Zimulti^® (Tablets) Instructions for Use

Marketing Authorization Holder

Sanofi-Aventis France (France)

Manufactured By

Sanofi Winthrop Industrie (France)

ATC Code

A08AX01 (Rimonabant)

Active Substance

Rimonabant (Rec.INN registered by WHO)

Dosage Form

Zimulti®

Film-coated tablets, 20 mg: 14, 28, or 56 pcs.

Dosage Form, Packaging, and Composition

Tablets, film-coated white, slightly biconvex, drop-shaped, with a bevel, with engraving “20” on one side, smooth on the other side.

Auxiliary substances : corn starch, lactose monohydrate, povidone K30, croscarmellose sodium, sodium lauryl sulfate, microcrystalline cellulose (90 mcm), magnesium stearate, hypromellose (15 mPa.s), titanium dioxide, macrogol 3000, carnauba wax.

14 pcs. – blisters (1) – carton packs.
14 pcs. – blisters (2) – carton packs.
14 pcs. – blisters (4) – carton packs.

Clinical-Pharmacological Group

Cannabinoid CB1 receptor antagonist. Drug for the treatment of obesity

Pharmacotherapeutic Group

Remedy for obesity

Indications

• Zimulti^® (rimonabant) is indicated as an adjunct to diet and physical activity for the management of obesity in adult patients (18 years and older) with an initial Body Mass Index (BMI) of 30 kg/m² or greater, or in patients with a BMI of 27 kg/m² or greater in the presence of one or more associated weight-related risk factors, such as type 2 diabetes, dyslipidemia (e.g., high triglycerides, low HDL cholesterol), or controlled hypertension.
• The primary goal of therapy is to achieve and maintain clinically significant weight loss, which in turn can lead to improvements in these comorbid conditions. Treatment should be initiated as part of a comprehensive weight management strategy that includes a reduced-calorie diet and regular physical exercise.

Contraindications

• Hypersensitivity to the active substance rimonabant or to any of the excipients listed in the composition.
• Patients with severe depressive disorder and/or patients being treated with antidepressant medications, due to the increased risk of psychiatric adverse reactions.
• Patients with uncontrolled serious psychiatric illnesses, such as major depression, suicidal ideation, or a history of suicide attempts.
• Pregnancy and lactation. Women of childbearing potential must use effective contraception during treatment. If pregnancy occurs, treatment must be discontinued immediately.
• Severe hepatic impairment (Child-Pugh class C) or severe renal impairment (creatinine clearance less than 30 mL/min), including patients with end-stage renal disease requiring dialysis, as the safety and efficacy in these populations have not been established.

Dosage Regimen

The recommended and maximum single dose of Zimulti^® is one 20 mg tablet taken orally once daily.

The tablet should be taken in the morning, with or without food. Adherence to a single daily dosing schedule is crucial for maintaining consistent therapeutic levels of the drug. Treatment should not be initiated at a higher dose.

Before initiating therapy, the patient’s BMI should be confirmed, and the presence of any contraindications, especially related to psychiatric history, must be thoroughly assessed. The efficacy and safety of continued treatment should be re-evaluated after the first 12 weeks (approximately 3 months).

If the patient has not lost at least 5% of their initial body weight after 12 weeks of treatment, discontinuation of therapy should be considered, as the likelihood of achieving and maintaining clinically meaningful weight loss long-term is reduced. Discontinuation should be decided in consultation with the prescribing physician.

No dose adjustment is required for elderly patients or for patients with mild to moderate hepatic or renal impairment. However, caution is advised when prescribing to these populations, and they should be monitored closely.

Adverse Reactions

During clinical trials and post-marketing surveillance, the following adverse reactions were observed with Zimulti^® (rimonabant). The most frequently reported adverse reactions were nausea, dizziness, anxiety, and mood alterations.

