Tadalafil dosing

Sildenafil doses should be decreased when any potent cytochrome P450 3A4 inhibitor is used (e g., cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and saquinavir). Vardenafil doses vary accordingto which agent is used (2.5 mg q 72 h for ritonavir, 2.5 mg q 24 h for indinavir, ketoconazole 400 mg daily, and itraconazole 400 mg daily and 5 mg q 24 h for ketoconazole 200 mg daily, itraconazole200 mg daily, and erythromycin). Tadalafil doses are reduced only when it is used with the most potent cytochrome P450 3A4 inhibitors (e g., ketoconazole or ritonavir). 

For maximal absorption, patients should avoid taking sildenafil or vardenafil with a fatty meal. A fatty meal does not affect absorption of tadalafil. / If the first dose is not effective, patients should continue trying for five to eight doses. Some patients benefit from titration up to 100 mg of sildenafil, 20 mg of vardenafil, or 20 mg of tadalafil. 

Sildenafil and vardenafil decrease systolic/diastolic blood pressure by 8 to 10/5 to 6 mm Hg for 1 to 4 hours after a dose. Although most patients are asymptomatic, multiple antihypertensives, nitrates, and baseline hypotension increase the risk of developing adverse effects. Although tadalafil does not decrease blood pressure, it should be used with caution in patients with cardiovascular disease because of the inherent risk associated with sexual activity. 

Tadalafil inhibits type 11 phosphodiesterase, which is thought to account for the dose-related back and muscle pain seen in 7% to 30% of patients. 

TADALAFIL 10 mg taken prior to anticipated sexual activity. The dose may be increased to 20 mg or decreased to 5 mg, based on individual efficacy and tolerability. The maximum recommended dosing frequency is once daily in most patients. Tadalafil may be taken without regard to food. 

Tadalafil was shown to improve erectile function compared with placebo up to 36 hours following dosing. Therefore, take this into consideration when advising patients on optimal use of tadalafil. 

Concomitant medications - For patients taking concomitant potent inhibitors of CYP3A4 (eg, ketoconazole, ritonavir), the maximum recommended dose of tadalafil is 10 mg, not to exceed once every 72 hours. 

Limit tadalafil to 5 mg not more than once daily in patients with severe renal insufficiency or end-stage renal disease. The starting dose in patients with a moderate degree of renal insufficiency should be 5 mg not more than once daily, and the maximum dose should be limited to 10 mg not more than once in every 48 hours. No dose adjustment is required in patients with mild renal insufficiency. 

Hepatic function impairment In volunteers with hepatic cirrhosis, sildenafil clearance was reduced. Consider an initial sildenafil dose of 25 mg in these patients. In patients with mild or moderate hepatic impairment, do not exceed a 10 mg dose of tadalafil. Because of insufficient information in patients with severe hepatic... 

Isosorbide Dinitrate Hydralazine (BiDil) [Antianginal, Antihypertensive/Vasodilator, Nitrate] Uses HF in African Amer-icans improve survival functional status, prolong time between hospitalizations Action Relaxes vascular smooth muscle peripheral vasodilator Dose Initially 1 tab tid PO (if not tol ated reduce to 1/2 tab tid), titrate >3-5 d as tolerated Max 2 tabs tid Caution [C, /-] recent MI, syncope, hypovolemia, hypotension, hep impair Contra For children, concomitant use w/ PDE5 inhibitors (sildenafil) Disp Tabs SE HA, dizziness, orthostatic hypotension, sinusitis, GI distress, tach, paresthesia, amblyopia Interactions t Risk of severe hypotension W/ antihypertensives, ASA, CCBs, MAOIs, phenothiazides, sildenafil, tadalafil, vardenafil, EtOH X pressor response Wf i -1- effects W7 NSAIDs EMS Use ASA, antihypertensives and CCBs w/ caution, may t hypotension concurrent Viagra-type drug use can lead to profound hypotension concurrent EtOH use can t effects OD May cause N/V, profound hypotension, skin flushing, HA from ICP, bradycardia, confusion, and circulatory collapse activated charcoal may be effective, epi use is contraindicated... 

Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A4, increased tadalafil 20-mg single-dose exposure (AUC) by 312%. Other CYP inhibitors—Although specific interactions have not been studied, other CYP3A4 inhibitors, such as erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure. 

Tadalafil has also been extensively evaluated in patients with cardiovascular disease and has a similar safety and efficacy profile to sildenafil (45). Studies have shown no adverse effects on cardiac contraction, ventricular repolarization, or ischemic threshold. A similar hypotensive effect has been recorded with a dose of doxazosin 8 mg so caution is needed. As hypotension does not occur in the supine position and as tadalafil has a long half-life it is suggested that tadalafil is taken in the morning and doxazosin in the evening. There is no interaction of tadalafil with the selective a-adrenoceptor antagonist tamsulosin, which can, therefore, be prescribed as an alternative to doxazosin for symptomatic benign prostate hypertrophy (46). 

Of particular interest is the daily use of tadalafil 10 mg which, after one week because of its half-life, is equivalent to 16-18 mg at steady state. In on-demand failures a regular dosing regime has been successful in 60% without increased adverse effects (47). This increases the chance of success with important implications for the more difficult cases and its use post radical prostatectomy as a daily regime is encouraging. There is no evidence of increased cardiovascular risk with on-demand, three times weekly, or daily dosing (48). 

McMahon C, Comparison of efficacy, safety, and tolerability of on demand tadalafil and daily dosed tadalafil for the treatment of erectile dysfunction, J Sex Med 2006 2 4I 5 -24,... 

Kloner RA, Jackson G, Hutter AM, et al. Cardiovascular safety update of tadalafil retrospective analysis of data from placebo-controlled and open-label clinical trials of tadalafil with as needed, three times-per-week or once-a-day dosing, Am J Cardiol 2006 97 1778-1784. 

AZOLES PHOSPHODIESTERASE TYPE 5 INHIBITORS t sildenafil, tadalafil, and vardenafil levels Inhibition of metabolism i dose of these phosphodiesterase inhibitors... 

PROTEASE INHIBITORS PHOSPHODIESTERASE TYPE 5 INHIBITORS-SILDENAFIL, TADALAFIL, VARDENAFIL t sildenafil, tadalafil and vardenafil levels Inhibition of CYP3A4- and possibly CYP2C9-mediated metabolism of sildenafil Use with caution monitor BP closely. UK manufacturers recommend avoiding co-administration of vardenafil with protease inhibitors in patients >75 years. US manufacturers recommend using with caution, starting with a daily dose of 2.5 mg... 

PHOSPHODIESTERASE TYPE 5 INHIBITORS (e.g. sildenafil, tadalafil, vardenafil) GRAPEFRUIT JUICE Possibly t efficacy and t adverse effects, e.g. hypotension Small t in bioavailability, t variability in pharmacokinetics, i.e. interindividual variations in metabolism Safest to advise against intake of grapefruit juice for at least 48 hours prior to intending to take any of these preparations. When necessaiy, the starting dose of sildenafil should not exceed 25-50 mg and that of tadalafil 10 mg. Avoid co-administration with vardenafil... 

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