Contrave weight loss
The FDA approved another new weight loss medication, Contrave which is a combination of Bupropion and Naltrexone in extended release formulation for the treatment of obesity and weight management, including for weightloss and maintenance of weight loss, used in conjunction with lifestyle modification.
Who can take Contrave?
Contrave is recommended for overweight or obese patients with an initial body mass index ≥30 kg/m2 or those that are overweight with a BMI of ≥27 kg/m2 with one or more obesity related risk factors (e.g. diabetes, dyslipidemia, sleep apnea, metabolic syndrome, osteoarthritis, or hypertension).
Obesity is a rapidly growing epidemic among adults, adolescents, and children in the United States. Currently, there are three main approaches to the treatment of obesity:
- diet, physical activity, and behavioral modification (diet and exercise);
- pharmacotherapy with weight loss diet pills; and
- weight loss surgery.
Diet and exercise is the mainstay of weight management and generally precedes other measures.
The strategy to implement pharmacotherapeutic or surgical approaches in addition to diet and exercise depends upon the patient’s BMI as well as the presence of obesity-related comorbidities.
However, unlike the situation for other metabolic diseases such as hypertension and type 2 diabetes, there are very limited obesity pharmacotherapies available. Although orlistat is approved for long-term use and provides efficacy beyond that usually achievable using diet and exercise alone, it is not tolerated well by some patients.
The other available pharmacotherapies, e.g. phentermine, are approved for short-term use only. Bariatric surgery is usually reserved for those with much higher BMI. The benefit of surgery offset by greater expense and risk. In the face of such limited options, patients often resort to the use of off-label medications or dietary supplements that may be ineffective or unsafe. In this context, agents such as Contrave, a combination of Naltrexone and Bupropion(NB), may offer viable alternatives for many obese patients.
Dosing of Contrave: The recommended daily dose of Contrave is two 8 mg naltrexone/90 mgbupropion (8/90) tablets taken twice daily for a total daily dose of 32 mg naltrexone/360 mg bupropion (32/360). Upon initiation, Contrave dosing should be escalated starting with one tablet taken daily for the first week, followed by the addition of another tablet each day during each subsequent week, until the total daily maintenance dose of two tablets twice a day (32/360) is reached at the start of Week 4.
How Effective is Contrave?
All four Phase 3 studies showed statistically significant improvement in each co-primary endpoint relative to placebo. Contrave met the second benchmark for weight loss efficacy in three of the four studies. Achieving 5% weight loss is not only an FDA guidance efficacy benchmark, but this degree of weight loss is known to confer significant cardiometabolic benefit. Similarly, the Contrave trials demonstrated beneficial effects on prespecified weight-related cardiometabolic parameters, including:
- waist circumference,
- triglycerides, HDL-cholesterol,
- high-sensitivity C-reactive protein (hs-CRP),
- glycemic control (fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance [HOMA-IR], and, in patients with diabetes, hemoglobin A1c [HbA1c]),
Improved quality of life and control of eating was noted with Contrave.
How long does it take before I know if it is working for me?
Most patients who respond to Contrave will havedone so by 4 months of treatment. If a patient has not exhibited clinically meaningful weight loss (e.g., at least 5%) after 4 months of treatment, the physician should consider discontinuation of Contrave and initiation of other weight management strategies should be considered.
Common side effects
Patients may experience elevated blood pressure or pulse during Contrave treatment; the risk may be greater during the initial 3 months of therapy. If clinically relevant and sustained (e.g., at least two consecutive measurements) increases in blood pressure or pulse occur, Contrave should be discontinued. As patients with hypertension or a history of hypertension may be at increased risk of blood pressure elevations, care should be exercised when initiating treatment with Contrave in such patients.
Side Effects. The most commonly reported side effects (those that occurred at a≥5% incidencein the Total NB group and greater than the incidence in the placebo group) for patients treated with NB are displayed in the table below.
Treatment-emergent Adverse Events Occurring in ≥5% of the Total NB Group and Greater Than Placebo: Primary Dataset, Double-Blind Treatment Phase
|Side effects||Placebo||NB16||NB32||Total NB|
|n (%)||n (%)||n (%)||n (%)|
|Patients with any side effect||1137||-75.00%||507||-80.10%||2221||-87.30%||2769||-85.50%|
How much weight loss is expected with Contrave?
All four Phase 3 Contrave studies demonstratedstatistically significant and clinically meaningful weight loss following up to 56 weeks of treatment with Contrave compared with placebo. The average percent weight loss from baseline observed with NB treatment across the four studies corresponded to between approximately 5 and 9 kg (11 to 22 pounds).
