Idiopathic Parkinson’s disease, especially for reducing “off” periods in patients who were previously treated with levodopa/decarboxylase inhibitors or levodopa alone and have developed motor fluctuations.

Levodopa serves as a metabolic precursor of dopamine. It crosses the blood-brain barrier and is converted into dopamine within the brain. Carbidopa acts as a dopa decarboxylase (DDC) inhibitor, decreasing the peripheral breakdown of levodopa into dopamine, thereby allowing a greater amount of levodopa to reach the brain.

Patients currently treated with conventional levodopa/decarboxylase inhibitor combinations: Dosage with Levodopa-Carbidopa prolonged-release tablet should be substituted initially 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 between doses should be prolonged by 30 to 50% at intervals ranging from 4 to 12 hours. It is recommended to give the smaller dose, if divided doses are not equal, at the end of the day. The dose needs to be titrated further depending on clinical response, as indicated below under ‘Titration’. Dosages that provide up to 30% more levodopa per day may be necessary. A guide for substitution of Levodopa Carbidopa prolonged-release tablet treatment for conventional levodopa/decarboxylase inhibitor combinations is shown in the table below:

Guideline for conversion from conventional Levodopa/Carbidopa tablet to Levodopa-Carbidopa prolonged-release tablet:

Caution is advised when the following medications are used together with Levodopa–Carbidopa prolonged-release tablets.

Antihypertensive agents: Postural hypotension may occur when levodopa/decarboxylase inhibitor combinations are added to patients already receiving antihypertensive therapy. Dose adjustment of the antihypertensive medication may be necessary when starting this treatment.

Antidepressants: Rare cases of adverse effects such as hypertension and dyskinesia have been reported when tricyclic antidepressants are used concurrently with carbidopa-levodopa preparations.

Anticholinergics: These drugs may influence the absorption of levodopa, thereby affecting the patient’s response.

Iron: Iron salts such as ferrous sulphate or ferrous gluconate may reduce the bioavailability of carbidopa and/or levodopa when taken together.

Other drugs: Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone) and isoniazid may decrease the therapeutic effect of levodopa. The beneficial effects of levodopa in Parkinson’s disease may be reversed by phenytoin and papaverine. Patients using these drugs alongside this therapy should be closely monitored for reduced effectiveness. Concomitant use with selegiline may lead to severe orthostatic hypotension. High-protein diets may reduce levodopa absorption due to competition with certain amino acids. The impact of antacids on levodopa bioavailability has not been clearly established.

Levodopa–Carbidopa prolonged-release tablets should not be used in patients where sympathomimetic amines are contraindicated. Non-selective monoamine oxidase (MAO) inhibitors must not be used concurrently and should be discontinued at least 2 weeks before starting this therapy. However, selective MAO-B inhibitors (e.g., selegiline hydrochloride) may be used at recommended doses. This medication is also contraindicated in patients with known hypersensitivity to any of its components and in those with narrow-angle glaucoma. Since levodopa may activate malignant melanoma, it should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma.

The most commonly reported adverse effect is dyskinesia (involuntary abnormal movements), which occurs more frequently with the prolonged-release formulation compared to standard levodopa-carbidopa tablets. Other reported side effects include nausea, hallucinations, confusion, dizziness, chorea, dry mouth, abnormal dreams, dystonia, insomnia, depression, weakness, vomiting, loss of appetite, chest pain, palpitations, constipation, diarrhea, indigestion, gastrointestinal discomfort, dark saliva, angioedema, urticaria, itching, weight loss, neuroleptic malignant syndrome, agitation, anxiety, reduced mental alertness, paresthesia, disorientation, fatigue, headache, extrapyramidal symptoms, movement disorders, falls, gait disturbances, muscle cramps, “on-off” phenomenon, increased libido, psychotic episodes, drowsiness, flushing, alopecia, rash, dark sweat, blurred vision, dark urine, cardiac rhythm disturbances, hypertension, phlebitis, bitter taste, excessive salivation, difficulty swallowing, bruxism, hiccups, gastrointestinal bleeding, flatulence, burning sensation of the tongue, duodenal ulcer, leukopenia, hemolytic and non-hemolytic anemia, thrombocytopenia, and agranulocytosis.

There is limited information available regarding the safety of this medicine during human pregnancy. It is unknown whether carbidopa is excreted in human breast milk, although levodopa has been detected in breast milk in at least one case. Therefore, this medication should be avoided during pregnancy and breastfeeding unless clearly necessary.

When switching from levodopa monotherapy, levodopa should be discontinued at least 8 hours (or at least 12 hours for slow-release forms) before starting this prolonged-release combination. Dyskinesia may occur due to increased dopamine levels in the brain, and dose adjustment may be required. This medication is not recommended for drug-induced extrapyramidal reactions or Huntington’s chorea. The onset of action for the first morning dose may be slower compared to conventional formulations. Dyskinesia may occur slightly more frequently in advanced patients with motor fluctuations. Use caution in patients with cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic, or endocrine disorders, or those with a history of peptic ulcer or seizures. Extra caution is required in patients with recent myocardial infarction and residual arrhythmias, with close cardiac monitoring during initial dosing and titration. This medicine may cause drowsiness and sudden sleep episodes during daily activities, sometimes without warning. Patients should avoid driving or operating machinery if affected. Dose reduction or discontinuation may be considered in such cases.

It may also cause involuntary movements and psychiatric symptoms. Patients with a history of severe dyskinesia or psychosis should be closely monitored. Depression with suicidal tendencies may develop and requires careful observation. Impulse control disorders may occur, including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, and binge eating. Patients and caregivers should be informed and monitored, and treatment should be reviewed if such symptoms appear.

Use in Children: Safety and effectiveness in infants and children have not been established; therefore, use in individuals under 18 years of age is not recommended.

Antiparkinson drugs

Store in a cool, dry place, protected from light.