Droxidopa

Drug overview for DROXIDOPA (droxidopa):

Generic name: DROXIDOPA (DROX-i-DOE-pa)
Drug class: Amphetamines/Anorexiants/Stimulants
Therapeutic class: Cardiovascular Therapy Agents

Droxidopa, a synthetic amino acid analog, is an orally active prodrug of norepinephrine, an adrenergic agonist.

No enhanced Uses information available for this drug.

DRUG IMAGES

DROXIDOPA 100 MG CAPSULE
DROXIDOPA 200 MG CAPSULE
DROXIDOPA 300 MG CAPSULE

The following indications for DROXIDOPA (droxidopa) have been approved by the FDA:

Indications:
Symptomatic orthostatic hypotension

Professional Synonyms:
Symptomatic OH
Symptomatic orthostatic hypopiesis
Symptomatic postural hypotension

The following dosing information is available for DROXIDOPA (droxidopa):

Dosing
Administration
DROXIDOPA
DROXIDOPA

For the management of symptomatic neurogenic orthostatic hypotension (NOH), the recommended initial dosage of droxidopa in adults is 100 mg 3 times daily, given upon arising in the morning, at midday, and in the late afternoon at least 3 hours before bedtime. Dosage may be increased in increments of 100 mg 3 times daily at intervals of 24-48 hours based on symptomatic response and tolerance. The maximum recommended dosage of droxidopa is 600 mg 3 times daily (1.8 g daily).

After dosage titration over 7-14 days in a study in patients with symptomatic NOH and Parkinson's disease (study 306B), less than 10% of patients remained at the initial droxidopa dosage of 100 mg 3 times daily, and approximately 40% of patients received the maximum dosage of 600 mg 3 times daily.

Efficacy of droxidopa beyond 2 weeks has not been established; continued benefit of droxidopa should be reassessed periodically during treatment.

Droxidopa is administered orally upon arising in the morning, at midday, and in the late afternoon at least 3 hours before bedtime. The drug may be taken either with or without food but should be taken consistently either way. Droxidopa capsules should be swallowed whole.

Supine blood pressure should be monitored prior to initiating droxidopa, periodically during treatment, and after dosage increases. To minimize the risk of supine hypertension, the manufacturer recommends that the head of the bed be elevated when resting or sleeping and that the last dose of the day be given at least 3 hours prior to bedtime. (See Supine Hypertension, under Warnings/Precautions: Warnings, in Cautions.) If a dose of droxidopa is missed, the dose should be skipped and the next dose taken at the regularly scheduled time. (See Advice to Patients.)

Dosing information for DROXIDOPA
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
DROXIDOPA 100 MG CAPSULE	Maintenance	Adults take 1 capsule (100 mg) by oral route 3 times per day in the morning, at midday, and in the late afternoon at least 3 hrs prior to bedtime
DROXIDOPA 200 MG CAPSULE	Maintenance	Adults take 1 capsule (200 mg) by oral route 3 times per day in the morning, at midday, and in the late afternoon at least 3 hrs prior to bedtime
DROXIDOPA 300 MG CAPSULE	Maintenance	Adults take 1 capsule (300 mg) by oral route 3 times per day in the morning, at midday, and in the late afternoon at least 3 hrs prior to bedtime

Generic dosing information for DROXIDOPA
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
DROXIDOPA 100 MG CAPSULE	Maintenance	Adults take 1 capsule (100 mg) by oral route 3 times per day in the morning,at midday, and in the late afternoon at least 3 hrs prior to bedtime
DROXIDOPA 200 MG CAPSULE	Maintenance	Adults take 1 capsule (200 mg) by oral route 3 times per day in the morning,at midday, and in the late afternoon at least 3 hrs prior to bedtime
DROXIDOPA 300 MG CAPSULE	Maintenance	Adults take 1 capsule (300 mg) by oral route 3 times per day in the morning,at midday, and in the late afternoon at least 3 hrs prior to bedtime

