CONTRAVE PROLONGED RELEASE TABLET 8MG/90MG

TABLET, FILM COATED, EXTENDED RELEASE

**6\. Dosage and Administration** CONTRAVE dosing should be escalated according to the following schedule:  A total daily dosage of two CONTRAVE 8 mg/90 mg tablets twice daily (32 mg/360 mg) is reached at the start of Week 4. CONTRAVE should be taken by mouth in the morning and in the evening. The tablets should not be cut, chewed, or crushed. Total daily doses greater than 32 mg/360 mg per day (two tablets twice daily) are not recommended. In clinical trials, CONTRAVE was administered with meals. However, CONTRAVE should not be taken with a high-fat meal because of a resulting significant increase in bupropion and naltrexone systemic exposure _\[see Warnings and Precautions and Clinical Pharmacology_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_. Patients may develop elevated blood pressure or heart rate during CONTRAVE treatment; the risk may be greater during the initial three months of therapy _\[see Warnings and Precautions_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_. Because patients with hypertension may be at increased risk for developing blood pressure elevations, such patients should be monitored for this potential effect when initiating treatment with CONTRAVE. Response to therapy should be evaluated after 12 weeks at the maintenance dosage. If a patient has not lost at least 5% of baseline body weight, discontinue CONTRAVE, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment. The need for continued treatment should be re-evaluated annually. The product is only for the intended population. Refer to the Contraindications and Warnings and Precautions to note the patient characteristics that place patients at higher risk of adverse reactions to CONTRAVE, to help ensure appropriate patient selection – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. BMI is calculated by dividing weight (in kg) by height (in meters) squared. A BMI chart for determining BMI based on height and weight is provided in _Table 6_.  **Dose Adjustment in Patients with Renal Impairment** In patients with moderate or severe renal impairment, the maximum recommended daily dose for CONTRAVE is two tablets (one tablet each morning and evening). No dose adjustment is required in patients with mild renal impairment. CONTRAVE is not recommended for use in patients with end-stage renal disease _\[see Use in Specific Population and Clinical Pharmacology_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_. **Dose Adjustment in Patients with Hepatic Impairment** CONTRAVE is contraindicated in patients with severe hepatic impairment. It is not recommended in patients with moderate hepatic impairment. In patients with mild hepatic impairment, the maximum recommended daily dose for CONTRAVE is two tablets (one tablet in the morning and one tablet in the evening). It is recommended that patients with mild hepatic impairment initiate treatment with one tablet in the morning for the first week of treatment, and escalate to one tablet in the morning and one tablet in the evening from week 2 onwards. Degree of hepatic impairment should be assessed using the Child-Pugh score _\[see Use in Specific Population and Clinical Pharmacology_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_. **Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Antidepressant** At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with CONTRAVE. Conversely, at least 14 days should be allowed after stopping CONTRAVE before starting an MAOI antidepressant _\[see Contraindications and Drug Interactions_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_. **Concomitant Use with CYP2B6 Inhibitors** During concomitant use with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel), the maximum recommended daily dose of CONTRAVE is two tablets (one tablet each morning and evening) _\[see Drug Interactions and Clinical Pharmacology_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_.