Chemical formula: C₂₁H₂₈O₂ Molecular mass: 312.446 g/mol PubChem compound: 13109
Levonorgestrel interacts in the following cases:
Levonorgestrel is not recommended in patients with severe hepatic dysfunction.
Drugs suspected of having similar capacity to plasma levels of levonorgestrel include barbiturates (including primidone), phenytoin, carbamazepine, herbal medicines containing Hypericum perforatum (St. John’s Wort), rifampicin, ritonavir, rifabutin, griseofulvin.
Levonorgestrel increases the possibility of cycle disturbances which can sometimes lead to earlier or later ovulation date. These changes can result in modified fertility date, however, there are no fertility data in the long term.
The use of a levonorgestrel-releasing intrauterine system does not alter the course of future fertility. Upon removal of the intrauterine system, women return to their normal fertility.
Medicines containing levonorgestrel may increase the risk of cyclosporin toxicity due to possible inhibition of cyclosporin metabolism.
The metabolism of levonorgestrel is enhanced by concomitant use of liver enzyme inducers, mainly CYP3A4 enzyme inducers. Concomitant administration of efavirenz has been found to reduce plasma levels of levonorgestrel (AUC) by around 50%.
Levonorgestrel should not be given to pregnant women. It will not interrupt a pregnancy. In the case of continued pregnancy, limited epidemiological data indicate no adverse effects on the fetus but there are no clinical data on the potential consequences if doses greater than 1.5 mg of levonorgestrel are taken.
The insertion of intrauterine delivery system containing levonorgestrel in pregnant women is contraindicated.
If a woman becomes pregnant while using intrauterine delivery system ectopic pregnancy should be excluded and timely removal of the system is recommended since any intrauterine contraceptive left in situ may increase the risk of abortion and preterm labour. Removal of intrauterine delivery system or probing of the uterus may also result in spontaneous abortion. If the woman wishes to continue the pregnancy and the system cannot be withdrawn, she should be informed about the risks and the possible consequences of premature birth to the infant. The course of such a pregnancy should be closely monitored. The woman should be instructed to report all symptoms that suggest complications of the pregnancy, like cramping abdominal pain with fever.
Because of the intrauterine administration and the local exposure to levonorgestrel, the possible occurrence of virilizing effects in a female fetus should be taken into consideration. Clinical experience of the outcomes of pregnancies under intrauterine delivery system treatment is limited due to the high contraceptive efficacy. Women should be informed that, to date, there is no evidence of birth defects caused by a levonorgestrel-releasing intrauterine system use in cases where pregnancy has continued to term with the levonorgestrel-IUS in place.
Levonorgestrel is secreted into breast milk. Potential exposure of an infant to levonorgestrel can be reduced if the breast-feeding woman takes the tablet immediately after feeding and avoids nursing at least 8 hours following levonorgestrel administration.
In general, there appears to be no deleterious effect on infant growth or development when using any progestogen-only method after 6 weeks postpartum. A levonorgestrel-releasing intrauterine system does not affect the quantity or quality of breast milk. Small amounts of progestogen (about 0.1% of the levonorgestrel dose) pass into the breast milk in nursing mothers.
Levonorgestrel increases the possibility of cycle disturbances which can sometimes lead to earlier or later ovulation date resulting in modified fertility date. Although there are no fertility data in the long term, after treatment with levonorgestrel a rapid return to fertility is expected and therefore, regular contraception should be continued or initiated as soon as possible after levonorgestrel EC use.
The use of a levonorgestrel-releasing intrauterine system does not alter the course of future fertility. Upon removal of the intrauterine system, women return to their normal fertility.
No studies on the effect on the ability to drive and use machines have been performed.
Intrauterine delivery system has no known influence on the ability to drive or use machines.
