Tadalafil (Generic) and Rosuvastatin Interaction: What Patients and Clinicians Need to Know

Do tadalafil and rosuvastatin interact?

The Cialis label's drug interactions section covers nitrates, alpha-blockers, antihypertensives, alcohol, antacids, H2 blockers, CYP3A4 inhibitors and inducers, and several CYP substrates such as warfarin and midazolam; rosuvastatin is not among them [2]. The Crestor label sets dose limits for a defined list of interacting drugs: cyclosporine at no more than 5 mg of rosuvastatin daily, gemfibrozil to be avoided or capped at 10 mg, several hepatitis C and HIV antivirals, ticagrelor, and others. Tadalafil is not on that list [1].

Not appearing on an interaction list is not the same as a trial showing that no effect exists. Neither label describes a study of the two drugs given together, so the accurate summary is that no interaction is listed and no direct data exist.

Two different clearance routes

Tadalafil is metabolized mainly by CYP3A4, and its label shows how much that route matters. Ketoconazole 400 mg daily raised exposure to a 20 mg dose by 312%, ritonavir 200 mg twice daily raised it by 124%, and rifampin 600 mg daily cut it by 88% [2]. Tadalafil's half-life is 17.5 hours [2].

Rosuvastatin sits outside that system. The Crestor label states that rosuvastatin clearance does not depend on CYP3A4 metabolism to a clinically significant extent. Itraconazole 200 mg daily raised exposure only about 1.4-fold. The interactions that matter involve transporters: cyclosporine raised rosuvastatin exposure about 7-fold, and the label caps the dose at 5 mg daily with it [1][3]. Rosuvastatin is a substrate of CYP2C9, which forms its minor N-desmethyl metabolite, and of the transporters OATP1B1 and BCRP [1].

In the other direction, the Cialis label states that tadalafil does not inhibit or induce CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 [2]. The one statin it reports on is lovastatin: tadalafil had no significant effect on lovastatin exposure [2]. Lovastatin is a different statin from rosuvastatin.

Muscle aches have two possible sources

The Crestor label lists myalgia at 2.8% on rosuvastatin 5 to 40 mg versus 1.3% on placebo in placebo-controlled trials of up to 12 weeks. In JUPITER (rosuvastatin 20 mg in 8,901 patients versus 8,901 on placebo, mean 2 years) the rates were 7.6% versus 6.6% [1][4]. Myopathy risk is greater on 40 mg daily than on lower doses. The label lists age 65 or older, uncontrolled hypothyroidism, renal impairment and certain other drugs as risk factors, and says Asian patients may be at higher risk [1]. The label says patients should promptly report unexplained muscle pain, tenderness or weakness, particularly with malaise or fever [1].

Tadalafil produces muscle symptoms too. In the as-needed erectile dysfunction trials, myalgia was reported by 3% on tadalafil 20 mg versus 1% on placebo, and back pain by 6% versus 3% [2]. The Cialis label says tadalafil-related back pain or myalgia generally began 12 to 24 hours after dosing and resolved within 48 hours [2].

A new ache in the lower back, buttocks or thighs while taking both drugs could therefore come from either one, and that timing alone does not establish which.

Blood pressure and heart risk

Tadalafil is a mild vasodilator: 20 mg lowered supine blood pressure by a mean maximal 1.6/0.8 mm Hg compared with placebo in healthy volunteers [2]. The label's blood pressure cautions concern alpha-blockers, antihypertensives, substantial alcohol (5 units or more) and nitrates. Organic nitrates in any form are contraindicated. For a life-threatening situation, the label says at least 48 hours should elapse after the last tadalafil dose before a nitrate is considered, and then only under close medical supervision with hemodynamic monitoring [2][5]. Rosuvastatin's warnings cover myopathy and rhabdomyolysis, liver enzyme rises, proteinuria and hematuria, and increases in HbA1c and fasting glucose; blood pressure is not among them [1].

The cardiovascular question that comes up more often is whether sexual activity is advisable at all. The Cialis label says the drug should not be used in men for whom sexual activity is inadvisable because of cardiovascular status. It lists groups not studied: myocardial infarction within 90 days, unstable angina or angina during intercourse, NYHA class 2 or greater heart failure within 6 months, uncontrolled arrhythmias, blood pressure below 90/50 mm Hg or uncontrolled hypertension, and stroke within 6 months [2]. Rosuvastatin is labeled to reduce the risk of major adverse cardiovascular events in adults at increased risk, so the two prescriptions can meet in the same patient [1].

Renal function changes each drug's dose separately

For as-needed tadalafil, the Cialis label recommends starting at 5 mg with a maximum of 10 mg not more often than every 48 hours when creatinine clearance is 30 to 50 mL/min. Below 30 mL/min or on hemodialysis, it recommends a maximum of 5 mg not more often than every 72 hours, and once-daily use is not recommended. For BPH or ED with BPH at 30 to 50 mL/min, it recommends starting at 2.5 mg and considering 5 mg [2].

The Crestor label recommends starting at 5 mg and not exceeding 10 mg daily in severe renal impairment (creatinine clearance under 30 mL/min, not on hemodialysis), where exposure is about 3-fold higher. It also recommends a 5 mg starting dose for Asian patients [1].

Neither adjustment is about the combination. Generic tadalafil tablets come in 2.5, 5, 10 and 20 mg strengths and follow the Cialis indications, erectile dysfunction and BPH [6]. HealthRX.com offers tadalafil by prescription.