Opicapon

Products

Opicapone was approved in the EU in 2016 and in many countries in 2018 in hard capsule form (Ongentys).

Structure and properties

Opicapone (C₁₅H₁₀Cl₂N₄O₆, M_r = 413.2 g/mol) is an oxadiazole derivative with a pyridine–oxide at position 3. The compound was designed with the goal of developing an effective and safer COMT inhibitor. This is because tolcapone is toxic to the liver and entacapone must be taken frequently. Because of its very high binding affinity, opicapone has a long duration of action.

Effects

Opicapone affects the pharmacokinetics of levodopa. The effects are due to peripheral, selective, and reversible inhibition of the enzyme catechol- methyltransferase (COMT). This reduces the degradation of concomitantly administered levodopa, increasing plasma concentrations and improving clinical response.

Indications

As add-on therapy to a fixed combination of levodopa with a decarboxylase inhibitor in adult patients with PD with motor “end-of-dose” fluctuations in whom stabilization cannot be achieved with this combination.

Dosage

According to the SmPC. Capsules are taken once daily at bedtime, at least one hour before or after levodopa combination medications.

Contraindications

• Hypersensitivity.
• Pheochromocytoma, paraganglioma, or other catecholamine-secreting neoplasm.
• History of malignant neuroleptic syndrome and/or atraumatic rhabdomyolysis.
• Concurrent treatment with an MAO inhibitor other than those used in PD.

For complete precautions, see the drug label.

Interactions

Drug-drug interactions may occur with the following agents:

• MAO inhibitors
• Agents metabolized by the COMT
• Tricyclic antidepressants and norepinephrine reuptake inhibitors.
• Repaglinide
• OATP1B1 substrates

Adverse effects

The most common possible adverse effects include dyskinesia.