Forest Laboratories, Inc. (NYSE:FRX) announced today that FETZIMA™ (levomilnacipran ER capsules), is now available in pharmacies throughout the United States. FETZIMA was approved by the U.S. Food and Drug Administration (FDA) for the treatment of Major Depressive Disorder (MDD), also known as depression, in adults in July 2013. “We are pleased to announce that FETZIMA is now available to patients,” said Dr. Marco Taglietti, Executive Vice President, Drug Development & Research and Chief Medical Officer. “Despite the number of available antidepressant medications, the treatment of depression remains a clinical challenge with a need for additional treatment options. In clinical studies, patients who received FETZIMA vs. placebo experienced meaningful improvement in their depressive symptoms and functional impairment. The availability of FETZIMA is a significant step forward in our goal of bringing a range of treatment options to adults living with MDD.” FETZIMA is a serotonin and norepinephrine reuptake inhibitor (SNRI). The efficacy of FETZIMA was established in three positive double-blind Phase III studies comprising two fixed-dose studies and one flexible-dose study that compared FETZIMA to placebo in adults with MDD. A total of more than 1,600 adult patients received a once-daily dose of either FETZIMA (40, 80, 120 mg) or placebo in the three studies. In all three studies, significant improvement in depressive symptoms was demonstrated across 3 FETZIMA dosage strengths (40, 80, and 120 mg) once daily, as measured by the change from baseline to Week 8 in the MADRS total score. MADRS is a widely used, physician-rated scale for assessing the severity of depressive symptoms. Each of the 10 symptoms is rated on a scale of 0-6; higher numbers denote greater severity of symptoms. For study 1, the mean baseline MADRS total score was 36 for all treatment groups. The LS mean difference from placebo in change from baseline was statistically significant at all three FETZIMA doses (-3.2 at 40 mg/day, -4.0 at 80 mg/day, and -4.9 at 120 mg/day). For study 2, the mean baseline MADRS total score was 31 for all treatment groups. The LS mean difference from placebo in change from baseline was statistically significant at both FETZIMA doses studied (-3.3 at 40 mg/day, -3.1 at 80 mg/day). For study 3, the mean baseline MADRS total score was 35 for both treatment groups. The LS mean difference from placebo in change from baseline was statistically significant for the FETZIMA dosing range studied (-3.1 at 40-120 mg/day).
FETZIMA also demonstrated significant improvement in functional impairment as measured by the mean change from baseline in the Sheehan Disability Scale (SDS) total score. SDS is a validated, patient-rated scale used to assess functional impairment in the three domains of work/school, social life, and family life as a result of psychiatric symptoms.The most commonly observed adverse reactions in MDD patients treated with FETZIMA in placebo-controlled studies (incidence ≥5% and at least twice the rate of placebo) were nausea, constipation, hyperhidrosis, heart rate increased, erectile dysfunction, tachycardia, vomiting, and palpitations. 9% of the 1583 patients who received FETZIMA (40 mg - 120 mg) discontinued treatment due to an AE, compared with 3% of the 1040 placebo-treated patients. The only dose-related AEs (>2%) in the fixed-dose studies were urinary hesitation and erectile dysfunction. About Major Depressive Disorder MDD is a serious medical condition often requiring treatment, affecting almost 16 million adults in the United States yearly or approximately 6.6% of the adult U.S. population. MDD, also known as depression, is a common debilitating disorder in which feelings of sadness and other symptoms occur nearly every day for at least two weeks and interfere with a person’s ability to work, sleep, study, eat, and enjoy once-pleasurable activities. Depression costs the U.S. an estimated $83 billion each year. Among all medical illnesses, MDD is a leading cause of disability in the U.S. The World Health Organization predicts depression will become the second leading cause of disability by the year 2020. About FETZIMA FETZIMA, an SNRI, is indicated for the treatment of Major Depressive Disorder (MDD) in adults. The recommended therapeutic dose range for FETZIMA is 40 mg to 120 mg once daily and can be taken with or without food. The exact mechanism of action (MOA) 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 SNRI.
Levomilnacipran potently inhibits serotonin (5-HT) and norepinephrine reuptake (IC 50=16-19 nM and 11 nM, respectively). Greater reuptake inhibition of norepinephrine over serotonin was shown in vitro.Levomilnacipran lacks significant affinity for any other receptors, ion channels, or transporters tested in vitro, including serotonergic (5-HT 1-7), α- and β-adrenergic, muscarinic, or histaminergic receptors and Ca2+, Na+, K+, or Cl- channels. Levomilnacipran was licensed to Forest Laboratories Inc. by Pierre Fabre, in the U.S. and Canada. Pierre-Fabre will also be the active pharmaceutical ingredient (API) supplier. Visit FETZIMA.com for more information on this once-daily option for the treatment of MDD in adults. FETZIMA Indication and Usage FETZIMA is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of Major Depressive Disorder (MDD) in adults. FETZIMA is not approved for the management of fibromyalgia, and its efficacy and safety have not been established for that use. Important Safety Information WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. FETZIMA is not approved for use in pediatric patients. Contraindications
- FETZIMA is contraindicated in patients with a hypersensitivity to levomilnacipran, milnacipran HCl, or to any excipient in the formulation.
