kar-IP-ra-zeen

Therapeutic Classification: antipsychotics

• Schizophrenia.
• Acute treatment of mania/mixed episodes associated with bipolar I disorder.
• Depressive episodes associated with bipolar I disorder.
• Adjunctive treatment of major depressive disorder (in combination with antidepressants).

• Acts as a partial agonist at dopamine D₂ receptors in the CNS and serotonin 5–HT_1A; also acts an antagonist at 5–HT_2A receptors.

• Decreased incidence and severity of symptoms of schizophrenia.
• Decreased occurrence and severity of mania associated with bipolar 1 disorder.
• Antidepressant action.

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: 91–97%.

Metabolism/Excretion: Two metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR), have antipsychotic activity. Metabolism occurs mostly via the CYP3A4 enzyme system, with further metabolism resulting in inactive metabolites; 21% excreted urine, 1.2% as unchanged drug.

Half-life: Cariprazine — 2–4 days; DDCAR: 1–3 wk.

(improvement in symptoms)

†Plasma concentrations of drug and active metabolites following discontinuation.

Contraindicated in:

• Hypersensitivity.

Use Cautiously in:

• Known cerebrovascular/cardiovascular disease, dehydration, concurrent use of diuretics/antihypertensives or syncope (↑ risk of orthostatic hypotension)
• Pre-existing ↓ WBC or ANC or history of drug-induced leukopenia/neutropenia
• At risk of aspiration or falls
• OB: Neonates exposed in the third trimester may experience extrapyramidal symptoms/withdrawal
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Safety and effectiveness not established; may ↑ risk of suicide attempt/ideation in children or adolescents
• Geri: Appears on Beers list. ↑ risk of stroke, cognitive decline, and mortality in older adults with dementia. Avoid use in older adults, except for schizophrenia, bipolar disorder, or adjunctive treatment of major depressive disorder.

CV: hypertension, orthostatic hypotension, tachycardia.

Derm: rash, STEVENS-JOHNSON SYNDROME.

EENT: blurred vision.

Endo: hyperglycemia/diabetes mellitus.

GI: dyspepsia, nausea, ↑ liver enzymes, constipation, diarrhea, dry mouth, dysphagia (↑ aspiration risk), vomiting.

Hemat: AGRANULOCYTOSIS, leukopenia, neutropenia.

Metab: ↓appetite, dyslipidemia, weight gain.

MS: arthralgia, back pain, extremity pain.

Neuro: akathisia, drowsiness, extrapyramidal symptoms, headache, agitation, dizziness, fatigue, insomnia, NEUROLEPTIC MALIGNANT SYNDROME, restlessness, SUICIDAL THOUGHTS/BEHAVIORS, tardive dyskinesia.

Resp: cough.
Misc: body temperature dysregulation.

Drug-Drug:

• Levels, effects, and risk of toxicity ↑ by concurrent use of strong CYP3A4 inhibitors including itraconazole and ketoconazole; concurrent use not recommended.
• Levels and effectiveness may be ↓ by concurrent use of strong CYP3A4 inducers including carbamazepine and rifampin; concurrent use not recommended.
• Concurrent use of diuretics or antihypertensives may ↑ risk of orthostatic hypotension/syncope.

Schizophrenia or Acute Treatment of Mania/Mixed Episodes Associated with Bipolar I Disorder

• PO (Adults): 1.5 mg once daily; may ↑ to 3 mg once daily on Day 2; further dosage adjustments can be made in increments of 1.5 mg or 3 mg depending on response/tolerability (max dose = 6 mg once daily). Initiation of strong CYP3A4 inhibitor while on stable dose of cariprazine:↓ dose by 50%; Initiation of cariprazine while on stable dose of strong CYP3A4 inhibitor: 1.5 mg once daily on Days 1 and 3 (no dose on Day 2), then 1.5 mg once daily starting on Day 4; may titrate depending on response/tolerance up to max dose of 3 mg once daily.

