DEPINAR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DEPINAR (DEPINAR).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DEPINAR (DEPINAR).

Breastfeeding

DEPINAR is excreted into breast milk with a milk-to-plasma (M/P) ratio of 0.01-0.1. The relative infant dose is 1-2% of maternal weight-adjusted dose. Although low, caution is advised due to potential hepatic toxicity and thrombocytopenia in neonates. Consider risk-benefit and monitor infant for jaundice or bleeding.

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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known or suspected pregnancy","Breast cancer or other estrogen-sensitive neoplasia","Undiagnosed abnormal genital bleeding","Active thromboembolic disorder or history","Liver disease or impaired liver function","Hypersensitivity to any component","Cigarette smoking in women over 35"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

DEPINAR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DEPINAR (DEPINAR).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DEPINAR (DEPINAR).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ 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.