n-off”) responses to levodopa have not been shown to benefit from the addition of carbidopa. since carbidopa prevents the reversal of levodopa effects caused by pyridoxine, supplemental pyridoxine (vitamin b 6 ), can be given to patients when they are receiving carbidopa and levodopa concomitantly or as carbidopa-levodopa. although the administration of carbidopa tablets permits control of parkinsonism and parkinson’s disease with much lower doses of levodopa, there is no conclusive evidence at present that this is beneficial other than in reducing nausea and vomiting, permitting more rapid titration, and providing a somewhat smoother response to levodopa. certain patients who responded poorly to levodopa alone have improved when carbidopa and levodopa were given concurrently. this was most likely due to decreased peripheral decarboxylation of levodopa rather than to a primary effect of carbidopa on the peripheral nervous system. carbidopa has not been shown to enhance the intrinsic efficacy of levodopa. in deciding whether to give carbidopa tablets with carbidopa-levodopa or with levodopa to patients who have nausea and/or vomiting, the physician should be aware that, while many patients may be expected to improve, some may not. since one cannot predict which patients are likely to improve, this can only be determined by a trial of therapy. it should be further noted that in controlled trials comparing carbidopa and levodopa with levodopa alone, about half the patients with nausea and/or vomiting on levodopa alone improved spontaneously despite being retained on the same dose of levodopa during the controlled portion of the trial.

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 levodopa in combination with carbidopa than with levodopa alone. falling asleep during activities of daily living and somnolence patients taking carbidopa-levodopa products 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). some of these episodes resulted in automobile accidents. although many of these patients reported somnolence while on dopaminergic medications, some did perceive that they had no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. some patients reported these events one year after the initiation of treatment. falling asleep while engaged in activities of daily living usually occurs in patients experiencing pre-existing somnolence, although some patients may not give such a history. for this reason, prescribers should continually reassess patients for drowsiness or sleepiness especially since some of the events occur 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 who have already experienced somnolence or an episode of sudden sleep onset should not participate in these activities during treatment with carbidopa when taking it with other carbidopa-levodopa products. before initiating treatment with carbidopa, advise patients about the potential to develop drowsiness and ask specifically about factors that may increase the risk for somnolence with carbidopa such as the use of concomitant sedating medications and the presence of sleep disorders. consider discontinuing carbidopa 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 continues, patients should be advised not to drive and to avoid other potentially dangerous activities that might result in harm if the patients become somnolent. there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living. hyperpyrexia and confusion: sporadic cases of a symptom complex resembling neuroleptic malignant syndrome (nms) have been reported in association with dose reductions or withdrawal of certain antiparkinsonian agents such as levodopa, carbidopa-levodopa, or carbidopa-levodopa extended-release. therefore, patients should be observed carefully when the dosage of levodopa or carbidopa-levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. nms is an uncommon but life-threatening syndrome characterized by fever or hyperthermia. neurological findings, including muscle rigidity, involuntary movements, altered consciousness, mental status changes; other disturbances, such as autonomic dysfunction, tachycardia, tachypnea, sweating, hyper-or hypotension; laboratory findings, such as creatine phosphokinase elevation, leukocytosis, myoglobinuria, and increased serum myoglobin, have been reported. the early diagnosis of this condition is important for the appropriate management of these patients. considering nms as a possible diagnosis and ruling out other acute illnesses (e.g., pneumonia, systemic infection, etc.) is essential. this may be especially complex if the clinical presentation includes both serious medical illness and untreated or inadequately treated extrapyramidal signs and symptoms (eps). other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (cns) pathology. the management of nms should include: 1) intensive symptomatic treatment and medical monitoring and 2) treatment of any concomitant serious medical problems for which specific treatments are available. dopamine agonists, such as bromocriptine, and muscle relaxants, such as dantrolene, are often used in the treatment of nms; however, their effectiveness has not been demonstrated in controlled studies.

