Quetiapine information from DrugsUpdate  

Pharmacodynamics

Pharmacokinetics

Quetiapine is an antagonist at multiple neurotransmitter receptors in the brain: Serotonin 5-HT1A and 5-HT2, dopamine D1 and D2, histamine H1 and adrenergic a1 and a2 receptors. It is used in the treatment of schizophrenia and bipolar disorder.

Absorption
Well absorbed after oral doses.

Distribution
Widely distributed throughout the body. 83% bound to plasma proteins.

Metabolism
Extensively metabolised in the liver by sulfoxidation and oxidation.

Excretion
Excreted mainly as inactive metabolites. Elimination half-life: about 6-7 hours.

Quetiapine Indications / Quetiapine Uses

Information Not Available

Quetiapine Adverse Reactions / Quetiapine Side Effects

Headache, asthenia, abdominal pain, back pain, fever, chest pain, postural and orthostatic hypotension, hypertension, constipation, dry mouth, dyspepsia, diarrhoea, leucopenia, elevations in serum transaminase level, weight gain, myalgia, somnolence, dizziness, anxiety, rhinitis, rash, dry skin, ear pain, UTI, syncope, neuroleptic malignant syndrome, variations in WBC count, neutropenia, eosinophilia, elevations in nonfasting serum triglyceride level and total cholesterol, decrease in thyroid hormone levels, prolongation of the QTc interval.

Precautions

Warnings

Increased mortality
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Over the course of a 10-wk controlled trial, the rate of death in drug-treated patients was about 4.5% compared with 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either CV (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Quetiapine is not approved for the treatment of patients with dementia-related psychosis.

Suicidality
Compared with placebo, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorders and other psychiatric disorders. Appropriately monitor patients of all ages who are started on antidepressant therapy and observe them closely for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the prescriber. Quetiapine is not approved for use in children.

Monitor

Monitor all patients for the emergence of agitation, irritability, clinical worsening, and other unusual changes in behavior, as well as the emergence of suicidality, especially during the initial few months of therapy or at times of dose changes. Monitor patients for symptoms of hyperglycemia. Perform fasting glucose testing in patients who develop hyperglycemia during treatment. Ensure that patients with risk factors for diabetes undergo fasting blood glucose testing at the start of therapy and periodically thereafter. Monitor patients with established diagnosis of diabetes mellitus regularly for worsening of glucose control. Perform eye exam at initiation of therapy to detect cataract formation and at 6-mo intervals during long-term treatment. Monitor patients for any unusual changes in behavior (eg, agitation, irritability). Monitor patients requiring antipsychotic drug treatment after recovery from NMS for recurrence of NMS if quetiapine therapy is reintroduced. Monitor WBC frequently during the first few months of therapy in patients with a preexisting low WBC or history of drug-induced leukopenia/neutropenia. Carefully monitor patients with neutropenia for fever or other symptoms or signs of infection.

Special Precautions

CV disease, cerebrovascular disease or conditions that predispose to hypotension. History of seizures; neuroleptic malignant syndrome; tardive dyskinesia. Monitor glycaemic control, especially in diabetics. Hepatic or renal impairment. Gradual withdrawal is recommended. Monitor for signs of clinical worsening, suicidality or unusual changes in behaviour. Pregnancy and lactation.

Other Drug Interactions

Increased risk of drowsiness and postural hypotension when used with alcohol. CYP3A4 inducers eg. phenytoin and carbamazepine may decrease plasma levels of quetiapine while CYP3A4 inhibitors eg. ketoconazole and erythromycin may increase its plasma levels.

Other Interactions

Information Not Available

Dosage

Oral
Schizophrenia
Adult: Initially, 25 mg bid on day 1, increased to 50 mg bid on day 2, 100 mg bid on day 3 and 150 mg bid on day 4. Usual dose range: 300-450 mg daily. Max: 750 mg/day.
Elderly: Initially, 25 mg daily, increased in steps of 25-50 mg daily according to response.
Renal impairment: Initially, 25 mg daily, may increase in steps of 25-50 mg daily according to response.
Hepatic impairment: Dose adjustment may be required.

Oral
Bipolar disorder
Adult: Manic phase: 50 mg bid on day 1, 100 mg bid on day 2, 150 mg bid on day 3 and 200 mg bid on day 4. Usual range: 400-800 mg/day; adjust dose according to response. Dosage increments should be ≤200 mg/day. Depressive phase: Initially, 50 mg at bedtime on day 1; 100 mg on day 2, 200 mg on day 3, and 300 mg on day 4. May increase to 400 mg on day 5 and 600 mg on day 8, if needed.
Elderly: Initially, 25 mg daily, increased in steps of 25-50 mg daily according to response.

Renal impairment
Initially, 25 mg daily, may increase in steps of 25-50 mg daily according to response.

Hepatic impairment
Dose adjustment may be required.

Food(before/after)

May be taken with or without food

Quetiapine and Pregnancy

Caution when used during pregnancy.

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Quetiapine and Lactation

Caution when used during lactation

Quetiapine and Children

Safety and efficacy not established; not approved for use in children.

Quetiapine and Geriatic

May be more susceptible to effects. Consider lower starting dose, slower titration, and careful monitoring. May be at increased risk of tardive dyskinesia, especially elderly women.

Quetiapine and Other Contraindications

Severe CNS depression, bone marrow suppression, coma.

Storage

Oral
Store at 25°C.

Lab interference

Oral
Store at 25°C.