Droxidopa
FDA Drug Information • Also known as: Droxidopa, Northera
- Brand Names
- Droxidopa, Northera
- Route
- ORAL
- Dosage Form
- CAPSULE
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
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 capsules [see Warnings and Precautions ( 5.1 )]. WARNING: SUPINE HYPERTENSION See full prescribing information for complete boxed warning. 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 capsules [see Warnings and Precautions ( 5.1 )] .
Description
11 DESCRIPTION Droxidopa capsules contain droxidopa, which is a synthetic amino acid precursor of norepinephrine, for oral administration. Chemically, droxidopa is (–)-threo-3-(3,4-Dihydroxyphenyl)-L-serine. It has the following structural formula: Droxidopa is an odorless, tasteless, white to light brown color powder. It is slightly soluble in water, and practically insoluble in methanol, glacial acetic acid, ethanol, acetone, ether, and chloroform. It is soluble in dilute hydrochloric acid. It has a molecular weight of 213.19 and a molecular formula of C 9 H 11 NO 5 . Droxidopa capsules also contain the following inactive ingredients: mannitol, pregelatinised starch (corn starch), and magnesium stearate. The capsule shell is printed with black ink. The black inks contain shellac, propylene glycol, black iron oxide, potassium hydroxide. The capsule shell contains the following inactive ingredients: 100 mg – gelatin, titanium dioxide, FD&C Blue No. 2, black and red iron oxide; 200 mg – gelatin, titanium dioxide, FD&C Blue No. 2, black and yellow iron oxide; 300 mg – gelatin, titanium dioxide, FD&C Blue No. 2, yellow iron oxide. Droxidopa capsules differ in size and color by strength [see Dosage Forms and Strengths ( 3 )] . droxi01
What Is Droxidopa Used For?
1 INDICATIONS & USAGE Droxidopa capsules is indicated for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson's disease [PD], 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 capsules should be assessed periodically. Droxidopa capsule is indicated for the treatment of orthostatic dizziness, light headedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson's disease [PD], 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 capsules should be assessed periodically ( 1 ).
Dosage and Administration
2 DOSAGE & ADMINISTRATION Starting dose is 100 mg three times during the day ( 2.1 ) Titrate by 100 mg three times daily, up to a maximum dose of 600 mg three times daily ( 2.1 ) Take consistently with or without food ( 2.1 ) To reduce the potential for supine hypertension, elevate the head of the bed and give the last dose at least 3 hours prior to bedtime ( 2.1 ) Take Droxidopa capsule whole ( 2.1 ) 2.1 Dosing Information The recommended starting dose of droxidopa capsules is 100 mg, taken orally three times daily: upon arising in the morning, at midday, and in the late afternoon at least 3 hours prior to bedtime (to reduce the potential for supine hypertension during sleep). Administer droxidopa capsules consistently, either with food or without food. Take droxidopa capsule whole. Titrate to symptomatic response, in increments of 100 mg three times daily every 24 to 48 hours up to a maximum dose of 600 mg three times daily (i.e., a maximum total daily dose of 1,800 mg). Monitor supine blood pressure prior to initiating droxidopa capsules and after increasing the dose. Patients who miss a dose of droxidopa capsules should take their next scheduled dose.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions with droxidopa capsules are included in more detail in the Warnings and Precautions section of the label: Supine Hypertension [see Warnings and Precautions ( 5.1 )] Hyperpyrexia and Confusion [see Warnings and Precautions ( 5.2 )] May exacerbate existing ischemic heart disease, arrhythmias, and congestive heart failure [see Warnings and Precautions ( 5.3 )] The most common adverse reactions (>5% and ≥3% compared to placebo) are headache, dizziness, nausea, and hypertension ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety evaluation of droxidopa capsules is based on two placebo-controlled studies 1 to 2 weeks in duration (Studies 301 and 302), one 8-week placebo-controlled study (Study 306), and two long-term, open-label extension studies (Studies 303 and 304). In the placebo-controlled studies, a total of 485 patients with Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, or non-diabetic autonomic neuropathy were randomized and treated, 245 with droxidopa capsules and 240 with placebo [see Clinical Studies ( 14 )] . Placebo-Controlled Experience The most commonly observed adverse reactions (those occurring at an incidence of greater than 5% in the droxidopa capsules group and with at least a 3% greater incidence in the droxidopa capsules group than in the placebo group) in droxidopa capsules -treated patients during the three placebo-controlled trials were headache, dizziness, nausea, and hypertension. The most common adverse reactions leading to discontinuation from droxidopa capsules were hypertension or increased blood pressure and nausea. Table 1. Most Common Adverse Reactions Occurring More Frequently in the droxidopa capsules Group Study 301 and Study 302 (1 to 2 Weeks Randomized Treatment) Study 306 (8 to 10 Weeks Randomized Treatment) Placebo (N=132) n (%) Droxidopa capsules (N=131) n (%) Placebo (N=108) n (%) Droxidopa capsules (N=114) n (%) Headache 4 (3.0) 8 (6.1) 8 (7.4) 15 (13.2) Dizziness 2 (1.5) 5 (3.8) 5 (4.6) 11 (9.6) Nausea 2 (1.5) 2 (1.5) 5 (4.6) 10 (8.8) Hypertension 0 2 (1.5) 1 (0.9) 8 (7.0) Note: n=number of patients. Adverse reactions that were reported in greater than 5% of patients in the droxidopa capsules group and with at least a 3% greater incidence in the droxidopa capsules group than in the placebo group were from Study 306. Long-Term, Open-Label Trials with droxidopa capsules In the long-term, open-label extension studies, a total of 422 patients, mean age 65 years, were treated with droxidopa capsules for a mean total exposure of approximately one year. The commonly reported adverse events were falls (24%), urinary tract infections (15%), headache (13%), syncope (13%), and dizziness (10%). