Indian Industry, Indian Manufacture company for Sodium Volpurate, tablets

		It is a broad spectrum anticonvulsant Mechanism of Action Valproate appears to act by multiple mechanisms: (a) A Phenytoin like frequency dependent prolongation of Na+ channel inactivation (b) Attenuation of Ca2+ mediated ‘T’ current (c) Augmentation of release of inhibitory transmitter GABA by inhibiting its degradation as well as increasing its synthesis. Oral absorption of Valproic acid is good. Peak plasma levels are achieved in 1-4 hrs. It is 90% bound to plasma proteins; 95% metabolized in liver by oxidation and glucuronide conjugation – excreted in urine. Plasma t½ is 15 hours; but anticonvulsant effects are longer lasting Indications Valproic acid is highly effective in absence seizures and is an alternative / adjuvant drug for generalized and partial seizures To prevent recurrent febrile seizures in children, also used in some cases of Myoclonic and Atonic seizures Dosage Adults : 200mg 3 times a day, gradually increased at weekly intervals upto a maximum of 600mg 3 times a day according to response. Children : 10-15mg/kg/day in three divided doses, increase according to response at weekly interval by 5mg/kg/day upto 30-40mg/kg/day Contraindications Known hypersensitivity Special Precautions Caution in patients in hepatic and renal diseases Monitor liver function test Adverse Drug Reactions Anorexia, nausea, vomiting, drowsiness, ataxia are dose related effects Alopecia, hyperammonemia, sedation, vertigo, tremor, nystagmus and confusion can occur with prolonged use Hypersensitivity reactions like rashes and thrombocytopenia Asymptomatic increase in serum transaminases, rarely hepatitis and pancreatitis It is teratogenic Status in 1. Pregnancy: Contraindicated 2. Lactation : Use with caution 3. Old age : May be given in reduced dose 4. Children : May be given in dose as advised Interactions Phenytoin: Increases its level by inhibiting metabolism and displacing it from protein binding Phenobarbital, primidone: Inhibits their metabolism Clonazepam: Simultaneous administration may precipitate absence syndrome Carbamazepine: Induce each other’s metabolism Presentation Wallbrurate Blister of 10 Tablets
		Note : This product information is intended only for residents of the India. Taj Pharmaceuticals Limited, medicines help to treat and prevent a range of conditions—from the most common to the most challenging—for people around the world.

Sodium 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. The intravenous formulations are used when oral administration is not possible.

In pregnancy, valproate has the highest risk of birth defects of any of the commonly-used antiepilepsy drugs. However, some epilepsy can only be controlled by valproate, and seizures also pose grave risk to mother and child.

Trade names are in bold, followed by the manufacturer.
U.S.
• Intravenous injection – Depacon by Abbott Laboratories.
• Syrup – Depakene by Abbott Laboratories. (Note Depakene capsules are valproic acid).
Australia
• Epilim Crushable Tablets Sanofi-Aventis
• Epilim Sugar Free Liquid Sanofi-Aventis
• Epilim Syrup Sanofi-Aventis
• Epilim Tablets Sanofi-Aventis
• Sodium Valproate Sandoz Tablets Sanofi-Aventis
• Valpro Tablets Alphapharm
• Valproate Winthrop Tablets Sanofi-Aventis
UK
• Tablets – Orlept by Wockhardt and Epilim by Sanofi-Aventis.
• Oral solution – Orlept Sugar Free by Wockhardt and Epilim by Sanofi-Aventis.
• Syrup – Epilim by Sanofi-Aventis.
• Intravenous injection – Epilim Intravenous by Sanofi-Aventis.
• Extended release tablets – Epilim Chrono by Sanofi-Aventis. A combination of sodium valproate and valproic acid in a 2.3:1 ratio.
• Enteric-coated tablets – Epilim EC200 by Sanofi-synthélabo. A 200 mg sodium valproate enteric-coated tablet.
UK only
• Capsules – Episenta prolonged release by Beacon.
• Sachets – Episenta prolonged release by Beacon.
• Intravenous solution for injection – Episenta solution for injection by Beacon.
Germany, Switzerland, Norway
• Tablets – Orfiril by Desitin Pharmaceuticals
• Intravenous injection – Orfiril IV by Desitin Pharmaceuticals
South Africa
• Syrup – Convulex by Byk Madaus
• Tablets – Epilim by sanofi~synthelabo
Canada
• Intravenous injection – Epival or Epiject by Abbott Laboratories.
• Syrup – Depakene by Abbott Laboratories. Generic formulations include Apo-Valproic and ratio-Valproic.
Japan
• Tablets – Depakene by Kyowa Hakko Kogyo.
• Extended release tablets – Depakene-R by Kyowa Hakko Kogyo and Selenica-R by Kowa.
• Syrup – Depakene by Kyowa Hakko Kogyo.
Europe
In much of Europe, Depakine and Depakine Chrono (tablets) are equivalent to Epilim and Epilim Chrono above.
Safety in pregnancy
The risk of birth defects with valproate is two to five times higher than other frequently-used anti-epileptic drugs (absolute rates of birth defects 6-11%). Children born to mothers using valproate have significantly lower I.Q. scores (9 points). However, some epilepsy can only be controlled by valproate, and seizures in pregnancy, which can have grave consequences for mother and child. Doctors recommend that women who intend to become pregnant should be switched to a different drug using combined therapy if possible, which takes several months. Women who are already pregnant and taking a high dose of valproate should try to lower their dose.

