Side Effects | IMCIVREE® (setmelanotide)
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Possible side effects of IMCIVREE

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IMCIVREE has a well-established safety and tolerability profile

The most common side effects of IMCIVREE include:

  • Darkening of the skin (hyperpigmentation)
  • Injection site reactions
  • Nausea
  • Headache
  • Diarrhea
  • Stomach pain
  • Vomiting
  • Depression
  • Erection that happens without
    any sexual activity in males

In the acquired HO clinical trial for IMCIVREE, nausea and vomiting were most often reported within the first month of treatment and then declined.

These are not all the possible side effects of IMCIVREE. Call your doctor for medical advice about side effects. Please see additional Important Safety Information below.

The safety of IMCIVREE has been evaluated in more than 700 people over 10+ years through clinical trials and real-world experience across multiple approved uses.

Select Monitoring Considerations

If you have adrenal insufficiency and/or diabetes insipidus (also called arginine vasopressin deficiency), talk to your healthcare provider.

Adrenal Insufficiency

Your healthcare provider should evaluate your adrenal function before starting IMCIVREE. You or your caregiver should call your healthcare provider if you have changes in feeling tired or exhausted (fatigue), lack of energy (lethargy), mental status, or dizziness, or fever, or signs of infection during treatment with IMCIVREE. Your healthcare provider should monitor and adjust any medicines that may be affected during treatment.

Diabetes Insipidus (also called arginine vasopressin deficiency)

You or your caregiver should watch for signs of dehydration. You or your caregiver should contact your healthcare provider if you have changes in fluid intake or urine output, confusion, lethargy, or nausea and vomiting during treatment with IMCIVREE. Your healthcare provider should closely monitor sodium levels in your blood and adjust your other medicines if needed.

A general darkening of the skin (hyperpigmentation) is expected because of how IMCIVREE works

Examples of hyperpigmentation

Example of hyperpigmentation
Example of hyperpigmentation
Example of hyperpigmentation
Example of hyperpigmentation
Example of hyperpigmentation
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  • Darkening of the skin and/or hair is expected, as IMCIVREE may lead to increased production of melanin (which gives color to your skin and hair)
  • The degree of skin darkening can vary from person to person and can sometimes include darkening of existing skin growths (such as moles); the degree of darkening may depend on how much natural melanin a person has
  • In the clinical trials, hyperpigmentation increased over the first several weeks of IMCIVREE use and generally leveled off in the initial months of treatment
  • Darkening of the skin went away after people stopped using IMCIVREE
  • If hyperpigmentation is a concern, talk to your doctor and they will assess your response to treatment and work with you to create a plan to check for skin changes

You should have a full-body skin exam before starting and during treatment with IMCIVREE to check for skin changes.

Please review all the possible side effects of IMCIVREE included in the Patient Information and talk to your doctor about any questions you may have.

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Your Rhythm InTune Patient Education Manager (PEM)* can provide one-on-one support throughout your treatment experience and share educational resources with you along the way.

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*Patient Education Managers are employees of Rhythm Pharmaceuticals and do not provide medical care or advice. We encourage you to always speak to your healthcare providers regarding your medical care.

Talk to your doctor about IMCIVREE with help from our discussion guide.

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Learn more about how to take IMCIVREE.

Starting IMCIVREE

What is IMCIVREE?

IMCIVREE is a prescription medicine used in adults and children 4 years of age and older with acquired hypothalamic obesity (HO) to help them lose weight and keep the weight off.

IMCIVREE is not for use in people with the following conditions because it may not work:

  • Other types of obesity not related to acquired HO or other FDA-approved uses of IMCIVREE, including obesity associated with other genetic conditions and general obesity

It is not known if IMCIVREE is safe and effective in children under 4 years of age with acquired HO.

Important Safety Information

Do not use IMCIVREE if you have had a serious allergic reaction to it or any of its ingredients. Serious allergic reactions, including anaphylaxis, can happen.

Before you use IMCIVREE, tell your healthcare provider about all your medical conditions, including if you:

  • Have or have had areas of darkened skin, including skin discoloration (hyperpigmentation)
  • Have or have had depression, or suicidal thoughts or behavior
  • Have kidney problems
  • Are pregnant or planning to become pregnant. Losing weight while pregnant may harm your unborn baby. Your healthcare provider may stop your treatment with IMCIVREE if you become pregnant. Tell your healthcare provider if you become pregnant or think you might be pregnant during treatment with IMCIVREE
  • Are breastfeeding or plan to breastfeed. It is not known if IMCIVREE passes into your breast milk. You should not breastfeed during treatment with IMCIVREE

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

See the detailed Instructions for Use that come with your IMCIVREE to learn how to prepare and inject IMCIVREE, and how to properly throw away (dispose of) used syringes and needles.

