Primidone adverse effects

Primidone is an other second line barbiturate used orally to control tonic-clonic and partial seizures. It is a pro-drug as it is metabolized to phenobarbital and phenylethylmalonamide (PEMA), however both the parent compound as well as the metabolites have anti seizure activity. Its use is more difficult to monitor and adverse effects occur even more frequently than with phenobarbital. 

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. 

Correct choice = D. Primidone does not cause hepatotoxicity. The adverse effects seen with this drug are the same as those seen with phenobarbital. 

Clozapine has been used to treat benign essential tremor refractory to the usual drugs (propranolol, primidone, alprazolam, phenobarbital, and botulinum toxin) in a randomized, double-blind, crossover study in 15 patients with essential tremor (58). Responders with more than 50% improvement after a single dose of clozapine 12.5 mg, compared with placebo, subsequently received 39-50 mg unblinded for a mean of 16 months. Tremor was effectively reduced by a single dose of clozapine in 13 of 15 patients sedation was the only adverse effect reported. 

Of 26 patients with complex partial seizures refractory to phenytoin, carbamazepine, phenobarbital, or primidone, mesuximide produced a 50% or greater reduction in seizure frequency in eight after 8 weeks, and five of those continued to benefit after 3-34 months (1). Drowsiness, gastrointestinal disturbances, hiccups, irritability, and headache were the common adverse effects. 

Primidone, a deoxybarbiturate, is partly metabolized to phenobarbital, which is responsible for most of its pharmacological effects. During chronic dosing, the adverse effects of primidone are identical to those of phenobarbital. However, at the start of treatment, primidone can cause a transient intolerance reaction with malaise, dizziness, nausea, vomiting, headache, and other symptoms. 

The use and adverse effects of primidone in the treatment of essential tremor has been reviewed (1). Acute reactions include vertigo, nausea, and unsteadiness chronic reactions include worsening of depression. 

As with phenobarbital, serious toxicity for primidone is rare, although it may cause disabling sedation. Irritability, and decreased mental functioning In a number of persons. Ataxia, dysphoria, idiosyncratic rash, leukopenia, agranulocytosis, lymphadenopathy, hepatitis, and a systemic lupus erythematosus-like syndrome have been reported adverse effects for primidone. Deficiencies of folic acid and of vitamins D and K are possible with long-term therapy of primidone, as Is a folate-responsive megaloblastic anemia. Measurement of the complete blood cell count should be performed at 6-month intervals (40). 

An established interaction. If felbamate is added to established treatment with phenobarbital or primidone, particularly in patients already taking substmtial doses, monitor well for any evidence of increased adverse effects (drowsiness, lethargy, anorexia, ataxia) and reduce the dosages of the phenobarbital or primidone if necessary. 

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. 

Antiepileptic drugs (AEDs) provide the best treatment option for most patients with epilepsy (Glauser et al. 2006). The first synthetic anticonvulsant was phe-nobarbital (PB) (1912). The other older AEDs still in clinical use include phe-nytoin (PHT), primidone (PRD), carbamazepine (CBZ) and valproate (VPA). There has been a significant influx of new AEDs during the past 20 years and more than 30 are available today. In approximately 75% of the patients, the age of onset is below 20 years and long-lasting therapy is often required. Therefore, the chronic adverse effects of AEDs are an important issue. 

Comparative studies In an open prospective comparison of valproate and primidone in 136 patients with partial epilepsy unresponsive to carbamazepine significantly more of those who took valproate (51%) achieved a greater than 50% seizure reduction than those who took primidone (34%) [231 ]. One patient withdrew from valproate because of dizziness and three because of nausea. Of those who took primidone, three withdrew because of dizziness, three patients because of drowsiness, and one because of gastrointestinal complaints. Adverse effects in other patients were mild and gradually disappeared during treatment. 

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