Duactam Drug Interactions

Tadalafil: Effects of other substances on Tadalafil: Cytochrome P450 inhibitors: Tadalafil is principally metabolized by CYP3A4. A selective inhibitor of CYP3A4, Ketoconazole (200 mg daily), increased Tadalafil (10 mg) exposure (AUC) 2-fold and Cmax by 15%, relative to the AUC and Cmax values for Tadalafil alone. Ketoconazole (400 mg daily) increased Tadalafil (20 mg) exposure (AUC) 4-fold and Cmax by 22%. Ritonavir, a protease inhibitor (200 mg twice daily), which is an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased Tadalafil (20 mg) exposure (AUC) 2-fold with no change in Cmax. 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.
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 by 88%, 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: In a patient prescribed any dose of Tadalafil (2.5 mg-20 mg), where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should have elapsed after the last dose of Tadalafil before nitrate administration is considered. In such circumstances, nitrates should only be administered under close medical supervision with appropriate hemodynamic monitoring.
Anti-hypertensives (including calcium channel blockers): The co-administration of doxazosin (4 and 8 mg daily) and Tadalafil (5 mg daily dose and 20 mg as a single dose) 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.
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.
However, appropriate clinical advice should be given to patients regarding a possible decrease in blood pressure when they are treated with antihypertensive medicinal products.
Riociguat: Preclinical studies showed an additive systemic blood pressure lowering effect when PDE5 inhibitors were combined with riociguat. In clinical studies, riociguat has been shown to augment the hypotensive effects of PDE5 inhibitors. There was no evidence of favorable clinical effect of the combination in the population studied.
Concomitant use of riociguat with PDE5 inhibitors, including Tadalafil, is contraindicated.
5-alpha reductase inhibitors: In a clinical trial that compared Tadalafil 5 mg co-administered with Finasteride 5 mg to placebo plus Finasteride 5 mg in the relief of BPH symptoms, no new adverse reactions were identified. However, as a formal drug-drug interaction study evaluating the effects of Tadalafil and 5-alpha reductase inhibitors (5-ARIs) has not been performed, 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) in a clinical pharmacology study, there was no pharmacokinetic interaction. The only pharmacodynamic effect was a small (3.5 bpm) 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.
Cytochrome P450 metabolized medicinal products: Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of medicinal products metabolized by CYP450 isoforms. Studies have confirmed that Tadalafil does not inhibit or induce CYP450 isoforms, including CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.
Antidiabetic medicinal products: Specific interaction studies with antidiabetic medicinal products were not conducted.
Tamsulosin: No interactions have been seen when tamsulosin was given concomitantly with atenolol, enalapril, or theophylline. Concomitant cimetidine brings about a rise in plasma levels of tamsulosin, and furosemide a fall, but as levels remain within the normal range, posology need not be changed.
In vitro, neither diazepam nor propranolol, trichlormethiazide, chlormadinon, amitriptyline, diclofenac, glibenclamide, simvastatin and warfarin change the free fraction of tamsulosin in human plasma. Neither does tamsulosin change the free fractions of diazepam, propranolol, trichlormethiazide, and chlormadinon.
Diclofenac and warfarin, however, may increase the elimination rate of tamsulosin.
Concomitant administration of tamsulosin hydrochloride with strong inhibitors of CYP3A4 may lead to increased exposure to tamsulosin hydrochloride. Concomitant administration with ketoconazole (a known strong CYP3A4 inhibitor) resulted in an increase in AUC and Cmax of tamsulosin hydrochloride by a factor of 2.8 and 2.2, respectively.
Tamsulosin hydrochloride should not be given in combination with strong inhibitors of CYP3A4 (e.g. ketoconazole) in patients with poor metabolizer CYP2D6 phenotype.
Tamsulosin hydrochloride should be used with caution in combination with strong (e.g. ketoconazole) and moderate inhibitors (e.g. erythromycin) of CYP3A4.
Concomitant administration of tamsulosin hydrochloride with paroxetine, a strong inhibitor of CYP2D6, resulted in a Cmax and AUC of tamsulosin that had increased by a factor of 1.3 and 1.6, respectively, but these increases are not considered clinically relevant.
There is a theoretical risk of enhanced hypotensive effect when given concurrently with drugs, which may reduce blood pressure, including anesthetic agents and other α1-adrenoceptor antagonists.