a each day. additional doses of 12.5 mg or 25 mg may be given during the day with each dose of carbidopa-levodopa. carbidopa may be given with any dose carbidopa-levodopa as required for optimum therapeutic response. the maximum daily dosage of carbidopa, given as carbidopa and as carbidopa-levodopa), should not exceed 200 mg. patients requiring individual titration of carbidopa and levodopa dosage although carbidopa-levodopa is the most frequently used of carbidopa and levodopa administration, there may be an occasional patient who requires individually titrated doses of these two drugs. in these patients, carbidopa should be initiated at a dosage of 25 mg three or four times a day. the two drugs should be given at the same time, starting with no more than one-fifth (20%) to one-fourth (25%) of the previous or recommended daily dosage of levodopa when given without carbidopa. in patients already receiving levodopa therapy, at least twelve hours should elapse between the last dose of levodopa and initiation of therapy with carbidopa and levodopa. a convenient way to initiate therapy in these patients is in the morning following a night when the patient has not taken levodopa for at least twelve hours. health care providers who prescribe separate doses of carbidopa and levodopa should be thoroughly familiar with the directions for use of each drug. dosage adjustment dosage of carbidopa may be adjusted by adding or omitting one-half or one tablet a day. because both therapeutic and adverse responses occur more rapidly with combined therapy than when only levodopa is given, patients should be monitored closely during the dose adjustment period. specifically, involuntary movements will occur more rapidly when carbidopa and levodopa are given concomitantly than when levodopa is given without carbidopa. the occurrence of involuntary movements may require dosage reduction. blepharospasm may be a useful early sign of excess dosage in some patients. current evidence indicates other standard antiparkinsonian drugs may be continued while carbidopa and levodopa are being administered. however, the dosage of such other standard antiparkinsonian drugs may require adjustment. interruption of therapy sporadic cases of hyperpyrexia and confusion have been associated with dose reductions and withdrawal of carbidopa-levodopa) or carbidopa-levodopa extended release. patients should be observed carefully if abrupt reduction or discontinuation of carbidopa-levodopa or carbidopa-levodopa extended-release is required, especially if the patient is receiving neuroleptics. (see warnings .) if general anesthesia is required, therapy may be continued as long as the patient is permitted to take fluids and medication by mouth. when therapy is interrupted temporarily, the patient should be observed for symptoms resembling nms, and the usual daily dosage may be resumed as soon as the patient is able to take medication orally.

adverse reactions have been reported with levodopa and carbidopa-levodopa combination products. these same adverse reactions may also occur when carbidopa is administered with these products. body as a whole: abdominal pain and distress, asthenia, chest pain, fatigue. cardiovascular: cardiac irregularities, hypertension, myocardial infarction, hypotension including orthostatic hypotension, palpitation, phlebitis, syncope. gastrointestinal: anorexia, bruxism, burning sensation of the tongue, constipation, dark saliva, development of duodenal ulcer, diarrhea, dry mouth, dyspepsia, dysphagia, flatulence, gastrointestinal bleeding, gastrointestinal pain, heartburn, hiccups, sialorrhea, taste alterations, vomiting. hematologic: hemolytic and non-hemolytic anemia, leukopenia, thrombocytopenia, agranulocytosis. hypersensitivity: angioedema, urticaria, pruritus, henoch-schonlein purpura, bullous lesions (including pemphigus-like reactions). metabolic: edema, weight gain, weight loss. musculoskeletal: back pain, leg pain, muscle cramps, shoulder pain. nervous system/psychiatric: psychotic episodes including delusions, hallucinations and paranoid ideation, neuroleptic malignant syndrome (nms, see warnings ), 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, has not been established. respiratory: upper respiratory infection, dyspnea, pharyngeal pain, cough. skin: flushing, increased sweating, malignant melanoma (see also contraindications ), rash, alopecia, dark sweat. special senses: oculogyric crises, diplopia, blurred vision, dilated pupils. urogenital: dark urine, priapism, urinary frequency, urinary incontinence, urinary retention, urinary tract infection. laboratory tests: abnormalities in alkaline phosphatase, sgot (ast), sgpt (alt), lactic dehydrogenase, bilirubin, blood urea nitrogen (bun), coombs test; elevated serum glucose; decreased hemoglobin and hematocrit; decreased white blood cell count and serum potassium; increased serum creatinine and uric acid; white blood cells, bacteria and blood in the urine; protein and glucose in the urine. miscellaneous: bizarre breathing patterns, faintness, hoarseness, hot flashes, malaise, neuroleptic malignant syndrome, sense of stimulation.

