Levodopa
FDA Drug Information • Also known as: Inbrija
- Brand Names
- Inbrija
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
11 DESCRIPTION INBRIJA consists of a dry powder formulation of levodopa for oral inhalation with the INBRIJA inhaler. The inhalation powder is packaged in white hypromellose capsules. Each capsule contains a spray-dried powder of 42 mg levodopa active ingredient with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and sodium chloride. The active component of INBRIJA is levodopa, an aromatic amino acid. Its chemical name is (2S)-2-amino-3-(3,4-dihydroxyphenyl) propanoic acid and its structural formula is: Levodopa has a molecular weight of 197.19 g/mol and molecular formula C 9 H 11 NO 4 . Levodopa is a white to slightly off-white powder and is readily soluble in formic acid, slightly soluble in water, and practically insoluble in ethanol and diethyl ether; it dissolves in dilute hydrochloric acid. The INBRIJA inhaler is a plastic device with a blue body, blue cap, and white mouthpiece used for inhaling INBRIJA powder. The INBRIJA inhaler is breath-actuated by the patient. Under standardized in vitro testing conditions, the INBRIJA inhaler delivered 36.1 mg of levodopa (emitted dose) for the 42 mg capsule from the mouthpiece. No significant difference in emitted dose was observed when varying the flow rate and volume from 20 liters per minute/1L up to 90 liters per minute/2L. Peak inspiratory flow rates (PIFR) achievable through the INBRIJA inhaler were evaluated in 24 adult patients with mild to moderate Parkinson's disease. The mean PIFR was 64 L/min (range 39–98 L/min) for patients in the ON state and 57 L/min (range 29–98 L/min) in the OFF state. Chemical Structure
What Is Levodopa Used For?
1 INDICATIONS AND USAGE INBRIJA is indicated for the intermittent treatment of OFF episodes in patients with Parkinson's disease treated with carbidopa/levodopa. INBRIJA is an aromatic amino acid indicated for the intermittent treatment of OFF episodes in patients with Parkinson's disease treated with carbidopa/levodopa ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION INBRIJA capsules are for oral inhalation only and should be used only with the INBRIJA inhaler. For oral inhalation only. DO NOT swallow INBRIJA capsules. Only use INBRIJA capsules with the INBRIJA inhaler ( 2.1 ) Inhale the contents of two INBRIJA capsules (84 mg) as needed for OFF symptoms, up to 5 times daily ( 2.2 ) The maximum dose per OFF period is 84 mg, and the maximum recommended daily dosage of INBRIJA is 420 mg ( 2.2 ) 2.1 Important Administration Instructions INBRIJA capsules are for oral inhalation only and should be used only with the INBRIJA inhaler. INBRIJA capsules must not be swallowed as the intended effect will not be obtained. INBRIJA capsules should be stored in their blister package and only removed immediately before use [see How Supplied/Storage and Handling (16.2) ] . 2.2 Recommended Dosage INBRIJA should be taken when symptoms of an OFF period start to return. The recommended dosage of INBRIJA is oral inhalation of the contents of two 42 mg capsules (84 mg) as needed, up to 5 times a day. The maximum dose per OFF period is 84 mg, and the maximum daily dosage is 420 mg. INBRIJA has been shown to be effective only in combination with carbidopa/levodopa [see Indications and Usage (1) ].
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reactions are discussed below and elsewhere in the labeling: Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions (5.1) ] Withdrawal-Emergent Hyperpyrexia and Confusion [see Warnings and Precautions (5.2) ] Hallucinations/Psychosis [see Warnings and Precautions (5.3) ] Impulse Control/Compulsive Behaviors [see Warnings and Precautions (5.4) ] Dyskinesia [see Warnings and Precautions (5.5) ] Bronchospasm in Patients with Lung Disease [see Warnings and Precautions (5.6) ] Glaucoma [see Warnings and Precautions (5.7) ] The most common adverse reactions (incidence ≥ 5% and higher than placebo) were cough, nausea, upper respiratory tract infection, and sputum discolored ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merz Pharmaceuticals, LLC at 1-800-367-5109 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. Adverse Reactions in Study 1 Table 1 lists the adverse reactions that occurred in at least 2% of patients with Parkinson's disease who were treated with INBRIJA 84 mg and higher than placebo for OFF periods in Study 1 [see Clinical Studies (14) ]. Study 1 was a double-blind, placebo-controlled study, in which 114 patients received INBRIJA 84 mg (two 42 mg capsules) for an average of 2 doses per day, to a maximum of 5 times a day, and 112 patients received placebo. INBRIJA-treated patients were 45-82 years of age (mean 63.5 years of age) and were predominantly male (72%) and white (94%). All patients were also treated with oral carbidopa/levodopa. The most common adverse reactions (≥ 5% and higher than placebo) in Study 1 were cough, nausea, upper respiratory tract infection, and sputum discolored. Table 1: Adverse Reactions at an Incidence ≥2% and More Frequent with INBRIJA than with Placebo in Study 1 Adverse Reactions INBRIJA 84 mg N=114 % Placebo N=112 % Respiratory, thoracic and mediastinal disorders Cough 15 2 Sputum discolored 5 0 Nasal discharge discoloration 2 0 Oropharyngeal pain 2 0 Gastrointestinal disorders Nausea 5 3 Vomiting 3 0 Infections and infestations Upper respiratory tract infection 6 3 Nasopharyngitis 3 2 Bronchitis/pneumonia 2 0 Nervous system disorders Dyskinesia 4 1 Headache 2 0 Injury, poisoning and procedural complications Fall 3 2 Laceration 2 0 Skin abrasion 2 0 General disorders and administration site conditions Chest discomfort 2 0 Investigations Blood bilirubin increased 2 0 Red blood cell count decreased 2 0 Musculoskeletal and connective tissue disorders Pain in extremity 2 1 Psychiatric disorders Insomnia 2 1 Vascular disorders Orthostatic hypotension/blood pressure decreased 2 0 Adverse Reactions Leading to Discontinuation in Study 1 In Study 1, 6 of 114 patients (5%) in the INBRIJA 84 mg group and 3 of 112 patients (3%) in the placebo group discontinued because of adverse reactions. The most common of these adverse reactions was cough, which lead to discontinuation in 2% of patients in the INBRIJA 84 mg group and none in the placebo group. 6.2 Postmarketing Experience The following adverse reaction has been identified during post approval use of INBRIJA. Because adverse 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: sensation of choking immediately following administration.
