Droxidopa is indicated for the treatment of orthostatic dizziness and light-headedness in adult patients with symptomatic neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson's disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy. Effectiveness beyond 2 weeks of treatment has not been established. The continued effectiveness of droxidopa should be assessed periodically.

According to IQVIA, US sales of Droxidopa Capsules, 100mg, 200mg and 300mg, were approximately $353 million in the 12 months ending November 2020.

Brian Hoffmann, President of Generics said, “We are pleased to launch Droxidopa Capsules and to be among the first wave of generics, making this important drug available to customers and patients in the US. We are committed to diversifying our portfolio through delivering on our pipeline and bringing new products to market, helping us to improve patients’ access to high-quality and affordable generic medicines around the world.”

Important Safety Information for Droxidopa Capsules, 100mg, 200mg and 300mg:

WARNING: SUPINE HYPERTENSION

Monitor supine blood pressure prior to and during treatment and more frequently when increasing doses. Elevating the head of the bed lessens the risk of supine hypertension, and blood pressure should be measured in this position. If supine hypertension cannot be managed by elevation of the head of the bed, reduce or discontinue droxidopa.

CONTRAINDICATIONS

Droxidopa is contraindicated in patients who have a history of hypersensitivity to the drug or its ingredients.

WARNINGS AND PRECAUTIONS

• Supine Hypertension

Droxidopa therapy may cause or exacerbate supine hypertension in patients with neurogenic orthostatic hypertension. Advise patients to elevate the head of the bed when resting or sleeping. Monitor blood pressure, both in the supine position and in the recommended head-elevated sleeping position. Reduce the dose or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well managed, droxidopa may increase the risk of cardiovascular events, particularly stroke.

• Hyperpyrexia and Confusion

Post marketing cases of a symptom complex resembling neuroleptic malignant syndrome (i.e., hyperthermia, muscle rigidity, involuntary movements, mental status changes, altered consciousness) have been reported with droxidopa use during postmarketing surveillance. The early diagnosis of this condition is important for appropriate management. Observe patients carefully when the dosage of droxidopa is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.

• Ischemic Heart Disease, Arrhythmias and Congestive Heart Failure

Droxidopa may exacerbate existing ischemic heart disease, arrhythmias and congestive heart failure. Carefully consider this potential risk before initiating therapy in patients with these conditions.

• Allergic Reactions

Hypersensitivity reactions, some requiring emergency treatment, have been reported during postmarketing surveillance. If a hypersensitivity reaction occurs, discontinue droxidopa and initiate appropriate therapy.

• Immunologic

This product contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although overall incidence of tartrazine sensitivity in the general population is low, it is frequently seen in patients who have aspirin hypersensitivity.

• Lactation

There is no information regarding the presence of droxidopa or its active metabolite(s) in human milk, the effects of droxidopa on the breastfed child, nor the effects of droxidopa on milk production/excretion. Because of the potential for serious adverse reactions in animal data, including reduced weight gain in breastfed infants, advise a woman not to breastfeeding during treatment with droxidopa.

ADVERSE REACTIONS

• The most common adverse reactions (>5% and ≥3% difference compared to placebo) were headache, dizziness, nausea, and hypertension.

• In the long-term, open-label extension studies, the most commonly reported adverse events were falls, urinary tract infections, headache, syncope and dizziness.

The following adverse reactions are described in more detail in the Warnings and Precautions section of the full Prescribing Information:

• Supine Hypertension
• Hyperpyrexia and Confusion
• May exacerbate existing ischemic heart disease, arrhythmias and congestive heart failure

The safety of droxidopa is based on 2 placebo-controlled studies 1 to 2 weeks in duration, an 8-week placebo-controlled study and 2 long-term, open-label extension studies.

For more information about adverse reactions, see the full Prescribing Information.

Monitoring

• Therapeutic/Efficacy

Improvement in symptoms of neurogenic orthostatic hypotension (eg, orthostatic dizziness, lightheadedness) is indicative of efficacy.

• Toxic

Monitor supine blood pressure (and with head elevated) prior to and during treatment. More frequent monitoring is required with dosage increases

DRUG INTERACTIONS

• Drugs That Increase Blood Pressure

Administering droxidopa in combination with other agents that increase blood pressure (e.g., norepinephrine, ephedrine, midodrine, and triptans) would be expected to increase the risk for supine hypertension.

• Parkinson’s Medications

Dopa-decarboxylase inhibitors may require dose adjustments for droxidopa.

• Non-Selective MAO Inhibitors

The concomitant use of selective MAO-B inhibitors was permitted in the droxidopa clinical trials. Based on mechanism of action, however, non-selective MAO inhibitors and linezolid should be avoided, as there is a potential for increased blood pressure when taken with droxidopa.

USE IN SPECIFIC POPULATIONS

• Pregnancy

There are no available data on the use of droxidopa in pregnant women and risk of major birth defects or miscarriage.

• Lactation

There is no information regarding the presence of droxidopa or its active metabolite(s) in human milk, the effects of droxidopa on the breastfed child or the effects of droxidopa on milk production/excretion.

• Pediatric Use

The safety and effectiveness of droxidopa in pediatric patients have not been established.

• Geriatric Use

In clinical trials, no overall differences in safety were observed between patients 75 years and older and younger patients. However, greater sensitivity of some older individuals to droxidopa cannot be ruled out.

• Renal Impairment

Clinical experience with droxidopa in patients with severe renal function impairment (GFR <30 mL/min) is limited; therefore, dosing recommendations cannot be provided for these patients.

DOSAGE AND ADMINISTRATION

.

• Dosage

Initial, 100 mg orally 3 times daily scheduled: upon arising in the morning, at midday, and in late afternoon at least 3 hours before bedtime. Titrate as needed in increments of 100 mg 3 times daily every 24 to 48 hours; MAX dose, 1800 mg/day. Efficacy beyond 2 weeks of treatment not established

• Administration

Oral route: Swallow capsule whole and take consistently either with or without food

• Storage

Store capsules at room temperature between 20 and 25 degrees C (68 and 77 degrees F);

For more information, please see the full Prescribing Information, including the Boxed Warning.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit https://www.fda.gov/medwatch or call 1-800-FDA-1088.

Manufactured by: West-Ward Columbus Inc., Columbus, OH 43228

Distributed by: Hikma Pharmaceuticals USA Inc., Berkeley Heights, NJ, 07922