Norethisterone is a progestogen (a hormone similar to progesterone) used in the progestogen-only pill, for treating very heavy or painful periods, and in endometriosis.
Also known as: Noretindrona, Primolut-N
Rifampicin strongly induces norethisterone metabolism, risking contraceptive failure with progestogen-only contraception.
Enzyme induction (CYP3A4 plus enhanced glucuronidation) accelerating progestogen elimination: the Prontuário (Annex 7, Oestrogens/contraceptives) records "Oestrogens (with possible reduction of contraceptive cover)" with inducers, and migration 267 already created the equivalent pairs for the combined pill (levonorgestrel-etinilestradiol × rifampicin/carbamazepine/phenytoin).
Pregnancy test if failure is suspected, withdrawal bleeding, intermenstrual spotting.
Amenorrhoea with unintended pregnancy, persistent spotting, absent withdrawal bleeding.
Add a barrier method throughout treatment and for the following 4 weeks; in prolonged antituberculous therapy, discuss non-hormonal or long-acting contraception.
INFARMED Prontuário Terapêutico (11th ed., 2012), Annex 7 — Oestrogens/contraceptives with enzyme inducers and Rifampicin entry; migration 267 (levonorgestrel-etinilestradiol × rifampicin, critical) for the combined pill.
Carbamazepine accelerates norethisterone metabolism, potentially reducing the contraceptive efficacy of progestogen-only contraception.
Enzyme induction of progestogen metabolism: the Prontuário (Carbamazepine entry 2.6) states "reduced effect of anticoagulants and oral contraceptives"; migration 267 already created the homologous pair with the combined pill (moderate).
Intermenstrual spotting, withdrawal bleeding, pregnancy test if failure is suspected; anticonvulsant levels if dosing changes.
Absent withdrawal bleeding, persistent spotting, unintended pregnancy.
Reinforce with a barrier method during treatment and for 4 weeks after stopping the inducer; reassess the need for hormonal contraception in epilepsy.
INFARMED Prontuário Terapêutico (11th ed., 2012), Carbamazepine entry 2.6 — reduced effect of oral contraceptives; Annex 7 — Oestrogens/contraceptives.
Phenytoin accelerates norethisterone metabolism, potentially reducing the contraceptive efficacy of progestogen-only contraception.
Enzyme induction: the Prontuário (Phenytoin entry 2.6) states that phenytoin "increases the metabolism of corticosteroids, oral contraceptives and nisoldipine"; migration 267 created the homologous pair with the combined pill (moderate).
Intermenstrual spotting, withdrawal bleeding, pregnancy test if failure is suspected; phenytoin levels if dosing changes.
Absent withdrawal bleeding, persistent spotting, unintended pregnancy.
Add a barrier method during treatment and for the following 4 weeks; reassess hormonal contraception in the epilepsy setting.
INFARMED Prontuário Terapêutico (11th ed., 2012), Phenytoin entry 2.6 — increased metabolism of oral contraceptives; Annex 7 — Oestrogens/contraceptives.
No clinically relevant food interaction is documented for oral norethisterone.
Take with or without food, at the same time.
EMC-UK — Norethisterone SmPC 4.2 (no dietary restrictions).
Progestogens (and levonorgestrel-EE) increase VTE risk — contraindicated in active/past VTE.
Exclude history of DVT/PE before starting; discontinue if VTE signs develop.
Site monograph (norethisterone — thrombosis history); EMC-UK norethisterone SmPC 4.3.
Hepatic metabolism and hepatotoxicity — contraindicated in liver disease (sex steroid pattern).
Exclude liver disease before starting.
Prontuário 8.3 (progestogens — class hepatic contraindication).
Annex 1 records "Do not institute replacement therapy during pregnancy" — norethisterone should not be started as hormonal therapy in pregnancy (no routine obstetric indication). Short-duration inadvertent exposure in the 1st trimester (e.g. pregnancy on hormonal contraception) will probably not harm the fetus (l. 41121-23).
Do not start during pregnancy; short-duration inadvertent exposure is not an indication for termination.
Progestogens pass little into milk and do not impair lactation (unlike oestrogens); compatible at usual doses.
Prontuário Terapêutico INFARMED — Annex 1: "Norethisterone" (l. 41120-23).
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Contraception with LH peak suppression; secretory endometrial transformation and cervical mucus thickening.
Progesterone receptor agonist (with residual androgenic activity): suppresses the LH peak through hypothalamic feedback, maintains hostile cervical mucus and stabilises the endometrium.
Good oral absorption (~ 65%); bioavailability reduced by enzyme inducers.
Hepatic reduction (CYP3A4) to inactive metabolites; renal and biliary excretion.
~ 8 h (norethisterone acetate).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
