Levonorgestrel


Generic Medicine Info
Indications and Dosage
Intrauterine
Menorrhagia
Adult: Insert into the uterine cavity within 7 days of menstruation or anytime if for replacement (use barrier methods for at least 7 days before), or if reasonably certain that the patient is not pregnant and there is no risk of conception (use barrier methods for the next 7 days), or immediately following termination of pregnancy below 24 weeks gestation; delay postpartum insertions until at least 4 weeks after delivery. Refer to individual product guidelines for further information. As 52 mg IUD: Initially releases at a rate of approx 20 mcg/day. The span of use and replacement guidelines may vary among countries and individual products (refer to specific product guidelines).

Intrauterine
Contraception
Adult: Insert into the uterine cavity within 7 days of menstruation or anytime if for replacement (use barrier methods for at least 7 days before), or if reasonably certain that the patient is not pregnant and there is no risk of conception (use barrier methods for the next 7 days), or immediately following termination of pregnancy below 24 weeks gestation; delay postpartum insertions until at least 4 weeks after delivery. Refer to individual product guidelines for further information. As 13.5 mg IUD: Releases levonorgestrel at a rate of approx 14 mcg/day after 24 days, then rate decreases progressively to approx 5 mcg/day after 3 years. Replace IUD after 3 years. As 19.5 mg IUD: Releases levonorgestrel at a rate of approx 17.5 mcg/day after 24 days, then rate decreases progressively to 7.4 mcg/day after 5 years. Replace IUD after 5 years. As 52 mg IUD: Initially releases levonorgestrel at a rate of approx 20 mcg/day. The span of use and replacement guidelines may vary among countries and individual products (refer to specific product guidelines).

Oral
Emergency contraception
Adult: 1 tab (1.5 mg) taken as soon as possible, preferably within 12 hours and no later than 72 hours after unprotected intercourse. In case vomiting occurs within 3 hours of taking the tablet, immediately take another tab.

