Levonorgestrel (Systemic)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Aftera: 1.5 mg

Aftera: 1.5 mg [contains corn starch]

EContra EZ: 1.5 mg

EContra One-Step: 1.5 mg [contains corn starch]

Fallback Solo: 1.5 mg [DSC]

My Choice: 1.5 mg [contains corn starch]

My Way: 1.5 mg [contains corn starch]

New Day: 1.5 mg [contains fd&c blue #1 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #6 aluminum lake]

Next Choice One Dose: 1.5 mg [DSC] [contains fd&c yellow #6 (sunset yellow)]

Opcicon One-Step: 1.5 mg

Plan B One-Step: 1.5 mg

Plan B One-Step: 1.5 mg [contains corn starch]

React: 1.5 mg [contains corn starch]

Take Action: 1.5 mg

Take Action: 1.5 mg [contains corn starch]

Generic: 1.5 mg

Pharmacology

Mechanism of Action

Pregnancy may be prevented through several mechanisms: Thickening of cervical mucus, which inhibits sperm passage through the uterus and sperm survival; inhibition of ovulation, from a negative feedback mechanism on the hypothalamus, leading to reduced secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH); altering the endometrium, which may affect implantation. Levonorgestrel is not effective once the implantation process has begun.

Pharmacokinetics/Pharmacodynamics

Absorption

Oral: Rapid and complete

Distribution

V_d: ~1.8 L/kg

Metabolism

Hepatic via CYP3A4; forms inactive metabolites

Excretion

Urine (45%); feces (32%)

Time to Peak

Oral: ~2 hours (Fotherby 1995)

Half-Life Elimination

Oral: ~27 hours

Protein Binding

Highly bound to albumin (~50%) and sex hormone-binding globulin (~47%) (Fotherby 1995)

Use in Specific Populations

Special Populations: Race

There was a higher increase in the rate of pregnancy in Chinese women using Next Choice or Plan B One-Step; the reason for this apparent increase is unknown.

Use: Labeled Indications

Emergency contraception: Prevention of pregnancy following unprotected intercourse or possible contraceptive failure

Contraindications

OTC labeling: When used for self-medication, do not use if you are already pregnant; do not use for regular birth control

Canadian labeling: Known or suspected pregnancy; hypersensitivity to levonorgestrel or any component of the formulation; undiagnosed vaginal bleeding

It is not known if the same contraindications associated with long-term progestin-only contraceptives apply to the levonorgestrel emergency contraception dose regimens.

Dosage and Administration

Dosing: Adult

Emergency contraception: Females: Oral: May be used at any time during menstrual cycle:

Two-dose regimen: One 0.75 mg tablet as soon as possible within 72 hours of unprotected sexual intercourse; a second 0.75 mg tablet should be taken 12 hours after the first dose.

Single-dose regimen: One 1.5 mg tablet as soon as possible within 72 hours of unprotected sexual intercourse.

Note: Treatment for emergency contraception should begin as soon as possible; however, treatment is still moderately effective if used within 5 days and should be made available to women up to 5 days after unprotected or inadequately protected intercourse. When using the two-dose emergency contraceptive regimen, the second dose is equally effective if taken 12 to 24 hours after the first (ACOG, 2015).

Dosing: Geriatric

Not indicated for use in postmenopausal women.

Dosing: Pediatric

Emergency contraception: Females: Refer to adult dosing. Not for use prior to menarche.

Administration

Oral: Consider repeating the dose if vomiting occurs within 2 hours.

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Acitretin: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Given the potential for progestin-only preparations to fail to prevent pregnancy during acitretin therapy, such products should not be relied upon. Alternative, nonhormonal forms of contraception must be employed during acitretin therapy. Consider therapy modification

Anticoagulants: Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Aprepitant: May decrease the serum concentration of Progestins (Contraceptive). Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Consider therapy modification

Artemether: May decrease the serum concentration of Progestins (Contraceptive). Management: Consider the use of an alternative (i.e., non-hormonal) means of contraception in all women of childbearing potential who are using artemether. Consider therapy modification

Atazanavir: May increase the serum concentration of Progestins (Contraceptive). However, atazanavir may lead to decreased ethinyl estradiol concentrations and decreased effectiveness of oral contraceptive products. Management: Consider an alternative or additional method of contraception, particularly with combined estrogen/progestin products. Depot medroxyprogesterone acetate may be used without a need for additional contraception. Consider therapy modification

