FDA Label for Sinemet
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Sinemet Product Label
The following document was submitted to the FDA by the labeler of this product Organon Llc. The document includes published materials associated whith this product with the essential scientific information about this product as well as other prescribing information. Product labels may durg indications and usage, generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, warnings, inactive ingredients, etc.
Description
SINEMET® (carbidopa and levodopa) is a combination of carbidopa and levodopa for the treatment of Parkinson's disease and syndrome.
Carbidopa, an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.3. It is designated chemically as (—)-L-α-hydrazino-α-methyl-β-(3,4-dihydroxybenzene) propanoic acid monohydrate. Its empirical formula is C10H14N2O4•H2O, and its structural formula is:
Tablet content is expressed in terms of anhydrous carbidopa which has a molecular weight of 226.3.
Levodopa, an aromatic amino acid, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 197.2. It is designated chemically as (—)-L-α-amino-β-(3,4-dihydroxybenzene) propanoic acid. Its empirical formula is C9H11NO4, and its structural formula is:
SINEMET is supplied as tablets in three strengths:
SINEMET 25-100, containing 25 mg of carbidopa and 100 mg of levodopa.
SINEMET 10-100, containing 10 mg of carbidopa and 100 mg of levodopa.
SINEMET 25-250, containing 25 mg of carbidopa and 250 mg of levodopa.
Inactive ingredients are microcrystalline cellulose, pregelatinized starch, starch (corn), and magnesium stearate. SINEMET 10-100 and 25-250 Tablets also contain FD&C Blue #2. SINEMET 25-100 Tablets also contain D&C Yellow #10.
Indications And Usage
SINEMET is indicated in the treatment of Parkinson's disease, post-encephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.
Carbidopa allows patients treated for Parkinson's disease to use much lower doses of levodopa. Some patients who responded poorly to levodopa have improved on SINEMET. This is most likely due to decreased peripheral decarboxylation of levodopa caused by administration of carbidopa rather than by a primary effect of carbidopa on the nervous system. Carbidopa has not been shown to enhance the intrinsic efficacy of levodopa.
Carbidopa may also reduce nausea and vomiting and permit more rapid titration of levodopa.
Contraindications
Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with SINEMET. These inhibitors must be discontinued at least two weeks prior to initiating therapy with SINEMET. SINEMET may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline HCl) (see PRECAUTIONS, Drug Interactions).
SINEMET is contraindicated in patients with known hypersensitivity to any component of this drug, and in patients with narrow-angle glaucoma.
Warnings
When SINEMET is to be given to patients who are being treated with levodopa, levodopa must be discontinued at least twelve hours before therapy with SINEMET is started. In order to reduce adverse reactions, it is necessary to individualize therapy. See DOSAGE AND ADMINISTRATION section before initiating therapy.
The addition of carbidopa with levodopa in the form of SINEMET reduces the peripheral effects (nausea, vomiting) due to decarboxylation of levodopa; however, carbidopa does not decrease the adverse reactions due to the central effects of levodopa. Because carbidopa permits more levodopa to reach the brain and more dopamine to be formed, certain adverse central nervous system (CNS) effects, e.g., dyskinesias (involuntary movements), may occur at lower dosages and sooner with SINEMET than with levodopa alone.
All patients should be observed carefully for the development of depression with concomitant suicidal tendencies.
SINEMET should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease.
As with levodopa, care should be exercised in administering SINEMET to patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias. In such patients, cardiac function should be monitored with particular care during the period of initial dosage adjustment, in a facility with provisions for intensive cardiac care.
As with levodopa, treatment with SINEMET may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer.
Adverse Reactions
The most common adverse reactions reported with SINEMET have included dyskinesias, such as choreiform, dystonic, and other involuntary movements, and nausea.
The following other adverse reactions have been reported with SINEMET:
Body as a Whole
Chest pain, asthenia.
Cardiovascular
Cardiac irregularities, hypotension, orthostatic effects including orthostatic hypotension, hypertension, syncope, phlebitis, palpitation.
Gastrointestinal
Dark saliva, gastrointestinal bleeding, development of duodenal ulcer, anorexia, vomiting, diarrhea, constipation, dyspepsia, dry mouth, taste alterations.
Hematologic
Agranulocytosis, hemolytic and non-hemolytic anemia, thrombocytopenia, leukopenia.
Hypersensitivity
Angioedema, urticaria, pruritus, Henoch-Schönlein purpura, bullous lesions (including pemphigus-like reactions).
Musculoskeletal
Back pain, shoulder pain, muscle cramps.
Nervous System/Psychiatric
Psychotic episodes including delusions, hallucinations, and paranoid ideation, bradykinetic episodes ("on-off" phenomenon), confusion, agitation, dizziness, somnolence, dream abnormalities including nightmares, insomnia, paresthesia, headache, depression with or without development of suicidal tendencies, dementia, pathological gambling, increased libido including hypersexuality, impulse control symptoms. Convulsions also have occurred; however, a causal relationship with SINEMET has not been established.
