Preparat: Furadantin®, Nitrofurantoin Alternova
ATC kod: J01XE01
Flera biverkningsstudier har visat att kvinnor har högre risk för biverkningar av nitrofurantoin än män. En holländsk studie från 1988 med 25 års registerdata fann att nitrofurantoin-inducerad leverskada var något vanligare hos kvinnor än män.
En stor studie har visat att gentamicin och nitrofurantoin var det mest optimala behandlingsalternativet vid urinvägsinfektion hos kvinnor och män oavsett ålder.
Vår bedömning är att de beskrivna skillnaderna i nuläget inte motiverar olika dosering eller behandling hos kvinnor och män, men man ska vara observant på att biverkningar är vanligare hos kvinnor.
No studies with a clinically relevant sex analysis regarding the pharmacokinetics or dosing of nitrofurantoin have been found.
In some settings urine cultures to identify pathogens and resistance pattern cannot always be obtained and therapy of urinary tract infections then has to be empirical. A Brazilian study analyzed urine isolates to identify suitable empirical therapy options for cystitis and urinary tract infections in relation to patient’s sex and age (1098 men, 8700 women). Drug classes analyzed was ampicillin, nitrofurantoin, fluoroquinolones (ciprofloxacin and levofloxacin), trimethoprim-sulfamethoxazole, gentamicin, and ceftriazone/cefotaxime, Women exhibited higher susceptibility values for all drug classes studied than men. For women in any age group, only nitrofurantoin and gentamicin provided adequate activity for empirical therapy (> 80% susceptibility). For men in any age group, only gentamicin was suitable for empirical therapy. In women aged over 60 years, few suitable empirical treatment options were identified .Another study of urinary E. coliisolates (2274 men, 32265 women) has described age- and sex-specific antibiotic susceptibility patterns for ampicillin, amoxicillin clavulanate, ciprofloxacin, nitrofurantoin and trimethoprim-sulfamethoxazole. Nitrofurantoin susceptibility was similar in men and women (96.4% vs. 97.6%). Age-specific susceptibilities differed between men and women for all antibiotics studies except trimethoprim-sulfamethoxazole. However, the magnitude of the observed differences was generally less than 5% and the authors suggest that they may not represent clinically meaningful differences . Resistance patterns for pathogens often differ between populations. A Dutch study comparing resistance in urinary samples from 560 men with historic data from urinary samples from 917 women  found no difference between men and women in E.colisusceptibility to nitrofurantoin . In contrast to this a Portuguese retrospective analysis of urinary samples (120,691 (78%) from women and 34,898 (22%) from men) nitrofurantoin resistance was more common in male urinary samples positive forE. coli, P vulgaris, Klebsiella spp, Enterobacter spp.
Allergic reactions to nitrofurantoin treatment have been reported to be almost identical in men and women (3.9% vs. 4.9%), while toxic reactions were more common in women (2.1% vs. 6.4%). The study found that the toxic reaction to nitrofurantoin was dependent on patient weight in both men and women . Since women generally have a lower body weight, they are more vulnerable to toxic reactions.
Adverse reactions to nitrofurantoin in Sweden during the period 1966-1976 have been studied. Women accounted for 86% of the patient reports and had most of the following types of reactions: pulmonary (acute and chronic), allergic, liver damage, and neuropathy. Among the blood dyscrasias reports, there were more men. The risk of having an adverse reaction to nitrofurantoin was approximately twice as high in women as in men .
Clinical studies have reported a higher incidence of drug-induced liver injury in women with certain drugs such as nitrofurantoin, flucloxacillin, erythromycin and isoniazid . A review reports female sex to be a risk factor for developing nitrofurantoin-induced liver injury . A Dutch study of reported cases of liver injury as an adverse event to nitrofurantoin between 1963-1987, found that 89% of the chronic liver failure cases occurred in women compared to 74% of all nitrofurantoin prescriptions . A possible explanation to this could be a hypersensitivity reaction among women .
Other adverse events from nitrofurantoin associated with women are diarrhea, abdominal pain, and gastrointestinal bleeding .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Fler kvinnor än män hämtade ut tabletter innehållande nitrofurantoin (ATC-kod J01XE01) på recept i Sverige år 2015, totalt 164 069 kvinnor och 18 744 män. Det motsvarar 34 repsektive 3,9 patienter per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 85 år och äldre hos båda könen. Totalt sett var tabletter innehållande nitrofurantoin 8,7 gånger vanligare hos kvinnor .
Faktagranskat av: Mia von Euler
Godkänt av: Karin Schenck-Gustafsson