Post by loretta on Sept 4, 2015 7:39:54 GMT
Sodium Valporate
Valproate is an acidic organic compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches. It comes in the form of a liquid at room temperature, but it can be reacted with a base such as sodium hydroxide to form the salt sodium valproate, which is a solid.
The acid, salt, or a mixture of the two (valproate semisodium) are marketed under a number of different brand names. Common brand names in Australia
Epilim Crushable Tablets Sanofi
Epilim Sugar Free Liquid Sanofi
Epilim Syrup Sanofi
Epilim Tablets Sanofi
Sodium Valproate Sandoz Tablets Sanofi
Valpro Tablets Alphapharm
Valproate Winthrop Tablets Sanofi
Valprease tablets Sigma
Dosage
Epilim 500 mg enteric-coated is recommended for patients requiring high doses.
Epilepsy
Monotherapy: Usual requirements are as follows:
Adults: Dosage should start with 600 mg daily increasing by 200 mg/day at three-day intervals
until control is achieved. This is generally within the range 1,000 to 2,000 mg/day, (i.e. 20 to
30 mg/kg/day). Where adequate control is not achieved within this range the dose may be
further increased to 2,500 mg/day.
Children > 20 kg: Initial dosage should be 400 mg/day (irrespective of weight) with spaced
increases until control is achieved; this is usually within the range 20 to 30 mg/kg/day.
Children < 20 kg: 20 mg/kg/day: in severe cases this may be increased but only in patients in
whom plasma valproic acid levels can be monitored. Above 40 mg/kg/day, clinical chemistry
and haematological parameters should be monitored.
General considerations: Optimum dosage is mainly determined by seizure control and routine
measurement of plasma levels is unnecessary. However, a method for measurement of plasma
levels is available and may be helpful where there is poor control or side effects are suspected.
Combined therapy: In certain cases it may be necessary to raise the dose by 5 to
10 mg/kg/day when used in combination with anticonvulsants which induce liver enzyme activity,
e.g. phenytoin, phenobarbitone and carbamazepine. Once known enzyme inducers have been
withdrawn it may be possible to maintain seizure control on a reduced dose of Epilim. When
barbiturates are being administered concomitantly, the dosage of barbiturate should be reduced
if sedation is observed.
Mania
Initially dosage should start with 600 mg daily increasing by 200 mg/day at three-day intervals
until control is achieved. This is generally within the range 1,000 to 2,000 mg/day, (i.e. 20 to
30 mg/kg/day). Where adequate control is not achieved within this range the dose may be
further increased to 2,500 mg/day.
The Bowden et al study (see PHARMACOLOGY, Clinical Trials) provided strong support for
the greater efficacy of serum levels above 45 µg/mL (these levels achieved 20% or greater
improvement on both subscales of the Mania Rating Scale). Bowden noted that > 125 µg/mL
had greater drug-related adverse events. Between these extremes there does not appear to be
a clear dose-response relationship.
Hepatic Impairment: Liver dysfunction, including hepatic failure resulting in fatalities, has
occurred in patients whose treatment included valproic acid or sodium valproate
Nausea
Gastric irritation
Diarrhoea
Weight gain
Hyperammonaemia (you have too much ammonia in your blood)
Thrombocytopenia (low levels of platelets in your blood, which may mean you bruise easily)
Transient hair loss (regrowth may be curly)
Increased alertness
Aggression
Hyperactivity
Behavioural disturbances
Ataxia (lack of coordination of muscle movements)
Tremor
Vasculitis
Contraindications
Pregnancy
Pre-existing acute or chronic liver dysfunction or family history of severe liver inflammation (hepatitis), particularly medicine related.
Known hypersensitivity to valproate or any of the excipients used in the preparation
Urea cycle disorders
Hepatic porphyria
Hepatotoxicity
Mitochondrial disease
Pancreatitis
Porphyria
Valproate is highly protein bound and hence may interact with drugs that are substrates for any of these enzymes or are highly protein bound themselves. It may also potentiate the CNS depressant effects of alcohol. It may also interact with:
Anticoagulants, due to its ability to prolong the bleeding time.
Psychotropic agents; potential pharmacokinetic interactions.
