Lodosyn Information
Lodosyn (Carbidopa)
Lodosyn (Carbidopa) Description
Carbidopa, an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.3. It is designated chemically as (–)-L-α-hydrazino-α-methyl-β-(3,4-dihydroxybenzene) propanoic acid monohydrate. Its empirical formula is CHNO•HO, and its structural formula is:
Lodosyn (Carbidopa) tablets contain 25 mg of carbidopa. Inactive ingredients are cellulose, FD&C Yellow 6, magnesium stearate and starch.
Tablet content is expressed in terms of anhydrous carbidopa which has a molecular weight of 226.3.
Lodosyn (Carbidopa) Clinical Pharmacology
Parkinson's disease is a progressive, neurodegenerative disorder of the extrapyramidal nervous system affecting the mobility and control of the skeletal muscular system. Its characteristic features include resting tremor, rigidity, and bradykinetic movements. Symptomatic treatments, such as levodopa therapies, may permit the patient better mobility.
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. 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 Lodosyn (Carbidopa) is used with levodopa than when levodopa is used without Lodosyn (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.
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) can be given to patients when they are receiving carbidopa and levodopa concomitantly or as SINEMET CR (Carbidopa-Levodopa) Sustained-Release or SINEMET (Carbidopa-Levodopa). Previous reports in the medical literature cautioned that high doses of vitamin B 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 SINEMET (Carbidopa-Levodopa) and SINEMET CR (Carbidopa-Levodopa) Sustained-Release tablets. These combination tablets are available in three strengths for SINEMET: SINEMET 10-100 (Carbidopa-Levodopa), SINEMET 25-250 (Carbidopa-Levodopa) (1:10 ratio of carbidopa to levodopa) and SINEMET 25-100 (Carbidopa-Levodopa) (1:4 ratio of carbidopa to levodopa), and in two strengths for SINEMET CR: SINEMET CR 50-200 (Carbidopa-Levodopa) Sustained-Release and SINEMET CR 25-100 (Carbidopa-Levodopa) Sustained-Release (1:4 ratio of carbidopa to levodopa). Clinical trials show that these ratios of carbidopa and levodopa provide useful therapeutic effects in most patients.
Lodosyn (Carbidopa) Indications And Usage
Lodosyn (Carbidopa) is indicated for use with SINEMET (Carbidopa-Levodopa) or with levodopa in the treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), postencephalitic parkinsonism, and symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication.
Lodosyn (Carbidopa) is for use with SINEMET (Carbidopa-Levodopa) in patients for whom the dosage of SINEMET (Carbidopa-Levodopa) provides less than adequate daily dosage (usually 70 mg daily) of carbidopa.
Lodosyn (Carbidopa) is for use with levodopa in the occasional patient whose dosage requirement of carbidopa and levodopa necessitates separate titration of each entity.
Lodosyn (Carbidopa) is used with SINEMET (Carbidopa-Levodopa) or with levodopa to permit the administration of lower doses of levodopa with reduced nausea and vomiting, more rapid dosage titration, and with a somewhat smoother response. However, patients with markedly irregular ("on-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), can be given to patients when they are receiving carbidopa and levodopa concomitantly or as SINEMET (Carbidopa-Levodopa).
Although the administration of Lodosyn (Carbidopa) 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 considering whether to give Lodosyn (Carbidopa) with SINEMET (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.
Lodosyn (Carbidopa) Contraindications
Lodosyn (Carbidopa) is contraindicated in patients with known hypersensitivity to any component of this drug.
Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with levodopa or carbidopa-levodopa combination products with or without Lodosyn (Carbidopa) . These inhibitors must be discontinued at least two weeks prior to initiating therapy with levodopa. SINEMET (Carbidopa-Levodopa), or levodopa may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline HCl) (see ).
Levodopa or carbidopa-levodopa products, with or without Lodosyn (Carbidopa) , are contraindicated in patients with narrow-angle glaucoma.
Because levodopa or carbidopa-levodopa products, with or without Lodosyn (Carbidopa) , may activate a malignant melanoma, they should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma.
Lodosyn (Carbidopa) Warnings
As with levodopa, concomitant administration of Lodosyn (Carbidopa) and levodopa may cause involuntary movements and mental disturbances. These reactions are thought to be due to increased brain dopamine following administration of levodopa. 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. Lodosyn (Carbidopa) Lodosyn (Carbidopa) The occurrence of dyskinesias may require levodopa dosage reduction.
Levodopa, with or without Lodosyn (Carbidopa) , 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 levodopa, with or without Lodosyn (Carbidopa) , 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 alone there is a possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer.
Lodosyn (Carbidopa) Precautions
As with levodopa alone, periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function are recommended during extended concomitant therapy with Lodosyn (Carbidopa) and levodopa, or with Lodosyn (Carbidopa) and SINEMET (Carbidopa-Levodopa), or any combination of these drugs.
Patients with chronic wide-angle glaucoma may be treated cautiously with Lodosyn (Carbidopa) and levodopa or SINEMET, or any combination of these drugs, just as with levodopa alone, provided the intraocular pressure is well controlled and the patient is monitored carefully for changes in intraocular pressure during therapy.
