Kalliga Drug Information

To achieve maximum contraceptive effectiveness, Kalliga TM must be taken exactly as directed and at intervals not exceeding 24 hours. Kalliga TM is available in the blister pack which is preset for a Sunday Start. Day 1 Start is also provided.

Day 1 Start The dosage of Kalliga TM for the initial cycle of therapy is one white to off-white “active” tablet administered daily from the 1st day through the 21st day of the menstrual cycle, counting the first day of menstrual flow as "Day 1". Tablets are taken without interruption as follows: One white to off-white “active” tablet daily for 21 days, then one green “reminder” tablet daily for 7 days. After 28 tablets have been taken, a new course is started and a white to off-white “active” tablet is taken the next day. The use of Kalliga TM for contraception may be initiated 4 weeks postpartum in women who elect not to breastfeed.

When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS: Nursing Mothers.) If the patient starts on Kalliga TM postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a white to off-white “active” tablet has been taken daily for 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

If the patient misses one white to off-white “active” tablet in Weeks 1, 2, or 3, the white to off-white “active” tablet should be taken as soon as she remembers. If the patient misses two white to off-white “active” tablets in Week 1 or Week 2, the patient should take two white to off-white “active” tablets the day she remembers and two white to off-white “active” tablets the next day; and then continue taking one white to off-white “active” tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven days after missing pills.

If the patient misses two white to off-white “active” tablets in the third week or misses three or more white to off-white “active” tablets in a row, the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven days after missing pills. Sunday Start When taking Kalliga TM, the first white to off-white “active” tablet should be taken on the first Sunday after menstruation begins.

If the period begins on Sunday, the first white to off-white “active” tablet is taken on that day. If switching directly from another oral contraceptive, the first white to off-white “active” tablet should be taken on the first Sunday after the last ACTIVE tablet of the previous product. Tablets are taken without interruption as follows: One white to off-white “active” tablet daily for 21 days, then one green “reminder” tablet daily for 7 days.

After 28 tablets have been taken, a new course is started and a white to off-white “active” tablet is taken the next day (Sunday). When initiating a Sunday start regimen, another method of contraception should be used until after the first 7 consecutive days of administration. The use of Kalliga TM for contraception may be initiated 4 weeks postpartum. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease.

See also PRECAUTIONS: Nursing Mothers.) If the patient starts on Kalliga TM postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a white to off-white “active” tablet has been taken daily for 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. If the patient misses one white to off-white active tablet in Weeks 1, 2, or 3, the white to off-white “active” tablet should be taken as soon as she remembers.

If the patient misses two white to off-white “active” tablets in Week 1 or Week 2, the patient should take two white to off-white “active” tablets the day she remembers and two white to off-white “active” tablets the next day; and then continue taking one white to off-white “active” tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven days after missing pills. If the patient misses two white to off-white “active” tablets in the third week or misses three or more white to off-white “active” tablets in a row, the patient should continue taking one white to off-white “active” tablet every day until Sunday.

On Sunday the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven days after missing pills. ADDITIONAL INSTRUCTIONS FOR ALL DOSING REGIMENS Breakthrough bleeding, spotting, and amenorrhea are frequent reasons for patients discontinuing oral contraceptives.

In breakthrough bleeding, as in all cases of irregular bleeding from the vagina, nonfunctional causes should be borne in mind. In undiagnosed persistent or recurrent abnormal bleeding from the vagina, adequate diagnostic measures are indicated to rule out pregnancy or malignancy. If pathology has been excluded, time or a change to another formulation may solve the problem.

Changing to an oral contraceptive with a higher estrogen content, while potentially useful in minimizing menstrual irregularity, should be done only if necessary since this may increase the risk of thromboembolic disease. Use of oral contraceptives in the event of a missed menstrual period: 1. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period and oral contraceptive use should be discontinued if pregnancy is confirmed. 2. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out.

