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 [1].

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 [2].

No sex differentiation in dosing has been recommended by the pharmaceutical company [3].

Effects

Resistance patterns for pathogens often differ between populations. A Dutch study comparing resistance in urinary samples (917 from women, 560 from men) found no difference between men and women in E.colisusceptibility to amoxicillin [4,5]. An American study of urinary E. coliisolates (2274 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 studieds 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 [6]. In contrast to this a Portuguese retrospective analysis of urinary samples (34 898 (22%) from men and 120 691 (78%) from women ) amoxicillin resistance was more common in male urinary samples positive for E. coliandP. mirabilis[7]. Also an Austrian study found amoxicillin resistance rates to be higher in male urinary samples positive for E.coli(24 967 (21%) from men and 95 068 (79%) from women) [8].

An American meta-analysis (in total 3624 men and women) evaluating risk factors for resistance to H. pylorifound no association between amoxicillin resistance and patient’s sex [9].

Urine cultures from pediatric patients (aged 0-36 months) at an emergency department was analyzed for age- and sex-specific differences. Fewer boys than girls were cultured at all ages, but their overall positive culture rate was higher than for girls (10.9% vs. 8.4%). Boys had a higher proportion of Gram-positive organisms than girls (52.3% vs. 18.6%), which suggests that boys might benefit more from trimethoprim-sulfamethoxazole or amoxicillin/clavulanic acid than from third-generation cephalosporins (cefotaxime, ceftazidime, ceftriaxone) [10].

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) [11,12]. In both studies, patients received cloxacillin or amoxicillin/clavulanic acid. Results showed that antibiotic prophylaxis decreased infections rates [11] but did not prevent meningitis [12]. Male sex was among risk factors for infection and meningitis.

Adverse effects

Amoxicillin use is associated with antibiotic-induced rash. In a retrospective study of pediatric patients (106 boys, 132 girls; mean age 6.13 years) with Epstein Barr acute infectious mononucleosis, amoxicillin was associated with higher incidence of antibiotic-induced rash than penicillin, amoxicillin/clavulanic acid, cephalosporines, and macrolides. Nno sex differences in rash incidence were seen between patients who did and did not develop antibiotic-induced rash [13].

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 [14]. A study of amoxicillin/clavulanic acid induced DILI (35 men, 26 women) showed association with certain HLA I and II genotypes [15].

Probiotic supplement to reduce occurrence of side effects of H. pyloriinfection were evaluated in a Spanish randomized, double-blind, placebo-controlled study. Patients with H. pyloriinfection (78 men, 131 women) received one of two eradication treatments (PPI, clarithromycin and amoxicillin, or PPI, clarithromycin, amoxicillin and metronidazole) were randomized to either receive probiotic or placebo. Female sex and quadruple therapy were independent predictors of side effects (taste disturbance, diarrhea, abdominal pain, constipation, bloating, nausea and vomiting) [16].

Reproductive health issues

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