Carbidopa/levodopa/entacapone

What is Carbidopa/levodopa/entacapone?

• Carbidopa/levodopa/entacapone (Stalevo) is a combination drug consisting of levodopa (an inert, metabolic precursor to dopamine), carbidopa (aromatic amino acid decarboxylation inhibitor), and entacapone (catechol-O-methyltransferase (COMT) inhibitor) are indicated for the treatment of Parkinson's disease.

Carbidopa2

Carbidopa ball-and-stick

Carbidopa2DACS

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Levodopa

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Levodopa 3D ball

Entacapone2DACS

Entacapone molecule ball

What are the uses of this medicine?

• Carbidopa/levodopa/entacapone (Stalevo) tablets are used for the treatment of Parkinson's disease.

Carbidopa, levodopa and entacapone tablets can be used:

• To substitute (with equivalent strengths of each of the three components) carbidopa/levodopa and entacapone previously administered as individual products.
• To replace carbidopa/levodopa therapy (without entacapone) when patients experience the signs and symptoms of end-of-dose “wearing-off” and when they have been taking a total daily dose of levodopa of 600 mg or less and have not been experiencing dyskinesias.

How does this medicine work?

Levodopa:

• 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 because it does not cross the blood-brain barrier.
• However, levodopa the metabolic precursor of dopamine, does cross the blood-brain barrier, and is presumably converted to dopamine in the brain.
• This is thought to be the mechanism whereby levodopa relieves the symptoms of Parkinson's disease.

Carbidopa:

• 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.
• Carbidopa inhibits the decarboxylation of peripheral levodopa, making more levodopa available for delivery to the brain.

Entacapone:

• Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT).
• COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure.
• Physiological substrates of COMT include DOPA, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites.
• When decarboxylation of levodopa is prevented by carbidopa, COMT becomes the major metabolizing enzyme for levodopa, catalyzing its metabolism to 3‑methoxy‑4‑hydroxy‑L‑phenylalanine (3‑OMD).

Who Should Not Use this medicine ?

This medicine have cannot be used in patients:

• Taking nonselective monoamine oxidase (MAO) inhibitors (e.g., phenelzine and tranylcypromine)
• With narrow-angle glaucoma

What drug interactions can this medicine cause?

Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. 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
• 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
• ampicillin, apomorphine (Zydis), bitolterol (Tornalate), chloramphenicol (AK-Chlor, Chloromycetin), cholestyramine (Cholybar, Questran, Questran Light, others)
• medications that cause drowsiness (including medications for anxiety and sleeping pills)
• dobutamine (Dobutrex)
• epinephrine (AsthmaHaler, EpiPen Auto-Injector, Primatene Mist, others)
• erythromycin (E-Base, E.E.S., E-Mycin, others)
• isoetharine (Arm-a-Med Isoetharine, Beta-2, Bronkometer, others)
• isoproterenol (Dispos-a-Med Isoproterenol, Isuprel, Medihaler-Iso, others)
• methyldopa (Aldomet)
• phenelzine (Nardil)
• probenecid (Benemid)
• rifampin (Rifadin, Rimactane)
• tranylcypromine (Parnate)

Is this medicine FDA approved?

• Carbidopa/levodopa/entacapone was approved by the U.S. Food and Drug Administration (FDA) in June 2003, to treat adults with Parkinson's disease of unknown cause in two scenarios.

How should this medicine be used?

• Carbidopa, levodopa and entacapone tablets should be used as a substitute for patients already stabilized on equivalent doses of carbidopa/levodopa and entacapone.

