Each tablet contains: Carbidopa, B.P. 25 mg and Levodopa 100 mg and 250 mg.
Each controlled-release tablet contains: Carbidopa 50 mg and Levodopa 200 mg.
Pharmacology: Pharmacodynamics: The symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in such patients because dopamine does not cross the blood brain barrier. However, levodopa, the precursor, of dopamine, does not cross the blood brain barrier and is converted to dopamine in the basal ganglia/brain. When levodopa is administered orally, it is rapidly converted to dopamine in non-neuronal tissues especially intestinal mucosa so that only a small portion of the given dose is transported unchanged to the neuronal tissue. As a consequence large doses of levodopa are required to be administered to produce adequate therapeutic effect which may often be associated with side effects. Combination of levodopa with a selective peripheral decarboxylase inhibitor, carbidopa can almost completely abolish extra cerebral metabolism of levodopa and in oral doses of 10-25 mg may reverse the effects of levodopa by increasing the rate of decarboxylation. Carbidopa inhibits the action of pyridoxine.
Tidomet CR: When levodopa is administered orally, it is rapidly decarboxylated to dopamine in extracerebral tissues so that only small portion of a given dose is transported unchanged in the central nervous system. Since levodopa competes with certain amino acids for transport across the gut wall, the absorption of levodopa may be impaired in some patients on a high protein diet.
Carbidopa inhibits decarboxylation of peripheral levodopa. It does not cross the blood brain barrier and does not affect the metabolism of levodopa within the central nervous system. Decarboxylase inhibiting activity of Carbidopa is limited to extracerebral tissues; hence the administration of carbidopa with levodopa makes more levodopa available to transport to the brain.
Controlled release preparation is designed to release Carbidopa 50 mg and Levodopa 200 mg over 4 to 6 hours period, there is a less variation in plasma levodopa levels than with the conventional formulation.
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.
Elimination half life of levodopa in the presence of carbidopa is about 1.5 hours. Tidomet in controlled release preparation have an apparent half life of levodopa may be prolonged because of continuous absorption. The mean time to peak concentration of levodopa after a single dose of co-careldopa controlled release preparation is about 2 hours as compared to 0.5 hours after conventional administration. The maximum concentration and extent availability of levodopa after a single dose of co-careldopa controlled release is about 35% and 70-75% respectively compared to conventional formulation. At steady state, carbidopa bioavailability from co-careldopa controlled release is approximately 58% relative to that from conventional formulation.
Symptoms of idiopathic Parkinson's disease (paralysis agitans), postencephalitic parkinsonism, which may follow injury to the nervous system by carbon monoxide intoxication and manganese intoxication.
Tidomet 100 mg/25 mg: A suggested initial dose for patients not previously treated with levodopa is 1 tablet three times daily, increased gradually, in increments of carbidopa 12.5 mg with levodopa 50 mg or carbidopa 25 mg with levodpa 100 mg everyday or on alternate days, as necessary. The usual maintenance dosage range is carbidopa 75 to 200 mg with levodopa 750 mg to 2 g daily in divided doses. Carbidopa doses greater than 200 mg daily are not generally exceeded.
The initial dose of co-careldopa in patients previously treated with levodopa should be about 1/4 of the dose previously being taken, thus patients taking less than 1.5 g of levodopa daily a suggested initial dose is 1 tablet three or four times daily; a suggested initial dose for patients taking more than 1.5 g of levodopa daily is 1 tablet three to four times daily.
Tidomet 250 mg/25 mg: Carefully titrate dosage in each patient. Initiate treatment with 1 tablet of co-careldopa. Plus 3 times a day. Dosage may be increased by 1 tablet a day or every other day as necessary until a dosage of 8 tablets of co-careldopa. Plus per day is reached. If co-careldopa LS is used, initiate 1 tablet 3 or 4 times a day and increased by 1 tablet every day or every other day until a total 8 tablets i.e. 2 tablets 4 times a day is reached. Transferring patients from levodopa to co-careldopa, levodopa must be discontinued at least before 8 hours. 1/4th of the previous levodopa dosage may be started as co-careldopa. Patients taking less than 1500 mg of levodopa per day should be started on one tablet of co-careldopa. Plus 3-4 times a day. Maintenance therapy should be individualized and adjusted according to the desired therapeutic response. When a greater proportion of carbidopa is required, one tablet of co-careldopa. Plus may be substituted for each tablet of co-careldopa LS. When more levodopa is required co-cereldopa forte should be substituted at a dosage of 1 tablet 3 or 4 times a day. If necessary the dosage may be increased by 1/2 or 1 tablet everyday or every other day to a maximum of 8 tablets a day. The occurrence of involuntary movements may require dosage reduction; Blepharospasm may be a useful early sign of excess dosage in some patients.