An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS ). Thrombophlebitis and venous thrombosis with or without embolism Arterial thromboembolism Pulmonary embolism Myocardial infarction Cerebral hemorrhage Cerebral thrombosis Hypertension Gallbladder disease Hepatic adenomas or benign liver tumors There is evidence of an association between the following conditions and the use of oral contraceptives: Mesenteric thrombosis Retinal thrombosis The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: Nausea Vomiting Gastrointestinal symptoms (such as abdominal cramps and bloating) Breakthrough bleeding Spotting Change in menstrual flow Amenorrhea Temporary infertility after discontinuation of treatment Edema Melasma which may persist Breast changes: tenderness, enlargement, secretion Change in weight (increase or decrease) Change in cervical erosion and secretion Diminution in lactation when given immediately postpartum Cholestatic jaundice Migraine Allergic reaction, including rash, urticaria, and angioedema Mental depression Reduced tolerance to carbohydrates Vaginal candidiasis Change in corneal curvature (steepening) Intolerance to contact lenses The following adverse reactions have been reported in users of oral contraceptives and a causal association has been neither confirmed nor refuted: Pre-menstrual syndrome Cataracts Changes in appetite Cystitis-like syndrome Headache Nervousness Dizziness Hirsutism Loss of scalp hair Erythema multiforme Erythema nodosum Hemorrhagic eruption Vaginitis Porphyria Impaired renal function Hemolytic uremic syndrome Acne Changes in libido Colitis Budd-Chiari Syndrome Post Marketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 to 1.12 (Figure 2). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2). One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19 to 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8 to 10 years of COC use.

Figure 2: Risk of Breast Cancer with Combined Oral Contraceptive Use RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females with current or past COC use; “never COC use” are females that never used COCs. Figure 2: Risk of Breast Cancer with Combined Oral Contraceptive Use

8. Drug Interactions Consult the labeling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Effects of Other Drugs on Combined Hormonal Contraceptives Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of CHCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St.

John’s wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with CHCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.

Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20 to 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 plasma hormone concentrations. Human immunodeficiency virus (HIV)/ Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease or increase ) /HCV protease inhibitors (decrease ) or with non-nucleoside reverse transcriptase inhibitors (decrease or increase ). Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation: Do not co-administer Kalliga TM with HCV drug combinations containing ombitasvir/ paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see section 5 in WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ). Colesevelam: Colesevelam, a bile acid sequestrant, given together with a combination oral hormonal contraceptive, has been shown to significantly decrease the AUC of EE. A drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart.

Effects of Combined Hormonal Contraceptives on Other Drugs COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs 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.

This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid-binding globulin increases with use of COCs.

11. Pregnancy Pregnancy Category X. See CONTRAINDICATIONS and WARNINGS.

13. Pediatric Use Safety and efficacy of Kalliga TM tablets have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated.

Kalliga TM is contraindicated in females who are known to have or develop the following conditions: Thrombophlebitis or thromboembolic disorders A past history of deep vein thrombophlebitis or thromboembolic disorders Known thrombophilic conditions Cerebral vascular or coronary artery disease (current or history) Valvular heart disease with complications Persistent blood pressure values of ≥ 160 mm Hg systolic or ≥ 100 mg Hg diastolic 102 Diabetes with vascular involvement Headaches with focal neurological symptoms Major surgery with prolonged immobilization Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia Undiagnosed abnormal genital bleeding Cholestatic jaundice of pregnancy or jaundice with prior pill use Acute or chronic hepatocellular disease with abnormal liver function Hepatic adenomas or carcinomas Known or suspected pregnancy Hypersensitivity to any component of this product Are receiving Hepatitis C drug combinations containing ombitasivir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see section 5 in WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ).

Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females. NON-CONTRACEPTIVE HEALTH BENEFITS The following non-contraceptive health benefits related to the use of oral contraceptives are supported by epidemiological studies which largely utilized oral contraceptive formulations containing estrogen doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol. 73 to 78 Effects on menses: increased menstrual cycle regularity decreased blood loss and decreased incidence of iron deficiency anemia decreased incidence of dysmenorrhea Effects related to inhibition of ovulation: decreased incidence of functional ovarian cysts decreased incidence of ectopic pregnancies Effects from long-term use: decreased incidence of fibroadenomas and fibrocystic disease of the breast decreased incidence of acute pelvic inflammatory disease decreased incidence of endometrial cancer decreased incidence of ovarian cancer