Quetiapine
Mechanism :
Quetiapine's antipsychotic activity is likely due to a combination of antagonism at D2 receptors in the mesolimbic pathway and 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia.
Indication :
- For the acute treatment of mania and for maintenance therapy following stabilization
- Schizophrenia
Contraindications :
Hypersensitivity, Hypokalemia, Hypomagnesemia, Congenital QT prolongation, Arrhythmia hx, Avoid abrupt withdrawal.
Dosing :
>10 years:
25 mg PO twice daily on Day 1, 50 mg PO twice daily on Day 2, 100 mg PO twice daily on Day 3, 150 mg PO twice daily on Day 4, and 200 mg PO twice daily beginning Day 5. Range: 400 to 800 mg/day based upon response and tolerability.
Adverse Effect :
Suicidal tendency, exacerbation of depression, extrapyramidal symptoms, tardive dyskinesia, dystonia, neuroleptic malignant syndrome, hyperthermia, hypothermia, anaphylaxis, Stevens-Johnson syndrome, hypotension, seizures, syncope, TIA, stroke, QT prolongation, diabetes mellitus, hypothyroidism, pancreatitis, agranulocytosis, leukopenia, neutropenia, cataracts, dysphagia, priapism, neonatal extrapyramidal seizures (3rd trimester use), neonatal withdrawal symptoms (3rd trimester use), somnolence, xerostomia, dizziness. hypotension, tachycardia, constipation, weight gain, increased appetite, dyspepsia, tremor, dysarthria, dysphagia, blurred vision, anemia, rash, transiently elevated ALT/AST, abdominal pain, back pain, hyperprolactinemia, hyperlipidemia, asthenia, headache, fatigue, insomnia, irritability, nausea/vomiting, peripheral edema, fever.
Interaction :
Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Clarithromycin, Erythromycin: The macrolide, clarithromycin, may increase the effect and toxicity of quetiapine.
Donepezil: Possible antagonism of action.
Ethotoin: Phenytoin decreases the effect of quetiapine.
Fosphenytoin: Phenytoin decreases the effect of quetiapine.
Galantamine: Possible antagonism of action.
Ketoconazole: Ketoconazole may increase the therapeutic and adverse effects of quetiapine.
Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Mephenytoin: Phenytoin decreases the effect of quetiapine.
Phenytoin: Phenytoin decreases the effect of quetiapine.
Quinupristin: This combination presents an increased risk of toxicity.
Rivastigmine: Possible antagonism of action.
Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Quetiapine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Telithromycin: Telithromycin may reduce clearance of Quetiapine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Quetiapine if Telithromycin is initiated, discontinued or dose changed.
Tetrabenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Trimethobenzamide: Trimethobenzamide and Quetiapine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Triprolidine, Trospium: Trospium and Quetiapine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects.
Trimipramine, Voriconazole, Vorinostat, Ziprasidone, Zuclopenthixol: Additive QTc prolongation may occur.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Initial dose 25 mg/day and increase in increments of 25–50 mg/day according to response |
| 10-20 | Initial dose 25 mg/day and increase in increments of 25–50 mg/day according to response |
| <10 | Initial dose 25 mg/day and increase in increments of 25–50 mg/day according to response |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unknown dialysability. Dose as in GFR<10 mL/min |
| HD | Unknown dialysability. Dose as in GFR<10 mL/min |
| HDF/High flux | Unknown dialysability. Dose as in GFR<10 mL/min |
| CAV/VVHD | Unknown dialysability. Dose as in GFR=10–20 mL/min |
Hepatic Dose :
As quetiapine undergoes hepatic metabolism and clearance, patients with hepatic impairment have a higher plasma level, dose reduction is therefore advised. Dose adjustment guidelines are according to experience with adults.
For the immediate release formulation: initial dose should be made 1/4th with daily increment of dose, based on patient’s response.
For extended release formulation: Initial dose should be made 1/6th, with daily increments of same dose from day 2 and double the dose from day 3 based on patients’ response (8mg/day).