weight control agents
Adjunct to calorie-reduced diet and increased physical activity for chronic weight management in obese patients (BMI ≥30 kg/m2 ) or overweight patients (BMI ≥27 kg/m2 ) with at least one other comorbidity (hypertension, type 2 diabetes, or dyslipidemia).
- Bupropion– an antidepressant that acts as a weak inhibitor of neuronal reuptake of dopamine and norepinephrine.
- Naltrexone– acts as an opioid antagonist.
- In combination they affect two different brain areas involved in food intake: the hypothalamic appetite regulatory center and mesolimbic dopamine circuit reward system.
Decreased appetite with associated weight loss.
Absorption: Well absorbed but rapidly metabolized by the liver. Absorption is enhanced by a high-fat meal.
Distribution: Parent drug and metabolites enter breast milk.
Metabolism and Excretion: Extensively metabolized; three metabolites are pharmacologically active. Excretion is mostly renal as metabolites, minimal renal excretion of unchanged drug.
Half-life: 21 hr (longer for some metabolites).
Absorption: Well absorbed orally, undergoes extensive first pass hepatic metabolism resulting in 5–40% bioavailability. Absorption is enhanced by a high-fat meal.
Distribution: Parent drug and metabolites enter breast milk.
Metabolism and Excretion: Metabolized to 6–beta-naltrexol. Both parent drug and metabolite are pharmacologically active. Excretion is mostly renal as metabolite, less than 2% as unchanged drug.
Half-life: naltrexone– 5 hr; 6–beta-naltrexol– 13 hr.
TIME/ACTION PROFILE (weight loss)
|PO||within 4 wk||6 mos||unknown|
- Known hypersensitivity to bupropion or naltrexone;
- Uncontrolled hypertension;
- End-stage renal disease;
- Seizure disorders;
- Anorexia or bulimia;
- During withdrawal from or discontinuation of alcohol, benzodiazepines, barbiturates or antiepileptics;
- Chronic opioid/opiate agonist or partial agonist use or acute opiate withdrawal;
- During/within 14 days of MAOIs;
- Concurrent use of CYP2B6 inducers;
- Concurrent use of other bupropion-containing medications;
- OB: Pregnancy (may cause fetal harm);
- Lactation: Discontinue bupropion/naltrexone or discontinue breast feeding;
- Pedi: Not recommended for use in children.
Use Cautiously in:
- History of suicidal behavior/ideation;
- History of seizure risk (avoid administration with a high-fat meal, adhere to recommended dose);
- History of cardiac/cerebrovascular disease;
- History of angle-closure glaucoma;
- Diabetes mellitus (weight loss may result in hypoglycemia if treatment is not adjusted);
- Concurrent use of drugs that ↓ seizure threshold;
- Moderate to severe renal impairment (use lower dose);
- Hepatic impairment (use lower dose);
- Geri: Elderly may be ↑ sensitive to adverse CNS reactions and ↓ renal elimination;
- Concurrent ingestion of alcohol (avoid or reduce consumption).
Adverse Reactions/Side Effects
CNS: HOMICIDAL THOUGHTS/BEHAVIOR, SEIZURES, SUICIDAL THOUGHTS/BEHAVIOR, headache, aggression, agitation, anxiety, delusions, depression, dizziness, hallucinations, hostility, insomnia, mania, panic, paranoia, psychosis
CV: hypertension, tachycardia
EENT: angle-closure glaucoma (bupropion), tinnitus
GI: nausea, constipation, vomiting, abdominal pain, diarrhea, dry mouth, dysgeusia, hepatotoxicity (naltrexone)
Derm: hot flush, sweating
Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS/ANAPHYLACTOID REACTIONS
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Concurrent or use within 14 days with MAOIs ↑ risk of hypertensive reactions.
- Bupropion inhibits the CYP2D6 enzyme system and can ↑ blood levels and risk of adverse reactions from antidepressants including SSRIs and many tricyclic antidepressants, antipsychotics including haloperidol, risperidone, and thioridazine, beta-blockers including metoprolol, and Type 1C antiarrhythmics including flecanide and propafenone. Dose adjustments may be necessary.
