Kariva - Drug Monograph

Introduction

Kariva is a combination oral contraceptive pill containing desogestrel (a progestin) and ethinyl estradiol (an estrogen). It is FDA-approved for pregnancy prevention and is also used for menstrual cycle regulation and treatment of acne in women seeking oral contraception.

Mechanism of Action

Kariva works through multiple mechanisms to prevent pregnancy:

• Suppression of gonadotropins (FSH and LH) via negative feedback on the hypothalamus and pituitary
• Inhibition of ovulation through prevention of the LH surge
• Thickening of cervical mucus, creating a barrier to sperm penetration
• Alteration of endometrial lining, reducing implantation potential

Indications

• Prevention of pregnancy
• Treatment of moderate acne vulgaris in females at least 15 years old who desire oral contraception, have achieved menarche, and are unresponsive to topical anti-acne medications
• Regulation of menstrual cycles

Dosage and Administration

• Standard regimen: One tablet daily for 28 days (21 active tablets containing 0.15 mg desogestrel/0.02 mg ethinyl estradiol, followed by 7 inert tablets)
• Administration: Taken orally at approximately the same time each day
• Missed dose guidelines: Specific instructions based on number of tablets missed and cycle week
• Special populations: Not recommended in women over 35 years who smoke or have specific cardiovascular risk factors

Pharmacokinetics

• Absorption: Rapidly absorbed from GI tract; desogestrel is converted to active metabolite etonogestrel
• Distribution: Ethinyl estradiol is highly protein-bound; desogestrel and metabolites bind to sex hormone binding globulin and albumin
• Metabolism: Hepatic metabolism via cytochrome P450 system (primarily CYP3A4)
• Elimination: Renal and fecal excretion; elimination half-life of ethinyl estradiol is approximately 24 hours, while etonogestrel has a half-life of approximately 30 hours

Contraindications

• Current or history of thrombophlebitis or thromboembolic disorders
• Known or suspected estrogen-dependent neoplasia
• Undiagnosed abnormal genital bleeding
• Known or suspected pregnancy
• Active liver disease or history of benign or malignant liver tumors
• Known or suspected breast cancer
• Hypersensitivity to any component of Kariva
• Heavy smoking (≥15 cigarettes/day) and age over 35 years

Warnings and Precautions

• Cardiovascular risks: Increased risk of thrombotic and thromboembolic events, including myocardial infarction, stroke, and venous thromboembolism
• Hypertension: Regular blood pressure monitoring recommended
• Lipid metabolism: May adversely affect lipid profiles
• Carbohydrate metabolism: May decrease glucose tolerance
• Liver function: May cause liver enzyme abnormalities and rare hepatic adenomas
• Gallbladder disease: May worsen existing gallbladder disease or precipitate new onset
• Depression: May exacerbate depression; monitor for mood changes
• Vision changes: May cause corneal curvature changes and contact lens intolerance

Drug Interactions

• Enzyme inducers: Carbamazepine, phenytoin, rifampin, St. John's wort may decrease efficacy
• Antibiotics: Broad-spectrum antibiotics may reduce enterohepatic recirculation
• HIV medications: Protease inhibitors and NNRTIs may affect contraceptive levels
• Anticoagulants: Potential alteration of anticoagulant effect
• Cyclosporine: Increased levels possible
• Lamotrigine: Possible decreased lamotrigine levels

Adverse Effects

• Nausea
• Headache
• Breast tenderness
• Breakthrough bleeding
• Weight changes

• Venous thromboembolism
• Arterial thromboembolism
• Hepatic adenomas
• Hypertension
• Gallbladder disease
• Mood changes and depression

Monitoring Parameters

• Blood pressure at baseline and periodically
• BMI and weight
• Lipid profile in high-risk patients
• Liver function tests if symptoms suggest hepatic dysfunction
• Signs and symptoms of thromboembolism
• Mood changes and depressive symptoms
• Headache pattern changes
• Visual changes

Patient Education

• Take at the same time daily to maintain effectiveness
• Use backup contraception during first 7 days of initial use
• Report severe abdominal pain, chest pain, shortness of breath, severe headaches, visual changes, or leg pain immediately
• Inform healthcare providers of Kariva use before any surgical procedures
• Understand that Kariva does not protect against HIV or other sexually transmitted infections
• Recognize potential drug interactions with other medications
• Report missed periods or suspected pregnancy
• Understand the increased risk of cardiovascular events with smoking

References

1. FDA Prescribing Information: Kariva (desogestrel and ethinyl estradiol tablets) 2. Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(3):1-103. 3. Practice Bulletin No. 152: Emergency Contraception. Obstet Gynecol. 2015;126(3):e1-e11. 4. Gallo MF, Nanda K, Grimes DA, Lopez LM, Schulz KF. 20 μg versus >20 μg estrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev. 2013;(8):CD003989. 5. Stegeman BH, de Bastos M, Rosendaal FR, et al. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ. 2013;347:f5298.