Naltrexone bupropion Wikipedia
As increase sperm count , using naltrexone-bupropion may cause episodes of low blood sugar when taken by people with diabetes who are taking certain oral medications to control blood sugar. Both medications have individually shown some evidence of effectiveness in weight loss, and the combination has been shown to have some synergistic effects on weight. Participants were overweight (body mass index of 27 or greater), had type 2 diabetes, and had not been able to reach a blood sugar level below 7% with oral antidiabetic medications or diet and exercise alone. CONTRAVE is a prescription medicine which contains 2 medicines (naltrexone and bupropion) that may help some obese or overweight adults, who also have weight related medical problems, lose weight and keep the weight off. Changes in glycemic control observed from baseline to Week 56 among patients with type 2 diabetes and obesity assigned to either CONTRAVE 32 mg/360 mg or placebo are shown in Table 8.
When CONTRAVE was administered with a high-fat meal, the AUC and Cmax for naltrexone increased 2.1-fold and 3.7-fold, respectively, and the AUC and Cmax for bupropion increased 1.4-fold and 1.8-fold, respectively. Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported mainly when bupropion was part of multiple drug overdoses. Other serious reactions reported with overdoses of bupropion alone included hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes such as conduction disturbances (including QRS prolongation) or arrhythmias, clonus, myoclonus, and hyperreflexia. In a lactation study of ten women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. In a pre-and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day (approximately 7 times the MRHD on a mg/m² basis) from embryonic implantation through lactation had no effect on pup growth or development.
Older individuals may be more sensitive to the central nervous system adverse effects of CONTRAVE. When given to pregnant rabbits during organogenesis, non-dose-related increases in incidence of fetal malformations and skeletal variations were observed at the lowest dose tested (25 mg/kg/day, approximately 2 times the MRHD on a mg/m² basis) and greater. The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international Pregnancy Registry was 1.3% (9 cardiovascular malformations out of 675 first-trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). (see Data).The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
valor da oxandrolona manipulada following findings are from studies performed individually with naltrexone and bupropion. Further advise patients that the attempt to administer large doses of any opioid or to bypass the blockade while on CONTRAVE may lead to serious injury, coma, or death.Patients should be off all opioids for a minimum of 7 to 10 days before starting CONTRAVE in order to avoid precipitation of withdrawal. If a patient develops hypoglycemia after starting CONTRAVE, appropriate changes should be made to the antidiabetic drug regimen.Advise the patient to read the FDA-approved patient labeling (Medication Guide)Patient information is printed at the end of this insert. Prior to initiating CONTRAVE, screen patients for a history of bipolar disorder and the presence of risk factors for bipolar disorder (e.g., family history of bipolar disorder, suicide, or depression). When patients presented with elevated transaminases, there were often other potential causative or contributory etiologies identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs.
Pooled analysis of CONTRAVE data suggested no clinically meaningful differences in the pharmacokinetic parameters of bupropion or naltrexone based on race. Pooled analysis of CONTRAVE data suggested no clinically meaningful differences in the pharmacokinetic parameters of bupropion or naltrexone based on gender. The fraction of the oral dose of bupropion excreted unchanged was 0.5%, a finding consistent with the extensive metabolism of bupropion. Urinary excretion of unchanged naltrexone accounts for less than 2% of an oral dose. At steady state, the food effect increased AUC and Cmax for naltrexone by 1.7-fold and 1.9-fold, respectively, and increased AUC and Cmax for bupropion by 1.1-fold and 1.3-fold, respectively.
In a two-year carcinogenicity study in rats with naltrexone, there were small increases in the numbers of testicular mesotheliomas in males and tumors of vascular origin in males and females. Safety margins were estimated using body surface area exposure (mg/m²) based on a body weight of 100 kg. Advise pregnant patients and all patients who can become pregnant of the potential risk to a fetus. Further advise patients that the attempt to administer large doses of any opioid or to bypass the blockade while on CONTRAVE may lead to serious injury, coma, or death. Patients should be advised that the excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizure.
In patients with moderate or severe renal impairment, the maximum recommended daily dose for CONTRAVE is two tablets (one tablet each morning and evening). 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. 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.
Apart from COR-Diabetes, which only enrolled patients with type 2 diabetes, the demographic characteristics of patients were similar across all four trials. Of the overall population from these four trials, 24% had hypertension, 54% had dyslipidemia at study entry, and 10% had type 2 diabetes. The COR-I, COR-II, and COR-BMOD trials enrolled patients with obesity (BMI 30 kg/m² or greater) or overweight (BMI 27 kg/m² or greater) and at least one comorbidity (hypertension or dyslipidemia). Four 56-week multicenter, double-blind, placebo-controlled obesity trials (CONTRAVE Obesity Research, or COR-I, COR-II, COR-BMOD, and COR-Diabetes) were conducted to evaluate the effect of CONTRAVE in conjunction with lifestyle modification in 4,536 patients randomized to CONTRAVE or placebo. In a study of seven patients with end-stage renal disease requiring dialysis, peak plasma concentrations of naltrexone were elevated at least 6-fold compared to healthy subjects. In ecampania with mild, moderate, and severe renal impairment, AUC of bupropion metabolites threohydrobupropion and erythrohydrobupropion increased approximately 1.3-, 1.9-, and 1.7-fold and 1.2-, 1.8-, and 1.5-fold, respectively.