Drug reference

Levonorgestrel

BNF 80 (2020–2021)

Source: BNF 80 (2020–2021)
PDF pages: 873, 874, 875, 876, 877

Review source pages for extracted sections and age labels. BNF dose snippets show only their first line.

Overview

Indications And Dose

Emergency contraception ▶BY MOUTH ▶Females of childbearing potential: 1.5 mg for 1 dose, taken as soon as possible after coitus, preferably within 12 hours and no later than after 72 hours (may also be used between 72–96 hours after coitus but efﬁcacy decreases with time), alternatively 3 mg for 1 dose, taken as soon as possible after coitus, preferably within 12 hours and no later than after 72 hours (may also be used between 72–96 hours after coitus but efﬁcacy decreases with time). Higher dose should be considered for patients with body-weight over 70 kg or BMI over 26 kg/m2 Contraception ▶BY MOUTH ▶Females of childbearing potential: 30 micrograms daily starting on day 1 of the cycle then continuously, dose is to be taken at the same time each day, if administration delayed for 3 hours or more it should be regarded as a "missed pill" JAYDESS ® 13.5MG INTRA-UTERINE DEVICE Contraception ▶BY INTRA-UTERINE ADMINISTRATION ▶Females of childbearing potential: Insert into uterine cavity within 7 days of onset of menstruation, or any time if replacement (additional precautions (e.g. barrier methods) advised for at least 7 days continued → before), or any time if reasonably certain woman is not pregnant and there is no risk of conception (additional precautions (e.g. barrier methods) necessary for next 7 days), or immediately following termination of pregnancy below 24 weeks’ gestation; postpartum insertions should be delayed until at least 4 weeks after delivery; effective for 3 years KYLEENA ® 19.5MG INTRA-UTERINE DEVICE Contraception ▶BY INTRA-UTERINE ADMINISTRATION ▶Females of childbearing potential: Insert into uterine cavity within 7 days of onset of menstruation, or any Genito-urinary system time if replacement (additional precautions (e.g. barrier methods) advised for at least 7 days before), or any time if reasonably certain woman is not pregnant and there is no risk of conception (additional precautions (e.g. barrier methods) necessary for next 7 days), or immediately following termination of pregnancy below 24 weeks’ gestation; postpartum insertions should be delayed until at least 4 weeks after delivery; effective for 5 years LEVOSERT ® 20MICROGRAMS/24HOURS INTRA-UTERINE DEVICE Contraception | Menorrhagia ▶BY INTRA-UTERINE ADMINISTRATION ▶Females of childbearing potential: Insert into uterine cavity within 7 days of onset of menstruation, or any time if replacement (additional precautions (e.g. barrier methods) advised for at least 7 days before), or any time if reasonably certain woman is not pregnant and there is no risk of conception (additional precautions (e.g. barrier methods) necessary for next 7 days), or immediately following termination of pregnancy below 24 weeks’ gestation; postpartum insertions should be delayed until at least 4 weeks after delivery; effective for 5 years MIRENA ® 20MICROGRAMS/24HOURS INTRA-UTERINE DEVICE Contraception | Menorrhagia ▶BY INTRA-UTERINE ADMINISTRATION ▶Females of childbearing potential: Insert into uterine cavity within 7 days of onset of menstruation, or any time if replacement (additional precautions (e.g. barrier methods) advised for at least 7 days before), or any time if reasonably certain woman is not pregnant and there is no risk of conception (additional precautions (e.g. barrier methods) necessary for next 7 days), or immediately following termination of pregnancy below 24 weeks’ gestation; postpartum insertions should be delayed until at least 4 weeks after delivery; effective for 5 years Prevention of endometrial hyperplasia during oestrogen replacement therapy ▶BY INTRA-UTERINE ADMINISTRATION ▶Females of childbearing potential: Insert during last days of menstruation or withdrawal bleeding or at any time if amenorrhoeic; effective for 4 years

