Cariprazine

Oral
Schizophrenia

Oral
Acute manic episodes of bipolar I disorder, Acute mixed episodes of bipolar I disorder

Oral
Bipolar I depression

Patients initiating a strong CYP3A4 inhibitor while on a stable dose: Decrease dose by 50%. Increase dose once CYP3A4 inhibitor is discontinued.

Patients initiating cariprazine while already on a strong CYP3A4 inhibitor: Administer 1.5 mg on Day 1 and Day 3 with no dose given on Day 2. Then, 1.5 mg daily from Day 4 onward, then increase to a Max of 3 mg daily. Increase dose once CYP3A4 inhibitor is discontinued.

Severe: Not recommended.

Severe: Not recommended.

May be taken with or without food.

Concomitant use with strong or moderate CYP3A4 inhibitors and inducers.

Patient with Parkinson's disease, history of seizures or conditions that lower seizure threshold; diabetes or other disorders of glucose regulation; known CV disease (e.g. history of MI, ischaemic heart disease, heart failure, conduction abnormalities), vulnerable to hypertension (e.g. hypovolaemia, dehydration, elderly), cerebrovascular disease, risk factors or exhibiting symptoms of akathisia. Strenuous activity, extreme heat exposure; concomitant use with anticholinergic medications. Renal and hepatic impairment. Elderly with dementia-related psychosis. Pregnancy and lactation. Avoid abrupt withdrawal.

Significant: Leucopenia, neutropenia; suicidal ideation and behaviour, CNS depression, extrapyramidal syndromes (e.g. pseudoparkinsonism, akathisia, restlessness, tardive dyskinesia, acute dystonic reactions), impaired temperature regulation; falls secondary to somnolence, orthostatic hypotension, and motor or sensory instability; orthostatic hypotension, syncope; dyslipidaemia, hyperglycaemia; oesophageal dysmotility and aspiration, weight gain.
Cardiac disorders: Tachycardia, hypertension.
Eye disorders: Blurred vision.
Gastrointestinal disorders: Nausea, vomiting, constipation, diarrhoea, dyspepsia, abdominal pain, dry mouth, toothache.
General disorders and admin site conditions: Fatigue.
Investigations: Increased liver enzymes, increased creatine phosphokinase.
Metabolism and nutrition disorders: Decreased or increased appetite.
Musculoskeletal and connective tissue disorders: Limb pain, back pain, muscle rigidity, arthralgia.
Nervous system disorders: Sedation, drowsiness, dizziness, dystonia, headache, agitation.
Psychiatric disorders: Anxiety, insomnia.
Skin and subcutaneous tissue disorders: Rash.
Potentially Fatal: Neuroleptic malignant syndrome; agranulocytosis.

This drug may cause drowsiness and may reduce alertness, if affected, do not drive or operate machinery.

Monitor blood pressure, vital signs; weight, height, BMI, waist circumference (baseline; at 4, 8, 12 weeks after initiating or changing therapy then quarterly); CBC (frequently during the 1st few months of therapy in patients with pre-existing low WBC or history of drug-induced leucopenia or neutropenia); electrolytes and LFT (annually and as clinically indicated); fasting blood sugar or HbA_1c (baseline; 3 months after therapy then yearly); fasting lipid panel (baseline; 3 months after therapy then if LDL is normal, 2-5 years intervals or more frequently if indicated). Monitor mental status; personal or family history of diabetes, dyslipidaemia, obesity, hypertension or CV disease (baseline and annually); changes in menstruation, libido, development of galactorrhoea, erectile and ejaculatory function (annually); Parkinson signs (baseline; weekly until dose stabilized for at least 2 weeks after initiation or changes in dose), and tardive dyskinesia (every 12 months; every 6 months for high-risk patients).

Symptoms: Orthostasis and sedation. Management: Supportive and symptomatic treatment (e.g. maintenance of adequate airway, ventilation, oxygenation). May perform ECG for possible arrythmia. May give anticholinergic in cases of severe extrapyramidal symptoms.

Potentially Fatal: Increased serum concentration with moderate and strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, boceprevir, cobicistat, ritonavir, nefazodone, diltiazem, verapamil). Decreased serum concentration with moderate and strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifampicin, efavirenz, bosentan, etravirine, modafinil, nafcillin).

Increased serum concentration with grapefruit juice. Decreased serum concentration with St. John's wort.

Description:
Mechanism of Action: Cariprazine, a 2nd generation antipsychotic, exerts its effects through a combination of partial agonist activity at serotonin 5-HT_1A and dopamine D₂ and D₃ receptors, and antagonist activity at serotonin 5-HT_2A and 5-HT_2B and histamine H₁ receptors.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract. Time to peak plasma concentration: 3-6 hours.
Distribution: Volume of distribution: 916 L; 475 L (DCAR); 1,568 L (DDCAR). Plasma protein binding: 91-97%.
Metabolism: Extensively metabolised in the liver by CYP3A4 and, to a lesser extent by CYP2D6 to active metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR). DCAR is further metabolised into DDCAR by CYP3A4 and CYP2D6 which is then metabolised by CYP3A4 to a hydroxylated metabolite.
Excretion: Via urine (21%; 1.2% as unchanged drug). Elimination half-life: 2-4 days; 1-2 days (DCAR); 1-3 weeks (DDCAR).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 11154555, Cariprazine. https://pubchem.ncbi.nlm.nih.gov/compound/Cariprazine. Accessed Nov. 25, 2021.

Store between 20-25°C. Protect from light.

Thuốc chống loạn thần

N05AX15 - cariprazine ; Belongs to the class of other antipsychotics.

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Anon. Cariprazine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/10/2021.

Buckingham R (ed). Cariprazine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/10/2021.

Joint Formulary Committee. Cariprazine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/10/2021.

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