Cases of serious sometimes fatal reactions have been reported in patients receiving Sertraline. In combination with monoamine oxidase inhibitor (MAOI), symptoms of a drug interaction between an SSRI and a MAOI include hyperthermia, rigidity, myoclonus autonomic instability with possible rapid fluctuations of vital signs, mental status changes that include confusion, irritability and extreme agitation progressing to delirium and coma. Some cases presented with features resembling neuroleptic malignant syndrome. Therefore, Sertraline should not be used in combination with a MAOI or within 14 days of discontinuing treatment with a MAOI. Similarly, at least 14 days should be allowed after stopping Sertraline before starting a MAOI.
Concurrent use of intravenous Diazepam with Sertraline may reduce the clearance and prolong the half-life of Diazepam.
Caution is recommended during concurrent use of Digitoxin and Warfarin with Sertraline because of possible displacement of either medication from protein binding sites. This may lead to increase plasma concentration sand increased risk of adverse effects. Prothrombin time should be carefully monitored when Sertraline therapy is initiated or stopped in patients taking Warfarin. Drugs metabolized with cytochrome P450 2D6, Sertraline inhibits the biochemical activity of the drug metabolizing isozyme P450 2D6 and, thus may increase the plasma concentration of co-administered drugs, (which are metabolized by P450 2D6) such as tricyclic antidepressants and Type IC antiarrythmics, Propafenone, and Flecainide. Dose reduction may be required.
Nonetheless, it is recommended that plasma lithium levels be monitored following initiations of Sertraline therapy with appropriate adjustment to the lithium dose.