SINEMET

What it is

SINEMET is a combination levodopa/carbidopa medicine available in tablet formulations. The medicine combines levodopa, the metabolic precursor of dopamine, and carbidopa, an aromatic amino acid decarboxylase inhibitor.

Approved indications

— Treatment of Parkinson's disease and syndrome.

Dosing overview

The optimum daily dosage of SINEMET must be determined by careful titration in each patient, with dosage titrated to individual patient needs. The peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg daily, and patients receiving less than this amount are more likely to experience nausea and vomiting. Dosage is best initiated with one tablet three times a day, which provides 75 mg of carbidopa per day. Usual maintenance dose is 3 tablets daily, with dosage increased by one tablet every day or every other day as necessary up to a maximum of 8 tablets daily, and most patients maintained on 3 to 6 tablets a day.

Key safety warnings

Levodopa has been associated with somnolence and episodes of sudden sleep onset, including sudden onset of sleep during daily activities in some cases without awareness or warning signs, and patients must be informed of this and advised to exercise caution while driving or operating machines. Dyskinesia may occur in patients previously treated with levodopa alone because carbidopa permits more levodopa to reach the brain and thus more dopamine to be formed, and the occurrence of dyskinesia may require dosage reduction. All patients should be monitored carefully for the development of mental changes, depression with suicidal tendencies, or other serious antisocial behaviour. Patients should be regularly monitored for the development of impulse control disorders, as behavioural symptoms including pathological gambling, hypersexuality, increased libido, compulsive spending/buying, and binge eating have been reported in patients taking dopamine-related treatments for Parkinson's disease, especially at high doses. Dopamine dysregulation syndrome, an addictive disorder leading to excessive use of medication, has been observed during treatment with carbidopa/levodopa, and review of treatment is recommended if such symptoms develop. Symptomatic postural hypotension has been reported occasionally, and SINEMET should be given cautiously to patients taking antihypertensive drugs, with dosage adjustment of the antihypertensive drug potentially required when therapy is started.

Contraindications

Monoamine oxidase inhibitors (MAOIs) and SINEMET should not be given concomitantly, and MAOIs must be discontinued at least 2 weeks prior to initiating therapy. SINEMET is contraindicated in patients with known hypersensitivity to this drug or any component of this medication, and in patients with narrow-angle glaucoma. Because levodopa may activate a malignant melanoma, it should not be used in patients with suspicious undiagnosed skin lesions or history of melanoma.

PBS listing

The source documents do not contain information about PBS listing details including strengths listed, item counts, restriction type, or ex-manufacturer price for SINEMET.

Regulatory history

SINEMET 100/25 levodopa/carbidopa tablets were first listed on the ARTG on 15 November 2019, and SINEMET 250/25 levodopa/carbidopa tablets were also first listed on the same date. SINEMET CR 200/50 levodopa/carbidopa modified release tablets were first listed on 18 June 2020.