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

Does liraglutide interact with tadalafil?

Neither liraglutide label nor the Cialis label names the other drug [1][2][3]. The liraglutide labels cover two interaction topics: delayed gastric emptying and its potential effect on absorption of oral medicines, and low blood sugar when liraglutide is combined with insulin or an insulin secretagogue such as a sulfonylurea [1][2]. The Cialis interaction section covers nitrates, alpha-blockers, antihypertensives, alcohol, and drugs that inhibit or induce CYP3A4 [3].

The nearest thing to a shared concern is blood pressure and circulation. The Cialis label describes a mild vasodilator effect that adds to other blood-pressure-lowering drugs [3]. The liraglutide cardiovascular warning is about heart rate, with a mean resting rise of 2 to 3 beats per minute in the Saxenda label [1].

Do the two drugs affect each other's blood levels?

Liraglutide is an acylated human GLP-1 receptor agonist with 97% amino acid sequence homology to native GLP-1, stable against DPP-4 breakdown, with a plasma half-life of about 13 hours after subcutaneous injection [1]. The Saxenda label describes it as metabolized like large proteins, without a specific organ of elimination; intact drug is not found in urine or feces [1].

Tadalafil is a PDE5 inhibitor metabolized mainly by CYP3A4, with a mean terminal half-life of 17.5 hours [3]. Once-daily dosing reaches steady state within 5 days at about 1.6 times the exposure of a single dose [3]. Tadalafil does not inhibit or induce CYP1A2, 3A4, 2C9, 2C19, 2D6 or 2E1 [3].

Whether liraglutide changes tadalafil levels is not addressed in these labels.

Does liraglutide's effect on the stomach change how tadalafil is absorbed?

Liraglutide delays gastric emptying, and both liraglutide labels say this has the potential to affect absorption of oral medicines. In clinical pharmacology trials it did not affect absorption of the tested oral drugs to a clinically relevant degree [1][2]. The Saxenda label says to monitor for potential consequences of delayed absorption; the Victoza label says caution should be exercised when oral medicines are given with it [1][2].

Tadalafil's rate and extent of absorption are not influenced by food, and its median peak concentration arrives about 2 hours after an oral dose [3]. The Cialis label notes that once-daily Cialis provides continuous plasma tadalafil levels and says to consider this when evaluating interactions with nitrates, alpha-blockers, antihypertensives, potent CYP3A4 inhibitors and substantial alcohol [3].

What about blood pressure?

The Cialis label describes PDE5 inhibitors as mild systemic vasodilators. In a clinical pharmacology study, tadalafil 20 mg produced a mean maximal decrease in supine blood pressure, relative to placebo, of 1.6/0.8 mm Hg in healthy subjects [3]. The label says this effect can add to alpha-blockers, to antihypertensives (amlodipine, angiotensin II receptor blockers, bendroflumethiazide, enalapril and metoprolol were studied, with small additional reductions in blood pressure versus placebo), and to substantial alcohol, meaning 5 units or more [3]. It also notes that patients with severely impaired autonomic control of blood pressure may be particularly sensitive to vasodilators [3].

On the liraglutide side, the Saxenda label reports a mean resting heart rate increase of 2 to 3 bpm, with a rise of more than 10 bpm at two consecutive visits in 34% of Saxenda-treated patients versus 19% on placebo, and says to monitor heart rate [1]. Both liraglutide labels warn about acute kidney injury from volume depletion and say to monitor renal function in patients reporting reactions that could lead to it [1][2].

What the Cialis label says to watch for

Any form of organic nitrate, used regularly or intermittently, is contraindicated with Cialis. The label says that in a life-threatening situation where a nitrate is medically necessary, at least 48 hours should pass after the last Cialis dose before a nitrate is considered, and then only under close medical supervision with appropriate hemodynamic monitoring [3]. In a 150-man crossover study, the nitrate interaction was still significant at 24 hours and was not detected at 48 hours [4].

The label says Cialis should not be used by men for whom sexual activity is inadvisable because of cardiovascular status, and that it is not recommended for men who have had a myocardial infarction within 90 days, unstable angina or angina during intercourse, NYHA class 2 or greater heart failure within 6 months, uncontrolled arrhythmia, blood pressure below 90/50 mm Hg or uncontrolled hypertension, or a stroke within 6 months [3]. It also says to seek emergency treatment for an erection lasting more than 4 hours, and to stop Cialis and seek medical care for sudden vision loss or sudden decrease or loss of hearing [3]. For BPH, the label does not recommend combining Cialis with an alpha-blocker; for ED in a man already stable on an alpha-blocker, the label says to start tadalafil at the lowest dose [3].

Dosing and availability

Saxenda and Victoza are both injected once daily at any time of day, without regard to meals; the recommended Saxenda dose is 3 mg daily and the Victoza maximum is 1.8 mg daily [1][2]. Cialis for ED as needed starts at 10 mg and may be raised to 20 mg or lowered to 5 mg, no more than once a day. Once-daily Cialis for ED starts at 2.5 mg and may rise to 5 mg. BPH and ED with BPH use 5 mg once daily [3]. The Cialis label says its tablets should not be split [3]. Generic liraglutide is FDA-approved, and generic labels follow either the Saxenda weight-management indication or the Victoza type 2 diabetes indication [5]. Cialis is listed as a prescription drug by FDA [6].

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