What is Droxidopa used for?

Droxidopa is a synthetic amino acid precursor of norepinephrine, also known under the trade name Northera. It was initially developed and researched by Dainippon Sumitomo Pharma in Japan and later brought to the United States by Lundbeck Inc. Droxidopa is primarily indicated for the treatment of orthostatic hypotension, a condition characterized by a significant drop in blood pressure upon standing up, which can lead to dizziness, lightheadedness, and even fainting. This makes it particularly useful for patients with neurogenic orthostatic hypotension (nOH) related to autonomic nervous system failure, such as Parkinson's disease, multiple system atrophy, and pure autonomic failure.

Approved by the U.S. Food and Drug Administration (FDA) in 2014, Droxidopa has undergone various clinical trials that demonstrated its efficacy and safety in managing symptoms of nOH. Its approval marked a significant step forward in the treatment of this debilitating condition, providing a valuable option for patients who previously had limited therapeutic choices.

Droxidopa Mechanism of Action

Droxidopa works by being converted into norepinephrine both in the peripheral and central nervous systems. Norepinephrine is a key neurotransmitter responsible for vasoconstriction, the narrowing of blood vessels, which in turn increases blood pressure. The enzyme responsible for this conversion is L-aromatic-amino-acid decarboxylase (AAAD), which is widely distributed throughout the body but particularly active in the sympathetic nervous system.

Once administered, Droxidopa crosses the blood-brain barrier and is converted into norepinephrine. This boosts the levels of norepinephrine, thereby improving vascular tone and increasing blood pressure. This mechanism allows Droxidopa to counteract the symptomatic drops in blood pressure experienced by patients with nOH, reducing episodes of dizziness and lightheadedness.

How to Use Droxidopa

Droxidopa is available in capsule form and is typically taken orally. The dosing regimen can vary depending on the individual patient’s needs and the severity of their condition. Generally, the starting dose is 100 mg, taken three times a day. The doses are typically taken in the morning, at midday, and in the late afternoon. However, the dose can be titrated up in increments of 100 mg, three times daily, until the optimal therapeutic effect is achieved, without exceeding a maximum daily dose of 1800 mg.

It is important for patients to follow their healthcare provider's instructions carefully and to take the medication consistently. The onset of action of Droxidopa can be quite rapid, with some patients experiencing symptomatic relief within hours of taking their first dose. However, it may take a few days for the full therapeutic effects to manifest.

Patients are usually advised to take Droxidopa at least three hours before bedtime to minimize the risk of supine hypertension, a condition where blood pressure increases abnormally when lying down, which could potentially lead to other complications.

What are Droxidopa Side Effects

As with any medication, Droxidopa can cause side effects. The most commonly reported side effects include headache, dizziness, nausea, and fatigue. Some patients may experience an increase in blood pressure while lying down, known as supine hypertension. This can be particularly concerning and requires careful monitoring by the healthcare provider.

Other possible side effects include urinary tract infection, falls, and syncope (fainting). Less commonly, patients may experience an allergic reaction, characterized by symptoms such as rash, itching, swelling, severe dizziness, and trouble breathing. If any of these symptoms occur, medical attention should be sought immediately.

Contraindications for Droxidopa use include patients with a history of hypersensitivity to the drug or any of its components. It is also not recommended for patients who have a history of severe supine hypertension, as Droxidopa can exacerbate this condition.

In addition, caution should be exercised when prescribing Droxidopa to patients with cardiovascular conditions such as heart disease, arrhythmias, or a history of stroke, as increased levels of norepinephrine can potentially aggravate these conditions.

What Other Drugs Will Affect Droxidopa

Several medications can interact with Droxidopa, potentially affecting its efficacy or increasing the risk of adverse effects. One key interaction is with monoamine oxidase inhibitors (MAOIs), a class of drugs used to treat depression and Parkinson's disease. MAOIs can inhibit the breakdown of norepinephrine, leading to dangerously high levels of this neurotransmitter when taken with Droxidopa.

Other drugs that can interact with Droxidopa include certain types of antidepressants, particularly tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), which also affect norepinephrine levels. Additionally, medications that affect blood pressure, such as beta-blockers, may interfere with Droxidopa's therapeutic effects.

Patients taking Droxidopa should inform their healthcare provider of all the medications they are currently taking, including over-the-counter drugs, supplements, and herbal products. This will help to avoid potential drug interactions and ensure the safe and effective use of Droxidopa.

In conclusion, Droxidopa offers a valuable treatment option for patients suffering from neurogenic orthostatic hypotension, providing significant symptomatic relief through its unique mechanism of action. However, it is essential to use this medication under the close supervision of a healthcare provider due to the potential for side effects and drug interactions. By following prescribed guidelines and monitoring for any adverse effects, patients can benefit from improved quality of life and reduced symptoms of nOH.