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SAVELLA (MILNACIPRAN): DRUG INTERACTIONS

Savella (Milnacipran Hydrochloride) 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 this drug is unlikely to be involved in clinically significant pharmacokinetic drug interactions.

Serotonergic Drugs

Due to the mechanism of action of SNRIs and SSRIs, including Milnacipran (Savella), and the potential for serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions, caution is advised when this medicine is co-administered with other drugs that may affect the serotonergic neurotransmitter systems. This includes drugs such as lithium, triptans, tryptophan, antipsychotics and dopamine antagonists.

Co-administration of Milnacipran HCl (Savella) with other inhibitors of serotonin re-uptake may result in hypertension and coronary artery vasoconstriction, through additive serotonergic effects. Concomitant use of this medication with other SSRIs, SNRIs, or tryptophan is not recommended.

Triptans

There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of Milnacipran Hydrochloride (Savella) with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.

Catecholamines

This drug inhibits the reuptake of norepinephrine. Therefore concomitant use of Savella with epinephrine and norepinephrine may be associated with paroxysmal hypertension and possible arrhythmia.

CNS-active drugs

Given the primary CNS effects of Savella (Milnacipran), caution should be used 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 (Milnacipran HCl).

Clinically Important Interactions with Select Cardiovascular Agents

Digoxin: Use of Savella (Milnacipran Hydrochloride) 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). Co-administration of Milnacipran (Savella) and intravenous digoxin should be avoided.

Clonidine: Because Milnacipran HCl (Savella) inhibits norepinephrine reuptake, co-administration with clonidine may inhibit clonidine's anti-hypertensive effect.

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