Drug Interactions between nitroglycerin and sildenafil
This report displays the potential drug interactions for the following 2 drugs:
- nitroglycerin
- sildenafil
Interactions between your drugs
nitroglycerin sildenafil
Applies to: nitroglycerin and sildenafil
CONTRAINDICATED: Phosphodiesterase-5 (PDE5) inhibitors may potentiate the hypotensive effect of organic nitrates. Severe hypotension, syncope, or myocardial ischemia may result from use of the combination. The mechanism involves peripheral vasodilation secondary to enhanced levels of cyclic guanosine monophosphate (cGMP) in vascular smooth muscle cells, as PDE5 inhibitors prevent degradation of cGMP while nitrates promote its synthesis. Single oral doses of the PDE5 inhibitors sildenafil (100 mg) and vardenafil (20 mg) have produced mean maximum decreases in supine blood pressure (systolic/diastolic) of approximately 8.4/5.5 and 7.0/8.0 mmHg, respectively, compared to placebo. The decrease in blood pressure was most notable approximately 1 to 2 hours after sildenafil dosing and 1 to 4 hours after vardenafil dosing and was additive with that produced by nitrates. A single 200 mg dose of avanafil produced transient decreases in sitting blood pressure of 8.0/3.3 mmHg in healthy volunteers, with maximum decrease observed at 1 hour after dosing. When given with sublingual nitroglycerin 0.4 mg to healthy males, avanafil 200 mg produced decreases from baseline in sitting and standing blood pressure of 8.2/6.4 and 6.9/7.0 mmHg, respectively, relative to placebo. Tadalafil 20 mg administered to healthy male subjects produced no significant difference in supine or standing blood pressure compared to placebo, although the drug did potentiate the hypotensive effect of nitrates at a dosage of 5 to 20 mg.
MANAGEMENT: The use of PDE5 inhibitors in patients receiving organic nitrates or other nitric oxide donors, either regularly or intermittently, is considered contraindicated. A suitable time interval following sildenafil or vardenafil use for the safe administration of nitrates has not been determined. For patients treated with avanafil or tadalafil, at least 12 hours after the last dose of avanafil and 48 hours after the last dose of tadalafil are recommended before nitrate administration, should it be deemed medically necessary in a life-threatening situation. Even then, nitrates should only be administered under close medical supervision with appropriate hemodynamic monitoring. Patients should be advised to seek immediate medical attention if they experience anginal chest pain after taking a PDE5 inhibitor.
References
- (2001) "Product Information. Viagra (sildenafil)." Pfizer U.S. Pharmaceuticals
- (2003) "Product Information. Levitra (vardenafil)." Bayer
- (2003) "Product Information. Cialis (tadalafil)." Lilly, Eli and Company
Drug and food interactions
sildenafil food
Applies to: sildenafil
GENERALLY AVOID: Coadministration with grapefruit juice may slightly increase the oral bioavailability and delay the onset of action of sildenafil. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In a randomized, crossover study with 24 healthy male volunteers, ingestion of 250 mL of grapefruit juice one hour before and concurrently with a 50 mg dose of sildenafil increased the mean area under the plasma concentration-time curve (AUC) of sildenafil and its pharmacologically active N-desmethyl metabolite by 23% and 24%, respectively, compared to water. Peak plasma concentrations (Cmax) were unaltered, but the time to reach sildenafil Cmax was prolonged by 0.25 hour. The observed increase in sildenafil bioavailability is unlikely to be of clinical significance in most individuals. However, pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability and may be significant in the occasional susceptible patient. Indeed, one subject in the study had a 2.6-fold increase in sildenafil concentrations.
MANAGEMENT: It may be advisable to avoid administration of sildenafil with grapefruit juice to prevent potential toxicity and delay in onset of action.
References
- Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. (2002) "Effects of grapefruit juice on the pharmacokinetics of sildenafil." Clin Pharmacol Ther, 71, p. 21-29
nitroglycerin food
Applies to: nitroglycerin
MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.
MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.
References
- Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
- Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
- Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
- Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
- Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
- Cerner Multum, Inc. "Australian Product Information."
- Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
- Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
Further information
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