What are the dosing schedule, indications, contraindications, precautions, adverse effects, drug interactions, and counseling points for Vestura (drospirenone 3 mg/ethinyl estradiol 0.02 mg) combined oral contraceptive?

Vestura (Drospirenone 3 mg/Ethinyl Estradiol 0.02 mg) Clinical Information

Indications

Vestura is FDA-approved for three specific indications: contraception, treatment of moderate acne vulgaris in women ≥14 years who desire oral contraception, and treatment of premenstrual dysphoric disorder (PMDD) in women who choose oral contraception. 1, 2, 3

• Contraceptive efficacy is excellent with a Pearl Index of 0.57 (overall) and 0.09 (method failure) 4
• For acne treatment, patients must be at least 14 years old and have achieved menarche 1, 5
• PMDD indication requires that the patient desires contraception as the primary goal 1, 3

Dosing Schedule

Take one tablet daily at the same time every day, following the order on the blister pack: 24 active brown tablets containing drospirenone 3 mg/ethinyl estradiol 0.02 mg, followed by 4 white inert tablets. 1

• This 24/4 regimen provides a shortened hormone-free interval compared to traditional 21/7 regimens 2, 6
• The extended active pill phase (24 days vs 21 days) takes advantage of drospirenone's >30-hour half-life 2
• Tablets must be taken in the exact order directed on the package 1

Missed Dose Management

• Take the missed pill as soon as remembered 5
• If more than one pill is missed, take only the most recently missed pill and continue with the regular schedule 5
• Use backup contraception (condoms or abstinence) for 7 days if pills are missed in the first week 5
• Consider emergency contraception if 2+ pills are missed in week one or if pills were missed late in the previous cycle 5

Absolute Contraindications

Vestura is absolutely contraindicated in women with renal impairment, adrenal insufficiency, high risk of arterial or venous thrombotic disease, undiagnosed abnormal uterine bleeding, breast cancer, liver tumors or disease, and co-administration with hepatitis C drugs containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir. 1

Specific High-Risk Conditions (WHO Category 4 - Do Not Use):

• Age ≥35 years AND smoking any amount 1, 5, 7
• History of deep vein thrombosis or pulmonary embolism 1, 5, 7
• Severe uncontrolled hypertension (systolic ≥160 mmHg or diastolic ≥100 mmHg) 5
• Migraine with focal neurologic symptoms at any age, or migraine without aura if ≥35 years 5, 7
• Active or history of ischemic heart disease, cerebrovascular accident, or complicated valvular heart disease 5, 7
• Active viral hepatitis, severe decompensated cirrhosis, or hepatic tumors (benign or malignant) 5
• Diabetes with end-organ damage (nephropathy, retinopathy, neuropathy, vascular disease) 5
• Current breast cancer or other estrogen/progestin-sensitive malignancies 5, 7
• Major surgery with prolonged immobilization 5

Critical Precautions and Warnings

Venous Thromboembolism Risk

Drospirenone-containing COCs carry a 50-80% higher VTE risk compared to levonorgestrel-containing pills, with an incidence of approximately 10 per 10,000 woman-years versus 6 per 10,000 for standard low-dose COCs. 7, 8

• Background VTE rate in non-users is 2 per 10,000 person-years 7
• The elevated risk is specifically attributed to the drospirenone component 7
• Discontinue immediately if signs of thrombosis occur: leg pain/swelling, sudden chest pain, shortness of breath, sudden severe headache, visual changes, or weakness 7, 1
• Stop at least 4 weeks before major surgery and do not restart until 2 weeks after 1
• Start no earlier than 4 weeks postpartum in non-breastfeeding women 1

Hyperkalemia Risk

Drospirenone has antimineralocorticoid activity similar to spironolactone; check serum potassium during the first treatment cycle in women taking medications that may increase potassium (ACE inhibitors, ARBs, potassium-sparing diuretics, NSAIDs, heparin). 1, 5

• Do not use in patients with renal impairment, adrenal insufficiency, or conditions predisposing to hyperkalemia 1
• Large retrospective studies found no increased hyperkalemia risk in healthy women, even when combined with spironolactone 7
• Routine potassium monitoring is not required in healthy women without risk factors 7

Cardiovascular Effects

Drospirenone's antimineralocorticoid properties typically decrease blood pressure by 1-4 mmHg systolic, unlike other progestins that may increase blood pressure. 8, 7, 9

• In women with baseline systolic BP ≥130 mmHg, drospirenone 4 mg decreases systolic BP by approximately 8 mmHg 8, 7
• One study showed mean systolic BP decreased from 109.2 to 103.4 mmHg after 12 months 7
• Absolute attributable risk for major cardiovascular events (MI, stroke) is approximately 2 per 10,000 person-years 7
• Monitor blood pressure at baseline and follow-up visits 5, 1

Hepatic Considerations

• Discontinue immediately if jaundice develops 1
• Contraindicated with active liver disease or hepatic tumors 1
• Do not co-administer with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir 1

Adverse Effects

Common (≥2% incidence):

Most common side effects resolve within the first 2-3 cycles and rarely necessitate discontinuation. 7