Barbiturates: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification

Bexarotene (Systemic): May decrease the serum concentration of Progestins (Contraceptive). Management: Women of childbearing potential receiving bexarotene should use two reliable forms of contraception (including at least one nonhormonal form). Consider therapy modification

Bile Acid Sequestrants: May decrease the serum concentration of Progestins (Contraceptive). Management: Administer oral progestin-containing contraceptives at least 1 to 4 hours prior to or 4 to 6 hours after administration of a bile acid sequestrant. Consider therapy modification

Bosentan: May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative (i.e., non-hormonal) means of contraception for all women of childbearing potential who are using bosentan, and do not rely on hormonal contraceptives alone. Consider therapy modification

Brigatinib: May decrease the serum concentration of Progestins (Contraceptive). Management: Females of childbearing potential should use an alternative, non-hormonal contraceptive during brigatinib therapy and for at least 4 months after the final brigatinib dose. Consider therapy modification

C1 inhibitors: Progestins may enhance the thrombogenic effect of C1 inhibitors. Monitor therapy

CarBAMazepine: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification

Carfilzomib: May enhance the thrombogenic effect of Progestins (Contraceptive). Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib. Consider therapy modification

Cenobamate: May decrease the serum concentration of Hormonal Contraceptives. Management: Women should use additional or alternative non-hormonal birth control while taking cenobamate. Consider therapy modification

Cladribine: May diminish the therapeutic effect of Hormonal Contraceptives. Management: Women using systemically acting hormonal contraceptives should add a barrier method during cladribine dosing and for at least 4 weeks after the last dose in each treatment course. Consider therapy modification

CloBAZam: May decrease the serum concentration of Progestins (Contraceptive). Consider therapy modification

Cobicistat: May increase the serum concentration of Progestins (Contraceptive). Management: Consider an alternative, nonhormone-based contraceptive in patients receiving cobicistat-containing products. Drospirenone is specifically contraindicated with atazanavir and cobicistat. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dabrafenib: May decrease the serum concentration of Progestins (Contraceptive). Management: Females of reproductive potential should use an alternative, highly effective, non-hormonal means of contraception during and at least 2 weeks (dabrafenib alone) or 4 months (dabrafenib + trametinib) after discontinuation of dabrafenib treatment. Consider therapy modification

Darunavir: May decrease the serum concentration of Progestins (Contraceptive). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate may be used without a need for additional contraception. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Efavirenz: May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification

Elexacaftor, Tezacaftor, and Ivacaftor: Hormonal Contraceptives may enhance the adverse/toxic effect of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the risk for rash may be increased. Monitor therapy

Encorafenib: May decrease the serum concentration of Progestins (Contraceptive). Avoid combination

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Eslicarbazepine: May decrease the serum concentration of Progestins (Contraceptive). Management: Alternative, non-hormonal means of birth control should be considered for women of child-bearing potential. Consider therapy modification

Exenatide: May decrease the serum concentration of Progestins (Oral Contraceptive). Management: Administer oral contraceptives at least one hour prior to exenatide. Consider therapy modification

Felbamate: May decrease the serum concentration of Progestins (Contraceptive). Management: Contraceptive failure is possible. Use of an alternative, nonhormonal method of contraception is recommended. Consider therapy modification

Flibanserin: Progestins (Contraceptive) may increase the serum concentration of Flibanserin. Monitor therapy

Fosamprenavir: Progestins (Contraceptive) may decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Progestins (Contraceptive). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate may be used without a need for additional contraception. Consider therapy modification

Fosaprepitant: May decrease the serum concentration of Progestins (Contraceptive). The active metabolite aprepitant is likely responsible for this effect. Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Consider therapy modification

Fosphenytoin: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification

Griseofulvin: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Avoid combination

Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the adverse/toxic effect of Progestins. Monitor therapy

Ivosidenib: May decrease the serum concentration of Progestins (Contraceptive). Management: Consider alternative methods of contraception (ie, non-hormonal) in patients receiving ivosidenib. Consider therapy modification

Ixazomib: May decrease the serum concentration of Progestins (Contraceptive). More specifically, use of ixazomib with dexamethasone may decrease the serum concentrations of contraceptive progestins. Management: Patients of childbearing potential should use a nonhormonal barrier contraceptive during and 90 days following ixazomib treatment. Avoid combination

