DROXIDOPA
Clinical safety rating
cautionComprehensive clinical and safety monograph for DROXIDOPA (DROXIDOPA).
Droxidopa is a synthetic precursor of norepinephrine that increases norepinephrine levels in the peripheral nervous system, thereby improving sympathetic tone and blood pressure regulation.
| Metabolism | Metabolized by aromatic L-amino acid decarboxylase (AAAD) to norepinephrine, and also undergoes catechol-O-methyltransferase (COMT) metabolism. |
| Excretion | Renal: ~75% as unchanged drug and metabolites (including 3-O-methyldroxidopa and other conjugates); biliary/fecal: minimal (<5%). |
| Half-life | 2–3 hours; terminal half-life approximately 2.5 hours, requiring 3–4 times daily dosing to maintain plasma levels. |
| Protein binding | ~75% (primarily to albumin). |
| Volume of Distribution | 1–1.5 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: ~40% (range 30–50%) due to first-pass metabolism. |
| Onset of Action | Oral: 1–2 hours (clinical effect on orthostatic hypotension). |
| Duration of Action | 4–6 hours; duration may be shorter in patients with autonomic failure. |
| Molecular Weight | 213.23 |
100-200 mg orally three times daily, with a maximum of 600 mg three times daily if needed.
| Dosage form | CAPSULE |
| Renal impairment | For GFR 15-29 mL/min: reduce dose to 100 mg twice daily. For GFR <15 mL/min or dialysis: 100 mg once daily or 100 mg every other day. |
| Liver impairment | No specific Child-Pugh based adjustments; contraindicated in severe hepatic impairment (Child-Pugh C). Use with caution in moderate impairment (Child-Pugh B) at reduced doses. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no standard weight-based dosing available. |
| Geriatric use | Start at lower end of dosing range (100 mg twice daily) due to increased risk of orthostatic hypotension and renal function decline; monitor blood pressure and adjust gradually. |
| 1st trimester | Limited human data; animal studies show developmental toxicity at high doses. Use only if potential benefit outweighs risk. |
| 2nd trimester | Avoid unless necessary; may affect fetal blood pressure due to alpha-adrenergic effects. |
| 3rd trimester | Avoid near term due to risk of premature labor or fetal hypertension. |
Clinical note
Comprehensive clinical and safety monograph for DROXIDOPA (DROXIDOPA).
| Placental transfer | Droxidopa crosses the placenta in animal studies; human data insufficient. |
| Breastfeeding | Droxidopa is excreted into breast milk in negligible amounts; however, safety in nursing infants has not been established. Monitor infant for signs of hypertension or gastrointestinal effects. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C. In animal studies, droxidopa caused decreased fetal weights and increased skeletal variations at doses 2.6 times the maximum recommended human dose. There are no adequate and well-controlled studies in pregnant women. Fetal risk cannot be ruled out; use only if potential benefit justifies potential risk to the fetus. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate periodically; monitor for signs of supine hypertension. Fetal monitoring as per standard obstetric care; no specific additional monitoring required. |
| Fertility Effects | No human data on fertility effects. In animal studies, no impairment of fertility was observed at doses up to 2.6 times the MRHD. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to droxidopa or any componentConcurrent use with selegiline or other MAO inhibitors (risk of hypertensive crisis)
| Precautions | May cause supine hypertension; monitor blood pressure and manage by reducing dose or discontinuing if severe., Risk of exacerbation of cardiovascular disease (e.g., arrhythmias, heart failure)., May cause hyperthermia and confusion in patients with Parkinson's disease (resembles neuroleptic malignant syndrome)., Potential for increased risk of hallucinations or other psychiatric effects., Use with caution in patients with pre-existing cerebrovascular or cardiovascular disease. |
| Food/Dietary | Avoid alcohol as it may exacerbate hypotension. No specific food interactions known; take with or without food. High-tyramine foods (e.g., aged cheeses, cured meats) are not contraindicated but monitor blood pressure if consuming large amounts. |
| Clinical Pearls | Droxidopa is a prodrug of norepinephrine used for symptomatic neurogenic orthostatic hypotension (NOH). Monitor supine hypertension closely; advise patients to avoid dose lying down. Onset of action is within 1 hour, peak effect at 3-4 hours, duration about 6-8 hours. Titrate based on symptoms and supine blood pressure. Do not administer within 5 hours of bedtime to reduce risk of nocturnal supine hypertension. Can be used with fludrocortisone or midodrine, but additive hypertension risk. |
| Patient Advice | Take droxidopa exactly as prescribed, usually three times daily: on waking, mid-day, and late afternoon—never within 5 hours of bedtime. · Do not lie down after taking a dose; remain upright (sitting or standing) to prevent severe high blood pressure while lying down. · Rise slowly from sitting or lying positions to reduce falls; symptoms of low blood pressure include dizziness, lightheadedness, and fainting. · Avoid alcohol, which can worsen low blood pressure and increase side effects like dizziness. · Report symptoms of high blood pressure when lying down: severe headache, blurred vision, chest pain, difficulty breathing. · Store at room temperature; keep away from moisture and heat. |
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