Epilepsy Research and Treatment / 2016 / Article / Tab 3

Research Article

Prevalence of Different Combinations of Antiepileptic Drugs and CNS Drugs in Elderly Home Care Service and Nursing Home Patients in Norway

Table 3

Mechanisms, clinical consequences, severity, and frequencies of pharmacokinetic drug-drug interactions involving antiepileptic drugs and other CNS-active drugs identified in patients ≥65 years () in home care services and nursing homes.

Antiepileptic drugSubstrates for these enzymes and possible interactionsClinical effects and potential consequences#SeverityFrequencies

Enzyme inducers

Carbamazepine, n = 189
 Enzyme-inducing properties, CYP 3A4, 2C9, 1A2, or UGTsBenzodiazepinesDecrease in serum concentrations of substrates of these enzymes and possibly a decrease in clinical efficacy. B32
Haloperidol Dose adjustment needed. Decreased serum concentration of haloperidol by 50% but varies with dose of carbamazepine.B7
LamotrigineDose adjustment needed. Decreased serum concentration of lamotrigine by 50%.B6
AmitriptylineDose adjustment needed. Decreased serum concentration of amitriptyline by 50–60%.B5
RisperidoneDose adjustment needed. Serum concentration of risperidone and active metabolite reduced by 65% and 50%, respectively.B4
QuetiapineDose adjustment needed. Maximum serum concentrations of quetiapine reduced by nearly 80%.A3
Valproic acidDose adjustments needed for both drugs. Carbamazepine concentration increased by 25–50%, while valproate concentration reduced by 30%.B2

Phenobarbital, n = 63
 Enzyme-inducing properties, CYP 3A4 or UGTHaloperidol Dose adjustment needed because of decreased serum concentration of haloperidol by 50%.B2
 Enzyme inhibitory properties on CYP 2C19RisperidoneDose adjustment needed. Increased serum concentration of risperidone and thus a potential increase of adverse effects or toxicity.B1

Phenytoin, n = 39
 Enzyme-inducing properties, CYP 3A4 or UGTHaloperidol Dose adjustment needed. Decrease in serum concentrations of substrates of these enzymes and possibly a decrease in clinical efficacy because of decreased serum concentration of haloperidol by 50%.B1

Enzyme inhibitors

Valproic acid, n = 93
 Enzyme inhibitory properties on CYP 2C9/19, 3A4?, UGTsLamotrigineDose adjustment needed because of an increase in the serum concentrations of substrates of these enzymes. Clearance of lamotrigine reduced by 50%, potentially causing skin rashes and neurotoxic effects. B11
Amitriptyline, carbamazepineDose adjustment needed because of decrease of first-pass metabolism of amitriptyline.
For carbamazepine, see above.
B2
Clomipramine, phenobarbital, phenytoinDose adjustment needed because clearance of phenobarbital reduces by 40% and thus there is a risk of intoxication.B3

In total79

Clinical effects and potential consequences based on Norwegian and Danish interaction databases in addition to a review by Johannessen and Landmark, 2010 [1]. Weak inhibition based on Johannessen and Landmark 2010 [1]. #According to the Danish drug interaction database. The Norwegian interaction database (DRUID) denotes severity of drug-drug interactions according to a three-point severity scale: A, should not be combined, B, take precautions, and C, of academic interest. Herein, only drug-drug interactions in categories A and B are shown. Drug-drug interactions involving the antiepileptic drugs felbamate (with carbamazepine, diazepam, phenobarbital, phenytoin, and valproic acid), oxcarbazepine (with lamotrigine, phenobarbital, and phenytoin), rufinamide (with carbamazepine and felbamate), stiripentol (with carbamazepine, felbamate, phenobarbital, phenytoin, and valproic acid), topiramate (>200 mg/day with phenytoin), and valproic acid (with clozapine, imipramine, nortriptyline, and rufinamide) were not identified and therefore not included. Duplicates not shown and not counted.

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