(eg, cyclosporine, prednisolone, theophylline, tizanidine, voriconazole) and increase their plasma concentrations CHCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam, and lamotrigine; significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation Estrogen component of CHCs may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin; dose of replacement thyroid hormone or cortisol therapy may need to be increased Pregnancy Contraindicated in pregnancy because there is no reason to use combined hormonal contraceptives (CHCs) in pregnancy (see Contraindications) Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy Lactation Combined hormonal contraceptives (CHCs) and/or metabolites are present in human milk and in breastfed infants CHCs, including levonorgestrel oral/ethinylestradiol/ferrous bisglycinate, can reduce milk production in breastfeeding females; reduction can occur at any time but is less likely to occur once breastfeeding Advise nursing female to use other methods of contraception until she discontinues breastfeedingPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Ethinyl Estradiol (EE): Reduces luteinizing hormone-releasing hormone release from hypothalamus; reduces gonadotropin release from pituitary; increases synthesis of DNA, RNA, and various proteins in target tissues Levonorgestrel: Synthetic progestin; ovulation is inhibited from a negative feedback mechanism on hypothalamus, leading to reduced secretion of follicle-stimulating hormone and luteinizing hormone and LH Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation Absorption AUC: 41.7 ng·hr/mL (levonorgestrel); 1167 pg·hr/mL (EE) Peak plasma concentration: 4.4 ng/mL (levonorgestrel); 115 pg/mL (EE) Bioavailability after first-pass metabolism: ~100% (levonorgestrel); 38-48% (EE) Peak plasma time, single dose of two levonorgestrel and EE: 1 hr (levonorgestrel); 1.5 hr (EE) Distribution Protein bound (albumin): ~97% (EE) Metabolism Levonorgestrel Most important metabolic pathway occurs in the reduction of the delta, 4-3-oxo group and hydroxylation at positions 2α, 1β, and 16β, followed by conjugation Most of the metabolites that circulate in the blood are sulfates of 3α, 5β-tetrahydro-levonorgestrel, while excretion occurs predominantly in the form of glucuronides Some of the parent levonorgestrel also circulates as 17β-sulfate Ethinyl estradiol CYP3A4 in the liver is responsible for the 2-hydroxylation that is the major oxidative reaction 2-Hydroxy metabolite is further transformed by methylation and glucuronidation prior to urinary and fecal excretion CYP3A levels vary widely among individuals and can explain the variation in rates of EE 2-hydroxylation EE is excreted in the urine and feces as glucuronide and sulfate conjugates, and undergoes enterohepatic circulation Elimination Half-life: 34 hr (single dose levonorgestrel); 17 hr (EE) Excretion: 40-68% (urine); 16-48% (feces) Oral Administration Starting CHCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start) Tablet color Active tablets: Orange (Day 1-21) Placebo tablet: Blue (Day 22-28) Day 1 start Administer 1 tablet qDay at the same time each day Take 1 orange tablet on the first day of period; take subsequent orange tablets once daily for a total of 21 days Take 1 blue tablet daily for 7 days Begin each subsequent pack on the same day of the week as the first cycle pack (eg, on the day after taking the last blue placebo tablet) Sunday start Administer 1 tablet qDay at the same time each day Take first orange tablet on the first Sunday after the onset of menses Owing to the potential risk of becoming pregnant, use additional nonhormonal contraception (eg, condoms or spermicide) for the first 7 days of the patient’s first cycle pack Take subsequent orange tablets once daily for a total of 21 days Take 1 blue tablet daily for the following 7 days Begin each subsequent pack on the same day of the week as the first cycle pack Missed dose If one orange tablet is missed in Weeks 1, 2, or 3: Take orange tablet as soon as possible; continue taking 1 tablet qDay until the pack is finished If two orange tablets are missed in Week 1 or 2: Take 2 missed tablets as soon as possible and the next 2 orange tablets the next day; continue taking 1 tablet qDay until the pack is finished; additional nonhormonal contraception (eg, condoms or spermicide) should be used as backup if the patient has sex within 7 days after missing tablets If two orange tablets are missed in Week 3 or ≥3 orange tablets are missed in a row in Weeks 1, 2, or 3 Day 1 start: Throw out remaining pack and start a new pack that same day Sunday start: Continue taking 1 tablet qDay until Sunday, then throw out the remaining pack and start a new pack that same day; additional nonhormonal contraception (such as condoms or spermicide) should be used as backup if the patient has sex within 7 days after missing tablets Gastrointestinal disturbances In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken If vomiting or diarrhea occurs within 3-4 hr after taking an orange tablet, handle this as a missed dose Storage Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) Protect from light Keep out of the reach of children BRAND FORM. UNIT PRICE PILL IMAGE Balcoltra oral- 0.1 mg-0.02 mg (21)/36.5 mg(7) tabletBalcoltra oral- 0.1 mg-0.02 mg (21)/36.5 mg(7) tabletCopyright © 2010 First DataBank, Inc.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. QL Quantity Limits Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered. ST Step Therapy Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription. OR Other Restrictions Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription. Plans Select State: Alabama Alaska Arizona Arkansas California Colorado Connecticut Delaware District of Columbia Florida Georgia Hawaii Idaho Illinois Indiana Iowa Kansas Kentucky Louisiana Maine Maryland Massachusetts Michigan Minnesota Mississippi Missouri Montana Nebraska Nevada New Hampshire New Jersey New Mexico New York North Carolina North Dakota Ohio Oklahoma Oregon Pennsylvania Puerto Rico Rhode Island South Carolina South Dakota Tennessee Texas Utah Vermont Virginia Washington West Virginia Wisconsin Wyoming Done Non-Medicare Plans Medicare Plans Done CLOSE Additional Offers CLOSE Email to Patient From: To: The recipient will receive more details and instructions to access this offer. By clicking send, you acknowledge that you have permission to email the recipient with this information. Send CLOSE Email Forms to Patient From: To: The recipient will receive more details and instructions to access this offer. By clicking send, you acknowledge that you have permission to email the recipient with this information. Send