Milnacipraninteractions

Milnacipran undergoes minimal CYP450 related metabolism, with the majority of the dose excreted unchanged in urine (55%) and has a low binding to plasma proteins (13%). In vitro and in vivo studies showed that SAVELLA is unlikely to be involved in clinically significant pharmacokinetic drug interactions.

SAVELLA is unlikely to be involved in clinically significant pharmacokinetic drug interactions.

Pharmacodynamic interactions of SAVELLA with other drugs can occur.

7.1 Monoamine

Oxidase Inhibitors (MAOIs) The concomitant use of SSRIs and SNRIs, including SAVELLA, with MAOIs increases the risk of serotonin syndrome. The use of MAOIs intended to treat psychiatric disorders with SAVELLA or within 5 days of stopping treatment with SAVELLA is contraindicated. The use of SAVELLA within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated. In addition, do not initiate SAVELLA in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with a MAOI such as linezolid or intravenous methylene blue in a patient taking SAVELLA, discontinue SAVELLA before initiating treatment with the MAOI.

7.2 Serotonergic

Drugs Serotonin syndrome can occur with use of SAVELLA and other serotonergic drugs (other SNRIs, SSRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort), or with drugs that impair metabolism of serotonin (i.e., monoamine oxidase inhibitors). Advise patients of the signs and symptoms associated with serotonin syndrome and to seek medical care immediately if they experience these symptoms.

7.3 Triptans

There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of SAVELLA with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. 7.4 Catecholamines SAVELLA inhibits the reuptake of norepinephrine. Therefore, concomitant use of SAVELLA with epinephrine and norepinephrine may be associated with paroxysmal hypertension and possible arrhythmia.

7.5 CNS-active drugs

Given the primary CNS effects of SAVELLA, use caution when it is taken in combination with other centrally acting drugs, including those with a similar mechanism of action.

Clomipramine: In a drug-drug interaction study, an increase in euphoria and postural hypotension was observed in patients who switched from clomipramine to SAVELLA.

7.6 Clinically

Important Interactions with Select Cardiovascular Agents Digoxin: Use of SAVELLA concomitantly with digoxin may be associated with potentiation of adverse hemodynamic effects. Postural hypotension and tachycardia have been reported in combination therapy with intravenously administered digoxin (1 mg). Avoid co-administration of SAVELLA and intravenous digoxin.

Clonidine: Because SAVELLA inhibits norepinephrine reuptake, co-administration with clonidine may inhibit clonidine’s anti-hypertensive effect.

7.7 Drugs that

Interfere with Hemostasis Concomitant use of SAVELLA with an antiplatelet or anticoagulant drug (e.g., NSAIDs, aspirin, and warfarin) may potentiate the risk of bleeding. This may be due to the effect of SAVELLA on the release of serotonin by platelets. Closely monitor for bleeding for patients receiving an antiplatelet or anticoagulant drug when SAVELLA is initiated or discontinued.