Ziprasidone
Mechanism :
It acts as antagonist at dopamine D2 and serotonin type 1 and 2 (5HT1D, 5HT2A) receptors. It also acts as agonist at serotonin 5HT1A receptor; moderately inhibits reuptake of norepinephrine and serotonin, it has alpha-blocking and antihistaminic activity.
Indication :
Contraindications :
Concomitant use of oral and IM ziprasidone.
Recent acute MI, decompensated heart failure, cardiac arrhythmias, conditions that may increase QT interval e.g., QT-interval prolongation or history of QT prolongation.
Prolactin dependent tumours.
Dosing :
Days 1-3: 5 mg/day PO; Days 4-28: Titrate to 40 mg/day PO divided every 12 hourly doses.
Adverse Effect :
Somnolence, respiratory tract infections, akathisia, extrapyramidal syndrome, tardive dyskinesia, hyperglycaemia, dizziness, dystonia, headache, GI disturbances, nausea, asthenia, agitation, rash, urticaria, visual disturbances, prolonged QT interval, orthostatic hypotension, increased prolactin levels, weight gain, sexual dysfunction, hyperlipidaemia, seizures.
Potentially Fatal adverse effects: Blood dyscrasias, neuroleptic malignant syndrome.
Interaction :
Levodopa and Dopamine: Antagonistic effect with levodopa and dopamine antagonists.
Antihypertensives: Additive hypotensive effect with antihypertensives.
CNS Agents, Alcohol: Additive sedative effects with other CNS agents, alcohol.
Drugs that prolong QT interval e.g. Dofetilide, Quinidine, Sotalol, and other Class Ia and III Antiarrhythmics, Moxifloxacin, Pimozide, Sparfloxacin, Thioridazine: Increased risk of torsades de pointes.
Hepatic Dose :
Dose adjustment guidelines are not available. Dose reduction may be needed as drug undergoes hepatic metabolism and clearance may be reduced and plasma levels may be increased.