Quetiapine oral standard release
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of quetiapine.
Drugs List
Therapeutic Indications
Uses
Bipolar disorder: prevention of recurrence
Treatment of depressive episodes associated with bipolar disorder
Treatment of manic episodes associated with bipolar disorder
Treatment of schizophrenia
Dosage
Adults
Treatment of Schizophrenia
Taken twice a day. For the first four days of therapy the total daily dose is 50mg on day one, 100mg on day two, 200mg on day three, and 300mg on day four. From day four onwards the dose should be titrated to the usual effective dose range of 300mg to 450mg per day.
Depending on the clinical response and tolerability of the individual patient, the dose may be adjusted within the range 150mg to 750mg per day.
Treatment of Manic Episodes associated with Bipolar Disorder
Taken twice a day. For the first four days of therapy the total daily dose is 100mg on day one, 200mg on day two, 300mg on day three, and 400mg on day four. Further dosage adjustments up to 800mg per day by day six should be increments of no greater than 200mg per day.
Depending on the clinical response and tolerability of the individual patient, the dose may be adjusted within the range 200mg to 800mg per day. The usual effective dose is in the range of 400mg to 800mg per day.
Treatment of depressive episodes associated with Bipolar Disorder
Taken once a day at bedtime. The daily dose at the start of therapy is 50mg on day one, 100mg on day two, 200mg on day three and 300mg on day four.
Recommended daily dose is 300mg.
Depending on the clinical response and tolerability of the individual patient, the dose may be adjusted within the range 200mg to 600mg per day.
Treatment should be initiated by physicians experienced in treating bipolar disorder.
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 300mg to 800mg per day administered twice daily. It is important that the lowest effective dose is used for maintenance therapy.
Elderly
Use with caution especially during the initial dosing period. Patients should be started on quetiapine 25mg per day. The dose should be increased daily in increments of 25mg to 50mg to an effective dose which may well be lower than in younger patients. The rate of dose titration may need to be slower, and the daily therapeutic dose lower in elderly patients. The mean plasma clearance of quetiapine is reduced by 30% to 50% in elderly patients compared to younger patients.
Safety and efficacy have not been evaluated in patients over 65 years with depressive episodes in bipolar disorder.
Elderly patients with dementia-related psychosis may be at an increased risk of death compared to placebo. However, the meta-analysis which produced these results, may be due to patients in the trial dying from a variety of causes that were consistent with expectations for this population, so a causal relationship between quetiapine use in this population age group was not established.
Children
Contraindicated by the manufacturer for use in children under 18 years old.
This is due to a lack data to support use in this age group. Furthermore in limited clinical trials, certain adverse side effects, for example increased appetite, elevations in serum prolactin and extrapyramidal symptoms, were at a higher frequency in children and adolescents compared to adults. Increases in blood pressure has been reported as a side effect in children which had not been previously reported in adults. Changes in thyroid function tests have also been observed in children and adolescents. Furthermore, the long-term safety implications of treatment on growth and maturation have not been studied beyond 26 weeks. Long-term implications for cognitive and behavioural development are not known.
Schizophrenia (unlicensed)
Children aged 12 to 18 years
Initial dose of 25mg twice a day, adjusted in steps of 25mg to 50mg according to individual patient response. Maximum of 750mg daily.
Treatment of mania in bipolar disorder (unlicensed)
Children aged 12 to 18 years
Day 1, 25mg twice a day. Day 2, 50mg twice a day. Day 3, 100mg twice a day. Day 4, 150mg twice a day. Day 5 200mg twice a day. Adjust doses according to individual patient response in steps no greater than 100mg a day. The usual dose is 400mg to 600mg a day in 2 divided doses.
Patients with Hepatic Impairment
Quetiapine is extensively metabolised by the liver. Consequently quetiapine should be used with caution in patients with known hepatic impairment, especially during the initial dosing period. Oral clearance is reduced by approximately 25% in patients with hepatic impairment.
Patients should be started on quetiapine 25 mg per day increasing in increments of 25 to 50 mg daily to an effective dose.
