Seroquel Indications, Dosage, Storage, Stability - Quetiapine Fumarate

Seroquel Indications, Dosage, Storage, Stability - Quetiapine Fumarate

INDICATIONS AND USAGE

SEROQUEL is indicated for the treatment of acute manic episodes associated with bipolar I disorder, as either monotherapy or adjunct therapy to lithium or divalproex.

The efficacy of SEROQUEL in acute bipolar mania was established in two 12-week monotherapy trials and one 3-week adjunct therapy trial of bipolar I patients initially hospitalized for up to 7 days for acute mania (See CLINICAL PHARMACOLOGY). Effectiveness has not been systematically evaluated in clinical trials for more than 12 weeks in monotherapy and 3 weeks in adjunct therapy. Therefore, the physician who elects to use SEROQUEL for extended periods should periodically reevaluate the long-term risks and benefits of the drug for the individual patient (See DOSAGE AND ADMINISTRATION).

SEROQUEL is indicated for the treatment of schizophrenia.

The efficacy of SEROQUEL in schizophrenia was established in short-term (6-week) controlled trials of schizophrenic inpatients (See CLINICAL PHARMACOLOGY).

The effectiveness of SEROQUEL in long-term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use SEROQUEL for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (See DOSAGE AND ADMINISTRATION).

Usual Dose: When used as monotherapy or adjunct therapy (with lithium or divalproex), SEROQUEL should be initiated in BID doses totaling 100 mg/day on Day 1, increased to 400 mg/day on Day 4 in increments of up to 100 mg/day in BID divided doses. Further dosage adjustments up to 800 mg/day by Day 6 should be in increments of no greater than 200 mg/day. Data indicates that the majority of patients responded between 400 to 800 mg/day. The safety of doses above 800 mg/day has not been evaluated in clinical trials.

Usual Dose: SEROQUEL should generally be administered with an initial dose of 25 mg bid, with increases in increments of 25-50 mg bid or tid on the second and third day, as tolerated, to a target dose range of 300 to 400 mg daily by the fourth day, given bid or tid. Further dosage adjustments, if indicated, should generally occur at intervals of not less than 2 days, as steady state for SEROQUEL would not be achieved for approximately 1-2 days in the typical patient. When dosage adjustments are necessary, dose increments/decrements of 25-50 mg bid are recommended. Most efficacy data with SEROQUEL were obtained using tid regimens, but in one controlled trial 225 mg bid was also effective.

Efficacy in schizophrenia was demonstrated in a dose range of 150 to 750 mg/day in the clinical trials supporting the effectiveness of SEROQUEL. In a dose response study, doses above 300 mg/day were not demonstrated to be more efficacious than the 300 mg/day dose. In other studies, however, doses in the range of 400-500 mg/day appeared to be needed. The safety of doses above 800 mg/day has not been evaluated in clinical trials.

Consideration should be given to a slower rate of dose titration and a lower target dose in the elderly and in patients who are debilitated or who have a predisposition to hypotensive reactions (see CLINICAL PHARMACOLOGY). When indicated, dose escalation should be performed with caution in these patients.

Patients with hepatic impairment should be started on 25 mg/day. The dose should be increased daily in increments of 25-50 mg/day to an effective dose, depending on the clinical response and tolerability of the patient.

The elimination of quetiapine was enhanced in the presence of phenytoin. Higher maintenance doses of quetiapine may be required when it is coadministered with phenytoin and other enzyme inducers such as carbamazepine and phenobarbital (See Drug Interactions under PRECAUTIONS).

While there is no body of evidence available to answer the question of how long the patient treated with SEROQUEL should remain on it, the effectiveness of maintenance treatment is well established for many other drugs used to treat schizophrenia. It is recommended that responding patients be continued on SEROQUEL, but at the lowest dose needed to maintain remission. Patients should be periodically reassessed to determine the need for maintenance treatment.

Although there are no data to specifically address reinitiation of treatment, it is recommended that when restarting patients who have had an interval of less than one week off SEROQUEL, titration of SEROQUEL is not required and the maintenance dose may be reinitiated. When restarting therapy of patients who have been off SEROQUEL for more than one week, the initial titration schedule should be followed.

There are no systematically collected data to specifically address switching patients with schizophrenia from antipsychotics to SEROQUEL, or concerning concomitant administration with antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized. When switching patients with schizophrenia from depot antipsychotics, if medically appropriate, initiate SEROQUEL therapy in place of the next scheduled injection. The need for continuing existing EPS medication should be reevaluated periodically.

25 mg Tablets (NDC 0310-0275) peach, round, biconvex, film coated tablets, identified with ‘SEROQUEL’ and ‘25’ on one side and plain on the other side, are supplied in bottles of 100 tablets and 1000 tablets, and hospital unit dose packages of 100 tablets.

100 mg Tablets (NDC 0310-0271) yellow, round, biconvex film coated tablets, identified with ‘SEROQUEL’ and ‘100’ on one side and plain on the other side, are supplied in bottles of 100 tablets and hospital unit dose packages of 100 tablets.

200 mg Tablets (NDC 0310-0272) white, round, biconvex, film coated tablets, identified with ‘SEROQUEL’ and ‘200’ on one side and plain on the other side, are supplied in bottles of 100 tablets and hospital unit dose packages of 100 tablets.

300 mg Tablets (NDC 0310-0274) white, capsule-shaped, biconvex, film coated tablets, intagliated with ‘SEROQUEL’ on one side and ‘300’ on the other side, are supplied in bottles of 60 tablets and hospital unit dose packages of 100 tablets.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [See USP].

Quetiapine caused a dose-related increase in pigment deposition in thyroid gland in rat toxicity studies which were 4 weeks in duration or longer and in a mouse 2 year carcinogenicity study. Doses were 10-250 mg/kg in rats, 75-750 mg/kg in mice; these doses are 0.1-3.0, and 0.1-4.5 times the maximum recommended human dose (on a mg/m² basis), respectively. Pigment deposition was shown to be irreversible in rats. The identity of the pigment could not be determined, but was found to be co-localized with quetiapine in thyroid gland follicular epithelial cells. The functional effects and the relevance of this finding to human risk are unknown.

In dogs receiving quetiapine for 6 or 12 months, but not for 1 month, focal triangular cataracts occurred at the junction of posterior sutures in the outer cortex of the lens at a dose of 100 mg/kg, or 4 times the maximum recommended human dose on a mg/m² basis. This finding may be due to inhibition of cholesterol biosynthesis by quetiapine. Quetiapine caused a dose related reduction in plasma cholesterol levels in repeat-dose dog and monkey studies; however, there was no correlation between plasma cholesterol and the presence of cataracts in individual dogs. The appearance of delta-8-cholestanol in plasma is consistent with inhibition of a late stage in cholesterol biosynthesis in these species. There also was a 25% reduction in cholesterol content of the outer cortex of the lens observed in a special study in quetiapine treated female dogs. Drug-related cataracts have not been seen in any other species; however, in a 1-year study in monkeys, a striated appearance of the anterior lens surface was detected in 2/7 females at a dose of 225 mg/kg or 5.5 times the maximum recommended human dose on a mg/m² basis.

SEROQUEL is a trademark of the AstraZeneca group of companies. © AstraZeneca 2004

AstraZeneca Pharmaceuticals LP Wilmington, DE 19850 Made in USA, 64251-00 Rev 07/04