Dosing and uses of Northera (droxidopa)
Adult dosage forms and strengths
capsule
- 100mg
- 200mg
- 300mg
Neurogenic Orthostatic Hypotension
Indicated for symptomatic neurogenic orthostatic hypotension (NOH) in patients with primary autonomic failure (Parkinson’s disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy
100 mg PO TID initially
Titrate to symptomatic response, in increments of 100 mg TID every 24-48 hr; not to exceed 600 mg TID (ie, 1800 mg/day)
Dosage modifications
Renal impairment
- Mild-to-moderate (GFR >30 mL/min): No dosage adjustment required
- Severe (GFR <30 mL/min): Limited data; caution advised
Dosing Considerations
Effectiveness beyond 2 weeks of treatment has not been demonstrated
Continued effectiveness of droxidopa should be assessed periodically
Pediatric dosage forms and strengths
Safety and efficacy not established
Northera (droxidopa) adverse (side) effects
>10%
8-10 week administration
- Headache (13.2%)
1-10%
1-2 week administration
- Headache (6.1%)
- Dizziness (3.8%)
- Nausea (1.5%)
- Hypertension (1.5%)
8-10 week administration
- Dizziness (9.6%)
- Nausea (8.8%)
- Hypertension (7%)
Postmarketing Reports
Hypersensitivity
Warnings
Black box warnings
Supine hypertension
- Monitor supine blood pressure prior to and during treatment and more frequently when increasing doses
- Elevating the head of the bed lessens the risk of supine hypertension, and blood pressure should be measured in this position
- If supine hypertension cannot be managed by elevation of the head of the bed, reduce dose or discontinue droxidopa
Contraindications
Known hypersensitivity to the drug or ingredients
Cautions
May cause or exacerbate supine hypertension in patients with NOH; advise patients to elevate the head of the bed when resting or sleeping (see Black box warnings)
Hypersensitivity reactions including anaphylaxis, angioedema, bronchospasm, urticaria, and rash (see Contraindications); if hypersensitivity reaction occurs, discontinue drug and initiate appropriate therapy
Sympathomimetic effect may exacerbate existing ischemic heart disease, arrhythmias, and congestive heart failure
Coadministration with other drugs that increase blood pressure are expected to increase risk of hypertension
Coadministration with dopa-decarboxylase inhibitors may decrease the conversion of droxidopa to norepinephrine
Contains FD+C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons; although overall incidence of this sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity
Hyperpyrexia and confusion
- Symptom complex resembling neuroleptic malignant syndrome (NMS) reported; monitor closely when dosage is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics
- NMS is an uncommon, but life-threatening syndrome characterized by fever or hyperthermia, muscle rigidity, involuntary movements, altered consciousness, and mental status changes
Pregnancy and lactation
Pregnancy: There are no available data on use of dorxidopa in pregnant women and risk of major birth defects or miscarriage
Lactation: There is no information regarding presence of drug or its active metabolite(s) in human milk, effects on breastfed child, nor effects on milk production/excretion; because of potential for serious adverse reactions, including reduced weight gain in breastfed infants, advise a woman not to breastfeed during treatment
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Northera (droxidopa)
Mechanism of action
Norepinephrine precursor; directly metabolized to norepinephrine by dopa-decarboxylase which is extensively distributed throughout the body
Peak droxidopa plasma concentrations are associated with increases in systolic and diastolic blood pressures
Droxidopa has no clinically significant effect on standing or supine heart rates in patients with autonomic failure
Absorption
Peak plasma concentration: 1-4 hr
High-fat meals have a moderate impact on droxidopa exposure (decreased Cmax and AUC by ~35% and 20% respectively); Cmax delayed by ~2 hr
Distribution
Can cross the BBB
Protein bound: 75% (100 ng/mL); 26% (10,000 ng/mL)
Vd: 200 L
Metabolism
The metabolism of droxidopa is mediated by catecholamine pathway and not through the cytochrome P450 system
Initially converted to methoxylated dihydroxyphenylserine (3-OM-DOPS), a major metabolite, by catechol-O-methyltransferase (COMT), to norepinephrine by DOPA decarboxylase (DDC), or to protocatechualdehyde by DOPS aldolase
After oral dosing in humans, plasma norepinephrine levels peak within 3-4 hr but are generally very low (<1 ng/mL) and variable with no consistent relationship with dose
The contribution of droxidopa metabolites (other than norepinephrine) to its pharmacological effects is not well understood
Elimination
Half-life: 2.5 hr
Excretion: 75% urine
Administration
Oral Administration
Administer upon arising in the morning, at midday, and in the late afternoon at least 3 hr prior to bedtime (to reduce the potential for supine hypertension during sleep)
Administer consistently, either with food or without food
Swallow capsule whole; do not chew, open, or dissolve contents
Monitor supine blood pressure prior to initiating and after increasing the dose
Patients who miss a dose should take their next scheduled dose; do not double the dose to make up for a missed dose
