PIMTREA
Clinical safety rating
cautionComprehensive clinical and safety monograph for PIMTREA (PIMTREA).
PIMTREA is a small molecule inhibitor of the interaction between the PD-1 receptor and its ligands PD-L1 and PD-L2, acting as an immune checkpoint inhibitor to restore anti-tumor T-cell activity.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2D6; minor contributions from CYP2C9 and CYP2C19. |
| Excretion | Primarily renal (approximately 70% as unchanged drug), with biliary/fecal excretion accounting for the remainder. Less than 5% metabolized. |
| Half-life | Terminal elimination half-life of 2.5 to 4 hours; prolonged in renal impairment (up to 6–12 hours in severe impairment). |
| Protein binding | Approximately 20% bound to plasma proteins (albumin). |
| Volume of Distribution | 0.3–0.4 L/kg; indicates distribution primarily into extracellular fluid. |
| Bioavailability | Oral: 30–40% due to incomplete absorption and first-pass metabolism. |
| Onset of Action | Oral: 0.5–1 hour. Intravenous: within minutes. |
| Duration of Action | Approximately 4–6 hours for bacteriologic effect; clinical duration varies with pathogen susceptibility and dose. |
| Molecular Weight | Desogestrel: 310.47 Da; Ethinyl Estradiol: 296.40 Da |
Intravenous 1000 mg/m2 over 10 minutes on days 1, 8, and 15 of a 28-day cycle.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-59 mL/min: reduce to 750 mg/m2; for GFR 15-29 mL/min: reduce to 500 mg/m2; for GFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25-50%; Child-Pugh C: avoid use due to lack of data. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dosing. |
| Geriatric use | No specific dose adjustment based solely on age; monitor renal function and adjust accordingly. |
| 1st trimester | Pimtrea (desogestrel/ethinyl estradiol) is contraindicated in pregnancy. Use during first trimester may be associated with a small increase in risk of cardiovascular and limb defects, but data are limited. Do not use for contraception once pregnancy is confirmed. |
| 2nd trimester | Avoid use during second trimester. There is no indication for use during pregnancy; continuous use may increase risk of adverse fetal outcomes. |
| 3rd trimester | Avoid use during third trimester. Exposure may increase risk of maternal thromboembolism and adverse fetal effects. Discontinue if pregnancy occurs. |
Clinical note
Comprehensive clinical and safety monograph for PIMTREA (PIMTREA).
| Placental transfer | Desogestrel and ethinyl estradiol cross the placenta. Studies show measurable levels in fetal tissues, with significant transfer. The degree is comparable to other contraceptive steroids. |
| Breastfeeding | Pimtrea reduces milk production and may pass into breast milk. Use is not recommended during breastfeeding, especially in the early postpartum period. Estrogen-containing contraceptives can decrease milk quantity and quality. Consider alternative non-hormonal contraception. |
| Lactation Rating | L4 (Possibly Hazardous) - According to Drugs and Lactation Database (LactMed) and clinical guidelines, estrogen-progestin contraceptives are generally avoided during breastfeeding due to potential effects on milk production and infant development. |
| Teratogenic Risk | Pimtrea (ethinyl estradiol and drospirenone) is contraindicated in pregnancy. First trimester exposure: no increased risk of major birth defects from population-based cohort studies, but data are limited. Second and third trimester exposure: may increase risk of fetal harm, including cardiovascular and genitourinary anomalies, due to hormonal effects. Use only if clearly needed after weighing risks; discontinue if pregnancy occurs. |
| Fetal Monitoring | If exposed during pregnancy, monitor fetal growth and anatomy via ultrasound. Maternal monitoring: blood pressure, liver function, and signs of thromboembolism. Postpartum: assess for jaundice and hypoglycemia in neonate if exposure near delivery. |
| Fertility Effects | Reversible suppression of ovulation and endometrial changes that impair implantation. After discontinuation, rapid return to baseline fertility within 1-3 months expected. No permanent effects on fertility. |
■ FDA Black Box Warning
Immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis, can be severe or fatal. Monitor for signs and symptoms. Withhold or permanently discontinue based on severity.
| Serious Effects |
Known or suspected pregnancyBreastfeeding (unless postpartum >6 weeks and established milk supply; generally avoided)History of or current thromboembolic disorders (e.g., DVT, PE)Cerebrovascular or coronary artery diseaseUndiagnosed abnormal uterine bleedingKnown or suspected estrogen-dependent neoplasia (e.g., breast cancer)Hepatic adenoma or carcinoma, or active liver disease with abnormal liver functionUse with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvirHypersensitivity to any component
| Precautions | Risk of immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and infusion-related reactions. Evaluate liver and renal function, thyroid function, and pregnancy status before initiation. |
| Food/Dietary | No specific food interactions. Grapefruit juice may slightly increase estrogen exposure but not clinically significant. Avoid St. John's Wort as it reduces efficacy. |
| Clinical Pearls | Pimtrea (desogestrel/ethinyl estradiol) is a monophasic combined oral contraceptive. Counsel patients that missed pills increase pregnancy risk. Use with caution in smokers over 35 due to thromboembolism risk. Consider ARB/ACEI interaction for blood pressure control. No need for routine monitoring if asymptomatic. |
| Patient Advice | Take one pill daily at the same time; if missed, refer to package insert for instructions. · Do not smoke while taking this pill, especially if over 35. · Report sudden severe headache, chest pain, leg pain, or vision changes. · May cause nausea, breast tenderness, or breakthrough bleeding initially. · Protection against pregnancy starts after 7 consecutive days of correct use. |
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