Milnacipran: uses, dosing, side effects & brands

The most frequently occurring adverse reactions (≥ 5% and greater than placebo) were nausea, headache, constipation, dizziness, insomnia, hot flush, hyperhidrosis, vomiting, palpitations, heart rate increased, dry mouth, and hypertension ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial s Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Patient Exposure SAVELLA was evaluated in three double-blind placebo-controlled trials involving 2209 fibromyalgia patients (1557 patients treated with SAVELLA and 652 patients treated with placebo) for a treatment period up to 29 weeks. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Adverse Reactions Leading to Discontinuation In placebo-controlled trials in patients with fibromyalgia, 23% of patients treated with SAVELLA 100 mg/day, 26% of patients…

Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with SAVELLA or within 5 days of stopping treatment with SAVELLA. Do not use SAVELLA within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start SAVELLA in a patient who is being treated with linezolid or intravenous methylene blue ( 4.1 , 5.2 ). 4.1 Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with SAVELLA or within 5 days of stopping treatment with SAVELLA is contraindicated because of an increased risk of serotonin syndrome. The use of SAVELLA within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration ( 2.5 ), Warnings and Precautions ( 5.2 )] . Starting SAVELLA in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration ( 2.6 ), Warnings and Precautions ( 5.2 )] .

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 [see Pharmacokinetics in Special Populations ( 12.3 )] . SAVELLA is unlikely to be involved in clinically significant pharmacokinetic drug interactions ( 7 ). Pharmacodynamic interactions of SAVELLA with other drugs can occur ( 7 ). 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 [see Dosage and Administration ( 2.5 , 2.6 ), Contraindications ( 4 ), Drug Interactions ( 7.1 )] . 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 [ s ee Dosage and Administration ( 2.5 , 2.6 ), Warnings and Precautions ( 5.2 )] . 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 [see Warnings and Precautions ( 5.2 )] . 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 [see Warnings and Precautions ( 5.3 , 5.4 )] . 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 [see Warnings and Precautions ( 5.3 , 5.4 )] . 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 [see Warnings and Precautions ( 5.9 )] .