Benzodiazepines; may potentiate CNS depression and there are possible pharmacokinetic interactions.
Ethosuximide; potential for ethosuximide toxicity.
Primidone; may reduce pyrimidone's clearance leading to toxicity.
Zidovudine; may raise its (zidovudine's) serum concentration and lead to toxicity.
Aspirin; may displace valproate from plasma proteins, leading to increased plasma concentrations. Also interferes with valproate's metabolism.
Felbamate; may increase plasma concentrations of valproate.
Mefloquine; potential for increased valproate metabolism combined with the direct epileptogenic effects of mefloquine.
Cimetidine; inhibits valproate's metabolism in the liver, hence leading to increased plasma concentrations of valproate.
Erythromycin; inhibits valproate's metabolism in the liver, hence leading to increased plasma concentrations of valproate.
Carbapenem antibiotics; reduces valproate levels, potentially leading to seizures.
Special monitoring
Excessive amounts of valproic acid can result in tremor, stupor, respiratory depression, coma, metabolic acidosis, and death. In general, serum or plasma valproic acid concentrations are in a range of 20–100 mg/l during controlled therapy, but may reach 150–1500 mg/l following acute poisoning. Monitoring of the serum level is often accomplished using commercial immunoassay techniques, although some laboratories employ gas or liquid chromatography.
Education for patient/carers
Education about side effects
Storage
If a dose is missed take one as soon as possible however if the next dose is due just take the next dose
Consult the doctor if experiencing any side effects or if there are any concerns
Take as directed
Alcohol taking not recommended
References
Citrome L (2009) Adjunctive lithium and anticonvulsants for the treatment of schizophrenia: what is the evidence? Expert Rev Neurother 9: 55–71. doi: 10.1586/14737175.9.1.55
Haw C, Stubbs J (2005) A survey of the off-label use of mood stabilizers in a large psychiatric hospital. J Psychopharmacol 19: 402–407. doi: 10.1177/0269881105053307
Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Guerreiro C, Kalviainen R, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2013;54:551-63.
www.health.vic.gov.au/mentalhealth/druginfo/index.htm
Valproate is an acidic organic compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches. It comes in the form of a liquid at room temperature, but it can be reacted with a base such as sodium hydroxide to form the salt sodium valproate, which is a solid.
The acid, salt, or a mixture of the two (valproate semisodium) are marketed under a number of different brand names. Common brand names in Australia
Epilim Crushable Tablets Sanofi
Epilim Sugar Free Liquid Sanofi
Epilim Syrup Sanofi
Epilim Tablets Sanofi
Sodium Valproate Sandoz Tablets Sanofi
Valpro Tablets Alphapharm
Valproate Winthrop Tablets Sanofi
Valprease tablets Sigma
Dosage
Epilim 500 mg enteric-coated is recommended for patients requiring high doses.
Epilepsy
Monotherapy: Usual requirements are as follows:
Adults: Dosage should start with 600 mg daily increasing by 200 mg/day at three-day intervals
until control is achieved. This is generally within the range 1,000 to 2,000 mg/day, (i.e. 20 to
30 mg/kg/day). Where adequate control is not achieved within this range the dose may be
further increased to 2,500 mg/day.
Children > 20 kg: Initial dosage should be 400 mg/day (irrespective of weight) with spaced
increases until control is achieved; this is usually within the range 20 to 30 mg/kg/day.
Children < 20 kg: 20 mg/kg/day: in severe cases this may be increased but only in patients in
whom plasma valproic acid levels can be monitored. Above 40 mg/kg/day, clinical chemistry
and haematological parameters should be monitored.
General considerations: Optimum dosage is mainly determined by seizure control and routine
measurement of plasma levels is unnecessary. However, a method for measurement of plasma
levels is available and may be helpful where there is poor control or side effects are suspected.
Combined therapy: In certain cases it may be necessary to raise the dose by 5 to
10 mg/kg/day when used in combination with anticonvulsants which induce liver enzyme activity,
e.g. phenytoin, phenobarbitone and carbamazepine. Once known enzyme inducers have been
withdrawn it may be possible to maintain seizure control on a reduced dose of Epilim. When
barbiturates are being administered concomitantly, the dosage of barbiturate should be reduced
if sedation is observed.