The following drug interaction information is available for DROXIDOPA (droxidopa):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Dihydroergotamine/Sympathomimetics SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Concurrent use of dihydroergotamine and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels.(1) CLINICAL EFFECTS: Concurrent use of dihydroergotamine and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Dihydroergotamine is contraindicated with sympathomimetics because the combination may result in additive or synergistic elevation of blood pressure.(1) DISCUSSION: Significant elevation in blood pressure has been reported in patients treated with dihydroergotamine.(1) Sympathomimetics can be expected to have additional effects on blood pressure.	DIHYDROERGOTAMINE MESYLATE, MIGRANAL, TRUDHESA

Drug Interaction

Drug Names

Dihydroergotamine/Sympathomimetics

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Concurrent use of dihydroergotamine and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels.(1)

CLINICAL EFFECTS: Concurrent use of dihydroergotamine and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Dihydroergotamine is contraindicated with sympathomimetics because the combination may result in additive or synergistic elevation of blood pressure.(1)

DISCUSSION: Significant elevation in blood pressure has been reported in patients treated with dihydroergotamine.(1) Sympathomimetics can be expected to have additional effects on blood pressure.

DIHYDROERGOTAMINE MESYLATE, MIGRANAL, TRUDHESA

There are 5 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Select Indirect-Acting Sympathomimetics/Tricyclic Compounds SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Unknown. However, it is speculated that indirect-acting sympathomimetics would have decreased activity due to tricyclic blockage of their uptake into the adrenergic neuron. CLINICAL EFFECTS: Decreased effect of indirect acting sympathomimetics. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Use of tricyclic compounds and indirect-acting sympathomimetics should be approached with caution. Montior patients receiving concurrent therapy for decreased sympathomimetic efficacy. DISCUSSION: The pressor effects of the indirect-acting sympathomimetic amines (e.g., amphetamines, ephedrine, and methylphenidate) are antagonized by tricyclic antidepressants.	AMITRIPTYLINE HCL, AMOXAPINE, ANAFRANIL, CHLORDIAZEPOXIDE-AMITRIPTYLINE, CLOMIPRAMINE HCL, DESIPRAMINE HCL, DOXEPIN HCL, IMIPRAMINE HCL, IMIPRAMINE PAMOATE, NORPRAMIN, NORTRIPTYLINE HCL, PAMELOR, PERPHENAZINE-AMITRIPTYLINE, PROTRIPTYLINE HCL, SILENOR, TRIMIPRAMINE MALEATE
Ergot Alkaloids/Sympathomimetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of ergot alkaloids and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels. CLINICAL EFFECTS: Concurrent use of ergot alkaloids and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid the concurrent use of ergot alkaloids and sympathomimetics. If concurrent use is warranted, monitor blood pressure and for signs of vasoconstriction. Decreasing the dose of one or both drugs may be necessary. DISCUSSION: There have been reports of severe vasoconstriction resulting in gangrene in patients receiving intravenous ergonovine with dopamine or norepinephrine.	ERGOLOID MESYLATES, ERGOMAR, ERGOTAMINE TARTRATE, ERGOTAMINE-CAFFEINE, METHYLERGONOVINE MALEATE, METHYSERGIDE MALEATE, MIGERGOT
Selected Inhalation Anesthetic Agents/Sympathomimetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. The anesthetics produce conduction changes that increase impulse re-entry into the myocardial tissue.(1) The anesthetics' ability to precipitate arrhythmias is enhanced by elevated arterial blood pressure, tachycardia, hypercapnia, and/or hypoxia, events that stimulate the release of endogenous catecholamines.(1) CLINICAL EFFECTS: Concurrent use of inhalation anesthetic agents and sympathomimetics may result in ventricular arrhythmias or sudden blood pressure and heart rate increase during surgery.(2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor blood pressure and avoid use of sympathomimetics in patients being treated with anesthetics on the day of surgery.(2) Intravenous use of epinephrine during surgery with halothane and related halogenated general anesthetics should be strongly discouraged. When intravenous epinephrine is necessary, nitrous oxide anesthesia supplemented with ether, muscle relaxants, or opioids should be used instead of halothane.