Drug products: Carbamazepine Essential Pharma, Hermolepsin®, Hermolepsin® Retard®, Tegretal Retard, Tegretol, Tegretol Retard, Tegretol®, Tegretol® Retard, Trimonil retard
ATC code: N03AF01
Carbamazepine may have negative effects on sex hormonal function in both men and women. Menstrual disturbances may occur in women on long term treatment.
One study has shown increased HDL leves in both men and women but more pronounced in women.
Carbamazepine induces metabolism of oral contraceptives and additional anticonceptive method should be used. During pregnancy, the unbound concentration of carbamazepine usually remains unchanged while the total plasma concentration may decrease. This is usually not of clinical significance. Pregnant women should use the lowest effective dose.
Pharmacokinetic studies have shown men/boys to have a lower clearance and a longer half-life of carbamazepine compared to women/girls [1, 2]. In one study, men had lower clearance than women (0.039 vs. 0.049 L/h/kg) and a longer half-life than women (22.7 vs. 17.5 h) . A significant difference in clearance have also been found in children (0.108 L/h/kg in boys vs. 0.72 L/h/kg in girls) . However, other studies have not found significant differences in clearance between men/boys and women/girls .
No studies with a clincally relevant sex analysis regarding the effects of carbamazepine have been found.
A comparative study found that HDL cholesterol concentration increased in both women and men taking carbamazepine. The increase was more pronounced in women. The HDL cholesterol levels in women were 27% higher than in healthy female controls. The increase of HDL cholesterol was less in men, 16% compared with healthy male controls. In healthy subjects, HDL cholesterol is higher in women than in men .
Carbamazepine treatment may have potentially negative effects on reproductive endocrine function in men and women. Several studies have shown that carbamazepine increased concentrations of sex hormone-binding globulin (SHBG), thus reducing unbound biologically active testosterone concentrations [4-6]. Carbamazepine is also an enzyme-inducing drug and may enhance the metabolism of sex hormones. However, these changes may be reversible. In a randomized controlled trial, withdrawal of medication three months after intervention resulted in statistically significant increases in total testosterone serum levels in both sexes, as compared to men and women in the non-withdrawal group. Women also demonstrated a significant increase in estradiol/SHBG ratio after withdrawal. These findings might explain the menstrual disorders that occur in some women after long-term treatment, due to low estradiol/SHBG ratio. It is suggested that men taking carbamazepine could have their sexual function improved by withdrawal of the agent. Likewise, withdrawal of carbamazepine in women would reduce menstrual disturbances . There is one study indicating that treatment with carbamazepine (as well as oxcarbazepine and valproic acid) is associated with sperm abnormalities in men with epilepsy. The clinical relevance of this finding is unclear .
Carbamazepine can induce hyponatremia and female sex may have played a role in the development of hyponatremia. A suggested explanation to this might be sex-related differences in the mechanisms of sodium transport .
A retrospective analysis of patients on AED treatment showed fertile women to have a higher risk for skin reactions than men when treated with carbamazepine .
Carbamazepine has an enzyme-inducing potential and can reduce plasma concentrations of estrogens and progestogens used in oral contraceptives. The effect of hormone therapy may be compromised . Swedish users, please consult Janusmed Interactions(Janusmed interaktioner).
Swedish users, please consult Janusmed Drugs and Birth Defects(Janusmed fosterpåverkan).
Date of litterature search: 2013-02-07
Reviewed by: Expertrådet för neurologiska sjukdomar, Ellen Vinge
Approved by: Mia von Euler