Droxidopa (Oral)

Overview

Droxidopa is a precursor of norepinephrine consisting of synthetic amino acid. Its main purpose is to increase blood pressure in a way that curtails feelings of dizziness, lightheadedness, and feelings of imminent loss of consciousness (blacking out) in patients with neurogenic orthostatic hypotension, or nOH. In cases where Droxidopa is prescribed, the nOH is caused by primary autonomic failure such as multiple system atrophy, Parkinson's disease, and pure autonomic failure, as well as other conditions such as dopamine beta-hydroxylase deficiency and diabetic neuropathy (non-diabetic). The body metabolizes the droxidopa and converts it to norepinephrine, which creates peripheral and arterial vasoconstriction, increasing blood pressure. Droxidopa is able to cross the blood-brain barrier, unlike pure norepinephrine, which increases its effectiveness.

Though droxidopa can be initially effective (over the course of the first two weeks) in the treatment of PAF related hypotension and its symptoms, its benefit beyond that point has not been noted. Patients taking Droxidopa should be monitored regularly to ensure continued effectiveness. Droxidopa also carries a high risk of serious side effects, such as supine hypertension, and a rare but potentially fatal condition known as neuroleptic malignant syndrome. There is also a high risk of exacerbation of pre-existing heart conditions.

Conditions Treated

  • Orthostatic hypotension

Type of drug

  • Cardiac stimulant

Side Effects

Droxidopa, like most medications, comes with the potential for side effects. The most serious possible reactions are supine hypertension, confusion and hyperpyrexia, as well as worsening of ischemic heart disease including arrhythmias and congestive heart failure. These are among the side effects that warrant immediate medical attention if they occur. A list of such reactions is provided below.

More common:

  • Bladder pain
  • Blood in urine, cloudy urine
  • Blurred vision
  • Difficult, burning, or painful urination
  • Dizziness
  • Fainting
  • Frequent urge to urinate
  • Pain in lower back or side
  • Nervousness
  • Pounding in the ears
  • Slow or fast heartbeat

Additionally, Droxidopa can cause side effects that are not as serious. These reactions may go away as the patient's body adjusts to the medication. Caregivers may be able to instruct the patient on how to avoid such side effects. These less harmful side effects are:

  • Headache
  • Nausea

Droxidopa may cause other side effects not listed here. If any of these occur, the patient should contact their caregiver.

Dosage

Patients begin Droxidopa with a dose of 100mg per day, taken three times daily. The first dose is taken when the patient wakes up, the second is taken around the middle of the day, and the third is taken at least three hours before the patient goes to bed at night to reduce the risk of supine hypertension. Droxidopa should be taken consistently and can be administered both with or without food. Droxidopa should be titrated in response to symptoms. Titration should occur in increments of 100mg over a 24-48 hour period (i.e. 100mg on Monday, 200mg on Tuesday or Wednesday), with new doses taken three times daily, up to a maximum single dose of 600mg (1800mg per day). Blood pressure should be monitored before beginning Droxidopa treatment, and after any dose increase.

Interactions

It is important for the patient to inform their doctor of any other medications they may be taking before beginning Droxidopa treatment, as the medication can interact with other drugs in ways that can cause adverse effects. Taking droxidopa in conjunction with other blood pressure increasing drugs (epinephrine, norepinephrine, etc.) puts the patient at greater risk of supine hypertension. If the patient is taking certain medications for Parkinson's disease, this may warrant a dose adjustment for droxidopa. Non-selective MAO inhibitors may also increase the patient's blood pressure excessively. An extensive, but not complete, list of possible droxidopa interactions is provided below.

