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Paracetamol

Classification: A

Drug products: Altermol, Alvedon Novum, Alvedon®, Alvedon® Dos, Alvedon® forte, Citodon®, Citodon® forte, Citodon® minor, Codalvonil, Curadon®, Curadon® forte, Oparap, Pamol, Panadol Junior, Panocod®, Panodil Retard, Panodil®, Panodil® Brus, Panodil® Forte, Panodil® Zapp, Paracetamol ABECE, Paracetamol Actavis, Paracetamol Alternova, Paracetamol Apofri, Paracetamol B. Braun, Paracetamol EQL Pharma, Paracetamol Evolan, Paracetamol Fresenius Kabi, Paracetamol NET, Paracetamol Novum ABECE, Paracetamol Novum Apofri, Paracetamol Orifarm, Paracetamol Panpharma, Paracetamol Teva, Paracetamol/Kodein Evolan, Paracut, Paracut Forte, Parapo, Perfalgan, Perfalgan®, Pinex, Pinex Cappuccino, Pinex Jordgubb, Quramol, Reliv®, Therimin Honung & Citron, Therimin Skogsbär, Zaldiar

ATC code: N02AJ06, N02AJ13, N02BE01

Substances: paracetamol, Paracetamol DC (PVP) 284N, paracetamol dc 90 (compap l, code 0093), paracetamol dc 90 fine (apap dc-90 fine)

Summary

The main indication for paracetamol (acetaminophen) is treatment of different types of pain and fever.

Information about differences between men and women on effect of paracetamol is lacking. Women can have a slightly higher expose of paracetamol given the same dose. Concomitant use of combined oral contraceptives can reduce the expose of paracetamol. The clinical effect of this is unclear.

Additional information

Paracetamol is also known as acetaminophenin English literature.

Pharmacokinetics and dosing

In a pharmacokinetic study, female volunteers were given paracetamol in follicular and luteal phase and pharmacokinetics was compared to male volunteers (8 men, 8 women). Compared to men, the mean AUC was increased in women by 39% and 51% and the Cmax increased by 48% and 66% in the follicular and luteal phase, respectively [1].

In a study in healthy volunteers (8 men, 8 women), paracetamol clearance was 22% greater in men compared to women not using oral contraceptives. However, half-life did not differ [2]. Also a British study (43 men, 71 women) described a 12% lower clearance in women than in men [3]. However, another study in healthy volunteers (16 men, 16 women, age 23-78 years) found that total clearance was lower in women than in men when uncorrected for weight (208 and 327 ml/min, respectively), but when the analysis included correction for weight, no significant difference remained [4].

In another study, data were pooled from 49 women at delivery, 8 women not using oral contraceptives, and 14 women using oral contraceptives. Of the 49 women, 8 were observed 10-15 weeks post-partum and 7 also 1 year after delivery. A higher median paracetamol clearance was found in women at delivery compared to postpartum or non-pregnant women (11.9 vs. 6.4 and 8.4 l/h•m2). There was an association between paracetamol clearance and estradiol. However, in non-pregnant women there was no effect on paracetamol clearance of exposure to oral contraceptives [5].

Effects

No studies with a clinically relevant sex analysis regarding the effect of paracetamol have been found.

Adverse effects

No studies with a clinically relevant sex analysis regarding the adverse effects of paracetamol have been found.

