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Allopurinol

Classification: A

Drug products: Allopurinol Nordic Drugs, Allopurinol Orion, Allopurinol Sandoz, Allopurinol Takeda, Allopurinol Teva, Zyloric®

ATC code: M04AA01

Substances: allopurinol

Summary

Gout is more prevalent in men and more men have been included in clinical studies making statistical meaningful comparison of effect between men and women difficult. Studies have shown women on allopurinol treatment to have more cutaneous hypersensitivity reactions and men to have a higher risk of fractures.
 
In our opinion, the described differences do not motivate differentiated dosing or treatment in men and women.

Additional information

Women have far lower prevalence of gout compared with men, the sex difference decreases with increasing age, but men still outnumber women with gout, even among the elderly [1]. A retrospective analysis of hyperuricemic gout patients (3 875 men, 226 women) compared the characteristics of women and men with gout. Women with gout were older and had significantly higher rates of cardiovascular, metabolic and renal comorbidities than the men [2].

Pharmacokinetics and dosing

A pharmacokinetic study (10 men, 9 women) aiming to study difference between young and old participants found no difference in pharmacokinetic variables between men and women [3].

Effects

No published placebo-controlled studies with a clinically relevant sex-analysis of the effects of allopurinol have been found. A retrospective analysis of pooled data from three studies comparing febuxostat and allopurinol (3875 men, 226 women) showed better effect of febuxostat [2], similarly to the overall results from the studies [4-5].Although specific risk factors (e.g. diuretics) are more common for women than for men, a recent review states that there is no evidence that treatment responses differ between men and women [1].

Adverse effects

In the retrospective analysis of pooled data from three studies comparing febuxostat and allopurinol (3,875 men, 226 women) mentioned earlier, similar frequencies of adverse effects were found in the female cohort compared to the entire cohort (including both men and women) [2].

A large nationwide population-based register study of Taiwanese adults investigated the incidence of, risk factors for, and mortality associated with allopurinol hypersensitivity in new users (360 652 men, 135 211 women). Risk factors for hypersensitivity included female sex, age 60 years or older, initial allopurinol dosage exceeding 100 mg/day, renal or cardiovascular comorbidities, and use for treating asymptomatic hyperuricemia [6].

In a study of patients with cutaneous adverse drug reactions in a dermatology ward in a Chinese hospital (247 men, 487 women), allopurinol was the most common single drug associated with any type of cutaneous reactions. In the entire study, female patients outnumbered male patients, although patients with severe reactions were more likely to be male [7].

The risk of fracture from allopurinol use was found to be higher in men in a nationwide Danish registry study (58 072 men, 27 967 women) [8].

Reproductive health issues

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

Updated: 2019-02-26

Date of litterature search: 2017-01-04

References

  1. Singh JA. Racial and gender disparities among patients with gout. Curr Rheumatol Rep. 2013;15:307. PubMed
  2. Chohan S, Becker MA, MacDonald PA, Chefo S, Jackson RL. Women with gout: efficacy and safety of urate-lowering with febuxostat and allopurinol. Arthritis Care Res (Hoboken). 2012;64:256-61. PubMed
  3. Turnheim K, Krivanek P, Oberbauer R. Pharmacokinetics and pharmacodynamics of allopurinol in elderly and young subjects. Br J Clin Pharmacol. 1999;48:501-9. PubMed
  4. Schumacher HR, Becker MA, Wortmann RL, Macdonald PA, Hunt B, Streit J et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008;59:1540-8. PubMed
  5. Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Eustace D, Palo WA et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353:2450-61. PubMed
  6. Yang CY, Chen CH, Deng ST, Huang CS, Lin YJ, Chen YJ et al. Allopurinol Use and Risk of Fatal Hypersensitivity Reactions: A Nationwide Population-Based Study in Taiwan. JAMA Intern Med. 2015;175:1550-7. PubMed
  7. Huang HY, Luo XQ, Chan LS, Cao ZH, Sun XF, Xu JH. Cutaneous adverse drug reactions in a hospital-based Chinese population. Clin Exp Dermatol. 2011;36:135-41. PubMed
  8. Dennison EM, Rubin KH, Schwarz P, Harvey NC, Bone KW, Cooper C et al. Is allopurinol use associated with an excess risk of osteoporotic fracture? A National Prescription Registry study. Arch Osteoporos. 2015;10:36. PubMed
  9. Zandman-Goddard G, Amital H, Shamrayevsky N, Raz R, Shalev V, Chodick G. Rates of adherence and persistence with allopurinol therapy among gout patients in Israel. Rheumatology (Oxford). 2013;52:1126-31. PubMed
  10. Riedel AA, Nelson M, Joseph-Ridge N, Wallace K, MacDonald P, Becker M. Compliance with allopurinol therapy among managed care enrollees with gout: a retrospective analysis of administrative claims. J Rheumatol. 2004;31:1575-81. PubMed
  11. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2017-01-09.] Socialstyrelsens statistikdatabas

Authors: Anna Frostenson Tengvall, Linnéa Karlsson Lind

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson