Drug Name

Seroquel (Quetiapine)

Generic Name

Quetiapine (kwe-TYE-a-peen)

Looks like

Quetiapine is available with a prescription under the brand name Seroquel. Other brand or generic formulations may also be available. Ask your pharmacist any questions you have about Seroquel, especially if it is new to you.

• Seroquel 25 mg - round, peach-colored tablets
• Seroquel 100 mg - round, yellow tablets
• Seroquel 200 mg - round, white tablets
• Seroquel 300 mg - white, capsule-shaped, film-coated tablets

Dosage Form

Tablets

Route Of Administration

ORAL

Imprint Code

Seroquel;25 / Seroquel;100 / Seroquel;200 / Seroquel;300

Size

6mm / 9mm / 11mm / 19mm

Alternatives

Bipolar Disorder
Zoloft (Sertraline), Lamictal (Lamotrigine), Abilify (Aripiprazole)
Schizophrenia
Abilify (Aripiprazole), Risperdal (Risperidone), Geodon (Ziprasidone), Zyprexa (Olanzapine)

Drug Uses

Seroquel is used to treat the symptoms of psychotic conditions such as schizophrenia and bipolar disorder (manic depression).

Drug class

Seroquel is an antipsychotic medication. It works by changing the actions of chemicals in the brain.

Contains

Seroquel is supplied for oral administration as 25 mg (round, peach), 50 mg (round, white), 100 mg (round, yellow), 200 mg (round, white), 300 mg (capsule-shaped, white), and 400 mg (capsule shaped, yellow) tablets.

Inactive ingredients are povidone, dibasic dicalcium phosphate dihydrate, microcrystalline cellulose, sodium starch glycolate, lactose monohydrate, magnesium stearate, hypromellose, polyethylene glycol and titanium dioxide.

The 25 mg tablets contain red ferric oxide and yellow ferric oxide and the 100 mg and 400 mg tablets contain only yellow ferric oxide.

Chemical formula

Seroquel (quetiapine fumarate) is a psychotropic agent belonging to a chemical class, the dibenzothiazepine derivatives. The chemical designation is 2 - [2 - (4 - dibenzo [b,f ] [1,4]thiazepin - 11 - yl - 1 - piperazinyl)ethoxy] - ethanol fumarate (2:1) (salt). It is present in tablets as the fumarate salt. All doses and tablet strengths are expressed as milligrams of base, not as fumarate salt. Its molecular formula is C42H50N6O4S2*C4H4O4 and it has a molecular weight of 883.11 (fumarate salt). The structural formula is:



Quetiapine fumarate is a white to off-white crystalline powder which is moderately soluble in water.

Mechanism of Action

Seroquel is an antagonist at multiple neurotransmitter receptors in the brain: serotonin 5HT1A and 5HT2 (IC50s=717 & 148nM respectively), dopamine D1 and D2 (IC50s=1268 & 329nM respectively), histamine H1 (IC50=30nM), and adrenergic a1 and a2 receptors (IC50s=94 & 271nM, respectively). Seroquel has no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors (IC50s>5000 nM).

The mechanism of action of Seroquel, as with other drugs having efficacy in the treatment of schizophrenia and bipolar disorder, is unknown. However, it has been proposed that the efficacy of Seroquel in schizophrenia and its mood stabilizing properties in bipolar depression and mania are mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5HT2) antagonism. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other effects of Seroquel.

Seroquel's antagonism of histamine H1 receptors may explain the somnolence observed with this drug.

Seroquel's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.

How Taken

Take Seroquel exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor.

Your doctor may occasionally change your dose to make sure you get the best results from Seroquel.

Take each dose with a full glass of water. Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. Breaking the pill may cause too much of the drug to be released at one time.
To be sure Seroquel is helping your condition, your doctor will need to check your progress on a regular basis. Do not miss any scheduled appointments.

Dosage and Administration

Bipolar Disorder
Depression

Usual Dose: Seroquel should be administered once daily at bedtime to reach 300 mg/day by day 4.

Recommended Dosing Schedule

Day	Day 1	Day 2	Day 3	Day 4
Seroquel	50 mg	100 mg	200 mg	300 mg

In the clinical trials supporting effectiveness, the dosing schedule was 50 mg, 100 mg, 200 mg and 300 mg/day for days 1-4 respectively. Patients receiving 600 mg increased to 400 mg on day 5 and 600 mg on day 8 (Week 1). Antidepressant efficacy was demonstrated with Seroquel at both 300 mg and 600 mg however, no additional benefit was seen in the 600 mg group.