Contraindications
Children under 12 years
Neutrophil count below 1.0 x 10 to the power of 9 / L
Galactosaemia
Long QT syndrome
Torsade de pointes
Precautions and Warnings
Children aged 12 to 18 years
Family history of long QT syndrome
Patients over 65 years
Predisposition to aspiration or regurgitation
Predisposition to hypotension
Predisposition to venous thromboembolism
Restricted sodium intake
Risk of cerebrovascular accident
Suicidal ideation
Breastfeeding
Cardiovascular disorder
Cerebrovascular disorder
Dementia
Diabetes mellitus
Electrolyte imbalance
Gastrointestinal obstruction
Gastrointestinal stenosis
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of alcohol abuse
History of drug misuse
History of gastrointestinal obstruction
History of raised intra-ocular pressure
History of seizures
History of torsade de pointes
History of urinary retention
Lactose intolerance
Narrow angle glaucoma
Pregnancy
Prostate disorder
Raised intra-ocular pressure
Renal impairment
Urinary retention
Correct electrolyte disorders before treatment
Reduce dose in patients with hepatic impairment
Some formulations contain more than 1mmol (23mg) sodium per dose
Advise patient somnolence may affect ability to drive or operate machinery
Oral liquid contains propylene glycol - may cause alcohol like symptoms
Contains lactose
Oral liquid contains hydroxybenzoate: caution in hypersensitivity
High dose and under 50kg: Risk of exceeding propylene glycol
Consider monitoring ECG in patients at risk of QT prolongation
Monitor patients at risk for signs & symptoms of venous thromboembolism
Monitor patients for signs and symptoms of Neuroleptic Malignant Syndrome
Monitor patients with existing or tendency towards diabetes mellitus
Monitor serum electrolytes
Monitor serum lipids
Symptoms of tardive dyskinesia can worsen or arise after discontinuation
Advise patients/carers to seek medical advice if suicidal intent develops
Consider discontinuation if signs of tardive dyskinesia occur
Do not increase dosage in patients who develop akathisia
Dysphagia & aspiration:caution in patients at risk for aspiration pneumonia
May cause postural hypotension especially in elderly
May cause weight gain
Potential for withdrawal symptoms
May affect results of some laboratory tests
Avoid abrupt withdrawal
Discontinue at first signs of jaundice
Discontinue if neutrophil count below 1 x 10 to the power of 9/L
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue if severe skin reaction occurs
Discontinue or interrupt treatment if neutropenia develops
Reduce dose in elderly
Advise patient grapefruit products may increase plasma level
Advise patients on the risk of neutropenia and the significance of fever
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 self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery.
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 disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.
Patients with a history of suicide related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.
Quetiapine treatment has been associated with somnolence and related symptoms, such as sedation. In clinical trials for treatment of patients with bipolar depression, onset was usually within the first 3 days of treatment and was predominantly of mild to moderate intensity. Bipolar depression 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.
There may be possible worsening of the metabolic risk profile in individual patients, which should be managed as clinically appropriate.
Use with caution in patients with risk factors for stroke. An approximately 3-fold increased risk of cerebrovascular adverse effects have been seen in clinical trials in patients with dementia. Quetiapine is not approved for the treatment of patients with dementia-related psychosis.
If neutrophil count drops below 1 x 10 to the power of 9 / litre, quetiapine should be discontinued and the patient observed for signs and symptoms of infection and neutrophil counts until neutrophil count is greater than 1.5 x 10 to the power of 9 / litre.
Caution should be exercised if quetiapine is prescribed to elderly patients with parkinsons disease.
Pregnancy and Lactation
Pregnancy
Quetiapine should be used with caution in pregnancy.
It is not known if quetiapine crosses the placenta, but it is thought likely due to its molecular weight, degree of protein binding and relatively long elimination half life. There is a general lack of data and published experience with quetiapine in pregnancy; Schaefer (2007) has found no teratogenic effects to date, and lists quetiapine among the preferred atypical antipsychotics during pregnancy. Animal studies in pregnant rats and rabbits have not found teratogenicity at oral doses up to 2.4 times the maximum human dose, but some minor soft tissue malformations were noted in rabbit foetuses. A decrease in mating and fertility in rats has also been reported with quetiapine.
Weight increase in pregnant women treated with quetiapine has been observed, which is a risk factor for pregnancy outcome. Neonates exposed to antipsychotics during the third trimester of pregnancy are at the risk of extrapyramidal and/or withdrawal symptoms including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorders. Seizures have also been reported. Regular psychiatric and obstetric care is recommended to diagnose relapse or pregnancy complications, and the neonate should be observed for at least 2 days for withdrawal symptoms or adaption problems if quetiapine has been used up to delivery. If dose reduction or interruption in the days immediately preceding delivery is deemed appropriate, this may prevent neonatal adaption disorders. Pre-pregnancy dosage should be then started immediately after delivery to prevent relapse.
Use of quetiapine during pregnancy is recommended by the manufacturer only if the benefits to the mother outweigh the potential risk to the foetus. However, antipsychotic medication should not be changed if patients are stable, and quetiapine is indicated for severe debilitating mental disease. Refer all women with bipolar disorder and/or schizophrenia who wish to become pregnant to a psychiatrist for assessment of bipolar disorder and/or schizophrenia and review of current medication. Hence Briggs concludes that the benefits to the mother do appear to outweigh risk to the foetus.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Quetiapine should be used with caution in breastfeeding.
