Introduction
Yaz is a combination oral contraceptive pill containing drospirenone (3 mg) and ethinyl estradiol (0.02 mg). It is classified as a fourth-generation progestin-containing contraceptive that offers both pregnancy prevention and additional therapeutic benefits for certain conditions.
Mechanism of Action
Yaz works through multiple mechanisms to prevent pregnancy:
- Inhibition of ovulation: Suppresses gonadotropin secretion via negative feedback on the hypothalamus
- Cervical mucus alteration: Progestin component thickens cervical mucus, creating a barrier to sperm penetration
- Endometrial changes: Alters endometrial lining to make it less receptive to implantation
Drospirenone has anti-mineralocorticoid and anti-androgenic properties, which contribute to its additional therapeutic effects.
Indications
- Contraception: Prevention of pregnancy
- Acne vulgaris: Treatment of moderate acne in women at least 14 years old who desire oral contraception, have no contraindications, and have achieved menarche
- Premenstrual Dysphoric Disorder (PMDD): Treatment of symptoms in women who choose oral contraception
Dosage and Administration
- Standard regimen: One tablet daily for 28 consecutive days (24 active tablets containing hormones followed by 4 inert tablets)
- Administration: Taken orally at approximately the same time each day
- Initiation:
- Day 1 start: Begin on first day of menstrual cycle - Sunday start: Begin on first Sunday after menstruation begins
- Special populations:
- Hepatic impairment: Contraindicated in acute or severe hepatic disease - Renal impairment: Contraindicated in renal insufficiency - Pediatrics: Not indicated before menarche
Pharmacokinetics
- Absorption: Ethinyl estradiol bioavailability ~60%; drospirenone bioavailability ~76%
- Distribution: Both components highly protein-bound (ethinyl estradiol to albumin; drospirenone to albumin)
- Metabolism: Hepatic metabolism via CYP3A4; ethinyl estradiol undergoes extensive first-pass metabolism
- Elimination:
- Ethinyl estradiol: Terminal half-life ~24 hours - Drospirenone: Terminal half-life ~31 hours - Excretion: Primarily fecal (~55-77%) and renal (~20-30%)
Contraindications
- Thrombophlebitis or thromboembolic disorders
- History of deep vein thrombosis or pulmonary embolism
- Cerebrovascular or coronary artery disease
- Known or suspected carcinoma of the breast
- Endometrial carcinoma or other estrogen-dependent neoplasia
- Undiagnosed abnormal genital bleeding
- Cholestatic jaundice of pregnancy or jaundice with prior pill use
- Hepatic tumors or active liver disease
- Known or suspected pregnancy
- Heavy smoking (≥15 cigarettes/day) in women over 35 years
- Renal impairment or adrenal insufficiency
- Hypersensitivity to any component
Warnings and Precautions
- Thromboembolic disorders: Increased risk of venous and arterial thrombosis and thromboembolism
- Cardiovascular risks: Increased risk of myocardial infarction, especially in smokers and women with other risk factors
- Hypertension: May increase blood pressure; monitor regularly
- Carbohydrate metabolism: May decrease glucose tolerance
- Lipid metabolism: May alter lipid profiles
- Liver function: May cause liver enzyme elevations and rare hepatic adenomas
- Gallbladder disease: May increase risk of gallbladder disease
- Depression: May exacerbate depression; monitor mood changes
- Vision changes: May cause corneal thickness changes affecting contact lens tolerance
Drug Interactions
- Enzyme inducers: Carbamazepine, phenytoin, rifampin, St. John's wort (may decrease efficacy)
- Antibiotics: Some broad-spectrum antibiotics may reduce contraceptive effectiveness
- HIV medications: Protease inhibitors and NNRTIs may affect contraceptive levels
- Anticoagulants: May alter warfarin metabolism
- Potassium-sparing drugs: Increased risk of hyperkalemia when combined with ACE inhibitors, ARBs, NSAIDs, or potassium supplements
- CYP3A4 inhibitors: Ketoconazole, itraconazole, clarithromycin (may increase drospirenone levels)
Adverse Effects
- Common (>10%): Headache, nausea, breast tenderness, irregular bleeding
- Less common (1-10%): Mood changes, weight changes, decreased libido, acne improvement
- Serious (<1% but significant):
- Venous thromboembolism - Arterial thromboembolism - Hepatic adenomas - Hypertension - Gallbladder disease - Hyperkalemia (particularly in patients with renal impairment or taking other medications that increase potassium)
Monitoring Parameters
- Baseline assessment: Blood pressure, BMI, personal and family history
- Regular monitoring:
- Blood pressure at least annually - Clinical evaluation for thromboembolic disorders - Serum potassium in high-risk patients - Lipid and glucose metabolism in women with risk factors - Liver function if symptoms suggest hepatic dysfunction
- Patient follow-up: Regular assessment of satisfaction and side effects every 6-12 months
Patient Education
- Take tablet at same time daily to maintain effectiveness
- Use backup contraception during first 7 days of initial cycle
- Report severe abdominal pain, chest pain, headaches, eye problems, or leg pain immediately
- Be aware of potential drug interactions, especially with antibiotics and supplements
- Understand signs and symptoms of hyperkalemia (muscle weakness, palpitations)
- Regular self-breast examinations and annual clinical breast examinations recommended
- Notify healthcare provider if scheduled for surgery or prolonged immobilization
- Understand that Yaz does not protect against HIV or other sexually transmitted infections
References
1. FDA Prescribing Information for Yaz (2023) 2. Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(4):1-66. 3. 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. 4. Practice Committee of the American Society for Reproductive Medicine. Combined hormonal contraception and the risk of venous thromboembolism: a guideline. Fertil Steril. 2017;107(1):43-51. 5. Zieman M, Hatcher RA. Managing Contraception. 16th ed. Bridging the Gap Foundation; 2020. 6. Lidegaard Ø, Nielsen LH, Skovlund CW, Skjeldestad FE, Løkkegaard E. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ. 2011;343:d6423.