LamoTRIgine: May decrease the serum concentration of Progestins (Contraceptive). Monitor therapy

Lesinurad: May decrease the serum concentration of Progestins (Contraceptive). Management: Use of an additional, nonhormonal contraceptive is recommended in patients being treated with lesinurad who desire effective contraception. Consider therapy modification

Lixisenatide: May decrease the serum concentration of Progestins (Contraceptive). Management: Administer oral contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Consider therapy modification

Lopinavir: May decrease the serum concentration of Progestins (Contraceptive). Lopinavir may increase the serum concentration of Progestins (Contraceptive). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate and etonogestrel implants may be used without a need for additional contraception. Consider therapy modification

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

Lumacaftor and Ivacaftor: May decrease the serum concentration of Hormonal Contraceptives. Management: Do not rely on hormone-based contraceptives with concurrent use of lumacaftor/ivacaftor; an alternative, non-hormonal, method of contraception should be used if this combination is required. Consider therapy modification

Metreleptin: May decrease the serum concentration of Progestins (Contraceptive). Metreleptin may increase the serum concentration of Progestins (Contraceptive). Monitor therapy

MiFEPRIStone: May diminish the therapeutic effect of Progestins (Contraceptive). MiFEPRIStone may increase the serum concentration of Progestins (Contraceptive). Management: Women of childbearing potential should use an effective, nonhormonal means of contraception during and 4 weeks following mifepristone treatment. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Mycophenolate: May decrease the serum concentration of Progestins (Contraceptive). Management: Use of an additional or alternative (nonhormonal) method of contraception should be considered. Consider therapy modification

Nelfinavir: May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification

OXcarbazepine: May decrease the serum concentration of Progestins (Contraceptive). Management: Contraceptive failure is possible. Use of an additional or alternative, nonhormonal method of contraception is recommended. Consider therapy modification

Perampanel: May decrease the serum concentration of Progestins (Contraceptive). Management: Patients should use an alternative, nonhormonal-based form of contraception both during the concurrent use of perampanel and for 1 month after discontinuing perampanel. Consider therapy modification

Phenytoin: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification

Pitolisant: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with pitolisant and for at least 21 days after discontinuation of pitolisant treatment. Consider therapy modification

Pomalidomide: Progestins may enhance the thrombogenic effect of Pomalidomide. Management: Canadian pomalidomide labeling recommends caution with use of hormone replacement therapy and states that hormonal contraceptives are not recommended. US pomalidomide labeling does not contain these specific recommendations. Consider therapy modification

Primidone: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification

Retinoic Acid Derivatives: May diminish the therapeutic effect of Progestins (Contraceptive). Retinoic Acid Derivatives may decrease the serum concentration of Progestins (Contraceptive). Management: Two forms of effective contraception should be used in patients receiving retinoic acid derivatives. Microdosed progesterone-only preparations (ie, minipills that do not contain estrogen) are considered an inadequate method of contraception. Exceptions: Adapalene; Alitretinoin (Topical); Bexarotene (Topical); Tretinoin (Topical). Consider therapy modification

Rifamycin Derivatives: May decrease the serum concentration of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification

Saquinavir: May decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Selegiline: Progestins (Contraceptive) may increase the serum concentration of Selegiline. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

St John's Wort: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Consider using a product other than St John's wort. Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification

Sugammadex: May decrease the serum concentration of Progestins (Contraceptive). Management: Patients receiving any hormonal contraceptive (oral or non-oral) should use an additional, nonhormonal contraceptive method during and for 7 days following sugammadex treatment. Consider therapy modification

Tazemetostat: May decrease the serum concentration of Hormonal Contraceptives. Management: Women of reproductive potential should use a non-hormonal contraceptive method during treatment with tazemetostat and for 6 months after. Men with female partners should use contraception during treatment and for 3 months after. Consider therapy modification

Tetrahydrocannabinol and Cannabidiol: May decrease the serum concentration of Hormonal Contraceptives. Management: Women using hormonal contraceptives should consider adding a barrier contraceptive due to the potential for tetrahydrocannabinol and cannabidiol to decrease concentrations and effectiveness of hormonal contraceptives. Consider therapy modification

Thalidomide: Progestins (Contraceptive) may enhance the thrombogenic effect of Thalidomide. Monitor therapy

