Primidone dosing

There seems to be little consistency about the effect of valproate on primidone levels. However, in the majority of cases phenobarbital levels seem to be raised (see also Phenobarbital + Valproate , p.547). It would seem prudent not to measure primidone levels without corresponding phenobarbital levels. Monitor the patient for increased signs of station, which may be resolved by a reduction in the primidone dose. 

Primidone has a comparatively short half-life of 10-12 hours (B17). Therefore, the time relationships between blood sampling and dose regimes acquire greater importance when interpreting the results than with either phenobarbitone or phenytoin. 

Adjunctive therapy For dosing guidelines below, enzyme-inducing antiepileptic drugs (ElAEDs) include phenytoin, carbamazepine, phenobarbital, and primidone. Patients 2 to 12 years of age ... 

Conversion from adjunctive therapy with AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate to monotherapy with lamothgine No specific dosing guidelines can be provided for conversion to monotherapy with lamothgine with AEDs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate. 

Stopping oral contraceptives - For women not taking carbamazepine, phenytoin, phenobarbital, primidone, or rifampin, the maintenance dose of lamotrigine may need to be decreased by as much as 50% of the maintenance dose with concurrent oral contraceptives. 

Carbamazepine also can induce the enzymes that metabolize other anticonvulsant drugs, including phenytoin, primidone, phenobarbital, valproic acid, clonazepam, and ethosuximide, and metabolism of other drugs the patient may be taking. Similarly, other drugs may induce metabolism of carbamazepine the end result is the same as for autoinduction, and the dose of carbamazepine must be readjusted. A common drug-drug interaction is between carbamazepine and the macrolide antibiotics erythromycin and trolean-domycin. After a few days of antibiotic therapy, symptoms of carbamazepine toxicity develop this is readily reversible if either the antibiotic or carbamazepine is discontinued. 

Approximately doubles widi valproate and decreases by approximately half with carbamazepine/primidone/phenytoin/phenobar-bital/rifampin therefore, initial doses may vary depending on concomitant medications. 

CBZ stimulates the CYP-450 enzyme system, increasing clearance of concomitantly prescribed drugs also metabolized by this system ( 377). Thus, the dose of these medications may need to be increased to maintain efficacy (372). Levels of CBZ may also be influenced by other hepatically metabolized, co-prescribed drugs. VPA, isonicotine, hydrazine, and erythromycin are some of the agents that can increase CBZ levels, while agents such as phenytoin and primidone can lower them. Table 10-25 summarizes the potentially clinically significant interactions between CBZ and other commonly co-prescribed medications ( 379, 380). 

Primidone has a larger clearance than most other antiseizure drugs (2 L/kg/d), corresponding to a half-life of 6-8 hours. clearance is approximately half that of primidone, but phenobarbital has a very low clearance. The appearance of phenobarbital corresponds to the disappearance of primidone. Phenobarbital therefore accumulates very slowly but eventually reaches therapeutic concentrations in most patients when therapeutic doses of primidone are administered. During chronic therapy, phenobarbital levels derived from primidone are usually two to three times higher than primidone levels. 

The dose-related adverse effects of primidone are similar to those of its metabolite, phenobarbital, except that drowsiness occurs early in treatment and may be prominent if the initial dose is too large. Gradual increments are indicated when starting the drug in either children or adults. 

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