Carbidopa/levodopa

What is Carbidopa/levodopa?

Carbidopa2

• Carbidopa/levodopa (Duopa; Parcopa; Rytary; Sinemet) also known as levocarb and co-careldopa, is the combination of the two medications carbidopa and levodopa used for the treatment of Parkinson’s disease and syndrome.
• Carbidopa, is an inhibitor of aromatic amino acid decarboxylation, and levodopa, is an inert, metabolic precursor to dopamine, with dopaminergic and antiparkinsonian properties.

What are the uses of this medicine?

Carbidopa ball-and-stick

• Carbidopa/levodopa (Duopa; Parcopa; Rytary; Sinemet) used in the treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), post-encephalitic parkinsonism, and symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication.
• Parkinson's symptoms, including tremors (shaking), stiffness, and slowness of movement, are caused by a lack of dopamine, a natural substance usually found in the brain.

How does this medicine work?

• An orally available combination of carbidopa, an inhibitor of aromatic amino acid decarboxylation, and levodopa, an inert, metabolic precursor to dopamine, with dopaminergic and antiparkinsonian properties.
• Upon oral administration, levodopa crosses the blood-brain barrier (BBB) and is decarboxylated to dopamine via dopa decarboxylase in the brain, promoting increased activation of dopamine receptors.
• Carbidopa inhibits dopa decarboxylase in the periphery, thereby preventing decarboxylation of levodopa in extracerebral tissues and increasing the delivery of dopamine to the central nervous system (CNS).
• As carbidopa does not cross the BBB, it does not interfere with CNS levodopa metabolism.
• Carbidopa prevents levodopa from being broken down before it reaches the brain.
• This allows for a lower dose of levodopa, which causes less nausea and vomiting.

Who Should Not Use this medicine ?

Carbidopa2DACS

This medicine cannot be used in patients who:

• use Nonselective monoamine oxidase (MAO) inhibitors.
• have hypersensitivity to any component of this drug.
• with narrow-angle glaucoma.
• with suspicious, undiagnosed skin lesions or a history of melanoma.

• These inhibitors must be discontinued at least two weeks prior to initiating therapy with carbidopa and levodopa.
• Carbidopa and levodopa may be administered concomitantly with the manufacturer’s recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline hydrochloride).

What drug interactions can this medicine cause?

• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Levodopa

Be sure to mention any of the following:

• antidepressants ('mood elevators') such as amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Adapin, Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil)
• antihistamines
• haloperidol (Haldol)
• ipratropium (Atrovent)
• iron pills and vitamins containing iron
• isocarboxazid (Marplan)
• isoniazid (INH, Nydrazid)
• medications for high blood pressure, irritable bowel disease, mental illness, motion sickness, nausea, ulcers, or urinary problems

Levodopa 3D ball

• metoclopramide (Reglan)
• other medications for Parkinson's disease
• papaverine (Pavabid)
• phenytoin (Dilantin)
• rasagiline (Azilect)
• risperidone (Risperdal)
• sedatives
• selegiline (Emsam, Eldepryl, Zelapar)
• sleeping pills
• tetrabenazine (Xenazine)
• tranquilizers

Is this medicine FDA approved?

• Yes it was FDA approved.
• It is available as a generic medication.
• In 2020, it was the 364th most commonly prescribed medication in the United States, with more than 500 thousand prescriptions.

How should this medicine be used?

• Carbidopa and levodopa tablets USP are available in a 1:4 ratio of carbidopa to levodopa (25 mg/100 mg) as well as a 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.

Recommended dosage:

• Dosage is best initiated with one carbidopa and levodopa tablet USP, 25 mg/100 mg three times a day.
• Dosage may be increased by one tablet every day or every other day, as necessary, until a dosage of eight carbidopa and levodopa tablets USP, 25 mg/100 mg a day is reached.
• If carbidopa and levodopa tablets USP, 10 mg/100 mg are 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 q.i.d.) is reached.

Administration:

• The combination of levodopa and carbidopa comes as a regular tablet, an orally disintegrating tablet, an extended-release tablet, and an extended-release capsule to take by mouth.
• The combination of levodopa and carbidopa also comes as a suspension to be given into your stomach through a PEG-J tube or sometimes through a naso-jejunal tube using a special infusion pump.
• The regular and orally disintegrating tablets are usually taken three or four times a day.
• The extended-release tablet is usually taken two to four times a day. The extended-release capsule is usually taken three to five times a day.
• The suspension is usually given as a morning dose and then as a continuous dose, with extra doses given no more than once every 2 hours as needed to control your symptoms.
• Take levodopa and carbidopa at around the same times every day.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As a regular tablet, an orally disintegrating tablet, an extended-release tablet, and an extended-release capsule
• As a suspension

This medicine is available in fallowing brand namesː

• Duopa; Parcopa; Rytary; Sinemet

What side effects can this medication cause?