Abnormalities in laboratory tests may include elevations of liver function tests such as alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase, and bilirubin. Abnormalities in blood urea nitrogen and positive Coombs test have also been reported. Commonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during concomitant administration of carbidopa and levodopa than with levodopa alone.
Levodopa and carbidopa-levodopa combination products may cause a false-positive reaction for urinary ketone bodies when a test tape is used for determination of ketonuria. This reaction will not be altered by boiling the urine specimen. False-negative tests may result with the use of glucose-oxidase methods of testing for glucosuria.
Symptomatic postural hypotension has occurred when Lodosyn (Carbidopa) , given with levodopa or carbidopa-levodopa combination products, was added to the treatment of a patient receiving antihypertensive drugs. Therefore, when therapy with Lodosyn (Carbidopa) , given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
For patients receiving monoamine oxidase inhibitors, see . Concomitant therapy with selegiline and carbidopa-levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa-levodopa alone (see ).
There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and carbidopa-levodopa preparations.
Dopamine D 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 Lodosyn (Carbidopa) and levodopa or carbidopa-levodopa combination products should be carefully observed for loss of therapeutic response.
Iron salts may reduce the bioavailability of carbidopa and levodopa. The clinical relevance is unclear.
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.
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.
Lodosyn (Carbidopa) Adverse Reactions
Carbidopa has not been demonstrated to have any overt pharmacodynamic actions in the recommended doses. The only adverse reactions that have been observed have been with concomitant use of carbidopa with other drugs such as levodopa, and with carbidopalevodopa combination products.
When Lodosyn (Carbidopa) is administered concomitantly with levodopa or carbidopa-levodopa combination products, the most common adverse reactions have included dyskinesias such as choreiform, dystonic, and other involuntary movements, and nausea. Other adverse reactions reported with Lodosyn (Carbidopa) when administered concomitantly with levodopa alone or carbidopa-levodopa combination products were psychotic episodes including delusions, hallucinations, and paranoid ideation, depression with or without development of suicidal tendencies, and dementia. Convulsions also have occurred; however, a causal relationship with concomitant use of Lodosyn (Carbidopa) and levodopa has not been established.
The following other adverse reactions have been reported with levodopa and carbidopa-levodopa combination products. These same adverse reactions may also occur when Lodosyn (Carbidopa) is administered with these products.
Lodosyn (Carbidopa) Overdosage
No reports of overdose with Lodosyn (Carbidopa) have been received. Management of overdosage with carbidopa is the same as that with levodopa or carbidopa-levodopa preparations.
In the event of overdosage, 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 Lodosyn (Carbidopa) should be taken into consideration. To date, no experience has been reported with dialysis; hence, its value in overdosage is not known. Pyridoxine is not effective in reversing the actions of Lodosyn (Carbidopa) .
Based on studies in which high doses of levodopa and/or carbidopa were administered, a significant proportion of rats and mice given single oral doses of levodopa of approximately 1500-2000 mg/kg are expected to die. A significant proportion of infant rats of both sexes are expected to die at a dose of 800 mg/kg. A significant proportion of rats are expected to die after treatment with similar doses of carbidopa. The addition of carbidopa in a 1:10 ratio with levodopa increases the dose at which a significant proportion of mice are expected to die to 3360 mg/kg.
Lodosyn (Carbidopa) Dosage And Administration
Whether given with SINEMET (Carbidopa-Levodopa) or with levodopa, the optimal daily dosage of Lodosyn (Carbidopa) must be determined by careful titration. Most patients respond to a 1:10 proportion of carbidopa and levodopa, provided the daily dosage of carbidopa is 70 mg or more a day. The maximum daily dosage of carbidopa should not exceed 200 mg, since clinical experience with larger dosages is limited. If the patient is taking SINEMET (Carbidopa-Levodopa), the amount of carbidopa in SINEMET (Carbidopa-Levodopa) should be considered when calculating the total amount of Lodosyn (Carbidopa) to be administered each day.
Dosage of Lodosyn (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 Lodosyn (Carbidopa) and levodopa are given concomitantly than when levodopa is given without Lodosyn (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.
Sporadic cases of a symptom complex resembling the Neuroleptic Malignant Syndrome (NMS) have been associated with dose reductions and withdrawal of SINEMET (Carbidopa-Levodopa) or SINEMET CR (Carbidopa-Levodopa) Sustained-Release. Patients should be observed carefully if abrupt reduction or discontinuation of SINEMET (Carbidopa-Levodopa) or SINEMET CR (Carbidopa-Levodopa) Sustained-Release is required, especially if the patient is receiving neuroleptics. (See .)
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.
Lodosyn (Carbidopa) How Supplied
Lodosyn (Carbidopa) Tablets, 25 mg, are round, orange-colored, compressed tablets that are scored and coded 711 on one side and Lodosyn (Carbidopa) on the other.
They are supplied as follows:
Lodosyn (Carbidopa)
Lodosyn (Carbidopa) Principal Display Panel - Mg Tablet Bottle Label
