Carbidopa and Levodopa: Package Insert and Label Information (Page 2 of 2)

ADVERSE REACTIONS

The most common adverse reactions reported with carbidopa and levodopa have included dyskinesias, such as choreiform, dystonic, and other involuntary movements, and nausea.

The following other adverse reactions have been reported with carbidopa and levodopa:

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 carbidopa and levodopa 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 this combination product 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.

To report SUSPECTED ADVERSE EVENTS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions.

OVERDOSAGE

Management of acute overdosage with carbidopa and levodopa is the same as management of acute overdosage with levodopa. Pyridoxine is not effective in reversing the actions of this product.

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 carbidopa and levodopa tablets 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 1,500 to 2,000 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 3,360 mg/kg.

DOSAGE AND ADMINISTRATION

The optimum daily dosage of carbidopa and levodopa must be determined by careful titration in each patient. Carbidopa and levodopa tablets are available in a 1:4 ratio of carbidopa to levodopa (25 mg/100 mg) as well as 1:10 ratio (25 mg/250 mg and 10 mg/100 mg). 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.

Usual Initial Dosage

Dosage is best initiated with one tablet of carbidopa and levodopa

25 mg/100 mg three times a day. This dosage schedule provides 75 mg of carbidopa per day. Dosage may be increased by one tablet every day or every other day, as necessary, until a dosage of eight tablets of carbidopa and levodopa 25 mg/100 mg a day is reached.

If carbidopa and levodopa 10 mg/100 mg is used, dosage may be initiated with one tablet three or four times a day. However, this will not provide an adequate amount of carbidopa for many patients. Dosage may be increased by one tablet every day or every other day until a total of eight tablets (2 tablets four times a day) is reached.

How to Transfer Patients from Levodopa

Levodopa must be discontinued at least twelve hours before starting this combination product. A daily dosage of carbidopa and levodopa should be chosen that will provide approximately 25% of the previous levodopa dosage. Patients who are taking less than 1,500 mg of levodopa a day should be started on one tablet of carbidopa and levodopa 25 mg/100 mg three or four times a day. The suggested starting dosage for most patients taking more than 1,500 mg of levodopa is one tablet of carbidopa and levodopa 25 mg/250 mg three or four times a day.

Maintenance

Therapy should be individualized and adjusted according to the desired therapeutic response. At least 70 to 100 mg of carbidopa per day should be provided. When a greater proportion of carbidopa is required, one 25 mg/100 mg tablet may be substituted for each 10 mg/100 mg tablet. When more levodopa is required, each 25 mg/250 mg tablet should be substituted for a 25 mg/100 mg tablet or a 10 mg/100 mg tablet. If necessary, the dosage of carbidopa and levodopa 25 mg/250 mg may be increased by one-half or one tablet every day or every other day to a maximum of eight tablets a day. Experience with total daily dosages of carbidopa greater than 200 mg is limited.

Because both therapeutic and adverse responses occur more rapidly with this combination product than with levodopa alone, patients should be monitored closely during the dose adjustment period. Specifically, involuntary movements will occur more rapidly with carbidopa and levodopa than with levodopa. The occurrence of involuntary movements may require dosage reduction. Blepharospasm may be a useful early sign of excess dosage in some patients.

Addition of Other Antiparkinsonian Medications

Standard drugs for Parkinson’s disease, other than levodopa without a decarboxylase inhibitor, may be used concomitantly while carbidopa and levodopa is being administered, although dosage adjustments may be required.

Interruption of Therapy

Sporadic cases of hyperpyrexia and confusion have been associated with dose reductions and withdrawal of carbidopa and levodopa. Patients should be observed carefully if abrupt reduction or discontinuation of carbidopa and levodopa is required, especially if the patient is receiving neuroleptics (see WARNINGS).

If general anesthesia is required, carbidopa and levodopa may be continued as long as the patient is permitted to take fluids and medication by mouth. If therapy is interrupted temporarily, the patient should be observed for symptoms resembling NMS, and the usual daily dosage may be administered as soon as the patient is able to take oral medication.