(3,4) Epinephrine may safely be used subcutaneously with the following precautions: the patient is adequately ventilated to prevent hypoxia or respiratory acidosis; the total dose of epinephrine is limited to 100 mcg/10 minute period or 300 mcg/hour in adults, 3.5 mcg/Kg in infants, 2.5 mcg/Kg in children up to two years of age, and 1.45 mcg/Kg in children over two years of age; a minimum effective concentration of anesthetic is maintained; the drugs are not co-administered in patients with hypertension or other cardiovascular disorders; and the cardiac rhythm is continuously monitored during and after injection.(3-10) If arrhythmias occur after the administration of the epinephrine, the drugs of choice are lidocaine or propranolol, depending on the type of arrhythmia.(1) DISCUSSION: Administration of epinephrine during halothane anesthesia may may lead to serious ventricular arrhythmias.(3-6,11-18) This has occurred when epinephrine was administered intravenously,(6) when it was administered with lidocaine as a dental block,(11,14) or when it was administered supraperiosteally.(5) Norepinephrine has been shown to interact with halothane in a manner similar to epinephrine.(1) In two case reports, patients were given terbutaline (0.25 to 0.35 mg) for wheezing following induction of anesthesia with halothane. One patient's heart rate increased from 68 to 100 beats/minute, and the ECG showed premature ventricular contractions and bigeminy, while the other patient developed multiple unifocal premature ventricular contractions and bigeminy. The arrhythmias resolved in both patients following lidocaine administration.(19) Although not documented, isoproterenol causes effects on the heart similar to terbutaline(20) and would probably interact with halothane in a similar manner. Other inhalation anesthetics that increase the incidence of arrhythmias with epinephrine include chloroform,(20) methoxyflurane,(20) and enflurane.(12) A similar interaction may be expected between the other inhalation anesthetics and sympathomimetics.	DESFLURANE, FORANE, ISOFLURANE, SEVOFLURANE, SUPRANE, TERRELL, ULTANE
Droxidopa/MAOIs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: MAOIs inhibit the enzyme responsible for degradation of norepinephrine which is formed by droxidopa. CLINICAL EFFECTS: Concurrent use of MAOIs and droxidopa may result in increased effects of droxidopa, including headache, dizziness, nausea, and hypertensive crisis. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of droxidopa recommends concurrent use with non-selective MAOIs should be avoided. Selective MAO-B inhibitors, including rasagiline and selegiline, were used concurrently in clinical trials without an increase in risk of hypertensive crisis. If concurrent therapy is warranted, monitor patient closely for increases in blood pressure. DISCUSSION: Hypertensive reactions are possible as a result of this interaction. This interaction may be possible for several weeks after the discontinuation of a MAO inhibitor. Furazolidone and linezolid have been shown to inhibit MAO. Metaxalone is a weak inhibitor of MAO.	FURAZOLIDONE, LINEZOLID, LINEZOLID-0.9% NACL, LINEZOLID-D5W, MARPLAN, MATULANE, METAXALONE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, TRANYLCYPROMINE SULFATE, XADAGO, ZYVOX
Iobenguane I 123/Agents that Affect Catecholamines SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Many compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells.(1) CLINICAL EFFECTS: Compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with imaging completed with iobenguane.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discuss the use of agents that affect catecholamines. Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores prior to imaging with iobenguane. Before imaging with iobenguane, discontinue agents that affect catecholamines for at least 5 biological half-lives, as clinically tolerated.(1) DISCUSSION: Many agents may reduce catecholamine uptake or deplete catecholamine stores.(1) Examples include: - CNS stimulants or amphetamines (e.g. cocaine, methylphenidate, dextroamphetamine) - norepinephrine and dopamine reuptake inhibitors (e.g. phentermine) - norepinephrine and serotonin reuptake inhibitors (e.g. tramadol) - monoamine oxidase inhibitors (e.g. phenelzine, linezolid) - central monoamine depleting drugs (e.g. reserpine) - non-select beta adrenergic blocking drugs (e.g. labetalol) - alpha agonists or alpha/beta agonists (e.g. pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline) - tricyclic antidepressants or norepinephrine reuptake inhibitors (e.g. amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine) - botanicals that may inhibit reuptake of norepinephrine, serotonin or dopamine (e.g. ephedra, ma huang, St. John's Wort, yohimbine)	ADREVIEW

