Cialis Interactions
Alpha-blockers
- Amiodarone
Anti-retroviral protease inhibitors
Barbiturates
- Bosentan
- Carbamazepine
- Cimetidine
- Clarithromycin
- Delavirdine
- Dexamethasone
- Diltiazem
- Efavirenz
- Erythromycin
- Ethanol
- Fluconazole
- Fluoxetine
- Fluvoxamine
- Fosphenytoin
- grapefruit juice
- Imatinib, STI-571
- Isoniazid, INH
- Itraconazole
- Ketoconazole
- Mibefradil
- Mifepristone, RU-486
- Nefazodone
- Nevirapine
Nitrates
- Phenytoin
- Quinidine
- Rifabutin
- Rifampin
- Troglitazone
- Troleandomycin
- Verapamil
- Voriconazole
- Zafirlukast
- Zileuton
Cialis (Tadalafil) Interactions
Tadalafil has been shown to potentiate the hypotensive effects of nitrates. This interaction is consistent with tadalafil’s known effects on the nitric oxide/cGMP pathway. Deaths have been reported in men who were using a similar agent, sildenafil, while taking nitrate or nitrite therapy for angina. Tadalafil administration to patients who are concurrently using organic nitrates or nitrites in any form is contraindicated.
Concurrent use of phosphodiesterase (PDE5) inhibitors and alpha-blockers may lead to symptomatic hypotension in some patients. Tadalafil, other PDE5 inhibitors, and alpha blockers are systemic vasodilators which can lower blood pressure. If vasodilators are used in combination, an additive effect on blood pressure is anticipated. Patients should be stable on alpha blocker therapy before starting PDE5 inhibitor therapy. If hemodynamic instability is evident on alpha-blocker therapy alone, there is an increased risk of symptomatic hypotension with concomitant PDE5 inhibitor therapy. For patients who are stable on alpha blocker therapy, PDE5 inhibitors should be started at the lowest recommended dose. If a patients is currently receiving an optimized dose of a PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Stepwise increases in the alpha blocker dose may be associated with further hypotension when taking a PDE5 inhibitor. Other variables, such as intravascular volume depletion and other antihypertensive drugs, may affect the safety of concomitant use of PDE5 inhibitors and alpha blockers. Studies have been conducted to determine the effects of tadalafil on the potentiation of the blood-pressure-lowering effects of the alpha-blockers doxazosin and tamsulosin. When tadalafil 20 mg was administered to healthy subjects taking doxazosin (8 mg daily), an alpha-1-blocker, there was significant augmentation of the hypotensive effects of doxazosin. In contrast, coadministration of a single 20-mg dose of tadalafil to healthy subjects taking 0.4 mg once-daily tamsulosin, a selective alpha-1A-blocker, resulted in no significant decreases in blood pressure.
Tadalafil is metabolized predominantly by the hepatic cytochrome P450 3A4 (CYP3A4) isoenzyme. Inhibitors of CYP3A4 may reduce tadalafil clearance. Increased systemic exposure to tadalafil may result in an increase in tadalafil-induced adverse effects, including hypotension. Studies have been conducted for interactions between tadalafil and the potent CYP3A4 inhibitors ketoconazole (azole antifungal) and ritonavir (an antiretroviral protease inhibitor). Ketoconazole (400 mg daily) increased tadalafil (20 mg single dose) AUC by 312% and Cmax by 22%, relative to the values for tadalafil (20 mg single dose) alone. Ketoconazole (200 mg daily) increased tadalafil (10 mg single dose) AUC by 107% and Cmax by 15%, relative to the values for tadalafil 10 mg alone. Ritonavir (inhibits CYPs 3A4, 2C9, 2C19, and 2D6) increased tadalafil (20 mg single dose) AUC by 124% with no change in Cmax, relative to the values for tadalafil 20 mg alone. It is recommended that in patients taking concomitant potent CYP3A4 inhibitors, the tadalafil dose should not exceed 10 mg and not taken more frequently than once every 72 hours. Although no interaction studies have been done, other potent CYP3A4 inhibitors such as other anti-retroviral protease inhibitors, delavirdine, efavirenz, mibefradil, imatinib, STI-571, some macrolides (i.e., clarithromycin, erythromycin, troleandomycin), or systemic azole antifungals (e.g., fluconazole, itraconazole, ketoconazole, voriconazole) would be expected to have the greatest effects on tadalafil clearance when co-administered. Other inhibitors of CYP3A4 may reduce the clearance of tadalafil, however, no interaction studies have been performed. Other CYP3A4 inhibitors include amiodarone, cimetidine, diltiazem, fluoxetine, fluvoxamine, isoniazid, INH, nefazodone, quinidine, verapamil, zafirlukast, and zileuton.
Tadalafil is metabolized via the CYP3A4 isozyme. Grapefruit juice (food) has been reported to decrease the metabolism of drugs metabolized via this enzyme. Grapefruit juice contains a furano-coumarin compound, 6,7-dihydroxybergamottin that inhibits CYP3A4 in enterocytes in the GI tract. Tadalafil levels may increase; it is possible that tadalafil-induced side effects could also be increased in some individuals.
