Droxidopa is an oral synthetic amino acid precursor of norepinephrine. It is used to increase blood pressure in adult patients with symptomatic neurogenic orthostatic hypotension (NOH) caused by primary autonomic failure (e.g., Parkinson's disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, or non-diabetic autonomic neuropathy. Effectiveness beyond 2 weeks has not been established. Droxidopa may cause supine hypertension and increase risk of cardiovascular events if not monitored and well-managed. Droxidopa was FDA-approved in February 2014.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Administer capsules three times daily at the following times: upon arising in the morning, at midday, and in the late afternoon at least 3 hours prior to bedtime (to reduce the potential for supine hypertension during sleep).
-May be administered with or without food, but should be taken consistently in regard to food to ensure consistent absorption of droxidopa.
-Swallow capsules whole.
-Instruct patients to rest and sleep in an upper body elevated position and to monitor blood pressure (to reduce the potential for supine hypertension).
Droxidopa may cause or exacerbate supine hypertension in patients with neurogenic orthostatic hypotension (NOH). If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events, particularly stroke. Stroke has been reported with the postmarketing use of droxidopa. In placebo-controlled trials of droxidopa, hypertension (1.5% to 7%) was one of the most commonly observed adverse reactions. Monitor supine blood pressure prior to and during treatment and more frequently when increasing doses. Advise patients to elevate the head of the bed when resting or sleeping in order to lessen the risk of supine hypertension. Blood pressure should be monitored, both in the supine position and in the recommended head-elevated sleeping position. Reduce or discontinue droxidopa if supine hypertension persists despite management by elevation of the head of the bed.
In placebo-controlled trials of droxidopa, the most commonly observed adverse reactions were headache (6.1% to 13.2%), dizziness (3.8% to 9.6%), and nausea (1.5% to 8.8%). During long-term open label extension studies, the commonly reported adverse events were falls (24%), urinary tract infection (15%), headache (13%), syncope (13%), and dizziness (10%).
Droxidopa has been associated with neuroleptic malignant syndrome-like symptoms during postmarketing use. Neuroleptic malignant syndrome is an uncommon but life-threatening syndrome characterized by hyperthermia, severe extrapyramidal dysfunction, alterations in consciousness, mental status changes, and autonomic instability (tachycardia, blood pressure fluctuations, diaphoresis). In patients with Parkinson's disease, this condition has been noted with the abrupt reduction or discontinuation of medications with dopaminergic properties. It is important that this condition is diagnosed early so that the patient can be managed appropriately. Observe patients carefully when the dosage of droxidopa is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.
Droxidopa is a precursor to norepinephrine, which may cause arrhythmia exacerbation and may also exacerbate existing ischemic cardiac disease (e.g., coronary artery disease, angina, history of myocardial infarction) and congestive heart failure. In patients with these conditions, carefully consider the potential risk prior to initiating therapy. Chest pain (unspecified) that occurs during treatment may require cardiac evaluation.
Hypersensitivity reactions including anaphylaxis/anaphylactoid reactions, angioedema, bronchospasm, urticaria, and rash (unspecified) have been reported with postmarketing use. If a hypersensitivity reaction occurs, discontinue droxidopa and initiate appropriate therapy.
Fatigue, blurred vision, psychosis, hallucinations, delirium, agitation, and memory impairment (memory disorder) have been reported with postmarketing use of droxidopa; however, frequency and causality have not been established.
Pancreatitis, abdominal pain, vomiting, and diarrhea have been reported with postmarketing use of droxidopa; however, frequency and causality have not been established.
Droxidopa may cause or exacerbate supine hypertension in patients with neurogenic orthostatic hypotension (NOH). If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events, particularly stroke. Monitor supine blood pressure prior to and during treatment and more frequently when increasing doses. Advise patients to elevate the head of the bed when resting or sleeping in order to lessen the risk of supine hypertension. Blood pressure should be monitored, both in the supine position and in the recommended head-elevated sleeping position. Reduce or discontinue droxidopa if supine hypertension persists despite management by elevation of the head of the bed.
