Adult: Initially, 1.5 mg once daily, increase slowly in 1.5 mg daily increments. Max: 6 mg daily if needed.
Oral Acute manic episodes of bipolar I disorder, Acute mixed episodes of bipolar I disorder
Adult: Initially, 1.5 mg once daily, then increase dose to 3 mg on Day 2; further adjust dose in increments of 1.5 or 3 mg according to response and tolerability. Recommended dose range: 3-6 mg once daily. Max: 6 mg daily.
Oral Bipolar I depression
Adult: Initially, 1.5 mg once daily. May increase dose to 3 mg once daily on Day 15, depending on the clinical response and tolerability. Max: 3 mg once daily.
Special Patient Group
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.
Renal Impairment
Severe: Not recommended.
Hepatic Impairment
Severe: Not recommended.
Administration
May be taken with or without food.
Contraindications
Concomitant use with strong or moderate CYP3A4 inhibitors and inducers.
Special Precautions
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.
Adverse Reactions
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.
Patient Counseling Information
This drug may cause drowsiness and may reduce alertness, if affected, do not drive or operate machinery.
Monitoring Parameters
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 HbA1c (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).
Overdosage
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.
Drug Interactions
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).
Food Interaction
Increased serum concentration with grapefruit juice. Decreased serum concentration with St. John's wort.
Action
Description: Cariprazine, a 2nd generation antipsychotic, exerts its effects through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 and D3 receptors, and antagonist activity at serotonin 5-HT2A and 5-HT2B 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).
Chemical Structure
Cariprazine 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.
N05AX15 - cariprazine ; Belongs to the class of other antipsychotics.
References
Anon. Cariprazine (Briggs Drugs in Pregnancy and Lactation). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/10/2021.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.Reagila 1.5 mg Hard Capsules (Gedeon Richter Plc.). MHRA. https://products.mhra.gov.uk. Accessed 08/10/2021.Symvenu (Gedeon Richter Plc.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 08/10/2021.Vraylar (Remedyrepack Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/10/2021.
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