Carbidopa and Levodopa Tablets

• It is used to treat Parkinson's disease.
• It is used to treat signs like Parkinson's disease caused by other health problems.
• It may be given to you for other reasons. Talk with the doctor.

• If you have an allergy to levodopa, carbidopa, or any other part of this medicine (carbidopa and levodopa tablets).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Glaucoma, a skin lump or growth, or a history of skin cancer.
• If you are taking any of these drugs: Reserpine or tetrabenazine.
• If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking this medicine within 14 days of those drugs can cause very bad high blood pressure.
• If you are taking another drug that has the same drug in it.

This is not a list of all drugs or health problems that interact with this medicine (carbidopa and levodopa tablets).

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine (carbidopa and levodopa tablets) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• If you take an iron product or a multivitamin that has iron, ask your doctor or pharmacist how to take it with this medicine. Iron may lower how well your body is able to absorb this medicine (carbidopa and levodopa tablets).
• Diets high in protein, fat, or calories may lower how well your body absorbs this medicine; tell your doctor if you have a diet like this or if you will be changing your diet. Talk with your doctor.
• Do not stop taking this medicine (carbidopa and levodopa tablets) all of a sudden or lower your dose without calling your doctor. Side effects may happen. Talk with your doctor.
• Take even during sign-free periods.
• Keep a diary of your signs.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• Take this medicine (carbidopa and levodopa tablets) at the same time of day.
• To gain the most benefit, do not miss doses.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low mood (depression), thoughts of killing yourself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
• Change in the way you act.
• Hallucinations (seeing or hearing things that are not there).
• Feeling confused.
• Strong urges that are hard to control (such as eating, gambling, sex, or spending money).
• A skin lump or growth.
• Change in color or size of a mole.
• Trouble controlling body movements that is new or worse.
• Throwing up blood or throw up that looks like coffee grounds.
• Black, tarry, or bloody stools.
• Belly pain.
• Chest pain or pressure or a fast heartbeat.
• A heartbeat that does not feel normal.
• Fever or chills.
• Sore throat.
• Any unexplained bruising or bleeding.
• Very bad dizziness or passing out.
• Very bad headache.
• Dark urine or yellow skin or eyes.
• Change in eyesight, eye pain, or very bad eye irritation.
• Shortness of breath.
• Feeling very tired or weak.

Carbidopa and levodopa tablet, USP is a combination of carbidopa and levodopa for the treatment of Parkinson’s disease and syndrome.
Carbidopa USP, an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.24. It is designated chemically as (-)-L-α-hydrazino-α-methyl-β-(3,4-dihydroxybenzene) propanoic acid monohydrate. Its molecular formula is C10H14N2O4•H2O and its structural formula is:

Tablet content is expressed in terms of anhydrous carbidopa which has a molecular weight of 226.23.
Levodopa USP, 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 molecular formula is C9H11NO4 and its structural formula is:

Carbidopa and levodopa is supplied as tablets in three strengths:

Carbidopa and Levodopa Tablets, USP, 25 mg/100 mg, containing 25 mg of carbidopa and 100 mg of levodopa.

Carbidopa and Levodopa Tablets, USP, 10 mg/100 mg, containing 10 mg of carbidopa and 100 mg of levodopa.

Carbidopa and Levodopa Tablets, USP, 25 mg/250 mg, containing 25 mg of carbidopa and 250 mg of levodopa.
Inactive ingredients are microcrystalline cellulose, corn starch, pregelatinized maize starch, sodium starch glycolate, magnesium stearate. Carbidopa and Levodopa Tablets, USP 10 mg/100 mg and 25 mg/250 mg also contain FD&C Blue 2. Carbidopa and Levodopa Tablets, USP 25 mg/100 mg also contain D&C Yellow 10 and FD&C Yellow 6.