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of droxidopa capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac Disorders: Chest pain Eye Disorders: Blurred vision Gastrointestinal Disorders: Pancreatitis, abdominal pain, vomiting, diarrhea General Disorders and Administration Site Conditions: Fatigue Nervous System Disorders: Cerebrovascular accident Psychiatric Disorders: Psychosis, hallucination, delirium, agitation, memory disorder
Drug Interactions
7 DRUG INTERACTIONS Use of DOPA decarboxylase inhibitors may require dose adjustments for droxidopa capsules ( 7.2 ) 7.1 Drugs that Increase Blood Pressure Administering droxidopa capsules 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. 7.2 Parkinson's Medications Dopa-decarboxylase inhibitors may require dose adjustments for droxidopa capsules. 7.3 Non-selective MAO Inhibitors The concomitant use of selective MAO-B inhibitors, such as rasagiline or selegiline, was permitted in the droxidopa capsules clinical trials. However, based on mechanism of action, the use of non-selective MAO inhibitors and linezolid should be avoided as there is a potential for increased blood pressure when taken with droxidopa capsules.
Contraindications
4 CONTRAINDICATIONS Droxidopa capsules is contraindicated in patients who have a history of hypersensitivity to the drug or its ingredients [see Warnings and Precautions ( 5.4 )]. History of hypersensitivity to the drug or its ingredients ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on use of droxidopa capsules in pregnant women and risk of major birth defects or miscarriage. droxidopa capsules did not produce significant reproductive toxicity in pregnant female rats or rabbits or in their fetuses. However, when pregnant female rats were dosed during days 7-17 of gestation (the period of fetal organogenesis) with doses of droxidopa capsules corresponding to 0.3, 1 and 3 times the maximum recommended daily dose of 1,800 mg in a 60 kg patient, based on body surface area, and when their male and female offspring (who were exposed only during fetal life) were subsequently bred, the female offspring exhibited a dose-dependent reduction in the number of live fetuses across all three doses and an increased number of embryonic/fetal deaths at the two higher doses (see Data). The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data During a multigenerational reproductive toxicity study in rats, pregnant females were dosed during days 7-17 of gestation (the period of fetal organogenesis) with doses of droxidopa capsules corresponding to 0.3, 1 and 3 times the maximum recommended daily dose of 1,800 mg in a 60 kg patient. Reduced weight gain, renal lesions, and a small number of deaths were observed in females treated with the two higher doses. When their male and female offspring (who were exposed to droxidopa capsules only during fetal life) were subsequently bred, the female offspring exhibited a dose-dependent reduction in the number of live fetuses across all three doses and an increased number of embryonic/fetal deaths at the two higher doses.
Overdosage
10 OVERDOSAGE 10.1 Symptoms There have been cases of overdose reported during postmarketing surveillance. A patient ingested 7,700 mg of droxidopa and experienced a hypertensive crisis that resolved promptly with treatment. Another patient treated with a total daily dose of 2,700 mg of droxidopa capsules experienced hypertension and an intracranial hemorrhage. 10.2 Treatment There is no known antidote for droxidopa capsules overdosage. In case of an overdose that may result in an excessively high blood pressure, discontinue droxidopa capsules and treat with appropriate symptomatic and supportive therapy. Counsel patients to remain in a standing or seated position until their blood pressure drops below an acceptable limit.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Droxidopa capsules are supplied in the following dosage strengths: 100 mg: Hard gelatin, size 3 capsule, with light blue to blue cap and white opaque body, imprinted with “100” on cap and “DRO” on body in black ink, filled with a white or off white to light brown powder. 200 mg: Hard gelatin, size 2 capsule, with light yellow to yellow cap and white opaque body, imprinted with “200” on cap and “DRO” on body in black ink, filled with a white or off white to light brown powder. 300 mg: Hard gelatin, size 1 capsule, with light green to green cap and white opaque body, imprinted with “300” on cap and “DRO” on body in black ink, filled with a white or off white to light brown powder. 100 mg 90-count bottle (NDC 82249-551-90) 200 mg 90-count bottle (NDC 82249-552-90) 300 mg 90-count bottle (NDC 82249-554-90) 16.2 Storage and Handling Droxidopa capsules should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.