There are 3 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Sympathomimetics (Direct, Mixed-Acting)/Guanethidine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Direct or mixed-acting sympathomimetics may inhibit uptake of guanethidine at the adrenergic neuron. CLINICAL EFFECTS: Decreased antihypertensive effectiveness. Effects may be seen for several days after discontinuation of the direct or mixed-acting sympathomimetic. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. If both drugs are administered, adjust the guanethidine dose as needed based on blood pressure. DISCUSSION: Documentation supports routine monitoring of this interaction. It should be noted that this interaction can occur quickly.	GUANETHIDINE HEMISULFATE
Sympathomimetics (Direct, Mixed-Acting)/Methyldopa SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown. CLINICAL EFFECTS: The pressor response to sympathomimetics may be increased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Start with low doses of sympathomimetics and monitor blood pressure of patients during concurrent administration of sympathomimetics and methyldopa. DISCUSSION: The pressor response to sympathomimetics has been reported to be increased during methyldopa administration. In addition to increased duration of pressor response, severe hypertension has been reported.	METHYLDOPA, METHYLDOPA-HYDROCHLOROTHIAZIDE, METHYLDOPATE HCL
Entacapone; Opicapone/COMT-Metabolized Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Entacapone and opicapone are selective and reversible inhibitors of catechol-O-methyltransferase (COMT) and drugs that are metabolized by COMT can not be fully metabolized when given with entacapone or opicapone.(1) CLINICAL EFFECTS: COMT-metabolized agents can interact with entacapone or opicapone and may result in an increased heart rates, arrhythmias, or an excessive change in blood pressure.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturers of entacapone and opicapone recommend using caution when administering entacapone or opicapone and a COMT-metabolized agent regardless of the route of administration (including inhalation).(1-3) DISCUSSION: In an interaction study, ventricular tachycardia was observed after epinephrine and entacapone administration.(1) Another study on the effect of entacapone given with isoproterenol and epinephrine concluded that entacapone may potentiate the chronotropic and arrhythmogenic effects of isoproterenol and epinephrine.(4)	CARBIDOPA-LEVODOPA-ENTACAPONE, ENTACAPONE, ONGENTYS

The following contraindication information is available for DROXIDOPA (droxidopa):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

The manufacturer states that there are no contraindications to the use of droxidopa.

There are 0 contraindications.

There are 2 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Neuroleptic malignant syndrome
Supine hypertension

There are 3 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Cardiac arrhythmia
Chronic heart failure
Coronary artery disease

The following adverse reaction information is available for DROXIDOPA (droxidopa):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects reported in more than 5% of patients receiving droxidopa and at an incidence at least 3% greater than that with placebo in controlled trials include headache, dizziness, nausea, and hypertension. In longer-term open-label trials, commonly reported adverse effects included falls, urinary tract infections, headache, syncope, and dizziness.

There are 11 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Acute cognitive impairment Anaphylaxis Angioedema Bronchospastic pulmonary disease Drug-induced psychosis Fever Myocardial ischemia Neuroleptic malignant syndrome Pancreatitis Supine hypertension Worsening of chronic heart failure

There are 16 less severe adverse reactions.

More Frequent	Less Frequent
Dizziness Fatigue Hypertension Nausea	None.

Rare/Very Rare
Acute abdominal pain Agitation Blurred vision Chest pain Delirium Diarrhea Hallucinations Headache disorder Memory impairment Skin rash Urticaria Vomiting

The following precautions are available for DROXIDOPA (droxidopa):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of droxidopa in pediatric patients have not been established.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Category C. (See Users Guide.) There are no adequate and well-controlled studies to date in pregnant women. In animal studies, droxidopa has been associated with reduced body weight and occurrence of undulant rib (which were slight and reversed after birth), reduced gestation period, and low incidences of renal lesions on the kidney surface; no other potentially teratogenic effects were observed. Droxidopa should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.

It is not known whether droxidopa is distributed into human milk. However, droxidopa is distributed into milk in rats and has been associated with reduced weight gain and reduced survival of offspring when administered to nursing dams during lactation. Because of the potential for serious adverse reactions to droxidopa in nursing infants, a decision should be made whether to discontinue nursing or the drug.

Clinical trials with droxidopa included 197 patients 75 years of age or older. Although no overall differences in safety or efficacy were observed between geriatric and younger patients in these trials, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.

Symptomatic orthostatic hypotension
I95.1	Orthostatic hypotension