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Dose Adjustments

DUE TO INTERACTIONS ▶When used orally as an emergency contraceptive, the effectiveness of levonorgestrel is reduced in women taking enzyme-inducing drugs (and for up to 4 weeks after stopping); a copper intra-uterine device should preferably be used instead. If the copper intra-uterine device is undesirable or inappropriate, the dose of levonorgestrel should be increased to a total of 3 mg taken as a single dose; pregnancy should be excluded following use, and medical advice sought if pregnancy occurs. ▶There is no need to increase the dose for emergency contraception if the patient is taking antibacterials that are not enzyme inducers. ▶With the progestogen-only intra-uterine device, levonorgestrel is released close to the site of the main contraceptive action (on cervical mucus and endometrium) and therefore progestogenic side-effects and interactions are less likely; in particular, enzyme- inducing drugs are unlikely to signiﬁcantly reduce the contraceptive effect of the progestogen-only intra- uterine system and additional contraceptive precautions are not required. l UNLICENSED USE ▶With intra-uterine use The Faculty of Sexual and Reproductive Healthcare (FSRH) advises levonorgestrel is used as detailed below, although these situations are considered unlicensed: . Insertion at any time if reasonably certain the woman is not pregnant or at risk of pregnancy; . Additional precautions (e.g. barrier methods) for at least 7 days before replacement even if immediate replacement is intended; . Insertion immediately following termination of pregnancy below 24 weeks’ gestation; . Postpartum insertions 4 weeks after delivery. ▶With oral use The FSRH advises levonorgestrel is used as detailed below, although these situations are considered unlicensed: . Higher dose option for emergency contraception in patients with body-weight over 70 kg or BMI over 26 kg/m2; . Use for emergency contraception between 72–96 hours after coitus. ▶With intra-uterine use or oral use in children Consult product literature for licensing status of individual preparations.

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Contra Indications

▶With intra-uterine use Active trophoblastic disease (until return to normal of urine- and plasma-gonadotrophin concentration. acute cervicitis. acute malignancies affecting the blood (use with caution in remission). acute vaginitis. distorted uterine cavity. history of breast cancer but can be considered for a woman in long-term remission who has menorrhagia and requires effective contraception . increased risk factors for pelvic infections. infected abortion during the previous three months. not suitable for emergency contraception. pelvic inﬂammatory disease . postpartum endometritis. unexplained uterine bleeding. unresolved cervical intraepithelial neoplasia. uterine or cervical malignancy ▶With oral use Acute porphyrias p. 1120 ▶With oral use for contraception History of breast cancer but can be used after 5 years if no evidence of disease and non- hormonal contraceptive methods unacceptable. severe arterial disease. undiagnosed vaginal bleeding

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Cautions

GENERAL CAUTIONS Risk factors for ectopic pregnancy (including previous ectopic pregnancy, tubal surgery or pelvic infection) SPECIFIC CAUTIONS ▶With intra-uterine use Disease-induced immunosuppression (risk of infection—avoid if marked immunosuppression). acute venous thromboembolism (consider removal). anaemia. anticoagulant therapy (avoid if possible). diabetes. drug-induced immunosuppression (risk of infection—avoid if marked immunosuppression). endometriosis. epilepsy (risk of seizure at time of insertion). fertility problems. history of pelvic inﬂammatory disease. increased risk of expulsion if inserted before uterine involution. jaundice (consider removal). marked increase of blood pressure (consider removal). migraine (consider removal). nulliparity. severe arterial disease (consider removal). severe cervical stenosis. severe headache (consider removal). severe primary dysmenorrhoea. severely scarred uterus (including after endometrial resection). young age ▶With oral use for contraception Active trophoblastic disease (until return to normal of urine- and plasma- gonadotrophin concentration)—seek specialist advice. arterial disease. functional ovarian cysts. history of jaundice in pregnancy. malabsorption syndromes. past ectopic pregnancy. sex-steroid dependent cancer. systemic lupus erythematosus with positive (or unknown) antiphospholipid antibodies ▶With oral use for emergency contraception Active trophoblastic disease (until return to normal of urine- and plasma-gonadotrophin concentration)—seek specialist advice. past ectopic pregnancy. severe malabsorption syndromes CAUTIONS, FURTHER INFORMATION ▶With intra-uterine use The Faculty of Sexual and Reproductive Healthcare advises intercourse should be avoided or another method of contraception used for at least 7 days before removal of intra-uterine device— emergency contraception may need to be considered if recent intercourse has occurred and the intra-uterine device is removed. ▶Risk of infection with intra-uterine devices ▶With intra-uterine use The main excess risk of infection occurs in the ﬁrst 20 days after insertion and is believed to be related to existing carriage of a sexually transmitted infection. Women are considered to be at a higher risk of sexually transmitted infections if: . they are under 25 years old or . they are over 25 years old and . have a new partner or . have had more than one partner in the past year or . their regular partner has other partners. In these women, pre-insertion screening (for chlamydia and, depending on sexual history and local prevalence of disease, Neisseria gonorrhoeae) should be performed. If results are unavailable at the time of ﬁtting an intra- uterine device for emergency contraception, appropriate prophylactic antibacterial cover should be given. The woman should be advised to attend as an emergency if she experiences sustained pain during the next 20 days. ▶Use as a contraceptive in co-morbidities ▶With oral use The product literature advises caution in patients with history of thromboembolism, hypertension, diabetes mellitus and migraine; evidence for caution in these conditions is unsatisfactory. MIRENA ® 20MICROGRAMS/24HOURS INTRA-UTERINE DEVICE Advanced uterine atrophy