Depressive Episodes Associated with Bipolar I Disorder or Adjunctive Treatment of Major Depressive Disorder

• PO (Adults): 1.5 mg once daily; may ↑ to 3 mg once daily on Day 15 depending on response/tolerability (max dose = 3 mg once daily); Initiation of strong CYP3A4 inhibitor while on stable dose of cariprazine:↓ dose by 50%; Initiation of cariprazine while on stable dose of strong CYP3A4 inhibitor: 1.5 mg once daily on Days 1 and 3 (no dose on Day 2), then 1.5 mg once daily starting on Day 4; may titrate depending on response/tolerance up to max dose of 3 mg once daily.

• Capsules: 1.5 mg; 3 mg; 4.5 mg; 6 mg;

• Assess mental status (orientation, mood, behavior) before and periodically during therapy. Monitor for worsening depression and emergence of suicidal thoughts and behaviors.
• Assess weight and BMI at baseline and frequently during therapy.
• Monitor BP (sitting, standing, lying), pulse, and respiratory rate before and periodically during therapy.
• Observe patient carefully when administering medication to ensure that medication is actually taken and not hoarded or cheeked.
• Monitor for adverse reactions and patient response for several wk after starting therapy and after each dose increase. Due to long action, may not occur for several wk. Consider reducing dose or discontinuing drug if severe adverse reactions occur.
• Monitor patient for onset of akathisia (restlessness or desire to keep moving) and extrapyramidal side effects (parkinsonian: difficulty speaking or swallowing, loss of balance control, pill rolling of hands, masklike face, shuffling gait, rigidity, tremors; and dystonic: muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) periodically throughout therapy. Report these symptoms.
• Monitor for tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue). Notify health care professional immediately if these symptoms occur, as these side effects may be irreversible.
• Monitor for development of neuroleptic malignant syndrome (fever, muscle rigidity, altered mental status, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness, loss of bladder control). Notify health care professional immediately if these symptoms occur.
• Assess for skin reactions (rash, toxic skin reactions, bullous exanthema).
• Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability increase risk. Institute prevention if indicated.

• Monitor CBC frequently during therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue therapy if severe neutropenia (ANC <1000 mm³) occurs.
  • Monitor fasting blood glucose and lipid profile before, soon after starting, and periodically during therapy.

• PO: Administer once daily without regard to food.

• Advise patient to take medication as directed and not to skip doses or double up on missed doses. Take missed doses as soon as remembered unless almost time for the next dose. Do not stop taking cariprazine without consulting health care professional.
• Inform patient of possibility of extrapyramidal symptoms and tardive dyskinesia. Instruct patient to report these symptoms immediately.
• Advise patient to make position changes slowly to minimize orthostatic hypotension. Protect from falls.
• Medication may cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient and family to notify health care professional of new or worse depression; new or worse anxiety; feeling very agitated or restless; panic attacks; trouble sleeping; new or worse irritability; acting aggressive; being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking; other unusual changes in behavior or mood; or rash occur.
• Inform patient that cariprazine may cause weight gain. Advise patient to monitor weight periodically. Notify health care professional of significant weight gain.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any new medications. Caution patient to avoid taking alcohol or other CNS depressants concurrently with this medication.
• Advise patient that extremes in temperature should be avoided, because this drug impairs body temperature regulation.
• Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
• May cause fetal harm. Advise female patients to notify health care professional if pregnancy is planned or suspected during therapy. Encourage pregnant patients to enroll in registry by contacting National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. May cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress feeding disorder) in neonates whose mothers were exposed to antipsychotic drugs during third trimester of pregnancy. Symptoms vary in severity. Some neonates recover within hrs or days without specific treatment; others required prolonged hospitalization. Monitor neonates of women pregnant while taking cariprazine for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.

• Decrease in excitable, paranoid, or withdrawn behavior.
• Decreased occurrence and severity of mania associated with bipolar 1 disorder.
• Increased sense of well-being.
  • Renewed interest in surroundings.

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