Quetiapine dosing

The UK manufacturers advise eaution if quetiapine is given with mac-rolides and azole antifungals, and suggest that lower quetiapine doses should be considered. The US manufaeturers also advise eaution, and specifically name itraconazole and fluconazole, erythromycin and protease inhibitors, all of which are inhibitors of CYP3A4. 

Quetiapine dose not appear to interact to a clinically relevant extent with cimetidine, fluoxetine, imipramine or lorazepam. Isolated cases of adverse outcomes have been reported with diphenhydramine, iovastatin and mirtazapine. 

A patient taking diphenhydramine 100 mg daily developed urinary retention when she increased her dose of quetiapine from 900 mg daily to 2.4 g daily. When the dose of quetiapine was reduced back to 900 mg daily, her urinary retention resolved. A further episode occurred when the patient again increased her quetiapine dose. Although quetiapine does not normally have antimuscarinic adverse effects at usual therapeutic doses, it is suggested by the authors that the likelihood of these adverse effects is increased at doses ofquetiapine greater than 900 mg daily. This effect may have occurred as a result of additive antimuscarinic activity of both diphenhydramine and high-dose quetiapine. ... 

A 3-week, double-blind, placebo-controlled trial of quetiapine monotherapy in children and adolescents with mania was reported [202 ]. The most common adverse events associated with quetiapine were somnolence, sedation, dizziness and headache most events were mild to moderate in intensity. Potentially clinically relevant increases in total cholesterol, LDL-cholesterol and triglyceride concentrations were more frequent and numericdly larger with quetiapine mean weight gain at end point (observed cases) was 1.7kg for both quetiapine doses and 0.4kg for placebo. 

Current or past anti-cholinergic side effects Risperidone, quetiapine, aripiprazole ziprasidone Olanzapine (low dose)... 

Quetiapine 3A4 2D6, 2C9 Carbamazepine and phenytoin topiramate prednisolone. Fluvoxamine fluoxetine sertraline (high dose) CYP3A4 substrates grapefruit juice. 

Quetiapine is predominantly metabolized by CYP3A4. Environmental rather than genetic differences are most likely to explain unusual differences in the serum concentration to dose ratio for this antipsychotic (de Leon etal, 2005b). 

Quetiapine Seroquel Tablet 25,50,100,200, 300, 400 mg 50-800 mj day in divided doses or once daily when stabilized... 

Most antipsychotics have half-fives of elimination in the range of 20 to 40 hours. After dosage stabilization, most antipsychotics (except quetiapine and ziprasidone) can be dosed once daily. It may be possible to dose SGAs less often than their plasma kinetics would suggest. 

Treatment with AChs is disappointing, and reduction in antipsychotic dose may be the best intervention. Another alternative is to switch to an SGA, although akathisia occasionally occurs with the SGAs. Quetiapine and clozapine appear to have the lowest risk for causing akathisia. 

Quetiapine (Seroquel). Another atypical antipsychotic, quetiapine has also been approved by the FDA for the treatment of acute mania. It is usually administered twice daily at doses of 150-750mg/day. Like its counterparts, quetiapine is a well-tolerated medication. Its common side effects are drowsiness, dizziness, and headache. It causes less weight gain than olanzapine or clozapine but more than ziprasidone or aripiprazole. Quetiapine also does not cause agranulocytosis nor does it increase the risk of seizures. It can occasionally cause mild changes in liver function tests, but these usually return to normal even if the patient continues taking quetiapine. 

Quetiapine (Seroquel). Quetiapine is the fourth of the atypical antipsychotics introduced in the United States. It is effective in both positive and negative symptoms of schizophrenia within a dose range of 150 to 750mg/day in two divided... 

Atypical antipsychotics may be helpful in managing the delusions and agitated behavior that can accompany dementia. These medications, include risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), and olanzapine (Zyprexa). All antipsychotics, typical and atypical, appear to increase the risk of death in patients with dementia and psychosis. This appears as a warning in the package inserts of the newer drugs. A prudent approach is to discuss this risk with the caregiver, use the lowest effective dose, and monitor for effectiveness. 

Brief Severe Agitation. Acute management of severe agitation with physical aggression requires more definitive treatment. The first choice is haloperidol given in low doses (0.25-1 mg) as needed. Lorazepam can also be helpful if used briefly. Risperidone, olanzapine, quetiapine, or trazodone can also be used but are not available in injectable forms. 

