DROSPIRENONE TAB
Clinical Criteria Summary
Document 283: MON Drosperinone SLYND Mar2022
Indication(s)
- Prevention of pregnancy in females of reproductive potential
- Progestin-only contraceptive pill (POP)
Contraindications
- Renal impairment
- Adrenal insufficiency
- Liver tumors (benign or malignant) or hepatic impairment
- Presence or history of cervical cancer or progestin-sensitive cancers
- Undiagnosed abnormal uterine bleeding
- Conditions predisposing to hyperkalemia
Warnings & Precautions
- Hyperkalemia: Monitor serum potassium in patients receiving concomitant daily/chronic medications that increase potassium, strong CYP3A4 inhibitors, or who develop conditions increasing hyperkalemia risk
- Thromboembolic disorders: Consider increased risk in postpartum period and history of thromboembolism; consider discontinuation during prolonged immobilization due to surgery or illness
- Bone loss: Unclear if causes clinically significant bone loss; FDA requires post-marketing study
- Uterine bleeding irregularities/amenorrhea: Evaluate for pregnancy or malignancy if bleeding persists or occurs after previously regular cycles; consider pregnancy if scheduled bleeding does not occur
- Liver disease: Discontinue if jaundice or symptoms of liver function disturbances develop
- Risk of hyperglycemia in patients with diabetes
- Ectopic pregnancy
- Cervical cancer
- Depression
Dosing & Administration
- 24 active tablets followed by 4 inert tablets daily (24-day on, 4-day off regimen)
- Take one tablet daily at about the same time each day to maintain a 24-hour interval
- 24-hour pill forgiveness for missed or late doses
- If more than one tablet is missed, use backup contraception for 7 days
Patient Selection & Clinical Context
- Desirable for breastfeeding women and those with contraindications or desire to avoid estrogen-containing products (e.g., history of venous thromboembolism, migraine with aura, smokers >35 years)
- May be considered in patients desiring a daily POP but unable to use or intolerant of norethindrone POP
- Patient examples include: tolerance issues on norethindrone (unscheduled bleeding/spotting); contraindication to estrogen with poor candidacy for progestin shot/implant/IUD or history of failure/intolerance to norethindrone; indication for ovulation suppression (e.g., recurrent ovarian cysts) with contraindications/intolerance to other options; difficulties adhering to the 3-hour window for norethindrone despite reasonable efforts
Efficacy Considerations
- Prevents pregnancy primarily by suppressing ovulation
- Pearl Index: 4.0 (95% CI: 2.3–6.4) pregnancies per 100 woman-years in non-breastfeeding women ≤35 years
- Subgroup analyses of higher BMI did not suggest greater pregnancy risk
- Effectiveness may be less than combination products with real-world use due to strict dosing schedule, though DRSP POP offers a 24-hour forgiveness window
Safety & Adverse Reactions
- Most common adverse reactions (≥1%): Acne, metrorrhagia, headache, breast pain, weight increased, dysmenorrhea, nausea, vaginal hemorrhage, libido decreased, breast tenderness, menstruation irregular
- Discontinuations due to adverse events: 11% in pooled data; most frequent: acne, metrorrhagia, irregular menstruation, increased weight, vaginal hemorrhage, decreased libido
- Hyperkalemia: Most common serious adverse event (0.2%); typically isolated, mild, and returns to normal despite continued treatment
- Unscheduled bleeding/spotting: Decreased over time but reported in 40% of patients in cycle 13; amenorrhea reported by nearly three-quarters by end of study
Drug Interactions
- CYP3A4 inducers (e.g., phenytoin, carbamazepine, barbiturates) may decrease DRSP concentrations, potentially reducing contraceptive effectiveness and increasing breakthrough bleeding
- CYP3A4 inhibitors (e.g., ketoconazole) may increase DRSP systemic exposure
- Caution with drugs that increase serum potassium (ACE inhibitors, angiotensin-II receptor antagonists, potassium-sparing diuretics, potassium supplements, heparin, aldosterone antagonists, NSAIDs)
Special Populations
- Pregnancy: Discontinue if pregnancy occurs; epidemiologic studies/meta-analysis show no increased risk of birth defects from early inadvertent use
- Lactation: Negligible amounts excreted in breast milk; no adverse effects on milk production or infant health/development found
- Renal impairment: Mild (CrCL 50-80 ml/min) has comparable DRSP concentrations to CrCL >80 ml/min; increased by 37% in CrCL 30-49 ml/min
- Hepatic impairment: DRSP exposure increased 3-fold in moderate hepatic impairment
Document 338: Contraceptive Agents Hormonal on VA National Formulary
Criteria for Monophasic Oral Contraceptive Pills
- 20 mcg Ethinyl Estradiol (EE) Combinations: Drospirenone 3 mg; Levonorgestrel 0.1 mg; Norethindrone 1 mg. Regimen: 21 active pills; 7 inert pills.
