Cialis Drug Interactions

Interaction studies were conducted with tadalafil 10 mg and/or 20 mg, as indicated as follows. With regard to those interaction studies where only the tadalafil 10-mg dose was used, clinically relevant interactions at higher doses cannot be completely ruled out.
Effects of Other Medicinal Products on Tadalafil: Tadalafil is principally metabolised by CYP3A4. A selective inhibitor of CYP3A4, ketoconazole (200 mg daily), increased tadalafil (10 mg) exposure (AUC) 2-fold and C_max by 15% relative to the AUC and C_max values for tadalafil alone. Ketoconazole (400 mg daily) increased tadalafil (20 mg) exposure (AUC) 4-fold and C_max by 22%. Ritonavir, a protease inhibitor (200-mg dose given twice daily), which is an inhibitor of CYP3A4, CYP2C9, CYP2C19 and CYP2D6, increased tadalafil (20 mg) exposure (AUC) 2-fold with no change in C_max. Although specific interactions have not been studied, other protease inhibitors eg, saquinavir and other CYP3A4 inhibitors eg, erythromycin, clarithromycin, itraconazole and grapefruit juice should be co-administered with caution as they would be expected to increase plasma concentrations of tadalafil (see Precautions). Consequently the incidence of the undesirable effects listed in Adverse Reactions might be increased.
The role of transporters (eg, p-glycoprotein) in the disposition of tadalafil is not known. There is, thus, the potential of drug interactions mediated by inhibition of transporters.
A selective CYP3A4 inducer, rifampicin 600 mg daily, reduced tadalafil AUC by 88%, relative to the AUC values for tadalafil alone (10-mg dose). This reduced exposure can be anticipated to decrease the efficacy of tadalafil; the magnitude of decreased efficacy is unknown. It can be expected that concomitant administration of other inducers of CYP3A4 eg, phenobarbital, phenytoin and carbamazepine may also decrease plasma concentrations of tadalafil.
Effects of Tadalafil on Other Medicinal Products: In clinical studies, tadalafil (5 mg and 20 mg) 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 (see Contraindications). Based on the results of a clinical study in which 150 subjects receiving daily doses of tadalafil 20 mg for 7 days and sublingual nitroglycerin 0.4 mg at various times, this interaction lasted for >24 hrs and was no longer detectable when 48 hrs had elapsed after the last tadalafil dose. Thus, in a patient prescribed tadalafil (2.5-20 mg), where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hrs 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 haemodynamic monitoring.
Cialis 20 mg: Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of drugs metabolised by CYP450 isoforms. Studies have confirmed that tadalafil does n ot inhibit or induce CYP450 isoforms, including CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.
Tadalafil (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.
Tadalafil (20 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid.
In clinical pharmacology studies, the potential for tadalafil to augment the hypotensive effects of antihypertensive agents was examined. Major classes of antihypertensive agents were studied, including calcium channel blockers (amlodipine), angiotensin converting enzyme (ACE) inhibitors (enalapril), β-adrenergic receptor blockers (metoprolol), thiazide diuretics (bendrofluazide) and angiotensin II receptor blockers (various types and doses, alone or in combination with thiazides, calcium channel blockers, β-blockers, and/or α-blockers). Tadalafil (10 mg except for studies with angiotensin II receptor blockers and amlodipine in which a 20-mg dose was applied) had no clinically significant interaction with any of these classes. In another clinical pharmacology study tadalafil (20 mg) was studied in combination with up to 4 classes of antihypertensives. In subjects taking multiple antihypertensives, the ambulatory-blood-pressure changes appeared to relate to the degree of blood-pressure control. In this regard, study subjects whose blood pressure was well controlled, the reduction was minimal and similar to that seen in healthy subjects. In study subjects whose blood pressure was not controlled, the reduction was greater although this reduction was not associated with hypotensive symptoms in the majority of subjects. In patients receiving concomitant antihypertensive medicines, tadalafil 20 mg may induce a blood pressure decrease, which (with the exception of α-blockers, see as follows) is, in general, minor and not like to be clinically relevant. Analysis of phase 3 clinical trial data showed no difference in adverse events in patients taking tadalafil with or without antihypertensive medications. However, appropriate clinical advice should be given to patients regarding a possible decrease in blood pressure when they are treated with antihypertensive medicines.
Cialis 5 mg: 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, incluing syncope. Therefore this combination is not recommended (see Precautions).
In interaction studies performed in a limited number of healthy volunteers, these effects were not reported with alfuzosin or tamsulosin. However, 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.
Cialis 20 mg: Alpha adrenergic-blockers: In two clinical pharmacology studies, no significant decreases in blood pressure were observed when tadalafil was co-administered to healthy subjects taking the selective alpha[1A]-adrenergic blocker, tamsulosin. When tadalafil was co-administered to healthy subjects taking doxazosin (4-8 mg daily), an alpha[1]-adrenergic blocker, there was an augmentation of the blood-pressure-lowering effect of doxazosin. The number of subjects with potentially clinically significant standing-blood-pressure decreases was greater for the combination. In these clinical pharmacology studies there were symptoms associated with the decrease in blood pressure including syncope.
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 hrs after co-administration with alcohol. Alcohol was administered in a manner to maximize the rate of alcohol absorption (overnight fast with no food until 2 hrs after alcohol). Tadalafil (20 mg) did not augment the mean blood pressure decrease produced by alcohol [0.7 g/kg or approximately 180 mL of 40% alcohol (vodka) in an 80-kg male] but in some subjects, postural dizziness and orthostatic hypotension were observed. When tadalafil was administered with lower doses of alcohol (0.6 g/kg), hypotension was not observed and dizziness occurred with similar frequency to alcohol alone. The effect of alcohol on cognitive function was not augmented by tadalafil (10 mg).
Tadalafil has been demonstrated to produce an increase in the oral bioavailabilty of ethinylestradiol; a similar increase may be expected with oral administration of terbutaline, although the clinical consequence of this is uncertain.
When tadalafil 10 mg was administered with theophylline (a nonselective 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 medications.
Cialis 5 mg: 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.
Tadalafil (10 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.
Tadalafil (10 and 20 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid.
Specific interaction studies with antidiabetic agents were not conducted.
Cialis 20 mg: H2 antagonists: An increase in gastric pH resulting from administration of nizatidine had no significant effect on tadalafil pharmacokinetics.
Antacids (magnesium hydroxide/aluminum hydroxide): Simultaneous administration of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduced the apparent rate of absorption of tadalafil without altering exposure (AUC) to tadalafil.