Valparin XR 500 Drug Interactions

Combinations requiring precautions: Imipramine antidepressant: Imipramine antidepressants may promote generalized convulsions. Clinical monitoring and possibly dosage increase of antiepileptics may be necessary.
Phenobarbital: Increase in plasma phenobarbital concentrations (due to inhibition of liver catabolism), may occur with sedation, most often in children. Clinical monitoring during the first 2 weeks of the combination and immediate phenobarbital dose reduction when signs of sedation develop; if necessary, monitor plasma phenobarbital levels.
Phenytoin: Generally, decreases total phenytoin plasma concentrations. In particular, increase in the concentrations of free phenytoin, which may lead to signs of overdosage (valproic displaces phenytoin from its plasma protein binding site and slows its liver catabolism). Clinical monitoring is recommended. If plasma phenytoin are determined, the free form is the most important to consider.
Primidone: Increase in plasma primidone levels with enhancement of its adverse effects (sedation). After prolonged use, this interaction ceases. Clinical monitoring recommended and if necessary, primidone dosage adjustments should be considered, especially at the beginning of the co-administration.
Carbamazepine: Clinical toxicity has been reported when administered with carbamazepine, as sodium valproate + valproic acid may potentiate toxic effects of carbamazepine.
Lamotrigine: Valproate may reduce lamotrigine metabolism necessitating dosage reduction of latter.
Felbamate: Valproic acid may decrease felbamate mean clearance by up to 16%.
Zidovudine: Valproate may raise zidovudine plasma concentration leading to increased zidovudine toxicity.
Mefloquine and Chloroquine: Increases valproic acid metabolism and has a convulsant effect; therefore epileptic seizures may occur in combined therapy.
Carbapenem antibiotics such as imipenem, panipenem and meropenem: A clinically significant reduction in serum valproic acid concentration has been reported in patients receiving carbapenem antibiotics and may result in loss of seizure control.
Colestyramine may decrease the absorption of sodium valproale + valproic acid.
Rifampicin: May decrease the valproic acid blood levels resulting in lack of therapeutic effect. Therefore, valproate dosage adjustment may be necessary when it is co-administered with rifampicin.
Topiramate: Concomitant administration of sodium valparoate + valproic acid and topiramate has been associated with encephalopathy and/or hyperammonaemia. In patients, taking these two drugs, careful monitoring of signs and symptoms is advised in particularly at-risk patients such as those with pre-existing encephalopathy.
Miscellaneous: In case of concomitant use of valproate and highly bound protein drugs (like aspirin), free serum levels of valproate may be increased.
The serum levels of valproate may be increased (as a result of reduced hepatic metabolism) in case of concomitant use with cimetidine or erythromycin.
Close monitoring of prothrombin time should be performed in case of concomitant use of Vitamin K dependent anti-coagulant.