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. |
| Molecular Weight | Ethinyl estradiol: 296.4 Da; Drospirenone: 366.5 Da |
| Action Class | Combined oral contraceptive (COC) with antiandrogenic and antimineralocorticoid activity |
| 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 | Contraindicated due to increased risk of congenital defects (e.g., cardiovascular, limb deficiencies) and potential for fetal harm. Use of estrogens/progestins during first trimester is associated with VACTERL anomalies. |
| 2nd trimester | Contraindicated. Risk of serious adverse effects including jaundice, cholestasis, and potential for fetal harm; avoid use during pregnancy. |
| 3rd trimester | Contraindicated. Use may induce premature closure of ductus arteriosus due to progestin component; also associated with neonatal hepatic toxicity. |
Clinical note
Comprehensive clinical and safety monograph for YAZ (YAZ).
| Placental transfer | Both ethinyl estradiol and drospirenone cross the placenta. Estrogens are known to cross readily; progestins also achieve significant fetal concentrations. |
| Breastfeeding | Small amounts of ethinyl estradiol and drospirenone are excreted in breast milk. Use during breastfeeding may reduce milk production and composition. Not recommended for nursing mothers until weaning is complete. |
■ 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 | Venous thromboembolism (VTE), Arterial thromboembolism (e.g., stroke, myocardial infarction), Hypertension, Liver tumors (benign and malignant), Gallbladder disease, Hyperkalemia (especially in patients with renal impairment or on potassium-sparing drugs) |
PregnancyCurrent or history of venous thromboembolismCerebrovascular or coronary artery diseaseHypertension (uncontrolled or with vascular disease)Diabetes with vascular involvementMigraine with focal neurological symptomsBreast cancer or other estrogen-dependent neoplasiaHepatic adenoma or liver disease (active or history)Renal impairment (creatinine clearance <30 mL/min)Adrenal insufficiencyUndiagnosed abnormal genital bleeding
| 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…
| Lactation Rating | L3 (Moderately Safe) – limited data, potential adverse effects on lactation. |
| 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 | 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. |
| Food/Dietary |
| Grapefruit juice may increase ethinyl estradiol exposure. No other significant food interactions. Avoid St. John's wort as it reduces contraceptive efficacy. |
| Clinical Pearls | YAZ (drospirenone/ethinyl estradiol) is a combined oral contraceptive with anti-mineralocorticoid activity; monitor potassium in patients with renal/hepatic impairment or on potassium-sparing diuretics. Increased risk of venous thromboembolism (VTE) compared to levonorgestrel-containing pills. Contraindicated in migraine with aura, hypertension (>160/100), and smoking >35 years old. |
| Patient Advice | Take daily at same time; missed dose instructions depend on timing. · Report leg swelling, chest pain, severe headache, or vision changes. · Avoid grapefruit juice due to potential interaction. · Smoking increases risk of serious cardiovascular side effects. |