Quetiapine Film Coated Tablets
Quetiapine 25 mg ,100 mg & 200 mg Film Coated Tabs
Usage and indications:
Quetiapine is indicated for treatment of Schizophrenia
Quetiapine is indicated for treatment of bipolar disorder:
Dosage and administration:
Different dosing schedules exist for each indication. It must therefore be ensured that patients receive clear information on the appropriate dosage for their condition. Quetiapine can be administered with or without food.
(1) For the treatment of schizophrenia:
Quetiapine should be administered twice a day. 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 to 450 mg/day. Depending on the clinical response and tolerability of the individual patient, the dose may be adjusted within the range 150 to 750 mg/day.
(2) For the treatment of moderate to severe manic episodes associated with bipolar disorder: Quetiapine should be administered twice a day. 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 800 mg per day by Day 6 should be in increments of no greater than 200 mg per day. The dose may be adjusted depending on clinical response and tolerability of the individual patient, within the range of 200 to 800 mg per day. The usual effective dose is in the range of 400 to 800 mg per day.
(3) For the treatment of depressive episodes in bipolar disorder:
Quetiapine should be administered once daily at bedtime. 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). The recommended daily dose is 300 mg. In clinical trials, no additional benefit was seen in the 600 mg group compared to the 300 mg group. Individual patients may benefit from a 600 mg dose. Doses greater than 300 mg should be initiated by physicians experienced in treating bipolar disorder. In individual patients, in the event of tolerance concerns, clinical trials indicated that dose reduction to a minimum of 200 mg could be considered.
(4) For preventing recurrence in bipolar disorder, for prevention of recurrence of manic, depressive and mixed episodes in bipolar disorder:
Patients who have responded to quetiapine for acute treatment of bipolar disorder should continue therapy at the same dose. The dose may then be adjusted depending on clinical response and tolerability of the individual patient, within the range of 300 to 800 mg/day administered twice daily. It is important that the lowest effective dose is used for maintenance therapy.
Elderly: As with other antipsychotics, Quetiapine should be used with caution in the elderly, especially during the initial dosing period. The rate of dose titration may need to be slower, and the daily therapeutic dose lower, than that used in younger patients, depending on the clinical response and tolerability of the individual patient.
The mean plasma clearance of quetiapine was reduced by 30% to 50% in elderly patients when compared to younger patients. Efficacy and safety has not been evaluated in patients over 65 years with depressive episodes in the framework of bipolar disorder.
Paediatric population: Quetiapine is not recommended for use in children and adolescents below 18 years of age, due to a lack of data to support use in this age group.
Renal impairment: Dosage adjustment is not necessary in patients with renal impairment.
Hepatic impairment: Quetiapine is extensively metabolised by the liver. Therefore, Quetiapine should be used with caution in patients with known hepatic impairment, especially during the initial dosing period. Patients with known hepatic impairment should be started with 25 mg/day. The dosage should be increased daily with increments of 25 – 50 mg/day until an effective dosage, depending on the clinical response and tolerability of the individual patient.
Blood and lymphatic system disorders:
Very common: decreased haemoglobin.
Common: leucopenia, decreased neutrophil count, eosinophils increased.
Uncommon: neutropenia, Thrombocytopenia, anaemia, platelet count decreased.
Immune system disorders:
Uncommon: hypersensitivity (including allergic skin reactions).
Very rare: anaphylactic reaction.
Common: hyperprolactinaemia, decreases in total T4, decreases in free T4, decreases in total T3, increases in TSH.
Uncommon: decreases in free t3, hypothyroidism.
Metabolism and nutritional disorders:
Very common: elevations in serum triglyceride levels, elevations in total cholesterol (predominantly LDL cholesterol), decreases in HDL cholesterol, weight gain.
Common: increased appetite, blood glucose increased to hyperglycaemic levels.
Uncommon: hyponatraemia, diabetes mellitus, exacerbation of pre-existing diabetes
Rare: metabolic syndrome.
Common: abnormal dreams and nightmares, suicidal ideation and suicidal behavior.
Rare: somnambulism and related reactions such as sleep talking and sleep related eating disorder.
Nervous system disorders:
Very common: dizziness, somnolence, headache, extrapyramidal symptoms.
Uncommon: seizure, restless legs syndrome, tardive dyskinesia, syncope.
Common: tachycardia, palpitations.
Uncommon: QT prolongation, bradycardia.
Common: vision blurred.
Common: orthostatic hypotension.
Rare: venous thromboembolism.
Respiratory, thoracic and mediastinal disorder:
Very common: dry mouth.
Common: constipation, dyspepsia, vomiting.
Rare: pancreatitis, intestinal obstruction/ileus.
Common: elevations in serum alanine aminotransferase (ALT), elevations in gamma-GT levels.
