Valproic Acid Full Prescribing Information
Brand Name: Depakene, Valproate, Valrelease
Generic Name: Valproic Acid
Depakene patient information (in plain English)
Valproic Acid is an anticonvulsant used to control seizures. It may also be used to treat other conditions as determined by your doctor.
Although valproic acid's mechanism of action has not yet been established, the drug's anticonvulsant activity may be related to increased brain concentrations of gamma-aminobutyric acid (GABA). The effect on the neuronal membrane is unknown.
Peak serum levels occur approximately 1 to 4 hours after a single oral dose. The therapeutic plasma concentration range is believed to be from 50 to 100 mcg/mL.
As sole or adjunctive therapy in the treatment of simple or complex absence seizures, including petit mal, and is useful in primary generalized seizures with tonic-clonic manifestations. Valproic acid may also be used adjunctively in patients with multiple seizure types which include either absence or tonic-clonic seizures.
Valproic Acid is contraindicated in those patients who are hypersensitive to it.
Patients with hepatic disease or significant dysfunction.
Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid. These incidences usually have occurred during the first 6 months of treatment with valproic acid.
A recent survey study of valproate use in the United States in nearly 400000 patients between 1978 and 1984, has shown that children under 2 years of age who received the drug as part of multiple anticonvulsant therapy were at greatest risk (nearly 20 fold increase) of developing fatal hepatotoxicity. These patients typically had other medical conditions such as congenital metabolic disorders, mental retardation or organic brain disease, in addition to severe seizure disorders. The risk in this age group decreased considerably in patients receiving valproate as monotherapy. Similarly, patients aged 3 to 10 years were at somewhat greater risk if they received multiple anticonvulsants than those who received only valproate. Risk generally declined with increasing age. No deaths have been reported in patients over 10 years of age who received valproate alone.
If valproic acid is to be used in children 2 years old or younger, it should be used with extreme caution and as a sole agent. The benefits of seizure control should be weighed against the risk.
Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as loss of seizure control, malaise, weakness, lethargy, anorexia and vomiting. Patients and parents should be instructed to report such symptoms. Because of the non-specific nature of some of the early signs, hepatotoxicity should be suspected in patients who become unwell, other than through obvious cause, while taking valproic acid.
Liver function tests should be performed prior to therapy and at frequent intervals thereafter especially during the first 6 months. However, physicians should not rely totally on serum biochemistry since these tests may not be abnormal in all instances, but should also consider the results of careful interim medical history and physical examination. Caution should be observed when administering valproic acid to patients with a prior history of hepatic disease. Patients with various unusual congenital disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease may be at particular risk.
The drug should be discontinued immediately in the presence of significant hepatic dysfunction, suspected or apparent. In some cases, hepatic dysfunction has progressed in spite of discontinuation of the drug. The frequency of adverse effects, particularly elevated liver enzymes, may increase with increasing doses. Therefore, the benefit gained by improved seizure control by increasing the dosage must be weighed against the increasing incidence of adverse effects sometimes seen at higher dosages.
Usage in Pregnancy
According to recent reports in the medical literature, valproic acid may produce teratogenicity in the offspring of human females receiving the drug during pregnancy. The incidence of neural tube defects in the fetus may be increased in the mothers receiving valproic acid during the first trimester of pregnancy.
Multiple reports indicate an association between the use of antiepileptic drugs and an elevated incidence of birth defects in children born to epileptic women taking such medication during pregnancy. The incidence of congenital malformations in the general population is regarded to be approximately 2%, in children of treated epileptic women, this incidence may be increased 2 to 3-fold. The increase is largely due to specific defects, e.g., congenital malformations of the heart, cleft lip and/or palate and neural tube defects. Nevertheless, the great majority of mothers receiving anticonvulsant medications deliver normal infants.
Antiepileptic drugs should not be discontinued in patients to whom the drug is administered to prevent major seizures, because of the strong possibility of precipitating status epilepticus with attendant hypoxia and risks to both the mother and the unborn child. The risks of discontinuing drugs given for minor seizures prior to or during pregnancy should be weighed against the risk of congenital defects in the particular case and with the particular family history.
IF YOU PLAN ON BECOMING PREGNANT, discuss with your doctor the benefits and risks of using this medicine during pregnancy. If you are or may be pregnant, check with your doctor for instructions on using this medicine during pregnancy.
Infant breast-feeding is not recommended for women taking this drug because valproic acid appears to be secreted in low concentrations in human milk.
