acid, is a straight-chain alkyl carboxylic acid with the chemical formula C5H10O2. Like other low-molecular-weight carboxylic acids, it has a very unpleasant odor. It is found naturally in the perennial flowering plant valerian , from...
, found naturally in
valerianValerian is a hardy perennial flowering plant, with heads of sweetly scented pink or white flowers. The flowers are in bloom in the northern hemisphere from June to September. Valerian was used as a perfume in the sixteenth century.Native to Europe and parts of Asia, Valerian has been introduced...
. A clear liquid fatty acid at room temperature, for many decades its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for anti-seizure activity. He found that it prevented
pentylenetetrazolPentylenetetrazol is the International Nonproprietary Name of Metrazol and also known as pentetrazol or pentamethylenetetrazol. It is a drug used as a circulatory and respiratory stimulant...
-induced convulsions in rodents. Since then it has also been used for migraine and bipolar disorder.
Pharmacology
Valproate is believed to affect the function of the
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
GABAGabâ or gabaa, for the Cebuano people , is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
(as a
GABA transaminaseIn biochemistry, a transaminase or an aminotransferase is an enzyme that catalyzes a type of reaction between an amino acid and an α-keto acid. Specifically, this reaction involves removing the amino group from the amino acid, leaving behind an α-keto acid, and transferring it to...
inhibitor) in the human brain, making it an alternative to
lithium saltLithium pharmacology refers to use of the lithium ion, Li
+, as a drug. A number of chemical salts of lithium are used medically as a mood stabilizing drug, primarily in the treatment of bipolar disorder, where they have a role in the treatment of depression and particularly of mania,...
s in treatment of bipolar disorder. In addition to blocking transamination of GABA, Valproate is believed to reverse the
transaminationThere are two chemical reactions known as transamination . The first is the reaction between an amino acid and an alpha-keto acid...
process to form more GABA. Hence, Valproate indirectly acts as a GABA
agonistAn agonist is a drug that binds to a receptor of a cell and triggers a response by the cell. An agonist often mimics the action of a naturally occurring substance.An agonist produces an action...
. However, several other mechanisms of action in neuropsychiatric disorders have been proposed for valproic acid in recent years.
Valproic acid also blocks the voltage-gated sodium channels and T-type Calcium channels. These mechanisms make Valproic Acid a Broad Spectrum Anticonvulsant drug.
Valproic acid is an
inhibitorEnzyme inhibitors are molecules that bind to enzymes and decrease their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
of the
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
histone deacetylase 1 (HDAC1) hence it is a
histone deacetylase inhibitorHistone deacetylase inhibitors are a class of compounds that interfere with the function of histone deacetylase.-Cellular biochemistry/pharmacology:...
.
Indications
As an anticonvulsant, valproic acid is used to control
absence seizureAbsence seizures are one of several kinds of seizures. These seizures are sometimes referred to as petit mal seizures ....
s,
tonic-clonic seizureTonic–clonic seizures are a type of generalized seizure that affects the entire brain. Formerly known as grand mal seizures or gran mal seizures, these terms are now discouraged and rarely used in a clinical setting...
s (grand mal),
complex partial seizureA complex partial seizure is an epileptic seizure that is limited to one cerebral hemisphere and causes impairment of awareness or responsiveness.-Presentation:...
s,
juvenile myoclonic epilepsyJuvenile myoclonic epilepsy , also known as Janz syndrome, is a fairly common form of idiopathic generalized epilepsy, representing 5-10% of all epilepsies. This disorder typically first manifests itself between the ages of 12 and 18 with myoclonus occurring early in the morning. Most patients also...
and the
seizureAn epileptic seizure is a transient symptom of excessive or synchronous neuronal activity in the brain. It can manifest as an alteration in mental state, tonic or clonic movements, convulsions, and various other psychic symptoms...
s associated with
Lennox-Gastaut syndromeLennox–Gastaut syndrome , also known as Lennox syndrome, is a difficult-to-treat form of childhood-onset epilepsy that most often appears between the second and sixth year of life, and is characterized by frequent seizures and different seizure types; it is often accompanied by mental retardation...
