CARLEVENT

What it is

CARLEVENT is a medicine containing levodopa, carbidopa monohydrate and entacapone. CARLEVENT is available in six strengths, each containing a 4:1 ratio of levodopa to carbidopa monohydrate combined with 200 mg of entacapone in a standard release formulation: 50/12.5/200 mg, 75/18.75/200 mg, 100/25/200 mg, 125/31.25/200 mg, 150/37.5/200 mg and 200/50/200 mg. The symptoms of Parkinson's disease are thought to be related to depletion of dopamine in the corpus striatum. Dopamine does not cross the blood-brain barrier. Levodopa, the precursor of dopamine, crosses the blood brain barrier and relieves the symptoms of the disease. Carbidopa is a peripheral dopa decarboxylase inhibitor which reduces the peripheral metabolism of levodopa to dopamine and thus more levodopa is available to the brain. Entacapone is a reversible, specific and mainly peripherally acting COMT inhibitor designed for concomitant administration with levodopa. Entacapone slows the clearance of levodopa from the bloodstream resulting in an increased area under the curve in the pharmacokinetic profile of levodopa. Consequently the clinical response to each dose of levodopa is enhanced and prolonged.

Approved indications

— Management of patients with Parkinson's disease who are experiencing motor fluctuations.

Dosing overview

The optimum daily dosage of CARLEVENT must be determined by careful titration in each patient. The daily dose should preferably be optimised using one of the six available tablet strengths (50/12.5/200 mg, 75/18.75/200 mg, 100/25/200 mg, 125/31.25/200 mg, 150/37.5/200 mg, or 200/50/200 mg levodopa/carbidopa monohydrate/entacapone). Patients should be instructed to take only one CARLEVENT tablet per dose administration. The maximum recommended daily dose of entacapone is 2000 mg, therefore the maximum CARLEVENT dose must not exceed 10 tablets per day, for the CARLEVENT strengths of 50/12.5/200 mg, 75/18.75/200 mg, 100/25/200 mg, 125/31.25/200 mg, and 150/37.5/200 mg. Using a maximum recommended daily dose of 375 mg of carbidopa monohydrate, the maximum daily dose of CARLEVENT 200/50/200 mg is 7 tablets per day. The maximum total daily levodopa dose administered in the form of CARLEVENT should not exceed 1500 mg.

Key safety warnings

CARLEVENT may induce orthostatic hypotension. Therefore CARLEVENT should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension. Neuroleptic Malignant Syndrome, including rhabdomyolysis and hyperthermia, is characterised by motor symptoms (rigidity, myoclonus, tremor), mental status changes (e.g., agitation, confusion, coma), hyperthermia, autonomic dysfunction (tachycardia, labile blood pressure) and elevated serum creatine phosphokinase. Isolated cases of NMS have been reported, especially following abrupt reduction or discontinuation of entacapone. For patients experiencing diarrhoea, a follow-up of weight is recommended in order to avoid potential excessive weight decrease. Prolonged or persistent diarrhoea suspected to be related to CARLEVENT may be a sign of colitis. In the event of prolonged or persistent diarrhoea, the drug should be discontinued and appropriate medical therapy and investigations considered. Patients should be regularly monitored for the development of impulse control disorders. Patients and caregivers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating, medication use and punding can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa including CARLEVENT. Review of treatment is recommended if such symptoms develop. CARLEVENT may cause dizziness, somnolence and episodes of sudden sleep onset, and symptomatic orthostatic hypotension. Therefore, caution should be exercised when driving or using machines.

Contraindications

Known hypersensitivity to the active substances or to any of the excipients. Pregnancy and breast feeding. Severe liver impairment. Patients with narrow-angle glaucoma. Patients with phaeochromocytoma due to the increased risk of hypertensive crisis. Co-administration of CARLEVENT with non-selective monoamine oxidase inhibitors (e.g. phenelzine, tranylcypromine) is contraindicated. Similarly, co-administration of a selective MAO-A inhibitor plus a selective MAO-B inhibitor and CARLEVENT is contraindicated. A previous history of neuroleptic malignant syndrome and/or non-traumatic rhabdomyolysis. Because levodopa may activate malignant melanoma, CARLEVENT should not be used in patients with suspicious undiagnosed skin lesions or a history of malignant melanoma.

Regulatory history

CARLEVENT levodopa/carbidopa/entacapone was first listed on the Australian Register of Therapeutic Goods on 3 October 2013.