Quetiapine

Registered South African indications:

• Schizophrenia
• Bipolar disorder
• Major depressive disorder

Contraindications

South African recommendations

Film-coated tablet and tablet

• Hypersensitivity to quetiapine or to any of any of its excipients
• Pregnancy as safety has not been demonstrated
• Lactation as safety has not been demonstrated
• Safety and efficacy in children and adolescents have not been demonstrated
• Advanced liver and renal function impairment, as safety has not been demonstrated

XR tablet

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy as safety has not been demonstrated
• Lactation as safety has not been demonstrated

Recommendations in other jurisdictions

• Hypersensitivity to the active substance or to any of the excipients
• Concomitant administration of cytochrome P450 3A4 inhibitors, such as HIV protease inhibitors, azole-antifungal agents, erythromycin, clarithromycin and nefazodone

Cautions

• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Mild to moderate renal impairment (fct, tab) (South African recommendations)
• Mild to moderate hepatic impairment (fct, tab) (South African recommendations)
• Hepatic impairment (XR tab) (South African recommendations)
• Hepatic impairment (Recommendations in other jurisdictions)
• Elderly
• Abrupt withdrawal
• Children
• History of drug-induced neutropenia
• History of drug or alcohol abuse
• History of suicidal ideation
• History of suicide-related events
• QT prolongation or risk factors thereof
• Cardiovascular disease
• Cerebrovascular disease
• Risk of sleep apnoea
• Risk of aspiration pneumonia
• Risk of venous thromboembolism
• Risk of pancreatitis
• Epilepsy
• Existing low white blood cell count
• History of urinary retention
• Prostatic hypertrophy
• Intestinal obstruction or related conditions
• Increased intraocular pressure 
• Narrow angle glaucoma
• Diabetes mellitus
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption 
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: fct, tab, extended release tab (XR tab)

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Film-coated tablet and tablet

Schizophrenia

• Oral (fct, tab): Initial: Day 1: 25mg, 12hrly; Day 2: 50mg, 12hrly; Day 3: 100mg, 12hrly; Day 4: 150mg, 12hrly with or without food; From Day 4 onwards: Titrate to an effective dose range of 300-450mg/day based on clinical response and patient tolerability; Dose may be adjusted in some patients within the range of 150-750mg/day; Max: 750mg/24hrs

Manic episodes associated with bipolar disorder

• Oral (fct, tab): Initial: Day 1: 50mg, 12hrly; Day 2: 100mg, 12hrly; Day 3: 150mg, 12hrly; Day 4: 200mg, 12hrly with or without food; Further dosages: Adjust dosage up to 800mg/day by day 6 in increments of no more than 200mg/day; Dose adjustment can be made based on clinical response and patient tolerability, within the range of 200-800mg/day; Usual effective dose: 400-800mg/day; Max: 800mg/24hrs

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Safety and efficacy beyond 12 weeks have not been demonstrated

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Continued treatment at higher doses should only be considered as a result of careful consideration of the benefit risk assessment for an individual patient

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XR tablet

Schizophrenia
Preventing relapse in stable schizophrenic patients who have been maintained on XR tab
Manic episodes associated with bipolar disorder

• Oral (XR tab): Day 1: 300mg, dly; Day 2: 600mg, dly; After day 2: Up to 800mg, dly; Effective dose range: 400-800mg/day, based on clinical response and patient tolerability; Max: 800mg/24hrs

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The safety of doses above 800mg/day has not been established in the clinical trials

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Depressive episodes associated with bipolar disorder

• Oral (XR tab): Day 1: 50mg, dly; Day 2: 100mg, dly; Day 3: 200mg, dly; Day 4: 300 mg, dly; Day 5: Up to 400mg, dly; Day 8: Up to 600mg, dly in the evening

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Antidepressant efficacy was demonstrated with quetiapine at 300mg and 600mg, however no additional benefit was seen in the 600mg group during short-term treatment

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Preventing recurrence in maintenance treatment of bipolar disorder
- Patients who have responded to quetiapine XR tab in combination therapy with a mood stabiliser (lithium or valproate) for acute treatment of bipolar disorder (Additional agent required)

• Oral (XR tab): Continue at the same dose; Re-adjust to 400-800mg, dly depending on clinical response and tolerability of the patient

- Patients who have responded to quetiapine XR tab for acute treatment of bipolar disorder

• Oral (XR tab): Continue at the same dose; Re-adjust to 300-800mg, dly depending on clinical response and tolerability of the patient

Major depressive disorder

• Oral (XR tab): Day 1-2: 50mg, dly; Day 3-4: 150mg, dly; Further adjustments can be made upwards or downwards: Recommended dose range: 50-300mg, dly depending on clinical response and tolerability of the patient

- Preventing relapse in stable major depressive disorder patients who have been maintained on XR tab

• Oral (XR tab): Continue at the effective dose used during initial treatment; Adjust dose within the recommended dose range depending upon the clinical response and tolerability of the patient

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Switching from quetiapine immediate-release tablets: For more convenient dosing, patients who are currently being treated with divided doses of quetiapine immediate release tablets may be switched to quetiapine XR tablets at the equivalent total daily dose taken once daily. Individual dosage adjustments may be necessary

