Cipran40 mg

Cipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) indicated for the following use:

Established / FDA-Approved Use

• Treatment of major depressive disorder (MDD) in adults.

Not Approved / Off-Label

Cipran is not approved for fibromyalgia or other pain syndromes, and is not approved for use in children or adolescents. Any use outside major depressive disorder in adults should only be under direct physician guidance.

Each capsule contains Levomilnacipran Hydrochloride equivalent to the labelled strength of levomilnacipran base, along with pharmaceutically acceptable excipients.

Cipran is the hydrochloride salt of levomilnacipran, the more active enantiomer of milnacipran. It belongs to the serotonin-norepinephrine reuptake inhibitor (SNRI) class of antidepressants and is used to treat major depressive disorder in adults. It is typically formulated as an extended-release oral capsule taken once daily.

Levomilnacipran Hydrochloride works by inhibiting the reuptake of both serotonin (5-HT) and norepinephrine (NE) at the neuronal synapse, increasing the availability of these neurotransmitters in the central nervous system. It shows greater potency for norepinephrine reuptake inhibition relative to serotonin compared to some other SNRIs, which contributes to its noradrenergic side-effect profile (e.g., increased heart rate, blood pressure, and urinary hesitancy).

Levomilnacipran is well absorbed orally, undergoes minimal first-pass metabolism, is partly metabolized via CYP3A4, and is eliminated mainly by the kidneys, with a plasma half-life of approximately 12 hours, supporting once-daily extended-release dosing.

Cipran extended-release capsules should be taken orally, once daily at the same time each day, with or without food, and swallowed whole without opening, chewing, or crushing.

The following are well-established, clinically significant interactions with Cipran:

• Monoamine oxidase inhibitors (MAOIs): Concurrent use, or use within 14 days of stopping an MAOI, is contraindicated due to a serious risk of serotonin syndrome. At least 7 days should elapse after stopping Cipran before starting an MAOI.
• Linezolid or intravenous methylene blue: These have MAOI activity and are contraindicated with Cipran due to serotonin syndrome risk.
• Other serotonergic drugs (e.g., other SNRIs/SSRIs, triptans, tramadol, St. John's Wort): Increased risk of serotonin syndrome when combined with Cipran; combine cautiously and monitor closely.
• Drugs affecting blood pressure/heart rate: Cipran can increase blood pressure and heart rate; caution is warranted with other agents that have similar effects.
• Anticoagulants/antiplatelets/NSAIDs: Concurrent use may increase risk of bleeding due to the effect of serotonergic drugs on platelet function.
• CYP3A4 inhibitors/inducers: Strong CYP3A4 inhibitors may increase levomilnacipran levels; dose adjustment may be needed with strong inhibitors in renal impairment.

Common side effects of Cipran (occurring in approximately 5% or more of patients and at a rate greater than placebo) include:

• Nausea and vomiting
• Constipation
• Excessive sweating (hyperhidrosis)
• Increased heart rate (tachycardia) and palpitations
• Erectile dysfunction and ejaculation disorders
• Dizziness, headache, and insomnia
• Urinary hesitancy

Less common but serious effects include increased blood pressure, serotonin syndrome, activation of mania/hypomania, and abnormal bleeding. See Precautions and Warnings for details.

Cipran should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Use of serotonergic antidepressants, including Cipran, during the third trimester has been associated with a risk of neonatal complications (poor adaptation syndrome) requiring extended hospitalization, respiratory support, and tube feeding in some newborns. There is no adequate data on whether Cipran is excreted in human breast milk; a decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the benefit of breastfeeding and the importance of the drug to the mother. Use only under medical supervision and consult a physician before use during pregnancy or breastfeeding.

Boxed Warning: Cipran, like other antidepressants, increases the risk of suicidal thinking and behavior in children, adolescents, and young adults (up to age 24), particularly during the initial months of treatment or after dose changes; it is not approved for use in pediatric patients. Close monitoring for clinical worsening and suicidality is required in all patients, especially at treatment initiation.

• Serotonin syndrome: Risk increases with concomitant serotonergic drugs; watch for agitation, hallucinations, tachycardia, fever, and muscle rigidity (see Interactions and Contraindications).
• Elevated blood pressure and heart rate: Blood pressure and pulse should be monitored before and during treatment, particularly in patients with pre-existing hypertension or cardiovascular disease.
• Urinary hesitancy/retention: Due to noradrenergic activity; caution in patients with predisposing conditions.
• Activation of mania/hypomania: Screen for bipolar disorder before starting; use with caution in patients with a personal or family history of bipolar disorder.
• Angle-closure glaucoma: Pupillary dilation can occur; avoid use in patients with uncontrolled angle-closure glaucoma.
• Abnormal bleeding: Increased risk of bruising or bleeding, especially when combined with NSAIDs, aspirin, or anticoagulants.
• Discontinuation symptoms: Abrupt discontinuation can cause dizziness, nausea, headache, and irritability; taper gradually under medical supervision.
• Use with caution in patients with a history of seizure disorder or severe hepatic/renal impairment.

Overdose with Cipran may cause symptoms such as tachycardia, dizziness, vomiting, and altered mental status. Seek immediate medical attention or contact a poison control center / emergency services right away if overdose is suspected. Treatment is supportive and should be provided in a healthcare facility; there is no specific antidote. Do not attempt home treatment for a suspected overdose.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric use: Safety and efficacy of Cipran have not been established in patients under 18 years of age; it is not approved for pediatric use and carries a boxed warning regarding suicidality risk in this age group.

Elderly: No overall differences in safety or effectiveness were observed relative to younger adults, but elderly patients should be monitored for hyponatremia, cardiovascular effects, and falls risk.

Renal impairment: Dose adjustment is required in moderate and severe renal impairment; use is not recommended in end-stage renal disease (see Dosage and Administration).

Hepatic impairment: Use is not recommended in patients with severe hepatic impairment.

Duration of treatment with Cipran is individualized based on clinical response, typically continued for several months after remission of depressive symptoms to prevent relapse, as advised by the prescribing physician. Long-term use should be periodically reassessed.

Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) antidepressant

Levomilnacipran Hydrochloride acts by inhibiting the reuptake of serotonin and norepinephrine in the central nervous system, with relatively greater potency for norepinephrine reuptake inhibition, thereby increasing synaptic levels of these neurotransmitters and improving depressive symptoms.

Cipran is not approved for use in children or adolescents; safety and efficacy in patients under 18 years of age have not been established. It carries a boxed warning for increased risk of suicidal thinking and behavior in pediatric and young adult patients.