olanzapine pamoate

olanzapine pamoate

Zyprexa Relprevv

Pharmacologic class: Thienobenzodiazepinc

Therapeutic class: Antipsychotic

Pregnancy risk category C

FDA Box Warning

• Elderly patients with dementia-related psychosis are at increased risk for death. Drug isn't approved for patients with dementia-related psychosis.

• When using olanzapine and fluoxetine in combination, refer to boxed warning section of package insert for Symbyax (olanzapine and fluoxetine).

• Adverse events with signs and symptoms consistent with olanzapine overdose, in particular sedation, including coma and delirium (postinjection delirium-sedation syndrome), have been reported after injections of Zyprexa Relprevv. Injections must be administered in a registered health care facility with ready access to emergency response services. After each injection, patients must be observed at the health care facility by a health care professional for at least 3 hours. Because of this risk, Zyprexa Relprevv is available only through a restricted distribution program called Zyprexa Relprevv Patient Care Program, which requires prescriber, health care facility, patient, and pharmacy enrollment.

Action

Unknown. Thought to antagonize dopamine and serotonin type 2 in CNS. Also antagonizes muscarinic receptors in respiratory tract, causing cholinergic activation.

Availability

Injection powder for suspension (extended-release): 210 mg/vial, 300 mg/vial, 405 mg/vial

Solution for injection: 10-mg vials

Tablets: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg

Tablets (orally disintegrating): 5 mg, 10 mg, 15 mg, 20 mg

Indications and dosages

Schizophrenia

Adults: Initially, 5 to 10 mg (Zyprexa, Zyprexa Zydis) P.O. daily with a target dosage of 10 mg/day within several days; may increase or decrease q week by 5 mg/day (not to exceed 20 mg/day). Periodically reevaluate long-term usefulness of drug for individual patient. Or, for Zyprexa Relprevv dosages corresponding to Zyprexa target oral dosages, see chart below:

Adolescents: Initially, 2.5 or 5 mg (Zyprexa, Zyprexa Zydis) P.O. daily with a target dosage of 10 mg/day. When dosage adjustments are needed, increments or decrements of 2.5 or 5 mg are recommended to a maximum of 20 mg/day.

Bipolar I disorder (manic or mixed episodes)

Adults: Initially, 10 or 15 mg (Zyprexa, Zyprexa Zydis) P.O. daily; may increase or decrease q 24 hours by 5 mg/day (not to exceed 20 mg/day). Or 10 mg I.M. (Zyprexa IntraMuscular); maximum dosage is three 10-mg doses I.M. 2 to 4 hours apart. Or initially, 10 mg (Zyprexa, Zyprexa Zydis) P.O. daily when administered as adjunctive treatment to lithium or valproate.

Adolescents: Initially, 2.5 or 5 mg (Zyprexa, Zyprexa Zydis) P.O. daily with a target dosage of 10 mg/day. When dosage adjustments are necessary, increments or decrements of 2.5 or 5 mg are recommended to a maximum of 20 mg/day.

Agitation associated with schizophrenia and bipolar I mania

Adults: 10 mg I.M. (Zyprexa IntraMuscular) or 5 mg or 7.5 mg I.M. when clinically warranted; maximum of three doses 2 to 4 hours apart. If agitation persists after initial dose, subsequent doses up to 10 mg may be given. If ongoing olanzapine therapy is clinically indicated, 5 to 20 mg/day (Zyprexa, Zyprexa Zydis) P.O. may be initiated as soon as clinically appropriate.

Depressive episodes associated with bipolar I disorder

Adults: Initially, 5 mg (Zyprexa, Zyprexa Zydis) P.O. and 20 mg fluoxetine P.O. daily in the evening. Dosage adjustments, if indicated, can be made according to efficacy and tolerability within ranges of 5 to 12.5 mg (Zyprexa or Zyprexa Zydis) and fluoxetine 20 to 50 mg.

Treatment-resistant depression

Adults: Initially, 5 mg (Zyprexa, Zyprexa Zydis) P.O. and 20 mg fluoxetine P.O. daily in the evening. Dosage adjustments, if indicated, can be made according to efficacy and tolerability within ranges of 5 to 20 mg (Zyprexa or Zyprexa Zydis) and fluoxetine 20 to 50 mg.

Dosage adjustment

• Elderly or debilitated patients
• Patients predisposed to hypotensive reactions
• Patients who otherwise exhibit a combination of factors that may result in slower metabolism of olanzapine, or who may be more pharmacodynamically sensitive to olanzapine

Off-label uses

• Borderline personality disorder (with oral use)

Contraindications

None

Precautions

Use cautiously in:
• hepatic impairment, cardiovascular or cerebrovascular disease, diabetes mellitus, prostatic hypertrophy, angle-closure glaucoma, phenylketonuria (with orally disintegrating tablets)
• history of seizures, paralytic ileus, or suicide attempt
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 18 (safety not established).

Administration

• Administer without regard to meals.
• When administering as combination therapy, give in the evening.
• To remove orally disintegrating tablet from package, peel back foil; don't push tablet through foil.
• Establish tolerability with oral olanzapine before initiating treatment with I.M. forms.
• Be aware that the two Zyprexa intramuscular formulations have different dosing schedules; Zyprexa IntraMuscular is a short-acting formulation and Zyprexa Relprevv is a long-acting formulation.

