Cariprazine is marketed as Reagila® in Germany. It is available in capsules of 1.5 mg, 3 mg, 4.5 mg and 6 mg.
Pharmacodynamics and Receptor Binding Profile
Cariprazine is a high-affinity partial agonist at dopamine D3 and D2 receptors, with six- to eightfold higher affinity for D3 over D2 receptors. The compound is also a high-affinity partial agonist at serotonin 5-HT1A receptors. Cariprazine acts as an antagonist at serotonin 5-HT2B, 5-HT2A and histamine H1 receptors (affinity in this order). Antagonism of 5-HT2C and α1 receptors is low. Cariprazine does not antagonize acetylcholine receptors.
The two pharmacologically active metabolites, desmethylcariprazine (DCAR) and didesmethylcariprazine (DDCAR), have a similar receptor affinity profile.
Cariprazine is metabolized mainly via CYP3A4, and to a lesser extent via CYP2D6. The elimination half-life of the parent compound is approximately 2 days, half-lives of the two metabolites is 2 days (DCAR) and 8 days (DDCAR).
In the EU, cariprazine is approved it for the treatment of schizophrenia only. The US FDA approved it for the treatment of schizophrenia and manic or mixed episodes associated with bipolar disorder.
The starting dose is 1.5 mg once daily, this is also the lowest effective dose in clinical studies. It is recommended to increase the dose, if necessary, in steps of 1.5 mg daily to the maximum dose of 6 mg daily.
Most common side-effects are extrapyramidal symptoms like akathisia and parkinsonism.
Cariprazine should not be administered together with moderate to potent inhibitors of CYP3A4 such as ketoconazole.