Mania
Initially dosage should start with 600 mg daily increasing by 200 mg/day at three-day intervals
until control is achieved. This is generally within the range 1,000 to 2,000 mg/day, (i.e. 20 to
30 mg/kg/day). Where adequate control is not achieved within this range the dose may be
further increased to 2,500 mg/day.
The Bowden et al study (see PHARMACOLOGY, Clinical Trials) provided strong support for
the greater efficacy of serum levels above 45 µg/mL (these levels achieved 20% or greater
improvement on both subscales of the Mania Rating Scale). Bowden noted that > 125 µg/mL
had greater drug-related adverse events. Between these extremes there does not appear to be
a clear dose-response relationship.
Hepatic Impairment: Liver dysfunction, including hepatic failure resulting in fatalities, has
occurred in patients whose treatment included valproic acid or sodium valproate
Nausea
Gastric irritation
Diarrhoea
Weight gain
Hyperammonaemia (you have too much ammonia in your blood)
Thrombocytopenia (low levels of platelets in your blood, which may mean you bruise easily)
Transient hair loss (regrowth may be curly)
Increased alertness
Aggression
Hyperactivity
Behavioural disturbances
Ataxia (lack of coordination of muscle movements)
Tremor
Vasculitis
Contraindications
Pregnancy
Pre-existing acute or chronic liver dysfunction or family history of severe liver inflammation (hepatitis), particularly medicine related.
Known hypersensitivity to valproate or any of the excipients used in the preparation
Urea cycle disorders
Hepatic porphyria
Hepatotoxicity
Mitochondrial disease
Pancreatitis
Porphyria
Valproate is highly protein bound and hence may interact with drugs that are substrates for any of these enzymes or are highly protein bound themselves. It may also potentiate the CNS depressant effects of alcohol. It may also interact with:
Anticoagulants, due to its ability to prolong the bleeding time.
Psychotropic agents; potential pharmacokinetic interactions.
Benzodiazepines; may potentiate CNS depression and there are possible pharmacokinetic interactions.
Ethosuximide; potential for ethosuximide toxicity.
Primidone; may reduce pyrimidone's clearance leading to toxicity.
Zidovudine; may raise its (zidovudine's) serum concentration and lead to toxicity.
Aspirin; may displace valproate from plasma proteins, leading to increased plasma concentrations. Also interferes with valproate's metabolism.
Felbamate; may increase plasma concentrations of valproate.
Mefloquine; potential for increased valproate metabolism combined with the direct epileptogenic effects of mefloquine.
Cimetidine; inhibits valproate's metabolism in the liver, hence leading to increased plasma concentrations of valproate.
Erythromycin; inhibits valproate's metabolism in the liver, hence leading to increased plasma concentrations of valproate.
Carbapenem antibiotics; reduces valproate levels, potentially leading to seizures.
Special monitoring
Excessive amounts of valproic acid can result in tremor, stupor, respiratory depression, coma, metabolic acidosis, and death. In general, serum or plasma valproic acid concentrations are in a range of 20–100 mg/l during controlled therapy, but may reach 150–1500 mg/l following acute poisoning. Monitoring of the serum level is often accomplished using commercial immunoassay techniques, although some laboratories employ gas or liquid chromatography.
Education for patient/carers
Education about side effects
Storage
If a dose is missed take one as soon as possible however if the next dose is due just take the next dose
Consult the doctor if experiencing any side effects or if there are any concerns
Take as directed
Alcohol taking not recommended
References
Citrome L (2009) Adjunctive lithium and anticonvulsants for the treatment of schizophrenia: what is the evidence? Expert Rev Neurother 9: 55–71. doi: 10.1586/14737175.9.1.55
Haw C, Stubbs J (2005) A survey of the off-label use of mood stabilizers in a large psychiatric hospital. J Psychopharmacol 19: 402–407. doi: 10.1177/0269881105053307
Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Guerreiro C, Kalviainen R, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2013;54:551-63.
www.health.vic.gov.au/mentalhealth/druginfo/index.htm