Carbidopa and Levodopa Extended-release Tablets

Carbidopa and levodopa extended-release tablets are indicated in the treatment of Parkinson's disease, postencephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.

Carbidopa and Levodopa Extended-release Tablets, USP are available containing 25 mg of carbidopa, USP and 100 mg of levodopa , USP or 50 mg of carbidopa, USP and 200 mg of levodopa, USP.

The 25 mg/100 mg tablets are purple, oval, unscored tablets debossed with MYLAN on one side of the tablet and 88 on the other side of the tablet. They are available as follows:

NDC 0378-0088-01 bottles of 100 tablets

The 50 mg/200 mg tablets are purple, oval, scored tablets debossed with MYLAN on one side of the tablet and 9 to the left of the score and 4 to the right of the score on the other side of the tablet. They are available as follows:

NDC 0378-0094-01 bottles of 100 tablets

Dispense in a tight, light resistant container as defined in the USP using a child-resistant closure. Keep container tightly closed.

Store at 25°C (77°F); excurs ions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.]

Mylan Pharmaceuticals Inc., Morgantown, WV 26505 U.S.A , Revised: Sep 2014

The patient should be informed that carbidopa and levodopa extended-release tablets are a sustainedrelease formulation of carbidopa and levodopa which releases these ingredients over a 4 to 6 hour period. It is important that carbidopa and levodopa extended-release be taken at regular intervals according to the schedule outlined by the physician. The patient should be cautioned not to change the prescribed dosage regimen and not to add any additional antiparkinson medications, including other carbidopa and levodopa preparations, without first consulting the physician.

If abnormal involuntary movements appear or get worse during treatment with carbidopa and levodopa extended-release, the physician should be notified, as dosage adjustment may be necessary.

Patients should be advised that sometimes the onset of effect of the first morning dose of carbidopa and levodopa extended-release may be delayed for up to one hour compared with the response usually obtained from the first morning dose of carbidopa and levodopa immediate-release. The physician should be notified if such delayed responses pose a problem in treatment.

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 extended-release. Although the color appears to be clinically insignificant, garments may become discolored.

The patient should be informed 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 must be advised that the whole or half tablet should be swallowed without chewing or crushing.

Patients should be alerted to the possibility of sudden onset of sleep during daily activities, in some cases without awareness or warning signs, when they are taking dopaminergic agents, including levodopa. 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 (see WARNINGS: Falling Asleep During Activities of Daily Living and Somnolence).

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 extended-release. Although it is not proven that the medications caused these events, these urges were reported to have stopped in some cases when the dose was reduced or the medication was stopped. Prescribers should ask patients about the development of new or increased gambling urges, sexual urges or other urges while being treated with carbidopa and levodopa extended-release. 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 extended-release. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking carbidopa and levodopa extended-release (See PRECAUTIONS: Impulse Control/Compulsive Behaviors).

In controlled clinical trials, patients predominantly with moderate to severe motor fluctuations while on carbidopa and levodopa immediate-release were randomized to therapy with either carbidopa and levodopa immediate-release or carbidopa and levodopa extended-release. The adverse experience frequency profile of carbidopa and levodopa extended-release did not differ substantially from that of carbidopa and levodopa immediate-release, as shown in Table 1.

Table 1: Clinical Adverse Experiences Occurring In 1% or Greater of Patients

Abnormal laboratory findings occurring at a frequency of 1% or greater in approximately 443 patients who received carbidopa and levodopa extended-release and 475 who received carbidopa and levodopa immediate-release during controlled clinical trials included: decreased hemoglobin and hematocrit; elevated serum glucose; white blood cells, bacteria and blood in the urine.

The adverse experiences observed in patients in uncontrolled studies were similar to those seen in controlled clinical studies.

Other adverse experiences reported overall in clinical trials in 748 patients treated with carbidopa and levodopa extended-release, listed by body system in order of decreasing frequency, include:

Body as a Whole: Asthenia, fatigue, abdominal pain, orthostatic effects.

Cardiovascular: Palpitation, hypertension, hypotension, myocardial infarction.

Gastrointestinal: Gastrointestinal pain, dysphagia, heartburn.

Metabolic: Weight loss.

Musculoskeletal: Leg pain.

Nervous System/Psychiatric: Chorea, somnolence, falling, anxiety, disorientation, decreased mental acuity, gait abnormalities, extrapyramidal disorder, agitation, nervousness, sleep disorders, memory impairment.

Respiratory: Cough, pharyngeal pain, common cold.

Skin: Rash.

Special Senses : Blurred vision.

Urogenital: Urinary incontinence.

Laboratory Tests : Decreased white blood cell count and serum potassium; increased BUN, serum creatinine and serum LDH; protein and glucose in the urine.

The following adverse experiences have been reported in post-marketing experience with carbidopa and levodopa extended-release:

Cardiovascular: Cardiac irregularities, syncope.

Gastrointestinal: Taste alterations, dark saliva.

Hypersensitivity: Angioedema, urticaria, pruritus, bullous lesions (including pemphigus-like reactions).

Nervous System/Psychiatric: Increased tremor, peripheral neuropathy, psychotic episodes including delusions and paranoid ideation, pathological gambling, increased libido including hypersexuality, impulse control symptoms.

Skin: Alopecia, flushing, dark sweat.

Urogenital: Dark urine.

Other adverse reactions that have been reported with levodopa alone and with various carbidopalevodopa formulations and may occur with carbidopa and levodopa extended-release are:

Cardiovascular: Phlebitis.

Gastrointestinal: Gastrointestinal bleeding, development of duodenal ulcer, sialorrhea, bruxism, hiccups, flatulence, burning sensation of tongue.

Hematologic: Hemolytic and nonhemolytic anemia, thrombocytopenia, leukopenia, agranulocytosis.

Hypersensitivity: Henoch-Schonlein purpura.

Metabolic: Weight gain, edema.

Nervous System/Psychiatric: Ataxia, depression with suicidal tendencies, dementia, euphoria, convulsions (however, a causal relationship has not been established); bradykinetic episodes, numbness, muscle twitching, blepharospasm (which may be taken as an early sign of excess dosage; consideration of dosage reduction may be made at this time), trismus, activation of latent Horner's syndrome, nightmares.

Skin: Malignant melanoma (see also CONTRAINDICATIONS), increased sweating.

Special Senses : Oculogyric crisis, mydriasis, diplopia.

Urogenital: Urinary retention, priapism.

Miscellaneous : Faintness, hoarseness, malaise, hot flashes, sense of stimulation, bizarre breathing patterns.

Laboratory Tests : Abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), bilirubin, Coombs test, uric acid.

Read the entire FDA prescribing information for Parcopa (Carbidopa and Levodopa Extended-release Tablets)