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Amoxicillin

Classification: A

Drug products: Amimox®, Amoclav, Amoxicillin 2care4, Amoxicillin Aurobindo, Amoxicillin Ebb, Amoxicillin Mylan, Amoxicillin Sandoz, Amoxicillin/Clavulanic acid 2care4, Amoxicillin/Clavulanic acid Actavis, Amoxicillin/Clavulanic acid Aurobindo, Amoxicillin/Clavulanic acid BB, Amoxicillin/Klavulansyra 2care4, Amoxicillin/Klavulansyra Ebb, Amoxil Vials for Injection 500 mg, Augmentin, Augmentin i.v., Betaklav, Bioclavid, Co-amoxiclav, DAP-amoxicillin, Imacillin®, Imaxi, Klaximol, Nexium® HP, Spektramox®

ATC code: A02BD06, J01CA04, J01CR02, V01AA20

Substances: amoxicillin, amoxicillin sodium, amoxicillin trihydrate

Summary

Some studies report more resistance to amoxicillin in urinary samples from boys/men while other studies find no sex differences. No sex-related adverse effects have been reported.

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).

Updated: 2020-12-27

Date of litterature search: 2020-04-22

References

  1. Philipson A, Sabath LD, Rosner B. Sequence effect on ampicillin blood levels noted in an amoxicillin, ampicillin, and epicillin triple crossover study. Antimicrob Agents Chemother. 1975;8:311-20. PubMed
  2. Andrew MA, Easterling TR, Carr DB, Shen D, Buchanan ML, Rutherford T et al. Amoxicillin pharmacokinetics in pregnant women: modeling and simulations of dosage strategies. Clin Pharmacol Ther. 2007;81:547-56. PubMed
  3. Amimox (amoxicillin). Summary of Product Characteristics. Swedish Medical Products Agency [updated 2019-10-23, cited 2020-04-22]
  4. den Heijer CD, Donker GA, Maes J, Stobberingh EE. Antibiotic susceptibility of unselected uropathogenic Escherichia coli from female Dutch general practice patients: a comparison of two surveys with a 5 year interval. J Antimicrob Chemother. 2010;65:2128-33. PubMed
  5. den Heijer CD, Penders J, Donker GA, Bruggeman CA, Stobberingh EE. The importance of gender-stratified antibiotic resistance surveillance of unselected uropathogens: a Dutch Nationwide Extramural Surveillance study. PLoS One. 2013;8:e60497. PubMed
  6. McGregor JC, Elman MR, Bearden DT, Smith DH. Sex- and age-specific trends in antibiotic resistance patterns of Escherichia coli urinary isolates from outpatients. BMC Fam Pract. 2013;14:25. PubMed
  7. Linhares I, Raposo T, Rodrigues A, Almeida A. Frequency and antimicrobial resistance patterns of bacteria implicated in community urinary tract infections: a ten-year surveillance study (2000-2009). BMC Infect Dis. 2013;13:19. PubMed
  8. Badura A, Feierl G, Pregartner G, Krause R, Grisold AJ. Antibiotic resistance patterns of more than 120 000 clinical Escherichia coli isolates in Southeast Austria, 1998-2013. Clin Microbiol Infect. 2015;21(6):569e1-7. PubMed
  9. Meyer JM, Silliman NP, Wang W, Siepman NY, Sugg JE, Morris D, Zhang J, Bhattacharyya H, King EC, Hopkins RJ. Risk factors for Helicobacter pylori resistance in the United States: the surveillance of H pylori antimicrobial resistance partnership (SHARP) study, 1993-1999. Ann Intern Med. 2002;136(1):13-24. PubMed
  10. Frumkin K. Bacteriology of urinary tract infections in emergency patients aged 0-36 months. J Emerg Med. 2015;84(4):405-15. PubMed
  11. Korinek AM, Golmard JL, Elcheick A, Bismuth R, van Effenterre R, Coriat P et al. Risk factors for neurosurgical site infections after craniotomy: a critical reappraisal of antibiotic prophylaxis on 4,578 patients. Br J Neurosurg. 2005;19:155-62. PubMed
  12. Korinek AM, Baugnon T, Golmard JL, van Effenterre R, Coriat P, Puybasset L. Risk factors for adult nosocomial meningitis after craniotomy: role of antibiotic prophylaxis. Neurosurgery. 2006;59:126-33; discussion 126-33. PubMed
  13. Chovel-Sella A, Ben Tov A, Lahav E, Mor O, Rudich H, Paret G et al. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Pediatrics. 2013;131(5):e1424-7. PubMed
  14. Leise MD, Poterucha JJ, Talwalkar JA. Drug-induced liver injury. Mayo Clin Proc. 2014;89:95-106. PubMed
  15. Donaldson PT, Daly AK, Henderson J, Graham J, Pirmohamed M, Bernal W et al. Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury. J Hepatol. 2010;53:1049-53. PubMed
  16. McNicholl AG, Molina-Infante J, Lucendo AJ, Calleja JL, Pérez-Aisa Á, Modolell I, Aldeguer X, Calafat M, Comino L, Ramas M, Callejo Á, Badiola C, Serra J, Gisbert JP. Probiotic supplementation with Lactobacillus plantarum and Pediococcus acidilactici for Helicobacter pylori therapy: A randomized, double-blind, placebo-controlled trial. Helicobacter. 2018;23(5):0. PubMed
  17. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Diana Rydberg, Carl-Olav Stiller

Approved by: Karin Schenck-Gustafsson