Primidone drug interactions

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. 

Geriatric Considerations - Summary Primidone is poorly tolerated in older adults avoid use if possible. Dosage adjustments are required in renal impairment. Numerous drug interactions with primidone exist. Primidone may reduce bone mineral den-sitybyinterferingwith vitamin D catabolism. Calcium and vitamin D supplementation and monitoring of bone mineral density are recommended for older adults taking this drug. 

Drug interactions involving AEDs are shown in Table 52-5. Phenobarbital, phoiytom, primidone and carbamazepine are potent inducers of cytochrome P450 (CYP450), epoxide hydrolase, and uridine diphosphate gjucuronosyltransferase enzyme systems. Valproic acid inhibits many hepatic enzjrme systems and displaces some drugs from plasma albumin. Felbamate and topiramate can act as inducers with some isoforms and inhibitors with others. 

Methylphenidate Phenytoin Primidone 2006 Elsevier B.V. All rights reserved. Risk of toxicity of the affected drugs interaction inconsistent Inhibition of metabolism of the object drugs Continued... 

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. 

Windorfer A, Sauer W. Drug interactions during anticonvulsant Iher y in childhood diphe-nylhydantoin, primidone, phenobarbitone, clonazepam, nitrazepam, carbamazepin and dipro-pylacetate. Neuropadiatrie (1977) 8, 29-41. 

Drugs that may interact with carbonic anhydrase inhibitors include cyclosporine, primidone, salicylates, and diflunisal. 

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). 

Corticosteroids interact with barbiturates, carbamazepine, phenytoin, primidone, frusemide, thiazide, NSAIDs, antidiabetics, and antihypertensive drugs. Benzquinamide hydrochloride is incompatible with chlordiazepoxide, diazepam, and some barbiturates. Care should be exercised when handling bisacodyl to avoid contact with skin and mucosal membranes. 

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

Most interactions of trimethoprim and co-trimoxazole with other drugs are due to fohc acid antagonism. This may be more pronounced with co-trimoxazole than with either drug alone. Such interactions have previously been suspected with anticonvulsants, such as barbiturates, phe-nytoin, and primidone, which themselves produce folic acid deficiency and megaloblastic anemia (88). In order to circumvent the risk of folate deficiency, folic acid or folinic acid can be given. There is some concern that folate replacement may antagonize the desired antimicrobial effect, particularly in some protozoal parasites, but this concern has been debated (89). 

The addition of piracetam (2 to 4 g three times daily, increased to a maximum of 18 to 24 g daily) did not affect plasma levels of sodium valproate or primidone in patients with myoclonus. The exact number of patients taking these drugs is unelear, sinee the report just states that 28 patients were taking clonazepam, sodium valproate, or primidone, alone or in combination. Another similar report, briefly noted the same finding. The manufacturer notes that, although based on a small number of patients, no interaction has been found between piracetam and clonazepam, carbamazepine, phenytoin, phenobarbital and sodium valproate. No special precautions appear to be required if piracetam is used with these antiepileptics. 

Primidone is substantially converted to phenobarbital within the body and it is therefore expected to interact with other drugs in the same way as phenobarbital. Some drugs may increase the conversion of primidone to phenobarbital. 

None of the interactions between the benzodiazepines and antiepileptics described here appear to be of major clinical importance, with the possible exception of the interaction between clobazam and felbamate. If both drugs are given be aware that additive sedative or other adverse effects may occur. This may also be possible in some rare cases with chlordiazepoxide or clobazam and phenobarbital clonazepam and lamotrigine or primidone and clorazepate and primidone. 

The manufacturers advise that if carbamazepine or other drugs that induce drug metabolism (such as phenytoin) are given with mirtazapine, the mirtazapine dose may have to be inereased. Further, if treatment with an inducer is stopped, the mirtazapine dosage may have to be reduced. - Although not specifically named, phenobarbital and primidone can also induce CYP3A4, and they therefore may interact similarly. Note that. 

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