Psychiatric disorders: Very common (≥1/10): Insomnia, mood alterations with depressive symptoms. Common (≥1/100 to <1/10): Anxiety, anxiety disorders, depressed mood, aggression, agitation, nervousness, stress symptoms, sleep disorders. Uncommon (≥1/1,000 to <1/100): Suicidal ideation, depressive disorders. The risk of psychiatric adverse events is higher in patients with a history of depression.

Nervous system disorders: Very common (≥1/10): Dizziness. Common (≥1/100 to <1/10): Headache, paresthesia, dysgeusia (taste disturbances), memory impairment, attention disturbances, lethargy, balance disorders, syncope.

Gastrointestinal disorders: Very common (≥1/10): Nausea. Common (≥1/100 to <1/10): Diarrhea, vomiting, dry mouth, constipation, abdominal pain, dyspepsia, gastroenteritis.

Skin and subcutaneous tissue disorders: Common (≥1/100 to <1/10): Pruritus, rash, hyperhidrosis (increased sweating), alopecia, eczema.

Musculoskeletal and connective tissue disorders: Common (≥1/100 to <1/10): Arthralgia (joint pain), muscle spasms, myalgia (muscle pain), back pain, tendonitis.

General disorders and administration site conditions: Common (≥1/100 to <1/10): Asthenia (fatigue), fatigue, irritability. Uncommon (≥1/1,000 to <1/100): Malaise.

Patients should be advised to report immediately any changes in mood, behavior, or the emergence of suicidal thoughts to their healthcare provider. Discontinuation of therapy should be considered if significant psychiatric symptoms develop.

Drug Interactions

Rimonabant is primarily metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme system. Concomitant use with potent inhibitors or inducers of this enzyme can significantly alter its plasma concentrations.

Strong CYP3A4 Inhibitors: Concomitant administration with potent inhibitors such as ketoconazole, itraconazole, clarithromycin, telithromycin, nefazodone, ritonavir, nelfinavir, and indinavir may lead to a substantial increase in rimonabant plasma levels. This increases the risk of dose-related adverse effects. Co-administration is not recommended, or if unavoidable, close clinical monitoring for adverse reactions is essential.

CYP3A4 Inducers: Concomitant use with potent inducers such as rifampicin, phenytoin, phenobarbital, and carbamazepine may significantly decrease rimonabant plasma concentrations, potentially reducing its therapeutic efficacy. Alternative treatments or dose adjustments should be considered, though the efficacy of a dose increase has not been established.

Drugs Requiring Narrow Therapeutic Index: Caution is advised when rimonabant is co-administered with drugs that have a narrow therapeutic index and are metabolized by CYP3A4, such as cyclosporine, tacrolimus, and sirolimus. Monitoring of drug levels (if available) and clinical effects is recommended.

Patients treated with anticoagulants like warfarin should be monitored more closely, as weight loss itself can affect the pharmacokinetics of warfarin, potentially requiring dose adjustment.

Due to its mechanism of action, rimonabant may potentially interact with centrally acting drugs, including other anti-obesity agents and psychotropic drugs. The concomitant use of Zimulti^® with other anti-obesity agents is not recommended.

Overdose

In the event of an overdose, the clinical presentation would be expected to be an extension of the known pharmacological and adverse effect profile of rimonabant.

Symptoms: Severe or exaggerated adverse reactions may occur, including pronounced nausea and vomiting, severe dizziness and vertigo, significant anxiety, agitation, confusion, and profound hypotension (low blood pressure). Given the drug’s mechanism, severe psychiatric manifestations such as acute depressive episodes or suicidal ideation are of particular concern.

Management: There is no specific antidote for rimonabant overdose. Management should be supportive and symptomatic. Gastric lavage or administration of activated charcoal may be considered if the overdose was ingested recently (within 1-2 hours). Close and continuous monitoring of vital signs, cardiac function, and neurological and psychiatric status is mandatory.

Patients should be observed in a controlled environment, especially for the development of serious psychiatric symptoms. Supportive care, including ensuring adequate hydration and managing hypotension with appropriate measures, should be instituted. Hemodialysis is not expected to be effective in enhancing the elimination of rimonabant due to its high protein binding and extensive tissue distribution.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.