Mechanism of Action

Parkinson's disease is a progressive, neurodegenerative disorder of the extrapyramidal nervous system affecting the mobility and control of the skeletal muscular system. Its characteristic features include resting tremor, rigidity, and bradykinetic movements. Symptomatic treatments, such as levodopa therapies, may permit the patient better mobility.
Current evidence indicates that symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in the treatment of Parkinson's disease apparently because it does not cross the blood-brain barrier. However, levodopa, the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa relieves symptoms of Parkinson's disease.

Pharmacodynamics

When levodopa is administered orally, it is rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system. For this reason, large doses of levodopa are required for adequate therapeutic effect, and these may often be accompanied by nausea and other adverse reactions, some of which are attributable to dopamine formed in extracerebral tissues.

Since levodopa competes with certain amino acids for transport across the gut wall, the absorption of levodopa may be impaired in some patients on a high protein diet.

Carbidopa inhibits decarboxylation of peripheral levodopa. It does not cross the blood-brain barrier and does not affect the metabolism of levodopa within the central nervous system.

The incidence of levodopa-induced nausea and vomiting is less with Carbidopa and Levodopa Tablets than with levodopa. In many patients, this reduction in nausea and vomiting will permit more rapid dosage titration.

Since its decarboxylase inhibiting activity is limited to extracerebral tissues, administration of carbidopa with levodopa makes more levodopa available for transport to the brain.

Pharmacokinetics

Carbidopa reduces the amount of levodopa required to produce a given response by about 75% and, when administered with levodopa, increases both plasma levels and the plasma half-life of levodopa, and decreases plasma and urinary dopamine and homovanillic acid.

The plasma half-life of levodopa is about 50 minutes, without carbidopa. When carbidopa and levodopa are administered together, the half-life of levodopa is increased to about 1.5 hours. At steady state, the bioavailability of carbidopa from Carbidopa and Levodopa Tablets is approximately 99% relative to the concomitant administration of carbidopa and levodopa.

In clinical pharmacologic studies, simultaneous administration of carbidopa and levodopa produced greater urinary excretion of levodopa in proportion to the excretion of dopamine than administration of the two drugs at separate times.

Pyridoxine hydrochloride (vitamin B6), in oral doses of 10 mg to 25 mg, may reverse the effects of levodopa by increasing the rate of aromatic amino acid decarboxylation. Carbidopa inhibits this action of pyridoxine; therefore, Carbidopa and Levodopa Tablets can be given to patients receiving supplemental pyridoxine (vitamin B6).

Special Populations

Geriatric: A study in eight young healthy subjects (21 to 22 yr) and eight elderly healthy subjects (69 to 76 yr) showed that the absolute bioavailability of levodopa was similar between young and elderly subjects following oral administration of levodopa and carbidopa. However, the systemic exposure (AUC) of levodopa was increased by 55% in elderly subjects compared to young subjects. Based on another study in forty patients with Parkinson’s disease, there was a correlation between age of patients and the increase of AUC of levodopa following administration of levodopa and an inhibitor of peripheral dopa decarboxylase. AUC of levodopa was increased by 28% in elderly patients (≥ 65 yr) compared to young patients (< 65 yr). Additionally, mean value of Cmax for levodopa was increased by 24% in elderly patients (≥ 65 yr) compared to young patients (< 65 yr) (see PRECAUTIONS, Geriatric Use).

The AUC of carbidopa was increased in elderly subjects (n=10, 65 to 76 yr) by 29% compared to young subjects (n=24, 23 to 64 yr) following IV administration of 50 mg levodopa with carbidopa (50 mg). This increase is not considered a clinically significant impact.

Management of acute overdosage with Carbidopa and Levodopa Tablets is the same as management of acute overdosage with levodopa. Pyridoxine is not effective in reversing the actions of Carbidopa and Levodopa Tablets.

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.

NDC 62756-518-83
Carbidopa and Levodopa Tablets, USP
25 mg/100 mg
Rx only
30 Tablets
SUN PHARMA