Mania
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.

Schizophrenia
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.

Dosing in Special Populations
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. 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.

Maintenance Treatment: While there is no body of evidence available to answer the question of how long the patient treated with Seroquel should be maintained, it is generally recommended that responding patients be continued beyond the acute response, but at the lowest dose needed to maintain remission. Patients should be periodically reassessed to determine the need for maintenance treatment.

Reinitiation of Treatment in Patients Previously Discontinued: 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.

Switching from Antipsychotics: 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.

Missed Dose

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

Overdose

Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include extreme drowsiness, fast heart rate, feeling light-headed, or fainting.

Storage

Store Seroquel at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Seroquel out of the reach of children and away from pets.

How Supplied

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.

50 mg Tablets (NDC 0310-0278) white, round, biconvex, film coated tablets, identified with 'Seroquel' and '50' 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.

400 mg Tablets (NDC 0310-0279) yellow, capsule-shaped, biconvex, film coated tablets, intagliated with 'Seroquel' on one side and '400' on the other side, are supplied in bottles of 100 tablets, and hospital unit dose packages of 100 tablets.

What is the most important information I should know about Seroquel (Quetiapine)?

Seroquel is not for use in psychotic conditions that are related to dementia. Seroquel has caused fatal pneumonia or heart failure in older adults with dementia-related conditions. Stop using Seroquel and call your doctor at once if you have the following symptoms: fever, stiff muscles, confusion, sweating, fast or uneven heartbeats, uncontrolled muscle movements, symptoms that come on suddenly such as numbness or weakness, severe headache, and problems with vision, speech, or balance.
You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

What should I discuss with my doctor before taking Seroquel (Quetiapine)?

Seroquel is not for use in psychotic conditions that are related to dementia. Seroquel has caused fatal pneumonia or heart failure in older adults with dementia-related conditions.
Before you take Seroquel, tell your doctor if you have:

• liver or kidney disease;
• heart disease, high blood pressure, heart rhythm problems;
• a history of heart attack or stroke;
• a thyroid disorder;
• seizures or epilepsy;
• high cholesterol or triglycerides;
• a personal or family history of diabetes; or
• trouble swallowing.

If you have any of these conditions, you may not be able to use Seroquel, or you may need a dosage adjustment or special tests during treatment.

Seroquel may cause you to have high blood sugar (hyperglycemia). Talk to your doctor if you have any signs of hyperglycemia such as increased thirst or urination, excessive hunger, or weakness. If you are diabetic, check your blood sugar levels on a regular basis while you are taking Seroquel.

You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Tell your doctor if you have worsening symptoms of depression or suicidal thoughts during the first several weeks of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether Seroquel passes into breast milk or if it could harm a nursing baby. Do not use Seroquel without telling your doctor if you are breast-feeding a baby. Do not give Seroquel to anyone younger than 18 years old without the advice of a doctor.

Absorption

Quetiapine fumarate is rapidly absorbed after oral administration, reaching peak plasma concentrations in 1.5 hours. The tablet formulation is 100% bioavailable relative to solution. The bioavailability of quetiapine is marginally affected by administration with food, with Cmax and AUC values increased by 25% and 15%, respectively.

Distribution

Quetiapine is widely distributed throughout the body with an apparent volume of distribution of 10±4 L/kg. It is 83% bound to plasma proteins at therapeutic concentrations. In vitro, quetiapine did not affect the binding of warfarin or diazepam to human serum albumin. In turn, neither warfarin nor diazepam altered the binding of quetiapine.

Metabolism and Elimination

Following a single oral dose of 14C-quetiapine, less than 1% of the administered dose was excreted as unchanged drug, indicating that quetiapine is highly metabolized. Approximately 73% and 20% of the dose was recovered in the urine and feces, respectively.

Quetiapine is extensively metabolized by the liver. The major metabolic pathways are sulfoxidation to the sulfoxide metabolite and oxidation to the parent acid metabolite; both metabolites are pharmacologically inactive. In vitro studies using human liver microsomes revealed that the cytochrome P450 3A4 isoenzyme is involved in the metabolism of quetiapine to its major, but inactive, sulfoxide metabolite.

