YAZ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for YAZ (YAZ).
Combination of ethinyl estradiol and drospirenone; suppresses gonadotropins (FSH and LH) inhibiting ovulation, and increases cervical mucus viscosity to impede sperm penetration. Drospirenone has antimineralocorticoid and antiandrogenic activity.
| Metabolism | Ethinyl estradiol is metabolized primarily by CYP3A4; drospirenone is metabolized via CYP3A4 and also undergoes reduction and sulfation. Both undergo enterohepatic recirculation. |
| Excretion | Approximately 50% of drospirenone is excreted renally (metabolites, with <10% unchanged), and 50% via feces (biliary) after hepatic conjugation. Ethinyl estradiol is primarily excreted renally (60%) and fecally (40%) as glucuronide and sulfate conjugates. |
| Half-life | Terminal elimination half-life of drospirenone is 31.2-32.5 hours; ethinyl estradiol: 13-27 hours. Steady-state achieved after 10 days of daily dosing. Clinically, once-daily dosing maintains stable concentrations. |
| Protein binding | Drospirenone: 95-97% bound to albumin (not SHBG). Ethinyl estradiol: 98-99% bound to albumin, with a small fraction bound to SHBG. |
| Volume of Distribution | Drospirenone: Vd/F approximately 4 L/kg (range 2.7-4.6 L/kg). Ethinyl estradiol: Vd/F approximately 2-4 L/kg. Large Vd indicates extensive tissue distribution (e.g., reproductive tissues, fat). |
| Bioavailability | Oral bioavailability: Drospirenone ~76% (high, due to minimal first-pass metabolism). Ethinyl estradiol ~40-50% (reduced by first-pass intestinal/hepatic conjugation). |
| Onset of Action | Oral administration: Contraceptive effect achieved after 7 consecutive days of dosing (requires backup contraception for first 7 days). Acne improvement generally seen after 3-6 cycles. |
| Duration of Action | 24-hour dosing interval for contraceptive efficacy. Acne and premenstrual dysphoric disorder effects require continuous daily administration; symptom relief persists with adherence. |
| Brand Substitutes | CRINA 0.02 MG/3 MG TABLET, Jazz 0.02mg/3mg Tablet, Drosmac 20mcg Tablet, Dafadros-LS Tablet, Dronis 20 Tablet |
One tablet (0.02 mg ethinyl estradiol and 3 mg drospirenone) orally once daily for 24 days, followed by 2 days of placebo.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with creatinine clearance <30 mL/min. No dose adjustment required for mild to moderate impairment (CrCl 30-80 mL/min), but monitor serum potassium. |
| Liver impairment | Contraindicated in Child-Pugh class C. Use with caution in mild to moderate hepatic impairment (Child-Pugh A or B) due to potential fluid and electrolyte disturbances. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults (one tablet daily). |
| Geriatric use | Not indicated for use after menopause. No specific geriatric dose adjustments; consider increased risk of thromboembolism and cardiovascular events. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for YAZ (YAZ).
| Breastfeeding | Small amounts of ethinyl estradiol and drospirenone excreted into breast milk; M/P ratio not established. Use caution in early postpartum period; may reduce milk production. |
| Teratogenic Risk | First trimester: No increased risk of major malformations based on large cohort studies. Second/third trimesters: Potential for adverse effects from progestins and estrogens, but data limited due to contraindication use. |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use YAZ.
| Serious Effects |
["Hypersensitivity to any component","Active or history of thromboembolic disorders (e.g., DVT, PE)","Cerebrovascular or coronary artery disease","Known or suspected breast cancer or other estrogen-sensitive neoplasia","Undiagnosed abnormal uterine bleeding","Liver tumors (benign or malignant) or active liver disease","Pregnancy","Renal insufficiency (CrCl <60 mL/min)","Adrenal insufficiency","Hyperkalemia with concurrent use of potassium-sparing medications"]
| Precautions | ["Thromboembolic disorders including VTE and arterial thrombosis","Hyperkalemia due to drospirenone's antimineralocorticoid effect (caution in renal/hepatic impairment and with concomitant potassium-sparing drugs)","Liver disease","Gallbladder disease","Carbohydrate and lipid effects","Hereditary angioedema","Chloasma","Depression"] |
Loading safety data…
| Not indicated for fetal monitoring as drug is contraindicated in pregnancy. For accidental exposure, no specific monitoring required. |
| Fertility Effects | Reversible inhibition of ovulation; no permanent fertility impairment. Rapid return to fertility after discontinuation. |