Moderate interactions:

  • Acetaminophen
  • Acrivastine / pseudoephedrine
  • Albuterol
  • Albuterol / ipratropium
  • Almotriptan
  • Aminophylline / amobarbital / ephedrine
  • Aminophylline / ephedrine / guaifenesin / phenobarbital
  • Aminophylline / ephedrine / phenobarbital / potassium iodide
  • Ammonium chloride / chlorpheniramine / codeine / phenylephrine
  • Ammonium chloride / chlorpheniramine / dextromethorphan / ephedrine / ipecac / phenylephrine
  • Amphetamine
  • Amphetamine / dextroamphetamine
  • Anhydrous calcium iodide / isoproterenol
  • Antipyrine / benzocaine / phenylephrine otic
  • Arformoterol
  • Articaine / epinephrine
  • Aspirin
  • Atropine
  • Benzocaine / phenylephrine / phenylpropanolamine
  • Benzoic acid / hyoscyamine / methenamine / methylene blue / phenyl salicylate
  • Benzphetamine
  • Bitolterol
  • Brompheniramine
  • Brompheniramine / phenylephrine / phenylpropanolamine
  • Brompheniramine / phenylpropanolamine
  • Brompheniramine / pseudoephedrine
  • Budesonide / formoterol
  • Bupivacaine / epinephrine
  • Caffeine / pheniramine / phenylephrine / sodium citrate / sodium salicylate
  • Caramiphen / phenylpropanolamine
  • Carbetapentane / carbinoxamine / phenylephrine
  • Carbetapentane / chlorpheniramine / ephedrine / phenylephrine
  • Carbetapentane / chlorpheniramine / phenylephrine
  • Carbetapentane / dexchlorpheniramine / phenylephrine
  • Carbetapentane / diphenhydramine / phenylephrine
  • Carbetapentane / guaifenesin / phenylephrine
  • Carbetapentane / guaifenesin / pseudoephedrine
  • Carbidopa
  • Carbidopa / entacapone / levodopa
  • Carbidopa / levodopa
  • Carbinoxamine / dextromethorphan / phenylephrine
  • Carbinoxamine / dextromethorphan / pseudoephedrine
  • Carbinoxamine / hydrocodone / phenylephrine
  • Carbinoxamine / hydrocodone / pseudoephedrine
  • Carbinoxamine / methscopolamine / pseudoephedrine
  • Carbinoxamine / phenylephrine
  • Carbinoxamine / pseudoephedrine
  • Cetirizine / pseudoephedrine
  • Chlophedianol
  • Chlorcyclizine / codeine / pseudoephedrine
  • Chlorcyclizine / phenylephrine
  • Chlorcyclizine / pseudoephedrine
  • Chlorpheniramine
  • Clemastine / phenylpropanolamine
  • Codeine
  • Cyclopentolate / phenylephrine ophthalmic
  • Desloratadine / pseudoephedrine
  • Dexbrompheniramine / hydrocodone / phenylephrine
  • Dexbrompheniramine / phenylephrine
  • Dexbrompheniramine / phenylephrine / pyrilamine
  • Dexbrompheniramine / pseudoephedrine
  • Dexchlorpheniramine / dextromethorphan / phenylephrine
  • Dexchlorpheniramine / dextromethorphan / phenylephrine / pyrilamine
  • Dexchlorpheniramine / dextromethorphan / pseudoephedrine
  • Dexchlorpheniramine / guaifenesin / pseudoephedrine
  • Dexchlorpheniramine / hydrocodone / phenylephrine
  • Dexchlorpheniramine / methscopolamine / phenylephrine
  • Dexchlorpheniramine / methscopolamine / pseudoephedrine
  • Dexchlorpheniramine / phenylephrine
  • Dexchlorpheniramine / pseudoephedrine
  • Dextroamphetamine
  • Diethylpropion
  • Dobutamine
  • Dopamine
  • Doxylamine / phenylephrine
  • Doxylamine / pseudoephedrine
  • Dyphylline / ephedrine / guaifenesin / phenobarbital
  • Eletriptan
  • Ephedrine
  • Ephedrine nasal
  • Ephedrine / guaifenesin
  • Ephedrine / guaifenesin / theophylline
  • Ephedrine / hydroxyzine / theophylline
  • Ephedrine / phenobarbital / potassium iodide / theophylline
  • Ephedrine / phenobarbital / theophylline
  • Ephedrine / potassium iodide
  • Epinephrine