Be aware that I.M. forms are intended for deep I.M. injection into the gluteal muscle only. Don't give I.V. or subcutaneously.
• Reconstitute Zyprexa IntraMuscular for I.M. injection with 2.1 ml of sterile water for injection only, into single-packaged vial.
• After reconstituting Zyprexa IntraMuscular solution for injection, withdraw total contents of vial for 10-mg dose; 1.5 ml for 7.5-mg dose; 1 ml for 5-mg dose, or 0.5 ml for 2.5-mg dose.
• Use Zyprexa IntraMuscular solution for I.M. injection within 1 hour of reconstitution.
• Be aware that total Zyprexa daily dosages above 30 mg P.O. or 10 mg I.M. given more often than 2 hours after initial dose and 4 hours after second dose aren't recommended.
• Be aware that Zyprexa Relprevv may be irritating to the skin. Use gloves when reconstituting and flush area with water if contact is made with skin.
• Before administering Zyprexa Relprevv injection, confirm that someone will accompany patient after a 3-hour observation period. If this can't be confirmed, don't give the injection.
• Know that Zyprexa Relprevv must be suspended using only the diluent provided. After following manufacturer's directions for reconstitution, suspension concentration is 150 mg/ml. Final volume to inject is 1 ml for 150-mg dose, 1.4 ml for 210-mg dose, 2 ml for 300-mg dose, and 2.7 ml for 405-mg dose.
• Use Zyprexa Relprevv suspension immediately after removing from vial.
• Inject Zyprexa Relprevv deep into the gluteal muscle only. Don't massage injection site after injection.
• Don't combine in syringe with diazepam, lorazepam, or haloperidol.

Adverse reactions

CNS: dizziness, headache, weakness, fatigue, restlessness, sedation, insomnia, mood changes, agitation, personality disorder, impaired speech, tardive dyskinesia, dystonia, tremor, extra-pyramidal effects, neuroleptic malignant syndrome, coma, postinjection delirium-sedation syndrome

CV: orthostatic hypotension, chest pain, tachycardia

EENT: amblyopia, rhinitis, pharyngitis

GI: nausea, constipation, abdominal pain, increased salivation, dry mouth

GU: urinary incontinence, urinary tract infection

Hematologic: leukopenia, neutropenia, agranulocytosis

Metabolic: goiter, increased thirst, hyperprolactinemia, hyperlipidemia, severe hyperglycemia

Musculoskeletal: hypertonia, joint pain

Respiratory: cough, dyspnea

Skin: ecchymosis, photosensitivity

Other: increased appetite, weight gain or loss, fever, flulike symptoms, impaired body temperature regulation, death

Interactions

Drug-drug.Antihypertensives, diazepam: additive hypotension

Carbamazepine, omeprazole, rifampin: decreased olanzapine effects

CNS depressants: additive CNS depression

Dopamine agonists, levodopa: antagonism of these drugs' effects

Fluvoxamine: decreased olanzapine clearance

Lorazepam: increased somnolence with I.M. olanzapine

Drug-diagnostic tests.Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, glucose, creatinine phosphokinase, gamma-glutamyltransferase, LDL cholesterol, lipids, prolactin, serum glucose, total cholesterol, triglycerides: elevated levels

Neutrophils, platelets: decreased count

Drug-behaviors.Alcohol use: additive CNS depression, potentiated orthostatic hypotension

Smoking: increased drug clearance

Sun exposure: increased risk of photosensitivity

Patient monitoring

• Assess patient's mental status during therapy.
• Monitor vital signs during dosage adjustment periods.
• Make sure patient takes drug and doesn't hoard it.

Watch for signs and symptoms of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, tiredness, severe muscle stiffness, loss of bladder control).
• Evaluate patient for onset of akathisia, tardive dyskinesia, and extrapyramidal effects.

Watch for signs of increasing depression.

Monitor blood glucose level closely, especially in patient with diabetes mellitus. Severe hyperglycemia, coma, and death may occur.
• Watch for orthostatic hypotension before I.M. injection. Keep patient recumbent if drowsiness or dizziness follows injection.
• Monitor baseline and periodic lipid and liver enzyme levels.

Monitor CBC frequently during first few months of therapy; consider discontinuing drug at first sign of a clinically significant decline in white blood cells (WBCs) in the absence of other causative factors. Discontinue drug in patients with severe neutrope-nia (absolute neutrophil count less than 1,000/mm3) and monitor WBC until recovery.

Monitor patient for signs and symptoms of postinjection delirium-sedation syndrome after Zyprexa Relprevv injections.

Be aware that the possibility of a suicide attempt is inherent in patients with schizophrenia or bipolar I disorder; close supervision of high-risk patients should accompany drug therapy.

Patient teaching

• Tell patient he may take without regard to meals.
• Instruct patient to remove orally disintegrating tablet from package by peeling back foil-not by pushing tablet through foil. Instruct him to remove tablet from foil using dry hands, and place entire tablet in mouth. Tell him tablet will disintegrate with or without liquid.
• Tell patient drug may cause extra-pyramidal symptoms, akathisia, and tardive dyskinesia leading to involuntary movements, tremors, rigidity, muscle contractions, and restlessness.

Caution patient with diabetes mellitus to monitor blood glucose closely.
• Tell patient to move slowly when sitting up or standing to avoid dizziness. Advise him to dangle legs briefly before getting out of bed.
• Advise patient to avoid smoking, alcohol, or other CNS depressants.
• Tell patient to exercise in moderation and to avoid overly hot baths and showers, because drug impairs body temperature regulation.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

Instruct patient or caregiver how to recognize and report signs and symptoms of infection and postinjection delirium-sedation syndrome.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.

References in periodicals archive ?
Patients who receive olanzapine pamoate must be monitored for 3 hours after an injection because of the risk of post-injection delirium sedation associated with the injection.
The FDA is not recommending changes to the prescribing information of olanzapine pamoate.