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Zyprexa Zydis 10 mg is an orally disintegrating tablet formulation of olanzapine, an atypical antipsychotic used to treat schizophrenia, bipolar disorder, and other mood-related conditions. It works by balancing certain neurotransmitters in the brain, improving symptoms such as delusions, mood swings, and disorganized thinking.

Mechanism of Action (MOA):

• Olanzapine (the active ingredient in Zyprexa Zydis) is an atypical antipsychotic. It works by modulating the effects of certain neurotransmitters in the brain, including dopamine and serotonin.
• Olanzapine has a high affinity for serotonin (5-HT2) and dopamine (D2) receptors, along with other receptors like histamine and alpha-adrenergic receptors, contributing to its antipsychotic and mood-stabilizing effects.
• By balancing dopamine and serotonin levels, it helps alleviate symptoms like hallucinations, delusions, mood instability, and cognitive disturbances seen in psychotic disorders.

Indications:

Zyprexa Zydis is indicated for the treatment of:

1. Schizophrenia:
   • Acute and maintenance treatment of schizophrenia, where it helps reduce positive (e.g., hallucinations, delusions) and negative (e.g., apathy, social withdrawal) symptoms.
2. Bipolar Disorder:
   • Acute manic episodes associated with bipolar disorder.
   • Maintenance treatment to prevent recurrence of mood episodes in bipolar disorder.
3. Other Off-Label Uses:
   • Occasionally used for treatment-resistant depression or adjunctive therapy in major depressive disorder, but this is not FDA-approved.

Dosage:

• Schizophrenia:
  • Initial dose: 5 mg to 10 mg once daily.
  • Maintenance dose: Typically 10 mg/day, can be adjusted based on response and tolerance (usually between 5 mg and 20 mg daily).
• Bipolar Disorder (Acute Manic Episode):
  • Initial dose: 10 mg once daily.
  • The dose may be adjusted based on clinical response, typically within 5 mg to 20 mg daily.
• Geriatric Patients:
  • Dose should generally be lower (e.g., 5 mg) due to potential increased sensitivity in older adults, particularly for sedation and orthostatic hypotension.
• Renal or Hepatic Impairment:
  • Dose reductions may be required for patients with severe liver impairment, as olanzapine is metabolized in the liver.

Side Effects:

Common side effects of Zyprexa Zydis include:

1. Sedation: Drowsiness or fatigue is a frequent side effect, especially during the early stages of treatment.
2. Weight Gain: Significant weight gain due to increased appetite is a well-documented side effect.
3. Metabolic Changes:
   • Hyperglycemia or new-onset diabetes, increased cholesterol, and triglycerides.
4. Extrapyramidal Symptoms (EPS):
   • While less common than with older antipsychotics, side effects like tremors, muscle stiffness, and restlessness may occur.
5. Orthostatic Hypotension: Dizziness or fainting when standing up due to lowered blood pressure.
6. Dry Mouth: Common anticholinergic side effect.
7. Dizziness or Headache: May occur, especially in the initial stages of treatment.

Serious Side Effects (rare but severe):

• Neuroleptic Malignant Syndrome (NMS): A life-threatening condition with symptoms such as high fever, muscle rigidity, altered mental status, and autonomic dysfunction.
• Tardive Dyskinesia (TD): Involuntary, repetitive movements, especially in long-term use.
• Severe Metabolic Effects: Hyperglycemia, diabetic ketoacidosis, weight gain, and metabolic syndrome.

Precautions:

1. Metabolic Effects:
   • Regular monitoring of weight, blood glucose levels, and lipid profile is recommended due to the risk of significant metabolic changes, including weight gain, hyperglycemia, and dyslipidemia.
2. Elderly Patients:
   • Increased sensitivity in older adults. Use with caution, especially in patients with dementia-related psychosis due to an increased risk of stroke and mortality.
3. Hepatic Impairment:
   • Patients with liver disease should be monitored closely and may require dose adjustments.
4. CNS Depressants:
   • Caution should be exercised when used with other CNS depressants like alcohol, sedatives, or other antipsychotics due to the sedating effects of Zyprexa Zydis.
5. Discontinuation:
   • Tapering is recommended if discontinuing treatment to minimize the risk of withdrawal symptoms or relapse.
6. Pregnancy and Lactation:
   • Pregnancy Category C: Should be used during pregnancy only if the benefits outweigh the risks. It is not recommended during breastfeeding as olanzapine is excreted in breast milk.