The most common side effects of this medicine include:

• 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-Schonlein 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, neuroleptic malignant syndrome, 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.

Respiratory: Dyspnea, upper respiratory infection.

Skin:

• Rash, increased sweating, alopecia, dark sweat.

Urogenital:

• Urinary tract infection, urinary frequency, dark urine.

What special precautions should I follow?

• When this combination product is to be given to patients who are being treated with levodopa, levodopa must be discontinued at least twelve hours before therapy with this product is started.
• The addition of carbidopa with levodopa in the form of the combination product 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.
• Levodopa alone, as well as carbidopa and levodopa, is associated with dyskinesias. The occurrence of dyskinesias may require dosage reduction.
• The combination product may cause mental disturbances. All patients should be observed carefully for the development of depression with concomitant suicidal tendencies. Patients with past or current psychoses should be treated with caution.
• Carbidopa and levodopa should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease.
• Care should be exercised in administering the combination product to patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias.
• Treatment with the combination product may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer.
• Sporadic cases of a symptom complex resembling Neuroleptic Malignant Syndrome (NMS) have been reported in association with dose reductions or withdrawal of therapy with carbidopa and levodopa. Therefore, patients should be observed carefully when the dosage of carbidopa and levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.
• Patients with chronic wide-angle glaucoma may be treated cautiously with carbidopa and levodopa provided the intraocular pressure is well-controlled and the patient is monitored carefully for changes in intraocular pressure during therapy.
• The patient should be informed that carbidopa and levodopa tablets are immediate-release formulations of carbidopa-levodopa that are designed to begin release of ingredients within 30 minutes.
• Patients should be advised that sometimes a ‘wearing-off’ effect may occur at the end of the dosing interval. The physician should be notified if such response poses a problem to lifestyle.
• Patients should be advised that occasionally, dark color (red, brown, or black) may appear in saliva, urine, or sweat after ingestion of carbidopa and levodopa. Although the color appears to be clinically insignificant, garments may become discolored.
• The patient should be advised that a change in diet to foods that are high in protein may delay the absorption of levodopa and may reduce the amount taken up in the circulation. Excessive acidity also delays stomach emptying, thus delaying the absorption of levodopa. Iron salts (such as in multivitamin tablets) may also reduce the amount of levodopa available to the body. The above factors may reduce the clinical effectiveness of the levodopa or carbidopa-levodopa therapy.
• Patients should be alerted to the possibility of sudden onset of sleep during daily activities. Patients should be advised to exercise caution while driving or operating machinery and that if they have experienced somnolence and/or sudden sleep onset, they must refrain from these activities.
• There have been reports of patients experiencing intense urges to gamble, increased sexual urges, and other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease, including carbidopa and levodopa.
• Patients should inform their physician if they experience new or increased gambling urges, increased sexual urges, or other intense urges while taking carbidopa and levodopa. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking carbidopa and levodopa.
• you should know that levodopa and carbidopa may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking levodopa and carbidopa. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• In a study of one nursing mother with Parkinson’s disease, excretion of levodopa in human breast milk was reported. Therefore, caution should be exercised when carbidopa and levodopa is administered to a nursing woman.

What to do in case of emergency/overdose?

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• 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.

Can this medicine be used in pregnancy?

• Pregnancy category C.
• There are no adequate or well-controlled studies in pregnant women.
• Use of carbidopa and levodopa in women of child-bearing potential requires that the anticipated benefits of the drug be weighed against possible hazards to mother and child.

Can this medicine be used in children?

• Safety and effectiveness in pediatric patients have not been established.
• Use of the drug in patients below the age of 18 is not recommended.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• CARBIDOPA
• LEVODOPA

Inactive ingredients:

• MAGNESIUM STEARATE
• CELLULOSE, MICROCRYSTALLINE
• STARCH, CORN
• FD&C BLUE NO. 2

Who manufactures and distributes this medicine?

Manufactured In Israel By:

• TEVA PHARMACEUTICAL IND. LTD.
• Jerusalem, Israel

Manufactured For:

• TEVA PHARMACEUTICALS USA
• Sellersville, PA

What should I know about storage and disposal of this medication?

• Store at 20° to 25°C (68° to 77°F).
• PROTECT FROM LIGHT.
• Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure.

• Dailymed label info on Carbidopa/levodopa
• FDA Carbidopa/levodopa

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