Drug Interaction:
Interacting drugs -summary-
Primodone +
Acetozolamide
co-administration decrease primidone concentrations.
Primidone + Carbamazepine/ or Carbamazepine + primidone
co-administration result in lower primidone and barbital. conc.
and higher carbamazepine conc.
+ Primidone
Hydantoin
primidone, phenobarbital and PEMA concentration may be increased
Isoniazid
primidone conc may be increased.
Nicotinamide
clearance rate of primidone may be decreased.
Succinimide
co-admin result in lower primidone and phenobarbital conc
Adverse Reaction:
CNS- Ataxia, vertigo, (these tend to disappear with continued therapy or with reduction in initial dosage) fatigue, emotional disturbances, diplopia, nystagmus, drowsiness, personality deterioration, with mood changes, and paronia.
GI- Nausea, anorexia, vomiting
Hematologic- Megaloblastic anemia may occur as rare idiosyncracy and responds to folic acid without the necessecity of discontinuing medication. Thrombocytopenia has also occured
Miscellaneous- Impotence, morbilliform and maculopapular skin eruption.
Contra-Indications:
Porphyria, hypersensitivity to phenobarbital.
Special precautions:
Abrupt withdrawal of antiepileptic medication may precipitate status epilepticus.
Monitoring- because therapy generally extends over prolonged periods perform complete blood counts and sequential
multiple analysis test every 6 months.
Hazardous tasks- patients should use cautin while driving or performing other tasks requiring alertness, coordination,
or physical dexterity.
Warnings-
Status epilepticus- abrupt withdrawal of antiepileptic medication may precipitate status epilepticus
Therapeutic efficacy- of a dosage regimen takes several weeks to assess.
Pregnancy- the effects of primidone in pregnancy is unknown
Lactation- it is suggested that undue somnolence and drowsiness in nursing newborns of
primidone-treated mothers be taken as an indicaton to discontinue nursing
Dosages/ Overdosage Etc:
Indications:
Grand mal,psychomotors seizures
Dosage::
Individualise dose.
Adults and children over 8 years- 100 to 125mg once, and increased to 3 times daily..
Maintenance- 250mg 3 or 4 times daily
Children below 8 years- 50 to 100mg gradually increased to 2 or 3 times a day.
Maintenance- 125 to 250mg 3 or 4 times daily.
Missed dose-
1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.
3. Do not double doses.
Other Information:
Megablastic anemia- ( 1518 )
The megablastic anemias are important examples of disordered erythroid maturation withdistinctive blood and bone
marrow morphology. These disordered are characterized by impairment of desoxyribonucleic acid ( DNA ) synthesis.
Drugs causing adverse reactions- ( 385 )
1.Folate antagonists
2. Cotrimoxazole
3. Phenytoin
4. Primidone
5. Phenobarbital
6. Triamterene
7. Trimethoprim
8. Oral contraceptives
Lymphadenopathy- ( 280 )
Lymphanopathy may be due to an increase in the number and size of lymphoid follicles with proliferation of lymphocytes or reticuloendothelial cells or to infiltration of the node by cells normally not present in it. Nodal cells proliferate inresponse to antigens to other stimuli which evoke greater phagocytic activity and to unknown stimuli which cause nodal cells to become tranformed to lymphoma cells and to proliferate autonomously.
Drugs causing adverse reactions - ( 585 )
1. Phenytoin
2. Primidone
Patient Information:
1.Drowsiness,dizziness or muscular incoordination may occur initially,but these symptoms
usually disappear without continued therapy.
2. Observe caution while driving or performing other tasks requiring alertness.
3. If GI upset occurs,take with food.
4 Do not discontinue medication abruptly or change dosage, except on advice of physician.
5. Notify physician,if skin or fever occurs or if patient becomes pregnant.
Pharmacology/ Pharmacokinetics:
Pharmacology:
Divalproex is a stable co-ordinatin compound of sodium valproate and valproic acid in a 1:1 molar relationship and formed during the partial neutralisation of valproic acid and with 0.5 equivalent of sodium hydroxide.
The mechanisms by which valproate exerts its therapeutic effects have not been established. It is suggested that that activity in epilepsy is related to increased brain concentrations of gamma-aminobutyric acid (GABA), possibly caused by decreased metabolism or decreased re-uptake in brain tissues.
Interaction with Food:
Not significant
Pregnancy and lactation:
Pregnancy: Effects unknown. Use with caution.
Lactation: Appears in breast milk in substantial quantities. Discontinue the drug while nursing.
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