Quantia 25/Quantia 100/Quantia 200

Quetiapine fumarate.

Each film coated tablet contains: Quetiapine fumarate eq. to Quetiapine 25 mg.
Each film coated tablet contains: Quetiapine fumarate eq. to Quetiapine 100 mg.
Each film coated tablet contains: Quetiapine fumarate eq. to Quetiapine 200 mg.

Pharmacology: The exact mechanism by which quetiapine exerts its antipsychotic effect is unknown. However, this effect may be mediated through antagonism of dopamine type 2 (D₂) and serotonin type 2 (5-HT₂) receptors. Quetiapine is an antagonist at serotonin 5-HT_1A and 5-HT₂, dopamine D₁ and D₂, histamine H₁ and adrenergic alpha₁ and alpha₂ receptors. Quetiapine has no significant affinity for cholinergic muscarinic or benzodiazepine receptors. Drowsiness and orthostatic hypotension associated with the use of quetiapine may be explained by its antagonism of histamine H₁ and adrenergic alpha₁ receptors, respectively.
Pharmacokinetics: Absorption: Rapidly and well-absorbed. Food increases peak plasma concentration (C_max ) and area under the plasma concentration-time curve (AUC) by 25% and 15%, respectively.
Distribution: Extensively distributed throughout the body, with an apparent volume distribution (Vd) of 10 ± 4 L/kg. Protein binding: High (83%) to plasma proteins; does not alter the binding of warfarin or diazepam to human serum albumin in vitro and quetiapine binding is not altered in vitro by warfarin or diazepam.
Biotransformation: Extensively metabolized in the liver. Less than 5% of an orally administered dose is excreted unchanged. The major metabolic pathways are sulfoxidation, which in vitro studies indicate is mediated by the cytochrome P450 3A4 (CYP3A4) isoenzyme and oxidation. The major metabolites of quetiapine are inactive. Elimination half-life: mean, about 6-7 hrs. Time to peak concentration: Peak plasma concentration is reached within 2 hrs of dosing.
Elimination: Renal - approximately 73% of an orally administered dose is excreted renally. Fecal - approximately 20% of an orally administered dose is excreted feces.

Treatment of psychotic disorder manifestations including schizophrenia.

Adults: Initially 25 mg (base) 2 times a day, with increases of 25-50 mg (base) 2 or 3 times daily to a target dosage range of 300-400 mg (base) a day, in divided doses given 2 or 3 times a day, by the 4th-7th day. Further dosage adjustments may be made in increments or decrements of 25-50 mg (base) 2 times a day at intervals of 2 days. Some patients may require as little as 150 mg a day.
Adult Prescribing Limits: 750 mg (base) a day.
Children: Antipsychotics safety and efficacy have not been established.
Note: A slower rate of dosage titration and a lower target dosage should be considered in geriatric patients and in patients with hepatic impairment, predisposition to hypotension, or other debilitation. A dose-response study did not find dosage of 300 mg (base) a day. When reinstituting quetiapine therapy in a patient who has discontinued quetiapine for >1 week, the initial titration schedule should be followed. If discontinuation has been for <1 week, quetiapine may be reinstituted at the previous maintenance dosage.

Clinical effects: Acute drowsiness, heart block (slow or irregular heartbeat), hypotension, hypokalemia (weakness), tachycardia.
Note: First degree heart block and hypokalemia were seen in one patient after an estimated overdose of quetiapine 9600 mg. In doses >10 g, patients recovered without sequelae, and no fatalities were reported.
Treatment: Treatment is symptomatic and supportive.
To Decrease Absorption: Gastric lavage, following intubation in unconscious patients, and administration of charcoal with a laxative should be considered. Induction of emesis is not recommended due to risk of aspiration if patient is obtunded or experiencing seizures or dystonic reactions of the head and neck.
Specific Treatment: Administering antiarrhythmic therapy, if needed. However, disopyramide, procainamide, and quinidine have the potential to add to the possible QT-interval-prolonging effects of quetiapine overdosage. Also, bretylium may add to the hypotensive effect of quetiapine, due to additive α-adrenergic receptor blockade. Hypotension may be treated with intravenous fluids and/or sympathomimetic agents. However, epinephrine and dopamine may exacerbate hypotension through β-adrenergic stimulation in the presence of quetiapine-induced α-adrenergic receptor blockade. Anticholinergic (antidyskinetic) medication should be administered in the presence of severe extrapyramidal symptoms.
Monitoring: Continuous ECG monitoring is recommended to detect possible arrhythmias.
Supportive Care: Establish and maintain airway and ensure adequate oxygenation and ventilation. Patients in whom intentional overdose is confirmed or suspected should be referred to psychiatric consultation.

