MAOIs: See Contraindications and Precautions.
Pimozide: Increased pimozide levels have been demonstrated in a study of a single low dose pimozide (2 mg) with sertraline co-administration. These increased levels were not associated with any changes in EKG. While the mechanism of this interaction is unknown, due to the narrow therapeutic index of pimozide, concomitant administration of sertraline and pimozide is contraindicated.
CNS Depressants and Alcohol: The co-administration of sertraline 200 mg daily did not potentiate the effects of alcohol, carbamazepine, haloperidol or phenytoin on cognitive and psychomotor performance in healthy subjects; however, the concomitant use of sertraline and alcohol is not recommended.
Lithium: In placebo-controlled trials in normal volunteers, the co-administration of sertraline with lithium did not significantly alter lithium pharmacokinetics, but did result in an increase in tremor relative to placebo, indicating a possible pharmacodynamic interaction. When co-administering sertraline with medications eg, lithium, which may act via serotonergic mechanisms, patients should be appropriately monitored.
Phenytoin: Placebo-controlled trials in normal volunteers suggest that chronic administration of sertraline 200 mg/day does not produce clinically important inhibition of phenytoin metabolism. Nonetheless, it is recommended that plasma phenytoin concentrations be monitored following initiation of sertraline therapy, with appropriate adjustments to the phenytoin dose. In addition, co-administration of phenytoin may cause a reduction of sertraline plasma levels.
Sumatriptan: There have been rare post-marketing reports describing patients with weakness, hyperreflexia, incoordination, confusion, anxiety and agitation following the use of sertraline and sumatriptan. If concomitant treatment with sertraline and sumatriptan is clinically warranted, appropriate observation of the patient is advised (see Other Serotonergic Drugs under Precautions).
Other Serotonergic Drugs: See Precautions.
Protein-Bound Drugs: Since sertraline is bound to plasma proteins, the potential of sertraline to interact with other plasma protein-bound drugs should be borne in mind. However, in 3 formal interaction studies with diazepam, tolbutamide and warfarin, respectively, sertraline was not shown to have significant effects on the protein binding of the substrate (see Warfarin and Other Drug Interactions as follows).
Warfarin: Co-administration of sertraline 200 mg daily with warfarin resulted in a small but statistically significant increase in prothrombin time, the clinical significance of which is unknown. Accordingly, prothrombin time should be carefully monitored when sertraline therapy is initiated or stopped.
Other Drug Interactions: Formal drug interaction studies have been performed with sertraline. Co-administration of sertraline 200 mg daily with diazepam or tolbutamide resulted in small, statistically significant changes in some pharmacokinetic parameters. Co-administration with cimetidine caused a substantial decrease in sertraline clearance. The clinical significance of these changes is unknown. Sertraline had no effect on the β-adrenergic-blocking ability of atenolol. No interaction of sertraline 200 mg daily was observed with glibenclamide or digoxin.
Electroconvulsive Therapy (ECT): There are no clinical studies establishing the risks or benefits of the combined use of ECT and sertraline.
Drugs Metabolized by Cytochrome P-450 (CYP)2D6: There is variability among antidepressants in the extent to which they inhibit the activity of isozyme CYP 2D6. The clinical significance of this depends on the extent of the inhibition and the therapeutic index of the co-administered drug. CYP 2D6 substrates with a narrow theapeutic index include TCAs and class 1C antiarrhythmics eg, propafenone and flecainide. In formal interaction studies, chronic dosing with sertraline 50 mg daily showed minimal elevation (mean 23-37%) of steady-state desipramine plasma levels (a marker of CYP 2D6 isoenzyme activity).
Drugs Metabolized by Other CYP Enzymes (CYP 3A3/4, CYP 2C9, CYP 2C19, CYP 1A2) CYP 3A3/4: In vivo interaction studies have demonstrated that chronic administration of sertraline 200 mg daily does not inhibit the CYP 3A3/4-mediated 6-β hydroxylation of endogenous cortisol or the metabolism of carbamazepine or terfenadine. In addition, the chronic administration of sertraline 50 mg daily does not inhibit the CYP 3A3/4-mediated metabolism of alprazolam. The data suggest that sertraline is not a clinically relevant inhibitor of CYP 3A3/4.
CYP 2C9: The apparent lack of clinically significant effects of the chronic administration of sertraline 200 mg daily on plasma concentrations of tolbutamide, phenytoin and warfarin suggests that sertraline is not a clinically relevant inhibitor of CYP 2C9 (see Other Drug Interactions, Phenytoin and Warfarin).
CYP 2C19: The apparent lack of clinically significant effects of the chronic administration of sertraline 200 mg daily on plasma concentrations of diazepam suggests that sertraline is not a clinically relevant inhibitor of CYP 2C19 (see Other Drug Interactions).
CYP 1A2: In vitro studies indicate that sertraline has little or no potential to inhibit CYP 1A2.