Sildenafil interactions

The most dramatic difference between the three agents is tadalahl s extended duration of action, earning it the nickname the weekender drug. While sildenafil and vardenafil have average half-lives of 3 to 4 hours, tadalafil s half life is approximately 18 hours.18 The extended half-life allows for more spontaneous sexual activity over a couple of days, but may increase the duration of adverse effects and liklihood of drug interactions or sildenafil. 

A drug-drug interaction is possible with sildenafil and which of the following agents ... 

Unless otherwise stated, general information applies to the entire class of phosphodiesterase inhibitors. Sildenafil is highlighted because it was the first to be marketed and is the most thoroughly studied. The newer agents tadalafil and vardenafil have different pharmacokinetic profiles (Table 83-3), drug-food interactions, and adverse effects. 

QIO A significant clinical interaction may occur if sildenafil is administered concomitantly v/ith ... 

Isordil is a proprietary (trade name) preparation of isosorbide dinitrate, a nitrate. Sildenafil, the active ingredient of Viagra, interacts with nitrates and the two active ingredients should not be administered concurrently, as a significant hypotensive effect may occur. 

Drugs that may interact with nitrates include alcohol, alteplase, aspirin, beta-blockers, calcium channel blockers, dihydroergotamine, heparin, nondepolarizing muscle relaxants, phenothiazines, phosphodiesterase inhibitors (eg, sildenafil, tadalafil, vardenafil), and vasodilators. 

Drug/Food interactions When taken with a high-fat meal, the rate of sildenafil absorption is reduced, with a mean delay in T ax minutes and a mean reduction in C ax 29%. High-fat meals caused a reduction in C ax vardenafil by 18% to 50%. 

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... 

Sildenafil has other minor adverse effects, such as headache, nasal congestion, and flushing. There are no clinically significant drug interactions between sildenafil and apomorphine. Apomorphine, like sildenafil, is orally active. However, unlike sildenafil, it exerts its action through the central nervous system. Apomorphine can produce dizziness, nausea, pallor, and hypotension, and in the presence of ethanol, it purportedly increases... 

GFJ has been shown to increase the exposure of carbamazepine (175), cisapride (176-179), fluvoxamine (184), losartan (188), methadone (189), scopolamine (191), and sertraline (192). However, only the interaction of GFJ with carbamazepine and cisapride seems to be clinically relevant. No alteration in exposure was observed for clozapine (180,181), heophylline (195), halo-peridol (196), and omeprazole (190). Reports of increased pharmacokinetic parameters of clozapine, theophylline, and haloperidol suggest that an interaction is unlikely to be clinically relevant. Contradicting results were reported for itraconazole (185-187), digoxin (75,183), and sildenafil (193,194). An increased effect on concomitant use of diclofenac and GFJ was observed in rats (182). Overall, the clinical relevance for this drug class appears to be low. 

Lee M, Min DI. Determination of sildenafil citrate in plasma by high-performance liquid chromatography and a case for the potential interaction of grapefruit juice with sildenafil citrate. Ther Drug Monit 2001 23(l) 21-26. 

Up to 2001, AERS indicated up to 39 case reports of possible drug interactions between St. John s wort and a prescription drug. In these case reports, the potential drug interactions occurred mostly with oral contraceptives, antidepressants, cyclosporine, and sildenafil. All cases were reported between 1997 and 2000. Most of the reported cases were in females (24),... 

Four cases of lack of effect or impotence were reported in patients using sildenafil while on St. John s wort and other concomitant drugs (what are they Are any of them significant from the standpoint of drug interaction ). The age range of the four male patients was between 55 to 73 years. Viagra... 

A physician reported that a 60-year-old male started sildenafil 50 mg while he was also taking 600 mg of St. John s wort daily for depression. When the patient increased the dose of St. John s wort to 1200 to 1800 mg daily for unknown reasons, the sildenafil was reported to be partially effective. Patient increased the dose of sildenafil to 100 mg but it was completely ineffective. The physician suspected that a drug interaction caused the adverse events. No other significant medical history was noted. 

The available case reports in the FDA AERS support the published literature that there are pharmacokinetic interactions between St. John s wort and CYP3A4 and/or p-glycoprotein substrates, such as cyclosporine, levonorgestrel/estradiol and sildenafil, and pharmacodynamic interactions with the SSRIs or MAOI. Subsequent clinical studies including those conducted via a CDER clinical pharmacology research cooperative agreement (14—16) provided mechanistic basis of many of these interactions (refer to Chapter 4). 

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