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Cipran 40 mgLevomilnacipran is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of Major Depressive Disorder (MDD) in adults.Limitation of Use: Levomilnacipran is not approved for the management of fibromyalgia. The efficacy and safety of Levomilnacipran for the management of fibromyalgia have not been established.Dosage of Cipran 40 mgRecommended dose: 40 mg to 120 mg once daily with or without food. Initiate dose at 20 mg once daily for 2 days and then increase to 40 mg once daily. Based on efficacy and tolerability, increase dose in increments of 40 mg at intervals of 2 or more days. The maximum recommended dose is 120 mg once daily. Take capsules whole; do not open, chew or crush.Renal Impairment: Do not exceed 80 mg once daily for moderate impairment. Do not exceed 40 mg once daily for severe renal impairment.Discontinuation: Reduce dose gradually whenever possible.Interaction of Cipran 40 mgStrong CYP3A4 inhibitors such as ketoconazole: Do not exceed 80 mg once daily.ContraindicationsHypersensitivity to levomilnacipran, milnacipran HCl or to any excipient in the formulation.The use of MAOIs intended to treat psychiatric disorders with Levomilnacipran or within 7 days of stopping treatment with Levomilnacipran is contraindicated because of an increased risk of serotonin syndrome. The use of Levomilnacipran within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated.Starting Levomilnacipran 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.Side Effects of Cipran 40 mg Hypersensitivity Suicidal Thoughts and Behaviors in Adolescents and Young Adults? Serotonin Syndrome Elevated Blood Pressure Elevated Heart Rate Increased Risk of Bleeding Angle Closure Glaucoma Urinary Hesitation or Retention Activation of Mania/Hypomania Seizure Discontinuation Syndrome Hyponatremia Storage ConditionsKeep below 30?C temperature, away from light & moisture. Keep out of the reach of children.Drug ClassesSerotonin-norepinephrine reuptake inhibitor (SNRI)Mode Of ActionThe exact mechanism of the antidepressant action of levomilnacipran is unknown, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of reuptake at serotonin and norepinephrine transporters. Non-clinical studies have shown that levomilnacipran is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI).Levomilnacipran binds with high affinity to the human serotonin (5-HT) and norepinephrine (NE) transporters (Ki = 11 and 91 nM, respectively) and potently inhibits 5-HT and NE reuptake (IC50 = 16-19 and 11 nM, respectively). Levomilnacipran lacks significant affinity for any other receptors, ion channels or transporters tested in vitro, including serotonergic (5HT1-7), ?- and ?-adrenergic, muscarinic, or histaminergic receptors and Ca2+, Na+, K+ or Cl- channels. Levomilnacipran did not inhibit monoamine oxidase (MAO).PregnancyPregnancy: Third trimester use may increase risk for symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, tremor, irritability) in the neonate.Pediatric UsesPediatric Use: Clinical studies on the use of Levomilnacipran in pediatric patients have not been conducted; therefore, the safety and effectiveness of Levomilnacipran in the pediatric population have not been established. Levomilnacipran is not approved for use in pediatric patients.Geriatric Use: No dose adjustment is recommended on the basis of age. In a multiple-dose clinical pharmacokinetic study, elderly subjects (> 65 years) had a slightly higher exposure (C max by 24% and AUC by 26%) of levomilnacipran than younger subjects (18-45 years). Of the total number of subjects in the 8-week clinical studies of Levomilnacipran, 2.8% of patients were age 65 or older. Because levomilnacipran is predominately excreted by the kidney, renal clearance of levomilnacipran should be considered when determining the dose. SSRIs and SNRIs, including Levomilnacipran, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event.Hepatic Impairment: Hepatic elimination of levomilnacipran is low. Dose adjustment is not recommended in subjects with mild (Child-Pugh score of 1-6), moderate (Child-Pugh score of 7-9), or severe (Child-Pugh score of 10-13) hepatic impairment.Renal Impairment: Renal excretion plays a predominant role in the elimination of levomilnacipran. Dose adjustment is not recommended for patients with mild (creatinine clearance of 60-89 ml/min) renal impairment. Dosing adjustment is recommended for patients with moderate (creatinine clearance of 30-59 ml/min) or severe (creatinine clearance of 15-29 ml/min) renal impairment. Levomilnacipran is not recommended for patients with end stage renal disease.