Recommended dosage:

Maximum Recommended Dose of Carbidopa, Levodopa and Entacapone Tablets in a 24-hour Period

Carbidopa, Levodopa and Entacapone Tablets Dosage Strength	Maximum Number of Tablets in a 24-hour Period
12.5 mg per 50 mg per 200 mg	8
18.75 mg per 75 mg per 200 mg	8
25 mg per 100 mg per 200 mg	8
31.25 mg per 125 mg per 200 mg	8
37.5 mg per 150 mg per 200 mg	8
50 mg per 200 mg per 200 mg	6

• Patients receiving one tablet of carbidopa/levodopa 25 mg/100 mg and one tablet of entacapone 200 mg at each administration can switch to a single carbidopa, levodopa and entacapone tablet containing 25 mg of carbidopa, 100 mg of levodopa and 200 mg of entacapone.

Administration:

• Do not split, crush or chew carbidopa, levodopa and entacapone tablets.
• Administer only one tablet at each dosing interval. All strengths of carbidopa, levodopa and entacapone tablets contain 200 mg of entacapone.
• Combining multiple tablets or portions of tablets to achieve a higher levodopa dose may lead to an overdose of entacapone.
• Administer carbidopa, levodopa and entacapone tablets with or without food.
• However, a high-fat, high-calorie meal may delay the absorption of levodopa by about 2 hours.

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

This medicine is available in fallowing doasage form:

• As Carbidopa, levodopa and entacapone tablets 12.5 mg per 50 mg per 200 mg
• Carbidopa, levodopa and entacapone tablets 18.75 mg per 75 mg per 200 mg
• Carbidopa, levodopa and entacapone tablets 25 mg per 100 mg per 200 mg
• Carbidopa, levodopa and entacapone tablets 31.25 mg per 125 mg per 200 mg
• Carbidopa, levodopa and entacapone tablets 37.5 mg per 150 mg per 200 mg
• Carbidopa, levodopa and entacapone tablets 50 mg per 200 mg per 200 mg

This medicine is available in fallowing brand namesː

• Stalevo

What side effects can this medication cause?

The most common side effects of this medicine include:

• Infection Bacterial
• Fatigue
• Asthenia
• Urine Discoloration
• Purpura
• Dyspnea
• Nausea
• Diarrhea
• Abdominal Pain
• Constipation
• Vomiting
• Mouth Dry
• Dyspepsia
• Flatulence
• Gastritis
• Anxiety
• Somnolence
• Agitation
• Taste Perversion
• Dyskinesia
• Hyperkinesia
• Hypokinesia
• Dizziness
• Sweating Increased
• Back Pain

The most serious adverse reactions may include:

• Falling Asleep During Activities of Daily Living and Somnolence
• Hypotension/Orthostatic Hypotension and Syncope
• Dyskinesia
• Depression and suicidality
• Impulse Control and/or Compulsive Behaviors
• Withdrawal-Emergent Hyperpyrexia and Confusion
• Diarrhea and Colitis
• Rhabdomyolysis
• Peptic Ulcer Disease

What special precautions should I follow?

