Droxidopa

Indications

Droxidopa is used for: Neurogenic Orthostatic Hypotension

Adult Dose

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)

Child Dose

Renal Dose

Renal impairment Mild-to-moderate (GFR >30 mL/min): No dosage adjustment required Severe (GFR <30 mL/min): Limited data; caution advised

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

Contra Indications

Known hypersensitivity to the drug or ingredients

Precautions

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); if supine hypertension is not well-managed, therapy may increase risk of cardiovascular events, particularly stroke 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

Pregnancy-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

Interactions

Adverse Effects

Side effects of Droxidopa : >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%)

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