Contraception/Acne Trials:

• Headache/migraine: 6.7% 1
• Menstrual irregularities (breakthrough bleeding/spotting): 4.7% 1
• Nausea/vomiting: 4.2% 1
• Breast pain/tenderness: 4.0% 1
• Mood changes: 2.2% 1

PMDD Trials:

• Menstrual irregularities: 24.9% 1, 7
• Nausea: 15.8% 1
• Headache: 13.0% 1
• Breast tenderness: 10.5% 1
• Fatigue: 4.2% 1
• Irritability: 2.8% 1
• Decreased libido: 2.8% 1
• Weight increase: 2.5% 1
• Affect lability: 2.1% 1

Breakthrough Bleeding Management:

Breakthrough bleeding occurs most frequently during the first 2-3 cycles and typically resolves spontaneously without intervention. 7

• Verify adherence to the dosing schedule, as missed pills are the primary cause 7
• Reassure patients that resolution within 2-3 cycles is expected 7
• If bleeding persists beyond 3 cycles, evaluate for pregnancy, STIs, cervical pathology, or drug interactions 10

Drug Interactions

Medications That Decrease Contraceptive Effectiveness:

Enzyme inducers (CYP3A4) may decrease effectiveness or increase breakthrough bleeding; counsel patients to use backup contraception when these are prescribed. 1, 5

• Anticonvulsants (carbamazepine, phenytoin, topiramate, barbiturates) 5, 1
• Rifampin and griseofulvin (only antibiotics proven to reduce COC effectiveness) 5, 1
• HIV protease inhibitors, nevirapine 5, 1
• St. John's wort 5, 1
• Modafinil, bosentan 5, 1

Important: Tetracycline-class antibiotics do NOT reduce contraceptive effectiveness and can be safely used concomitantly. 5

Medications Requiring Monitoring:

• ACE inhibitors, ARBs, potassium-sparing diuretics, NSAIDs, heparin (hyperkalemia risk) 1, 5
• Anticoagulants (may alter coagulation parameters) 5

Baseline and Ongoing Monitoring

Before Prescribing:

Obtain thorough medical history and blood pressure measurement; pelvic examination and Papanicolaou smear are no longer mandatory before initiating COCs. 5

• Assess pregnancy status 5
• Blood pressure measurement 5, 1
• Screen for contraindications (thrombotic risk factors, liver disease, migraines, smoking status if ≥35 years) 5
• For sexually active patients, STI screening is recommended but not required to prescribe 5

Follow-Up Monitoring:

• Routine follow-up visit 1-3 months after initiation to address adverse effects or adherence issues 5
• Blood pressure monitoring at follow-up visits 5, 7
• Serum potassium during first cycle if patient takes medications that increase potassium 1
• Assess bleeding patterns at 3-month intervals 10

Patient Counseling Points

Efficacy and Timing:

Start on the same day as the visit ("quick start") in healthy, nonpregnant adolescents; use backup contraception (condoms or abstinence) for the first 7 days. 5

• Acne improvement takes time; statistically significant reduction typically occurs by cycle 3, but patients may not appreciate improvement for several months 5
• Condoms should be used at all times for STI protection regardless of contraceptive method 5

Adherence Strategies:

• Take at the same time every day using reminders (cell phone alarms, support from family/partner) 5, 1
• Prescribe up to 1 year supply at a time to improve continuation 5
• Seven consecutive hormone pills are needed to prevent ovulation 5

Managing Common Side Effects:

• Nausea: Take with food or at bedtime; typically resolves within first few cycles 7
• Breakthrough bleeding: Reassure that resolution within 2-3 cycles is expected; verify adherence 7
• Weight gain concerns: Unlike other COCs, drospirenone formulations may cause slight weight decrease due to antimineralocorticoid effects 4, 6

Emergency Discontinuation Criteria:

Seek immediate medical attention for signs of stroke (sudden severe headache, visual changes, weakness), myocardial infarction (chest pain, jaw pain, diaphoresis), or new-onset migraine with aura. 7

• Leg pain/swelling, sudden shortness of breath, or chest pain (possible VTE) 7, 1
• Jaundice or severe abdominal pain (possible hepatic complications) 1

Noncontraceptive Benefits

COCs provide multiple health benefits beyond contraception, including regulation of menstrual cycles, reduction of menorrhagia and associated anemia, and decreased risk of benign ovarian tumors. 5

• 29% reduction in gynecologic malignancies with net decrease in overall cancer risk 7
• Significant risk reductions for colon, uterine, and ovarian cancers 7
• May be used for extended/continuous cycles to treat dysmenorrhea, endometriosis, heavy menstrual bleeding, and conditions exacerbated cyclically (migraine without aura, epilepsy) 5

Special Populations

Adolescents:

• FDA-approved for females ≥14 years who have achieved menarche 5, 1
• Smoking is not a contraindication in teenagers and adults <35 years 5
• Safety and efficacy established in this population 5

Lactation:

Can reduce milk production in breastfeeding females; World Health Organization advises avoiding if possible. 1, 5

• Start no earlier than 4 weeks postpartum 1
• Consider progestin-only methods as preferred option during breastfeeding 1