Short answer: In the label's placebo-controlled trial in acquired hypothalamic obesity, the most common Imcivree side effects were skin darkening (58% vs 10% on placebo), nausea (55% vs 25%), vomiting (38% vs 19%) and headache (37% vs 31%). In the BBS and POMC/PCSK1/LEPR trials, injection-site reactions, skin darkening, nausea and spontaneous erections were common. Imcivree has no boxed warning.
What Imcivree is approved for: Imcivree is approved to reduce excess body weight and keep it off long term in people 4 and older with acquired hypothalamic obesity (HO), and in people 2 and older with obesity due to Bardet-Biedl syndrome (BBS) or POMC, PCSK1 or LEPR deficiency confirmed by genetic testing (section 1). The label says it is not expected to work for general obesity or other types of obesity (section 1.1).
Source
IMCIVREE (setmelanotide) injection, for subcutaneous use, prescribing information and Patient Information. Rhythm Pharmaceuticals. DailyMed, version published April 2, 2026. DailyMed setid 70c3ccf7-4df0-4c75-ba07-fede9970c8d9
No. The current Imcivree label has no boxed warning.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Imcivree.
| Adverse reaction | IMCIVREE (N=94) % | Placebo (N=48) % |
|---|---|---|
| Skin hyperpigmentation (1) | 58 | 10 |
| Nausea | 55 | 25 |
| Vomiting | 38 | 19 |
| Headache (2) | 37 | 31 |
| Melanocytic naevus (3) | 15 | 6 |
| Constipation | 12 | 6 |
| Dizziness | 12 | 4 |
| Oropharyngeal pain | 11 | 4 |
| Gastroenteritis | 9 | 2 |
| Ear infection | 5 | 0 |
Randomized placebo-controlled trial of 142 people aged 4 and older with acquired HO: a 4- to 8-week dose titration, then 52 weeks of treatment. (1) Includes skin hyperpigmentation, skin discoloration, nail pigmentation, freckles and pigmentation disorder. (2) Includes headache and migraine. (3) New moles and darkening or growth of existing moles.
| Adverse reaction | IMCIVREE-treated Patients N = 43 % |
|---|---|
| Skin hyperpigmentation (2) | 63 |
| Injection site reactions (3) | 51 |
| Nausea | 26 |
| Spontaneous penile erection (4) | 25 |
| Vomiting | 19 |
| Diarrhea | 14 |
| Melanocytic nevus (5) | 14 |
| Headache | 7 |
| Skin striae | 7 |
| Aggression | 5 |
| Fatigue | 5 |
43 people with BBS treated with at least 1 dose. This period had no placebo column; in the earlier 14-week placebo-controlled part, skin darkening was 67% vs 0% and vomiting 11% vs 0%. (2) Includes skin hyperpigmentation, hair color changes and melanoderma. (3) Includes injection-site redness, itching, hardening, pain, bruising, swelling, reaction, bleeding, irritation and mass. (4) n = 20 male patients. (5) New moles, larger moles and darkening of existing moles.
| Adverse reaction | IMCIVREE-treated Patients N = 27 % |
|---|---|
| Injection site reaction (1) | 96 |
| Skin hyperpigmentation (2) | 78 |
| Nausea | 56 |
| Headache | 41 |
| Diarrhea | 37 |
| Abdominal pain (3) | 33 |
| Back pain | 33 |
| Fatigue | 30 |
| Vomiting | 30 |
| Depression (4) | 26 |
| Upper respiratory tract infection | 26 |
| Spontaneous penile erection (5) | 23 |
| Arthralgia | 19 |
| Asthenia | 19 |
| Melanocytic nevus (6) | 19 |
| Dizziness | 15 |
| Dry mouth | 15 |
| Dry skin | 15 |
| Insomnia | 15 |
| Vertigo | 15 |
| Alopecia | 11 |
| Chills | 11 |
| Constipation | 11 |
| Influenza-like illness | 11 |
| Muscle spasm | 11 |
| Pain in extremity | 11 |
| Rash | 11 |
| Suicidal ideation | 11 |
Two 52-week open-label trials of 27 people; no placebo group. (1) Includes redness, itching, swelling, pain, hardening, bruising, hypersensitivity, hematoma, nodule and discoloration at the injection site. (2) Includes skin hyperpigmentation, pigmentation disorders, skin and gum discoloration. (3) Abdominal pain and upper abdominal pain. (4) Includes depressed mood. (5) n = 13 male patients. (6) New moles, larger moles and darkening of existing moles.
In acquired HO (Trial 1): spontaneous or more frequent erections 7% vs 4% on placebo; serious acute adrenal insufficiency 5% vs none; in people who also had central diabetes insipidus, low sodium 6% vs 2% and high sodium 5% vs 4%.
In children aged 2 to under 6 with POMC or LEPR deficiency or BBS (Trial 5, 12 children, open-label): spontaneous erections 8% and depressed mood 8%.
Children with BBS or POMC, PCSK1 or LEPR deficiency had more vomiting, skin darkening and new or darkening moles than adults with these conditions.
Skin darkening happened in most people on Imcivree in trials and goes away when the medicine is stopped.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Sexual arousal changes. Spontaneous erections and more frequent erections in males, and sexual reactions in females, have occurred. An erection lasting longer than 4 hours needs emergency medical care.
Depression and suicidal thoughts. Depression and suicidal thoughts have occurred. People with a past history may be at higher risk. People are watched for new or worse depression, suicidal thoughts or unusual mood changes, and stopping Imcivree may be considered.
Serious allergic reactions. Serious allergic reactions, including anaphylaxis, have been reported, usually within minutes to hours of an injection. If one happens, Imcivree is stopped and medical help sought promptly.
Skin darkening and moles. Imcivree can darken the skin, darken existing moles and cause new moles because of how it works. A full-body skin exam is done before starting and periodically during treatment.
Adrenal insufficiency in acquired HO. In people with acquired HO and secondary adrenal insufficiency, serious acute adrenal insufficiency was reported in 5% on Imcivree and none on placebo. These people are watched for its signs.
Sodium imbalance in acquired HO with diabetes insipidus. Both low and high blood sodium were reported. In people with acquired HO and central diabetes insipidus, sodium is checked with changes in fluid intake and hydration, and their diabetes insipidus treatment adjusted as needed.
From the Patient Information that comes with Imcivree:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.