Respiratory
Dyspnea, upper respiratory infection.
Skin
Rash, increased sweating, alopecia, dark sweat.
Urogenital
Urinary tract infection, urinary frequency, dark urine.
Laboratory Tests
Decreased hemoglobin and hematocrit; abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), LDH, bilirubin, BUN, Coombs test; elevated serum glucose; white blood cells, bacteria, and blood in the urine.
Other adverse reactions that have been reported with levodopa alone and with various carbidopa and levodopa formulations, and may occur with SINEMET are:
Body as a Whole
Abdominal pain and distress, fatigue.
Cardiovascular
Myocardial infarction.
Gastrointestinal
Gastrointestinal pain, dysphagia, sialorrhea, flatulence, bruxism, burning sensation of the tongue, heartburn, hiccups.
Metabolic
Edema, weight gain, weight loss.
Musculoskeletal
Leg pain.
Nervous System/Psychiatric
Ataxia, extrapyramidal disorder, falling, anxiety, gait abnormalities, nervousness, decreased mental acuity, memory impairment, disorientation, euphoria, blepharospasm (which may be taken as an early sign of excess dosage; consideration of dosage reduction may be made at this time), trismus, increased tremor, numbness, muscle twitching, activation of latent Horner's syndrome, peripheral neuropathy.
Respiratory
Pharyngeal pain, cough.
Skin
Malignant melanoma, flushing.
Special Senses
Oculogyric crises, diplopia, blurred vision, dilated pupils.
Urogenital
Urinary retention, urinary incontinence, priapism.
Miscellaneous
Bizarre breathing patterns, faintness, hoarseness, malaise, hot flashes, sense of stimulation.
Laboratory Tests
Decreased white blood cell count and serum potassium; increased serum creatinine and uric acid; protein and glucose in urine.
Overdosage
Management of acute overdosage with SINEMET is the same as management of acute overdosage with levodopa. Pyridoxine is not effective in reversing the actions of SINEMET.
General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered judiciously and an adequate airway maintained. Electrocardiographic monitoring should be instituted and the patient carefully observed for the development of arrhythmias; if required, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs as well as SINEMET should be taken into consideration. To date, no experience has been reported with dialysis; hence, its value in overdosage is not known.
Based on studies in which high doses of levodopa and/or carbidopa were administered, a significant proportion of rats and mice given single oral doses of levodopa of approximately 1500-2000 mg/kg are expected to die. A significant proportion of infant rats of both sexes are expected to die at a dose of 800 mg/kg. A significant proportion of rats are expected to die after treatment with similar doses of carbidopa. The addition of carbidopa in a 1:10 ratio with levodopa increases the dose at which a significant proportion of mice are expected to die to 3360 mg/kg.
Dosage And Administration
The optimum daily dosage of SINEMET must be determined by careful titration in each patient. SINEMET tablets are available in a 1:4 ratio of carbidopa to levodopa (SINEMET 25-100) as well as 1:10 ratio (SINEMET 25-250 and SINEMET 10-100). Tablets of the two ratios may be given separately or combined as needed to provide the optimum dosage.
Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg a day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.
Other
Distributed by: Organon LLC, a subsidiary of
ORGANON & Co.,
Jersey City, NJ 07302, USA
For patent information: www.organon.com/our-solutions/patent/
Copyright © 2021 Organon Global Inc.
All rights reserved.
Revised: 6/2021
uspi-og0295b-t-2106r000
Rx Only
Principal Display Panel - 10 Mg/100 Mg Tablet Bottle Label
NDC 78206-166-01
Sinemet®
(carbidopa and levodopa)
Tablets
10 mg/100 mg
Each tablet contains 10 mg carbidopa
(anhydrous equivalent) and 100 mg levodopa.
Store at 25°C (77°F), excursions permitted to
15-30°C (59-86°F) [see USP Controlled Room
Temperature]. Store in a tightly closed container,
protected from light and moisture.
Rx only
100 Tablets
Principal Display Panel - 25 Mg/100 Mg Tablet Bottle Label
NDC 78206-168-01
Sinemet®
(carbidopa and levodopa)
Tablets
25 mg/100 mg
Each tablet contains 25 mg carbidopa
(anhydrous equivalent) and 100 mg levodopa.
Store at 25°C (77°F), excursions permitted to
15-30°C (59-86°F) [see USP Controlled Room
Temperature]. Store in a tightly closed container,
protected from light and moisture.
Rx only
100 Tablets
Principal Display Panel - 25 Mg/250 Mg Tablet Bottle Label
NDC 78206-167-01
Sinemet®
(carbidopa and levodopa)
Tablets
25 mg/250 mg
Each tablet contains 25 mg carbidopa
(anhydrous equivalent) and 250 mg levodopa.
Store at 25°C (77°F), excursions permitted to
15-30°C (59-86°F) [see USP Controlled Room
Temperature]. Store in a tightly closed container,
protected from light and moisture.
Rx only
100 Tablets
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