All antiepilepic medications have been shown to be associated with higher risks of fetal abnormalities (mostly for spina bifida) since at least 1983 with the risks being related to the strength of medication used and use of more than one drug

Valproate has also been recognised as sometimes causing a specific facial changes ("facial phenotype") termed "fetal valproate syndrome"Sodium valproate has been associated with the rare condition paroxysmal tonic upgaze of childhood, also known as Ouvrier-Billson syndrome, from childhood or fetal exposure (this condition resolved after discontinuing valproate therapy

While developmental delay is usually associated with altered physical characteristics (dysmorphic features), this is not always the case.

A 2005 study found rates of autism among children exposed to sodium valproate before birth in the cohort studied were 8.9%.The normal incidence for autism in the general population is estimated at less than one percent. It has been suggested that Valproate may best be avoided in women with localisation epilepsy, where there are more effective and less risky alternatives such as carbamazepine. A 2008 study also suggested a correlation between higher rates of autism in children whose mothers were treated for seizure disorders during pregnancy using sodium valproate (less than 1% for children who didn't receive the drug in vitro vs. 6.3% for children who did). However, only 632 children were followed in this study, prompting criticism that this study was too small to rely on to say whether there was a definitive correlation between the use of sodium valproate in pregnant mothers and higher autism rates in their children, or whether other anti-seizure medications used during pregnancy don't cause this effect.

One multi-centre trial in the UK and US looked at cognitive function in 309 children born to mothers with epilepsy and found that sodium valproate-use was associated with an IQ level eight points lower in children born to mothers taking sodium valproate than mothers taking other anti-epileptic drugs.The authors of the study attempted to correct for confounding factors, but this is an observational study, and therefore cannot prove a causal link. It should be noted, however, that to prove a causal link requires a randomised-controlled trial, which is not possible to perform.[14] It is therefore unlikely that any stronger evidence will become available

A class action is currently underway in the United Kingdom regarding the claim that the drug used in pregnancy caused a range of problems in children, including autism, learning and social difficulties, ADHD, spinal stenosis, facial abnormalities, vision defects, dyslexia, dyspraxia, delayed speech and motor development.

Valproic acid (VPA) is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and less commonly major depression. It is also used to treat migraine headaches and schizophrenia. It is marketed under the brand names Depakote, Depakote ER, Depakene, Depacon, Stavzor.
Related drugs include the sodium salts sodium valproate, used as an anticonvulsant, and a combined formulation, valproate semisodium, used as a mood stabilizer and additionally in the U.S. also as an anticonvulsant

Valproate causes birth defects: exposure during pregancy is associated with about three times as many major anomalies as usual, mainly spina bifida 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 acid and be offered antenatal screening (alpha-fetoprotein and second trimester ultrasound scans), although screening and scans don't find all birth defects.[18]

Valproate is a known folate antagonist, which can cause neural tube defects. 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.[19][20] Exposure of the human embryo to valproic acid is also associated with risk of autism, and it is possible to duplicate features characteristic of autism by exposing rat embryos to valproic acid at the time of neural tube closure.[21] One study found that valproate exposure on embryonic day 11.5 led to significant local recurrent connectivity in the juvenile rat neocortex, consistent with the underconnectivity theory of autism.[22] 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 cancer, hepatitis, pancreatitis, end-stage AIDS HIV infection, bone marrow depression, urea cycle disorders, and coagulation hematological disorders are absolute contraindications.

