Zipradon

Approved Uses

• Schizophrenia: treatment of acute psychotic episodes and maintenance therapy in adults.
• Acute agitation in schizophrenia: intramuscular injection for rapid control (up to 3 days).
• Bipolar I Disorder:
• Acute mania or mixed episodes (monotherapy).
• Maintenance treatment in combination with lithium or valproate.

Off‑Label/Clinically Accepted

• Agitation in schizoaffective disorder.
• Post-traumatic stress disorder (adjunctive).
• Second-line augmentation in treatment-resistant depression.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Oral (Capsules; with food)

• Schizophrenia (Adults):
• Start: 20 mg twice daily.
• Titrate by 20 mg every 1–2 days based on response.
• Usual maintenance: 40–80 mg twice daily.
• Max: 80 mg twice daily.
• Bipolar I:
• Acute: 40 mg twice daily; may increase to 60–80 mg twice daily from Day 2.

Intramuscular (Acute Agitation)

• 10–20 mg IM as single dose; may repeat 10 mg every 2 hours or 20 mg every 4 hours.
• Max cumulative of 40 mg per day.
• Limit IM use to ≤3 days, then transition to oral.

Special Populations

• Elderly: no dosage adjustment based on age.
• Renal impairment: no adjustment needed.
• Hepatic impairment: mild-to-moderate may prolong half-life; monitor closely; no formal adjustment.
• Pediatric: safety in individuals <18 years not established.

Administration Notes

• Capsules: swallow whole with food.
• IM: reconstitute with sterile water to yield 20 mg/mL solution; use immediately.
• Avoid mixing IM with other medications.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Ziprasidone is a second-generation (atypical) antipsychotic that antagonizes dopamine D₂ and serotonin 5‑HT₂A receptors, with partial agonism at 5‑HT₁A and antagonism at 5‑HT₁D, 5‑HT₂C, α₁-adrenergic, and H₁ receptors. It also moderately inhibits serotonin and norepinephrine reuptake. This receptor profile underlies its antipsychotic, mood-stabilizing, and sedative effects, with minimal anticholinergic activity.

• Absorption: ~60% oral bioavailability; doubled with food; IM is 100% bioavailable.
• T_max: 6–8 hours (oral); ~60 minutes (IM).
• Distribution: V_d ~1.5 L/kg; >99% protein-bound (albumin and α₁-acid glycoprotein).
• Metabolism: Extensively hepatic; primarily via reduction (aldehyde oxidase) and oxidation (CYP3A4, CYP1A2).
• Half-Life: ~7 hours oral; 2–5 hours IM.
• Excretion: ~66% feces, ~20% urine as metabolites; <1% unchanged urine.
• Special Populations:
• Renal: no significant change.
• Hepatic: AUC increased 13–34% in mild-to-moderate impairment; half-life prolonged to ~7.1 h.

• Pregnancy: Cat C. Animal studies show developmental toxicity and teratogenicity at high doses; limited human data. Use only if benefits outweigh risks.
• Lactation: Present in human milk; potential for infant sedation, irritability, feeding issues, and extrapyramidal symptoms. Breastfed infants should be monitored if mother is treated. Use with caution.

• Primary: Atypical (Second‑Generation) Antipsychotic
• Subclass: Dopamine D₂ / Serotonin 5‑HT₂ antagonist & 5‑HT₁A partial agonist

• Hypersensitivity to ziprasidone or formulation components
• Concomitant medications that prolong QT interval or risk torsades de pointes
• Recent acute myocardial infarction
• Uncompensated heart failure

• QT prolongation: Risk increased with high doses, electrolyte imbalances, and QT-prolonging drugs. Monitor ECG.
• Torsades de pointes: Avoid in patients with QT >500 ms or cardiac risk factors.
• Metabolic effects: Monitor weight, glucose, and lipids.
• Orthostatic hypotension: In elderly or volume-depleted; due to α₁-blockade.
• Neuroleptic malignant syndrome: Watch for rigidity, fever, altered mental status.
• Hyperglycemia/diabetes risk: Monitor in diabetics.
• Leuko/neutropenia: CBC monitoring may be needed.
• CNS depression: Risk with alcohol or other CNS depressants.
• Elderly with dementia-related psychosis: Increased mortality; use not approved.
• Skin rash: Rare severe reactions; discontinue if rash appears.

Common (>10%)

• Somnolence, headache, dizziness, nausea, extrapyramidal symptoms

Moderate (1–10%)

• Dry mouth, tachycardia, orthostatic hypotension, constipation, dyspepsia, rash, restlessness, myalgia, akathisia

Rare/Serious (<1%)

• Syncope, seizures, neuroleptic malignant syndrome, hyperglycemia, diabetes, leukopenia, agranulocytosis, severe rash (e.g., SJS), torsades de pointes

Timing & Dose Dependence

• Sedation and hypotension typically occur early in treatment.
• Metabolic and blood dyscrasias may emerge with chronic use.

• CYP3A4 inducers (e.g., carbamazepine, rifampin): decrease levels → risk relapse.
• CYP3A4 inhibitors (e.g., ketoconazole): increase levels by ~35–40% → increased adverse effects.
• QT-prolonging drugs: additive risk for arrhythmia (e.g., macimorelin, many psychotropics, antiarrhythmics).
• Antihypertensives: enhanced orthostatic hypotension.
• CNS depressants: additive sedation.
• No significant interactions with cimetidine, antacids, oral contraceptives, lithium, dextromethorphan.

• FDA boxed warning reinforced for QT prolongation and risk of sudden death in elderly dementia-related psychosis.
• APA guidelines list ziprasidone among preferred options for acute schizophrenia and bipolar mania; caution with QT interval indicated.
• Recent metabolic monitoring standards emphasize regular metabolic parameter checks for all atypical antipsychotics.

• Store at 20–25 °C (68–77 °F); excursions permitted to 15–30 °C (59–86 °F).
• Keep capsules in original container, protected from light and moisture.
• IM lyophilized vials: store under same temperature; reconstitute with sterile water only; use immediately after reconstitution.
• Do not freeze.