Except under special circumstances, Quantia should not be used when hypersensitivity to quetiapine exists.
Risk-benefit should be considered when the following medical problems exist: Alzheimer's dementia: Dysphagia associated with use of antipsychotic medications may increase risk of aspiration pneumonia. Possible increased risk of seizures because of lowered seizure threshold with Alzheimer's dementia.
*Breast cancer, or history of: Although elevated prolactin concentrations have not been demonstrated in clinical trials of Quetiapine, elevations have occurred with use of other antipsychotic medications and in animal studies of Quetiapine; studies have found approximately one third of human breast cancers to be prolactin-dependent in vitro.
*Cardiovascular disease, including: Conduction abnormalities or heart failure or myocardial infarction or ischemia, or history of.
*Cerebrovascular disease.
*Conditions that would predispose to hypotension, including: Dehydration or hypovolemia. Orthostatic hypotension may exacerbate pre-existing cardiovascular or cerebrovascular conditions. If hypotension occurs during dosage titration, it is recommended that dosage be returned to the previous level. Dehydration may predispose patient to increased core body temperature, and antipsychotic medications may disrupt that body's ability to lower core body temperature, thus increasing the risk of heatstroke.
Drug abuse or dependence, or history of: Patients should be closely monitored for signs of misuse or abuse of Quetiapine, as with any new CNS medication.
*Hepatic function impairment.
Severe renal function impairment: High blood concentrations of Quetiapine may occur. Dosage adjustments may be necessary, especially in the initial dosing period.
Hypothyroidism: Decreases in total and free Thyroxine (T₄) occurred during clinical trials of Quetiapine.
Seizures or history of: Seizures occurred rarely in premarketing studies of Quetiapine. It is recommended that Quetiapine be used with caution in patients with a history of seizures or a decreased seizure threshold).
*Major clinical significance.

Neonates exposed to antipsychotic drugs during 3rd semester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity. While in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Quetiapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Carcinogenicity/Tumorigenicity: Statistically significant increases in the incidence of thyroid gland follicular cell adenomas were seen in male mice receiving quetiapine at daily dosages that were equivalent to 1.5 and 4.5 times the maximum recommended human dose (MRHD) on a mg per square meter of body surface area (mg/m²) basis and in male rats receiving 3 times the MRHD on a mg/m² basis, possibly as a result of chronic stimulation of the thyroid gland by thyroid-stimulating hormones (TSH). Although the results were not definitive, quetiapine toxicity studies in rats and mice showed changes in thyroxine concentrations, thyroxine clearance, and TSH concentrations that are consistent with the proposed mechanism of increased thyroxine clearance leading to increased TSH concentrations and increased thyroid gland stimulation. Statistically significant increases in the incidence of mammary gland adenocarcinomas were seen in rats receiving quetiapine at daily dosages that were equivalent to 0.3-3 times the MRHD on a mg/m² basis. In a 1-year quetiapine toxicity study, median serum prolactin concentrations were increased to a maximum of 32-fold in male rats, and 13-fold in female rats. The mammary gland neoplasms seen in rodents, due to chronic administration of antipsychotic medications, are considered to be prolactin-mediated. The relevance of these findings to humans is unknown.
Mutagenicity: Quetiapine produced a reproducible increase in mutations in 1 of 6 strains in in vitro bacterial gene mutation assays in the presence of metabolic activation. An in vitro chromosomal aberration assay in cultured human lymphocytes and an in vivo micronucleus assay in rats found no evidence of clastogenic potential.
Fertility: In male Sprague-Dawley rats, the interval to mate and the number of matings required to produce pregnancy increased at quetiapine doses equivalent to 0.6 and 1.8 times the MRHD on a mg/m² basis. These effects were still present 2 weeks after discontinuation of quetiapine in the rats that had received 1.8 times of MRHD. No effects on mating or fertility were seen in male rats receiving ≤0.3 times the MRHD on a mg/m² basis. In female Sprague-Dawley rats, the interval to mate increased and the number of matings and the number of matings resulting in pregnancy decreased at a quetiapine dose equivalent to 0.6 times the MRHD on a mg/m_² basis. Irregular estrus cycles increased at doses equivalent to 0.1 and 0.6 times the MRHD on a mg/m² basis. No effects on estrus, mating, or fertility were seen in female rats receiving ≤0.01 times the MRHD on a mg/m² basis.
Use in Children: No information is available on the relationship of age to the effects of quetiapine in pediatric patients. Safety and efficacy have not been established.
Use in Elderly: No geriatrics-specific problems that would limit the usefulness of quetiapine in the elderly were seen in studies that included subject ≥65 years of age. However, the mean plasma clearance of quetiapine in elderly patients was 30-50% less than in younger patients. Reduced initial and target dosages, and slower dosage titration may be necessary in elderly patients.

