Important Drug-Drug Interactions

Valproic acid (VPA) + Lamotrigine:

• Valproic acid (VPA) increases lamotrigine levels

• Increases risk of Steven-Johnson’s Syndrome (SJS/TEN)

• When using both, decrease the dose of lamotrigine by 50%

Carbamazepine (CBZ) is an inducer of CYP3A4:

• CBZ induces its own metabolism

• CBZ induces the metabolism of numerous other medications including oral contraceptives, clozapine, alprazolam, buspirone, and clonazepam

Lithium + NSAIDs (not aspirin), ACE Inhibitors, Thiazide diuretics, low sodium diet:

• Increases lithium levels

Lithium + caffeine, theophylline, high sodium diet:

• Decreases lithium levels

Grapefruit Juice

• Grapefruit juice is a potent inhibitor of CYP3A4 and P-glycoprotein

• Grapefruit juice increases blood levels of many medications metabolized by CYP3A4

Smoking Tobacco cigarettes:

• Induces activity of CYP1A2

• The induction does not appear to be from the nicotine, but from the hydrocarbons in smoke

• Decreases blood levels of medications metabolized by CYP1A2 (Olanzapine, Clozapine, Caffeine)

Tyramine:

• Increased risk of hypertensive crisis when eating tyramine containing foods while taking MAOIs, SSRIs, TCAs, Pseudoephedrine, and Stimulants

• Tyramine-rich foods include banana peel, beer, fava beans, aged cheese, sauerkraut, sausage, soy sauce, concentrated yeast extract.

Fluoxetine, Paroxetine, and Bupropion are potent inhibitors of CYP2D6:

• They can raise blood levels of medications metabolized by CYP2D6.

• Tamoxifen and Codeine are prodrugs requiring metabolism by CYP2D6. Efficacy of these drugs may be decreased when used with inhibitors of CYP2D6.

Antimicrobial-Psychotropic Drug Interactions:

• Antimalarials: Increase phenothiazine (e.g. chlorpromazine) levels

• Azoles: Increase alprazolam, midazolam, and buspirone levels

• Clarithromycin, Erythromycin: Increase alprazolam, midazolam, carbamazepine, clozapine, and buspirone levels

• Quinolones: Increase clozapine and benzodiazepine levels but decreases benzodiazepine effects

• Isoniazid: Increases haloperidol and carbamazepine levels. Isoniazid + disulfiram can cause ataxia

• Linezolid: Serotonin syndrome if used with serotonergic drugs

Other Interactions/Adverse Reactions:

• Erythromycin, Clarithromycin, and Ketoconazole: QT prolongation and ventricular arrythmias with TCAs and antipsychotics

• Linezolid is an irreversible MAO-A inhibitor: Serotonin syndrome and Hypertensive crisis

• Isoniazid is a weaker MAO inhibitor: Reports of Serotonin syndrome and hypertensive crisis