Uncommon: elevations in serum aspartate aminotransferase (AST).
Rare: jaundice, hepatitis.
Skin and subcutaneous tissue disorders:
Very rare: angioedema, Stevens-Johnson syndrome.
Not known: toxic epidermal necrolysis, erythema multiforme.
Musculoskeletal and connective tissue disorders:
Very rare: rhabdomyolysis.
Renal and urinary disorders:
Uncommon: urinary retention.
Pregnancy, puerperium and perinatal conditions:
Not known: drug withdrawal syndrome neonatal.
Reproductive system and breast disorders:
Uncommon: sexual dysfunction.
Rare: priapism, galactorrhoea, breast swelling, menstrual disorder.
General disorders and administration site conditions:
Very common: withdrawal (discontinuation) symptoms.
Common: mild asthenia, peripheral oedema, irritability, pyrexia.
Rare: neuroleptic malignant syndrome, hypothermia.
Rare: elevations in blood creatine phosphokinase.
Warnings and precautions:
As quetiapine has several indications, the safety profile should be considered with respect to the individual patient's diagnosis and the dose being administered.
Quetiapine is not recommended for use in children and adolescents below 18 years of age, due to a lack of data to support use in this age group.
Clinical trials with quetiapine have shown that in addition to the known safety profile identified in adults, certain adverse events occurred at a higher frequency in children and adolescents compared to adults (increased appetite, elevations in serum prolactin, vomiting, rhinitis and syncope), or may have different implications for children and adolescents (extrapyramidal symptoms and irritability) and one was identified that has not been previously seen in adult studies (increases in blood pressure). Changes in thyroid function tests have also been observed in children and adolescents.
Furthermore, the long-term safety implications of treatment with quetiapine on growth and maturation have not been studied beyond 26 weeks. Long-term implications for cognitive and behavioural development are not known.
In placebo-controlled clinical trials with children and adolescent patients, quetiapine was associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in patients treated for schizophrenia, bipolar mania and bipolar depression.
Suicide/suicidal thoughts or clinical worsening:
Depression in bipolar disorder is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery. In addition, physicians should consider the potential risk of suicide-related events after abrupt cessation of quetiapine treatment, due to the known risk factors for the disease being treated.
Other psychiatric conditions for which Quetiapine is prescribed can also be associated with an increased risk of suicide related events. In addition, these conditions may be co-morbid with major depressive episodes. The same precautions observed when treating patients with major depressive episodes should therefore be observed when treating patients with other psychiatric disorders. Patients with a history of suicide related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present. In shorter-term placebo controlled clinical studies of patients with major depressive episodes in bipolar disorder an increased risk of suicide-related events was observed in young adult patients (younger than 25 years of age) who were treated with quetiapine as compared to those treated with placebo (3.0% vs. 0%, respectively).
Given the observed risk for worsening of their metabolic profile, including changes in weight, blood glucose (see hyperglycemia) and lipids, which was seen in clinical studies, patients' metabolic parameters should be assessed at the time of treatment initiation and changes in these parameters should be regularly controlled for during the course of treatment. Worsening in these parameters should be managed as clinically appropriate.
Quetiapine was associated with an increased incidence of extrapyramidal symptoms (EPS) in patients treated for major depressive episodes in bipolar disorder. The use of quetiapine has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
If signs and symptoms of tardive dyskinesia appear, dose reduction or discontinuation of quetiapine should be considered. The symptoms of tardive dyskinesia can worsen or even arise after discontinuation of treatment
Somnolence and dizziness:
Quetiapine treatment has been associated with somnolence and related symptoms, such as sedation.). In patients with bipolar depression, onset is usually within the first 3 days of treatment and was predominantly of mild to moderate intensity. Patients experiencing somnolence of severe intensity may require more frequent contact for a minimum of 2 weeks from onset of somnolence, or until symptoms improve and treatment discontinuation may need to be considered.
Quetiapine treatment has been associated with orthostatic hypotension and related dizziness which, like somnolence has onset usually during the initial dose-titration period. This could increase the occurrence of accidental injury (fall), especially in the elderly population. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication. Quetiapine should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or other conditions predisposing to hypotension. Dose reduction or more gradual titration should be considered if orthostatic hypotension occurs, especially in patients with underlying cardiovascular disease.
No data is available about the incidence of seizures in patients with a history of seizure disorder. As with other antipsychotics, caution is recommended when treating patients with a history of seizures.
Neuroleptic malignant syndrome:
Neuroleptic malignant syndrome has been associated with antipsychotic treatment, including Quetiapine. Clinical manifestations include hyperthermia, altered mental status, muscular rigidity, autonomic instability, and increased creatine phosphokinase. In such an event, Quetiapine should be discontinued and appropriate medical treatment given.
