Overview:
Bremelanotide is a synthetic peptide developed as a potential treatment for sexual dysfunction, specifically in women with hypoactive sexual desire disorder (HSDD). It works by activating melanocortin receptors in the brain, which can enhance sexual arousal and desire. Bremelanotide is administered as a subcutaneous injection. The U.S. Food and Drug Administration (FDA) approved Bremelanotide for use in premenopausal women with HSDD in 2019. The drug is not approved for use in men or postmenopausal women. The drug can also cause an increase in blood pressure, so individuals with high blood pressure or heart disease should be cautious when using this drug. The patients are advised to use effective contraception while using the drug.
How Does Bremelanotide Work?
Bremelanotide is a synthetic peptide analog of the naturally occurring hormone alpha-melanocyte-stimulating hormone (alpha-MSH), which is produced in the pituitary gland. Bremelanotide works by activating melanocortin receptors in the brain, particularly the MC4 receptor, which regulates a variety of physiological processes, including sexual function, appetite, and skin pigmentation.
When Bremelanotide binds to the MC4 receptor, it activates a signaling pathway that leads to the release of dopamine, a neurotransmitter involved in the regulation of mood. This activation of the dopamine pathway is thought to be responsible for Bremelanotide's effects on sexual function, including increased libido and improved sexual satisfaction.
Dosage and Administration:
Bremelanotide is administered as a subcutaneous injection. The recommended dose is 1.75 mg, which should be injected into the abdomen or thigh at least 45 minutes before anticipated sexual activity.
The injection site should be rotated with each dose, and the injection should be given under the skin, not into a muscle or a vein. Patients should be instructed on proper injection techniques and should not use the medication if they are unsure of how to administer the injection. It is important to follow the dosing instructions provided by the healthcare provider and not adjust the dose or frequency of administration without first consulting with the healthcare provider.
Warnings:
Following are some of the precautions associated with Bremelanotide:
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Heart Diseases: Bremelanotide can cause an increase in blood pressure, which may be particularly concerning for people with a history of cardiovascular disease or uncontrolled hypertension. Before prescribing Bremelanotide, healthcare providers should assess the patient's cardiovascular risk factors and consider monitoring blood pressure during treatment.
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Skin: Bremelanotide may cause temporary skin darkening, particularly in areas exposed to sunlight or ultraviolet (UV) light. This effect is more prominent in dark skin people. Patients should be advised to avoid excessive sun exposure and use appropriate sun protection measures during treatment.
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Gastrointestinal: Bremelanotide may cause nausea with the administration of the first dose of the drug and gradually lessens with subsequent use. Medications for nausea may be prescribed by the doctor if the effect is persistent.
Note that Bremelanotide should only be used under the supervision of a healthcare provider and in accordance with the prescribing information.
For Patients:
What Is Hypoactive Sexual Desire Disorder?
Hypoactive sexual desire disorder (HSDD) is a sexual dysfunction characterized by a persistent or recurrent deficiency or absence of sexual fantasies and desire for sexual activity that causes significant distress or interpersonal difficulties. The disorder can affect both men and women and can occur at any age.
The causes of HSDD are not fully understood, but they can include psychological factors such as depression, anxiety, and stress, as well as hormonal imbalances and certain medical conditions.
When and Why to Take Bremelanotide?
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Bremelanotide is taken as a self-administered injection, typically about 45 minutes before anticipated sexual activity.
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The recommended starting dose is 1.75 mg, but the healthcare provider may adjust the dose based on the patient’s response.
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The drug should only be used as prescribed by a healthcare provider and is not recommended for individuals with uncontrolled high blood pressure or cardiovascular disease.
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It can also interact with certain medications, so it is important to inform the healthcare provider of any other medications the patient is taking.
How Effective Is Bremelanotide?
Bremelanotide has been shown to be effective in treating hypoactive sexual desire disorder (HSDD) in premenopausal women. In clinical trials, bremelanotide has been shown to significantly increase sexual desire and decrease distress related to low sexual desire compared to a placebo. It is important to note that the effectiveness of Bremelanotide may vary among individuals and that it may not be effective for all women with HSDD. Also, the drug is intended for short-term use, and its safety and effectiveness extend beyond five months (24 months).
What Are the Things to Inform the Doctor Before Taking Bremelanotide?
It is necessary to inform the doctor if any of the following conditions are present before taking Bremelanotide.
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High Blood Pressure or Heart Diseases: Since Bremelanotide can cause transient increases in blood pressure levels. Precaution should be taken in patients with pre-existing high blood pressure.
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Kidney or Liver Diseases: Use only if directed by the doctor.
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Pregnancy: Bremelanotide can cause harm to the fetus if the drug is administered during pregnancy. Hence, effective contraception is advised. However, if pregnancy is suspected, inform the doctor immediately.
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Breastfeeding: The presence of Bremelanotide in breast milk is not yet been fully researched. Hence, it is important for nursing mothers to always talk with the doctor before taking the drug.
What Are the Side Effects of Bremelanotide?
The common side effects of the drug include:
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Flushing.
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Vomiting.
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Extreme nausea.
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Cough.
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Tingling.
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Injection site reactions.
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Headache.
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Dizziness.
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Fatigue.
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Hot flush.
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Nasal congestion.
If these effects are not resolved on their own or become persistent or worsen, immediate medical intervention is necessary.
Dietary Alterations for Bremelanotide:
There are no specific dietary alterations that are required when taking Bremelanotide for the treatment of hypoactive sexual desire disorder (HSDD). It is important to maintain a healthy and balanced diet while taking Bremelanotide, as good nutrition is important for overall health and well-being. Eating a diet rich in fruits, vegetables, whole grains, and lean protein can provide the nutrients the body needs to function optimally.
Missed Dose:
If the patient has any concerns about missed doses or how to take Bremelanotide, it is important to speak with the healthcare provider. They can provide personalized advice based on your individual needs and circumstances.
Overdose:
The effects of an overdose of Bremelanotide are not well known. There have been reports of adverse events, including nausea, vomiting, and blood pressure changes, in some individuals who have received higher than recommended doses of Bremelanotide. If an overdose of Bremelanotide is suspected, seek emergency medical attention or call the local poison control center immediately.
Storage:
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Bremelanotide should be stored in a refrigerator between 2°Celsius to 8°Celsius (36°Fahrenheit to 46°Fahrenheit). It should not be frozen.
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Before using Bremelanotide, allow the vial to come to room temperature by leaving it at room temperature for at least 30 minutes. Do not use a microwave or warm water to warm the medication.
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For any concerns about the storage of Bremelanotide, it is important to speak with the healthcare provider or pharmacist.
For Doctors
Indication:
Bremelanotide is indicated to treat lack or loss of sexual desire in premenopausal women.
Dosing: 1.75 mg subcutaneously in the abdomen or thigh once as needed, at least 45 minutes prior to sexual activity.
Maximum Dose: 1 dose/24 hours and eight doses/month.
Dosing Considerations:
No data had yet been published regarding dosing adjustments in various conditions.
What Are the Pharmacological Aspects of Bremelanotide?
Mechanism of Action:
Bremelanotide is an agonist for numerous melanocortin receptors, including the MC1R, MC4R, MC3R, MC5R, and MC2R, in order of potency. Although MC4R receptors are found in numerous regions of the central nervous system, it is still unknown how agonism of these receptors leads to a reduction in hypoactive sexual desire disease. The hypothalamus is home to the MC3R and MC4R receptors, which regulate food intake and energy homeostasis.
Pharmacodynamics:
Bremelanotide is administered as a subcutaneous injection 45 minutes before planned sexual activity. Increased melanin expression is also brought on by MC1R antagonistic activity. Patients on Bremelanotide may also experience vomiting, nausea, and headaches.
Pharmacokinetics:
Absorption:
Bremelanotide is administered subcutaneously, and its absorption is rapid and complete. The maximum plasma concentration is achieved within 45 minutes after the injection.
Distribution:
Bremelanotide is rapidly distributed to tissues after absorption. The volume of distribution of Bremelanotide is approximately 25 liters.
Metabolism:
Bremelanotide is metabolized by peptidases, primarily by neutral endopeptidase (NEP) and aminopeptidase N (APN). The primary metabolite, des-tyrosyl-bremelanotide, is less active than the parent compound and is excreted mainly in the urine.
Excretion:
Bremelanotide and its metabolites are primarily excreted in the urine, with approximately 70 percent of the dose excreted within 24 hours after administration. The elimination half-life of Bremelanotide is approximately two to three hours.
Clinical Studies:
Two randomized phase 3 clinical trials were conducted to evaluate the safety and efficacy of bremelanotide in premenopausal women with HSDD. In both trials, women were randomly assigned to receive either Bremelanotide or a placebo for a period of 24 weeks. The primary outcome measured was an increase in the number of satisfying sexual events (SSEs) per month, as reported by the women themselves.
The results showed that women who received Bremelanotide had a statistically significant increase in the number of SSEs per month compared to those who received the placebo. In addition, a greater proportion of women in the Bremelanotide group reported an improvement in their sexual desire and distress related to low sexual desire compared to the placebo group.
The most common adverse effects reported were nausea, flushing, and headache. These side effects were generally mild to moderate in severity and resolved on their own without any treatment. More research is needed to further evaluate the long-term safety and efficacy of this medication.
Warnings and Precautions:
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Cardiovascular: Each dose causes a brief increase in blood pressure and a brief decrease in heart rate; monitoring is advised; use is not advised in patients who have a high risk of cardiovascular disease.
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Dermatologic: Patients may experience focal hyperpigmentation of the face, gingiva, and breasts. It was observed particularly in patients with dark complexion; discontinuation may be necessary in such cases.
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Gastrointestinal: Nausea frequently happens with the first dose and gets better with successive use. If prolonged, nausea may be treated with antiemetics; withdrawal may be necessary.
Contraindications:
Bremelanotide is contraindicated in the following conditions:
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In patients with cardiovascular diseases.
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In patients with uncontrolled hypertension.
Specific Population:
Bremelanotide in Pregnant Women:
Animal studies have shown adverse effects on fetal development and reproduction at doses higher than the recommended human dose. Bremelanotide can also cause significant changes in blood pressure, which may be harmful to the developing fetus. Therefore, women who are pregnant or plan to become pregnant should avoid using Bremelanotide. If a woman becomes pregnant while taking Bremelanotide, then her healthcare provider should be informed immediately to assess the risks and benefits of continuing or discontinuing Bremelanotide during pregnancy and make appropriate recommendations based on the individual case.
Bremelanotide in Lactating Women:
It is not known whether Bremelanotide is excreted in human milk, and the potential risks to the infant are unknown. Hence, the safety of Bremelanotide in lactating women has not been established, and it is not recommended for use during breastfeeding. Breastfeeding women who are considering Bremelanotide should discuss the potential risks and benefits with their healthcare provider. If Bremelanotide is deemed necessary for the lactating mother, the healthcare provider may recommend discontinuing breastfeeding or closely monitoring the infant for any adverse effects.