What are the possible side effects of IMCIVREE?
IMCIVREE may cause serious side effects, including:

  • Male and female sexual function problems. IMCIVREE can cause an erection that happens without any sexual activity in males (spontaneous penile erection) and unwanted sexual reactions (changes in sexual arousal that happen without any sexual activity) in females. If you have an erection lasting longer than 4 hours, get emergency medical help right away
  • Depression and suicidal thoughts or actions. You or a caregiver should call your healthcare provider right away if you have any new or worsening symptoms of depression, suicidal thoughts or behaviors, or any unusual changes in mood or behavior
  • Serious allergic reactions. Stop taking IMCIVREE and get medical help right away if you have any symptoms of a serious allergic reaction including: swelling of your face, lips, tongue, or throat; problems breathing or swallowing; severe rash or itching; fainting or feeling dizzy; rapid heartbeat
  • Increased skin pigmentation, darkening of skin lesions (moles or nevi) you already have, and development of new skin lesions. These changes happen because of how IMCIVREE works in the body and will go away when you stop using IMCIVREE. You should have a full body skin exam before starting and during treatment with IMCIVREE to check for skin changes
  • Adrenal insufficiency. If you have acquired HO and adrenal insufficiency, your healthcare provider should evaluate your adrenal function before starting IMCIVREE. You or your caregiver should call your healthcare provider if you have changes in feeling tired or exhausted (fatigue), lack of energy (lethargy), mental status, or dizziness, or fever, or signs of infection during treatment with IMCIVREE. Your healthcare provider should monitor and adjust any medicines that may be affected during treatment
  • Low sodium levels in the blood. If you have acquired HO and diabetes insipidus, you or your caregiver should watch for signs of dehydration. You or your caregiver should contact your healthcare provider if you have changes in fluid intake or urine output, confusion, lethargy, or nausea and vomiting during treatment with IMCIVREE. Your healthcare provider should closely monitor sodium levels in your blood and adjust your other medicines if needed

The most common side effects of IMCIVREE include darkening of the skin, injection site reactions, nausea, headache, diarrhea, stomach pain, vomiting, depression, and an erection that happens without any sexual activity in males.

These are not all the possible side effects of IMCIVREE. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see full Prescribing Information, including Patient Information.

Use and Important Safety Information

What is IMCIVREE?

IMCIVREE is a prescription medicine used in adults and children 4 years of age and older with acquired hypothalamic obesity (HO) to help them lose weight and keep the weight off.

IMCIVREE is not for use in people with the following conditions because it may not work:

  • Other types of obesity not related to acquired HO or other FDA-approved uses of IMCIVREE, including obesity associated with other genetic conditions and general obesity

It is not known if IMCIVREE is safe and effective in children under 4 years of age with acquired HO.

Important Safety Information

Do not use IMCIVREE if you have had a serious allergic reaction to it or any of its ingredients. Serious allergic reactions, including anaphylaxis, can happen.

Before you use IMCIVREE, tell your healthcare provider about all your medical conditions, including if you:

  • Have or have had areas of darkened skin, including skin discoloration (hyperpigmentation)
  • Have or have had depression, or suicidal thoughts or behavior
  • Have kidney problems
  • Are pregnant or planning to become pregnant. Losing weight while pregnant may harm your unborn baby. Your healthcare provider may stop your treatment with IMCIVREE if you become pregnant. Tell your healthcare provider if you become pregnant or think you might be pregnant during treatment with IMCIVREE
  • Are breastfeeding or plan to breastfeed. It is not known if IMCIVREE passes into your breast milk. You should not breastfeed during treatment with IMCIVREE

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

See the detailed Instructions for Use that come with your IMCIVREE to learn how to prepare and inject IMCIVREE, and how to properly throw away (dispose of) used syringes and needles.

What are the possible side effects of IMCIVREE?
IMCIVREE may cause serious side effects, including:

  • Male and female sexual function problems. IMCIVREE can cause an erection that happens without any sexual activity in males (spontaneous penile erection) and unwanted sexual reactions (changes in sexual arousal that happen without any sexual activity) in females. If you have an erection lasting longer than 4 hours, get emergency medical help right away
  • Depression and suicidal thoughts or actions. You or a caregiver should call your healthcare provider right away if you have any new or worsening symptoms of depression, suicidal thoughts or behaviors, or any unusual changes in mood or behavior
  • Serious allergic reactions. Stop taking IMCIVREE and get medical help right away if you have any symptoms of a serious allergic reaction including: swelling of your face, lips, tongue, or throat; problems breathing or swallowing; severe rash or itching; fainting or feeling dizzy; rapid heartbeat
  • Increased skin pigmentation, darkening of skin lesions (moles or nevi) you already have, and development of new skin lesions. These changes happen because of how IMCIVREE works in the body and will go away when you stop using IMCIVREE. You should have a full body skin exam before starting and during treatment with IMCIVREE to check for skin changes
  • Adrenal insufficiency. If you have acquired HO and adrenal insufficiency, your healthcare provider should evaluate your adrenal function before starting IMCIVREE. You or your caregiver should call your healthcare provider if you have changes in feeling tired or exhausted (fatigue), lack of energy (lethargy), mental status, or dizziness, or fever, or signs of infection during treatment with IMCIVREE. Your healthcare provider should monitor and adjust any medicines that may be affected during treatment
  • Low sodium levels in the blood. If you have acquired HO and diabetes insipidus, you or your caregiver should watch for signs of dehydration. You or your caregiver should contact your healthcare provider if you have changes in fluid intake or urine output, confusion, lethargy, or nausea and vomiting during treatment with IMCIVREE. Your healthcare provider should closely monitor sodium levels in your blood and adjust your other medicines if needed

The most common side effects of IMCIVREE include darkening of the skin, injection site reactions, nausea, headache, diarrhea, stomach pain, vomiting, depression, and an erection that happens without any sexual activity in males.

These are not all the possible side effects of IMCIVREE. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see full Prescribing Information, including Patient Information.

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US-SET-2600039 (01.05/2026)