What are the necessary checks and considerations before prescribing naltrexone (opioid receptor antagonist) and bupropion (dopamine-norepinephrine reuptake inhibitor) for weight loss?

Pre-Prescription Screening for Naltrexone/Bupropion in Weight Loss

Before prescribing naltrexone/bupropion for weight loss, you must screen for absolute contraindications including current or anticipated opioid use, uncontrolled hypertension, seizure history or predisposing conditions, recent MAOI use (within 14 days), and end-stage renal disease. 1

Absolute Contraindications to Verify

Opioid-Related Exclusions

• Any patient requiring short-term or long-term opiate therapy must be excluded, as naltrexone will precipitate withdrawal and block therapeutic opioid effects 1
• This includes patients with chronic pain on opioid regimens, those who may need post-operative opioids, or anyone with anticipated opioid requirements 1

Neurological Contraindications

• History of seizures or conditions that lower seizure threshold are absolute contraindications 2, 1, 3
• Specifically exclude patients with:
  • Prior seizure disorder of any etiology 2
  • Bulimia or anorexia nervosa (increased seizure risk with bupropion) 2
  • Abrupt discontinuation of alcohol or benzodiazepines 1
  • Structural brain lesions or head trauma 1

Cardiovascular Screening

• Uncontrolled hypertension is an absolute contraindication 2, 1
• Measure baseline blood pressure before initiating therapy, as the combination increases blood pressure compared to placebo 3, 4
• Note that naltrexone/bupropion showed less improvement in systolic blood pressure and pulse compared to placebo in trials 4

Medication Interactions

• MAOI use within the past 14 days is contraindicated 2, 1
• Verify the patient is not taking tamoxifen, as bupropion is contraindicated with this medication 2

Organ Function Assessment

Renal Function

• Check GFR/creatinine clearance before prescribing 2, 1
• For moderate to severe renal impairment (GFR <90 mL/min), reduce dose to 1 tablet twice daily maximum 2, 1
• End-stage renal disease is an absolute contraindication 1

Hepatic Function

• Obtain baseline liver function tests 2, 1
• For moderate to severe hepatic impairment, maximum dose is 1 tablet daily (do not exceed 150 mg bupropion total) 2, 1

Patient Eligibility Criteria

BMI Requirements

• BMI ≥30 kg/m² (obese), OR 5
• BMI ≥27 kg/m² (overweight) with at least one weight-related comorbidity such as type 2 diabetes, hypertension, or dyslipidemia 5

Ideal Candidate Profile

• Patients describing food cravings or addictive eating behaviors are particularly suitable 1
• Those with comorbid depression benefit from dual mechanism 1
• Patients attempting smoking cessation or alcohol reduction simultaneously 1

Baseline Monitoring Parameters

Vital Signs

• Blood pressure (must be controlled before initiation) 2, 1
• Pulse rate (combination increases pulse vs placebo) 4
• Weight (for efficacy tracking) 1

Laboratory Studies

• Fasting glucose or HbA1c if diabetic 4
• Lipid panel (triglycerides, HDL) 4
• Liver function tests 2
• Renal function (creatinine, GFR) 2, 1

Psychiatric Assessment

• Screen for neuropsychiatric conditions, particularly in patients younger than 24 years 2
• Assess for history of depression, suicidal ideation, psychotic symptoms, or aggressive behavior 6
• Document baseline mood and cognitive function 6

Critical Safety Warnings to Discuss

Common Adverse Effects (Counsel Patient)

• Nausea (most common—occurs in approximately 50% of patients) 1, 4, 5
• Constipation, vomiting, dizziness, dry mouth 1, 4
• Headache and insomnia 1, 3

Serious Adverse Effects (Red Flags)

• Neuropsychiatric disorders: aggressiveness, depression, suicidal ideation, seizures, cognitive impairment, anxiety, psychotic symptoms 6
• Cardiovascular: cardiac arrhythmias, hypertension exacerbation 3, 6
• Allergic reactions: Stevens-Johnson syndrome, DRESS syndrome, angioedema 3

Discontinuation Criteria to Establish

• If <5% total body weight loss after 12 weeks on maintenance dose, discontinue therapy as the patient is a poor responder 1
• This is the FDA-approved efficacy threshold for continuing treatment 1

Drug Interaction Review

CYP2B6 Interactions

• Inhibitors (ticlopidine, clopidogrel): may require bupropion dose adjustment 3
• Inducers (ritonavir, lopinavir, efavirenz): may require dose increase but not exceeding maximum 3

Pharmacodynamic Interactions

• Avoid medications that lower seizure threshold additively 1
• Caution with antihypertensives (naltrexone/bupropion may undermine their action) 6
• Warfarin: monitor PT/INR closely due to risk of hemorrhagic or thrombotic complications 3

Pregnancy and Reproductive Considerations

• Teratogenic effect of bupropion cannot be ruled out 6
• Verify pregnancy status in women of childbearing potential before initiating 6
• Discuss contraception requirements during therapy 6