HOW SUPPLIED

Carbidopa and Levodopa Tablets, USP are supplied as follows:

10 mg/100 mg — Each dark blue, mottled, round tablet imprinted with ‘TV’ on one side and ‘9701’on the other side contains 10 mg of carbidopa, USP and 100 mg of levodopa, USP and is supplied in bottles of 100 (NDC 0093-9701-01) and 500 (NDC 0093-9701-05).

25 mg/100 mg — Each yellow, mottled, round tablet imprinted with ‘TV’ on one side and ‘9702’on the other side contains 25 mg of carbidopa, USP and 100 mg of levodopa, USP and is supplied in bottles of 100 (NDC 0093-9702-01), 500 (NDC 0093-9702-05) and 1,000 (NDC 0093-9702-10).

25 mg/250 mg — Each light blue, mottled, round tablet imprinted with ‘TV’ on one side and ‘9703’ on the other side contains 25 mg of carbidopa, USP and 250 mg of levodopa, USP and is supplied in bottles of 100 (NDC 0093-9703-01), 500 (NDC 0093-9703-05) and 1,000 (NDC 0093-9703-10).

Store at 25ºC (77ºF); excursions permitted to 15º to 30ºC (59º to 86ºF) [see USP Controlled Room Temperature].

Protect from light.

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Manufactured In Czech Republic by:
Teva Czech Industries, s.r.o.
Opava-Komarov, Czech Republic

Manufactured for:
Teva Pharmaceuticals USA, Inc.
Parsippany, NJ 07054

Rev. C 1/2021

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 0093-9701-01

Carbidopa and Levodopa Tablets, USP

10 mg/100 mg

Rx only

100 Tablets

CL 10 mg/100 mg -100s
(click image for full-size original)

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 0093-9702-01

Carbidopa and Levodopa Tablets, USP

25 mg/100 mg

Rx only

100 Tablets

label
(click image for full-size original)

CARBIDOPA AND LEVODOPA
carbidopa and levodopa tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0093-9701
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
CARBIDOPA (CARBIDOPA ANHYDROUS) CARBIDOPA ANHYDROUS 10 mg
LEVODOPA (LEVODOPA) LEVODOPA 100 mg
Inactive Ingredients
Ingredient Name Strength
STARCH, CORN
MAGNESIUM STEARATE
CELLULOSE, MICROCRYSTALLINE
FD&C BLUE NO. 2–ALUMINUM LAKE
Product Characteristics
Color blue (dark blue, mottled) Score no score
Shape ROUND Size 9mm
Flavor Imprint Code TV;9701
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0093-9701-01 100 TABLET in 1 BOTTLE None
2 NDC:0093-9701-05 500 TABLET in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA074260 01/18/2022
CARBIDOPA AND LEVODOPA
carbidopa and levodopa tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0093-9702
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
CARBIDOPA (CARBIDOPA ANHYDROUS) CARBIDOPA ANHYDROUS 25 mg
LEVODOPA (LEVODOPA) LEVODOPA 100 mg
Inactive Ingredients
Ingredient Name Strength
STARCH, CORN
MAGNESIUM STEARATE
CELLULOSE, MICROCRYSTALLINE
D&C YELLOW NO. 10 ALUMINUM LAKE
FD&C YELLOW NO. 6
Product Characteristics
Color yellow (mottled) Score no score
Shape ROUND Size 9mm
Flavor Imprint Code TV;9702
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0093-9702-01 100 TABLET in 1 BOTTLE None
2 NDC:0093-9702-05 500 TABLET in 1 BOTTLE None
3 NDC:0093-9702-10 1000 TABLET in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA074260 01/18/2022
Labeler — Teva Pharmaceuticals USA, Inc. (001627975)

Revised: 01/2021 Teva Pharmaceuticals USA, Inc.

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