. It is also used in treatment of
myoclonusMyoclonus is brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief lapses of contraction. Contractions...
. In some countries,
parenteralParenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...
(administered intravenously) preparations of valproate are used also as second-line treatment of
status epilepticusStatus epilepticus refers to a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 30 minutes , or recurrent seizures without regaining consciousness between...
, as an alternative to
phenytoinPhenytoin sodium is a commonly used antiepileptic. Phenytoin acts to dampen the unwanted, runaway brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage gated sodium channels...
. Valproate is one of the most common drugs used to treat
post-traumatic epilepsyPost-traumatic epilepsy is a form of epilepsy that results from brain damage caused by physical trauma to the brain . A person with PTE suffers repeated post-traumatic seizures more than a week after the initial injury...
.
Valproic acid is also FDA approved for the treatment of manic episodes associated with
bipolar disorderBipolar disorder, also known as manic depressive disorder, manic depression or bipolar affective disorder, is a serious mental disorder that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated mood clinically referred to as mania or, if...
, adjunctive therapy in multiple seizure types (including epilepsy), and prophylaxis of migraine headaches.
It is more recently being used to treat neuropathic pain, as a second line agent, particularly lancinating pain from A* fibres.
Investigational
Histone deacetylaseHistone deacetylases are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. Its action is opposite to that of histone acetyltransferase.-Subtypes:...
HDAC1Histone deacetylase 1 is an enzyme that in humans is encoded by the HDAC1 gene.-Interactions:HDAC1 has been shown to interact with RAD9A, DNMT3L, MTA1, FKBP3, CDC20, CDH1, Host cell factor C1, BUB3, Nuclear receptor co-repressor 2, IKZF1, Prohibitin, EVI1, DDX5, DNMT3A, Mothers against...
is needed for
HIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid,...
to remain in infected cells. A study published in August 2005 found that three of four patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a mean 75% reduction in latent HIV infection. Subsequent trials, however, have found no long term benefits of valproic acid in HIV infection.
According to the U.S. National Institutes of Health and others, valproic acid appears to have wide implications in the treatment of various
cancerCancer is a class of diseases in which a group of cells display uncontrolled growth , invasion , and sometimes metastasis...
s, including
multiple myelomaMultiple myeloma , also known as MM, myeloma, plasma cell myeloma, or as Kahler's disease is a cancer of the white blood cells known as plasma cells. A type of B cell, plasma cells are a crucial part of the immune system responsible for the production of antibodies in humans and other vertebrates...
(bone marrow cancer),
gliomaA glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
(an aggressive type of
brain tumorA brain tumor is an abnormal growth of cells within the brain or inside the skull, which can be cancerous or non-cancerous .It is defined as any intracranial tumor created by abnormal and uncontrolled cell division, normally either in the brain itself , in the cranial nerves...
), and melanoma. Valproic acid is cytotoxic to many different cancer types through its action as a
histone deacetylaseHistone deacetylases are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. Its action is opposite to that of histone acetyltransferase.-Subtypes:...
inhibitor. A phase I trial showed the maximum tolerated dose was 60 mg/kg.
Another potential indication may be
leukemiaLeukemia is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation of blood cells, usually white blood cells . Leukemia is a broad term covering a spectrum of diseases...
in juvenile patients. Studies conducted by several European centres are ongoing. Although it is too early to make a definitive statement, preliminary results are encouraging.
Valproic acid has given encouraging results for breast cancer when used alongside a standard
chemotherapyChemotherapy, in its most general sense, is the treatment of disease by chemicals especially by killing micro-organisms or cancerous cells. In popular usage, it refers to antineoplastic drugs used to treat cancer or the combination of these drugs into a cytotoxic standardized treatment regimen...
.
