Droxidopa (Northera) causes vasoconstriction and increases blood pressure. It is used to treat patients with postural hypotension as in patients with neurogenic orthostatic hypotension caused by autonomic failure.

Droxidopa Uses:

• Neurogenic orthostatic hypotension:

  • It is indicated for the treatment postural hypotension (orthostatic hypotension) that may manifest as light-headedness, dizziness, and blackouts in adults with neurogenic orthostatic hypotension (NOH) caused by primary autonomic failure as in:
    • Parkinson's disease [PD],
    • multiple system atrophy [MSA],
    • pure autonomic failure [PAF]),
    • dopamine beta-hydroxylase deficiency, and
    • nondiabetic autonomic neuropathy.

Adult dose:

Droxidopa (Northera) Dose in the treatment of Neurogenic orthostatic hypotension:

• The initial dose is 100 mg orally three times a day.
• The dose should be titrated every 24 to 48 hours in increments of 100 mg thrice daily until an adequate response is observed.
• The maximum dose is 1,800 mg/day.

Use in Children:

Not indicated.

Pregnancy Category: C

• Although it has not been tested in human pregnancies or animal reproduction studies, it has been shown to cause adverse reactions.

Use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• It is not recommended to be used during lactation as it can cause adverse drug reactions in infants.

Renal dose:

Dose in Kidney disease:

• GFR >30 mL/minute:

  • No dose adjustments are necessary.

• GFR ≤30 mL/minute:

  • There are no dosage adjustments provided in the manufacturer's labeling (it has not been studied).

Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer's labeling.

Side effects:

Common Side Effects of Droxidopa (Northera):

• Central nervous system:

  • Headache
  • Dizziness

• Cardiovascular:

  • Hypertension

• Gastrointestinal:

  • Nausea

Contraindications to Droxidopa (Northera):

Allergies to droxidopa and any component of the formulation

Warnings and precautions

• Anaphylaxis, allergic reactions

  • There have been reports of allergic reactions to it, including angioedema and bronchospasm as well as rash, urticaria and anaphylaxis. 
  • The patient should immediately stop using the medication if they develop symptoms that indicate an allergic reaction.

• Hypertension: [US Boxed Warning]:

  • It is a vasoconstrictor and can cause or exacerbate supinehypertension.
  • When sleeping or resting, patients should elevate their heads.
  • Patients should have their blood pressure checked during the supine or elevated head position.
  • Supine hypertension is a condition that can lead to the need for treatment. 
  • Supine hypertension can lead to exacerbation or worsening of existing cardiovascular diseases.

• Neuroleptic malignant syndrome:

  • Patients have reported neuroleptic malignant syndrome-type clinical features. 
  • It has been reported that patients suffer from confusion and hyperpyrexia.
  • These symptoms should be noted in all patients receiving treatment, especially if the concomitant dose of levodopa has been reduced or abruptly stopped. 
  • Patients taking concomitant neuroleptic medications should be cautious.

• Cardiovascular disease

  • It can exacerbate existing heart disease, congestive or severe cardiac failure, and may cause arrhythmias. Before treatment is initiated, patients should be evaluated.

Droxidopa: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Monitor supine blood pressure before treatment initiation and during the treatment.
• Blood pressure should be frequently monitored after dosage adjustment.

How to administer Droxidopa (Northera)?

• It should be administered whole without chewing, biting, or opening the capsule. the drug should be taken in the early morning preferably.
• It can be taken until late afternoon at least three hours before bedtime (because of the risks of supine hypertension). 

Mechanism of action of Droxidopa (Northera):

• It is a synthetic analog of an amino acid that is converted into norepinephrine using the enzyme dopa–decarboxylase. 
• It causes blood vessels to contract, causing arterial and venous vasoconstriction. This results in an increase of blood pressure.

Absorption:

• The Cmax and AUC decrease by 35% and 20%, respectively, when the meal is high-fat. To reach the Cmax, absorption takes around 2 hours.

Protein binding:

• 26% to 75%

Metabolism:

• It is mostly metabolized via the catecholamine pathway. Initially, it is converted to its major metabolite, methoxylated dihydroxyphenylserine (3-OM-DOPS), by catechol-O-methyltransferase (COMT), by DOPA decarboxylase (DDC) to norepinephrine, or to protocatechualdehyde by DOPS aldolase.

Half-life elimination:

• About 2.5 hours

Time to peak, plasma:

• 1 to 4 hours

Excretion:

• 75% of the drug is excreted in the urine.

International Brand Names of Droxidopa:

• Northera
• Dops

Droxidopa Brand Names in Pakistan:

No Brands Available in Pakistan.