Contraindications (CI):

1. Hypersensitivity:
   • Contraindicated in patients with a known allergy or hypersensitivity to olanzapine or any of its components.
2. Comatose States:
   • Contraindicated in patients who are in a coma or have severe central nervous system depression.
3. Severe Hepatic Impairment:
   • Olanzapine should be used with caution or avoided in patients with severe liver disease due to metabolism in the liver.

Pharmacist Related Data

Chemical Formula:

• Olanzapine: C17H20N4S
  • This represents the molecular structure of olanzapine, which contains carbon (C), hydrogen (H), nitrogen (N), and sulfur (S) atoms.

Half-Life:

• Olanzapine has a half-life of approximately 21 to 54 hours, which may vary depending on individual factors like age, liver function, and other health conditions.
• The half-life of olanzapine is prolonged in elderly individuals and those with liver impairment.

Metabolism:

• Olanzapine is metabolized in the liver by the cytochrome P450 (CYP450) enzyme system, particularly by CYP1A2, and to a lesser extent by CYP2D6.
• After metabolism, olanzapine is converted into inactive metabolites, with the major metabolite being 7-hydroxymethyl olanzapine.
• Olanzapine is extensively metabolized, and only small amounts are excreted unchanged in the urine.

Drug Interactions:

1. With Other Medications:
   • CNS Depressants: Olanzapine has sedating properties and may increase the sedative effects of other CNS depressants such as alcohol, benzodiazepines, opioids, or other antipsychotics. Caution is advised when combining these medications.
   • CYP1A2 Inhibitors: Medications like fluvoxamine or ciprofloxacin, which inhibit the CYP1A2 enzyme, may increase olanzapine levels, potentially increasing the risk of side effects.
   • CYP1A2 Inducers: Drugs like carbamazepine, smoking, or rifampin, which induce CYP1A2, can lower olanzapine levels, potentially reducing its effectiveness.
   • Antihypertensives: Olanzapine may add to the hypotensive effects of antihypertensive medications.
2. With Food:
   • Food does not significantly alter the absorption of olanzapine, and it can be taken with or without food. However, the Zydis formulation (orally disintegrating tablet) allows the medication to dissolve without the need for water, making it convenient for those who have difficulty swallowing tablets.
3. With Other Psychotropic Medications:
   • Antidepressants (SSRIs/SNRIs): Care should be taken when combining olanzapine with antidepressants because both types of drugs can affect serotonin levels in the brain, possibly increasing the risk of serotonin syndrome.
   • Lithium: Combined use of olanzapine with lithium in the treatment of bipolar disorder should be done with caution, as both can influence mood and neurological functioning.

Pharmacodynamics:

• Mechanism of Action (MOA):
  • Olanzapine is an atypical antipsychotic that works by modulating various neurotransmitters in the brain, particularly dopamine and serotonin.
  • It blocks dopamine D2 receptors and serotonin 5-HT2 receptors in the brain, which helps reduce psychotic symptoms like hallucinations, delusions, and cognitive disturbances.
  • It also has activity at histamine, adrenergic, and muscarinic receptors, which contributes to some of its sedative and anticholinergic side effects.
• Therapeutic Effects:
  • Reduces positive and negative symptoms of schizophrenia, including delusions, hallucinations, and disorganized thinking.
  • Stabilizes mood in bipolar disorder, particularly acute manic episodes, and prevents recurrence of mood episodes.
  • Sedative effects can also be beneficial in managing agitation associated with psychiatric disorders.

Pharmacokinetics:

1. Absorption:
   • Olanzapine is well absorbed from the gastrointestinal tract after oral administration, and the oral disintegrating form (Zydis) allows for rapid absorption.
   • The bioavailability of olanzapine is about 60% to 80% when taken orally, and peak plasma concentrations are reached within 5 to 8 hours after administration.
   • Food does not significantly affect the absorption of olanzapine.
2. Distribution:
   • Olanzapine is extensively distributed throughout the body, including the central nervous system (CNS). It has a high volume of distribution (Vd), indicating it is widely distributed in tissues.
   • It is approximately 93% protein-bound in plasma, mainly to albumin.
3. Metabolism:
   • Olanzapine is extensively metabolized in the liver by CYP1A2, with minor contributions from CYP2D6. It is converted to inactive metabolites, with the major one being 7-hydroxymethyl olanzapine.
   • The CYP1A2 enzyme plays a key role in its metabolism, which is influenced by both genetic factors (variability in enzyme activity) and environmental factors (e.g., smoking).
4. Excretion:
   • Olanzapine and its metabolites are primarily eliminated via the urine, with approximately 57% of the dose excreted in urine and 30% in feces.
   • The half-life of olanzapine is about 21 to 54 hours, and it may be longer in elderly patients and those with liver dysfunction.