Three distinct formulations of valproic acid have been investigated in clinical trials for the treatment of colorectal polyps in
familial adenomatous polyposisFamilial adenomatous polyposis is an inherited condition in which numerous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs when not treated....
patients; treatment of hyperproliferative skin diseases (e.g.
basal cell carcinomaBasal cell carcinoma is the most common type of skin cancer. It rarely metastasizes or kills, but it is still considered malignant because it can cause significant destruction and disfigurement by invading surrounding tissues. Statistically, approximately 3 out of 10 Caucasians develop a basal cell...
); and treatment of inflammatory skin diseases (e.g.
acneAcne is a group of skin rashes that have different causes.* Acne vulgaris - most commonly experienced around puberty, typically of the face and shoulders/chest* Cystic acne, a severe form of acne wherein small cysts form...
) by
TopoTargetTopoTarget is an international biotechnology company focused on the discovery and development of drugs and therapies to treat cancer. While the company has offices around the world, its headquarters are based in Copenhagen, Denmark. It was founded in 2000 by a group of clinicians.TopoTarget is...
. The current names for these therapeutics are Savicol, Baceca and Avugane, respectively.
In October, 2008 a research team at the University of British Columbia in Vancouver, Canada announced that in a study doses of valproic acid reversed the early stages of Alzheimer's disease in mice. Human trials are underway.
Valproic acid's function as an
HDAC inhibitorHistone deacetylase inhibitors are a class of compounds that interfere with the function of histone deacetylase.-Cellular biochemistry/pharmacology:...
has also led to its use in
direct reprogramming in generation of induced pluripotent stem (iPS) cellsInduced pluripotent stem cells, commonly abbreviated as iPS cells are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of certain genes....
, where it has been shown that addition of VPA allows for reprogramming of human fibroblasts to iPS cells without addition of genetic factors
Klf4Krueppel-like factor 4 is a protein that in humans is encoded by the KLF4 gene.-Interactions:KLF4 has been shown to interact with CREB binding protein.- External links :*...
and
c-myc. This function has also been investigated as an epigenetic therapy for treatment of lupus.
Contraindications
Valproate causes birth defects: exposure during pregnancy is associated with about three times as many major anomalies as usual, mainly
spina bifidaSpina bifida is a developmental birth defect caused by the incomplete closure of the embryonic neural tube. Some vertebrae overlying the spinal cord are not fully formed and remain unfused and open. If the opening is large enough, this allows a portion of the spinal cord to stick out through the...
and more rarely with several other defects, possibly including a "valproate syndrome".
Women who intend to become pregnant should switch to a different drug if possible. Women who become pregnant while taking valproate should be warned that it causes birth defects, and cognitive impairment in the newborn, especially at high doses (although vaproate is sometimes the only drug that can control seizures, and seizures in pregnancy would have even worse consequences.) They should take high dose
folic acidFolic acid and folate , as well as pteroyl-L-glutamic acid and pteroyl-L-glutamate, are forms of the water-soluble vitamin B
9...
and be offered antenatal screening (
alpha-fetoproteinAlpha-fetoprotein is a protein that in humans is encoded by the AFP gene.This gene encodes alpha-fetoprotein, a major plasma protein produced by the yolk sac and the liver during fetal life. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin...
and second
trimesterThe term Trimester usually means* A period of 3 months.* The division of the academic year. There is, in the Northern Hemisphere, a winter term , a spring term , a summer term and an autumn term...
ultrasound scans), although screening and scans don't find all birth defects.
Valproate is a known folate antagonist, which can cause
neural tube defectsA neural tube defect will occur in human embryos if there is an interference with the closure of the neural tube that occurs around the 28th day after fertilization. The incidence of neural tube defects is 2.6 in 1,000 worldwide. -Causes:...
. Thus, folic acid supplements may alleviate the teratogenic problems. A recent study showed that children of mothers taking valproate during pregnancy are at risk for significantly lower IQs. Exposure of the human
embryoAn embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
to valproic acid is also associated with risk of
autismAutism is a disorder of neural development that is characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism involves many parts of the brain; how this occurs is not well understood...
, and it is possible to duplicate features characteristic of autism by exposing rat embryos to valproic acid at the time of neural tube closure. One study found that valproate exposure on embryonic day 11.5 led to significant local recurrent connectivity in the juvenile rat
neocortexThe neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...