Tadalafil is metabolized principally by cytochrome P450 (CYP) 3A4. Studies have shown that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of tadalafil. Rifampin (600 mg daily) reduced tadalafil (10 mg single dose) AUC by 88% and Cmax by 46%, relative to values for tadalafil 10 mg alone. Although specific interaction studies have not been performed, other CYP3A4 inducers would likely decrease tadalafil AUC. Other CYP3A4 inhibitors include barbiturates, bosentan, carbamazepine, dexamethasone, fosphenytoin, nevirapine, phenytoin, rifabutin, and troglitazone.
Mifepristone, RU-486 inhibits CYP3A4 in vitro. Coadministration of mifepristone may lead to an increase in serum levels of drugs metabolized via CYP3A4, such as tadalafil. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
The combination of tadalafil and substantial consumption of ethanol can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. Ethanol and PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. As reported by the manufacturer, the interaction of tadalafil with ethanol was evaluated in 3 clinical pharmacology studies. In 2 of the studies, ethanol was administered at a dose of 0.7 g/kg, which is equivalent to approximately 6 ounces of 80-proof vodka in an 80-kg male, and tadalafil was administered at a dose of 10 mg in 1 study and 20 mg in another. In both of these studies, all patients consumed the entire ethanol dose within 10 minutes of starting. In one of these studies, blood ethanol concentrations of 0.08% were confirmed. In these two studies, more patients had clinically significant decreases in blood pressure on the combination of tadalafil and ethanol as compared to ethanol alone. Some subjects reported postural dizziness, and orthostatic hypotension was observed in some subjects. When tadalafil 20 mg was administered with a lower dose of ethanol (0.6 g/kg, which is equivalent to approximately 4 ounces of 80-proof vodka, administered in less than 10 minutes), orthostatic hypotension was not observed, dizziness occurred with similar frequency to ethanol alone, and hypotensive effects of ethanol were not potentiated. Tadalafil did not affect ethanol plasma concentrations and ethanol did not affect tadalafil plasma concentrations.
Studies have shown that tadalafil does not inhibit or induce cytochrome P450 (CYP) enzymes CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP2E1. Therefore, tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of drugs metabolized by CYP enzymes. When tadalafil was administered with theophylline, a CYP1A2 substrate, a small augmentation (3 beats per minute) of the increase in heart rate associated with theophylline was observed. However, tadalafil had no clinically significant effect on the pharmacokinetics of theophylline. Tadalafil had no clinically significant on the AUCs of the CYP3A4 substrates midazolam or lovastatin. Additionally, no clinically significant effect was observed on S-warfarin and R-warfarin AUC when coadministered with tadalafil; prothrombin time changes induced by warfarin were not affected by tadalafil.
Tadalafil and other PDE5 inhibitors are mild systemic vasodilators. A study was conducted to assess the interaction of amlodipine (5 mg daily) and tadalafil 10 mg. There was no effect of tadalafil on amlodipine blood concentrations and no effect of amlodipine on tadalafil blood concentrations. The mean reduction in supine systolic/diastolic blood pressure due to tadalafil 10 mg in subjects taking amlodipine was 3/2 mmHg, compared to placebo. In a similar study using tadalafil 20 mg, there were no clinically significant differences between tadalafil and placebo in subjects taking amlodipine.
Tadalafil and other PDE5 inhibitors are mild systemic vasodilators. Studies were conducted to assess the interaction of tadalafil 10 mg and sustained-release metoprolol (25 to 200 mg daily), bendroflumethiazide (2.5 mg daily), or enalapril (10 to 20 mg daily). Following dosing of tadalafil with metoprolol, the mean reduction in supine systolic/diastolic blood pressure was 5/3 mmHg, compared to placebo. After dosing of tadalafil with bendroflumethiazide, the mean reduction in supine systolic/diastolic blood pressure was 6/4 mmHg, compared to placebo. Following dosing of tadalafil with enalapril, the mean reduction in supine systolic/diastolic blood pressure was 4/1 mmHg, compared to placebo.
Tadalafil and other PDE5 inhibitors are mild systemic vasodilators. A study was conducted to assess the interaction of tadalafil 20 mg and angiotensin II receptor blockers. Study subjects were taking any marketed angiotensin II receptor blocker, either alone, as a component of a combination product, or as part of a multiple antihypertensive regimen. Following dosing, ambulatory measurements of blood pressure revealed differences between tadalafil and placebo of 8/4 mmHg in systolic/diastolic blood pressure.
Tadalafil did not potentiate the increase in bleeding time caused by aspirin.
The increase in pH associated with nizatidine administration had no significant effect on tadalafil pharmacokinetics. Additionally, simultaneous administration of an antacid (magnesium hydroxide; aluminum hydroxide) and tadalafil reduced the apparent rate of absorption of tadalafil without altering the AUC of tadalafil.
[ Last revised: 4/19/2005 10:45:00 AM ]
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