today [25:50 years of age. 1 6 7 8 9 Patients 75 years of age may be more likely to develop hallucinations but less likely to develop dystonia than younger patients. 1 No evidence of age-related differences in tolcapone pharmacokinetics. 1 4 5 Hepatic Impairment Do not initiate therapy in patients with clinical evidence of active liver disease, ALT or AST concentrations exceeding the ULN, or any other evidence of hepatocellular dysfunction. 1 Renal Impairment Use with caution in patients with severe renal impairment. 1 Common Adverse Effects Many CNS and psychiatric disturbances in patients receiving tolcapone in conjunction with levodopa are likely to result from increased levodopa concentrations and CNS bioavailability induced by tolcapone. 1 7 9 16 24 33 Dyskinesia, dystonia, nausea, anorexia, sleep disturbances/insomnia, orthostatic instability, muscle cramping, excessive dreaming, somnolence; these are dopaminergic effects associated with levodopa therapy. 7 9 15 16 28 Most frequent nondopaminergic adverse effect: diarrhea. 7 9 15 16 28 29 Interactions for Tasmar Metabolized in part by COMT 1 2 27 28 and by CYP3A4 and CYP2A6. 1 28 Inhibits COMT; has affinity for CYP2C9 in vitro. 1 20 Drugs Metabolized by Hepatic Microsomal Enzymes Clinically important interactions with drugs metabolized by CYP2C9 and CYP2D6 are not expected to occur. 1 In vitro studies did not reveal important interactions with substrates for CYP isoenzymes 2A6, 1A2, 3A4, 2C19, or 2D6. 1 Drugs Metabolized by COMT Tolcapone may alter the metabolism of drugs metabolized by COMT. 1 Drugs Affecting CNS Monoaminergic or Cholinergic System Symptom complex resembling neuroleptic malignant syndrome reported in patients receiving tolcapone in combination with other drugs that affect brain monoaminergic or anticholinergic systems; caution is advised if such combinations are used. 1 Specific Drugs Drug Interaction Comments Antidepressants, SSRIs Symptom complex resembling neuroleptic malignant syndrome reported in patients receiving tolcapone in combination with other drugs that affect brain monoaminergic systems 1 Caution advised if such combinations are used 1 Antidepressants, tricyclics Symptom complex resembling neuroleptic malignant syndrome reported in patients receiving tolcapone in combination with other drugs that affect brain monoaminergic systems 1 No alteration of desipramine pharmacokinetics; however, regimens that include tolcapone, levodopa/carbidopa, and desipramine are not tolerated as well as regimens that do not include desipramine 1 Caution advised if such combinations are used 1 Carbidopa No alteration of carbidopa pharmacokinetics 1 Catecholamines (methyldopa, dobutamine, apomorphine, isoproterenol) Effect on pharmacokinetics not evaluated 1 28 Consider dosage reduction of drugs metabolized by COMT 1 28 CNS depressants Possible additive sedative effects 1 Ephedrine No apparent change in tolerability of ephedrine (hemodynamic parameters or plasma catecholamine concentrations at rest or during exercise) 1 Can administer concomitantly 1 Levodopa Levodopa AUC increased 2-fold and half-life increased from 2 hours to 3.5 hours without an increase in peak plasma levodopa concentration or a change in the time to peak plasma concentration; the result is more stable plasma levodopa concentrations and enhanced clinical efficacy 1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 18 19 26 Used for therapeutic effect 1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 18 19 26 Levodopa dosage reduction may be required 1 6 7 9 16 23 MAO inhibitors, nonselective (e.g., phenelzine, tranylcypromine) Possible inhibition of the principal pathways of catacholamine metabolism 1 28 Symptom complex resembling neuroleptic malignant syndrome reported in patients receiving tolcapone in combination with other drugs that affect brain monoaminergic systems 1 Avoid concomitant administration 1 28 MAO-B inhibitors, selective (e.g., selegiline) Adverse effect profile associated with regimens that include tolcapone, levodopa/carbidopa, and selegiline is similar to that associated with regimens that do not include selegiline 1 19 Can be administered concomitantly 1 19 Phenytoin No displacement of phenytoin from protein binding sites in vitro 1 Tolbutamide No effect on tolbutamide pharmacokinetics; no displacement of tolbutamide from protein binding sites in vitro 1 Warfarin Possible increased plasma warfarin concentrations; 1 28 33 no displacement of warfarin from protein binding sites in vitro 1 Determine PT and INR frequently and adjust dosage, if needed 1 28 33 Tasmar Pharmacokinetics Absorption Bioavailability Absolute bioavailability following oral administration is about 65 68%. 1 27 Rapidly absorbed following oral administration, with peak plasma concentrations generally attained within 2 hours. 1 2 3 4 5 8 14 27 28 Onset Maximum inhibition of erythrocyte COMT activity is achieved within 1 hour and exceeds 80% following a single oral 200-mg dose in healthy individuals; 1 2 4 5 8 maximum inhibition is about 80% following administration of 200 mg 3 times daily for 7 days. 1 8 Duration COMT inhibitory activity persists for 16 24 hours following a single oral 200-mg dose in healthy individuals; 1 2 4 5 8 inhibition at trough tolcapone concentrations is 30 45% following administration of 200 mg 3 times daily for 7 days. 1 8 Food Administration within 1 hour before or 2 hours after a meal reduces bioavailability by 10 20% compared with administration in the fasting state. 1 Distribution Extent Distribution into body tissues and fluids is not fully characterized; 1 33 however, the drug is not widely distributed. 1 2 13 Distributes into brain tissue. 1 2 13 Distributes into milk in rats; not known whether tolcapone distributes into human milk. 1 Plasma Protein Binding >99.9% (principally albumin). 1 27 Special Populations In patients with moderate cirrhotic liver disease (Child-Pugh class B), volume of distribution of unbound tolcapone is reduced almost 50%. 1 27 Elimination Metabolism Extensively metabolized by a variety of mechanisms: 1 27 28 glucuronidation (principal metabolic pathway), 1 27 28 metabolism by COMT to catechol-3- O -methyltolcapone, 1 2 27 28 hydroxylation followed by oxidation to a carboxylic acid derivative, 1 28 and reduction followed by N -acetylation. 1 In vitro data indicate that CYP3A4 and CYP2A6 catalyze the oxidation reaction. 1 28 Elimination Route Excreted in urine (60%) and feces (40%); 1 minimally excreted in urine as unchanged drug (] FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug 10 + years Approval History FDA approved 1998 Manufacturer Valeant Pharmaceuticals International, Inc. Drug Class Dopaminergic antiparkinsonism agents Related Drugs Parkinson's Disease Exelon , ropinirole , pramipexole , Sinemet , Requip , benztropine , carbidopa / levodopa , Mirapex , amantadine , rivastigmine , Azilect , Cogentin , selegiline , trihexyphenidyl , bromocriptine , entacapone , Neupro , Rytary , rasagiline , Stalevo , Artane , carbidopa / entacapone / levodopa , Comtan , belladonna , More... Tasmar Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first! Tasmar Images Tasmar 200 mg (TASMAR 200 V) View larger images quite a lot of
of fake Tasmar left out
EmoticonEmoticon