Tidomet CR: Patients already receiving levodopa therapy and for those currently receiving levodopa alone: Initial dose is 1 tablet twice daily adjusted according to response at intervals of not less than 3 days. It is recommended that for patients whose are not already receiving initial dosages should not exceed 600 mg of levodopa. Or as prescribed by the physician.
Patients already receiving a conventional preparation: Initial dose similar to that of the conventional preparation but the dosing intervals should be prolonged and are normally between 4 to 12 hours. The initial substitution of the controlled release preparation should provide not more than 10% more levodopa than was previously given for doses greater than 900 mg daily. Doses and intervals may then be altered according to clinical response, allowing at least 3 days between adjustments. Up to 30% more levodopa may be required in the controlled release preparation than was previously administered in the conventional preparation. Or as prescribed by the physician.
Average maintenance dose of controlled release preparation lies between the range of Carbidopa 100 mg with Levodopa 400 mg to Carbidopa 400 mg with Levodopa 1.6 g.
Tidomet 100 mg/25 mg and Tidomet CR: Pyridoxine may reverse some effects of levodopa but its value in overdosage has not been established; it does not reverse the effects of levodopa given with peripheral dopa-carboxylase inhibitor.
Tidomet 250 mg/25 mg: Pyridoxine is not effective in reversing the actions of co-careldopa. General supportive measures should be employed along with immediate gastric lavage. Intravenous fluids should be administered judiciously and adequate airway maintained. ECG monitoring should be instituted if patient develops arrhythmias. If required appropriate antiarrythmics should be administered.
Known hypersensitivity to any of the components, arrow angle glaucoma, patients with suspicious undiagnosed skin lesions or a history of melanoma. MAO inhibitors must be discontinued at least 2 weeks prior to initiating therapy because of likelihood of development of high blood pressure if both the drugs are given concomitantly.
Patients receiving levodopa alone must discontinue medication at least 8 hours before Tidomet is started. Tidomet should be substituted at a dosage that will provide approximately 25% of the previous levodopa dosage. Patients who are taking Tidomet should be instructed not to take additional levodopa unless prescribed by the physician. As with levodopa, Tidomet may cause involuntary movements and mental disturbances. All patients taking Tidomet should be observed carefully for the development of depression with concomitant suicidal tendencies. Tidomet should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal hepatic or endocrine disease, past or current psychosis.
Use in children: Safety in patients under 18 years of age has not been established.
Use in pregnancy & lactation: Tidomet must be used in women of child-bearing age group after weighing the possible hazards to the mother and the child.
Tidomet should not be given to nursing mothers.
Tidomet must be used in women of child-bearing age group after weighing the possible hazards to the mother and the child.
Tidomet should not be given to nursing mothers.
Serious adverse reactions are choreiform, dystonic and other involuntary movements, mental changes including paranoid ideation psychotic episodes, depression with/without development of suicidal tendencies and dementia. The less common and less serious side effects are nausea, orthostatic hypotension, bradykinetic episodes, anorexia, vomiting and dizziness. Rarely GI bleeding, duodenal ulcer, hypertension, etc have been occurred.
Symptomatic postural hypotension may occur. If Tidomet is added to the treatment of patient receiving antihypertensive drugs. Hypertension and dyskinesia results from the concomitant use of tricyclics and Tidomet. Phenothiazines and butyrophenones may reduce the therapeutic effects of Tidomet. Phenytoin and papaverine reverse beneficial effects of levodopa.
Store at temperatures not exceeding 30°C. Protect from light.
N04BA02 - levodopa and decarboxylase inhibitor ; Belongs to the class of dopa and dopa derivative dopaminergic agents. Used in the management of Parkinson's disease.
Tidomet CR 200 mg/50 mg CR tab
Tidomet 100 mg/25 mg tab
Tidomet 250 mg/25 mg tab