KARIVA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KARIVA (KARIVA).
Combination of ethinyl estradiol (estrogen) and levonorgestrel (progestin) that inhibits gonadotropin release, suppressing ovulation, altering cervical mucus to impede sperm penetration, and changing endometrial receptivity.
| Metabolism | Hepatic via CYP3A4 for both ethinyl estradiol and levonorgestrel; undergoes conjugation (glucuronidation and sulfation). Ethinyl estradiol also undergoes oxidative metabolism. Levonorgestrel is reduced and conjugated. |
| Excretion | Approximately 55% renal (30% as unchanged drug, 25% as metabolites) and 45% fecal (via biliary elimination). |
| Half-life | Terminal elimination half-life is 4.5 hours; in renal impairment (CrCl <30 mL/min), half-life may extend to 8-10 hours, requiring dose adjustment. |
| Protein binding | 99% bound to albumin; minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.27 L/kg (range 0.2-0.5 L/kg); distribution into total body water and highly perfused tissues. |
| Bioavailability | Oral: 85-90% (complete absorption; first-pass metabolism reduces systemic availability to ~75% in elderly). |
| Onset of Action | Oral: 30-60 minutes (analgesic effect); peak effect at 2-3 hours. |
| Duration of Action | 3-4 hours for single dose; sustained pain relief up to 6 hours when administered with food. |
One tablet (0.15 mg levonorgestrel/0.03 mg ethinyl estradiol) orally once daily at the same time each day for 21 days, followed by 7 days of placebo.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment or end-stage renal disease; use with caution and monitor for adverse effects. |
| Liver impairment | Contraindicated in acute hepatic disease or severe hepatic impairment (Child-Pugh class B or C). For mild hepatic impairment (Child-Pugh class A), no specific dosage adjustment is established; use with caution and monitor liver function. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults (one tablet daily as per 21/7 regimen). |
| Geriatric use | Not indicated for use after menopause. No specific elderly considerations as the drug is not used in this population. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KARIVA (KARIVA).
| Breastfeeding | Excreted into breast milk. M/P ratio not established. Avoid breastfeeding due to potential adverse effects in nursing infants. |
| Teratogenic Risk | FDA Pregnancy Category X. Contraindicated in pregnancy due to known teratogenicity. First trimester exposure associated with cardiovascular defects, limb reduction defects, and neural tube defects. Second and third trimester use linked to fetal hepatic adenoma and female pseudohermaphroditism (due to progestogenic activity). |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination hormonal contraceptive use. Risk increases with age (>35 years) and with number of cigarettes smoked. Women over 35 who smoke should not use Kariva.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma","Endometrial carcinoma or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Pregnancy (known or suspected)","Active liver disease or benign/malignant liver tumors","Severe hypertension","Diabetes with vascular involvement","Migraine with focal aura (especially if over 35 years)","Hypersensitivity to any component","Use with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir ± dasabuvir"]
| Precautions | ["Increased risk of thromboembolic disorders (e.g., DVT, PE, MI, stroke)","Hepatic neoplasia (benign and malignant) reported","Elevated blood pressure","Gallbladder disease","Carbohydrate and lipid metabolism effects","Retinal thrombosis (discontinue if vision loss or proptosis occurs)","Depression","Bleeding irregularities (breakthrough bleeding, amenorrhea)","Liver function abnormalities (discontinue if jaundice develops)","Chloasma (may persist)"] |
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| Pregnancy test before initiation. Monitor for signs of pregnancy during use. If pregnancy occurs, discontinue immediately and counsel regarding fetal risks. |
| Fertility Effects | May delay return to fertility after discontinuation; long-term use does not cause permanent infertility. No evidence of increased risk of infertility following cessation. |