The most commonly reported undesirable effect was nausea.
| System Organ Class | Frequency of adverse reactions | |
|---|---|---|
| Very common (≥1/10) | Common (≥1/100 to <1/10) | |
| Nervous system disorders | Headache | Dizziness |
| Gastrointestinal disorders | Nausea Abdominal pain lower | Diarrhoea Vomiting |
| Reproductive system and breast disorders | Bleeding not related to menses* | Delay of menses more than 7 days** Menstruation irregular Breast tenderness |
| General disorders and administration site conditions | Fatigue | |
* Bleeding patterns may be temporarily disturbed, but most women will have their next menstrual period within 5-7 days of the expected time.
** If the next menstrual period is more than 5 days overdue, pregnancy should be excluded.
From Post-marketing surveillance additionally, the following adverse events have been reported:
Very rare (<1/10,000): abdominal pain
Very rare (<1/10,000): rash, urticaria, pruritus,
Very rare (<1/10,000): pelvic pain, dysmenorrhoea
Very rare (<1/10,000): face oedema
The majority of women experience changes in menstrual bleeding pattern after insertion of levonorgestrel IUD. Over time, the frequency of amenorrhoea and infrequent bleeding increases, and the frequency of prolonged, irregular and frequent bleeding decreases. The following bleeding patterns were observed in clinical trials:
Bleeding patterns reported with levonorgestrel IUD in clinical trials:
| Levonorgestrel IUD | First 90 days | Second 90 days | End of year 1 | End of year 3 |
|---|---|---|---|---|
| Amenorrhea | <1% | 3% | 6% | 12% |
| Infrequent bleeding | 8% | 19% | 20% | 22% |
| Frequent bleeding | 31% | 12% | 8% | 4% |
| Irregular bleeding* | 39% | 25% | 18% | 15% |
| Prolonged bleeding* | 55% | 14% | 6% | 2% |
* Subjects with irregular bleeding and prolonged bleeding may also be included in one of the other categories (excluding amenorrhea)
The frequencies of Adverse Drug Reactions (ADRs) reported with levonorgestrel IUD are summarised in the table below. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000).
| System Organ Class | Very Common | Common | Uncommon |
|---|---|---|---|
| Psychiatric disorders | Depressed mood/Depression Decreased libido | ||
| Nervous system disorders | Headache | Migraine | |
| Vascular disorders | Dizziness | ||
| Gastrointestinal disorders | Abdominal/pelvic pain | Nausea | |
| Skin and subcutaneous tissue disorders | Acne/Seborrhoea | Alopecia | Hirsutism |
| Reproductive system and breast disorders | |||
| Bleeding changes including increased and decreased menstrual bleeding, spotting, infrequent bleeding and amenorrhoea Ovarian cyst* Vulvovaginitis | Upper genital tract infection Dysmenorrhea Breast pain/discomfort Device expulsion (complete and partial) Genital discharge | Uterine perforation** | |
| Investigations | Increased weight |
* In clinical trials ovarian cysts had to be reported as AEs if they were abnormal, non-functional cysts and/or had a diameter >3 cm on ultrasound examination.
** This frequency is based on a large prospective comparative non-interventional cohort study with women using another LNG-IUS and copper IUDs which showed that breastfeeding at the time of insertion and insertion up to 36 weeks after giving birth are independent risk factors for perforation. In clinical trials with levonorgestrel that excluded breastfeeding women the frequency of perforation was “rare”.
With the use of LNG-IUS, cases of hypersensitivity including rash, urticaria and angioedema have been reported.
If a woman becomes pregnant while using levonorgestrel IUD, the relative likelihood of this pregnancy being ectopic is increased.
The removal threads may be felt by the partner during intercourse.
The following ADRs have been reported in connection with the insertion or removal procedure of levonorgestrel IUD: Procedural pain, procedural bleeding, insertion-related vasovagal reaction with dizziness or syncope. The procedure may precipitate a seizure in an epileptic patient.
Cases of sepsis (including group A streptococcal sepsis) have been reported following IUD insertion.
The safety profile of levonorgestrel IUD observed in a study of 304 adolescents was consistent with that in the adult population.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