Subcutaneous
Contraception
Adult: Using the provided surgical instrument, insert 2 implants (75 mg/implant) beneath the skin within 7 days of menstruation. Refer to individual product guidelines for the specific instructions on administration and removal, recommendations for switching to or from different methods of contraception, and duration of use.
Special Patient Group
Emergency contraception
Women who have used enzyme-inducing drugs (in the past 4 weeks): Increase the dose to 2 tabs (3 mg) taken as a single dose (if Cu IUD is undesirable or inappropriate to use).
Hepatic Impairment
Contraindicated.
Administration
May be taken with or without food.
Contraindications
Known or suspected sex hormone dependent malignancies (e.g. breast cancer), undiagnosed vaginal bleeding, active or history of thromboembolism (e.g. MI, stroke); acute hepatic disease, hepatic tumours (benign or malignant), severe hepatic disease wherein LFTs have not returned to normal. Oral: Severe diabetes with vascular changes. IUD: Uterine bleeding of unknown aetiology; known or suspected uterine, cervical, or endometrial malignancy; cervical intraepithelial neoplasia (until resolved); untreated acute cervicitis or vaginitis (e.g. bacterial vaginosis, chlamydial or gonococcal cervical infection), other lower genital tract infections (until control of infection), conditions that increase the risk to pelvic infections; congenital or acquired uterine anomaly, including fibroids that impair the uterine activity; history of or active acute pelvic inflammatory disease, postpartum endometriosis or infected abortion (within the past 3 months); postcoital contraception, unremoved IUD. Pregnancy.
Special Precautions
Patient with a predisposition to ectopic pregnancy (e.g. history of ectopic pregnancy, salpingitis, tubal surgery, or pelvic infection) or endometritis, history of symptomatic functional ovarian cysts, bradycardia, syncope, seizure, depression, coagulopathy or use of anticoagulants, migraine, focal migraine with asymmetrical visual loss, or other symptoms indicating TIA, exceptionally severe headache, marked increase of blood pressure, malignancies affecting the blood or leukaemias in remission, jaundice; incomplete involution of the uterus (IUD); diabetes, history of chloasma gravidarum (oral). Obese patients (BMI ≥30 kg/m2). Lactation.
Adverse Reactions
Significant: Bleeding pattern alterations (e.g. spotting, irregular bleeding, heavy bleeding, oligomenorrhoea, amenorrhoea), ectopic pregnancy, thromboembolism, hypertension, depression, breast cancer; implant or IUD expulsion. Oral: Carbohydrate intolerance, chloasma, hepatic disease. Rarely, hepatic adenoma. Implant: Cholestatic hepatitis or jaundice. Rarely, idiopathic intracranial hypertension. IUD: intrauterine pregnancy, ovarian cysts, group A streptococcal sepsis, pelvic inflammatory disease, endometritis, actinomycosis, perforation (total or partial), seizure, bradycardia, syncope.
Cardiac disorders: Palpitations, chest pain (implant).
Gastrointestinal disorders: Nausea, vomiting, lower abdominal pain, diarrhoea, abdominal distention.
General disorders and administration site conditions: Fatigue; pain. Itching at insertion site (implant).
Immune system disorders: Hypersensitivity reactions (e.g. rash, urticaria, angioedema).
Investigations: Weight gain or loss, increase in total serum bilirubin (implant).
Musculoskeletal and connective tissue disorders: Back pain (IUD/implant).
Nervous system disorders: Headache, dizziness, migraine.
Psychiatric disorders: Decreased libido, nervousness, mood changes (IUD/implant).
Reproductive system and breast disorders: Dysmenorrhoea, breast pain, pelvic pain (oral/IUD); vulvovaginitis, bacterial vaginosis, vaginal mycosis, genital discharge, upper genital tract infection (IUD); breast discharge, benign breast nodules, vaginitis (implant).
Respiratory, thoracic and mediastinal disorders: Dyspnoea (implant).
Skin and subcutaneous tissue disorders: Acne, alopecia (IUD/implant); hirsutism (IUD); contact dermatitis, rash, pruritus, skin discolouration, hypertrichosis (implant).
Potentially Fatal: Rarely, intra-abdominal haemorrhage associated with benign or malignant liver tumours (implant).
Monitoring Parameters
Evaluate pregnancy status before administration. Following oral emergency contraception, monitor spontaneous abortion, ectopic pregnancy, delayed (≥1 week) normal menstrual period, development of lower abdominal pain or occurrence of persistent bleeding. Before insertion of IUD, perform a bimanual examination and cervical inspection, obtain weight, and screen for STD. Following insertion, check placement through transvaginal ultrasound. Re-examine patient as necessary (refer to specific product guidelines). Assess thread visibility. Monitor blood pressure, serum glucose (in diabetic patients); significant changes in menstrual bleeding (during prolonged use). Perform Pap smear. Evaluate patients presenting with lower abdominal pain for ovarian cysts or ectopic pregnancy. Monitor for signs and symptoms of infection and thromboembolism (in patients who require surgery with prolonged immobilisation).
Overdosage
Oral: Symptoms: Nausea and withdrawal bleeding. Management: Symptomatic treatment.
Drug Interactions
Decreased serum concentration with CYP3A4 enzyme inducers (e.g. rifampicin, phenytoin, carbamazepine, primidone, efavirenz, ritonavir, griseofulvin). Increased serum concentration with strong and moderate CYP3A4 inhibitors (e.g. voriconazole, ketoconazole, itraconazole, verapamil, diltiazem, erythromycin, clarithromycin). May increase the risk of ciclosporin toxicity. Increased or decreased serum concentration with protease inhibitors.
Food Interaction
Decreased serum concentration with St. John's Wort.
Lab Interference
May impair the results of certain tests (e.g. coagulation factors, lipids, glucose tolerance, binding proteins).
Action
Description: Levonorgestrel prevents pregnancy in several mechanisms. It thickens the cervical mucus which inhibits sperm passage through the uterus and sperm survival. It inhibits ovulation from the negative feedback mechanism on the hypothalamus, resulting in reduced secretion of FSH and LH. It can also alter the endometrium which may affect implantation.
Duration: IUD: Prevention of pregnancy: Can vary among brands (refer to specific product guidelines).
Pharmacokinetics:
Absorption: Rapidly and almost completely absorbed (oral). Time to peak plasma concentration: Approx 2 hours (oral).
Distribution: Enters breast milk. Volume of distribution: Approx 1.8 L/kg. Plasma protein binding: 30-56% (albumin); 42-68% (sex hormone-binding globulin).
Metabolism: Metabolised in the liver by the CYP3A4 isoenzyme to inactive metabolites. Undergoes minimal first-pass metabolism in the liver.
Excretion: Mainly via urine (45%); faeces (32%). Elimination half-life: 30-46 hours (oral); approx 17 hours (IUD).
Chemical Structure

