NORTHERA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORTHERA (NORTHERA).
Selective norepinephrine reuptake inhibitor (NRI); increases norepinephrine and epinephrine levels at the synaptic cleft, resulting in increased vascular tone and elevated blood pressure.
| Metabolism | Primarily via CYP2D6; major metabolite is N-desethyl droxidopa (active); minor pathways include O-methylation and sulfation. |
| Excretion | Renal: Approximately 90% of the dose is excreted unchanged in urine via active tubular secretion; biliary/fecal: <2%. |
| Half-life | Terminal elimination half-life is approximately 9-10 hours in healthy subjects; in patients with autonomic failure, half-life may be prolonged due to reduced renal function. |
| Protein binding | Approximately 50-70% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 4-5 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Oral: Approximately 50% due to first-pass metabolism. |
| Onset of Action | Oral: Onset of blood pressure elevation occurs within 1-2 hours following administration. |
| Duration of Action | Oral: Clinically significant blood pressure elevation lasts approximately 4-6 hours after a single dose, with a duration up to 8 hours in some patients; dosing is typically three times daily. |
Initial: 100 mg orally twice daily; titrate in 100 mg increments every 3-4 days to a maximum of 600 mg twice daily.
| Dosage form | CAPSULE |
| Renal impairment | eGFR 30-59 mL/min: maximum 300 mg twice daily. eGFR 15-29 mL/min: maximum 200 mg twice daily. eGFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: maximum 300 mg twice daily. Child-Pugh Class C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | Use with caution due to increased risk of hypotension, syncope, and urinary retention; consider starting at 100 mg twice daily and titrate slowly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORTHERA (NORTHERA).
| Breastfeeding | It is not known whether droxidopa is excreted in human breast milk. No data available on M/P ratio. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | NORTHERA (droxidopa) is pregnancy category C. In animal studies, droxidopa caused decreased fetal body weight and increased skeletal variations at doses 4 times the maximum recommended human dose. There are no adequate and well-controlled studies in pregnant women. In the first trimester, the risk is unknown but potential for harm exists; use only if potential benefit justifies risk to the fetus. In second and third trimesters, similar caution applies. No specific fetal toxicity syndrome identified. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to droxidopa or any component of the formulation","Concomitant use with nonselective monoamine oxidase inhibitors (MAOIs)"]
| Precautions | ["Supine hypertension (monitor supine BP, advise sleeping with head elevated)","Increased risk of arrhythmias (use with caution in patients with atrial fibrillation or other tachyarrhythmias)","May exacerbate ischemic heart disease, heart failure, or stroke risk","May cause hyperglycemia (monitor blood glucose in diabetic patients)","May impair ability to drive or operate machinery (dizziness, syncope)"] |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and symptoms of supine hypertension. Fetal monitoring includes standard obstetric monitoring for fetal well-being (e.g., fetal heart rate monitoring) as clinically indicated. No specific additional monitoring required beyond routine prenatal care. |
| Fertility Effects | No human data on fertility effects. In animal studies, droxidopa did not impair fertility in rats at doses up to 4 times the maximum recommended human dose. There are no known effects on human spermatogenesis or oogenesis. |