Droxidopa has been associated with a symptom complex resembling neuroleptic malignant syndrome (NMS) during post-market use. NMS is an uncommon but life-threatening syndrome characterized by hyperthermia, severe extrapyramidal dysfunction, alterations in consciousness, mental status changes, and autonomic instability (tachycardia, blood pressure fluctuations, diaphoresis). It is important that this condition is diagnosed early so that the patient can be managed appropriately. Observe patients carefully when the dosage of droxidopa is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.
Droxidopa may exacerbate existing ischemic cardiac disease (e.g., coronary artery disease, angina, history of myocardial infarction), cardiac arrhythmias, and congestive heart failure. In patients with these conditions, carefully consider the potential risk prior to initiating therapy.
Droxidopa is contraindicated in patients who have a history of hypersensitivity to the drug or any of its ingredients. Hypersensitivity reactions including anaphylaxis, angioedema, bronchospasm, urticaria, and rash have been reported with postmarketing use. If a hypersensitivity reaction occurs, discontinue droxidopa and initiate appropriate therapy. Droxidopa capsules contain tartrazine dye (FD&C yellow No. 5) which may also cause allergic-type reactions (i.e., tartrazine dye hypersensitivity), including bronchial asthma, in susceptible individuals. Although the incidence of this dye hypersensitivity is low, it is frequently seen in patients with salicylate hypersensitivity.
There are no available data on the use of droxidopa during human pregnancy or the risk of major birth defects and miscarriage. Droxidopa did not produce significant reproductive toxicity in pregnant female rats or rabbits or their fetuses. However, when pregnant female rats were given doses corresponding to 0.3, 1, and 3 times the maximum recommended human dose during organogenesis and when their male and female offspring were subsequently bred, the female offspring exhibited a dose-dependent reduction in the number of live fetuses at all 3 doses and an increased number of embryonic/fetal deaths at the 2 higher doses.
There is no information available on the presence of droxidopa or its active metabolite in human milk or the effects of droxidopa on the breast-fed child or milk production/excretion. Women should avoid breast-feeding during droxidopa treatment because of the potential for serious adverse reactions, including reduced weight gain in breast-fed infants.
For the treatment of symptomatic neurogenic orthostatic hypotension due to primary autonomic failure (e.g., Parkinson's disease, multiple system atrophy, pure autonomic failure), dopamine beta-hydroxylase deficiency, or non-diabetic autonomic neuropathy:
Oral dosage:
Adults: 100 mg PO 3 times daily, initially. Titrate dose by 100 mg 3 times daily every 24 to 48 hours to symptomatic response up to 600 mg PO 3 times daily (Max: 1,800 mg/day). Effectiveness beyond 2 weeks of treatment has not been established.
Maximum Dosage Limits:
-Adults
1,800 mg/day PO.
-Geriatric
1,800 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
eGFR >= 30 mL/min/1.73 m2: No dosage adjustment needed.
eGFR < 30 mL/min/1.73 m2: Clinical experience is limited. Droxidopa and its metabolites are primarily excreted renally. Therefore, the benefit-risk for the use of droxidopa in these patients should be individually assessed.
*non-FDA-approved indication
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Acetaminophen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Acrivastine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Almotriptan: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
Atomoxetine: (Major) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as droxidopa. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine.
Brompheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Carbidopa: (Major) Droxidopa is directly metabolized to norepinephrine by dopa-decarboxylase; therefore, coadministration with dopa-decarboxylase inhibitors (e.g., carbidopa) may prevent the conversion of droxidopa to norepinephrine outside of the central nervous system (CNS). Patients in the clinical trials with droxidopa received concomitant medications used to treat Parkinson's disease. Patients taking droxidopa with levodopa/dopa-decarboxylase inhibitor combinations (e.g., carbidopa; levodopa or carbidopa; levodopa; entacapone) had decreased clearance of droxidopa, an increase in exposure (AUC) to droxidopa of approximately 100%, and an increase in exposure to 3-OM-DOPS of approximately 50%. However, in clinical trials, it was found that the decreased clearance was not associated with a significant need for a different treatment dose or increases in associated adverse events. No dose adjustments are expected to be required. However, the manufacturer states that in some patients, it is possible that dose adjustments for droxidopa will be required.