Special Populations

Age

Oral clearance of quetiapine was reduced by 40% in elderly patients (≥ 65 years, n=9) compared to young patients (n=12), and dosing adjustment may be necessary.

Gender

There is no gender effect on the pharmacokinetics of quetiapine.

Race

There is no race effect on the pharmacokinetics of quetiapine.

Smoking

Smoking has no effect on the oral clearance of quetiapine.

Renal Insufficiency

Patients with severe renal impairment (Clcr=10-30 mL/min/1.73 m2, n=8) had a 25% lower mean oral clearance than normal subjects (Clcr > 80 mL/min/1.73 m2, n=8), but plasma quetiapine concentrations in the subjects with renal insufficiency were within the range of concentrations seen in normal subjects receiving the same dose. Dosage adjustment is therefore not needed in these patients.

Hepatic Insufficiency

Hepatically impaired patients (n=8) had a 30% lower mean oral clearance of quetiapine than normal subjects. In two of the 8 hepatically impaired patients, AUC and Cmax were 3-times higher than those observed typically in healthy subjects. Since quetiapine is extensively metabolized by the liver, higher plasma levels are expected in the hepatically impaired population, and dosage adjustment may be needed.

Drug-Drug Interactions

In vitro enzyme inhibition data suggest that quetiapine and 9 of its metabolites would have little inhibitory effect on in vivo metabolism mediated by cytochromes P450 1A2, 2C9, 2C19, 2D6 and 3A4.

Quetiapine oral clearance is increased by the prototype cytochrome P450 3A4 inducer, phenytoin, and decreased by the prototype cytochrome P450 3A4 inhibitor, ketoconazole. Dose adjustment of quetiapine will be necessary if it is coadministered with phenytoin or ketoconazole.

Quetiapine oral clearance is not inhibited by the non-specific enzyme inhibitor, cimetidine.

Quetiapine at doses of 750 mg/day did not affect the single dose pharmacokinetics of antipyrine, lithium or lorazepam.

Possible side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Other serious side effects include:

• fever, stiff muscles, confusion, sweating, fast or uneven heartbeats;
• jerky muscle movements you cannot control;
• sudden numbness or weakness, especially on one side of the body;
• sudden headache, confusion, problems with vision, speech, or balance;
• increased thirst, frequent urination, excessive hunger, or weakness;
• feeling like you might pass out; or
• urinating less than usual or not at all.

Less serious side effects may include:

• dizziness, drowsiness, or weakness;
• dry mouth, runny nose, sore throat;
• nausea, vomiting, stomach pain, constipation;
• blurred vision, headache, anxiety, agitation;
• breast swelling or discharge;
• missed menstrual periods; or
• weight gain.

This is not a complete list of Seroquel side effects and others may occur. Tell your doctor about unusual or bothersome side effect.

What other drugs will affect Seroquel (Quetiapine)?

Before taking Seroquel, tell your doctor if you are taking any of the following medicines:

• cimetidine (Tagamet);
• lorazepam (Ativan);
• rifabutin (Mycobutin) or rifampin (Rifadin, Rimactane, Rifater);
• steroids (prednisone and others);
• thioridazine (Mellaril);
• an antibiotic such as erythromycin (E-Mycin, E.E.S, Ery-Tab), fluconazole (Diflucan), ketoconazole (Nizoral), itraconazole (Sporanox);
• medicine for depression or mental illness, such as fluoxetine (Prozac), haloperidol (Haldol), imipramine (Tofranil), or risperidone (Risperdal);
• a medication to treat high blood pressure or a heart condition; or
• seizure medication such as carbamazepine (Tegretol), divalproex (Depakote), phenobarbital (Luminal, Solfoton), phenytoin (Dilantin), or valproate (Depakene).

This list is not complete and there may be other drugs that can interact with Seroquel. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

What should I avoid while taking Seroquel (Quetiapine)?

Seroquel can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.
Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Avoid drinking alcohol, which can increase some of the side effects of Seroquel. Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by Seroquel. Tell your doctor if you need to use any of these other medicines while you are taking Seroquel.

Contraindications

Seroquel is contraindicated in individuals with a known hypersensitivity to this medication or any of its ingredients.

Warnings

Increased Mortality in Elderly Patients with Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Seroquel (quetiapine) is not approved for the treatment of patients with dementia-related psychosis.

Clinical Worsening and Suicide Risk
Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications.

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritabili