PT-141

Bremelanotide (PT-141) is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone. The FDA-approved product is Vyleesi, a 1.75 mg subcutaneous autoinjector. Lake Hills Pharmacy compounds bremelanotide as a 503A pharmacy, pursuant to patient-specific prescriptions, in non-sterile preparations such as nasal sprays and sublingual rapid dissolve tablets, alone or in combination. Bremelanotide is not a controlled substance.

• Vyleesi (subcutaneous): premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) not due to a coexisting medical or psychiatric condition, relationship problems, or the effects of a medication or drug.
• Vyleesi labeling states it is not indicated for postmenopausal women or men, or to enhance sexual performance. Labeling limits use to one dose per 24 hours and eight doses per month, and advises stopping after 8 weeks if there is no improvement.
• No FDA-labeled indication or dose exists for bremelanotide by the nasal or sublingual route, or in men. Prescribers use compounded bremelanotide in sexual health, and dosing is individualized by the prescriber.

Bremelanotide is a non-selective melanocortin receptor agonist with highest activity at the MC4 receptor, which is expressed in the central nervous system, followed by MC1R, MC3R, MC5R and MC2R. How it improves sexual desire in HSDD is not known. MC1R activation on melanocytes accounts for the focal hyperpigmentation seen with use.

After subcutaneous injection, bioavailability is about 100%, peak concentration is reached in about 1 hour, and half-life is about 2.7 hours. Plasma protein binding is about 21%. Bremelanotide is metabolized by hydrolysis of its peptide bonds and excreted about 65% in urine and 23% in feces. Bremelanotide transiently slows gastric emptying. Pharmacokinetics by the nasal or sublingual route have not been established in labeling.

• Uncontrolled hypertension.
• Known cardiovascular disease.
• Hypersensitivity to bremelanotide or any component of the preparation.

• Transient increase in blood pressure and decrease in heart rate occur after each dose, generally peaking within hours and resolving within 12 hours. Not recommended for patients at high risk of cardiovascular disease. Control blood pressure before use and monitor it periodically.
• Focal hyperpigmentation of the face, gums and breasts has been reported, more often with daily dosing; it may not resolve after stopping. Patients with dark skin may be at higher risk.
• Nausea is very common, most often with the first dose, and may need an antiemetic or lead to discontinuation; vomiting can occur.
• Use caution in severe renal or hepatic impairment, where bremelanotide has not been studied.

• Oral naltrexone: bremelanotide significantly lowers naltrexone exposure; avoid use with oral naltrexone used for alcohol or opioid dependence, since reduced levels may lead to treatment failure.
• Other oral drugs: slowed gastric emptying may reduce the rate and extent of absorption of oral drugs; take care with drugs that need threshold concentrations to work, such as some antibiotics, and drugs with a narrow therapeutic index. Labeling reports reduced indomethacin and delayed acetaminophen absorption.
• Antihypertensives and PDE5 inhibitors: the transient rise in blood pressure and drop in heart rate may interact with drugs that affect hemodynamics; combined use with PDE5 inhibitors has not been studied.

Labeled adverse reactions include nausea, flushing, injection site reactions, headache, vomiting, cough, fatigue, hot flush, paresthesia, dizziness and nasal congestion. Focal hyperpigmentation, transient blood-pressure increase and heart-rate decrease are described under Warnings. Nasal formulations may also cause local nasal irritation.

Human data in pregnancy are limited; labeling advises discontinuing bremelanotide if pregnancy is suspected. It is not known whether bremelanotide is present in human milk or affects the breastfed infant or milk production; the prescriber weighs benefits and risks.

Check blood pressure and cardiovascular risk before starting and periodically during use. Ask about nausea, flushing and new skin or gum pigmentation. Review oral medicines, especially naltrexone, for absorption interactions. Confirm pregnancy status in anyone who could be pregnant.

• Vyleesi (bremelanotide injection) Prescribing Information, Cosette Pharmaceuticals.
• USP General Chapter <795> Pharmaceutical Compounding, Nonsterile Preparations.