, consistent with the underconnectivity theory of autism. A 2009 study demonstrated that children of pregnant women taking valproate had an I.Q. nine points lower than a well-matched control group.
Valproate is contraindicated in overweight patients because it might cause weight gain.
Preexisting hepatic (liver) and/or renal (kidney) damage or
cancerCancer is a class of diseases in which a group of cells display uncontrolled growth , invasion , and sometimes metastasis...
,
hepatitisHepatitis implies injury to the liver characterized by the presence of inflammatory cells in the tissue of the organ. The name is from ancient Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
,
pancreatitisPancreatitis is inflammation of the pancreas that can occur in two very different forms. Acute pancreatitis is sudden while chronic pancreatitis "is characterized by recurring or persistent abdominal pain with or without steatorrhea or diabetes mellitus."...
, end-stage
AIDSAcquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus ....
HIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid,...
infection,
bone marrowBone marrow is the flexible tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells. It constitutes 4% of total body weight, i.e...
depression, urea cycle disorders, and
coagulationCoagulation is a complex process by which blood forms clots. It is an important part of hemostasis , wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
hematological disorders are absolute contraindications.
Adverse effects
Common
side effectsAn adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dose. The meaning of this expression differs from the meaning of "side effect", as this last expression might also imply that the effects can be beneficial...
are
dyspepsiaDyspepsia , popularly known as indigestion, meaning hard or difficult digestion, is a medical condition characterized by chronic or recurrent pain in the upper abdomen, upper abdominal fullness and feeling full earlier than expected when eating. It can be accompanied by bloating, belching, nausea...
and/or weight gain. Less common are fatigue,
peripheral edemaPeripheral edema is the swelling of tissues, usually in the lower limbs, due to the accumulation of fluids.The condition is commonly associated with aging, but can be caused by many other conditions, including congestive heart failure, trauma, alcoholism, altitude sickness, pregnancy, hypertension...
, acne,
dizzinessDizziness refers to an impairment in spatial perception and stability. It is considered imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or for a non-specific feeling such as giddiness or foolishness....
, drowsiness, hair loss, headaches,
nauseaNausea is the sensation of unease and discomfort in the stomach with an urge to vomit.-Causes:...
,
sedationSedation is a medical procedure involving the administration of sedative drugs, generally to facilitate a medical procedure with local anaesthesia.- Uses :...
and
tremorA tremor is an unintentional, somewhat rhythmic, muscle movement involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, head, face, vocal cords, trunk, and legs. Most tremors occur in the hands. In some people,...
s. Valproic acid also causes
hyperammonemiaHyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to encephalopathy and death. It may be primary or secondary....
, which can lead to brain damage. Valproate levels within the normal range are capable of causing hyperammonemia and ensuing
encephalopathyEncephalopathy /ɛnˌsɛfəˈlɒpəθi/ literally means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses.-Terminology:In some contexts it...
. There have been reports of brain encephalopathy developing without hyperammonemia or elevated valproate levels.
Rarely, valproic acid can cause
blood dyscrasiaDyscrasia, is a concept from ancient Greek medicine with the word "dyskrasia", meaning bad mixture.-Ancient use:To the Greeks, it meant an imbalance of the four humors: blood, black bile, yellow bile, and water...
, impaired
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
function,
jaundiceJaundice, also known as icterus , is a yellowish discoloration of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia...
,
thrombocytopeniaThrombocytopenia is the presence of relatively few platelets in blood.Generally speaking, in humans, a normal platelet count ranges from 150,000 and 450,000 per mm3. These limits, however, are determined by the 2.5th lower and upper percentile, and a deviation does not necessarily imply...