- Blood levels and effectiveness may be ↓ by CYP2B6 inducers including carbamazepine, efavirenz, ritonavir, lopinavir, phenobarbital, and phenytoin ; concurrent use should be avoided.
- Blood levels and risk of toxicity of bupropion may be ↑ by CYP2B6 inhibitors including clopidogrel (dose should not exceed one tablet twice daily).
- Concurrent use of drugs that ↓ seizure threshold may ↑ risk of seizures.
- Dopaminergic drugs including amantadine and levodopa may ↑ risk of CNS toxicity.
- Concurrent use with opioids may ↑ risk of overdose.
- Concurrent ingestion of alcohol may ↑ risk of neuropsychiatric reactions (reduce consumption or avoid).
- May ↓ renal excretion of and ↑ blood levels/risk of toxicity from amantadine, amiloride, cimetidine, dopamine, famotidine, memantine, metformin, pindolol, procainamide, ranitidine, varenicline, and oxaliplatin (careful monitoring is recommended).
- May ↑ sensitivity to opioids.
PO (Adults): Wk 1– one tablet in the morning; wk 2– one tablet in the morning and one tablet in the evening; wk 3– two tablets in the morning and one tablet in the evening; wk 4 and onward– two tablets in the morning and two tablets in the evening; concurrent use of CYP2B6 inhibitors– dose should not exceed one tablet twice daily.
PO (Adults): Moderate to severe renal impairment– dose should not exceed one tablet in the morning and one tablet in the evening.Hepatic Impairment
PO (Adults): Dose should not exceed one tablet in the morning.
Extended-release tablets: 90 mg bupropion/8 mg naltrexone
- Monitor for weight loss and adjust concurrent medications (antihypertensives, antidiabetics, lipid-lowering agents) as needed.
- Assess mental status and mood changes, especially during initial few mo of therapy. Risk may be increased in children, adolescents, and adults ≤24 yrs. Inform health care professional if patient demonstrates significant increase in signs of depression (depressed mood, loss of interest in usual activities, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, irritability, hostility, suicide or homicide attempt or suicidal ideation). Restrict amount of drug available to patient.
- Monitor BP and heart rate periodically during therapy, especially in patient with hypertension.
- Monitor for signs and symptoms of anaphylactic reactions (pruritus, urticaria, hives, angioedema, dyspnea). Discontinue therapy and treat symptomatically.
Lab Test Considerations:
Monitor blood glucose prior to and during therapy in patients with type 2 diabetes; may cause hypoglycemia.
- May cause false-positive urine test for amphetamines.
Administer in the morning and evening according to dose escalation schedule. Swallow tablets whole; do not break, crush, or chew.
- Do not administer with a high-fat meal; may increase risk of seizures.
- Instruct patient to take medication as directed, following the dose escalation schedule. If a dose is missed, omit and wait until next scheduled dose; do not double doses. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
- Instruct patient to adhere to a reduced-calorie diet and increased physical activity.
- Advise patient, family, and caregivers to look for suicidality, especially during early therapy. Notify health care professional immediately if thoughts about suicide, homicide, or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, hostility, acting on dangerous impulses, mania, or other changes in mood or behavior occur.
- Advise patient to notify health care professional if signs and symptoms of liver damage (stomach pain lasting more than a few days, dark urine, yellowing of skin and whites of eyes, tiredness) occurs.
- Advise patients they may be more sensitive to opioids, even at lower doses, during therapy. Patients physically dependant on opioid analgesics should wait at least 7–10 days without opioids, or 2 wk without methadone, before beginning bupropion/naltrexone.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications and to minimize or avoid alcohol during therapy.
- Instruct female patients to inform health care professional if pregnancy is planned or suspected and to avoid breast feeding during therapy.
Decreased appetite with associated weight loss. Evaluate therapy after 12 wk at maintenance dose. If patient has not lost 5% of baseline body weight discontinue medication; clinically meaningful weight loss is unlikely.
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