- 30 mcg EE Combinations: Desogestrel 0.15 mg; Drospirenone 3 mg; Levonorgestrel 0.15 mg; Norethindrone 1.5 mg; Norethindrone 1 mg; Norgestimate 0.25 mg. Regimen: 21 active pills; 7 inert pills.
- 35 mcg EE Combinations: Levonorgestrel 0.05/0.075/0.125 mg; Norethindrone 0.5/0.75/1 mg; Norgestimate 0.18/0.215/0.25 mg. Regimen: 21 active pills; 7 inert pills.
Criteria for Triphasic Oral Contraceptive Pills
- Contains varying doses of levonorgestrel, norethindrone, or norgestimate across the cycle.
- Regimen: 21 active pills; 7 inert pills.
Criteria for Extended Cycle Oral Contraceptive Pills
- Levonorgestrel 0.15 mg with 30 mcg EE.
- Regimen: 84 active pills; 7 inert pills.
Criteria for Progestin-Only Oral Contraceptive Pills
- Norethindrone 0.35 mg.
- Regimen: Active pill daily continuously; no inert pills.
Criteria for Vaginal Ring
- Etonogestrel 15 mcg EE/day.
- Regimen: 1 ring inserted for 3 weeks, 1 week off.
Criteria for Transdermal Patch
- Norelgestromin 150 mcg/day with 35 mcg EE/day.
- Regimen: 1 patch weekly for 3 weeks, 1 week off.
Criteria for Injectable Contraceptives
- Intramuscular (IM): Medroxyprogesterone acetate 150 mg. Regimen: 1 injection Q3 months (13 weeks).
- Subcutaneous (SQ): Medroxyprogesterone acetate 104 mg. Regimen: 1 injection Q3 months (12 to 14 weeks).
Criteria for Emergency Contraception
- Levonorgestrel 1.5 mg or Ulipristal 30 mg.
- Regimen: 1 pill x1.
General Class-Wide Clinical Criteria & Formulary Guidance
- Highly effective in preventing pregnancy when used as directed, without significant differences between formulations.
- Combination agents differ mainly in strength of estrogen, type and strength of progestin, regimen, and route of administration.
- Nuisance side effects may be managed by adjusting the estrogen/progestin content or ratio.
- Progestin-only products may be considered for patients with contraindications to estrogen or a desire to avoid estrogen.
- Non-oral hormonal contraceptives (medroxyprogesterone depot injection, vaginal ring, transdermal patch, contraceptive implant) may be useful for patients with compliance issues who do not require daily dosing.
Prerequisites for 12-Month Dispensing of Contraceptive Agents
- Patient must be stable on the product for at least 3 months.
- Contraceptive must be on the Consolidated Mail Outpatient Pharmacy (CMOP) greater than 90-day supply list.
- Patient must accept the copay burden, if applicable.
Guidance for Self-Administration of Subcutaneous Depot Medroxyprogesterone Acetate (DMPA-SQ)
- Although package labeling states the product is intended for healthcare professional administration, self-administration is a safe and effective alternative.
- Self-administration may be offered in the context of shared decision making per CDC U.S. Selected Practice Recommendations.