Not established for use in children

Pregnancy

South African recommendations

• Contraindicated
• Quetiapine is contraindicated during pregnancy, as safety has not been demonstrated
• Following some pregnancies in which quetiapine was used, neonatal withdrawal symptoms have been reported

Recommendations in other jurisdictions

• Caution; positive evidence of risk in animal studies
• First trimester: The moderate amount of published data from exposed pregnancies (i.e. between 300-1,000 pregnancy outcomes), including individual reports and some observational studies do not suggest an increased risk of malformations due to treatment
• However, based on all available data, a definite conclusion cannot be drawn
• Animal studies have shown reproductive toxicity. Therefore, quetiapine should only be used during pregnancy if the benefits justify the potential risks
• Third trimester: Neonates exposed to antipsychotics (including quetiapine) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery
• There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully

Breastfeeding

South African recommendations

• Contraindicated
• Quetiapine is contraindicated during lactation, as safety has not been demonstrated
• There have been published reports of quetiapine excretion into human breast milk, however the degree of excretion was not consistent

Recommendations in other jurisdictions

• Caution; not recommended
• Based on very limited data from published reports on quetiapine excretion into human breast milk, excretion of quetiapine at therapeutic doses appears to be inconsistent
• Due to lack of robust data, a decision must be made whether to discontinue breastfeeding or to discontinue quetiapine therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Renal Impairment

South African recommendations

Film-coated tablet and tablet

• Mild to moderate: Caution; no dose adjustment recommended
• The clearance of quetiapine is reduced by approximately 25% in patients with renal impairment
• Severe: Contraindicated

XR tab

• No dose adjustment recommended

Recommendations in other jurisdictions

• No dose adjustment recommended

Hepatic Impairment

South African recommendations

Film-coated tablet and tablet

• Mild to moderate: Caution; no dose adjustment recommended
  The clearance of quetiapine is reduced by approximately 25% in patients with hepatic impairment
  Quetiapine is extensively metabolised by the liver, and therefore should be used with caution in patients with known hepatic impairment
• Severe: Contraindicated

XR tab

• Caution; dose adjustment recommended
  Oral (XR tab): Initial: 50mg, daily; Titrate by 50mg, at intervals of 1 day; Until an effective dosage, depending on the clinical response and tolerability of the individual patient

Recommendations in other jurisdictions

• Caution; dose adjustment recommended
  Oral (XR tab): Initial: 50mg, daily; Titrate by 50mg, at intervals of 1 day; Until an effective dosage, depending on the clinical response and tolerability of the individual patient
  Oral (fct, tab): Initial: 25mg/day; The dosage should be increased daily with increments of 25-50mg/day until an effective dosage, depending on the clinical response and tolerability of the individual patient

Elderly

South African recommendations

Film-coated tablet and tablet

• Caution; dose adjustment recommended
  Oral (tab): Initiate at 25mg/day; Increased daily in increments of 25-50mg, to an effective dose

XR tab

• Caution; dose adjustment recommended
  Oral (XR tab): Initial: 50mg, daily; Titrate by 50mg, at intervals of 1 day; Until an effective dosage, depending on the clinical response and tolerability of the individual patient
  Major depressive disorder: Oral (XR tab): Initial: Day 1-3: 50mg, daily; Day 4: Increase to 100mg, if required; Day 8: Increase to 150mg, if required; Titrate up to 300mg, depending on the clinical response and tolerability of the individual patient

Recommendations in other jurisdictions

• Caution; dose adjustment recommended
  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 30-50% in elderly subjects when compared to younger patients. Efficacy and safety have not been evaluated in patients over 65 years with depressive episodes in the framework of bipolar disorder.
  Oral (XR tab): Initial: 50mg/day; The dose can be increased in increments of 50mg/day to an effective dose, depending on the clinical response and tolerability of the individual patient
  Major depressive disorder: Oral (XR tab): Initial: Day 1-3: 50mg/day; Day 4: Increase to 100mg/day; Day 8: Increase to 150mg/day; Based on individual patient evaluation, if dose increase to 300mg/day is required this should not be prior to Day 22 of treatment

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Neuroleptic malignant syndrome
• Headache
• Dizziness
• Somnolence
• Extrapyramidal symptoms
• Tardive dyskinesia
• Seizures
• Syncope
• Restless legs syndrome
• Nightmares
• Sleep apnoea syndrome
• Suicidal ideation
• Suicidal behaviour
• Somnambulism
• Sexual dysfunction
• Irritability
• Fatigue
• Hypothermia
• Withdrawal symptoms
• Neonatal drug withdrawal syndrome

Cardiovascular Disorders

• Tachycardia
• Palpitations
• Bradycardia
• QT prolongation
• Orthostatic hypotension
• Venous thromboembolism

Respiratory Disorders

• Dyspnoea
• Rhinitis

Gastrointestinal Disorders

• Dry mouth
• Constipation
• Dyspepsia
• Vomiting
• Dysphagia
• Intestinal obstruction
• Ileus

