Is there a risk of an interaction between Roaccutan (isotretinoin) and Lexinor (norfloxacin) or oth

Fråga: Is there a risk of an interaction between Roaccutan (isotretinoin) and Lexinor (norfloxacin) or other drugs that are recommended for urinary tract infection?

A 30-year-old female patient is treated with isotretinoin for acne. The physician is considering treatment with norfloxacin for uncomplicated urinary tract infection. The patient has no other known diseases and is not treated with other drugs.

Sammanfattning: There are no reports of any interaction between isotretinoin and norfloxacin or trimethoprin, nitrofurantion and pivmecillinam. No theoretical pharmacokinetic or pharmacodynamic interactions are expected. Norfloxacin is not suggested as first line treatment for urinary tract infection.

Svar: No reports of interactions between isotretinoin and norfloxacin have been found in available literature.

Isotretinoin is metabolized, by cytocrome P-450, in the liver into the major active metabolite, 4-oxo-isotretinoin and other active metabolites (1). These are then glucoronidated before excretion in bile and urine (2).

Norfloxacin is mainly excreted by tubular secretion and glomerular filtration and about 30% of the administered dose is excreted unchanged in the urine. Metabolism in other tissues, mainly the liver, occurs and several metabolites are found in the urine. Norfloxacin inhibits CYP1A2 and CYP3A4 enzymes (3). About 30% of the administered dose is found in the faeces (4). Due to ecological reasons norfloxacin is not the drug of choice. Trimethoprim, nitrofurantoin or pivmecillinam are suggested as first line treatment in uncomplicated urinary tract infection (5).

Trimethoprim is excreted by glomerular filtration and tubular secretion. Up to 50% of administered trimethoprim is excreted in the urine in unchanged form (6). Nitrofurantoin is mainly excreted unchanged in the urine but some of the drug is reduced in the liver and by the intestinal flora (7). Pivmecillinam is rapidly hydrolysed into mecillinam that is the active drug. About 45% of the dose of pivmecillinam can be found unchanged in the urine (4).

There is no theoretical ground for a pharmacokinetic interaction between isotretinoin and norfloxacin or trimethoprim, nitrofurantoin and pivmecillinam. 1 Drugline no 12394 (year 1995) 2 Drugline no 18897 (year 2002) 3 FASS 2002 (The Swedish catalogue of approved medical products), interaction chapter 4 Parfitt K, editor. Martindale, The complete drug reference. 32nd ed. London: Pharmaceutical Press; 1999 5 Kloka listan: rekommenderade läkemedel vid vanliga sjukdomar. Läksak, Stockholms läns Landsting 2003. 6 Drugline no 14007 (year 1997) 7 Drugline no 15922 (year 1999)