Drug Interactions
7 DRUG INTERACTIONS Monitor patients on MAO-B inhibitors for orthostatic hypotension ( 7.1 ) Dopamine D2 antagonists, isoniazid, and iron salts: May reduce the effectiveness of INBRIJA ( 7.2 , 7.3 ) 7.1 Monoamine Oxidase (MAO) Inhibitors The use of nonselective MAO inhibitors with INBRIJA is contraindicated [see Contraindications (4) ] . Discontinue use of any nonselective MAO inhibitors at least two weeks prior to initiating INBRIJA. The use of selective MAO-B inhibitors with INBRIJA may be associated with orthostatic hypotension. Monitor patients who are taking these drugs concurrently. 7.2 Dopamine D2 Receptor Antagonists and Isoniazid Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone, metoclopramide) and isoniazid may reduce the effectiveness of levodopa. Monitor patients for worsening Parkinson's symptoms. 7.3 Iron Salts Iron salts or multivitamins containing iron salts can form chelates with levodopa and consequently reduce the bioavailability of levodopa.
Contraindications
4 CONTRAINDICATIONS INBRIJA is contraindicated in patients currently taking a nonselective monoamine oxidase (MAO) inhibitor (e.g., phenelzine and tranylcypromine) or who have recently (within 2 weeks) taken a nonselective MAO inhibitor. Hypertension can occur if these drugs are used concurrently [see Drug Interactions (7.1) ]. INBRIJA is contraindicated in patients currently taking a nonselective monoamine oxidase (MAO) inhibitor or who have recently (within 2 weeks) taken a nonselective MAO inhibitor ( 4 , 7.1 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of INBRIJA in pregnant women. In animal studies, carbidopa/levodopa has been shown to be developmentally toxic (including teratogenic effects) [see Data ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data When administered to pregnant rabbits throughout organogenesis, carbidopa/levodopa caused both visceral and skeletal malformations in rabbits. No teratogenic effects were observed when carbidopa/levodopa was administered to pregnant mice throughout organogenesis. There was a decrease in the number of live pups delivered by rats receiving carbidopa/levodopa during organogenesis.
Overdosage
10 OVERDOSAGE Based on the limited available information, the acute symptoms of carbidopa/levodopa overdosage can be expected to arise from dopaminergic overstimulation. Using more than one dose (84 mg) to treat the same OFF period may result in CNS disturbances, with an increasing risk for cardiovascular disturbance (e.g., hypotension, tachycardia) and increased risk for new or worsening psychiatric problems at higher doses. Reports of rhabdomyolysis and transient renal insufficiency suggest that levodopa overdosage may give rise to systemic complications. Monitor patients and provide supportive care. Patients should receive electrocardiographic monitoring for the development of arrhythmias; if needed, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs, increasing the risk of drug interactions (especially catechol-structured drugs) should be taken into consideration.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied INBRIJA 42 mg contains foil blister strips of INBRIJA (levodopa inhalation powder) white capsules with two black bands on the body and "A42" in black on the cap, and one INBRIJA inhaler. Carton containing 60 INBRIJA capsules (15 blister cards containing 4 capsules each) and 1 INBRIJA inhaler: NDC 0259-6142-60 INBRIJA inhaler consists of a blue cap, blue handle with "INBRIJA" imprinted on it, and white mouthpiece covering the capsule chamber. 16.2 Storage and Handling Store in a dry place between 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). INBRIJA capsules should always be stored in the blister packaging and only removed immediately before use. INBRIJA capsules should not be stored inside the INBRIJA inhaler. INBRIJA capsules should be used only with the INBRIJA inhaler. The INBRIJA inhaler should not be used to administer any other medicines.
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.