Use in Pregnancy: Adequate and well-controlled studies in humans have not been done. Quetiapine showed no teratogenic potential in rats and rabbits, dosed at 0.3 to 2.4 and 0.6 to 2.4 times the MRHD on a mg/m² basis, respectively, during the period of organogenesis. However, in rats, delays in skeletal ossification were seen in fetuses at all doses. Also, reduced fetal body weight and reduced maternal weight gain and/or increased maternal deaths were seen at all doses, delays in skeletal ossification in the fetuses were seen at doses of 1.2 and 2.4 times the MRHD on a mg/m² basis, and reduced fetal body weight and an increased incidence of minor soft tissue anomaly in the fetuses were seen at the highest dose used. In a perinatal/postnatal study in rats receiving 0.01 to 0.24 times the MRHD on a mg/m² basis, no drug-related effects were observed. However, in a preliminary perinatal/postnatal study in rats receiving 3 times the MRHD on a mg/m² basis, increase in fetal and pup deaths and decreases in mean litter weight were found.
Use in Lactation: Quetiapine is distributed into the milk of animals. It is not known whether quetiapine is distributed into breast milk, but breast-feeding while taking quetiapine is not recommended.

Those Indicating Need for Medical Attention: Incidence Less Frequent: Dysarthia (trouble in speaking), dyspnea (trouble in breathing), extrapyramidal symptoms, pakinsonian (trouble in speaking or swallowing, loss of balance control, mask-like face, shuffling walk, slowed movements, stiffness of arms or legs, trembling and shaking of hands and fingers), flu-like symptoms (fever, chills, muscle aches), leukopenia (fever, chills, or sore throat), orthostatic hypotension (dizziness, lightheadedness, or fainting, especially when getting up from a lying or sitting position), peripheral edema (swelling of feet or lower legs), skin rash.
Incidence Rare: Changes in lenses of eyes- usually asymptomatic, galactorrhea (unusual secretion of milk)- in females, hypothyroidism (loss of appetite, weight gain, dry and puffy skin, tiredness), hypotension, menstrual changes, neuroleptic malignant syndrome (NMS) (difficult or unusually fast breathing, fast heartbeat or irregular pulse, high fever, high or low [irregular] blood pressure, increased sweating, loss of bladder control, severe muscle stiffness, seizures, unusual pale skin, unusual tiredness or weakness), seizures, tachycardia (fast, pounding or irregular heartbeat; fainting)
Note: Changes in the lenses of the eyes have been observed in patients during long-term quetiapine therapy and cataracts have developed in dogs during chronic quetiapine dosing. Regular ophthalmologic examinations are recommended during quetiapine therapy.
Those Indicating Need for Medical Attention Only if Continuous or are Bothersome: Incidence More Frequent: Constipation, dizziness, drowsiness, dry mouth, dyspepsia (indigestion), increased weight.
Note: Dyspepsia and increased weight are dose-related. In pooled data from 3- to 6-week trials, 23% of patients receiving quetiapine and 6% of patients receiving placebo gained ≥ 7% of their baseline body weight.
Incidence Less Frequent: Abdominal pain, abnormal vision, anorexia (decreased appetite), asthenia (decreased strength and energy), headache, hypertonia (increased muscle tone), increased sweating, palpitation (feeling of fast or irregular heartbeat), pharyngitis (sore throat), rhinitis (stuffy or runny nose).
Note: Abdominal pain is dose-related.

Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
*Alcohol.
*Other central nervous system (CNS) depression-producing medications: Quetiapine has been shown to potentiate the cognitive and motor effects of alcohol.
Antihypertensive agents: Hypotensive effects of these medications may be enchanced.
Cimetidine: Oral clearance of quetiapine was decreased by 20% when co-administered with cimetidine 400 mg 3 times a day.
*Cytochrome P450 3A (CYP3A) isoenzyme inhibitors (eg, diltiazem, erythromycin, fluconazole, itraconazole, ketoconazole, nafazodone, verapamil): Although there is no experience with the combination of quetiapine and a potent CYP3A enzyme inhibitor, caution is advised since quetiapine's major route of metabolism involves CYP3A4.
Dopamine agonists or Levodopa: Effects of these medications may be antagonized by quetiapine.
*Hepatic enzyme inducers, cytochrome P450: Mean oral clearance of quetiapine was increased 5-fold in patients receiving phenytoin. Higher doses of quetiapine may be required during concomitant therapy with an enzyme-inducing medication. A decrease in quetiapine dosage may be required when enzyme-inducer therapy is discontinued.
Lorazepam: Mean oral clearance of lorazepam was decreased by 20% when co-administered with quetiapine 250 mg 3 times a day.
Thioridazine: Oral clearance of quetiapine was increased by 65% when co-administered with thioridazine 200 mg 2 times a day.
*Major clinical significance.

Store at temperature not more than 30°C.

Antipsychotics

N05AH04 - quetiapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics.

P₁S₁S₃