Levodopa/ Carbidopa

Registered South African indications: 

• Parkinson's disease
• Parkinsonism

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Non-selective monoamine oxidase inhibitors (MAO) (except for low doses of selective MAO-B inhibitors, such as selegiline) should not be given concomitantly with levodopa/carbidopa. These MAO inhibitors must be discontinued at least 2 weeks prior to initiating therapy
• Patients with narrow-angle glaucoma
• Levodopa may activate a malignant melanoma, therefore levodopa/carbidopa should not be used in patients with suspicious, undiagnosed skin lesions, or a history of melanoma
• Severe heart failure or severe cardiac dysrhythmia
• Severe psychosis
• Safety and efficacy in children under the age of 18 have not been established
• Pregnancy
• Breastfeeding

South African recommendations

• Renal impairment
• Hepatic impairment
• Switching from levodopa to combination product
• History of severe involuntary movements 
• History of psychotic episodes 
• Severe cardiovascular disease
• Severe respiratory disease
• Endocrine disease
• History of convulsions
• Peptic ulcer disease 
• Recent myocardial infarction
• Chronic wide-angle glaucoma
• May impair ability to drive and operate machinery
• Huntington's chorea
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab, controlled release tab (tab CR)

Parkinson's disease - Levodopa therapy naive

Initial dose

Carbidopa/ Levodopa
50/200 (mg)

• Oral (tab CR): 1 tab, 8-12hrly; Max levodopa: 600mg/24hrs; Minimum dosing interval: 6hrs

25/100 (mg)

• Oral (tab): 1 tab, 8hrly

25/250 (mg)  

• Oral (tab): 1/2 tab, 12-24hrly; Titrate by 1/2 tab at intervals of 1-2 days until response adequate; Max: 8 tab/24hrs

Maintenance

Carbidopa/ Levodopa
50/200 (mg)

• Oral (tab CR): 2-8 tabs/24hrs, 4-12hrly; Titrate slowly at intervals of 3 days

25/100 (mg)

• Oral (tab): 1 tab, 8hrly; Titrate by 1 tab at intervals of 1-2 days; Max: 8 tabs/24hrs

25/250 (mg) ₅

• Oral (tab): Titrate by 1/2-1 tab at intervals of 1-2 days until response adequate; Max: 8 tab/24hrs

See additional prescribing points for further dosing instructions

If given at intervals of less than 4hrs or if the divided doses are not equal, it is recommended to administer the lowest dose at the end of the day

Not established for use in children younger than 18 years

Pregnancy

South African recommendations

• Contraindicated
• The safety of levodopa/carbidopa in pregnancy has not been established. As teratogenicity has been demonstrated in experimental animals, the use of levodopa/carbidopa in women of childbearing potential requires that the anticipated benefit of levodopa/carbidopa be weighed against possible hazards should pregnancy occur
• It is preferable to delay the administration of levodopa/carbidopa after the first trimester; in case of no possibility to delay the beginning of treatment or no alternative, prenatal monitoring is necessary

Breastfeeding

South African recommendations

• Contraindicated
• The safety of levodopa/carbidopa in breastfeeding mothers has not been established. Breastfeeding during treatment with levodopa/carbidopa is not recommended

Fertility

South African recommendations

• No information available

South African recommendations

• Caution; no dose adjustment recommended

South African recommendations

• Caution; no dose adjustment recommended

South African recommendations

• No dose adjustment recommended
  There is extensive experience in the use of this product in elderly patients. The recommendations set out in the dose recommendations reflect the clinical data from this experience

Central Nervous System Disorders

• Hallucinations
• Confusion
• Dizziness
• Nightmares
• Somnolence
• Fatigue
• Sleeplessness
• Depression
• Euphoria
• Dementia
• Feeling of stimulation
• Agitation
• Fear
• Reduced thinking capacity
• Disorientation
• Headache
• Numbness 
• Convulsions
• Psychotic episodes 
• Paranoid ideation
• Impulse control disorders
• Pathological gambling
• Increased libido
• Hypersexuality
• Compulsive spending
• Compulsive eating 
• Extrapyramidal movement disorders
• Bradykinesia
• Ataxia
• Increased tremor of the hands
• Neuroleptic malignant syndrome
• Paraesthesia
• Falling
• Walking defects
• Trismus
• Muscle twitching
• Asthenia
• Weakness