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Prescribing And Dispensing Information

▶With intra-uterine use Levonorgestrel-releasing intra- uterine devices vary in licensed indication, duration of use and insertion technique—the MHRA recommends to prescribe and dispense by brand name to avoid inadvertent switching.

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National Funding Access Decisions

Scottish Medicines Consortium (SMC) decisions SMC No. 1299/18 The Scottish Medicines Consortium has advised (February 2018) that levonorgestrel (Kyleena ®) is accepted for use within NHS Scotland as a contraceptive device for up to 5 years. All Wales Medicines Strategy Group (AWMSG) decisions AWMSG No. 3582 The All Wales Medicines Strategy Group has advised (September 2018) that levonorgestrel (Kyleena ®) is recommended as an option for use within NHS Wales for contraception for up to ﬁve years.

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Exceptions To Legal Category

Levonelle ® One Step can be sold to women over 16 years; when supplying emergency contraception to the public, pharmacists should refer to guidance issued by the Royal Pharmaceutical Society.

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Safety

Important Safety Information

MHRA/CHM ADVICE (JUNE 2015) INTRA-UTERINE CONTRACEPTION: UTERINE PERFORATION—UPDATED INFORMATION ON RISK FACTORS Uterine perforation most often occurs during insertion, but might not be detected until sometime later. The risk of uterine perforation is increased when the device is inserted up to 36 weeks postpartum or in patients who are breastfeeding. Before inserting an intra-uterine contraceptive device, inform patients that perforation occurs in approximately 1 in every 1000 insertions and signs and symptoms include: . severe pelvic pain after insertion (worse than period cramps); . pain or increased bleeding after insertion which continues for more than a few weeks; . sudden changes in periods; . pain during intercourse; . unable to feel the threads. Patients should be informed on how to check their threads and to arrange a check-up if threads cannot be felt, especially if they also have signiﬁcant pain. Partial perforation may occur even if the threads can be seen; consider this if there is severe pain following insertion and perform an ultrasound.

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Interactions

→Appendix 1: levonorgestrel

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Side Effects

GENERAL SIDE-EFFECTS ▶Common or very common Gastrointestinal discomfort. headaches. menstrual cycle irregularities. nausea. skin reactions Genito-urinary system SPECIFIC SIDE-EFFECTS ▶Common or very common ▶With intra-uterine use Back pain. breast abnormalities. depression. device expulsion. hirsutism. increased risk of infection. libido decreased. nervousness. ovarian cyst. pelvic disorders. uterine haemorrhage (on insertion). vaginal haemorrhage (on insertion). vulvovaginal disorders. weight increased ▶With oral use Breast tenderness. diarrhoea. dizziness. fatigue. haemorrhage. vomiting ▶Uncommon ▶With intra-uterine use Alopecia. endometritis. oedema. uterine rupture ▶Rare or very rare ▶With oral use Face oedema. pelvic pain ▶Frequency not known ▶With oral use Cerebrovascular insufﬁciency. depressed mood. diabetes mellitus. embolism and thrombosis. neoplasms. sexual dysfunction. weight changes SIDE-EFFECTS, FURTHER INFORMATION Breast cancer There is a small increase in the risk of having breast cancer diagnosed in women using, or who have recently used, a progestogen-only contraceptive pill; this relative risk may be due to an earlier diagnosis. The most important risk factor appears to be the age at which the contraceptive is stopped rather than the duration of use; the risk disappears gradually during the 10 years after stopping and there is no excess risk by 10 years. A possible small increase in the risk of breast cancer should be weighed against the beneﬁts. With intra-uterine use There is no evidence of an association between the levonorgestrel intra-uterine system and breast cancer. The levonorgestrel intra-uterine system should be avoided in patients with a history of breast cancer; any consideration of it’s use should be by a specialist in contraception and in consultation with the patients cancer specialist. Patients should be informed about the device that has been inserted and when it should be removed or replaced (including refering them to a patient information leaﬂet and other sources of information). Patients may experience irregular, prolonged or infrequent menstrual bleeding in the 3–6 months following insertion; bleeding pattern improves with time but persists in some patients. Progestogenic side-effects resolve with time (after the ﬁrst few months).