SODIUM VALPROATE (EPILIM)

The drug valproate is an epilepsy drug, which has been studied for the treatment of spinal muscular atrophy (SMA), a motor neuron disease. Sodium volproate is also used for mania (a condition in which a person is very excited, agitated, talking quickly, sleeping little and with expansive ideas). Sodium valproate has been used for prevention of migraine, and pain conditions including trigeminal neuralgia. Usually the medicine is started as a low dose and increased gradually to get the best benefit. Epilim comes in a cherry flavored liquid or syrup, chewable tablets or enteric-coated tablets. The syrup contains regular sugar and artificial sweeteners and the liquid contains artificial sweeteners.

Like all medicines, sodium valporate may have side effects. But mostly all people will not get these problems. Most commonly stomach effects can occur, especially when starting with this medicine. The enteric-coated tablets are intended to stay intact in the stomach and not dissolve until they get to the intestine, so can reduce the stomach effects. The syrup liquid or chewable tablets can be taken with meals.

Liver effects - watch for weakness, lethargy, tiredness or drowsiness, generally feeling unwell, vomiting, stomach pain, not wanting to eat, jaundice (person looks yellow) - these symptoms happens suddenly. Can prolong bleeding time - if bruising without a cause or bleeding occurs talk immediately to your physician. Skin rash (immediately talk to the physician). Sedation - is only temporary as the body gets used to the medicine. Some people will become more alert in its place. Tremor or lack of coordination (occasionally with high dose only). Increased hunger and increase in weight. Some other important drugs are dutasteride, dapoxetine, androz, fluticasone and rimoslim.

There are other side effects, which are not listed here. If the dose is too high to start with or is increased too fast there may be a higher chance of side effects. Talk to your doctor if you think you have any of these side affects or other symptons.

Does it work?

We don't know. Different studies say different things.
What is it?

Sodium valproate (also called divalproex sodium or valproic acid) is normally used to treat people who have epilepsy. But some doctors have prescribed it for people with dementia.

It's one of a group of drugs that doctors call anticonvulsants. Its brand names are Epilim, Orlept, Depakote and Convulex.

How can it help?

We don't know if it can help. Some of the research isn't very good-quality. One study found that sodium valproate didn't help people with symptoms like becoming upset or aggressive
Why should it work?

We don't know exactly how sodium valproate might work to improve symptoms like agitation and aggression. It may stop certain signals travelling through the brain. And it may stop cells in the brain being destroyed.
Can it be harmful?

People who take sodium valproate are about twice as likely to get some side effects as those who take a dummy pill (a placebo). The most common side effects are:

* Feeling sleepy
* Feeling sick
* Vomiting
* Getting diarrhoea
* Getting infections in the bladder or the urinary tract (tube that carries urine out of the body).

Valproic acid tablets
United States Patent 5049586
A moisture stable solid valproic acid formulation is provided. The formulation comprises:
55 to 65 weight percent valproic acid,
10 to 25 weight percent fillers,
10 to 20 weight percent disintegrants,
3 to 6 weight percent binders, and
0.5 to 1.2 weight percent lubricants
A preferred formulation is:
60 weight percent of valproic acid,
20 weight percent of magnesium oxide,
15 weight percent corn or potato starch,
3 weight percent polyvinylpyrrolidone,
1 weight percent sodium carboxymethylcellulose,
0.8 weight percent magnesium stearate.
The formulations are manufactured by mxing an alcohol solution of valproic acid with the fillers, drying and then milling the mixture, adding the disintegrants and wet granulating with at least a portion of the binder. The wet granulate is dried, sized and to it is added the lubricant and any remaining binder.

The lubricated granulate can be compressed into tablets without a protective coating.
Valproic acid may cause serious or life threatening damage to the liver. The risk of developing liver damage is greatest in children who are younger than 2 years of age and in people who are taking more than one medication to prevent seizures or who have any of the following conditions: a severe seizure disorder and mental retardation; certain inherited diseases that prevent the body from changing food to energy normally; any condition that affects the ability to think, learn, and understand; or liver disease. Tell your doctor or your child's doctor if you or your child have any of these conditions. Your child should not take any other medications to control seizures while he or she is taking valproic acid. If you notice that your seizures are more severe or happen more often or if you experience any of the following symptoms, call your doctor immediately: excessive tiredness, lack of energy, weakness, stomach pain, loss of appetite, nausea, vomiting, or swelling of the face.