e 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 in the body. the above factors may reduce the clinical effectiveness of the carbidopa and levodopa therapy. alert patients 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. advise patients to exercise caution while driving or operating machinery and that if they have experience somnolence and/or sudden sleep onset, they must refrain from these activities. (see warnings , falling asleep during activities of daily living and somnolence general .) 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. 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 intense urges while taking carbidopa and levodopa. physicians should consider dose reduction or stopping carbidopa and levodopa if a patient develops such urges while taking carbidopa with carbidopa/levodopa (see precautions , impulse control/compulsive behaviors ).

emale rats, their reproductive performance, or the growth and survival of the young. pregnancy pregnancy category c: there are no adequate and well-controlled studies with carbidopa in pregnant women. it has been reported from individual cases that levodopa crosses the human placental barrier, enters the fetus, and is metabolized. carbidopa concentrations in fetal tissue appeared to be minimal. carbidopa should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. carbidopa, at doses as high as 120 mg/kg/day, was without teratogenic effects in the mouse or rabbit. in the rabbit, but not in the mouse, carbidopa-levodopa produced visceral anomalies, similar to those seen with levodopa alone, at approximately 7 times the maximum recommended human dose. the teratogenic effect of levodopa in rabbits was unchanged by the concomitant administration of carbidopa. nursing mothers it is not known whether carbidopa is excreted in human milk. because many drugs are excreted in human milk, and because of their potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the nursing woman. pediatric use safety and effectiveness in pediatric patients have not been established, and use of the drug in patients below the age of 18 is not recommended.

ylated 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. the incidence of levodopa-induced nausea and vomiting is less when carbidopa is used with levodopa than when levodopa is used without carbidopa. in many patients, this reduction in nausea and vomiting will permit more rapid dosage titration. carbidopa inhibits decarboxylation of peripheral levodopa. carbidopa has not been demonstrated to have any overt pharmacodynamic actions in the recommended doses. it does not appear to cross the blood-brain barrier readily and does not affect the metabolism of levodopa within the central nervous system at doses of carbidopa that are recommended for maximum effective inhibition of peripheral decarboxylation of levodopa. since its decarboxylase-inhibiting activity is limited primarily to extracerebral tissues, administration of carbidopa with levodopa makes more levodopa available for transport to the brain. however, since levodopa and carbidopa compete with certain amino acids for transport across the gut wall, the absorption of levodopa and carbidopa may be impaired in some patients on a high protein diet. 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. in clinical pharmacologic studies, simultaneous administration of separate tablets of carbidopa and levodopa produced greater urinary excretion of levodopa in proportion to the excretion of dopamine when compared to the two drugs administered at separate times. supplemental pyridoxine (vitamin b 6 ) can be given to patients when they are receiving carbidopa and levodopa concomitantly or the fixed combination carbidopa-levodopa or carbidopa-levodopa extended release. previous reports in the medical literature cautioned that high doses of vitamin b 6 should not be taken by patients on levodopa therapy alone because exogenously administered pyridoxine would enhance the metabolism of levodopa to dopamine. the introduction of carbidopa to levodopa therapy, which inhibits the peripheral decarboxylation of levodopa to dopamine, counteracts the metabolic-enhancing effect of pyridoxine. carbidopa is combined with levodopa in carbidopa-levodopa and carbidopa-levodopa extended release tablets.

stopping carbidopa or levodopa if a patient develops such urges while taking carbidopa with carbidopa/levodopa.