Reproductive health issues

Paracetamol is metabolized to a large extent by glucoronidation and sulphation and concomitant use of oral contraceptive steroids can therefore increase its metabolism. A study compared paracetamol pharmacokinetics in women, 7 with and 7 without combined oral contraceptives. Cmax of paracetamol were similar and occurred at the same time whereas clearance of paracetamol was 64% higher and half-life was reduced in patients on oral contraceptives [6]. Another study found paracetamol clearance increased by 49% and half-life reduced in users of combined oral contraceptives [4]. In both studies, the effects were considered to be due to enhanced glucoronidation [2, 6].In another study, ethinylestradiol 50 µg and levonorgestrel 250 µg were given orally to 6 women who had been on combined oral contraceptives for at least 3 months. At approximately the same time in the subsequent cycle this was repeated and 1g paracetamol was added. Mean AUC for ethinylestradiol was increased 22% by concomitant paracetamol. A decrease in AUC of ethinylestradiol sulphate was seen in association to this whereas levonorgestrel concentrations were not affected [7, 8].Thus, concomitant medication of oral contraceptives and paracetamol results in a lower concentration of paracetamol whereas minor effects on the concentrations of oral contraceptives are found. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).

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

Other information

In a study of hospital admissions for poisoning in five Oslo hospitals during 2008 paracetamol was utilized by 16% of females and 6% of males [9]. In another cross sectional multicenter study on acute poisonings from Oslo conducted in 2003 paracetamol was utilized by 18% of women and 5% of men [9]. In an English study of self-harm in six hospitals conducted in 2000, more women (41,4%) than men (37,8%) used paracetamol [10].

Updated: 2018-12-18

Date of litterature search: 2014-06-16

References

  1. Wójcicki J, Gawrońska-Szklarz B, Kazimierczyk J, Baskiewicz Z, Raczyński A. Comparative pharmacokinetics of paracetamol in men and women considering follicular and luteal phases. Arzneimittelforschung. 1979;29:350-2. PubMed
  2. Miners JO, Attwood J, Birkett DJ. Influence of sex and oral contraceptive steroids on paracetamol metabolism. Br J Clin Pharmacol. 1983;16:503-9. PubMed
  3. Mucklow JC, Fraser HS, Bulpitt CJ, Kahn C, Mould G, Dollery CT. Environmental factors affecting paracetamol metabolism in London factory and office workers. Br J Clin Pharmacol. 1980;10:67-74. PubMed
  4. Divoll M, Abernethy DR, Ameer B, Greenblatt DJ. Acetaminophen kinetics in the elderly. Clin Pharmacol Ther. 1982;31:151-6. PubMed
  5. Beleyn B, Vermeersch S, Kulo A, Smits A, Verbesselt R, de Hoon JN et al. Estradiol and weight are covariates of paracetamol clearance in young women. Gynecol Obstet Invest. 2014;77:211-6. PubMed
  6. Mitchell MC, Hanew T, Meredith CG, Schenker S. Effects of oral contraceptive steroids on acetaminophen metabolism and elimination. Clin Pharmacol Ther. 1983;34:48-53. PubMed
  7. Lund C, Teige B, Drottning P, Stiksrud B, Rui TO, Lyngra M et al. A one-year observational study of all hospitalized and fatal acute poisonings in Oslo: epidemiology, intention and follow-up. BMC Public Health. 2012;12:858. PubMed
  8. Rogers SM, Back DJ, Stevenson PJ, Grimmer SF, Orme ML. Paracetamol interaction with oral contraceptive steroids: increased plasma concentrations of ethinyloestradiol. Br J Clin Pharmacol. 1987;23:721-5. PubMed
  9. Hovda KE, Bjornaas MA, Skog K, Opdahl A, Drottning P, Ekeberg O et al. Acute poisonings treated in hospitals in Oslo: a one-year prospective study (I): pattern of poisoning. Clin Toxicol (Phila). 2008;46:35-41. PubMed
  10. Hawton K, Bergen H, Casey D, Simkin S, Palmer B, Cooper J et al. Self-harm in England: a tale of three cities Multicentre study of self-harm. Soc Psychiatry Psychiatr Epidemiol. 2007;42:513-21. PubMed
  11. Läkemedelsstatistik. Stockholm: Socialstyrelsen 2015 [cited 2016-03-14.] Socialstyrelsens statistikdatabas
  12. Conicse. Stockholm: eHälsomyndigheten. 2015 [cited 2016-03-23.] länk

Authors: Johan Holm, Desirée Loikas

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson