annovera

One ANNOVERA is inserted in the vagina. The vaginal system must remain in place continuously for 3 weeks (21 days) followed by a 1-week (7-day) vaginal system-free interval. One vaginal system provides contraception for thirteen 28-day cycles (1 year). ( 2 ) 2.1 How to Use ANNOVERA Instruct patients that ANNOVERA should be used as directed [see How to Start ANNOVERA (2.2) ] . One ANNOVERA should be placed in the vagina. For maximum contraceptive effectiveness, ANNOVERA is to remain in the vagina continuously for 21 days (3 complete weeks). It is removed for a 1-week dose-free interval, and during this time a withdrawal bleed usually occurs. The removed vaginal system should be cleaned with mild soap and warm water, patted dry with a clean cloth towel or paper towel, and placed in its case during the 1-week dose- free interval. At the end of the dose-free interval, the vaginal system should be cleaned prior to being placed back in the vagina for another 21 continuous days (3 complete weeks). This pattern of ANNOVERA use made up of 3-weeks in and 1-week out is a cycle of use; one ANNOVERA vaginal system will provide contraception for 13 cycles. With clean hands, the user can choose an insertion position that is comfortable, such as lying down, squatting, or standing. The sides of the vaginal system are pressed together for insertion into the vagina. When properly inserted, the…

The following adverse reactions are described elsewhere in other sections of the labeling: Serious cardiovascular events and stroke [see Boxed Warning and Warnings and Precautions (5.1) ] Vascular events [see Warnings and Precautions (5.1) ] Liver disease [see Warnings and Precautions (5.2) ] The most common adverse reactions (>5%) are headache/migraine, nausea/vomiting, vulvovaginal mycotic infection/candidiasis, abdominal pain lower/upper, dysmenorrhea, vaginal discharge, urinary tract infection, breast tenderness/pain/discomfort, bleeding irregularities including metrorrhagia, diarrhea, genital pruritus. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice. The clinical trials that evaluated the safety of ANNOVERA were obtained from three 13- cycle trials. One trial was conducted entirely in the U.S. (15 sites), and the other two were global studies that included 5 U.S. sites and 7 international sites (Australia, Brazil, Chile, Dominican Republic, Finland, Hungary, Sweden). All three trials were open…

ANNOVERA is contraindicated in females who are known to have or develop the following conditions: A high risk of arterial or venous thrombotic diseases. Examples include females who are known to: - Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1) ]. - Have current or history of deep vein thrombosis or pulmonary embolism [see Warnings and Precautions (5.1) ] . - Have cerebrovascular disease [see Warnings and Precautions (5.1) ]. - Have coronary artery disease [see Warnings and Precautions (5.1) ]. - Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions (5.1) ] . - Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1) ] . - Have uncontrolled hypertension or hypertension with vascular disease [see Warnings and Precautions (5.4) ] . - Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or vascular disease, or other end-organ damage, or diabetes mellitus of >20 years duration [see Warnings and Precautions (5.5) , (5.7) ] . - Have headaches with focal neurological symptoms, migraine headaches with aura, or are over age 35 with any migraine headaches [see Warnings and Precautions (5.8) ] . Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.11) ] . Liver tumors, acute hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6) ]. Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.9) ] . Hypersensitivity to any of the components of ANNOVERA. Hypersensitivity reactions reported include: throat constriction, facial edema, urticaria, hives, and wheezing [see Adverse Reactions (6.1) ] . Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for alanine transaminase (ALT) elevations [see Warnings and Precautions (5.3) ]. A high risk of arterial or venous thrombotic diseases ( 4 ) Breast cancer ( 4 ) Liver tumors, acute hepatitis, or severe (decompensated) cirrhosis ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Hypersensitivity to any of the components of ANNOVERA ( 4 ) Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir ( 4 )

There have been no reports of serious ill effects from overdose of CHCs. Overdosage may cause withdrawal bleeding in females and nausea. In case of suspected overdose, all ANNOVERA vaginal systems should be removed and symptomatic treatment given.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

The sections below provide information on substances for which data on drug interactions with CHCs are available. There is little information available about the clinical effect of most drug interactions that may affect ANNOVERA. However, based on the known pharmacokinetic effects of these drugs, clinical strategies to minimize any potential adverse effect on contraceptive effectiveness or safety are suggested. Consult the approved product labeling of all concurrently used drugs to obtain further information about interactions with ANNOVERA or the potential for metabolic enzyme or transporter system alterations. Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of ANNOVERA or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with ANNOVERA. ( 7.1 ) 7.1 Effects of Other Drugs on Combined Hormonal Contraceptives Substances Decreasing the Systemic Exposure of CHCs and Potentially Diminishing the Efficacy of ANNOVERA : Table 3 includes substances that demonstrated an important drug interaction with CHCs. Table 3: Significant Drug Interactions Involving Substances That Decrease Systemic Exposure of CHCs Metabolic Enzyme Inducers Clinical effect Concomitant use of CHCs with metabolic enzyme inducers may decrease the systemic concentrations of the estrogen and/or progestin component of CHCs [see Clinical Pharmacology (12.3) ] . Decreased exposure of the estrogen and/or progestin component of CHCs may potentially diminish the effectiveness of CHCs and may lead to contraceptive failure or an increase in breakthrough bleeding. Prevention or management Counsel females to use an alternative method of contraception or a back-up method when enzyme inducers are used with CHCs. Continue back-up contraception for 28 days after discontinuing the enzyme inducer to maintain contraceptive reliability. Examples Aprepitant, barbiturates, bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, rifabutin, rufinamide, topiramate, products containing St. John's wort Induction potency of St. John's wort may vary widely based on preparation. , and certain protease inhibitors (see separate section on protease inhibitors below). Substances Increasing the Systemic Exposure of CHCs and Potentially Increasing Exposure to Estrogen and/or Progestin in ANNOVERA : Co- administration of atorvastatin or rosuvastatin and certain CHCs containing EE increase systemic exposure of EE by approximately 20–25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of ANNOVERA. Human Immunodeficiency Virus (HIV)/ Hepatitis C Virus (HCV) Protease Inhibitors and Non-nucleoside Reverse Transcriptase Inhibitors : Significant decreases in systemic exposure of estrogen and/or progestin have been noted when CHCs are co-administered with some HIV protease inhibitors (eg, nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some HCV protease inhibitors (eg, boceprevir and telaprevir), and some non-nucleoside reverse transcriptase inhibitors (eg, nevirapine). In contrast, significant increases in systemic exposure of estrogen and/or progestin have been noted when CHCs are co-administered with certain other HIV protease inhibitors (eg, indinavir and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (eg, etravirine). 7.2 Effects of Combined Hormonal Contraceptives on Other Drugs Table 4 provides significant drug interaction information for drugs co-administered with CHCs. Table 4: Significant Drug Interaction Information for Drugs Co-Administered with CHCs Lamotrigine Clinical effect Concomitant use of CHCs with lamotrigine may significantly decrease systemic exposure of lamotrigine due to induction of lamotrigine glucuronidation. Prevention or management Dose adjustment for lamotrigine may be necessary. Consult the approved product labeling for lamotrigine. Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy Clinical effect Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin [see Warnings and Precautions (5.12) ] . Prevention or management The dose of replacement thyroid hormone or cortisol therapy may need to be increased. Consult the approved product labeling for the therapy in use [see Warnings and Precautions (5.12) ] . Other Drugs Clinical effect Concomitant use of CHCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. Concomitant use with ethinyl estradiol-containing CHCs may increase systemic exposure of other drugs (eg, cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole). Prevention or management The dosage of drugs that can be affected by this interaction may need to be increased or decreased. Consult the approved product labeling for the concomitantly used drug. 7.3 Use of Vaginal Products with ANNOVERA In a drug-drug interaction study with ANNOVERA and the concurrent use of three different formulations of vaginal miconazole, the use of water-based vaginal miconazole cream resulted in no change in exposure to EE or SA from the vaginal system. However, the use of either the 1- day or the 3-day oil-based miconazole suppository was associated with an overall increase in exposure up to 67% for EE and 32% for SA. Considering the potential long-term effect on vaginal system performance, concurrent use of oil-based vaginal suppositories should not occur with ANNOVERA use. If there is a need to treat a vaginal condition, water-based vaginal cream or oral therapy may be used concurrently with the vaginal system [see Clinical Pharmacology (12.3) ] . Lubricants: Water-based vaginal lubricants have no effect on ANNOVERA; however, oil- based (including silicone-based) vaginal lubricants will alter the vaginal system and/or exposure to EE and SA and should not be used. ANNOVERA use is compatible with male condoms made with natural rubber latex, polyisoprene, and polyurethane. The effect of tampon use on the systemic exposure of SA and EE from ANNOVERA has not been studied. 7.4 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer ANNOVERA with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Contraindications (4) and Warnings and Precautions (5.3) ] . 7.5 Interference with Laboratory Tests The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.