Combination0.15 mg+0.03 mg

Combination is a combined oral contraceptive (COC) approved for the following use:

• Prevention of pregnancy in women who elect to use oral contraception as their method of birth control. This is the sole FDA-approved indication for this fixed-dose combination product.

Certain formulations of Combination are also guideline-supported for additional, product-label-specific uses such as reduction of heavy menstrual bleeding without an identifiable pathologic cause in women who choose oral contraception for birth control, when specifically indicated on that product's label. These secondary uses are not universal to every brand and should be confirmed against the specific product's approved labeling.

Combination does not protect against sexually transmitted infections, including HIV, and does not have any role in the treatment of an existing pregnancy.

Each tablet contains Levonorgestrel (a synthetic progestin) and Ethinyl Estradiol (a synthetic estrogen) in a fixed-dose combination. Strengths and the number of active/inactive (placebo) tablets per cycle vary by brand and regimen (e.g., monophasic, biphasic, or triphasic formulations, and 21-day, 28-day, or extended-cycle packs); refer to the specific product's pack insert for exact strengths per tablet.

Combination is a combined hormonal oral contraceptive containing a progestin (levonorgestrel) and an estrogen (ethinyl estradiol). It is supplied as blister packs of tablets taken once daily, typically in 21-active/7-placebo, 24-active/4-placebo, or continuous/extended-cycle regimens depending on the specific brand.

By supplying steady low-dose hormone levels, Combination suppresses ovulation and produces additional contraceptive effects on cervical mucus and the endometrium, making it a highly effective, reversible method of birth control when taken correctly and consistently.

Combined oral contraceptive (progestin + estrogen); Sex hormone and modulator of the genital system.

Levonorgestrel + Ethinyl Estradiol prevents pregnancy through several complementary mechanisms:

• Suppression of ovulation: The combination suppresses the hypothalamic-pituitary axis, reducing the release of gonadotropins (FSH and LH) and preventing the LH surge required for ovulation.
• Thickening of cervical mucus: The progestin component (levonorgestrel) increases the viscosity of cervical mucus, impeding sperm penetration.
• Endometrial changes: The endometrial lining becomes less receptive to implantation.

Levonorgestrel is a potent synthetic progestin with high progestational and androgenic activity, while ethinyl estradiol is a synthetic estrogen that stabilizes the endometrium and provides cycle control. Both components are well absorbed orally, undergo hepatic metabolism (levonorgestrel primarily via reduction/hydroxylation and conjugation; ethinyl estradiol via CYP3A4-mediated hydroxylation and conjugation), and are excreted mainly in urine and feces as metabolites.

Take by mouth at approximately the same time every day, with or without food. Follow the tablets in the exact order indicated on the blister pack to ensure correct hormone sequencing.

The following interactions with Combination are clinically significant and well-documented:

• Hepatic enzyme inducers (e.g., rifampin, rifabutin, certain anticonvulsants such as phenytoin, carbamazepine, barbiturates, topiramate, and the herbal product St. John's Wort): induce CYP3A4 metabolism of both hormone components, lowering their plasma levels and reducing contraceptive efficacy, which may result in breakthrough bleeding or unintended pregnancy. A backup non-hormonal contraceptive method is recommended during and for a period after concurrent use.
• HIV protease inhibitors and certain hepatitis C direct-acting antivirals (e.g., ombitasvir/paritaprevir/ritonavir-containing regimens): can alter hormone levels substantially and are associated with risk of ALT elevations; concurrent use with such hepatitis C regimens is contraindicated (see Contraindications).
• Lamotrigine: Combined oral contraceptives can significantly lower lamotrigine plasma concentrations, potentially reducing seizure control; dose adjustment of lamotrigine may be required under physician supervision.
• Other hormonal or estrogen/progestin-containing products: Concurrent use is generally not recommended due to additive hormonal effects.

This is not an exhaustive list. Patients should inform their physician of all medications, supplements, and herbal products being used before starting Combination.

Side effects of Combination vary in seriousness and frequency:

Serious (uncommon but require immediate medical attention)

• Venous thromboembolism (deep vein thrombosis, pulmonary embolism)
• Arterial thromboembolism (myocardial infarction, stroke) — see boxed warning for smoking-related risk
• Hepatic adenoma or, rarely, hepatocellular carcinoma
• Gallbladder disease
• Significant blood pressure elevation

Common

• Nausea and vomiting, especially in the first cycles
• Unscheduled (breakthrough) bleeding or spotting
• Breast tenderness or enlargement
• Headache
• Weight change and fluid retention/bloating
• Mood changes
• Decreased tolerance to contact lenses

Patients should seek prompt medical attention for symptoms such as severe leg pain/swelling, chest pain, shortness of breath, severe headache, visual disturbances, or yellowing of the skin/eyes.

Pregnancy: Combination is contraindicated in known or suspected pregnancy. There is no indication for its use during pregnancy, and it should be discontinued immediately if pregnancy is confirmed or suspected. A physician should be consulted promptly.

Lactation: Combined hormonal contraceptives may reduce the quantity and alter the composition of breast milk, and small amounts of hormone are excreted in milk. Use during breastfeeding, particularly in the early postpartum period, should only occur if clearly needed and after the potential benefits and risks have been discussed with a physician; progestin-only methods are often preferred while breastfeeding. Consult a physician before use while breastfeeding.

Boxed Warning: Cigarette smoking increases the risk of serious cardiovascular side effects (including myocardial infarction and stroke) from combined oral contraceptive use. This risk increases with age and with the number of cigarettes smoked, and is markedly increased in women over 35 years of age. Women who use Combination should be strongly advised not to smoke.

Other precautions:

• An individualized risk assessment for venous and arterial thromboembolic risk factors (e.g., obesity, immobilization, family history of clotting disorders, prolonged surgery) should be performed before and periodically during use.
• Blood pressure should be monitored periodically during use.
• Missed pills increase the risk of breakthrough ovulation and unintended pregnancy; refer to the product's specific missed-pill instructions and use backup contraception as advised.
• This product does not protect against sexually transmitted infections, including HIV.
• Use caution in women with a history of depression, gallbladder disease, or conditions that may be aggravated by fluid retention.
• See Contraindications for conditions in which this product must not be used at all.

There is no documented specific serious toxicity from acute overdose of Combination. Symptoms that may occur include nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness, and withdrawal bleeding in females. There is no specific antidote. If overdose is suspected, seek immediate medical attention or contact a poison control center; treatment should be supportive and symptomatic under medical supervision.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal impairment: No specific dose adjustment guidance is established; use with caution and physician supervision.

Hepatic impairment: Contraindicated in women with active liver disease or hepatic tumors (see Contraindications). Use with caution in women with a history of liver dysfunction.

Elderly: Not indicated in postmenopausal women; this product is intended for use in women of reproductive age.

Obesity: May be associated with reduced contraceptive efficacy and increased thromboembolic risk; individualized risk-benefit assessment recommended.

Smokers, especially over age 35: Increased cardiovascular risk — see Precautions and Contraindications.

Used continuously for as long as pregnancy prevention (or another approved indication) is desired, taken cyclically per the specific pack regimen. Duration of use should be reassessed periodically by the prescribing physician, considering age, risk factors, and evolving health status.

Combined oral contraceptive; progestin-estrogen combination; sex hormone.

Levonorgestrel (progestin) and ethinyl estradiol (estrogen) act together to inhibit gonadotropin release from the pituitary, thereby suppressing ovulation; the progestin component additionally thickens cervical mucus to impede sperm transport and produces endometrial changes that reduce the likelihood of implantation.

X

Combination is indicated only for use in women of reproductive age who have experienced menarche. Safety and efficacy have not been established in pre-menarchal females, as there is no indication for its use before menstruation begins. Use in adolescent females after menarche is generally considered similar in safety and efficacy to use in older reproductive-age women, though individualized assessment of risk factors is advised.