Cariprazine (Reagila) – New antipsychotic from Recordati Pharmaceuticals Ltd

Cariprazine (Reagila) is a new second-generation antipsychotic which is licensed to treat schizophrenia in adults (over 18 years). It is only available as an oral capsule and is presented in strengths of 1.5mg, 3mg, 4.5mg and 6mg.

It has potential to be considered as a second-line therapy for treating schizophrenia where predominant negative symptoms are an important feature.

The recommended initial dose is 1.5mg once daily (with or without food), increased in 1.5mg increments up to a maximum of 6mg per day. It has a long half-life of one week, which means that dose changes will take several weeks to stabilise. In practice, the full therapeutic effects may take longer to emerge, and this will also apply to adverse side effects. The time for plasma levels of the cariprazine to reach stable optimum ‘steady state’ levels is three weeks. So several weeks may be required before the treatment response will reach its optimum level, so this should be taken into account when making dose changes.

Also, gradual dose increases will help to reduce the risk of akathisia, or restlessness, which can be a particularly troublesome adverse side effect.

Switching antipsychotics

When switching from other antipsychotics to cariprazine, a gradual cross-titration should be considered, with gradual dose discontinuation of the original whilst cariprazine is started.

When switching from cariprazine, then this should be stopped abruptly without dose tapering. The new antipsychotic can be initiated at its lowest dose and gradually increased over the following weeks. Cariprazine levels should be expected to fall by 50% each week.

Pharmacology

Cariprazine is a partial agonist at dopamine D3 and D2 receptors. It has a preferential binding at the D3 receptor, which is considered to have a role in modulating mood and cognition. Also, cariprazine has affinity for the serotonin 5-HT1A receptor which could provide clinical benefit for the treatment of predominant negative symptoms in schizophrenia.

Main side effects

The main side effects of cariprazine are characteristic of other atypical antipsychotics, and were found to be similar in trials to risperidone which was used as a comparator.

These side effects include akathisia and extrapyramidal side effects (EPSE) (14%), insomnia (9.1%), headache (5.7%), anxiety (5.7%), somnolence (3.9%) and nausea (3.9%). In addition, significant weight gain can occur.

Precautions and contraindications

Cariprazine should be avoided in pregnancy and used with caution for adolescents (under 18) and elderly patients, as there is limited data for its use. Avoid use with patients having severe renal or hepatic impairment.

There are known risks with antipsychotic medication in general, such as:

• Suicide ideation and behaviour
• Tardive dyskinesia
• Exacerbating Parkinson’s disease
• Ocular symptoms
• Neuroleptic malignant syndrome (NMS)
• Seizures
• Cerebrovascular accidents – particularly for dementia patients and increased risk of stroke
• Cardiovascular disorders – orthostatic hypotension or hypertension, so monitor blood pressure
• ECG changes – QT prolongation (but does not appear to be a problem with cariprazine)
• Venous thromboembolism (VTE) – risk assess all patients before and during treatment
• Hypoglycaemia and diabetes mellitus – monitor for serum glucose levels as cariprazine can have adverse effects

Further details about the potential adverse effects can be found in the summary of product characteristics, together with information about adverse drug interactions with other medicines.

For more information, refer to the manufacturer’s summary of product characteristics: 

For assessment of evidence, see the SIGN appraisal.