Chemical Structure Image
Levonorgestrel

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 13109, Levonorgestrel. https://pubchem.ncbi.nlm.nih.gov/compound/Levonorgestrel. Accessed Nov. 24, 2021.

Storage
Store below 30°C. Protect from light (tab). Storage recommendations may vary among countries or individual products. Refer to specific product guidelines.
MIMS Class
Depot Contraceptives / Oestrogens, Progesterones & Related Synthetic Drugs / Oral Contraceptives / Other Contraceptives
ATC Classification
G03AD01 - levonorgestrel ; Belongs to the class of emergency contraceptives. Used as systemic contraceptives.
G03AC03 - levonorgestrel ; Belongs to the class of progestogens. Used as systemic contraceptives.
References
Anon. Levonorgestrel (IUD). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/09/2021.

Anon. Levonorgestrel (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/09/2021.

Benilexa 20 mcg/24 hours Intrauterine Delivery System (Gedeon Richter Plc.). MHRA. https://products.mhra.gov.uk. Accessed 21/09/2021.

Benilexa One Handed 20 mcg/24 hours Intrauterine Delivery System (Gedeon Richter Plc.). MHRA. https://products.mhra.gov.uk. Accessed 21/09/2021.

Buckingham R (ed). Norgestrel. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/09/2021.

Escapelle 1.5 mg Tablet (Gedeon Richter Plc.). MIMS Malaysia. http://www.mims.com/malaysia. Accessed 21/09/2021.

Gynostrel 1.5 (Vexxa Lifesciences PVT, Ltd.). MIMS Myanmar. http://www.mims.com/myanmar. Accessed 21/09/2021.

Jadelle 2 x 75 mg Implants (Bayer Oy). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 21/09/2021.

Jaydess 13.5 mg Intrauterine Delivery System (Bayer plc). MHRA. https://products.mhra.gov.uk. Accessed 21/09/2021.

Joint Formulary Committee. Levonorgestrel. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/09/2021.

Kyleena (Bayer HealthCare Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 21/09/2021.

Kyleena 19.5 mg Intrauterine Delivery System (Bayer plc). MHRA. https://products.mhra.gov.uk. Accessed 21/09/2021.

Levonorgestrel 1.5 mg Tablet (Gedeon Richter Plc.). MHRA. https://products.mhra.gov.uk. Accessed 21/09/2021.

Levosert 20 mcg/24 hours Intrauterine Delivery System (Gedeon Richter Plc.). MHRA. https://products.mhra.gov.uk. Accessed 21/09/2021.

Liletta (Allergan, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 21/09/2021.

Lydia Implanex II (Modern Choice Experts Co. Ltd.). MIMS Myanmar. http://www.mims.com/myanmar. Accessed 21/09/2021.

Mirena (Bayer HealthCare Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 21/09/2021.

Mirena 20 mcg/24 hours Intrauterine Delivery System (Bayer plc). MHRA. https://products.mhra.gov.uk. Accessed 21/09/2021.

Mirena 20 micrograms/24 hours Intrauterine Delivery System (Bayer Schering Pharma Oy). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 21/09/2021.

Revoke-1.5 Levonorgestrel Tablet (Mylan Laboratories Ltd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 21/09/2021.

Skyla (Bayer HealthCare Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 21/09/2021.

Disclaimer: This information is independently developed by MIMS based on Levonorgestrel from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2022 MIMS. All rights reserved. Powered by MIMS.com
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