Cardiovascular Disorders

• Palpitations
• Irregular heartbeat
• Orthostatic hypotension
• Syncope
• Hypertension
• Phlebitis

Respiratory Disorders

• Hoarseness
• Chest pain
• Dyspnoea
• Abnormal breathing pattern

Gastrointestinal Disorders

• Nausea and vomiting
• Dry mouth
• Bitter taste
• Constipation
• Diarrhoea
• Sialorrhoea
• Dysphagia
• Flatulence
• Dyspepsia
• Gastrointestinal pain
• Dark saliva
• Bruxism
• Hiccups
• Gastrointestinal bleeding
• Burning sensation of the tongue
• Duodenal ulceration

Genitourinary Disorders

• Dark urine
• Urinary retention
• Urinary incontinence
• Priapism

Endocrine and Metabolic Disorders

• Anorexia
• Weight fluctuation

Musculoskeletal Disorders

• Muscle spasms

Skin and Subcutaneous Tissue Disorders

• Oedema
• Angioedema
• Urticaria
• Pruritus
• Facial redness
• Hair loss
• Exanthema
• Increased perspiration
• Dark perspiration fluid 
• Schönlein-Henoch purpura

Immune, Blood and Lymphatic System Disorders

• Leukopenia
• Haemolytic
• Non-haemolytic anaemia
• Thrombocytopenia
• Agranulocytosis

Sensory Disorders

• Hazy vision
• Blepharospasm
• Activation of a latent Horner's syndrome
• Double vision
• Dilated pupils
• Oculogyric crises
• Blepharospasm 

• Monoamine oxidase inhibitors
• Tricyclic antidepressants
• Antihypertensives
• Anticholinergics
• Dopamine D2 receptor antagonists 
• Benzodiazepines
• Isoniazid 
• Phenytoin 
• Papaverine
• Selegiline 
• Catechol-O-Methyl transferase inhibitors 
• Amantadine 
• Metoclopramide
• Sympathomimetics 
• Ferrous sulphate 
• Antacids  

None routine. Specific cases may require

• Intraocular pressure
• Hepatic function
• Renal function
• Full blood count

How to transfer patients from levodopa

Oral (tab): Levodopa must be discontinued at least 12hrs before Levodopa/Carbidopa is started (24hrs for slow-release preparations of levodopa). A daily dosage of Levodopa/Carbidopa should be chosen that will provide approximately 20% of the previous levodopa daily dosage. Patients who are taking less than 1500mg levodopa a day should be started on 1 tablet of Levodopa/Carbidopa 25/100, 6-8hrly. The suggested starting dosage for most patients taking more than 1500mg levodopa is 1 tablet of Levodopa/Carbidopa 25/250, 6-8hrly.

Oral (CR tab): Levodopa must be discontinued at least 8hrs before therapy with Levodopa/Carbidopa CR is started, In patients with mild to moderate disease, the initial recommended dose is 1 tablet of Levodopa/Carbidopa CR 8-12hrly.

Patients currently treated with conventional Levodopa/Decarboxylase inhibitor combination

Oral (CR tab): Levodopa/Carbidopa CR should be substituted at an amount that provides approximately 10-30% more levodopa per day depending on the clinical response. The interval between doses should be 4-8hrs during the waking day.

Guideline for initial conversion

Tablet 25mg/100mg, Tablet 25mg/250mg - EML (Hospital)

Carbidopa is an aromatic amino acid peripheral dopa-decarboxylase inhibitor and levodopa is the metabolic precursor of dopamine. Levodopa is decarboxylated to dopamine in the brain. Carbidopa, which does not cross the blood/brain barrier, inhibits only the extracerebral decarboxylation of levodopa, making more levodopa available for transport to the brain and subsequent conversion to dopamine.

COMBINATION PREPARATIONS

Carbidopa/ Levodopa

Tablet 25mg/100mg

• Carbilev (Pharmacare)
• Lecardop (Ranbaxy Pharmaceuticals)
• Sinemet (MSD) originator
• Teva Carbi-Levo (Teva)

Tablet 25mg/250mg

• Carbilev (Pharmacare)
• Lecardop (Ranbaxy Pharmaceuticals)
• Sinemet (MSD) originator
• Teva Carbi-Levo (Teva)

Tablet cr 50mg/200mg

• Sinemet cr (MSD) originator