Slower weight loss in diabetics
Patients with type 2 diabetes in Contrave Study showed the smallest degree of weight loss, although a significantly greater proportion of Contrave-treated patients benefitted with at least 5% weight loss at endpoint compared to placebo.
Key benefits of Contrave
Key benefits following treatment with Contrave(NB)are summarized below:
- Clinically meaningful weight loss was apparent early in treatment, and was greater than that observed with either naltrexone or bupropion alone. Weight loss was on average sustained, and those patients who continued treatment through 56 weeks experienced the most substantial weight loss. The efficacy of NB was observed across all demographic and clinical subgroups evaluated, including patients with hypertension, dyslipidemia, history of cardiovascular disease, type 2 diabetes, impaired fasting glucose, or history of depression.
- Significant effects of NB treatment were observed on a number of weight-related cardiometabolic parameters (e.g., waist circumference, triglycerides, HDL-cholesterol, and hs-CRP); HDL increases and triglyceride reductions were observed irrespective of history of dyslipidemia or treatment for this condition.
- Patients with type 2 diabetes benefitted from weight loss, improvements in waist circumference, HDL and triglycerides, and clinically significant improvements in glycemic control (particularly decreased HbA1c). A lower proportion of NB-treated patients required adjustments to their antidiabetic medications due to poor glycemic control.
- Greater proportions of NB-treated patients reported clinically meaningful improvements in weight-related quality of life compared with placebo, providing further evidence of the range of clinical benefits that can be derived from NB treatment.
- Greater effects of NB treatment were observed on multiple items of the COE questionnaire.
How Safe is Contrave?
- The use of NB was generally well-tolerated, with the frequency and distribution of safety findings being consistent with the established profiles for naltrexone and bupropion.
- Common AEs such as nausea and vomiting tended to occur early in treatment (during the dose-escalation phase), were mostly mild to moderate in severity, and were generally self-limiting.
- The incidence of treatment-emergent SAEs overall was low; the vast majority of SAEs in NB-treated patients were considered unrelated to study drug.
- Initiation of treatment with NB was associated with transient increases from baseline of approximately 1 mm Hg in mean blood pressure, followed by small reductions below baseline. These increases are consistent with the known hemodynamic effects of bupropion and were attenuated by weight loss in patients who responded to therapy, although mean blood pressure reductions with NB were always less than that observed with comparable placebo patients. The small elevations in heart rate seen with NB treatment (compared with decreases with placebo) are also consistent with known bupropion effects.
- The hemodynamic effects of NB are due to bupropion. Bupropion has been extensively prescribed since its original approval more than 20 years ago, and has a long history of safe use even in populations considered at risk for CV disease.
- The incidence of major cardiovascular events (cardiovascular death, myocardial infarction and cerebrovascular accident) and revascularization procedures were low and comparable between NB- and placebo-treated patients, although the number of events is too low to draw firm conclusions.
- Seizures occurred infrequently at a rate that is consistent with that observed for the lowest approved dose of bupropion SR.
- Treatment with NB in the target patient population does not appear to be associated with an increased risk for depression or suicidality.
- No hepatotoxicity was observed with long-term NB treatment.
- Clinical laboratory evaluations were generally unremarkable, and values outside of normal ranges tended to be sporadic and unrelated to dose.
- Neither bupropion nor naltrexone has historically been associated with prolongation of QTc intervals, and review of QT, QTc and the other ECG parameters in patients during long-term NB treatment revealed no noteworthy findings.
Coupon for Contrave (Contrave Complete Card)
Cost of Contrave without Coupon: the retail cost of Contrave is about $270.00 or so at most pharmacies.
Cost of Contrave with Coupon using Contrave Complete Card
If you have commercial insurance(non government issued insurance), you might only pay $30.00 to $100 per month!
Contrave with no insurance but with discount coupon
If you have no commercial insurance, and still want to try Contrave, you can still use the Contrave Complete Card and only pay $100.00.
Free smart scale called Scale Down Program with Contrave
Of note, the population of patients receiving currently approved bupropion-containing therapies has important similarities to patients enrolled in the NB clinical program, as well as the population of patients who receive currently marketed obesity pharmacotherapy. In addition, clinical experience and investigation in relevant patient populations, including those with cardiovascular risk factors or established cardiovascular disease, have not identified specific safety signals for clinical cardiovascular events.
Overall, the NB safety profile is well-understood, with known risks that are predictable and manageable via appropriate risk mitigation approaches. Orexigen is developing a plan for additional clinical studies to assess: 1) prescription utilization patterns, 2) physician and patient adherence to labeling, and 3) the impact of Contrave on cardiovascular outcomes.
Locations for physicians that are familiar with Contrave and other weight loss medications.