Is there a risk for interaction between Viagra (sildenafil) and Madopark (levodopa/benserazide), No

Fråga: Is there a risk for interaction between Viagra (sildenafil) and Madopark (levodopa/benserazide), Norvasc (amlodipine), Mianserin NMP (mianserin), Sobril (oxazepam), Cabaser (cabergoline) or Imovane (zopiclone)? A man with Parkinson´s disease and hypertension is suffering from erectile dysfunction and his physician is considering prescribing sildenafil.

Sammanfattning: We have not found any documentation indicating a significant risk for a metabolic interaction between sildenafil and the other drugs coadministered in the present case. This is to some extent due to lack of data. There is, however, a potential for a hemodynamic effect since many of the drugs mentioned including sildenafil lower the blood pressure. This could be of potential importance if the patient has low blood pressure and has a history of or is at risk of a cardiovascular incident, indicating a need for a cardiovascular examination before starting sildenafil treatment at a low dose.

Svar: Tests in vitro have shown that sildenafil is metabolised mainly by CYP3A4 and to some extent by CYP2C9 and is a weak inhibitor of CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (1). Metabolic enzymes involved in the metabolism of benzerazide and cabergoline are unclear and we have not found any documentation concerning interaction between these drugs and sildenafil in the literature. Levodopa is metabolised by decarboxylas (2). A study performed to assess whether coadministration with grapefruit juice, an inhibitor of CYP3A4, significantly affects the pharmakokinetics of amlodipine showed some increase in Cmax and AUC when amlodipine was coadministered with grapefruit juice instead of water, but no significant change in blood pressure or heart rate was found (3). In a clinical interaction study on hypertensive patients where amlodipine was coadministered with sildenafil, the mean decrease in supine systolic/diastolic blood pressure was 8/7 mmHg. The same range was found in healthy volunteers (1). Zopiclone is metabolised by CYP3A4 (4). It seems, however, unlikely that single doses of sildenafil would significantly influence the level of zopiclone. Oxazepam is mainly metabolised in the liver and undergoes glucuronidation (5). Mianserin is to a large extent metabolised by CYP2D6 (6). Thus, pharmacokinetic interactions between sildenafil and these drugs are less likely.

Many of the drugs used by the patient including sildenafil decrease the blood pressure. Hypotension (<90/50 mmHg) is considered a contraindication (1) for the use of sildenafil. If the patient has a blood pressure in the lower range and a history of or is at risk for cardiovascular incidents caution is warranted and may indicate a need for a cardiovascular examination before starting the treatment with sildenafil.