Carbidopa and Levodopa 25 mg; 250 mg Tablet, 30-count — NDC 0615-8516-39 (Billing 00615-8516-39)

WARNINGS When carbidopa and levodopa tablets are to be given to patients who are being treated with levodopa, levodopa must be discontinued at least twelve hours before therapy with carbidopa and levodopa tablets is started. In order to reduce adverse reactions, it is necessary to individualize therapy. See DOSAGE AND ADMINISTRATION section before initiating therapy.

The addition of carbidopa with levodopa in the form of carbidopa and levodopa tablets 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. Because carbidopa permits more levodopa to reach the brain and more dopamine to be formed, certain adverse central nervous system (CNS) effects, e.g., dyskinesias (involuntary movements), may occur at lower dosages and sooner with carbidopa and levodopa tablets than with levodopa alone.

All patients should be observed carefully for the development of depression with concomitant suicidal tendencies. Carbidopa and levodopa tablets should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease. As with levodopa, care should be exercised in administering carbidopa and levodopa tablets, to patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias.

In such patients, cardiac function should be monitored with particular care during the period of initial dosage adjustment, in a facility with provisions for intensive cardiac care. As with levodopa, treatment with carbidopa and levodopa tablets may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer. Falling Asleep During Activities of Daily Living and Somnolence Patients taking carbidopa and levodopa tablets alone or with other dopaminergic drugs have reported suddenly falling asleep without prior warning of sleepiness while engaged in activities of daily living (includes operation of motor vehicles).

Road traffic accidents attributed to sudden sleep onset have been reported. Although many patients reported somnolence while on dopaminergic medications, there have been reports of road traffic accidents attributed to sudden onset of sleep in which the patient did not perceive any warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Sudden onset of sleep has been reported to occur as long as one year after the initiation of treatment.

Falling asleep while engaged in activities of daily living usually occurs in patients experiencing preexisting somnolence, although some patients may not give such a history. For this reason, prescribers should reassess patients for drowsiness or sleepiness especially since some of the events occur well after the start of treatment. Prescribers should be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.

Patients should be advised to exercise caution while driving or operating machines during treatment with carbidopa and levodopa tablets. Patients who have already experienced somnolence or an episode of sudden sleep onset should not participate in these activities during treatment with carbidopa and levodopa tablets. Before initiating treatment with carbidopa and levodopa tablets, advise patients about the potential to develop drowsiness and ask specifically about factors that may increase the risk for somnolence with carbidopa and levodopa tablets such as the use of concomitant sedating medications and the presence of sleep disorders.

Consider discontinuing carbidopa and levodopa tablets in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.). If treatment with carbidopa and… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS The most common adverse reactions reported with carbidopa and levodopa tablets 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 tablets: 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 tablets 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 carbidopa and levodopa tablets 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.

Drug Interactions Caution should be exercised when the following drugs are administered concomitantly with carbidopa and levodopa tablets. Symptomatic postural hypotension occurred when carbidopa and levodopa tablets was added to the treatment of a patient receiving antihypertensive drugs. Therefore, when therapy with carbidopa and levodopa tablets is started, dosage adjustment of the antihypertensive drug may be required.

For patients receiving MAO inhibitors (Type A or B), see CONTRAINDICATIONS . Concomitant therapy with selegiline and carbidopa and levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa and levodopa alone (see CONTRAINDICATIONS ). There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and carbidopa and levodopa tablets.

Dopamine D 2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone) and isoniazid may reduce the therapeutic effects of levodopa. In addition, the beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine. Patients taking these drugs with carbidopa and levodopa tablets should be carefully observed for loss of therapeutic response.

Use of carbidopa and levodopa tablets with dopamine-depleting agents (e.g., reserpine and tetrabenazine) or other drugs known to deplete monoamine stores is not recommended. Carbidopa and levodopa tablets and iron salts or multivitamins containing iron salts should be coadministered with caution. Iron salts can form chelates with levodopa and carbidopa and consequently reduce the bioavailability of carbidopa and levodopa.

Although metoclopramide may increase the bioavailability of levodopa by increasing gastric emptying, metoclopramide may also adversely affect disease control by its dopamine receptor antagonistic properties.

PRECAUTIONS General As with levodopa, periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function are recommended during extended therapy. Patients with chronic wide-angle glaucoma may be treated cautiously with carbidopa and levodopa tablets provided the intraocular pressure is well-controlled and the patient is monitored carefully for changes in intraocular pressure during therapy. Dyskinesia Levodopa alone, as well as carbidopa and levodopa tablets, is associated with dyskinesias.

The occurrence of dyskinesias may require dosage reduction. Hallucinations/Psychotic-Like Behavior Hallucinations and psychotic-like behavior have been reported with dopaminergic medications. In general, hallucinations present shortly after the initiation of therapy and may be responsive to dose reduction in levodopa.

Hallucinations may be accompanied by confusion and to a lesser extent sleep disorder (insomnia) and excessive dreaming. Carbidopa and levodopa tablets may have similar effects on thinking and behavior. This abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.

Ordinarily, patients with a major psychotic disorder should not be treated with carbidopa and levodopa tablets, because of the risk of exacerbating psychosis. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of carbidopa and levodopa tablets. Impulse Control/Compulsive Behaviors Reports of patients taking dopaminergic medications (medications that increase central dopaminergic tone), suggest that patients may experience an intense urge to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges.

In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or the caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with carbidopa and levodopa tablets. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking carbidopa and levodopa tablets (see Information for Patients ).

Melanoma Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson's disease or other factors, such as drugs used to treat Parkinson's disease, is unclear. For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using carbidopa and levodopa tablets for any indication.

Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists). Information for Patients The patient should be informed that carbidopa and levodopa tablets are an immediate-release formulation of carbidopa and levodopa that is designed to begin release of ingredients within 30 minutes. It is important that carbidopa and levodopa tablets 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. 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 shoul… [Excerpted — this section continues on DailyMed.]