INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
CARBILEV 25/100 Tablet
CARBILEV 25/250 Tablet

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

CARBILEV 25/100 Tablet
CARBILEV 25/250 Tablet

COMPOSITION:
Each Carbilev 25/100 tablet contains carbidopa monohydrate equivalent to 25 mg anhydrous carbidopa and 100 mg levodopa.
Each Carbilev 25/250 tablet contains carbidopa monohydrate equivalent to 25 mg anhydrous carbidopa and 250 mg levodopa.

PHARMACOLOGICAL CLASSIFICATION:
A 5.4.1 Anti-Parkinsonism Preparations.

PHARMACOLOGICAL ACTION:
Carbilev 25/100 and Carbilev 25/250 contains carbidopa and levodopa.
Carbidopa, which does not cross the blood-brain barrier, inhibits the peripheral decarboxylation of levodopa, thus slowing its conversion to dopamine in extracerebral tissues. This results in an increased availability of levodopa for transport to the brain where it undergoes decarboxylation to dopamine, stimulating dopaminergic receptors in the basal ganglia. This improves the balance between cholinergic and dopaminergic activity, resulting in improved modulation of voluntary nerve impulses transmitted to the motor cortex.

INDICATIONS:

1.	Treatment of Parkinson's disease and syndrome.
2.	To reduce "off" time in patients previously treated with levodopa/decarboxylase inhibitor preparations, or with levodopa alone, who have had motor fluctuations characterized by end-of-dose deterioration, peak dose dyskynesias, akinesia, or similar evidence of short-duration motor disturbances.

CONTRAINDICATIONS:
Monoamine oxidase (MAO) inhibitors and Carbilev should not be given concurrently. It is recommended that MAO inhibitors be discontinued at least two weeks prior to initiating Carbilev therapy.
Pregnancy and lactation. Carbidopa/levodopa combination has been associated with foetal abnormalities in animals, and should therefore not be given to women of childbearing age. Patients with a history of malignant melanoma or skin disorders suggestive of it.
Patients with known hypersensitivity to carbidopa or levodopa.
Closed-angle glaucoma.
Safety and efficacy in children under the age of 18 has not been established.