Valproic acid may cause serious or life-threatening damage to the pancreas. This may occur at any time during your treatment. If you experience any of the following symptoms, call your doctor immediately: stomach pain, nausea, vomiting, or loss of appetite.
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to valproic acid.
Talk to your doctor about the risks of taking valproic acid or of giving valproic acid to your child.
How should this medicine be used? Return to top

Valproic acid comes as a capsule, an extended-release (long-acting) tablet, a delayed-release (slow to begin working) tablet, a sprinkle capsule (capsule that contains small beads of medication that can be sprinkled on food), and a syrup (liquid) to take by mouth. The syrup, capsules, delayed-release tablets, and sprinkle capsules are usually taken two or more times daily. The extended-release tablets are usually taken once a day. Take valproic acid at around the same time(s) every day. Take valproic acid with food to help prevent the medication from upsetting your stomach. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take valproic acid exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the regular capsules and extended-release tablets whole; do not split, chew, or crush them.

You can swallow the sprinkle capsules whole, or you can open the capsules and sprinkle the beads they contain on a teaspoonful of soft food, such as applesauce or pudding. Swallow the mixture of food and medication beads right after you prepare it. Be careful not to chew the beads. Do not store unused mixtures of food and medication.
Do not mix the syrup into any carbonated drink.
Your doctor may start you on a low dose of valproic acid and gradually increase your dose, not more often than once a week.

Valproic acid may help to control your condition but will not cure it. Continue to take valproic acid even if you feel well. Do not stop taking valproic acid without talking to your doctor, even if you experience side effects such as unusual changes in behavior or mood. If you suddenly stop taking valproic acid, you may experience a severe, long-lasting and possibly life-threatening seizure. Your doctor will probably decrease your dose gradually.

DEPAKOTE Tablets
(divalproex sodium) Delayed Release Tablets
BOX WARNING: HEPATOTOXICITY:
Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid and its derivatives. Experience has indicated that children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. When depakote is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. Above this age group, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.

These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months.

TERATOGENICITY:
Valproate can produce teratogenic effects such as neural tube defects (e.g., spina bifida). Accordingly, the use of depakote tablets in women of childbearing potential requires that the benefits of its use be weighed against the risk of injury to the fetus. This is especially important when the treatment of a spontaneously reversible condition not ordinarily associated with permanent injury or risk of death (e.g., migraine) is contemplated. See warnings, information for patients.

An information sheet describing the teratogenic potential of valproate is available for patients.
Pancreatitis:
Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with a rapid progression from initial symptoms to death. Cases have been reported shortly after initial use as well as after several years of use. Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, valproate should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated. (see warnings and precautions.)

GENERIC NAME: valproic acid, divalproex
BRAND NAME: Depakote, Depakote ER, Depakene, Depacon, Stavzor
DRUG CLASS AND MECHANISM: Valproic acid and its derivative, divalproex, are oral drugs that are used for the treatment of convulsions, migraines and bipolar disorder. The active ingredient in both products is valproic acid or valproate. Scientists do not know the mechanism of action of valproate. The most popular theory is that valproate exerts its effects by increasing the concentration of gamma-aminobutyric acid (GABA) in the brain. Gamma-aminobutyric acid is a neurotransmitter, a chemical that nerves use to communicate with one another.
PRESCRIPTION: yes
GENERIC AVAILABLE: yes (valproic acid and divalproex)
PREPARATIONS: Depakote delayed release tablets: 125, 250 and 500 mg. Depakote sprinkle capsules: 125 mg. Depakote ER tablets: 500 mg. Depakene capsules: 250 mg. Depakene syrup: 250 mg/5 ml. Depacon (valproate sodium) injection: 100 mg/5 ml. Valproic acid capsules: 250 mg. Valproic acid syrup: 250 mg/5ml
STORAGE: Store at room temperature, 15-30 C (59-86 F).
PRESCRIBED FOR: Valproic acid and divalproex are used for the treatment of seizures, bipolar disorder and prevention of migraines. Depakote extended- release (ER) is used 1) for the prevention of migraine 2) as sole and adjunctive therapy for complex partial seizures in isolation or in association with other types of seizures and simple and complex absence seizures in children with epilepsy ages 10 and above 3) for the treatment of acute manic or mixed episodes associated with bipolar disorder.