Tipranavir: May increase the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Topiramate: May decrease the serum concentration of Progestins (Contraceptive). Management: Caution patients that this combination may be associated with reduced contraceptive effectiveness. Consider adding an additional (non-hormonal) contraceptive method. Consider therapy modification

Tranexamic Acid: Progestins (Contraceptive) may enhance the thrombogenic effect of Tranexamic Acid. Avoid combination

Triazolam: Hormonal Contraceptives may increase the serum concentration of Triazolam. Monitor therapy

Ulipristal: Progestins may diminish the therapeutic effect of Ulipristal. Ulipristal may diminish the therapeutic effect of Progestins. Management: Ulipristal for uterine fibroids (Canadian indication): avoid progestins within 12 days of stopping ulipristal; as emergency contraceptive (U.S. indication): avoid progestins within 5 days of stopping ulipristal. Avoid combination

Vitamin K Antagonists (eg, warfarin): Progestins (Contraceptive) may diminish the anticoagulant effect of Vitamin K Antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. Management: When possible, concomitant hormonal contraceptives and coumarin derivatives should be avoided in order to eliminate the risk of thromboembolic disorders. Consider using an alternative, nonhormonal contraceptive. Consider therapy modification

Voriconazole: May increase the serum concentration of Progestins (Contraceptive). Progestins (Contraceptive) may increase the serum concentration of Voriconazole. Monitor therapy

Adverse Reactions

Frequency not always defined.

>10%:

Central nervous system: Fatigue (13%)

Endocrine & metabolic: Hypermenorrhea (31%)

Gastrointestinal: Nausea (14%), abdominal pain (13%)

1% to 10%:

Central nervous system: Dizziness (10%), headache (10%)

Endocrine & metabolic: Suppressed menstruation (5%)

Genitourinary: Breast tenderness (8%)

Postmarketing and/or case reports: Dysmenorrhea, irregular menses, oligomenorrhea, pelvic pain, vomiting

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding irregularities: Spotting may occur following use; the possibility of pregnancy should be considered if menstruation is delayed for >7 days of the expected menstrual period (ACOG 2015).
• Ectopic pregnancy: A history of ectopic pregnancy is not a contraindication for use as an emergency contraceptive (Curtis 2016b). The possibility of ectopic pregnancy should be considered in patients with lower abdominal pain, especially in association with missed periods or vaginal bleeding in women with prior amenorrhea (ACOG 2015).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Not intended to be used for routine contraception and is not effective in terminating an existing pregnancy (ACOG 2015).
• Body weight: Use as an emergency contraceptive may be less effective in women with a BMI ≥30 kg/m² compared with women with a BMI ≤25 kg/m²; however, no safety concerns exist and the advantages of use generally outweigh potential risks (Curtis 2016b). The CDC recommends that obese women can generally use any type of contraceptive but suggests that levonorgestrel may be less efficacious in obese women compared to ulipristal acetate (Curtis 2016a).
• Fertility: Barrier contraception is recommended immediately following emergency contraception (ACOG 2015; Curtis 2016a).
• HIV infection protection: Emergency contraceptives do not protect against HIV infection or other sexually transmitted diseases (Curtis 2016a).

Monitoring Parameters

Evaluate for pregnancy, spontaneous abortion or ectopic pregnancy if normal (expected) menstrual period is delayed for ≥1 week following emergency contraception, or if lower abdominal pain or persistent irregular bleeding develops (ACOG 2015).

Pregnancy

Pregnancy Considerations

Not for use in women confirmed to be pregnant. Adverse effects to the mother or fetus have not been observed following inadvertent exposure during pregnancy (Curtis 2016b).

Levonorgestrel may be used as an emergency contraceptive in women with contraindications to conventional hormonal contraceptive agents (eg, cardiovascular disease, migraines, liver disease) (ACOG 2015; Curtis 2016b).

A rapid return of fertility is expected following use for emergency contraception; routine contraceptive measures should be initiated or continued following use to ensure ongoing prevention of pregnancy. Any regular contraceptive method can be started immediately after levonorgestrel; however, a barrier method (or abstinence from sexual intercourse) is also needed for 7 days (ACOG 2015; Curtis 2016a).

Patient Education

What is this drug used for?

• It is used to lower the chance of pregnancy after unprotected sex.

Frequently reported side effects of this drug

• Headache
• Nausea
• Breast soreness
• Dizziness
• Menstrual changes
• Loss of strength and energy

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe abdominal pain
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.