Amoxicillin

Additional information

Pharmacokinetics and dosing

In a pharmacokinetic study (without significance calculations) in healthy volunteers (6 men, 6 women) amoxicillin mean half-life was shorter in men than in women (54 min vs. 73 min) after a single dose (500 mg). Higher concentration of amoxicillin was found in the men’s urine. However, no differences in exposure between men and women were shown [2].

A pharmacokinetic study (17 women) described significant changes in amoxicillin pharmacokinetics during pregnancy, in comparison to postpartum circumstances. Amoxicillin exposure was lower in the second and third trimesters of pregnancy than three months postpartum. On the contrary, creatinine clearance and amoxicillin renal clearance and secretion were higher during pregnancy. Plasma half-life of amoxicillin was shorter in the second and third trimesters than postpartum [3].

No sex differentiation in dosing has been recommended by the manufacturer [4].

Effects

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 [5] found no difference between men and women in E.colisusceptibility to amoxicillin [6]. In contrast to this a Portuguese retrospective analysis of urinary samples (120 691 (78%) from women and 34 898 (22%) from men) amoxicillin resistance was more common in male urinary samples positive for E. coliandP. mirabilis[7].

Another study of urinary E. coliisolates (2 274 men, 32 265 women) has described age- and sex-specific antibiotic susceptibility patterns for ampicillin, amoxicillin clavulanate, ciprofloxacin, nitrofurantoin and trimethoprim-sulfamethoxazole. Amoxicillin/clavulanic acid susceptibility was similar in men and women (56.9% vs. 67.3%). 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 [8].

The benefit of antibiotic prophylaxis in preventing infections after craniotomy has been evaluated based on surveillance data of infections after craniotomy (one including 4 878 men and women, the other study 3134 men, 3109 women) [9,10]. In both studies, patients received cloxacillin or amoxicillin-clavulanate. Results showed that antibiotic prophylaxis decreased infections rates [9] but did not prevent meningitis [10]. Male sex was among risk factors for infection and meningitis.

Adverse effects

Amoxicillin/clavulanic acid can induce idiosyncratic drug-induced liver injury (DILI). Clinical studies have reported a higher incidence of DILI in women with certain drugs such as nitrofurantoin, flucloxacillin, erythromycin and isoniazid [11]. A study of amoxicillin/clavulanic acid induced DILI (35 men, 26 women) showed association with certain HLA I and II genotypes [12].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

A retrospective study, including 1921 patients (794 men, 1122 women, lack of access to 5 medical records), found a greater occurrence of positive penicillin skin test result in female patients than in male patients with self-reported penicillin allergy. The risk was calculated from the whole set of 64 positive results (11 men, 53 women), including different penicillins [1].A retrospective cohort study, analyzing data for antibiotic prescriptions in outpatient care in Belgium, revealed that girls/women were prescribed amoxicillin to a greater extent than boys/men, compared to broad-spectrum antibiotics. Also, female physicians (general practitioners and pediatricians) prescribed more amoxicillin, compared with broader spectrum alternatives, than male colleagues [13].