Severe neutropenia and agraulocytosis:
Severe neutropenia (neutrophil count <0.5 X 109/L) has been reported in quetiapine clinical trials. Most cases of severe neutropenia have occurred within a couple of months of starting therapy with quetiapine. There was no apparent dose relationship. During post-marketing experience, some cases were fatal. Possible risk factors for neutropenia include pre-existing low white blood cell count (WBC) and history of drug induced neutropenia. However, some cases occurred in patients without pre-existing risk factors. Quetiapine should be discontinued in patients with a neutrophil count <1.0 X 109/L. Patients should be observed for signs and symptoms of infection and neutrophil counts followed (until they exceed 1.5 X 109/L). Neutropenia should be considered in patients presenting with infection or fever, particularly in the absence of obvious predisposing factor(s), and should be managed as clinically appropriate.
Patients should be advised to immediately report the appearance of signs/symptoms consistent with agranulocytosis or infection (e.g. fever, weakness, lethargy, or sore throat) at any time during Quetiapine therapy. Such patients should have a WBC count and an absolute neutrophil count (ANC) performed promptly, especially in the absence of predisposing factors.
Concomitant use of Quetiapine with a strong hepatic enzyme inducer such as carbamazepine or phenytoin substantially decreases quetiapine plasma concentrations, which could affect the efficacy of Quetiapine therapy. In patients receiving a hepatic enzyme inducer, initiation of Quetiapine treatment should only occur if the physician considers that the benefits of Quetiapine outweigh the risks of removing the hepatic enzyme inducer. It is important that any change in the inducer is gradual, and if required, replaced with a non-inducer (e.g. sodium valproate).
Weight gain has been reported in patients who have been treated with quetiapine, and should be monitored and managed as clinically appropriate as in accordance with utilised antipsychotic guidelines.
Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported rarely, including some fatal cases. In some cases, a prior increase in body weight has been reported which may be a predisposing factor. Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines. Patients treated with any antipsychotic agent including quetiapine, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and weakness), and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly.
Increases in triglycerides, LDL and total cholesterol, and decreases in HDL cholesterol have been observed in clinical trials with quetiapine. Lipid changes should be managed as clinically appropriate.
In clinical trials and use in accordance with the SPC, quetiapine was not associated with a persistent increase in absolute QT intervals. In post-marketing, QT prolongation was reported with quetiapine at the therapeutic doses and in overdose. As with other antipsychotics, caution should be exercised when quetiapine is prescribed in patients with cardiovascular disease or family history of QT prolongation. Also, caution should be exercised when quetiapine is prescribed either with medicines known to increase QT interval, or with concomitant neuroleptics, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia
Cardiomyopathy and Myocarditis:
Cardiomyopathy and myocarditis have been reported in clinical trials and during the post-marketing experience, however, a causal relationship to quetiapine has not been established. Treatment with quetiapine should be reassessed in patients with suspected cardiomyopathy or myocarditis.
Acute withdrawal symptoms such as insomnia, nausea, headache, diarrhoea, vomiting, dizziness and irritability have been described after abrupt cessation of quetiapine. Gradual withdrawal over a period of at least one to two weeks is advisable.
Elderly patients with dementia-related psychosis:
Quetiapine is not approved for the treatment of dementia-related psychosis. Quetiapine should be used with caution in patients with risk factors for stroke.
An approximately 3-fold increased risk of cerebrovascular adverse events has been seen in randomised placebo controlled trials in the dementia population with some atypical antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Quetiapine should be used with caution in patients with risk factors for stroke.
If jaundice develops, quetiapine should be discontinued.
Dysphagia has been reported with quetiapine. Quetiapine should be used with caution in patients at risk for aspiration pneumonia.
Constipation and intestinal obstruction:
Constipation represents a risk factor for intestinal obstruction. Constipation and intestinal obstruction have been reported with quetiapine. This includes fatal reports in patients who are at higher risk of intestinal obstruction, including those that are receiving multiple concomitant medications that decrease intestinal motility and/or may not report symptoms of constipation. Patients with intestinal obstruction/ileus should be managed with close monitoring and urgent care.
Venous Thromboembolism “VTE”:
Cases of venous thromboembolism “VTE” have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE,
all possible risk factors for VTE should be identified before and during treatment with quetiapine and preventive measures undertaken.
Pancreatitis has been reported in clinical trials and during post marketing experience. Among post marketing reports, while not all cases were confounded by risk factors, many patients had factors which are known to be associated with pancreatitis such as increased triglycerides, gallstones, and alcohol consumption.
Quetiapine tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
Quetiapine 25mg, 100mg, 200mg Film Coated Tablets: Carton box containing 1, 2, or 3 (AL/PVC) blisters, each of 10 film coated tablets.