Topiramate 15mg | Bupropion 100mg | Naltrexone 10mg

Administered orally. Swallow capsule(s) whole with water as directed by the prescriber. May be taken with or without food; avoid high-fat meals if the formulation contains extended-release bupropion (increased bupropion absorption). Do not crush or chew capsules unless specifically instructed.

Dosing is individualized by the prescriber based on patient weight, comorbidities, and tolerability. This compounded formulation allows lower starting doses than commercially fixed-dose combinations to allow slower titration.

• Typical initiation approach: start at the lowest dose strengths once daily and gradually titrate upward based on tolerability and response
• The prescriber determines the dose escalation schedule
• Assess therapeutic response (weight loss ≥5% from baseline) at 12–16 weeks to determine whether continuation is appropriate

• Topiramate: Suppresses appetite through multiple mechanisms: augments GABA-A receptor activity (inhibitory), antagonizes glutamate at AMPA/kainate receptors (excitatory), blocks voltage-gated sodium channels, and inhibits carbonic anhydrase isoenzymes. Together these actions reduce caloric intake and may lower the body weight set-point.
• Bupropion: Inhibits reuptake of norepinephrine and dopamine in the CNS. In the hypothalamus, bupropion activates proopiomelanocortin (POMC) neurons, triggering release of melanocortin peptides (α-MSH) that reduce appetite and increase energy expenditure via MC4 receptors. Endogenous opioids provide auto-inhibitory feedback on POMC neurons, limiting this effect.
• Naltrexone: Blocks μ-opioid receptors, removing the opioid-mediated auto-inhibitory brake on hypothalamic POMC neurons, thereby amplifying bupropion's anorexigenic signal. Naltrexone also reduces the hedonic reward associated with food intake by antagonizing the mesolimbic opioid system.

This combination is used prescriber-directed as an adjunct to diet and exercise for chronic weight management in adults with obesity (BMI ≥30 kg/m²) or overweight (BMI 27–29.9 kg/m²) with at least one weight-related comorbidity (hypertension, type 2 diabetes, dyslipidemia). The triple combination offers complementary and potentially synergistic mechanisms targeting appetite, satiety, and food reward.

Monitoring parameters:

• Blood pressure and heart rate at baseline and periodically (bupropion and naltrexone can increase BP and HR)
• Suicidality screening (bupropion carries a boxed warning for suicidal thoughts)
• Liver function tests (naltrexone—hepatotoxicity risk)
• Ophthalmic pressure (topiramate—acute myopia/glaucoma risk)
• Serum bicarbonate (topiramate—metabolic acidosis risk)
• Blood glucose in patients with diabetes (weight loss may require anti-diabetic dose adjustment)
• Body weight at 12–16 weeks to assess response

Contraindications:

• Uncontrolled hypertension
• Seizure disorder or history of seizures (bupropion)
• Concomitant use of other bupropion-containing products
• Bulimia or anorexia nervosa (increased seizure risk with bupropion)
• Chronic opioid or opioid partial agonist use (naltrexone precipitates withdrawal)
• Concurrent or recent (<14 days) MAOI use
• Acute angle-closure glaucoma (topiramate risk)
• Hypersensitivity to any component
• Pregnancy (topiramate—Category D; teratogenic)

Warnings & Precautions:

• Suicidal behavior and ideation (bupropion—boxed warning)
• Seizures: bupropion lowers seizure threshold; dose-related risk
• Acute angle-closure glaucoma and acute myopia: topiramate can cause secondary glaucoma within hours to weeks of initiation—seek immediate care for acute visual changes
• Metabolic acidosis: topiramate inhibits carbonic anhydrase; monitor serum bicarbonate
• Hepatotoxicity: naltrexone—monitor LFTs; contraindicated in acute hepatitis/hepatic failure
• Opioid sensitivity: naltrexone blockade may increase opioid sensitivity after discontinuation—risk of fatal opioid overdose
• Cognitive and neuropsychiatric effects: topiramate—word-finding difficulty, psychomotor slowing
• Increased BP and HR: bupropion and naltrexone
• Teratogenicity: topiramate is a known teratogen (oral clefts); confirm negative pregnancy test in women of reproductive potential before initiation

Drug Interactions:

• MAOIs: dangerous hypertensive crisis with bupropion
• CYP2D6 substrates: bupropion inhibits CYP2D6; dose reduction of CYP2D6-metabolized drugs (antidepressants, antipsychotics, beta-blockers) may be needed
• CYP2B6 inhibitors: increase bupropion exposure
• Opioid analgesics: naltrexone blocks opioid analgesia; do not use concurrently
• Drugs that lower seizure threshold (antipsychotics, TCAs, theophylline): additive seizure risk with bupropion

Common Side Effects: Nausea, constipation, headache, insomnia, dry mouth, dizziness (bupropion/naltrexone); paresthesias, cognitive slowing, decreased appetite, metabolic acidosis, kidney stones (topiramate); and increased heart rate and blood pressure.

Store at room temperature (15–30°C) in a tightly sealed container, away from moisture and heat. Do not freeze. Keep out of reach of children. Use within the beyond-use date established by Genesis Compounding.

Why are three medications combined into one formula?

Each ingredient targets a different brain pathway involved in appetite, food reward, and weight regulation. Topiramate reduces appetite through CNS inhibitory mechanisms; bupropion activates the hypothalamic hunger-suppressing POMC pathway; and naltrexone removes the braking mechanism that limits bupropion's effect—creating synergistic weight-management benefits.

Is this combination FDA-approved?

Naltrexone/bupropion (Contrave) and phentermine/topiramate (Qsymia) are FDA-approved combinations for weight management, but this specific three-drug combination is not FDA-approved. This 503A compounded preparation allows the prescriber to customize doses of all three components for an individual patient.

Can I take opioid pain medications while on this?

No. Naltrexone blocks opioid receptors and will prevent opioid pain medications from working. It may also precipitate acute opioid withdrawal in opioid-dependent patients. Inform all your providers you are taking naltrexone.

What eye symptoms should I report immediately?

Topiramate can cause acute secondary angle-closure glaucoma, presenting as sudden eye pain, redness, and blurry vision. This is a medical emergency—seek immediate ophthalmologic evaluation.

Is this safe in pregnancy?

No. Topiramate is a known teratogen associated with oral clefts and other fetal malformations. Women of reproductive potential must use effective contraception throughout treatment.