Droxidopa is a medication used primarily in the treatment of orthostatic hypotension (low blood pressure upon standing) and neurogenic orthostatic hypotension. It is a synthetic precursor of norepinephrine, a neurotransmitter involved in regulating blood pressure. Droxidopa works by increasing the levels of norepinephrine in the body, thereby helping to raise blood pressure and alleviate symptoms associated with orthostatic hypotension, such as dizziness, lightheadedness, and fainting.

Orthostatic hypotension can occur in various conditions, including Parkinson's disease, multiple system atrophy, pure autonomic failure, and other neurodegenerative disorders. Droxidopa can help improve symptoms and quality of life for individuals affected by these conditions.

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.

Droxidopa Adult dose:

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

• Start with 100 milligrams (mg) of droxidopa three times a day.
• If needed, your doctor may increase the dose by adding 100 mg three times a day every 24 to 48 hours until you feel better.
• The highest dose you can take in a day is 1,800 mg.

So, you begin with a small amount and gradually increase it until it helps you feel better, but you shouldn't take more than 1,800 mg per day.

Use in Children:

Not indicated.

Pregnancy Category: C

• In studies with animals, some negative effects on reproduction have been seen.

Use during breastfeeding:

• We're not sure if droxidopa passes into breast milk.
• Because there's a chance it could cause serious problems for a breastfeeding baby, the company that makes it advises against breastfeeding while taking this medication.

Dose in Kidney disease:

• If your kidney function is good with a glomerular filtration rate (GFR) above 30 milliliters per minute, you don't need to change the dose of droxidopa.
• If your GFR is 30 milliliters per minute or less, the manufacturer hasn't studied whether you need to change the dose, so there are no specific recommendations available.

Dose in Liver disease:

• The manufacturer's instructions don't include any specific changes to the dosage for people with liver problems.

Common Side Effects of Droxidopa (Northera):

• Central nervous system:
  • Headache
  • Dizziness

• Cardiovascular:
  • Hypertension
• Gastrointestinal:
  • Nausea

Contraindications to Droxidopa (Northera):

• If someone is allergic or hypersensitive to droxidopa or any of the ingredients in the medication, they should not take it.

Warnings and precautions

Anaphylaxis, allergic reactions

• Some people may have hypersensitivity reactions to droxidopa.
• Reactions could include severe allergic responses like anaphylaxis (a serious allergic reaction), swelling of the face or throat (angioedema), difficulty breathing (bronchospasm), rash, or hives (urticaria).
• If any of these reactions happen, seek emergency medical help immediately. Stop using droxidopa and get medical support right away.

Hypertension: [US Boxed Warning]:

• Droxidopa might lead to high blood pressure, especially when lying down (supine hypertension).
• Tell patients to raise the head of their bed when resting or sleeping.
• Regularly check blood pressure while lying down and while in the recommended head-elevated sleeping position.
• If supine hypertension continues, consider lowering or stopping droxidopa to avoid heart problems.
• Not managing supine hypertension well might raise the risk of heart-related events.

Neuroleptic malignant syndrome:

• Sometimes, droxidopa can cause a condition that looks like neuroleptic malignant syndrome.
• Symptoms may include very high fever and confusion.
• Be extra careful when changing doses or stopping levodopa suddenly, especially if the patient is also taking neuroleptic medications.
• Watch patients closely for these symptoms.

Cardiovascular disease

• Droxidopa could make existing heart conditions like ischemic heart disease (reduced blood flow to the heart), irregular heartbeats (arrhythmias), or congestive heart failure (when the heart can't pump blood well) worse.
• Before starting treatment, think about the possible risks if the patient already has heart problems.

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:

Monitoring Supine Blood Pressure:

• Before starting treatment with droxidopa and while using it, it's important to check the patient's blood pressure when lying down (supine).
• Increase the frequency of blood pressure checks, especially when raising the dose of droxidopa.
• Regular monitoring helps in understanding how droxidopa affects blood pressure when the patient is lying down, which is crucial for managing supine hypertension and preventing related complications.

How to administer Droxidopa (Northera)?

• Take the droxidopa capsule whole; do not crush or chew it.
• Take it the same way every time, whether with or without food.
• Take one capsule in the morning when you wake up, another at midday, and one more in the late afternoon.
• Make sure there's at least a 3-hour gap between taking the last dose and going to bed. This helps reduce the risk of developing high blood pressure while sleeping (supine hypertension).

Mechanism of action of Droxidopa (Northera):

• Droxidopa is a man-made compound similar to an amino acid.
• When it's in the body, it gets turned into norepinephrine by an enzyme called dopadecarboxylase.
• Norepinephrine is a chemical that has various effects in the body.
• One of its main jobs is to tighten up blood vessels, both the small ones (arterioles) and the larger ones (veins).
• This tightening, called vasoconstriction, helps raise blood pressure by making it harder for blood to flow through these vessels.
• Droxidopa works by increasing the levels of norepinephrine, which then boosts blood pressure by causing these blood vessels to constrict.

Absorption:

• Eating high-fat meals can decrease the amount of droxidopa absorbed by about 35% and delay its arrival in the bloodstream by roughly 2 hours.

Distribution:

• The volume of distribution (V) of droxidopa in the body is approximately 200 liters.

Protein Binding:

• Droxidopa binds to proteins in the blood to varying extents, ranging from 26% to 75%.

Metabolism:

• Droxidopa undergoes metabolism primarily through the catecholamine pathway in the body.
• It can be converted into methoxylated dihydroxyphenylserine (3-OM-DOPS), which is a significant metabolite.
• Alternatively, it can be transformed into norepinephrine by an enzyme called DOPA decarboxylase (DDC), or into protocatechualdehyde by DOPS aldolase.

Elimination:

• The half-life of droxidopa, meaning the time it takes for half of the drug to be removed from the bloodstream, is around 2.5 hours.

Time to Peak Plasma Concentration:

• It typically takes between 1 to 4 hours for droxidopa to reach its highest concentration in the blood after being taken.

Excretion:

• The body eliminates droxidopa primarily through urine, accounting for about 75% of the drug's total elimination.

International Brand Names of Droxidopa:

• Northera
• Dops

Droxidopa Brand Names in Pakistan:

No Brands Available in Pakistan.