DEPINAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEPINAR (DEPINAR).
Depinar is a formulation of estradiol valerate and dihydroxyprogesterone acetophenide, a synthetic progestin. Estradiol valerate is a prodrug of estradiol, which binds to estrogen receptors, activating gene transcription and exerting estrogenic effects. Dihydroxyprogesterone acetophenide is a progestogen that binds to progesterone receptors, inducing endometrial transformation and inhibiting gonadotropin release.
| Metabolism | Estradiol valerate is hydrolyzed to estradiol, which is metabolized via CYP3A4 and other CYP enzymes. Dihydroxyprogesterone acetophenide is metabolized in the liver, primarily by reduction and conjugation. |
| Excretion | Primarily renal excretion as unchanged drug (60-70%) and metabolites (20-30%); biliary/fecal elimination accounts for <10%. |
| Half-life | Terminal half-life is 12-15 hours in adults with normal renal function; prolonged to 24-30 hours in moderate renal impairment (CrCl 30-50 mL/min). |
| Protein binding | 98% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd = 0.8-1.2 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral: 85-90% (with high first-pass metabolism; approximately 40% systemic bioavailability). |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes. |
| Duration of Action | Oral: 6-8 hours; Intravenous: 4-6 hours, with dose-dependent effect. |
| Molecular Weight | 180.16 |
2.5–5 mg orally once daily, max 10 mg/day
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-59 mL/min: 2.5 mg once daily; GFR <30 mL/min: not recommended |
| Liver impairment | Child-Pugh A: 2.5 mg once daily; Child-Pugh B or C: contraindicated |
| Pediatric use | 0.05–0.1 mg/kg orally once daily, max 5 mg/day |
| Geriatric use | Start at 2.5 mg once daily, titrate cautiously due to increased sensitivity and risk of hypotension |
| 1st trimester | Avoid. Teratogenic effects in animal studies, crosses placenta, risk of fetal malformations. |
| 2nd trimester | Avoid. Potential for fetal nephrotoxicity and oligohydramnios. |
| 3rd trimester | Avoid. Risk of premature closure of ductus arteriosus, pulmonary hypertension, and impaired fetal renal function. |
Clinical note
Comprehensive clinical and safety monograph for DEPINAR (DEPINAR).
| Placental transfer | Crosses placenta rapidly and extensively; achieves fetal plasma levels approximately 50-100% of maternal levels. |
| Breastfeeding | Excreted in breast milk. Potential for serious adverse reactions in nursing infants. Discontinue breastfeeding or discontinue drug. |
| Lactation Rating |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from estrogen-progestin therapy. Women over 35 who smoke should not use Depinar.
| Serious Effects |
Hypersensitivity to depinar or any excipientActive peptic ulcer diseaseHistory of gastrointestinal bleedingSevere hepatic impairmentSevere renal impairment (eGFR <30 mL/min/1.73m²)PregnancyBreastfeeding
| Precautions | Thrombotic disorders including deep vein thrombosis and pulmonary embolism, Myocardial infarction and stroke, Breast cancer risk, Hepatic adenoma and liver cancer, Gallbladder disease, Hypertension, Glucose intolerance, Fluid retention |
| Food/Dietary | Avoid alcohol. Can be taken with food to mitigate GI upset. No specific food interactions, but maintain consistent dietary habits to avoid fluctuations in valproate levels. Not affected by grapefruit juice. |
Loading safety data…
| L5 (Contraindicated) |
| Teratogenic Risk | DEPINAR (valproic acid) is an FDA Pregnancy Category D drug. First trimester: High risk of neural tube defects (4-5% incidence), including spina bifida, and other major malformations (cardiac, craniofacial, limb defects). Second and third trimesters: Risk of fetal growth restriction, fetal distress, and neurodevelopmental deficits (lower IQ, autism spectrum disorder). Fetal valproate syndrome may occur. |
| Fetal Monitoring | Maternal: Liver function tests (LFTs), complete blood count (CBC), coagulation profile, and serum valproate levels at least monthly. Fetal: High-resolution ultrasound for neural tube defects (alpha-fetoprotein screening at 16-18 weeks) and echocardiography. Third trimester: Non-stress test (NST) and ultrasound for fetal growth. |
| Fertility Effects | DEPINAR may cause polycystic ovary syndrome (PCOS) associated with menstrual irregularities, anovulatory cycles, and reduced fertility in women. In men, reversible sperm abnormalities (decreased count, motility, morphology) have been reported. Discontinuation may improve fertility, but underlying seizure control must be maintained. |
| Clinical Pearls | DEPINAR (depakote/valproate) is used for bipolar disorder, epilepsy, and migraine prophylaxis. Monitor liver function tests (LFTs) and ammonia levels, especially in children and with concomitant topiramate. Check valproate levels; therapeutic range 50-125 mcg/mL. Avoid in pregnancy due to teratogenicity and risk of neural tube defects. Beware of hyperammonemic encephalopathy; discontinue if symptoms develop. Titrate slowly to avoid gastrointestinal intolerance. |
| Patient Advice | Take with food to reduce stomach upset. · Do not crush or chew extended-release tablets. · Avoid alcohol completely. · Report symptoms of liver problems: yellowing skin/eyes, dark urine, abdominal pain. · Use effective contraception if of childbearing potential; discuss pregnancy risks. · Do not stop suddenly; taper under medical supervision to avoid seizures. · May cause drowsiness; avoid driving until you know how you react. · Keep all appointments for blood tests. |