PT-141 (Bremelanotide) and Sildenafil Interaction

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Is a bremelanotide-sildenafil interaction listed anywhere?

The Vyleesi label has a short Drug Interactions section. It covers two things: bremelanotide may slow stomach emptying and reduce absorption of oral medicines, and it may significantly decrease exposure to oral naltrexone, which the label says to avoid [1]. Sildenafil is not named there. Sildenafil is taken by mouth, so the label's general statement about oral medicines is the nearest language. The label says that in clinical pharmacology studies only naltrexone and indomethacin were meaningfully affected [1].

The Viagra label's Drug Interactions section covers nitrates, alpha-blockers, amlodipine, ritonavir and other CYP3A4 inhibitors, and alcohol [4]. Bremelanotide is not named there.

What the Vyleesi label says about blood pressure

Each 1.75 mg dose transiently increases blood pressure and reduces heart rate. In clinical studies the maximal increases were 6 mmHg systolic and 3 mmHg diastolic, peaking 2 to 4 hours after the dose, with a heart rate reduction of up to 5 beats per minute; blood pressure and heart rate usually returned to baseline within 12 hours [1]. Those are maximal figures, not averages.

In a separate open-label ambulatory monitoring study of 127 premenopausal women dosed once daily for 8 days, the mean daytime increase was 1.9 mmHg systolic (95% CI 1.0 to 2.7) and 1.7 mmHg diastolic (95% CI 0.9 to 2.4), with a mean heart rate decrease of 0.5 beats per minute [1].

The label says not to administer more than one dose within 24 hours. It notes that the efficacy of consecutive doses within 24 hours has not been established and that doses given close together may increase the risk of additive effects on blood pressure [1].

What the Viagra label says about blood pressure

Sildenafil is a PDE5 inhibitor, and the label notes that it has systemic vasodilatory properties [4]. In healthy volunteers, single 100 mg doses produced a mean maximum fall in supine blood pressure of about 8.4/5.5 mmHg [4].

The label describes additive lowering with other drugs. Viagra 100 mg with amlodipine 5 or 10 mg in hypertensive patients produced an additional mean supine reduction of 8 mmHg systolic and 7 mmHg diastolic [4]. With alpha-blockers the label advises caution and starting Viagra at 25 mg once the patient is stable on the alpha-blocker. In a doxazosin study, Viagra 25 mg gave a placebo-subtracted maximum standing systolic fall of 6.0 mmHg (7.4 mmHg supine), and one of four men given 100 mg had severe postural hypotension [4].

Could the two effects overlap in time?

After a 1.75 mg injection, bremelanotide reaches peak blood levels at a median of about 1.0 hour, with a mean terminal half-life of about 2.7 hours (range 1.9 to 4.0). Its blood-pressure effect peaks 2 to 4 hours after the dose and usually resolves within 12 hours [1]. Sildenafil peaks 30 to 120 minutes after a fasting dose (median 60 minutes), and sildenafil and its active metabolite each have a terminal half-life of about 4 hours [4].

The timing windows can therefore overlap. No blood-pressure study of the two drugs taken together is described on either label, so the combined effect has not been measured [1][4].

Where the labels draw hard lines

Vyleesi is contraindicated in patients with uncontrolled hypertension or known cardiovascular disease, and the label says it is not recommended for patients at high risk for cardiovascular disease [1]. It is not indicated for men or for postmenopausal women, and not indicated to enhance sexual performance [1].

Viagra is contraindicated with nitric oxide donors such as organic nitrates or organic nitrites in any form, and with guanylate cyclase stimulators such as riociguat [4]. After a dose of Viagra, the label says it is unknown when nitrates can safely be given and gives no waiting time [4]. The label also says erectile dysfunction treatments including Viagra generally should not be used in men for whom sexual activity is inadvisable because of cardiovascular status. It reports no controlled data in patients who had a heart attack, stroke or life-threatening arrhythmia within the past 6 months, resting blood pressure below 90/50 mmHg or above 170/110 mmHg, or unstable angina [4].

PT-141 products that are not Vyleesi

Vyleesi's approved use is premenopausal women with acquired, generalized hypoactive sexual desire disorder, and the label says it is not indicated for men [1]. PT-141 sold as a compounded or research-use peptide is not Vyleesi and is not an FDA-approved drug. Compounded drugs are not reviewed by FDA for safety, effectiveness or quality before marketing [5][1]. The dose, the limit of one dose per 24 hours and the limit of 8 doses a month all come from the Vyleesi label and describe that product [1].

Dose facts from the two labels

The Viagra label gives a usual dose of 50 mg as needed about 1 hour before sexual activity, which may be taken anywhere from 30 minutes to 4 hours beforehand. It sets a maximum of once a day and allows adjustment to 100 mg or down to 25 mg [4]. The label says to consider a 25 mg starting dose for age over 65, hepatic impairment, severe renal impairment, strong CYP3A4 inhibitors or erythromycin, and when starting in a patient already stable on an alpha-blocker [4].

The Vyleesi label gives 1.75 mg injected subcutaneously into the abdomen or thigh at least 45 minutes before anticipated sexual activity, with no more than one dose in 24 hours and no more than 8 doses a month. It says to stop after 8 weeks if there is no improvement in symptoms [1].

Both labels list dizziness among their adverse reactions: 2.2% with Vyleesi versus 0.5% with placebo in the pooled phase 3 trials [1], and 3% to 4% with Viagra versus 2% with placebo in fixed-dose trials [4].