Male Fertility: The effect of valproic acid on the development of the testes and on sperm production and fertility in humans is unknown. Long-term toxicity studies in rats and mice indicate a potential carcinogenic risk.
Valproic acid may produce CNS depression, especially when combined with another CNS depressant such as alcohol.
Because valproic acid may interact with other antiepileptic drugs, periodic serum level determinations of concurrently administered antiepileptics are recommended during the early part of therapy. There have been reports of breakthrough seizures occurring with the combination of valproic acid and phenytoin.
Hyperammonemia with or without lethargy or coma has been reported and may be present in the absence of abnormal liver function tests; if elevation occurs the valproic acid should be discontinued.
There have been reports of thrombocytopenia and inhibition of platelet aggregation. Platelet counts and bleeding time determination are recommended before instituting therapy and at periodic intervals. It is recommended that patients be monitored for platelet count prior to planned surgery. Clinical evidence of hemorrhage, bruising or a disorder of hemostasis/coagulation is an indication for reduction of dosage or withdrawal of therapy pending investigation.
Interference with Cognitive or Motor Performance: This medicine may cause drowsiness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to this medicine.
BEFORE USING THIS MEDICINE: INFORM YOUR DOCTOR OR PHARMACIST of all prescription and over-the-counter medicine that you are taking. This includes medicines used to treat seizures, anxiety, infections, and medicines containing aspirin or salicylates. Inform your doctor of any other medical conditions including liver conditions, allergies, pregnancy, or breast-feeding.
Valproic acid will add to the effects of alcohol and other depressants.
Caution is recommended when valproic acid is administered with drugs affecting coagulation, e.g., ASA and warfarin.
CHECK WITH YOUR DOCTOR AS SOON AS POSSIBLE if you experience diarrhea, abdominal cramps, bruising, change in weight, tremor, changes in mood or behavior, change in menstrual period, swelling of the face, loss of appetite, vomiting, or extreme tiredness. If you notice other effects not listed above, contact your doctor, nurse, or pharmacist.
Other less serious side effects, that may go away during treatment, include nausea, indigestion, drowsiness, or hair loss. If they continue or are bothersome, check with your doctor.
Symptoms of overdose may include deep sleep, irregular heartbeat, and loss of consciousness.
In acute overdosage the possibility of other CNS depressants, including alcohol, should be borne in mind.
If you or someone you know may have used more than the recommended dose of this medicine, contact your local poison control center or emergency room immediately.
Treatment should be symptomatic and supportive. Naloxone has been reported to reverse the CNS depressant effects of valproic acid overdose. Because naloxone could theoretically also reverse the antiepileptic effects of valproic acid it should be used with caution.
Do not exceed the recommended dosage.
Do not stop taking this medicine without first checking with your doctor. Keep all doctor and laboratory appointments while you are taking this medicine.
- Follow the directions for using this medicine provided by your doctor.
- Swallow whole. Do not break, crush, or chew before swallowing.
- This medicine may be taken with food if it upsets your stomach.
- Store this medicine at room temperature, away from heat and light.
- If you miss a dose of this medicine, and it is within 6 hours of the missed dose, take it as soon as possible. Take the remaining doses of the day at evenly spaced intervals. If you miss a dose of this medicine and you are taking 1 dose daily, take the missed dose if you remember the same day. Skip the missed dose if you do not remember until the next day. DO NOT take 2 doses at once.
Additional Information:: Do not share this medicine with others for whom it was not prescribed. Do not use this medicine for other health conditions. Keep this medicine out of the reach of children.
IF USING THIS MEDICINE FOR AN EXTENDED PERIOD OF TIME, obtain refills before your supply runs out.
The recommended initial dose is 15 mg/kg/day orally, increasing at 1-week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. Maximum recommended dose is 60 mg/kg/day. When the total daily dose exceeds 250 mg, it should be given in a divided regimen. The frequency of adverse effects (particularly elevated liver enzymes) may increase with increasing dose. Therefore, the benefit gained by improved seizure control must be weighed against the increased incidence of adverse effects.
250 mg and 500 mg capsules.
Syrup: Each 5 mL of syrup contains the equivalent of 250 mg valproic acid, as the sodium salt.
Depakene patient information (in plain English)
The information in this monograph is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects. This information is generalized and is not intended as specific medical advice. If you have questions about the medicines you are taking or would like more information, check with your doctor, pharmacist, or nurse.
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