Milnacipran hydrochloride

What is Milnacipran hydrochloride?

• Milnacipran hydrochloride (Savella) is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the management of fibromyalgia.

Milnacipran

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What are the uses of this medicine?

• Milnacipran hydrochloride (Savella) used for the management of fibromyalgia.
• Savella is not approved for use in pediatric patients.

How does this medicine work?

• The exact mechanism of the central pain inhibitory action of milnacipran and its ability to improve the symptoms of fibromyalgia in humans are unknown.
• Milnacipran is a potent inhibitor of neuronal norepinephrine and serotonin reuptake; milnacipran inhibits norepinephrine uptake with approximately 3-fold higher potency in vitro than serotonin without directly affecting the uptake of dopamine or other neurotransmitters.

Who Should Not Use this medicine ?

• Concomitant use of Savella in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated.
• Do not use Savella in patients with uncontrolled narrow-angle glaucoma.

What drug interactions can this medicine cause?

• Concomitant use of Savella in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated.
• Concomitant use of Savella with other SSRIs, SNRIs, or tryptophan is not recommended. This includes drugs such as triptans, lithium, tryptophan, antipsychotics and dopamine antagonists.
• Concomitant treatment of Savella with a triptan is clinically warranted, careful observation of the patient is advised, , particularly during treatment initiation and dose increases.
• Therefore concomitant use of Savella with epinephrine and norepinephrine may be associated with paroxysmal hypertension and possible arrhythmia.
• Caution should be used when it is taken in combination with other centrally acting drugs, including those with a similar mechanism of action.
• Co-administration of Savella and intravenous digoxin should be avoided.

Is this medicine FDA approved?

• Initial U.S. Approval: 2009

How should this medicine be used?

Recommended dosage:

• The recommended dose of Savella is 100 mg/day (50 mg twice daily).

Based on efficacy and tolerability dosing may be titrated according to the following schedule:

• Day 1: 12.5 mg once
• Days 2-3: 25 mg/day (12.5 mg twice daily)
• Days 4-7: 50 mg/day (25 mg twice daily)
• After Day 7: 100 mg/day (50 mg twice daily)

• Based on individual patient response, the dose may be increased to 200 mg/day (100 mg twice daily).
• Doses above 200 mg/day have not been studied.

Patients with Renal Insufficiency:

• No dosage adjustment is necessary in patients with mild renal impairment.
• Savella should be used with caution in patients with moderate renal impairment.
• For patients with severe renal impairment (indicated by an estimated creatinine clearance of 5-29 mL/min), the maintenance dose should be reduced by 50% to 50 mg/day (25 mg twice daily).
• Based on individual patient response, the dose may be increased to 100 mg/day (50 mg twice daily).
• Savella is not recommended for patients with end-stage renal disease.

Patients with Hepatic Insufficiency: No dosage adjustment is necessary for patients with hepatic impairment.

• Savella should be tapered and not abruptly discontinued after extended use.

• At least 14 days should elapse between discontinuation of a MAOI and initiation of therapy with Savella. In addition, at least 5 days should be allowed after stopping Savella before starting a MAOI.

Administration:

• Savella is given orally with or without food.
• Taking Savella with food may improve the tolerability of the drug.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 12.5 mg, 25 mg, 50 mg, 100 mg

This medicine is available in fallowing brand namesː

• Savella

What side effects can this medication cause?

The most common side effects of this medicine include:

• nausea
• headache
• constipation
• dizziness
• insomnia
• hot flush
• hyperhidrosis
• vomiting
• palpations
• heart rate increased
• dry mouth
• hypertension

What special precautions should I follow?

• Savella is a selective serotonin and norepinephrine re-uptake inhibitor (SNRI), similar to some drugs used for the treatment of depression and other psychiatric disorders. Monitor for worsening of depressive symptoms and suicide risk.
• Serotonin syndrome has been reported with SNRIs and SSRIs. Concomitant use of serotonergic drugs is not recommended.
• SNRIs, including Savella, have been associated with reports of increase in blood pressure. Monitor blood pressure and heart rate prior to initiating treatment with Savella and periodically throughout treatment.
• Savella has not been systematically evaluated in patients with a seizure disorder. Prescribe Savella with care in patients with a history of seizure disorder.
• More patients treated with Savella than with placebo experienced mild elevations of ALT and AST. Rarely, fulminant hepatitis has been reported in patients treated with Savella. Avoid concomitant use of Savella in patients with substantial alcohol use or chronic liver disease.
• Withdrawal symptoms have been reported in patients when discontinuing treatment with Savella. A gradual dose reduction is recommended.
• Savella may increase the risk of bleeding events. Caution patients about the risk of bleeding associated with the concomitant use of Savella and NSAIDs, aspirin, or other drugs that affect coagulation.
• Male patients with a history of obstructive uropathies may experience higher rates of genitourinary adverse events
• Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Savella. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Discontinuation of Savella should be considered in patients with symptomatic hyponatremia.
• Mydriasis has been reported in association with SNRIs and Savella; therefore, Savella should be used cautiously in patients with controlled narrow-angle glaucoma.
• Savella should not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• increased blood pressure, cardio-respiratory arrest, changes in the level of consciousness (ranging from somnolence to coma), confusional state, dizziness, and increased hepatic enzymes.

Treatment of overdosage:

• There is no specific antidote to Savella, but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/or temperature control) may be considered.
• In case of acute overdose, treatment should consist of those general measures employed in the management of overdose with any drug.
• An adequate airway, oxygenation, and ventilation should be assured and cardiac rhythm and vital signs should be monitored.
• Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients.
• Activated charcoal should be considered as soon as possible for patients who experience a Savella overdose.

Can this medicine be used in pregnancy?

• There are no adequate and well-controlled studies in pregnant women.
• Savella should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Can this medicine be used in children?

• Safety and effectiveness of Savella in a fibromyalgia pediatric population below the age of 17 have not been established.
• The use of Savella is not recommended in pediatric patients.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• MILNACIPRAN HYDROCHLORIDE

Inactive ingredients:

• DIBASIC CALCIUM PHOSPHATE DIHYDRATE
• POVIDONE
• CARBOXYMETHYLCELLULOSE CALCIUM
• SILICON DIOXIDE
• MAGNESIUM STEARATE
• TALC
• POLYETHYLENE GLYCOL
• TITANIUM DIOXIDE
• HYPROMELLOSES

Who manufactures and distributes this medicine?

Manufactured for: Forest Pharmaceuticals, Inc. Manufactured by: Forest Laboratories, Inc.

What should I know about storage and disposal of this medication?

• Store at 25°C (77°F); excursions permitted between 15°C and 30°C (between 59°F and 86°F).

• Dailymed label info on Milnacipran hydrochloride
• FDA Milnacipran hydrochloride

Milnacipran hydrochloride Resources
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The following are antidepressant subclasses and drugs

MAO Inhibitors Isocarboxazid, Phenelzine, Tranylcypromine

SNRIs Duloxetine, Levomilnacipran, Venlafaxine

SSRIs Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Vilazodone, Vortioxetine

Tricyclics Amitriptyline, Amoxapine, Clomipramine, Desipramine, Doxepin, Imipramine, Nortriptyline, Protriptyline, Trimipramine

Miscellaneous Bupropion, Flibanserin, Mirtazapine, Nefazodone, Trazodone