Paracetamol

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].