Contrave (naltrexone HCl/bupropion HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Naltrexone hydrochloride and bupropion hydrochloride (naltrexone/bupropion) is a fixed combination of naltrexone (an opiate antagonist) and bupropion (an aminoketone antidepressant agent). The combination preparation is an anorexigenic agent.
Naltrexone/bupropion is a fixed combination extended-release preparation consisting of naltrexone, an opiate antagonist, and bupropion, an aminoketone antidepressant agent with weak dopamine and norepinephrine reuptake inhibitor properties; the fixed combination preparation is an anorexigenic agent. The precise mechanism of action of naltrexone/bupropion in producing weight loss has not been fully elucidated. Both drugs appear to decrease food intake through independent but complementary effects on two areas of the brain involved in regulating food intake: the hypothalamic melanocortin system and the mesolimbic dopamine system (reward system).
The drugs have been shown in animal studies to produce a synergistic effect on food intake when combined.
Following single-dose, oral administration of the fixed-combination naltrexone hydrochloride and bupropion hydrochloride extended-release tablets in healthy individuals, peak plasma concentrations of naltrexone and bupropion occur at 2 and 3 hours, respectively. When administered with a high fat meal, AUC and peak plasma concentrations of naltrexone and bupropion are increased 2.1- and 3.7-fold, respectively, and 1.4- and 1.8-fold, respectively. Bupropion is extensively metabolized to 3 active metabolites: hydroxybupropion, which is principally mediated by CYP2B6, and threohydrobupropion and erythrohydrobupropion, which are formed through non-CYP pathways.
These metabolites have a longer elimination half-life than bupropion and account for the majority of bupropion exposure. Naltrexone is metabolized to its major active metabolite, 6-beta-naltrexol, through non-CYP pathways. Both naltrexone and bupropion are excreted primarily in the urine, mainly as metabolites; less than 2% of an oral dose of naltrexone is excreted in urine as unchanged drug and 0.5% of an oral dose of bupropion is excreted as unchanged drug.
Following single-dose administration of the fixed-combination naltrexone hydrochloride and bupropion hydrochloride extended-release tablet, elimination half-lives of naltrexone and bupropion, are approximately 5 and 21 hours, respectively.
USES: This medication is used with a doctor-approved exercise, behavior change, and reduced-calorie diet program to help you lose weight. It is used by certain overweight people, such as those who are obese or have weight-related medical problems. Losing weight and keeping it off can lessen the many health risks that come with obesity, including heart disease, diabetes, high blood pressure, and a shorter life.
Naltrexone belongs to a class of drugs known as opiate antagonists. Bupropion is an antidepressant that helps to restore the balance of certain natural substances (dopamine, norepinephrine) in the brain. These two medications work together on separate parts of the brain to reduce appetite and how much you eat.
Most opiates should not be used for 7 to 10 days before starting naltrexone, but some opiate drugs (such as methadone) should not be used for 10 to 14 days before starting naltrexone. Ask your doctor or pharmacist for more details. Other forms of naltrexone or bupropion are used to treat a variety of conditions including depression, other mental/mood disorders, smoking cessation, addiction to opioid medication, and alcohol abuse.
This combination product is not approved for these other uses. Discuss the risks and benefits of this medication, as well as other ways to lose weight, with your doctor.
Generic name: naltrexone HCl/bupropion HCl
Pronunciation: (nal-TREX-one/bue-PROE-pee-on)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Contrave
Indications
The following indications are listed for Contrave:
- Weight Loss Management For Obese Patient (body mass index 30 or greater)
- Weight Loss Management For Overweight Patient With Weight-Related Comorbidity
Dosing
Naltrexone/bupropion is available as extended-release tablets; each tablet contains 8 mg of naltrexone hydrochloride and 90 mg of bupropion hydrochloride. Dosages of both drugs are expressed in terms of the salt. Dosage should be titrated slowly over several weeks to the recommended dosage to reduce the risk of seizures.
If a dose of naltrexone/bupropion is missed, the missed dose should be skipped and the next dose should be taken at the regularly scheduled time.
The recommended initial adult dosage of the fixed combination of naltrexone/bupropion for chronic weight management is 1 tablet once daily in the morning for 1 week; dosage should then be titrated until a maintenance dosage of 2 tablets twice daily (total daily dose of naltrexone 32 mg and bupropion 360 mg) is reached. (See Table 1.) Do not take more than 4 tablets (32 mg of naltrexone hydrochloride and 360 mg of bupropion hydrochloride) in one day, and do not take more than 2 tablets at one time. In patients receiving a CYP2B6 inhibitor (e.g., clopidogrel, ticlopidine) concomitantly, the maximum recommended daily dosage of naltrexone/bupropion is 2 tablets (administered as 1 tablet twice daily).
Table 1. Naltrexone/Bupropion Dosage Titration Schedule
Morning Dose Evening Dose Week 1 1 tablet None Week 2 1 tablet 1 tablet Week 3 2 tablets 1 tablet Week 4 - Onward 2 tablets 2 tablets
Evaluate patient response after 12 weeks of treatment at the recommended maintenance dosage. Discontinuance of therapy is recommended in patients who have not lost at least 5% of their baseline body weight since such patients are unlikely to achieve and sustain meaningful weight loss with continued therapy.
Administer fixed-combination naltrexone/bupropion extended-release tablets orally twice daily in the morning and in the evening. The fixed-combination drug may be taken with meals; however, avoid administration with a high-fat meal because this may increase systemic exposures of bupropion and naltrexone systemic. Swallow tablets whole and do not cut, chew, or crush.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
When naltrexone/bupropion is used, interactions associated with each drug in the fixed combination should be considered.
Bupropion is metabolized to hydroxybupropion, principally by cytochrome P-450 (CYP) 2B6; CYP isoenzymes are not involved in the formation of the other bupropion metabolites.
Bupropion and its metabolites inhibit CYP2D6. Naltrexone and its major metabolite do not inhibit CYP1A2, 2B6, 2C8, 2E1, 2C9, 2C19, 2D6 or 3A4 nor induce CYP1A2, 2B6, or 3A4.
Bupropion and its metabolites inhibit renal organic cation transporter (OCT) 2 in vitro.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Uncontrolled hypertension.
*Seizure disorder or history of seizures.
*Concurrent use of any other bupropion-containing products (e.g., Aplenzin(R), Forfivo XL(R), Wellbutrin(R), Wellbutrin(R) SR, Wellbutrin(R) XL, Zyban(R)).
*Current or past diagnosis of bulimia or anorexia nervosa.
*Chronic use of opiate agonists or opiate partial agonists, or acute opiate withdrawal.
*Patients undergoing abrupt discontinuance of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.
*Concurrent or recent (i.e., within 2 weeks) therapy with a monoamine oxidase (MAO) inhibitor. Initiating naltrexone/bupropion in patients receiving reversible MAO inhibitors such as linezolid or IV methylene blue is also contraindicated.
*Known hypersensitivity to bupropion, naltrexone, or to any other ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Common adverse reactions reported in >=5% of patients receiving naltrexone/bupropion in clinical studies include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of naltrexone/bupropion in patients <18 years of age have not been established; use of naltrexone/bupropion is not recommended in pediatric patients.
Weight loss offers no potential benefit to pregnant women and may result in fetal harm. If a patient becomes pregnant, discontinue naltrexone/bupropion and advise the patient of the risk to the fetus. Available pharmacovigilance data and data from clinical trials with the individual components of the combination drug in pregnant patients have not demonstrated a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcome.
Naltrexone, bupropion, and their metabolites are distributed into human milk. There is no information regarding whether the drugs have an effect on milk production. Consider the known benefits of breastfeeding along with the mother's need for naltrexone/bupropion and any potential adverse effects on the infant from the drug or underlying maternal condition.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Clinical trials of naltrexone/bupropion did not include sufficient numbers of patients >=65 years of age to determine whether geriatric patients respond differently than younger adults; in controlled studies in obese and overweight patients, 2% of patients were >=65 years of age and none were >=75 years of age. Older individuals may be more sensitive to CNS effects of naltrexone/bupropion. Because geriatric patients may have decreased renal function, use naltrexone/bupropion with caution in such patients.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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