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Co-careldopa (carbidopa and levodopa) oral modified release


Modified release tablets containing co-careldopa (carbidopa and levodopa)

Drugs List

  • CARAMET CR 25mg+100mg tablets
  • co-careldopa (carbidopa 25mg and levodopa 100mg) modified release tablet
  • co-careldopa (carbidopa 50mg and levodopa 200mg) modified release tablet
  • HALF SINEMET CR 25mg+100mg tablets
  • LECADO 25mg+100mg modified release tablet
  • LECADO 50mg+200mg modified release tablet
  • SINEMET CR 50mg+200mg tablets
  • Therapeutic Indications


    Parkinson's disease (not drug induced)

    Antiparkinson agent.

    Idiopathic Parkinson's disease, in particular to reduce off-period in patients who previously have been treated with levodopa/decarboxylase inhibitors, or with levodopa alone and who have experienced motor fluctuations. The experience is limited with modified release co-careldopa in patients who have not been treated with levodopa before.


    The optimum daily dose of co-careldopa should be carefully titrated for each patient. Patients should be closely monitored during the dose adjustment period, particularly with regard to appearance or worsening of nausea or abnormal involuntary movements (e.g. dyskinesias, chorea and dystonia).

    Standard antiparkinson drugs, other than levodopa alone, may be continued while co-careldopa is being administered, however their dosage may need to be adjusted.

    Proportions are expressed in the form x/y where x and y are the strengths in milligrams of carbidopa and levodopa respectively.


    Patients currently treated with conventional levodopa/decarboxylase inhibitor combinations
    Initially doses of modified-release co-careldopa should be substituted at an amount that provides no more than approximately 10% more levodopa per day when higher dosages are given (more than 900 mg per day). The dosing interval should be prolonged by 30 to 50% at intervals ranging from 4 to 12 hours. If divided doses are not equal, the smaller dose should be given at the end of the day. Depending on clinical response, the dose may need further titration, with doses that provide up to 30% more levodopa per day sometimes being required. At least 12 hours should be allowed between the last intake of standard release levodopa/decarboxylase inhibitor and the first dose of co-careldopa modified release preparations.

    Guideline for transferring from standard release preparations to modified release preparations of co-careldopa

    100 to 200 mg levodopa daily in standard release formulation will require 200 mg levodopa daily in two divided doses of the modified release formulation
    300 to 400 mg levodopa daily in standard release formulation will require 400 mg levodopa daily in two divided doses of the modified release formulation
    500 to 600 mg levodopa daily in standard release formulation will require 600 mg levodopa daily in three divided doses of the modified release formulation
    700 to 800 mg levodopa daily in standard release formulation will require 800 mg levodopa daily in three or more divided doses of the modified release formulation
    900 to 1000 mg levodopa daily in standard release formulation will require 1000 mg levodopa daily in three or more divided doses of the modified release formulation
    1100 to 1200 mg levodopa daily in standard release formulation will require 1200 mg levodopa daily in three or more divided doses of the modified release formulation
    1300 to 1400 mg levodopa daily in standard release formulation will require 1400 mg levodopa daily in three or more divided doses of the modified release formulation
    1500 to 1600 mg levodopa daily in standard release formulation will require 1600 mg levodopa daily in three or more divided doses of the modified release formulation

    Patients currently treated with levodopa alone

    Levodopa must be discontinued at least 12 hours before therapy with modified release co-careldopa is initiated. Some manufacturers recommend 8 hours; refer to product information for further details. In patients with mild to moderate disease, the recommended starting dose is one modified release tablet of co-careldopa 50 mg + 200 mg twice daily.

    N.B. At the time that this monograph was reviewed there were no licensed preparations for levodopa monotherapy in routine use.

    Patients not receiving levodopa

    Dosage recommendations vary between brands.

    In patients with mild to moderate disease, the initial recommended dose is one modified release tablet of co-careldopa 25 mg + 100 mg twice daily, or one modified release tablet of co-careldopa 50 mg + 200 mg twice daily. In patients who need more levodopa, a daily dose of three to four tablets of co-careldopa 25 mg + 100 mg is usually well tolerated. Initial doses should not exceed 600 mg levodopa per day, and should not be given at intervals of less than six hours.


