milnacipran hydrochloride

milnacipran hydrochloride

Savella

Pharmacologic class: Selective serotonin and norepinephrine reuptake inhibitor

Therapeutic class: Antidepressant

Pregnancy risk category C

FDA Box Warning

• Drug causes increased risk of suicidal ideation, thinking, and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders.

• Drug isn't approved for use in children.

Action

Unknown

Availability

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

Indications and dosages

Management of fibromyalgia

Adults: Initially, 12.5 mg P.O. on day 1; increase to 100 mg daily over 1 week by giving 12.5 mg b.i.d. on days 2 and 3; then 25 mg b.i.d. on days 4 to 7; after day 7, give 50 mg b.i.d.; may increase to 100 mg b.i.d. based on patient response

Dosage adjustment

• Severe renal impairment

Contraindications

• Monoamine oxidase (MAO) inhibitor use within past 14 days
• Uncontrolled narrow-angle glaucoma

Precautions

Use cautiously in:
• severe hepatic or moderate renal impairment
• seizures, significant hypertension, cardiac disease
• history of mania, patients with depressive symptoms, those at risk for suicide
• controlled narrow-angle glaucoma
• concomitant use of serotonin precursors (such as tryptophan) and selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors (use not recommended)
• concomitant use of drugs that increase blood pressure or heart rate
• concomitant use of I.V. digoxin
• concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, or other drugs that affect coagulation
• significant alcohol use or chronic hepatic disease (avoid use)
• obstructive uropathies (in males)
• elderly patients
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Check blood pressure and pulse rate before starting drug.
• Administer with or without food.

Don't give concurrently or within 14 days of MAO inhibitor therapy; allow 5 days after stopping drug before starting MAO inhibitor.

Adverse reactions

CNS: headache, tension headache, migraine, dizziness, insomnia, paresthesia, hypoesthesia, tremor, anxiety, fatigue, irritability, somnolence, depression, stress, seizures, neuroleptic malignant syndrome, suicidal behavior or ideation (especially in child or adolescent)

CV: increased heart rate, hypertension, tachycardia, palpitations, peripheral edema

EENT: blurred vision

GI: nausea, vomiting, constipation, dry mouth, abdominal pain, decreased appetite, diarrhea, dyspepsia, gastroesophageal reflux disease, flatulence, abdominal distention

GU: dysuria; ejaculation disorder; ejaculation failure; erectile dysfunction; decreased libido; prostatitis; scrotal, testicular, and urethral pain; testicular swelling; urinary hesitation and retention; decreased urine flow (males); urinary tract infection, cystitis

Hematologic: bleeding

Hepatic: fulminant hepatitis (rare)

Metabolic: hyponatremia, hypercholesterolemia

Respiratory: upper respiratory tract infection, dyspnea

Skin: rash, pruritus

Other: hot flushes, flushing, hyperhidrosis, chest pain or discomfort, chills, weight loss or gain, pyrexia, injury, poisoning, procedural complications, abnormal taste, night sweats, serotonin syndrome

Interactions

Drug-drug.Catecholamines (such as epinephrine, norepinephrine): increased risk of paroxysmal hypertension, cardiac arrhythmias

Clonidine: inhibited clonidine antihypertensive effects

Digoxin (I.V.): increased risk of adverse hemodynamic effects (such as orthostatic hypotension, tachycardia)

Drugs that affect coagulation (such as aspirin, NSAIDS): increased risk of bleeding

Drugs that affect serotonergic neurotransmitter system (such as antipsychotics, dopamine antagonists, lithium, triptans, tryptophan, and inhibitors of serotonin uptake [such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline]): increased risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions, increased risk of hypertension, coronary artery vasoconstriction

MAO inhibitors (such as isocarboxazid, phenelzine, tranylcypromine): increased risk of potentially fatal reactions (hyperthermia, myoclonus, autonomic instability)

Other centrally acting drugs: increased risk of CNS effects

Drug-diagnostic tests.Alanine aminotransferase, aspartate aminotransferase, cholesterol: increased levels

Sodium: decreased level

Drug-behaviors.Substantial alcohol use: aggravation of preexisting hepatic disease

Patient monitoring

Monitor patient's mental status carefully. Stay alert for mood changes and indications of suicidal ideation, especially in child or adolescent.

Discontinue drug and provide appropriate treatment if signs and symptoms of serotonin syndrome or neuroleptic malignant syndrome occur.

Discontinue drug if signs and symptoms of hepatic dysfunction occur; don't restart drug unless another cause can be determined.
• Consider discontinuing drug if symptomatic hyponatremia occurs.
• Monitor blood pressure and pulse rate periodically throughout treatment; consider discontinuing drug if sustained increases persist.
• Monitor liver function tests.

Patient teaching

• Instruct patient to take drug with or without food but that taking with food may increase tolerability.

Advise patient (and significant other as appropriate) to monitor patient's mental status carefully and to immediately report increased depression or suicidal thoughts or behavior (especially in child or adolescent).

Instruct patient to immediately report signs and symptoms of serotonin syndrome (from shivering and diarrhea to severe symptoms such as muscle rigidity, fever, and seizures).

Instruct patient to immediately report signs and symptoms of neuroleptic malignant syndrome, such as fever, muscle rigidity, altered mental status (including catatonic signs), irregular pulse or blood pressure, rapid heartbeat, and excessive sweating.

Tell patient to immediately report signs and symptoms of liver problems (such as yellowing of skin or eyes).

Caution patient not to stop taking drug suddenly and that drug must be tapered.
• Instruct patient to report headache, difficulty concentrating, memory impairment, weakness, or unsteadiness.
• Tell patient to monitor blood pressure and pulse rate regularly and report sustained increases.
• Tell patient to report signs and symptoms of bleeding, including easy bruising.
• Advise patient to avoid alcohol use while taking drug.
• Advise patient to consult prescriber before taking other prescription or nonprescription drugs, especially aspirin or NSAIDs.
• Caution patient to avoid driving and other hazardous activities until drug's effects on concentration and alertness are known.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.

References in periodicals archive ?
A Settlement deal has been signed by Glenmark Pharmaceuticals and Glenmark Pharmaceuticals Inc with Forest Laboratories, LLC, Forest Laboratories Holdings, and Royalty Pharma Collection Trust to settle and terminate the outstanding patent litigation affiliated with Glenmarks Abbreviated New Drug Application for Milnacipran Hydrochloride 12.
The terms of the Settlement deal includes that Glenmark would have an alternative to market and distribute its Milnacipran Hydrochloride tablets or an authorized generic version of Savella tablets.
and Royalty Pharma Collection Trust for the settlement and dismissal of the outstanding patent litigation in the USA associated with Glenmark's Abbreviated New Drug Application (ANDA) for Milnacipran Hydrochloride 12.