Carbidopa; Levodopa: (Major) Droxidopa is directly metabolized to norepinephrine by dopa-decarboxylase; therefore, coadministration with dopa-decarboxylase inhibitors (e.g., carbidopa) may prevent the conversion of droxidopa to norepinephrine outside of the central nervous system (CNS). Patients in the clinical trials with droxidopa received concomitant medications used to treat Parkinson's disease. Patients taking droxidopa with levodopa/dopa-decarboxylase inhibitor combinations (e.g., carbidopa; levodopa or carbidopa; levodopa; entacapone) had decreased clearance of droxidopa, an increase in exposure (AUC) to droxidopa of approximately 100%, and an increase in exposure to 3-OM-DOPS of approximately 50%. However, in clinical trials, it was found that the decreased clearance was not associated with a significant need for a different treatment dose or increases in associated adverse events. No dose adjustments are expected to be required. However, the manufacturer states that in some patients, it is possible that dose adjustments for droxidopa will be required.
Carbidopa; Levodopa; Entacapone: (Major) Droxidopa is directly metabolized to norepinephrine by dopa-decarboxylase; therefore, coadministration with dopa-decarboxylase inhibitors (e.g., carbidopa) may prevent the conversion of droxidopa to norepinephrine outside of the central nervous system (CNS). Patients in the clinical trials with droxidopa received concomitant medications used to treat Parkinson's disease. Patients taking droxidopa with levodopa/dopa-decarboxylase inhibitor combinations (e.g., carbidopa; levodopa or carbidopa; levodopa; entacapone) had decreased clearance of droxidopa, an increase in exposure (AUC) to droxidopa of approximately 100%, and an increase in exposure to 3-OM-DOPS of approximately 50%. However, in clinical trials, it was found that the decreased clearance was not associated with a significant need for a different treatment dose or increases in associated adverse events. No dose adjustments are expected to be required. However, the manufacturer states that in some patients, it is possible that dose adjustments for droxidopa will be required.
Cardiac glycosides: (Moderate) Carefully monitor patients receiving cardiac glycosides and vasopressors concurrently due to the increased risk of arrhythmia.
Cetirizine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Chlorpheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Desloratadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Dexbrompheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Dexmethylphenidate: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Diethylpropion: (Major) Diethylpropion has vasopressor effects. Coadministration with other vasopressors may have the potential for serious cardiac adverse effects such as hypertensive crisis and cardiac arrhythmias.
Digoxin: (Moderate) Carefully monitor patients receiving cardiac glycosides and vasopressors concurrently due to the increased risk of arrhythmia.
Dihydroergotamine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Dopamine: (Moderate) Monitor blood pressure during concomitant use of dopamine and other vasopressors, such as droxidopa, due to the risk for severe hypertension.
Eletriptan: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
Ergotamine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Ergotamine; Caffeine: (Contraindicated) Concomitant use of ergotamine with vasopressors is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Ethiodized Oil: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Fexofenadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Frovatriptan: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Ibuprofen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Iodixanol: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Iohexol: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Iomeprol: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Ionic Contrast Media: (Major) The intravascular injection of a contrast medium should never be made after the administration of vasopressors since they strongly potentiate neurologic effects. Serious neurologic sequelae, including permanent paralysis, have been reported after cerebral arteriography, selective spinal arteriography, and arteriography of vessels supplying the spinal cord.
Iopamidol: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Iopromide: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Ioversol: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Isocarboxazid: (Major) Avoid concurrent use of droxidopa and isocarboxazid, a non-selective MAOI, as there is a potential for increased blood pressure when taken together.
Isosulfan Blue: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Linezolid: (Major) Avoid concurrent use of droxidopa and linezolid, a non-selective MAOI, as there is a potential for increased blood pressure when taken together.
Loratadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Methylergonovine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Methylphenidate Derivatives: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Methylphenidate: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Naproxen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Naratriptan: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
Non-Ionic Contrast Media: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects.
Phendimetrazine: (Major) Phendimetrazine is a phenylalkaline sympathomimetic agent. All sympathomimetics and psychostimulants, including other anorexiants, should be used cautiously or avoided in patients receiving phendimetrazine. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmia.
Phenelzine: (Major) Avoid concurrent use of droxidopa and phenelzine, a non-selective MAOI, as there is a potential for increased blood pressure when taken together.
Phentermine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias.
Phentermine; Topiramate: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias.
Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Pseudoephedrine; Triprolidine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
Racepinephrine: (Major) Racepinephrine is a sympathomimetic drug with agonist actions at both the alpha and beta receptors. Patients using racepinephrine inhalation are advised to avoid other non-prescription products containing sympathomimetics since additive adverse effects on the cardiovascular and nervous system are possible, some which may be undesirable. Side effects such as nausea, tremor, nervousness, difficulty with sleep, and increased heart rate or blood pressure may be additive. Patients should avoid use of non-prescription decongestants, such as phenylephrine and pseudoephedrine, while using racepinephrine inhalations. Patients should avoid dietary supplements containing ingredients that are reported or claimed to have a stimulant or weight-loss effect, such as ephedrine and ephedra, Ma huang, and phenylpropanolamine.
Rizatriptan: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
Serotonin-Receptor Agonists: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
Solriamfetol: (Moderate) Monitor blood pressure and heart rate during coadministration of solriamfetol, a norepinephrine and dopamine reuptake inhibitor, and vasopressors. Concurrent use of solriamfetol and other medications that increase blood pressure and/or heart rate may increase the risk of such effects. Coadministration of solriamfetol with other drugs that increase blood pressure or heart rate has not been evaluated.
Sumatriptan: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
Sumatriptan; Naproxen: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
Tranylcypromine: (Major) Avoid concurrent use of droxidopa and tranylcypromine, a non-selective MAOI, as there is a potential for increased blood pressure when taken together.
Zolmitriptan: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
The exact mechanism of action of droxidopa in the treatment of neurogenic orthostatic hypotension is unknown. Droxidopa is a synthetic amino acid analog that is directly metabolized to norepinephrine by dopa-decarboxylase, which is extensively distributed throughout the body. It is believed that the pharmacological effects of droxidopa are through norepinephrine and not through the parent molecule or other metabolites. Droxidopa in humans induces small and transient rises in plasma norepinephrine. Norepinephrine increases blood pressure by inducing peripheral arterial and venous vasoconstriction. Droxidopa has no clinically significant effect on standing or supine heart rates in patients with autonomic failure.
Droxidopa is administered orally. Pre-clinical studies suggest that droxidopa can cross the blood-brain barrier. Droxidopa exhibits plasma protein binding of 75% at 100 ng/mL and 26% at 10,000 ng/mL. The estimated apparent volume of distribution of droxidopa is about 200 L. Total clearance is approximately 400 mL/hour. The metabolism of droxidopa is via the catecholamine pathway. Droxidopa is 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. The contribution of the metabolites of droxidopa other than norepinephrine to its pharmacological effects is not well understood. The mean elimination half-life of droxidopa is approximately 2.5 hours. The major route of elimination of droxidopa and its metabolites is via the kidneys. Studies in animals showed that approximately 75% of the radiolabeled dose was excreted in urine within 24 hours of oral dosing.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Oral Route
After oral dosing in humans, plasma norepinephrine levels peak within 3 to 4 hours but are generally very low (less than 1 ng/mL) and variable with no consistent relationship with dose. Peak plasma concentrations (Cmax) of droxidopa were reached by 1 to 4 hours post-dose (mean of approximately 2 hours) in healthy volunteers. High-fat meals have a moderate impact on droxidopa exposure with Cmax and area under the plasma concentration-time curve (AUC) decreasing by 35% and 20%, respectively. The Cmax was delayed by approximately 2 hours with a high-fat meal.
-Special Populations
Hepatic Impairment
Hepatic function did not influence the exposure to droxidopa in a population pharmacokinetic analysis that assessed aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and total bilirubin.
Renal Impairment
Patients with mild or moderate renal impairment (eGFR >= 30 mL/minute/1.73 m2) were included in clinical trials and did not have a higher frequency of adverse reactions. Clinical experience with droxidopa in patients with severe renal impairment (eGFR < 30 mL/minute/1.73 m2) is limited.
Pediatrics
Pharmacokinetic studies of droxidopa have not been performed in pediatric patients.
Geriatric
There was no effect of age on the pharmacokinetics of droxidopa.
Gender Differences
There was no effect of gender on the pharmacokinetics of droxidopa.
Obesity
There was no effect of weight on the pharmacokinetics of droxidopa.