  • Epinephrine ophthalmic
  • Epinephrine topical
  • Epinephrine / etidocaine
  • Epinephrine / lidocaine
  • Epinephrine / lidocaine / tetracaine topical
  • Epinephrine / pilocarpine ophthalmic
  • Epinephrine / prilocaine
  • Fenfluramine
  • Fexofenadine / pseudoephedrine
  • Fluticasone / salmeterol
  • Fluticasone / umeclidinium / vilanterol
  • Fluticasone / vilanterol
  • Formoterol
  • Formoterol / glycopyrrolate
  • Formoterol / mometasone
  • Frovatriptan
  • Furazolidone
  • Glycopyrrolate / indacaterol
  • Guaifenesin / hydrocodone / pheniramine / phenylephrine / phenylpropanolamine
  • Guaifenesin / hydrocodone / pheniramine / phenylpropanolamine / pyrilamine
  • Guaifenesin / hydrocodone / phenylephrine
  • Guaifenesin / hydrocodone / pseudoephedrine
  • Guaifenesin / phenylephrine
  • Guaifenesin / phenylephrine / phenylpropanolamine
  • Guaifenesin / phenylephrine / pyrilamine
  • Guaifenesin / phenylpropanolamine
  • Guaifenesin / pseudoephedrine
  • Hydrocodone / pheniramine / phenylephrine / phenylpropanolamine / pyrilamine
  • Hydrocodone / phenylephrine
  • Hydrocodone / phenylephrine / pyrilamine
  • Hydrocodone / phenylpropanolamine
  • Hydrocodone / potassium guaiacolsulfonate / pseudoephedrine
  • Hydrocodone / pseudoephedrine
  • Hydrocodone / pseudoephedrine / triprolidine
  • Hydroxyamphetamine ophthalmic
  • Hydroxyamphetamine / tropicamide ophthalmic
  • Hyoscyamine / methenamine / methylene blue / phenyl salicylate
  • Hyoscyamine / methenamine / methylene blue / phenyl salicylate / sodium biphosphate
  • Hyoscyamine / methenamine / methylene blue / sodium biphosphate
  • Ibuprofen / phenylephrine
  • Ibuprofen / pseudoephedrine
  • Indacaterol
  • Isocarboxazid
  • Isoetharine
  • Isoproterenol
  • Isoproterenol / phenylephrine
  • Ketorolac / phenylephrine ophthalmic
  • Levalbuterol
  • Levonordefrin / mepivacaine
  • Linezolid
  • Lisdexamfetamine
  • Loratadine / pseudoephedrine
  • Ma huang
  • Mazindol
  • Mephentermine
  • Metaproterenol
  • Metaraminol
  • Methamphetamine
  • Methoxamine
  • Methscopolamine / phenylephrine
  • Methscopolamine / pseudoephedrine
  • Methylene blue
  • Midodrine
  • Mineral oil / petrolatum / phenylephrine topical
  • Naphazoline / phenylephrine / pyrilamine
  • Naproxen / pseudoephedrine
  • Naproxen / sumatriptan
  • Naratriptan
  • Norepinephrine
  • Phendimetrazine
  • Phenelzine
  • Pheniramine / phenylephrine nasal
  • Pheniramine / phenylpropanolamine / phenyltoloxamine / pyrilamine
  • Pheniramine / phenylpropanolamine / pyrilamine
  • Pheniramine / phenyltoloxamine / pseudoephedrine / pyrilamine
  • Phentermine
  • Phentermine / topiramate
  • Phenylephrine
  • Phenylephrine nasal
  • Phenylephrine ophthalmic
  • Phenylephrine topical
  • Phenylephrine / potassium guaiacolsulfonate
  • Phenylephrine / pramoxine topical
  • Phenylephrine / promethazine
  • Phenylephrine / pyrilamine
  • Phenylephrine / pyrilamine nasal
  • Phenylephrine / scopolamine ophthalmic
  • Phenylephrine / sulfacetamide sodium ophthalmic
  • Phenylephrine / thonzylamine
  • Phenylephrine / triprolidine
  • Phenylephrine / zinc sulfate ophthalmic
  • Phenylpropanolamine
  • Pirbuterol
  • Procarbazine
  • Pseudoephedrine
  • Pseudoephedrine / pyrilamine
  • Pseudoephedrine / terfenadine
  • Pseudoephedrine / triprolidine
  • Racepinephrine
  • Ritodrine
  • Rizatriptan
  • Salmeterol
  • Sumatriptan
  • Terbutaline
  • Tranylcypromine
  • Umeclidinium / vilanterol
  • Zolmitriptan