    Dose and dosing intervals may need to be increased or decreased according to therapeutic response following initiation of therapy. Most patients are adequately maintained on two to eight tablets of modified release co-careldopa 50 mg + 200 mg, administered as divided doses at intervals ranging from four to twelve hours. Higher doses (up to 12 co-careldopa 50 mg + 200 mg tablets) and shorter intervals (less than 4 hours) have been used, but are not recommended.

    If a dosing interval of less than 4 hours is used, or if the divided doses are not equal, it is recommended that the smaller dose is given at the end of the day. In some patients the onset of effect of the first morning dose of co-careldopa modified tablets may be delayed for up to 1 hour when compared with the response usually obtained from the first dose of standard co-careldopa tablets.

    An interval of at least two to four days between dosage adjustments is recommended.

    Depending on the severity of the disease, six months of treatment may be required to achieve optimal disease control.


    Periodic clinical evaluations are recommended because Parkinson's disease is progressive, and adjustment of the co-careldopa regimen may be required.

    Addition of other antiparkinson medication

    Anticholinergic agents, dopamine agonists and amantadine can be given concurrently with modified release co-careldopa, although dosage adjustment may be necessary.

    Interruption of therapy

    Observe patients carefully, if abrupt reduction or discontinuation of therapy is required, especially if the patient is also receiving antipsychotics.

    If anaesthetic is necessary, administration of modified release co-careldopa can be continued as long as the patient is allowed to take oral medications. In case of a temporary interruption of the therapy, the usual dose can be administered as soon as the patient is able to take oral medication.


    (See Dosage; Adult)


    Children under 18 years
    Suspected malignant melanoma
    Within 2 weeks of discontinuing MAOIs
    Acute phase of cerebrovascular accident
    Confusional states
    History of malignant melanoma
    Malignant melanoma
    Narrow angle glaucoma
    Serious cardiac arrhythmias
    Severe cardiac failure
    Severe psychiatric disorder

    Precautions and Warnings

    Females of childbearing potential
    Predisposition to narrow angle glaucoma
    Cardiac arrhythmias
    Cushing's disease
    Diabetes mellitus
    Endocrine disease
    Glucose-galactose malabsorption syndrome
    Hepatic impairment
    History of haematemesis
    History of myocardial infarction
    History of peptic ulcer
    History of postural hypotension
    History of seizures
    Lactose intolerance
    Open angle glaucoma
    Psychiatric disorder
    Pulmonary disease
    Renal impairment
    Severe cardiovascular disorder

    Advise patient/carer risk of dopamine dysregulation syndrome (DDS)
    Not recommended for treatment of drug induced extrapyramidal reactions
    Advise ability to drive/operate machinery may be affected by side effects
    Advise patient that sudden onset sleep episodes may affect ability to drive
    Some formulations contain lactose
    Take at a different time from iron supplement
    Monitor closely patient with a history of myocardial infarction
    Monitor for melanoma regularly
    Monitor for mental changes, suicidal depression and antisocial behaviour
    Monitor patients at risk of glaucoma for increases in intraocular pressure
    Monitor patients for impulse control disorders
    Monitor renal, hepatic and haematological parameters
    Review treatment if impulse control disorders symptoms occur
    Reduce dose if dyskinesia occurs
    May affect results of some laboratory tests
    May colour urine red
    Avoid abrupt withdrawal: May cause signs of neuroleptic malignant syndrome
    Reduce dose or discontinue if sudden onset of sleep during daily activities
    Female: Ensure adequate contraception during treatment
    Advise patient/carer about symptoms of impulse control disorders
    Advise patients that hallucinations can occur

    Modified release co-careldopa preparations may be given concurrently with MAO inhibitors with selectivity for MAO type B (e.g. selegiline hydrochloride) according to manufacturers dosage recommendations.

    Patients with a history of severe involuntary movements or psychotic episodes when treated with levodopa alone, or levodopa/decarboxylase inhibitor combination, should be carefully observed during substitution with co-careldopa. These reactions are thought to be due to increased levels of dopamine in the brain following administration of levodopa. Dose reduction may be required.

    Dyskinesias may occur, especially in patients previously treated with levodopa alone. The occurrence of such symptoms may require dosage reduction. The onset of action with modified release preparations of co-careldopa may be slower in patients with early morning dyskinesias when compared with standard release preparations of co-careldopa. The incidence of dyskinesias may also be slightly higher in advanced patients with motor fluctuations treated with modified release preparations of co-careldopa.

    Pregnancy and Lactation


    Co-careldopa is contraindicated in pregnancy.