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Pregnancy

▶With oral use Not known to be harmful. ▶With intra-uterine use If an intra-uterine device fails and the woman wishes to continue to full-term the device should be removed in the ﬁrst trimester if possible. Avoid; if pregnancy occurs remove intra-uterine system.

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Breast Feeding

Progestogen-only contraceptives do not affect lactation.

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Hepatic Impairment

▶With intra-uterine use or oral use for Contraception Manufacturer advises avoid in liver tumour. ▶With oral use for Contraception or Emergency contraception Manufacturer advises avoid in severe impairment. ▶With intra-uterine use Manufacturer advises avoid in acute hepatic disease or in severe impairment (no information available)—consult product literature.

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Monitoring Requirements

▶With intra-uterine use Gynaecological examination before insertion, 4–6 weeks after insertion, then annually.

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Dose and formulations

Directions For Administration

▶With intra-uterine use The doctor or nurse administering (or removing) the system should be fully trained in the technique and should provide full counselling reinforced by the patient information leaﬂet. Genito-urinary system

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Medicinal Forms

There can be variation in the licensing of different medicines containing the same drug. Intra-uterine device ▶Jaydess (Bayer Plc) A Levonorgestrel 13.5 mg Jaydess 13.5mg intra-uterine device | 1 device P £69.22 DT = £69.22 ▶Kyleena (Bayer Plc) Levonorgestrel 19.5 mg Kyleena 19.5mg intra-uterine device | 1 device P £76.00 DT = £76.00 ▶Levosert (Gedeon Richter (UK) Ltd) Levonorgestrel 20 microgram per 24 hour Levosert 20micrograms/24hours intra-uterine device | 1 device P £66.00 DT = £88.00 ▶Mirena (Bayer Plc) Levonorgestrel 20 microgram per 24 hour Mirena 20micrograms/24hours intra-uterine device | 1 device P £88.00 DT = £88.00 Tablet ▶Levonorgestrel (Non-proprietary) Levonorgestrel 1.5 mg Levonorgestrel 1.5mg tablets | 1 tablet p £13.83 DT = £5.20 | 1 tablet P £3.74–£5.20 DT = £5.20 ▶Emerres (Morningside Healthcare Ltd) Levonorgestrel 1.5 mg Emerres Una 1.5mg tablets | 1 tablet p £13.83 DT = £5.20 Emerres 1.5mg tablets | 1 tablet P £3.65 DT = £5.20 ▶Ezinelle (Mylan) Levonorgestrel 1.5 mg Ezinelle 1.5mg tablets | 1 tablet p £9.64 DT = £5.20 ▶Levonelle (Bayer Plc) Levonorgestrel 1.5 mg Levonelle 1500microgram tablets | 1 tablet P £5.20 DT = £5.20 ▶Levonelle One Step (Bayer Plc) Levonorgestrel 1.5 mg Levonelle One Step 1.5mg tablets | 1 tablet p £13.83 DT = £5.20 ▶Melkine (Crescent Pharma Ltd) Levonorgestrel 1.5 mg Melkine 1.5mg tablets | 1 tablet P £4.16 DT = £5.20 ▶Norgeston (Bayer Plc) Levonorgestrel 30 microgram Norgeston 30microgram tablets | 35 tablet P £0.92 DT = £0.92 ▶Upostelle (Gedeon Richter (UK) Ltd) Levonorgestrel 1.5 mg Upostelle 1500microgram tablets | 1 tablet P £3.75 DT = £5.20 3.5 Contraception, parenteral progestogen-only Other drugs used for Contraception, parenteral progestogen-only Norethisterone, p. 806 PROGESTOGENS

