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Safety profile

IMCIVREE has a well-established safety and tolerability profile1,2

Adverse Reactions (≥5% and More Frequently Than Placebo) in IMCIVREE-treated Patients Aged 4 Years and Older With Acquired HO1

Adverse reactionIMCIVREE
N=94
%		Placebo
N=48
%
Skin hyperpigmentation*5810
Nausea5525
Vomiting3819
Headache†3731
Melanocytic naevus‡156
Constipation126
Dizziness124
Oropharyngeal pain114
Gastroenteritis92
Ear infection50

*Includes skin hyperpigmentation, skin discoloration, nail pigmentation, freckles, pigmentation disorder.

†Includes headache and migraine.

‡Development of new melanocytic nevi and darkening or increase in size of existing melanocytic nevi.

Please see additional Important Safety Information below.

Nausea and vomiting occurred most frequently within the first month of treatment, then declined.1

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In patients with secondary adrenal insufficiency, monitor for clinical signs of acute adrenal insufficiency.1

In patients with concomitant diabetes insipidus/arginine vasopressin deficiency, monitor serum sodium levels with changes in fluid intake and hydration status. Adjust the doses of concomitant therapies as needed.1

The safety of IMCIVREE has been evaluated across multiple indications in more than 700 patients over 10+ years, through clinical trials and real-world experience.2

Hyperpigmentation with IMCIVREE is common and variable1,3

Mechanism: IMCIVREE is an MC4 receptor agonist that has some residual activity at the MC1 receptor. Activation of the MC1 receptor can lead to the accumulation of melanin, resulting in hyperpigmentation. Because hyperpigmentation is a result of residual MC1 receptor activity, it is reversible after treatment discontinuation.1

Onset and duration: Hyperpigmentation is common and expected. In clinical trials, measures of hyperpigmentation increased throughout the dose escalation period and generally plateaued in the initial months of treatment.1,3

Variability: The degree and presentation of hyperpigmentation is variable across patients. Hyperpigmentation may be influenced by a patient's individual baseline melanin levels.3

If hyperpigmentation is a concern, assess patient response to treatment to optimize tolerability and efficacy as you would with other adverse events. It is important to remember that continued treatment with IMCIVREE is necessary to sustain clinical benefits, including reduced weight and hunger.1

Examples of hyperpigmentation

Example of hyperpigmentation
Example of hyperpigmentation
Example of hyperpigmentation
Example of hyperpigmentation
Example of hyperpigmentation
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Individual experiences may vary.

Questions about the safety profile of IMCIVREE? Talk to a Rhythm representative.

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Find information about dosing and administration.

See Dosing

HO=hypothalamic obesity, MC1=melanocortin-1, MC4=melanocortin-4.

Indication

IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 4 years and older with acquired hypothalamic obesity (HO).

Limitations of Use

IMCIVREE is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective:

  • Other types of obesity not related to acquired hypothalamic obesity or other FDA-approved indications for IMCIVREE, including obesity associated with other genetic syndromes and general (polygenic) obesity

Important Safety Information

Contraindications

Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported.

Warnings and Precautions

Disturbance in Sexual Arousal: Spontaneous penile erections and increased frequency of penile erections in males have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention.

Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur.

Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue IMCIVREE.

Skin Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic Nevi: Generalized or focal increases in skin pigmentation occurred in the majority of IMCIVREE-treated patients. IMCIVREE may also cause development of new melanocytic nevi or darkening of pre-existing nevi. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmented lesions.

Acute Adrenal Insufficiency with Acquired HO: Patients with acquired HO and secondary adrenal insufficiency reported serious adverse reactions related to acute adrenal insufficiency in 5% of IMCIVREE-treated patients and no placebo-treated patients. In patients with secondary adrenal insufficiency, monitor for clinical signs of acute adrenal insufficiency.

Sodium Imbalance in Patients with Acquired HO and Central Diabetes Insipidus: Patients with acquired HO and concomitant central diabetes insipidus (DI)/arginine vasopressin (AVP) deficiency reported hyponatremia in 6% of IMCIVREE-treated patients and 2% of placebo-treated patients and hypernatremia in 5% of IMCIVREE-treated patients and 4% of placebo-treated patients. Monitor serum sodium levels with changes in fluid intake and hydration status. Adjust the doses of concomitant therapies for DI/AVP deficiency as needed.

Adverse Reactions

  • Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, nausea, vomiting, and headache

Use in Specific Populations

Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Please see full Prescribing Information for additional Important Safety Information.

References: 1. IMCIVREE [prescribing information]. Boston, MA. Rhythm Pharmaceuticals, Inc., 2026. 2. Data on file. Rhythm Pharmaceuticals, Inc. Boston, MA. 3. Kanti V, Puder L, Jahnke I, et al. A melanocortin-4 receptor agonist induces skin and hair pigmentation in patients with monogenic mutations in the leptin-melanocortin pathway. Skin Pharmacol Physiol. 2021;34(6):307-316. doi:10.1159/000516282

Indication and Important Safety Information

Indication

IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 4 years and older with acquired hypothalamic obesity (HO).

Limitations of Use

IMCIVREE is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective:

  • Other types of obesity not related to acquired hypothalamic obesity or other FDA-approved indications for IMCIVREE, including obesity associated with other genetic syndromes and general (polygenic) obesity

Important Safety Information

Contraindications

Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported.

Warnings and Precautions

Disturbance in Sexual Arousal: Spontaneous penile erections and increased frequency of penile erections in males have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention.

Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur.

Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue IMCIVREE.

Skin Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic Nevi: Generalized or focal increases in skin pigmentation occurred in the majority of IMCIVREE-treated patients. IMCIVREE may also cause development of new melanocytic nevi or darkening of pre-existing nevi. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmented lesions.

Acute Adrenal Insufficiency with Acquired HO: Patients with acquired HO and secondary adrenal insufficiency reported serious adverse reactions related to acute adrenal insufficiency in 5% of IMCIVREE-treated patients and no placebo-treated patients. In patients with secondary adrenal insufficiency, monitor for clinical signs of acute adrenal insufficiency.

Sodium Imbalance in Patients with Acquired HO and Central Diabetes Insipidus: Patients with acquired HO and concomitant central diabetes insipidus (DI)/arginine vasopressin (AVP) deficiency reported hyponatremia in 6% of IMCIVREE-treated patients and 2% of placebo-treated patients and hypernatremia in 5% of IMCIVREE-treated patients and 4% of placebo-treated patients. Monitor serum sodium levels with changes in fluid intake and hydration status. Adjust the doses of concomitant therapies for DI/AVP deficiency as needed.

Adverse Reactions

  • Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, nausea, vomiting, and headache

Use in Specific Populations

Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Please see full Prescribing Information for additional Important Safety Information.

References:1. IMCIVREE [prescribing information]. Boston, MA. Rhythm Pharmaceuticals, Inc., 2026.2. Data on file. Rhythm Pharmaceuticals, Inc. Boston, MA.3. Kanti V, Puder L, Jahnke I, et al. A melanocortin-4 receptor agonist induces skin and hair pigmentation in patients with monogenic mutations in the leptin-melanocortin pathway. Skin Pharmacol Physiol. 2021;34(6):307-316. doi:10.1159/000516282
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