Table 4.
AED | Added Drug | Clinical Consequence | Level of Importance (1-2) | Precautions |
---|---|---|---|---|
Carbamazepine | Oral contraceptives | Induction of estrogen metabolism, reduction in serum concentrations, and loss of contraceptive effect | Level 1: Should be avoided | Avoid the combination (or use of oral contraceptives with >50 µg ethinylestradiol), utilize barrier contraception. Addition of 4 mg folic acid daily for women of child bearing potential if used |
Carbamazepine | Antibiotics: Clarithromycin, erythromycin, troleandomycin | Inhibition of carbamazepine metabolism, elevated serum concentrations, giving rise to potential serious toxicity if the antibiotics are added | Level 1: Should be avoided | Avoid macrolide antibiotics that inhibit CYP3A4, prefer azithromycin or spiramycin |
Carbamazepine | Dextropropoxyphene | Inhibition of carbamazepine metabolism, elevated serum concentrations, giving rise to potential serious toxicity if the analgesic drug is added | Level 1: Should be avoided | The combination should be avoided. |
Lamotrigine | Oral contraceptives | Induction of lamotrigine metabolism, reduction in serum concentrations by 50 %, and reduced seizure control, if OCs are added | Level 1: Should be avoided | The combination should be avoided. Alternatively, increase in lamotrigine dose and monitor closely |
Valproic acid | Lamotrigine |
|
Level 2: Dosage adjustments and monitoring are needed |
|
Valproic acid | Phenobarbital | Inhibition of phenobarbital metabolism resulting in elevated serum concentrations, and risk of intoxication if valproic acid is added as a second drug | Level 2: Dosage adjustments and monitoring are needed | A reduction in phenobarbital dose by up to 80 % |
Carbamazepine (or phenobarbital, phenytoin, primidone) | Oral anticoagulant: Warfarin | Induction of warfarin metabolism, reduced serum concentrations, increasing the risk of coagulation that may be fatal if enzyme-inducing AEDs are added | Level 2: Dosage adjustments and monitoring are needed | An increase in the warfarin dose required to maintain the INR, close monitoring of INR. |
Carbamazepine (or phenobarbital, phenytoin, primidone) | Immunsuppressants: Ciclosporin, tacrolimus | Induction of immunosuppressant metabolism, reduction in serum concentrations, and potential therapeutic failure if enzymeinducing AEDs are added | Level 2: Dosage adjustments and monitoring are needed | Increase in the dose of immunosuppressant to avoid therapeutic failure, important for drugs with a narrow therapeutic range |
AEDs=Antiepileptic drugs. Several references are used, see text for details.