We prefer low doses of atypical antipsychotics as a first-line treatment. In this way, the threat of extrapyramidal symptoms is largely avoided without having to use a second anticholinergic medication to offset antipsychotic side effects. Risperidone 0.25-0.5mg/day, olanzapine 2.5mg/day, quetiapine 25mg/day, ziprasidone 20mg/day, or aripiprazole 2.5-5mg/day are reasonable starting doses. The typically higher doses used to treat schizophrenia are usually not necessary. 

Antipsychotics in a few small studies have been shown to be helpful. To date this research is limited to typical antipsychotics. Nevertheless, the excellent track record of atypical antipsychotics in treating schizophrenia and the lower burden of side effects lead us to recommend atypical antipsychotics as a first-line treatment for STPD as well. Low doses of risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole are all reasonable options. If no therapeutic effect is observed, doses should be increased. 

Hypothyroidism Quetiapine demonstrated a dose-related decrease in total and free thyroxine (T4) of approximately 20% at the higher end of the therapeutic dose range... 

Usual dose When used as monotherapy or adjunct therapy (with lithium or divalproex), initiate quetiapine in twice-daily 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 twice-daily divided doses. Further dosage adjustments up to 800 mg/day by day 6 should be in increments of no more than 200 mg/day. The safety of doses above 800 mg/day has not been evaluated in clinical trials. 

Reinitiation of treatment in patients previously discontinued -Wr en restarting patients who have had an interval of less than 1 week off quetiapine, titration of quetiapine is not required and the maintenance dose may be reinitiated. For patients who have been off quetiapine for more than 1 week, follow the initial titration schedule. 

This group includes risperidone, quetiapine, olanzapine, ziprasidone, and aripiprazole. But all these agents cause dose-related EPS and appear in general more likely to cause diabetes and other metabolic problems than some of the older drugs (see Duggan et ah, 2005). 

There is only one study in (open trial) examining the efficacy of quetiapine in the treatment of EOS (Mc-Conville et ah, 2000). Patientes were treated with 100 or 400 mg/day. Quetiapine was well tolerated and improved both positive and negative symptoms as determined by the BPRS, the CGI Scale, and the Modified SANS. Quetiapine pharmacokinetics were dose proportional in adolescents and resembled those reported in adult patients. The most common side effects in the study were postural tachycardia and insomnia. The EPS occurred and improved during the course of treatment. There were no serious adverse events or clinically important changes in hematology or clinical chemistry. 

Quetiapine is indicated for the treatment of schizophrenia and acute mania. Results from a recent study also showed that this medication is an effective treatment for bipolar depression (Calabrese et al. 2005). Quetiapine therapy is initiated at a dose of 25 mg twice a day for patients with schizophrenia, with increases to 50 mg twice a day on day 2, 100 mg twice a day on day 3, and 100 mg in the morning and 200 mg in the evening on day 4. The optimal dose for most patients appears to range between 400 and 600 mg/day, although the drug is safe and efficacious for some patients within a dose range of... 

In terms of EPS and changes in serum prolactin levels, quetiapine at doses of up to 750 mg/day was no different from placebo (Arvan-itis and Miller 1997). 

Somnolence. Somnolence is one of the most common side effects of quetiapine. Somnolence and psychomotor slowing are dose dependent, and patients often become tolerant to these side effects over time. 

Cardiovascular effects. Given aj-adrenergic receptor antagonism, quetiapine may induce orthostatic hypotension and concomitant symptoms of dizziness, tachycardia, and syncope. The risk of symptomatic hypotension is particularly pronounced during initial dose titration. Quetiapine should be used with caution in patients with cardiovascular disease, cerebrovascular disease, or other illnesses predisposing to hypotension. 

Quetiapine is metabolized by hepatic CYP 3A3/4. Concurrent administration of cytochrome P450-inducing drugs, such as carbamazepine, decreases blood levels of quetiapine. In such circumstances, increased doses of quetiapine are appropriate. Quetiapine does not appreciably affect the pharmacokinetics of other medications. Pharmacodynamic effects are expected if quetiapine is combined with medications that also have antihistaminic or a-adrenergic side effects. Because of its potential for inducing hypotension, quetiapine also may enhance the effects of certain antihypertensive agents. 

---