APO-LEVODOPA/CARBIDOPA

What it is

APO-LEVODOPA/CARBIDOPA is a combination of levodopa, the metabolic precursor of dopamine, and carbidopa, an aromatic amino acid decarboxylase inhibitor, for the treatment of Parkinson's disease and syndrome. The registered variants contain either 100 mg levodopa with 25 mg carbidopa (as monohydrate) or 250 mg levodopa with 25 mg carbidopa (as monohydrate).

Approved indications

— Treatment of Parkinson's disease and syndrome.

Dosing overview

The optimum daily dosage of APO-LEVODOPA/CARBIDOPA must be determined by careful titration in each patient. Dosage is best initiated with one tablet three times a day, providing 75 mg of carbidopa per day, and may be increased by one tablet every day or every other day, as necessary, until a dosage equivalent of eight tablets a day is reached. At least 70 to 100 mg of carbidopa per day should be provided for optimal inhibition of extracerebral decarboxylation of levodopa; the usual 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.

Key safety warnings

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. Levodopa has been associated with somnolence and episodes of sudden sleep onset, and sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported very rarely; patients must be informed of this and advised to exercise caution while driving or operating machines during treatment. Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population, although whether the increased risk was due to Parkinson's disease or other factors such as drugs used to treat it is unclear. Patients should be regularly monitored for the development of impulse control disorders; behavioural symptoms including pathological gambling, hypersexuality, increased libido, compulsive spending or buying, and binge eating have been reported in patients taking dopamine agonists for the treatment of Parkinson's disease, especially at high doses. Dopamine dysregulation syndrome (DDS), an addictive disorder which leads to excessive use of the medication, has been observed during treatment with carbidopa and levodopa, and review of treatment is recommended if such symptoms develop.

Contraindications

Monoamine oxidase inhibitors (MAOIs) and APO-LEVODOPA/CARBIDOPA should not be given concomitantly, and MAOIs must be discontinued at least 2 weeks prior to initiating therapy. APO-LEVODOPA/CARBIDOPA 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.

Regulatory history

APO-LEVODOPA/CARBIDOPA was first listed on the Australian Register of Therapeutic Goods on 11 January 2018, with four registered variants: two formulations containing 100 mg levodopa with 25 mg carbidopa (as monohydrate) in blister pack and bottle, and two formulations containing 250 mg levodopa with 25 mg carbidopa (as monohydrate) in blister pack and bottle.