DOSING: For seizures, therapy is initiated at 10-15 mg/kg/day and increased by 5-10 mg/kg/day every week to achieve the desired response. Response is usually seen when the blood concentration of valproic acid is 50-100 mcg/ml.

For acute mania due to bipolar disorder, treatment is started at 750 mg per day of divalproex delayed-release tablets in divided doses. The dose should be increased rapidly to achieve the desired effect. The maximum dose is 60 mg/kg/day.

The recommended dose for prevention of migraines is 250 mg twice daily of divalproex delayed-release tablets. The maximum recommended dose is 1000 mg/day. When using divalproex ER tablets, the recommended dose is 500-1000 mg given once daily.

DRUG INTERACTIONS: Valproic acid and divalproex have numerous suspected or proven drug interactions. Although the following drug interactions refer to valproic acid, similar interactions would be expected to occur with divalproex.

Valproic acid can reduce the number of platelets or inhibit the ability of platelets to stick together and form a blood clot. Therefore, it may exaggerate the effects of other medications which inhibit the stickiness of platelets or inhibit other steps in the clotting of blood. This can lead to abnormal bleeding due to the inability of blood to clot. Such medications include warfarin (Coumadin), heparin or low-molecular weight heparin (Lovenox), clopidogrel (Plavix), ticlopidine (Ticlid), and nonsteroidal antiinflammatory drugs (nsaids) such as ibuprofen (Motrin, Advil), naproxen (Naprosyn, Aleve), indomethacin (Indocin), nabumetone (Relafen), diclofenac (Voltaren, Cataflam, Arthrotec), ketorolac (Toradol) and aspirin.
Aspirin and felbamate (Felbatol) can reduce the elimination of valproic acid and result in elevated blood concentrations of valproic acid.

Rifampin (Rifadin; Rimactane), carbamazepine (Tegretol), phenytoin (Dilantin) can increase the elimination of valproic acid, thereby reducing blood concentrations. Since this can result in loss of seizure control and seizures, adjustments in the dose of valproic acid may be necessary if these medications are begun.

Cholestyramine (Questran) can reduce the absorption of valproic acid from the intestine. Therefore, valproic acid should be taken at least 2 hours before or 6 hours after doses of cholestyramine.

Valproic acid can significantly decrease the elimination of lamotrigine (Lamictal), ethosuximide (Zarontin), diazepam (Valium), zidovudine (AZT) and phenobarbital, thereby increasing their concentrations in blood. Valproic acid also increases the blood levels of warfarin and phenytoin by displacing them from blood proteins that they bind to. Since increased blood concentrations of these drugs may lead to an increase in side effects, the dose of warfarin and phenytoin may need to be altered when they are taken with valproic acid.
Valproic Acid and Derivatives
( Divalproex Sodium , Sodium Valproate ) Pronunciation: (val-PROE-ik AS-id)
Class: Anticonvulsant Divalproex Sodium

Trade Names:
Depakote
- Tablets, delayed-release 125 mg
- Tablets, delayed-release 250 mg
- Tablets, delayed-release 500 mg
- Capsules, sprinkle 125 mg

Trade Names:
Depakote ER
- Tablets, ER 250 mg
- Tablets, ER 500 mg
Sodium Valproate

Trade Names:
Depacon
- Injection 100 mg/ml

Trade Names:
Depakene
- Capsules 250 mg (as valproic acid)
- Syrup 250 mg per 5 ml

Trade Names:
Stavzor
- Capsules, delayed-release 125 mg (as valproic acid)
- Capsules, delayed-release 250 mg (as valproic acid)
- Capsules, delayed-release 500 mg (as valproic acid)
Apo-Divalproex (Canada)
Apo-Valproic Acid (Canada)
Epival (Canada)
Gen-Valproic (Canada)
Nu-Divalproex (Canada)
PMS-Valproic Acid (Canada)
PMS-Valproic Acid E.C. (Canada)
Ratio-Valproic (Canada)
Sandoz Valproic (Canada)