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Clinical care

Patient And Carer Advice

Diarrhoea and vomiting with use as an oral contraceptive Vomiting and persistent, severe diarrhoea can interfere with the absorption of oral progestogen-only contraceptives. If vomiting occurs within 2 hours of taking an oral progestogen-only contraceptive, another pill should be taken as soon as possible. If a replacement pill is not taken within 3 hours of the normal time for taking the progestogen-only pill, or in cases of persistent vomiting or very severe diarrhoea, additional precautions should be used during illness and for 2 days after recovery. Starting routine ▶With oral use for Contraception One tablet daily, on a continuous basis, starting on day 1 of cycle and taken at the same time each day (if delayed by longer than 3 hours contraceptive protection may be lost). Additional contraceptive precautions are not required if levonorgestrel is started up to and including day 5 of the menstrual cycle; if started after this time, additional contraceptive precautions are required for 2 days. Changing from a combined oral contraceptive Start on the day following completion of the combined oral contraceptive course without a break (or in the case of ED tablets omitting the inactive ones). After childbirth Oral progestogen-only contraceptives can be started up to and including day 21 postpartum without the need for additional contraceptive precautions. If started more than 21 days postpartum, additional contraceptive precautions are required for 2 days. ▶With oral use for Emergency contraception When prescribing or supplying hormonal emergency contraception, manufacturer advises women should be told: . if vomiting occurs within 3 hours, a replacement dose should be taken; . that their next period may be early or late; . to seek medical attention promptly if any lower abdominal pain occurs because this could signify an ectopic pregnancy. The Faculty of Sexual and Reproductive Healthcare also advises women should be told: . that a barrier method of contraception needs to be used—see Emergency contraception p. 838 for further information; . that a pregnancy test should be performed if the next menstrual period is delayed by more than 7 days, is lighter than usual, or is associated with abdominal pain that is not typical of the woman’s usual dysmenorrhoea; . that a pregnancy test should be performed if hormonal contraception is started soon after use of emergency contraception even if they have bleeding; bleeding associated with the contraceptive method may not represent menstruation. ▶With intra-uterine use Counsel women on the signs, symptoms and risks of perforation and ectopic pregnancy. Missed doses When used as an oral contraceptive, the following advice is recommended ‘If you forget a pill, take it as soon as you remember and carry on with the next pill at the right time. If the pill was more than 3 hours overdue you are not protected. Continue normal pill-taking but you must also use another method, such as the condom, for the next 2 days’. The Faculty of Sexual and Reproductive Healthcare recommends emergency contraception if one or more progestogen-only contraceptive tablets are missed or taken more than 3 hours late and unprotected intercourse has occurred before 2 further tablets have been correctly taken.

PDF page 876

Age labels are extracted for navigation. Check the complete source section and current local guidance before clinical use.

Drug reference

Levonorgestrel

BNF 80 (2020–2021)

Source: BNF 80 (2020–2021)
PDF pages: 873, 874, 875, 876, 877

Review source pages for extracted sections and age labels. BNF dose snippets show only their first line.

Overview

Indications And Dose

PDF pages 873, 874

Dose Adjustments

PDF page 874

Contra Indications

PDF pages 874, 875

Cautions

PDF page 875

Prescribing And Dispensing Information

PDF page 876

National Funding Access Decisions

PDF page 876

Exceptions To Legal Category

Levonelle ® One Step can be sold to women over 16 years; when supplying emergency contraception to the public, pharmacists should refer to guidance issued by the Royal Pharmaceutical Society.

PDF page 876

Safety

Important Safety Information

PDF page 874

Interactions

→Appendix 1: levonorgestrel

PDF page 875

Side Effects

PDF page 875

Pregnancy

PDF page 875

Breast Feeding

Progestogen-only contraceptives do not affect lactation.

PDF page 875

Hepatic Impairment

PDF pages 875, 876

Monitoring Requirements

▶With intra-uterine use Gynaecological examination before insertion, 4–6 weeks after insertion, then annually.

PDF page 876

Dose and formulations

Directions For Administration

PDF page 876

Medicinal Forms

PDF pages 876, 877

Clinical care

Patient And Carer Advice

PDF page 876

Age labels are extracted for navigation. Check the complete source section and current local guidance before clinical use.