Vyleesi and Tadalafil Interaction: What Patients and Clinicians Need to Know

What does the Vyleesi label say about other drugs?

Section 7 of the Vyleesi prescribing information has two entries, and tadalafil is not one of them [1].

The first entry concerns absorption. Vyleesi may slow gastric emptying and so reduce the rate and extent of absorption of oral medicines. The label instructs patients to avoid Vyleesi when taking oral drugs that depend on threshold blood concentrations, such as antibiotics, and to consider skipping a dose when a fast effect from an oral drug such as indomethacin is wanted [1].

The second concerns naltrexone. Vyleesi may significantly decrease the systemic exposure of oral naltrexone, and the label says to avoid it with naltrexone-containing products intended to treat alcohol or opioid addiction [1]. In the clinical pharmacology studies, only naltrexone and indomethacin were meaningfully affected [1].

For comparison, tadalafil is metabolized mainly by CYP3A4, and potent CYP3A4 inhibitors raise its exposure sharply: ketoconazole 400 mg daily increased tadalafil 20 mg AUC by 312% and peak level by 22% [2]. The Vyleesi label describes no enzyme-based interaction of that kind [1].

How do their blood pressure effects compare?

Vyleesi transiently raises blood pressure and lowers heart rate after each dose. 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. Values usually returned to baseline within 12 hours, and no additive effect was seen with repeat daily dosing 24 hours apart for up to 16 days [1]. Those are maximal figures, not averages. In an open-label ambulatory 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].

Tadalafil is a mild vasodilator. In a clinical pharmacology study, 20 mg produced a mean maximal decrease in supine blood pressure, relative to placebo, of 1.6/0.8 mmHg in healthy volunteers [2].

We found no published study that tested bremelanotide with tadalafil, so the combined effect on blood pressure, and any effect of timing, has not been reported.

Both labels address cardiovascular status. The Vyleesi label contraindicates the drug in patients with uncontrolled hypertension or known cardiovascular disease and says it is not recommended for people at high cardiovascular risk [1]. The Cialis label says treatments for erectile dysfunction, including Cialis, should not be used in men for whom sexual activity is inadvisable because of cardiovascular status [2].

Who would actually be taking both?

Vyleesi is indicated for premenopausal women with acquired, generalized hypoactive sexual desire disorder. The label states it is not indicated for postmenopausal women or for men, and not for enhancing sexual performance [1].

Cialis is indicated for erectile dysfunction, for the signs and symptoms of benign prostatic hyperplasia, and for both together, and its label states that Cialis is not indicated for use in females [2].

Tadalafil is also approved for pulmonary arterial hypertension (PAH) as Adcirca (20 mg tablets, taken as 40 mg once daily), the branded generic Alyq, and Tadliq oral suspension [3][4][5]. These are not restricted by sex in the way Cialis is. Adcirca is a different product, strength and dose from Cialis, and its label tells patients not to take other PDE5 inhibitors, including Cialis [3].

What does the Vyleesi label say about monitoring?

The Vyleesi label says to consider the patient's cardiovascular risk before starting and periodically during treatment, and to make sure blood pressure is well controlled [1]. It also says not to give more than one dose in 24 hours, noting that doses given close together may increase additive effects on blood pressure, and that more than 8 doses a month is not recommended [1].

In the pooled phase 3 trials (Vyleesi n=627, placebo n=620), the common adverse reactions were nausea 40.0% versus 1.3%, flushing 20.3% versus 0.3%, injection site reactions 13.2% versus 8.4% and headache 11.3% versus 1.9% [1]. Focal hyperpigmentation, including the face, gums and breasts, was reported by 1% of patients taking up to 8 doses a month, versus none on placebo [1].

On the tadalafil side, the Cialis label documents additive blood pressure effects with alpha-blockers, antihypertensives and substantial alcohol (5 units or more), and contraindicates any form of organic nitrate [2].

Bottom line

The Vyleesi label does not name tadalafil as an interacting drug, and we found no study of the pair, so whether they interact is not known [1]. The labels do give cardiovascular limits: Vyleesi is contraindicated in uncontrolled hypertension or known cardiovascular disease, and Cialis should not be used by men for whom sexual activity is inadvisable for cardiovascular reasons [1][2].