    Animal studies have shown teratogenicity. Both levodopa and combinations of levodopa and carbidopa have caused visceral and skeletal malformations in rabbits. No adverse outcomes associated with this drug have been observed in a limited number of human pregnancies though. Data published in 1995 describes the two pregnancies which were terminated at 8 weeks and 10 weeks by a women with juvenile parkinson's disease who had been taking 200/800 mg/day of carbidopa/levodopa. The relatively high concentrations of dopamine in foetal peripheral organs and neural tissue implied that the foetuses had metabolised levodopa. Neurotransmitters have been shown to alter early neural development in animals and cultured cells, therefore the investigators cautioned that the increased amounts of dopamine found in this study suggested that chronic use of levodopa during gestation could induce long term damage. Because of this potential risk to the foetus, co-careldopa should not be used during pregnancy.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    Co-careldopa is contraindicated in breastfeeding.

    Levodopa is excreted into human breast milk but it is unknown whether carbidopa is excreted. A study in 1974 provided clinical evidence that levodopa inhibits lactation. Doses of 500 to 3500 mg/day of levodopa were given orally to ten female patients with a history of inappropriate galactorrhoea. Partial to complete suppression of lactation was observed but when the treatment was stopped, lactation returned to normal. Briggs (2011) classifies levodopa and carbidopa separately as probably being compatible with breastfeeding. However, Hale (2010) puts levodopa in a risk category of possibly hazardous because there is positive evidence of risk to a breastfed infant or to breast milk production. Because of the potential for adverse effects in the newborn and the suppression of lactation, co-careldopa should not be administered to women who are breastfeeding.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at

    Side Effects

    Activation of latent Horner's syndrome
    Alterations in hepatic enzymes
    Binge eating
    Bitter taste
    Blurred vision
    Burning tongue
    Cardiac disorders
    Chest pain
    Compulsive behaviour
    Dark saliva
    Dark sweat
    Darkening of urine
    Dopamine dysregulation syndrome
    Dream abnormalities
    Dry mouth
    Duodenal ulcer
    Extrapyramidal effects
    Gait abnormality
    Gastro-intestinal pain
    Gastrointestinal bleeding
    Henoch-Schonlein purpura
    Hot flushes
    Hypersensitivity reactions
    Increased libido
    Loss of mental acuity
    Malignant melanoma
    Motor disturbances
    Muscle spasm
    Neuroleptic malignant syndrome
    Orthostatic hypotension
    Pathological gambling
    Peripheral neuropathy
    Pupillary dilatation
    Sudden sleep onset episodes
    Suicidal tendencies
    Urinary incontinence
    Urinary retention
    Weight changes

    Effects on Laboratory Tests

    Co-careldopa has caused abnormalities in numerous laboratory tests and may occur with co-careldopa modified release preparation. These include elevated levels of blood urea nitrogen, AST (SGOT), ALT (SGPT), LDH, bilirubin, alkaline phosphatase, creatinine and uric acid.

    Decreased haemoglobin, haematocrit, elevated serum glucose and white blood cells, bacteria and blood in the urine have been reported.

    Positive Coombs' tests have been reported.

    False negative results may occur with the use of glucose-oxidase methods of testing for glucosuria.

    Co-careldopa may give false positive results for ketone bodies if test strips are use to test for ketonuria. This is not changed by boiling the urine sample.

    There have been rare cases of falsely diagnosed phaeochromocytoma in patients treated with co-careldopa


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review: October 2014

    Reference Sources

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press Accessed on 20 October, 2014.

    Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

    Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

    Summary of Product Characteristics: Apodespan PR 50 mg/200 mg Prolonged release Tablets. Accord Healthcare Limited. Revised October 2012.

    Summary of Product Characteristics: Caramet 25 mg/100 mg CR Tablets. TEVA UK Ltd. Revised December 2012.
    Summary of Product Characteristics: Caramet 50 mg 200 mg CR Tablets. TEVA UK Ltd. Revised December 2012.

    Summary of Product Characteristics: Lecado 100/25 mg Modified-release tablets. Sandoz Ltd. Revised August 2013.
    Summary of Product Characteristics: Lecado 200/50 mg Modified-release tablets. Sandoz Ltd. Revised October 2013.

    Summary of Product Characteristics: Sinemet CR and Half Sinemet CR. Merck Sharp & Dohme Ltd. Revised February 2013.

    The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

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