Tadalafil Stella Drug Interactions

Effects of other substances on tadalafil: Cytochrome P450 inhibitors: Tadalafil is principally metabolised by CYP3A4. A selective inhibitor of CYP3A4, ketoconazole, increased tadalafil exposure (AUC) and C_max, relative to the AUC and C_max values for tadalafil alone. Ritonavir, a protease inhibitor (200 mg twice daily), which is an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased tadalafil exposure (AUC) with no change in C_max. Although specific interactions have not been studied, other protease inhibitors, such as saquinavir, and other CYP3A4 inhibitors, such as erythromycin, clarithromycin, itraconazole, and grapefruit juice, should be co-administered with caution, as they would be expected to increase plasma concentrations of tadalafil. Consequently, the incidence of the adverse reactions might be increased.
Transporters: The role of transporters (for example, p-glycoprotein) in the disposition of tadalafil is not known. Therefore, there is the potential of drug interactions mediated by inhibition of transporters.
Cytochrome P450 inducers: A CYP3A4 inducer, rifampicin, reduced tadalafil AUC relative to the AUC values for tadalafil alone (10 mg). This reduced exposure can be anticipated to decrease the efficacy of tadalafil; the magnitude of decreased efficacy is unknown. Other inducers of CYP3A4, such as phenobarbital, phenytoin, and carbamazepine, may also decrease plasma concentrations of tadalafil.
Effects of tadalafil on other medicinal products: Nitrates: Tadalafil was shown to augment the hypotensive effects of nitrates. Therefore, administration of tadalafil to patients who are using any form of organic nitrate is contraindicated.
Doxazosin: The co-administration of doxazosin (4 and 8 mg daily) and tadalafil increases the blood pressure-lowering effect of this alpha-blocker in a significant manner. This effect lasts at least twelve hours and may be symptomatic, including syncope. Therefore, this combination is not recommended.
Alpha-blockers: Caution should be exercised when using tadalafil in patients treated with any alpha-blockers, and notably in the elderly. Treatments should be initiated at minimal dosage and progressively adjusted.
Antihypertensive medicinal products [calcium-channel blockers, angiotensin converting enzyme (ACE) inhibitors, beta-adrenergic receptor blockers, thiazide diuretics, and angiotensin II receptor blockers (various types and doses, alone or in combination with thiazides, calcium-channel blockers, beta-blockers, and/or alpha-blockers)]: Tadalafil had no clinically significant interaction with any of these antihypertensive medicinal products.
Riociguat: Riociguat has been shown to augment the hypotensive effects of PDE5 inhibitors. There was no evidence of favourable clinical effect of the combination in the population studied. Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated.
5-alpha reductase inhibitors: Caution should be exercised when tadalafil is co-administered with 5-ARIs.
CYP1A2 substrates (e.g. theophylline): When tadalafil 10 mg was administered with theophylline (a non-selective phosphodiesterase inhibitor), there was no pharmacokinetic interaction. The only pharmacodynamic effect was a small increase in heart rate. Although this effect is minor and was of no clinical significance in this study, it should be considered when co-administering these medicinal products.
Ethinylestradiol and terbutaline: Tadalafil has been demonstrated to produce an increase in the oral bioavailability of ethinylestradiol; a similar increase may be expected with oral administration of terbutaline, although the clinical consequence of this is uncertain.
Alcohol: Alcohol concentrations (mean maximum blood concentration 0.08%) were not affected by co-administration with tadalafil (10 mg or 20 mg). In addition, no changes in tadalafil concentrations were seen 3 hours after co-administration with alcohol.
Cytochrome P450 metabolised medicinal products: Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of medicinal products metabolised by CYP450 isoforms. Studies have confirmed that tadalafil does not inhibit or induce CYP450 isoforms, including CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.
CYP2C9 substrates (e.g. R-warfarin): Tadalafil (10 mg and 20 mg) had no clinically significant effect on exposure (AUC) to S-warfarin or R-warfarin (CYP2C9 substrate), nor did tadalafil affect changes in prothrombin time induced by warfarin.
Aspirin: Tadalafil did not potentiate the increase in bleeding time caused by acetylsalicylic acid.
Antidiabetic medicinal products: Specific interaction studies with antidiabetic medicinal products were not conducted.