, and prolonged
coagulationCoagulation is a complex process by which blood forms clots. It is an important part of hemostasis , wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
times. In about 5% of pregnant users, valproic acid will cross the
placentaThe placenta is an organ unique to mammals that connects the developing fetus to the uterine wall. The placenta supplies the fetus with oxygen and food, and allows fetal waste to be disposed of via the maternal kidneys...
and cause congenital anomalies. Due to these side effects, most doctors will ask for blood tests, initially as often as once a week and then once every 2 months. Temporary liver enzyme increase has been reported in 20% of cases during the first few months of taking the drug. Inflammation of the liver (
hepatitisHepatitis implies injury to the liver characterized by the presence of inflammatory cells in the tissue of the organ. The name is from ancient Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
), the first symptom of which is
jaundiceJaundice, also known as icterus , is a yellowish discoloration of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia...
, is found in rare cases.
Valproic acid may also cause acute hematological toxicities, especially in children, including rare reports of myelodysplasia and acute leukemia-like syndrome.
There have also been reports of cognitive dysfunction, Parkinsonian symptoms, and even (reversible) pseudoatrophic brain changes in long-term treatment with valproic acid.
Interactions
Valproic acid may interact with
carbamazepineCarbamazepine is an anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
, as valproates inhibit
microsomal epoxide hydrolaseEpoxide hydrolase functions in detoxication during drug metabolism. It converts epoxides to trans-dihydrodiols, which can be conjugated and excreted from the body. Epoxides result from the degradation of aromatic compounds....
(mEH), the
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
responsible for the breakdown of carbamazepine-10,11 epoxide (the main active metabolite of carbamazepine) into inactive metabolites. By inhibiting mEH, valproic acid causes a buildup of the active metabolite, prolonging the effects of carbamazepine and delaying its excretion.
Valproic acid also decreases the
clearanceIn medicine, the clearance is a measurement of the renal excretion ability. Although clearance may also involve other organs than the kidney, it is almost synonymous with renal clearance or renal plasma clearance. Each substance has a specific clearance that depends on its filtration characteristics...
of
amitriptylineAmitriptyline is a psychoactive drug and pharmaceutical of the tricyclic antidepressant chemical class which is used primarily as an antidepressant and anxiolytic agent. It is the most widely prescribed TCA and perhaps also the most efficient against depressive symptoms.- Approved :Amitriptyline...
and
nortriptylineNortriptyline is a second-generation tricyclic antidepressant marketed as the hydrochloride under the trade names Sensoval, Aventyl, Pamelor, Norpress, Allegron and Nortrilen. It is used in the treatment of major depression and childhood nocturnal enuresis...
.
Also, Valproic acid should not be used with the benzodiazopine clonazepam and aspirin to avoid adverse effects.
Valproic acid (and Sodium Valproate) reduces the apparent clearance of lamotrigine(lamictal), in most patients the lamotrigine dosage for coadministration with valproate must be reduced to half the monotherapy dosage.
Formulations
Branded products include:
Depakene (
Abbott LaboratoriesAbbott Laboratories is a diversified pharmaceuticals health care company. It has 72,000 employees and operates in over 130 countries. The corporate headquarters are in Abbott Park, Illinois, located near North Chicago, Illinois....
in U.S. & Canada)
Convulex (
PfizerPfizer Incorporated is a pharmaceutical company, ranking number one in sales in the world. The company is based in New York City, with its research headquarters in Groton, Connecticut...
in the UK and Byk Madaus in South Africa)
Stavzor (Noven Pharmaceuticals Inc.)
Depakine (Sanofi Aventis)
Epival (
Abbott LaboratoriesAbbott Laboratories is a diversified pharmaceuticals health care company. It has 72,000 employees and operates in over 130 countries. The corporate headquarters are in Abbott Park, Illinois, located near North Chicago, Illinois....
U.S. & Canada)
Epilim (Sanofi Synthelabo Australia)
Encorate (
Sun PharmaceuticalsSun Pharmaceutical is an international pharmaceutical company based in Mumbai, India. It makes many generic and brand name drugs that are distributed in the United States, Europe, Asia and worldwide...
India)
Valcote (
Abbott LaboratoriesAbbott Laboratories is a diversified pharmaceuticals health care company. It has 72,000 employees and operates in over 130 countries. The corporate headquarters are in Abbott Park, Illinois, located near North Chicago, Illinois....
Argentina)
Further reading
External links