- The use of MAOIs intended to treat psychiatric disorders with FETZIMA or within 7 days of stopping treatment with FETZIMA is contraindicated due to an increased risk of serotonin syndrome. The use of FETZIMA within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated.
- Starting FETZIMA in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated due to an increased risk of serotonin syndrome.
- Do not use FETZIMA in patients with uncontrolled narrow-angle glaucoma. In clinical studies, FETZIMA was associated with an increased risk of mydriasis.
- All patients being treated with antidepressants should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of treatment and when increasing or decreasing the dose. Consider changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or includes symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, or suicidality that are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants should be alerted about the need to monitor patients daily. Prescriptions for FETZIMA should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.
- Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Symptoms of serotonin syndrome may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms. If symptoms of serotonin syndrome occur, discontinue FETZIMA immediately and initiate supportive treatment. If concomitant use of FETZIMA with other serotonergic drugs is clinically warranted, patients should be aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
- SNRIs, including FETZIMA, have been associated with increases in blood pressure. Blood pressure should be measured prior to initiating treatment and periodically throughout FETZIMA treatment. Pre-existing hypertension should be controlled before initiating treatment with FETZIMA. Use with caution in patients with pre-existing hypertension, cardiovascular, or cerebrovascular conditions that might be compromised by increases in blood pressure. Concomitant use of FETZIMA with drugs that increase blood pressure and heart rate has not been evaluated and such combinations should be used with caution. For patients who experience a sustained increase in blood pressure, discontinuation or other appropriate medical intervention should be considered.
- SNRIs, including FETZIMA, have been associated with an increase in heart rate. Heart rate should be measured prior to initiating treatment and periodically throughout FETZIMA treatment. Pre-existing tachyarrhythmia’s and other cardiac disease should be treated before starting therapy with FETZIMA. For patients who experience a sustained increase in heart rate, discontinuation or other appropriate medical intervention should be considered.
- SSRIs and SNRIs, including FETZIMA, may increase the risk of bleeding events, some serious. Concomitant use of aspirin, NSAIDs, warfarin, and other anticoagulants may add to this risk.
- Mydriasis has been reported in association with SNRIs including FETZIMA; therefore, FETZIMA should be used with caution in patients with controlled narrow-angle glaucoma. Patients with raised intraocular pressure or those at risk of acute narrow-angle (angle-closure) glaucoma should be monitored. DO NOT use FETZIMA in patients with uncontrolled narrow-angle glaucoma.
- FETZIMA can affect urethral resistance. In clinical studies, urinary hesitation occurred in 4%, 5% and 6% of FETZIMA-treated patients receiving doses of 40, 80, and 120 mg, respectively, compared to no patients in the placebo group. Caution is advised when using FETZIMA in patients prone to obstructive urinary disorders.
- Symptoms of mania/hypomania were reported in 0.2% of FETZIMA-treated patients and 0.2% of placebo-treated patients in clinical studies. As with all antidepressants, FETZIMA should be used cautiously in patients with a history or family history of bipolar disorder, mania or hypomania. Prior to initiating treatment with FETZIMA, patients should be adequately screened to determine if they are at risk for bipolar disorder. FETZIMA is not approved for use in treating bipolar depression.
- FETZIMA should be prescribed with caution in patients with a seizure disorder.
- Discontinuation symptoms, some serious, have been reported with discontinuation of serotonergic antidepressants such as FETZIMA. Gradual dose reduction is recommended, instead of abrupt discontinuation, whenever possible. Monitor patients when discontinuing FETZIMA. If intolerable symptoms occur following a dose decrease or upon discontinuation of treatment, consider resuming the previously prescribed dose and decreasing the dose at a more gradual rate.
- Advise patients that if they are treated with diuretics or are otherwise volume depleted, or are elderly, they may be at greater risk of developing hyponatremia while taking FETZIMA. Although no cases of hyponatremia resulting from FETZIMA treatment were reported in the clinical studies, hyponatremia has occurred as a result of treatment with SSRIs and SNRIs. FETZIMA should be discontinued in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted.
About Forest Laboratories and Its ProductsForest Laboratories (NYSE:FRX) is a leading, fully integrated, specialty pharmaceutical company largely focused on the United States market. The Company markets a portfolio of branded drug products and develops new medicines to treat patients suffering from diseases principally in five therapeutic areas: central nervous system, cardiovascular, gastrointestinal, respiratory, and anti-infective. Our strategy of acquiring product rights for development and commercialization through licensing, collaborative partnerships and targeted mergers and acquisitions allows us to take advantage of attractive late-stage development and commercial opportunities, thereby managing the risks inherent in drug development. The Company is headquartered in New York, NY. To learn more, visit www.FRX.com. Except for the historical information contained herein, this release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements involve a number of risks and uncertainties, including the difficulty of predicting FDA approvals, the acceptance and demand for new pharmaceutical products, the impact of competitive products and pricing, the timely development and launch of new products, and the risk factors listed from time to time in Forest Laboratories' Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and any subsequent SEC filings. Forest assumes no obligation to update forward-looking statements contained in this release to reflect new information or future events or developments.