• Patients with Parkinson's disease treated with carbidopa, levodopa and entacapone tablets or other carbidopa/levodopa products have reported suddenly falling asleep without prior warning of sleepiness while engaged in activities of daily living. patients should be advised not to drive and to avoid other potentially dangerous activities.
• Hypotension, orthostatic hypotension, and syncope are observed in patients treated with drugs that increase central dopaminergic tone including carbidopa, levodopa and entacapone tablets.
• Dyskinesia (involuntary movements) may occur or be exacerbated at lower dosages and sooner with carbidopa, levodopa and entacapone tablets. The occurrence of dyskinesias may require dosage reduction.
• 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.
• Dopaminergic therapy in patients with Parkinson's disease has been associated with hallucinations.
• patients treated with anti-Parkinson medications can experience intense urges to gamble, increased sexual urges, intense urges to spend money uncontrollably, and other intense urges. Physicians should consider dose reduction or stopping carbidopa, levodopa and entacapone tablets if a patient develops such urges while taking carbidopa, levodopa and entacapone tablets.
• Cases of hyperpyrexia and confusion resembling neuroleptic malignant syndrome (NMS) have been reported in association with dose reduction or withdrawal of therapy with carbidopa, levodopa and entacapone. If a patient needs to discontinue or reduce their daily dose of carbidopa, levodopa and entacapone tablets, the dose should be decreased slowly, with supervision from a health care provider.
• Diarrhea and Colitis may occur. If prolonged diarrhea is suspected to be related to carbidopa, levodopa and entacapone tablets, the drug should be discontinued and appropriate medical therapy considered.
• Cases of severe rhabdomyolysis have been reported with entacapone when used in combination with carbidopa and levodopa.
• Advise patients with Parkinson's disease that they have a higher risk of developing melanoma. Advise patients to have their skin examined on a regular basis by a qualified healthcare provider (e.g., dermatologist) and to monitor for melanomas frequently and on a regular basis when using carbidopa, levodopa and entacapone tablets.
• Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and pleural thickening have been reported in some patients treated with ergot derived dopaminergic agents.
• As with levodopa, treatment with carbidopa, levodopa and entacapone tablets may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer.
• Patients with hepatic impairment should be treated with caution . As with levodopa, periodic evaluation of hepatic function is recommended during extended therapy.
• Inform patients that carbidopa, levodopa and entacapone tablets may cause nausea and vomiting may occur more frequently during initial therapy and may require dose adjustment.
• Advise patients that a change in diet to foods that are high in protein may delay the absorption of levodopa. Excessive acidity also delays stomach emptying, thus delaying the absorption of levodopa. Iron salts (such as in multi-vitamin tablets) may also reduce the effectiveness of carbidopa, levodopa and entacapone tablets.
• Advise patients that dark coloration (red, brown, or black) may appear in saliva, urine, or sweat after taking carbidopa, levodopa and entacapone tablets. Although the color appears to be clinically insignificant, garments may become discolored.
• Advise patients that “off” episodes (“wearing-off” of drug effect) occur at the end of the dosing interval but unpredictable “off” episodes may occur at any time. Advise the patient to notify a health care provider for possible treatment adjustments if such response poses a problem to the patient's everyday life.
• Carbidopa is known to be excreted into milk in rats. Because of the possibility that carbidopa and levodopa may be excreted into human milk, instruct patients to notify their physicians if they intend to breastfeed or are breastfeeding an infant.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• hypotension
• tachycardia
• psychiatric problems
• rhabdomyolysis
• Abdominal pain
• loose stools

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.
• Hospitalization is advised, and general supportive measures should be employed, along with immediate gastric lavage and repeated doses of charcoal over time.
• Intravenous fluids should be administered judiciously and an adequate airway maintained.
• Respiratory, circulatory and renal function should be monitored and appropriate supportive measures employed.
• Electrocardiographic monitoring should be instituted and the patient carefully observed for the development of arrhythmias; if required, appropriate antiarrhythmic therapy should be given.
• Hemodialysis or hemoperfusion is unlikely to reduce entacapone levels due to its high binding to plasma proteins.
• Pyridoxine is not effective in reversing the actions of carbidopa, levodopa and entacapone tablets.

Can this medicine be used in pregnancy?

• Pregnancy Category C.
• There are no adequate and well-controlled studies in pregnant women.
• Carbidopa, levodopa and entacapone tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Can this medicine be used in children?

• Safety and effectiveness in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• CARBIDOPA
• LEVODOPA
• ENTACAPONE

Inactive ingredients:

• STARCH, CORN
• CROSCARMELLOSE SODIUM
• GLYCERIN
• HYPROMELLOSE, UNSPECIFIED
• MAGNESIUM STEARATE
• MANNITOL
• POLYSORBATE 80
• POVIDONE, UNSPECIFIED
• SUCROSE
• FERRIC OXIDE RED
• TITANIUM DIOXIDE

Who manufactures and distributes this medicine?

Manufactured by:

• Orion Corporation
• Orion Pharma
• Espoo, Finland

for:

• Sandoz Inc., Princeton, NJ

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

• Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
• Dispense in tight container.

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

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