DROXIDOPA
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DROXIDOPA (DROXIDOPA).
| Breastfeeding | No data available on presence in human milk, effects on breastfed infant, or milk production. Caution advised. M/P ratio unknown. |
| 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 |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to droxidopa or any component of the formulation.","Use in patients with significant cardiovascular disease (e.g., unstable angina, recent myocardial infarction, or severe ventricular arrhythmias) is contraindicated.","Concomitant use with non-selective MAO inhibitors (e.g., phenelzine, tranylcypromine) due to 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."] |
Loading safety data…
| 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. |