Tadalafil (Generic) and Prednisone Interaction: What Patients and Prescribers Need to Know

Tadalafil and prednisone: what the labels say [1]

Is there a direct interaction between tadalafil and prednisone?

The Cialis label does not describe a direct tadalafil-prednisone interaction. Its drug interactions section covers nitrates, alpha-blockers, antihypertensives, alcohol, CYP3A4 inhibitors and inducers, and specific probes such as warfarin, midazolam and digoxin, and corticosteroids are not named [1].

Prednisone is a glucocorticoid used for inflammatory and immune conditions. Tadalafil is a PDE5 inhibitor labeled for erectile dysfunction, benign prostatic hyperplasia, and both together [1].

Could prednisone lower tadalafil levels through CYP3A4?

Tadalafil is a substrate of and is predominantly metabolized by CYP3A4. The Cialis label's inducer example is rifampin 600 mg daily, which reduced tadalafil 10 mg exposure (AUC) by 88% and peak concentration by 46% [1]. The label says no dose adjustment is warranted with CYP3A4 inducers, but the reduced exposure can be anticipated to decrease the efficacy of once-daily Cialis, and the size of that decrease is unknown [1]. Prednisone was not the inducer studied.

Does tadalafil change prednisone?

The Cialis label states that tadalafil does not inhibit or induce CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 [1].

What about blood pressure?

Tadalafil has mild vasodilatory properties. In healthy volunteers, 20 mg produced a mean maximal fall in supine blood pressure of 1.6/0.8 mm Hg compared with placebo [1]. The Cialis label lists the combinations that add to this blood-pressure lowering: nitrates, alpha-blockers, antihypertensives and 5 units or more of alcohol [1].

What about blood glucose?

High-dose corticosteroids can raise blood glucose [2]. In a single-center hospital review, 32 of 50 patients receiving corticosteroids at the equivalent of 40 mg/day of prednisone or more for at least 2 days (64%) had a glucose of 200 mg/dL or higher, including 19 of 34 patients (56%) with no history of diabetes [2]. This describes hospitalized patients on high doses, not everyday low-dose use, and it is an effect of the steroid rather than a tadalafil interaction.

What about the 40 mg PAH regimen?

Adcirca is tadalafil labeled for pulmonary arterial hypertension at 40 mg once daily, a different product and dose from Cialis [3]. The Adcirca label says patients taking it should not take other PDE5 inhibitors [3]. It is also firmer about enzyme inducers than the Cialis label: it says to avoid Adcirca in people chronically taking potent CYP3A inducers such as rifampin [3].

Which tadalafil interactions matter more?

Nitrates are the interaction with the largest consequence. The Cialis label contraindicates any form of organic nitrate with tadalafil. It says that in a life-threatening situation where a nitrate is medically necessary, 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 [1]. In a 150-man crossover study, the nitroglycerin interaction was still significant at 24 hours and was not seen at 48 hours by most blood-pressure measures [1][4].

Strong CYP3A4 inhibitors come next: ketoconazole 400 mg daily raised tadalafil 20 mg exposure (AUC) by 312% [1], and the label limits as-needed tadalafil to 10 mg no more often than every 72 hours and once-daily tadalafil to 2.5 mg with such drugs [1]. Alpha-blockers add to tadalafil's blood-pressure lowering [1].