Drug Interactions between ketoconazole and sildenafil
This report displays the potential drug interactions for the following 2 drugs:
- ketoconazole
- sildenafil
Interactions between your drugs
ketoconazole sildenafil
Applies to: ketoconazole and sildenafil
Consumer information for this interaction is not currently available.
GENERALLY AVOID: Coadministration with the highly potent CYP450 3A4 inhibitors itraconazole, levoketoconazole, ketoconazole, and/or ritonavir may significantly increase the plasma concentrations and effects of sildenafil, which is primarily metabolized by the isoenzyme. Pharmacokinetic models predict that this interaction may be more significant for oral rather than intravenous formulations of sildenafil, due at least partly to effects from first pass metabolism. In healthy adult volunteers (n=14), administration of a single dose of sildenafil (100 mg) during treatment with ritonavir (500 mg twice a day for 7 days) increased the mean sildenafil peak plasma concentration (Cmax) and systemic exposure (AUC) by 300% and 1000%, respectively, compared to administration alone. At 24 hours, sildenafil plasma levels were approximately 200 ng/mL as opposed to about 5 ng/mL with sildenafil alone. In a parallel study of healthy adult volunteers (n=14), un-boosted saquinavir (soft gelatin capsule 1200 mg three times a day for 7 days) increased single-dose sildenafil's (100 mg) Cmax and AUC by 140% and 210%, respectively. No change in safety or tolerability of sildenafil was observed with either CYP450 3A4 inhibitor. However, other studies of sildenafil in combination with potent inhibitors have observed increases in AUC and adverse effects (headache, flushing, dyspepsia, rhinitis, hypotension). Potent CYP450 3A4 inhibitors like clarithromycin, telithromycin, and nefazodone are generally assumed to increase sildenafil's exposure by 7-fold, an effect in between that of ritonavir and saquinavir. Despite the potential risks, there are a few case studies available in the literature which describe the successful use of sildenafil in combination with ritonavir and 1 case study of use in combination with cobicistat in HIV-infected patients being treated for pulmonary arterial hypertension (PAH). These cases report the use of therapeutic drug monitoring for sildenafil. Data regarding this drug interaction in pediatric patients has not been reported by the manufacturers of sildenafil.
MANAGEMENT: Concurrent use of the highly potent CYP450 3A4 inhibitors ketoconazole, itraconazole, and/or ritonavir in combination with sildenafil indicated for pulmonary arterial hypertension (PAH) should generally be avoided and is considered contraindicated by some authorities. The product labeling for both sildenafil and the potent CYP450 3A4 inhibitor should be consulted for more detailed guidance. For example, some authorities recommend avoiding sildenafil for PAH during and for 2 weeks after treatment with itraconazole. Although the manufacturer considers the combination to be contraindicated, consultation with available clinical guidelines and literature may be considered as some data are available which describe the use of therapeutic drug monitoring of sildenafil in HIV-infected PAH patients who are also on ritonavir. When indicated for erectile dysfunction, the initial dose of sildenafil should not exceed 25 mg, and in some cases should be limited to 25 mg in a 48-hour time frame. Additionally, if concomitant use is clinically necessary, all patients should be monitored closely for adverse effects and advised to promptly notify their doctor if they experience pain or tightness in the chest or jaw, irregular heartbeat, nausea, shortness of breath, hypotension, sudden decrease or loss of hearing, visual disturbances, syncope, or prolonged erection (greater than 4 hours).
Drug and food interactions
ketoconazole food
Applies to: ketoconazole
You should avoid the use of alcohol while being treated with ketoconazole. Ketoconazole may cause liver damage and using it with alcohol or products containing alcohol may increase that risk. In addition, consumption of alcoholic beverages or products containing alcohol during treatment with ketoconazole may trigger a disulfiram-like reaction in some patients, with unpleasant symptoms such as flushing, palpitations, and nausea. Ketoconazole may be taken with or without food. You should avoid consumption of grapefruit, grapefruit juice, or any supplements that contain grapefruit extract during treatment with ketoconazole unless directed otherwise by your doctor. Grapefruit juice may increase the blood levels of ketoconazole. This may increase the risk and/or severity of side effects and liver problems. You should seek immediate medical attention if you develop signs and symptoms of liver damage during treatment with ketoconazole, such as joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, light colored stools, and yellowing of the skin or eyes. Talk to your doctor if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.
sildenafil food
Applies to: sildenafil
If you are receiving therapy with sildenafil you should avoid the regular consumption of large amounts of grapefruits and grapefruit juice. Grapefruit can raise the levels of sildenafil in your body and delay the time it takes for the medication to work. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.
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
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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