There is limited data available on the excretion of quetiapine into breast milk, and the manufacturer does not recommend breastfeeding whilst taking quetiapine. Due to the fact that there is little published experience on the use of quetiapine during breastfeeding and little long-term follow-up data, LactMed suggests that other agents such as haloperidol, olanzapine or risperidone may be preferred, particularly with newborn or premature infants.
Studies suggest that an exclusively breastfed infant would ingest a maximum of 0.43% of the weight-adjusted maternal dose, which is considered minimal. Schaefer (2007) includes quetiapine as among those atypical neuroleptics acceptable during lactation, but cautions that there is insufficient experience in the long-term effects on breastfed children.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Anaphylactic reaction
Angioedema
Anxiety
Asthenia
Blood lipid changes
Blurred vision
Breast swelling
Cardiac arrest
Constipation
Creatine phosphokinase increased
Dizziness
Dose-related decrease in thyroid hormone levels
Dream abnormalities
Drowsiness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dysarthria
Dyspepsia
Dysphagia
Dyspnoea
Elevated triglyceride levels
Eosinophilia
Erythema multiforme
Exacerbation of diabetes
Exfoliative dermatitis
Extrapyramidal effects
Falls
Fever
Galactorrhoea
Gamma glutamyl transferase (GGT) increased
Haemoglobin decrease
Headache
Hepatitis
Hyperglycaemia
Hyperprolactinaemia
Hypersensitivity reactions
Hyponatraemia
Hypothermia
Inappropriate secretion of antidiuretic hormone
Increase in serum ALT/AST
Increase in total cholesterol
Increased appetite
Increased blood pressure
Irritability
Jaundice
Lens changes
Leucopenia
Lymphadenopathy
Menstrual disturbances
Neuroleptic malignant syndrome
Neutropenia
Nightmares
Orthostatic hypotension
Palpitations
Peripheral oedema
Priapism
Prolongation of QT interval
Pyrexia
Rash
Reduced neutrophil count
Reduced platelet count
Restless legs
Rhabdomyolysis
Rhinitis
Seizures
Sexual dysfunction
Sleep walking
Somnolence
Stevens-Johnson syndrome
Stroke
Sudden unexplained death
Syncope
Tachycardia
Tardive dyskinesia
Thrombocytopenia
Torsades de pointes
Toxic epidermal necrolysis
Venous thrombosis
Ventricular arrhythmias
Vomiting
Weight gain
Withdrawal symptoms
Effects on Laboratory Tests
There have been reports of false positive results in enzyme immunoassays for methadone and tricyclic antidepressants in patients who have taken quetiapine. Confirmation of questionable immunoassay screening results by an appropriate chromatographic technique is recommended.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: September 2014
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Quetiapine 25mg film-coated tablets. Actavis UK Ltd. Revised February 2013.
Summary of Product Characteristics: Quetiapine 100mg film-coated tablets. Actavis UK Ltd. Revised February 2013.
Summary of Product Characteristics: Quetiapine 150mg film-coated tablets. Actavis UK Ltd. Revised February 2013.
Summary of Product Characteristics: Quetiapine 200mg film-coated tablets. Actavis UK Ltd. Revised February 2013.
Summary of Product Characteristics: Quetiapine 300mg film-coated tablets. Actavis UK Ltd. Revised February 2013.
Summary of Product Characteristics: Quetiapine 25mg film-coated tablets. Aurobindo Pharma - Milpharm Ltd. Revised August 2012.
Summary of Product Characteristics: Quetiapine 100mg film-coated tablets. Aurobindo Pharma - Milpharm Ltd. Revised August 2012.
Summary of Product Characteristics: Quetiapine 150mg film-coated tablets. Aurobindo Pharma - Milpharm Ltd. Revised August 2012.
Summary of Product Characteristics: Quetiapine 200mg film-coated tablets. Aurobindo Pharma - Milpharm Ltd. Revised August 2012.
Summary of Product Characteristics: Quetiapine 300mg film-coated tablets. Aurobindo Pharma - Milpharm Ltd. Revised August 2012.
Summary of Product Characteristics: Quetiapine Rosemont 20mg/ml Oral Suspension. Revised June 2016.
Summary of Product Characteristics: Seroquel 25mg, 100mg, 150mg, 200mg, 300mg film-coated tablets. AstraZeneca UK Ltd. Revised May 2020.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed). Record 233 - Quetiapine
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last revised: June 8, 2014
Last accessed: September 4, 2014
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 14 September 2017
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