Additionally, droxidopa may have symptomatic interactions with drugs not listed here. If any of these occur, please notify your caregiver at once.

Warnings

Droxidopa can initiate or worsen supine hypertension in nOH patients. Patients should be told to elevate the head of their bed during periods of sleep or rest. Blood pressure should be monitored when the patient is supine and when the patient is in the elevated-head sleep position. If supine hypertension is persistent, droxidopa should be discontinued or reduced. Unmanaged hypertension in conjunction with droxidopa can lead to increased risk of cardiovascular events such as stroke.

Droxidopa has been associated with a condition similar to neuroleptic malignant syndrome (NMS), which can cause the following symptoms

  • Altered consciousness
  • Fever or hyperthermia
  • Involuntary movements
  • Mental status changes
  • Muscle rigidity

Patients who have had their droxidopa dosage changed, or have had an abrupt reduction or discontinuation of their concomitant levodopa, should be closely monitored for NMS symptoms. This is especially true in cases in which the patient is also taking neuroleptics.

Droxidopa can worsen preexisting arrhythmias, congestive heart disease and ischemic heart disease. Caregivers must exercise caution before treating patients affected by these conditions with droxidopa.

Droxidopa can cause allergic reactions such as

  • Anaphylaxis
  • Angioedema
  • Bronchospasm
  • Urticaria
  • Rash

If any of these reactions occur, droxidopa should be immediately discontinued, and the condition treated with the appropriate therapy.

A test of droxidopa on pregnant rats saw the deaths of several female rat fetuses. It is possible that the drug can be harmful to human fetuses.

Droxidopa is not recommended for use by lactating women, as there is a possible risk for insufficient weight gain in breastfed infants when droxidopa is present in breastmilk.

The effectiveness of droxidopa in pediatric patients is not yet known.

When droxidopa is used by older patients, there is no significant difference in response from that of younger patients, though an increased risk of hypersensitivity to droxidopa may be present in the elderly.

Droxidopa is primarily processed through the kidneys. However, there was no greater occurrence of adverse reactions among patients with mild to moderate impairment of renal function than there was among those with normal renal function. It is not known whether patients with several renal impairments respond differently than those with mild/moderate renal impairment or normal renal function.

Droxidopa overdoses have been known to cause hypertensive crisis and hemorrhage. In the case of an overdose, droxidopa should be discontinued and appropriate treatment and support therapy for the symptoms should be initiated. Patients will be advised to remain standing or seated until blood pressure reaches a normal level.

Droxidopa is contraindicated in patients who are hypersensitive to the medication as well as its ingredients.

Storage

Droxidopa capsules should be stored in an appropriate container at a temperature of 68-77 degrees Fahrenheit.

Summary

Droxidopa can be an effective treatment for primary autonomic failure induced hypotension. Droxidopa is a very powerful medication, especially due to its ability to cross the blood-brain barrier, which can allow it to be more effective than other remedies. However, this can also come with great risk. The patient should inform their doctor of any other medications they are taking or any conditions they are diagnosed with.

Droxidopa carries the risk of serious conditions such as supine hypertension, neuroleptic malignant syndrome, and hypersensitive reactions. As such the patient should be monitored for these and other serious reactions during treatment with droxidopa, and development of these adverse effects should be met with the appropriate treatment. The effectiveness of droxidopa should be monitored throughout treatment, to be sure that the drug is worth any potential risk. Very close attention should be paid to the patient's blood pressure during droxidopa treatment.