Drug interactions valproate

Lamotrigine is not approved for the acute treatment of depression, and the dose must be started low and slowly titrated up to decrease adverse effects if used for maintenance therapy of bipolar I disorder. A drug interaction and a severe dermatologic rash may occur when lamotrigine is combined with valproate (i.e., lamotrigine doses must be halved from standard dosing titration). 

Carbamazepine is also most beneficial for patients with mixed episodes and rapid cycling. However, many patients find the side effects of carbamazepine more troublesome than those of valproate, and becanse carbamazepine has a penchant for nntoward drug-drug interactions, we reserve the use of carbamazepine for those patients who are unable to tolerate valproate, lithium, and the atypical antipsychotic... 

As with carbamazepine, the historical use of valproate for anxiety is not supported by robust clinical trials. A randomised study showed efficacy in panic disorder (Lum et al. 1991) and benefit has been reported in open studies in OCD and PTSD. The major side-effects are tremor, nausea, ataxia and weight gain and there is the potential for drug interactions via inhibition of hepatic enzymes. 

Booth CL, Pollack GM, Brouwer KL. Hepatobiliary disposition of valproic acid and valproate glucuronide use of a pharmacokinetic model to examine the rate-limiting steps and potential sites of drug interactions. Hepatology 1996 23(4) 771-780. 

Consider the difference in response to drugs between older and younger people. Treatment should reflect biological age (rather than chronological). Pharmacokinetics, pharmacodynamics, tolerability, adverse reactions, economy and patient choice will all influence therapy chosen. Most commonly, car-bamazepine or sodium valproate are chosen for older people as their effects in older people are well documented. Both show a favourable balance of safety, efficacy and economy. Phenytoin is less preferable because of drug interactions, adverse effects and potential for toxicity (zero order kinetics). 

Serious drug interactions are uncommon with valproate. Approximately 25% of valproate metabolism is dependent on CYP isoenzymes. Valproic acid can cause severe liver damage during the first 6 months of treatment. Note interactions with aspirin and the need to monitor plasma free valproate levels. 

Clobazam Carbamazepine Primidone Valproate Phenytoin Interaction inconsistent, usually of little clinical significance Inhibition of metabolism of the object drug... 

Lamotrigine 25-50 mg/day 150 mg/day 1% 100% 100% 100% Autoinduction, major drug-drug interaction with valproate No data No data Dose for GFR10-50 ml/min... 

Drug Interactions. Enzyme inducers, such as carbamazepine and phenytoin, increase tiagabine clearance and decrease the half-life. Food decreases the rate but not the extent of absorption. Tiagabine is displaced from protein by naproxen, salicylates, and valproate. However, tiagabine does not displace phenytoin, valproic acid, amitrypty-line, tolbutamide, or warfarin. ... 

I Drug-Drug Interactions. Carbamazepine induces the hepatic cytochrome P450 isoenzymes (1A2, 3A4, 2C9/10, and 2D6), which increases the metabolism of many medications, such as anticonvulsants (i.e., lamotrigine, topiramate, and valproate), antidepressants (i.e., tricyclics and bupropion), antipsychotics (i.e., clozapine, haloperi-dol, fluphenazine, olanzapine, and thiothixene), benzodiazepines, oral contraceptives, and protease inhibitors. " Women who receive carbamazepine require higher dosages of oral contraceptives or alternative contraceptive methods." ... 

Legend Drugs that can increase the serum 1 levels/effects of 1 valproate s r Drugs whose serum levels/effects can be increased by 1 valproate ( ) Questionable interaction... 

The combined use of valproate and paroxetine has not been found to result in any significant drug-drug interaction. 

DeVane CL. Pharmacokinetics, drug interactions, and tolerability of valproate. Psychopharmacol Bull 2003 (Summer) 37 25-42. 

Because of its inducing effect on hepatic enzymes, phenobarbitai has many drug interactions, decreasing plasma levels of CBZ, valproate, lamotrigine, tiagabine, zonisamide, warfarin, theophylline, cimetidine, and those of other CYP3A4 substrates. Serum concentrations of phenobarbitai are increased by valproate. 

Valproate, a substrate for hepatic CYP2C19 and CYP2C9, has an extensive pattern of drug interactions. It increases the plasma concentrations of lamotrigine, CBZ, and phenobarbital and the free fraction of phenytoin by either displacing these drugs from plasma proteins or inhibiting their metabolism. Phenytoin, phenobarbital, and CBZ cause decreased plasma concentrations of valproate, whereas felbamate increases valproate levels. 

Succinimides are indicated for the monotherapy of absence seizures or with concomitant therapy when additional forms of seizures occur in combination with absence seizures. These drugs are readily absorbed from the gastrointestinal tract and display very low protein binding. The drug interactions for the succinimides are less extensive than with the oxazolidinediones. They may increase plasma phenytoin levels, decrease plasma primidone levels, and either increase or decrease valproate levels, although the changes may not be clinically significant. 

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