Setmelanotide
IMCIVREE
What it isMC4 receptor agonist restoring signaling downstream of leptin; obesity from POMC, PCSK1 or LEPR deficiency and Bardet-Biedl syndrome.
Why this oneIt treats the specific genetic defect, producing weight loss where lifestyle and other agents cannot.
What limits itGenotype-restricted, so confirm the diagnosis first. Skin hyperpigmentation and spontaneous erections; daily injection and very high cost.
FDA label
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| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Acquired hypothalamic obesity (HO) | adults & peds ≥6 yr | SC 0.5 mg QD × 2 wk | SC 3 mg QD (maintenance) | SC 3 mg QD |
| Acquired hypothalamic obesity (HO) | peds 4–<6 yr | SC 0.5 mg QD × 2 wk | Weight-based maintenance (label Table 2) | Weight-based (label Table 2) |
| BBS or POMC/PCSK1/LEPR deficiency obesity | adults & peds ≥12 yr | SC 2 mg QD × 2 wk (if not tolerated: SC 1 mg QD ≥1 wk, then 2 mg) | SC 3 mg QD (maintenance); if 3 mg not tolerated, SC 2 mg QD | SC 3 mg QD |
| BBS or POMC/PCSK1/LEPR deficiency obesity | peds 6–<12 yr | SC 1 mg QD × 2 wk (if not tolerated: SC 0.5 mg QD ≥1 wk, then 1 mg) | SC 2 mg QD × 2 wk, then SC 3 mg QD (maintenance) | SC 3 mg QD |
| BBS or POMC/PCSK1/LEPR deficiency obesity | peds 2–<6 yr | SC 0.5 mg QD × 2 wk (discontinue if not tolerated) | Weight-based increase (label Table 3) | Weight-based (label Table 3) |
Titration Increase only after starting dose tolerated for 2 weeks; intermediate step-downs require ≥1 week of tolerability before re-escalating
Renal Mild–moderate (eGFR 30–89): no adjustment. Severe (eGFR 15–29): acquired HO — not recommended; BBS/POMC/PCSK1/LEPR — start SC 0.5 mg QD × 2 wk, maintenance max SC 1.5 mg QD (≥12 yr) or SC 1 mg QD (6–<12 yr and 2–<6 yr ≥20 kg; not recommended 2–<6 yr <20 kg). ESRD (eGFR <15): not recommended
Hepatic Undefined
If starting dosage not tolerated in acquired HO or in peds 2–<6 yr: discontinue
Instructions
- Inject SC in abdomen, thigh, or arm; rotate site daily; do NOT give IV or IM
- Administer QD at beginning of the day, without regard to meals
- Use 1-mL syringe with 28- or 29-gauge needle; train patients/caregivers on injection technique
- Remove from refrigerator ~15 min before injection, or roll vial between palms 60 sec; inspect — clear to slightly opalescent, colorless to slightly yellow; discard if particulates/discoloration
- Monitor for GI adverse reactions during initiation and titration
- Full-body skin examination before initiation and periodically during treatment
- Missed dose: skip; resume with next scheduled dose
Cautions
- Disturbance in sexual arousal — spontaneous penile erections; erection >4 h requires emergency care
- Depression and suicidal ideation — monitor; consider discontinuing for suicidal thoughts/behaviors or significant persistent depression
- Serious hypersensitivity reactions incl. anaphylaxis (minutes–hours after injection) — discontinue
- Skin hyperpigmentation, darkening of pre-existing nevi, new melanocytic nevi (majority of patients; reversible) — baseline and periodic full-body skin exam
- Acute adrenal insufficiency in acquired HO with secondary adrenal insufficiency — monitor
- Sodium imbalance (hypo-/hypernatremia) in acquired HO with central diabetes insipidus/AVP deficiency — monitor serum sodium; adjust DI therapy
Adverse reactions
- Skin hyperpigmentation
- Injection site reactions
- Nausea
- Headache
- Diarrhea
- Abdominal pain
- Vomiting
- Depression
- Spontaneous penile erection
Pregnancy Discontinue when pregnancy recognized unless benefit outweighs fetal risk — weight loss offers no benefit in pregnancy and may cause fetal harm
Lactation Not recommended while breastfeeding (present in rat milk; contains benzyl alcohol though infant exposure unlikely)
NO BOXED WARNINGS
Principal riskGenotype-restricted; hyperpigmentation and cost
Classes and tags
Clinical profile
Mechanism of action: Setmelanotide ballicule
