Milnacipran


Generic Medicine Info
Indications and Dosage
Oral
Depression
Adult: Dose is individualised according to the response and tolerability. Usual dose: 50 mg bid. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).

Oral
Fibromyalgia
Adult: Initially, 12.5 mg as a single dose on Day 1, then 12.5 mg bid on Days 2-3, 25 mg bid on Days 4-7, and 50 mg bid thereafter. Doses may be increased to 100 mg bid, according to individual response. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
What are the brands available for Milnacipran in Hong Kong?
Renal Impairment
ESRD: Not recommended.
CrCl (mL/min) Dosage
5-29 25 mg bid, may be increased to 50 mg bid according to individual response.
Administration
Milnacipran May be taken with or without food.
Contraindications
Treatment initiation in patient receiving linezolid or IV methylthioninium chloride. Use of MAOIs (intended to treat psychiatric disorders) either concurrently, or within 2 weeks of discontinuing the MAOI, or within 5 days of discontinuing milnacipran.
Special Precautions
Patient with history of seizure disorder, conditions predisposing to seizures (e.g. brain damage); major depressive disorder, bipolar disorder, and other psychiatric disorders; hypertension, tachyarrhythmias (e.g. atrial fibrillation), or other CV disease; substantial alcohol intake or alcoholism, evidence of chronic liver disease; history of dysuria (particularly in males with prostatic hypertrophy, prostatitis or other lower urinary tract disorders). Avoid abrupt withdrawal. Severe hepatic and moderate to severe renal impairment including ESRD. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Suicidal thoughts and behaviour, mania or hypomania; increased blood pressure and heart rate; bone fracture; hepatotoxicity (e.g. increased liver enzymes, severe liver injury [including fulminant hepatitis]); mild pupillary dilation that may lead to an episode of narrow-angle glaucoma; decreased libido, erectile dysfunction, ejaculation delay or failure, delayed or absent orgasm in females; increased urinary resistance; bleeding events (e.g. ecchymoses, haematoma, epistaxis, petechiae) and postpartum bleeding (particularly in the month before delivery); discontinuation syndrome.
Cardiac disorders: Palpitations, tachycardia, chest pain, chest discomfort.
Eye disorders: Blurred vision.
Gastrointestinal disorders: Nausea, constipation, vomiting, dry mouth, abdominal pain.
General disorders and administration site conditions: Chills, fever.
Metabolism and nutrition disorders: Decreased appetite.
Nervous system disorders: Headache, dizziness, migraine, paraesthesia, tremor.
Psychiatric disorders: Anxiety, insomnia.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, URTI.
Skin and subcutaneous tissue disorders: Hyperhidrosis, rash, pruritus.
Vascular disorders: Hypertension, flushing.
Potentially Fatal: Serotonin syndrome, haemorrhage, hyponatraemia (usually as a result of SIADH).
PO: Z (Risk of postpartum haemorrhage, persistent pulmonary hypertension in infant and neonatal withdrawal/toxicity in late pregnancy use. Monitor closely.)
Monitoring Parameters
Monitor blood pressure and heart rate (at baseline and as necessary); renal function; intraocular pressure (particularly in patients with history of glaucoma and baseline elevations). Closely monitor mental status for clinical worsening, suicidal ideation, and other unusual behaviours at treatment initiation or when doses are increased or decreased. Assess for signs and symptoms of sexual dysfunction and serotonin syndrome.
Overdosage
Symptoms: Increased blood pressure, increased hepatic enzymes, confusional state, dizziness, changes in the level of consciousness (ranging from somnolence to coma), cardiorespiratory arrest. Management: Supportive and symptomatic treatment. May consider gastric lavage and administration of activated charcoal soon after ingestion or in symptomatic patients. Ensure adequate airway, oxygenation and ventilation.
Drug Interactions
May inhibit the antihypertensive effect of clonidine. May increase the risk of hyponatraemia with diuretics. Increased risk of postural hypotension and tachycardia with IV digoxin. May increase the risk of paroxysmal hypertension and cardiac arrythmia with epinephrine and norepinephrine.
Potentially Fatal: Increased risk of serotonin syndrome with other serotonergic agents (e.g. other SNRIs and SSRIs, triptans, TCAs, fentanyl, lithium, meperidine, methadone, tramadol, buspirone, amphetamines, tryptophan) or agents that impair metabolism of serotonin (e.g. MAOIs, linezolid, and IV methylthioninium chloride). Increased risk of bleeding with aspirin, NSAIDs, or anticoagulants (e.g. warfarin, heparin).
Food Interaction
May increase the risk of serotonin syndrome with St. John's wort. Alcohol may enhance the hepatotoxic effect of milnacipran.
Action
Description:
Mechanism of Action: Milnacipran, an antidepressant, is a serotonin and norepinephrine reuptake inhibitor (SNRI). Its exact mechanism to improve the symptoms of fibromyalgia remains to be determined. It prevents norepinephrine uptake with approx threefold higher potency in vitro than serotonin without directly affecting the uptake of dopamine or other neurotransmitters.
Onset: Antidepressant effect: 1-3 weeks.
Pharmacokinetics:
Absorption: Well absorbed. Bioavailability: Approx 85-90%. Time to peak plasma concentration: 2-4 hours.
Distribution: Enters breastmilk. Plasma protein binding: 13%.
Metabolism: Metabolised in the liver to inactive metabolites.
Excretion: Via urine (approx 55%, as unchanged drug). Elimination half-life: Approx 6-8 hours.
Chemical Structure

Chemical Structure Image
Milnacipran

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 65833, Milnacipran. https://pubchem.ncbi.nlm.nih.gov/compound/Milnacipran. Accessed June 25, 2024.

Storage
Store between 15-30°C.
MIMS Class
Antidepressants / Neuromuscular Disorder Drugs
ATC Classification
N06AX17 - milnacipran ; Belongs to the class of other antidepressants.
References
Anon. Milnacipran. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 08/05/2024.

Buckingham R (ed). Milnacipran Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/05/2024.

Milnacipran Hydrochloride Tablet (Amneal Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/05/2024.

Milnacipran. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 08/05/2024.

Milpran Capsules 25 mg and 50 mg (Weidar Chemical & Pharmaceutical Co Ltd [HK]). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 24/06/2024.

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