DOSAGE AND DIRECTIONS FOR USE:
General dosage information.
Titrated dosage is necessary to achieve the individual therapeutic blood concentration requirements and to avoid side effects. Patients should be monitored closely during the dose adjustment period, particularly with regard to appearance or worsening of nausea or abnormal involuntary movements, including dyskinesia, chorea and dystonia. This is especially important for geriatric patients and those receiving other medication.
The tablets should be taken with or after meals. When carbidopa/levodopa combination is to be discontinued, the dosage should be reduced gradually to prevent the occurrence of a syndrome that resembles the neuroleptic malignant syndrome.
Usual adult dosage
For patients not already treated with levodopa, dosage is best initiated with one tablet of Carbilev 25/100, three times a day. Dosage may be increased by one tablet daily, or on alternate days, as necessary to a maximum of eight tablets daily. For patients starting with Carbilev 25/250, the initial dose is, half a tablet taken once or twice daily. An additional half a tablet may be added every day, or every other day, if necessary, until optimal response is reached. Carbidopa doses greater than 200 mg daily are not generally exceeded.
Maintenance dosage
One Carbilev 25/250 tablet three times a day.
This dosage may be increased by half a tablet, or one tablet, every day, or every other day, to a maximum of eight tablets daily.
Patient conversion from Levodopa
Levodopa must be discontinued for at least eight hours prior to conversion to Carbilev therapy. As high central dopamine concentrations can be achieved quickly with carbidopa/levodopa, both beneficial and adverse effects tend to occur more rapidly than with levodopa alone, and patients should be monitored carefully during the dose adjustment period. A daily dosage of Carbilev 25/100 of the previous levodopa daily dosage. Patients who are taking less than 1500 mg levodopa a day should be started on one tablet of Carbilev 25/100 three to four times daily. The suggested starting dosage for most patients taking more than 1500 mg levodopa daily is one tablet of Carbilev 25/250 three to four times daily.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
The addition of carbidopa to levodopa results in certain central nervous system side-effects of levodopa, such as dyskinesias and mental effects to develop sooner and at lower levodopa doses because of the resultant greater efficiency per dose of levodopa.
Patients receiving carbidopa/levodopa combination long term may experience sudden, unexpected akinesia, tremor and rigidity. Emotional stress may precipitate akinesia paradoxica in these patients.
A syndrome resembling neuroleptic malignant syndrome, which includes intermittent dystonia alternating with substantial agitation, hyperthermia, and mental changes has been reported after the abrupt discontinuation of levodopa therapy.
Gastro-intestinal effects, notably nausea, vomiting and anorexia are common early in treatment, particularly if the dosage is increased too rapidly. Gastro-intestinal bleeding has been reported in patients with a history of peptic ulcer.
The most common cardio-vascular effect is orthostatic hypotension, usually asymptomatic, but may be associated with faintness and dizziness. Cardiac arrhythmias have been reported and hypertension has occasionally occurred.
Psychiatric symptoms occur in a high proportion of patients, especially the elderly, and include agitation, anxiety, euphoria, nightmares and insomnia, or sometimes drowsiness and depression.
More serious effects, usually requiring a reduction in dosage or withdrawal of treatment, include: aggression, paranoid delusions, hallucinations, delirium, severe depression with or without suicidal behaviours, and unmasking of dementia.
Psychotic reactions are more likely in patients with postencephalitic parkinsonism or a history of mental disorders.
Abnormal involuntary movements or dyskinesias are the most serious dose-limiting adverse effects and are very common at the optimum dose required to control Parkinsonism; their frequency increasing with duration of treatment. Uncontrolled movements of the face, tongue, lips and jaw often appear first and those of the trunk and extremities later.
Severe generalised choreoathetoid and dystonic movements may occur after prolonged administration. Muscle twitching and blepharospasm may be early signs of excessive dosage.
Exaggerated respiratory movements and exacerbated oculogyric crises have been reported in patients with postencephalitic parkinsonism. Re-emergence of akinesia, in the form of "end of dose" deterioration and the "on-off" phenomenon, in patients with parkinsonism, is a complication of long-term treatment, but may probably be due to progression of the disease.
A positive response to the direct Coomb's test may occur, usually without evidence of haemolysis although autoimmune haemolytic anaemia has been reported less frequently. Transient leucopenia has been reported less frequently.
Levodopa is excreted in breast milk and may inhibit lactation.
Darkening of urine, sweat or other body fluids may occur.
Carbilev should be administered cautiously to patients with bronchial asthma, emphysema and other severe pulmonary and cardiovascular disease. Care should be exercised in administering Carbilev to patients with a history of myocardial infarction, peptic ulcer, psychotic states, open-angle glaucoma, renal function impairment and urinary retention. These patients should be monitored with particular care during the period of initial dosage adjustment.
Patients with diabetes mellitus should note that the use of Carbilev may adversely affect control of glucose in blood.

INTERACTIONS:
Care should be exercised when administering Carbilev with anaesthetics, anticonvulsants, haloperidol, phenothiazines, antihypertensives, monoamine oxidase (MAO) inhibitors (see contra-indications) and selegiline.
Cocaine: concurrent use with levodopa may increase the risk of cardiac arrhythmías; if use of cocaine is necessary in patients receiving levodopa, it is recommended that cocaine be administered with caution, in reduced dosage and in conjuction with electrocardiographic monitoring.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See side-effects and special precautions.
General symptomatic and supportive measures should be employed along with immediate gastric lavage. The patient should be carefully monitored for the possible development of arrhythmias and The appropriate therapy should be administered, if required.
To date the value of dialysis in the treatment of overdose is not known.

IDENTIFICATION:

25/100 tablet -	A flat, yellow tablet with bevelled edges, bisected on one side and embossed with a mortar and pestle on the other side.
25/250 tablet -	A light blue, biconvex tablet, bisected on one side and embossed with a mortar and pestle on the other side.

PRESENTATION:
Carbilev 25/100 tablets are supplied in packs of 100 in securitainers.
Carbilev 25/250 tablets are supplied in packs of 100 in securitainers.

STORAGE INSTRUCTIONS:
Store below 25°C in an airtight container, and protect from light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
Carbilev 25/100 : 30/5.4.1/0271
Carbilev 25/250 : 30/5.4.1/0269

NAME AND BUSINESS ADDRESS OF APPLICANT:
Pharmacare Limited, 7 Fairclough Road, PORT ELIZABETH 6001

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
19 April 1996

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Current: Jan 2004
Source: Community Pharmacy
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