Generic

Quetiapine Fumarate

Indications

Quetiapine is used to treat acute and chronic psychoses, such as schizophrenia, as well as bipolar disorder, including: treatment of manic episodes that meet DSM-IV criteria for mania in bipolar disorder, treatment of depressive episodes in bipolar disorder, and maintenance treatment of bipolar I disorder in combination with a mood stabilizer to prevent relapse.

Pharmacology

Quetiapine’s mechanism of action, like those of other medications used to treat schizophrenia and acute manic episodes associated with bipolar illness, remains unclear. However, it has been suggested that the drug’s effectiveness in schizophrenia is mediated through antagonism of dopamine type 2 (D2) and serotonin type 2 (5HT2). Some of the additional effects of Quetiapine might be explained by antagonistic interactions with receptors other than dopamine and 5HT 2 that have comparable receptor affinities. The inhibition of histamine H1 receptors by quetiapine might explain the drug’s somnolence. The inhibition of adrenergic 1 receptors by quetiapine might explain the orthostatic hypotension seen with this medication.

Dosage & Administration

Acute and chronic psychoses, including schizophrenia: Quetiapine should be administered twice daily, with or without food. The total daily dose for the first four days of therapy is 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4). From Day 4 onwards, the dose should be titrated to the usual effective dose range of 300-450 mg/day. However, this may be adjusted, depending on the clinical response and tolerability of the individual patient, within the range 150 to 750 mg/day.

Manic episodes associated with bipolar disorder: Quetiapine should be administered twice daily, with or without food. The total daily dose for the first four days of therapy is 100 mg (Day 1), 200 mg (Day 2), 300 mg (Day 3) and 400 mg (Day 4). Further dosage adjustments up to 800mg/day by Day 6 should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response & tolerability of the individual patient, within the range of 200 to 800 mg/day. The usual effective dose is in the range of 400 to 800mg/day.

Depressive episodes associated with bipolar disorder: Quetiapine should be administered once daily at bedtime, with or without food. The usual dose is 300 mg/day. The daily dose for the first four days of therapy is 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4). Quetiapine can be titrated to 400 mg on Day 5 and up to 600mg by Day 8. Antidepressant efficacy was demonstrated with Quetiapine at 300mg and 600 mg, however no additional benefit was seen in the 600mg group during short term treatment.

Maintenance treatment of bipolar I disorder in combination with mood stabilizers: Patients who have responded to Quetiapine in combination therapy with a mood stabiliser for acute treatment of bipolar disorder should continue on Quetiapine therapy at the same dose. Quetiapine dose can be re-adjusted depending on clinical response and tolerability of the individual patient. Efficacy was demonstrated with Quetiapine (administered twice daily totalling 400mg to 800mg a day) as combination therapy with a mood stabilizer.

Interaction

When Quetiapine is used with other medications that are known to induce electrolyte imbalance or increase the QT interval, caution should be maintained. When Quetiapine was taken with thioridazine or carbamazepine, the clearance of Quetiapine increased. Quetiapine clearance was also increased when it was given in combination with another microsomal enzyme inducer, phenytoin.

Contraindications

Patients who are hypersensitive to quetiapine should avoid it.

Side Effect

Somnolence, dizziness, dry mouth, withdrawal (discontinuation) symptoms, elevations in serum triglyceride levels, elevations in total cholesterol (predominantly LDL cholesterol), decreases in HDL cholesterol, weight gain, decreased haemoglobin, and extrapyramidal symptoms are the most commonly reported Adverse Drug Reactions (ADRs) with Quetiapine.

Pregnancy & Lactation

Quetiapine’s safety and effectiveness during human pregnancy have yet to be determined. As a result, quetiapine should only be taken during pregnancy if the benefits outweigh the dangers, and the dose and duration of therapy should be kept as low as feasible. It is unknown how much Quetiapine is secreted in human milk. Breast-feeding mothers should be warned about using Quetiapine while they are nursing.

Precautions & Warnings

• Suicide/suicidal thoughts or clinical worsening: Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs.
• Concomitant Illness: Quetiapine should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or other conditions predisposing to hypotension. Quetiapine may induce orthostatic hypotension especially during the initial dose-titration period.
• Seizures: As with other antipsychotics, caution is recommended when treating patients with a history of seizures.
• Tardive Dyskinesia and Extrapyramidal Symptoms (EPS): If signs and symptoms of tardive dyskinesia appear, dose reduction or discontinuation of Quetiapine should be considered.
• Neuroleptic Malignant Syndrome: This syndrome has been associated with antipsychotic treatment. Quetiapine should be discontinued and appropriate medical treatment given.
• QT Prolongation: As with other antipsychotics, caution should be exercised when Quetiapine is prescribed in patients with cardiovascular disease or family history of QT prolongation.
• Neutropenia: Severe neutropenia (<0.5×109/L) has been uncommonly reported in Quetiapine clinical trials. Most cases of severe neutropenia have occurred within the first two months of starting therapy with Quetiapine.
• Hyperglycemia & diabetes mellitus: Increases in blood glucose and hyperglycaemia, and occasional reports of diabetes, have been observed in clinical trials with Quetiapine.

Therapeutic Class

Atypical neuroleptic drugs

Storage Conditions

Keep this medication out of children’s sight and reach. After the expiration date on the blister pack and the carton, do not use this drug. The expiration date refers to the month’s final day. Store away from light in a cool, dry area.

Pharmaceutical Name

General Pharmaceuticals Ltd..