Hepatobiliary Disorders

• Increased hepatic enzymes
• Jaundice
• Hepatitis
• Pancreatitis

Genitourinary Disorders

• Urinary retention
• Priapism
• Menstrual disorder

Endocrine and Metabolic Disorders

• Hyperprolactinaemia
• Hypothyroidism
• Syndrome of inappropriate antidiuretic hormone secretion
• Dyslipidaemia
• Hyperglycaemia
• Increased appetite
• Hyponatraemia
• Metabolic syndrome
• Galactorrhoea
• Breast swelling
• Increased serum creatine phosphokinase

Musculoskeletal Disorders

• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Angioedema
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Erythema multiforme

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis
• Agranulocytosis
• Fever
• Anaemia
• Leukopenia
• Neutropenia
• Eosinophilia
• Thrombocytopenia

Sensory Disorders

• Blurred vision

• CYP3A4 inhibitors
• HIV protease inhibitors
• Azole-antifungal agents
• Erythromycin
• Clarithromycin
• Nefazodone
• CYP3A4 inducers
• QT prolonging agents 
• Central nervous system depressants
• Agents with anticholinergic effects
• Lithium
• Sodium valproate

• Blood pressure
• Weight
• Electrolytes
• Hepatic function
• Thyroid function tests
• Blood glucose
• Lipid profile

Specific cases may require

• Vital signs
• Full blood count
• Ophthalmic examination

Quetiapine is an atypical antipsychotic agent. Quetiapine and the active human plasma metabolite, norquetiapine interact with a broad range of neurotransmitter receptors. Quetiapine and norquetiapine exhibit affinity for brain serotonin (5HT) and dopamine D- and D- receptors. It is this combination of receptor antagonism with a higher selectivity for 5HT relative to D- receptors, which is believed to contribute to the clinical antipsychotic properties and low extrapyramidal undesirable effect (EPS) liability of quetiapine compared to typical antipsychotics. Additionally, norequetiapine has high affinity for the norepinephrine transporter (NET). Quetiapine and norquetiapine have no appreciable affinity at benzodiazepine receptors but high affinity at histaminergic and adrenergic α- receptors, moderate affinity at adrenergic αreceptors. Quetiapine also has low or no affinity for muscarinic receptors, while norquetiapine has moderate to high affinity at several muscarinic receptors, which may explain anti-cholinergic (muscarinic effects). Inhibition of NET and partial agonist action at 5HT1A sites by norquetiapine may contribute to quetiapine prolonged release's therapeutic efficacy as an antidepressant.

Tablet 25mg

• Aroquet (Accord)
• Dopaquel (Dr Reddy's)
• Kizofrin (Aurobindo)
• Mylan Quetiapine (Xixia)
• Psyquet (Sandoz)
• Quesara 25mg (Macleods Pharmaceuticals SA)
• Quetiapine Biotech (Biotech)
• Quetoser (Cipla)
• Quetz 25mg (Aurobindo Pharma)
• Serez (Adcock)
• Seroquel (AstraZeneca) originator
• Sizocam 25mg (Alkem Laboratories)
• Sizonorm (Ranbaxy)
• Spec Quetiapine fct (Specpharm) 
• Truvalin (AstraZeneca)
• Zimbiquet (Zimbili Pharma)

Tablet 100mg

• Aroquet (Accord)
• Dopaquel (Dr Reddy's)
• Kizofrin (Aurobindo)
• Mylan Quetiapine (Xixia)
• Psyquet (Sandoz)
• Quesara 100mg (Macleods Pharmaceuticals SA)
• Quetiapine Biotech (Biotech)
• Quetoser (Cipla)
• Quetz 100mg (Aurobindo Pharma)
• Serez (Adcock Ingram)
• Seroquel (AstraZeneca) originator
• Sizocam 100mg (Alkem Laboratories)
• Sizonorm (Ranbaxy)
• Spec Quetiapine fct (Specpharm)
• Truvalin (AstraZeneca)
• Zimbiquet (Zimbili Pharma)

Tablet 150mg

• Spec Quetiapine fct (Specpharm)

Tablet 200mg

• Aroquet (Accord)
• Dopaquel (Dr Reddy's)
• Kizofrin (Aurobindo)
• Mylan Quetiapine (Xixia)
• Psyquet (Sandoz)
• Quesara 200mg (Macleods Pharmaceuticals SA)
• Quetiapine 200 Teva (Teva Pharmaceuticals)
• Quetiapine Biotech (Biotech)
• Quetoser (Cipla)
• Quetz 200mg (Aurobindo Pharma)
• Serez (Adcock)
• Seroquel (AstraZeneca) originator
• Sizocam 200mg (Alkem Laboratories)
• Sizonorm (Ranbaxy)
• Spec Quetiapine fct (Specpharm)
• Truvalin (AstraZeneca)
• Zimbiquet (Zimbili Pharma)

Tablet 300mg

• Aroquet (Accord)
• Dopaquel (Dr Reddy's)
• Kizofrin (Aurobindo)
• Mylan Quetiapine (Xixia)
• Psyquet (Sandoz)
• Quesara 300mg (Macleods Pharmaceuticals SA)
• Quetoser (Cipla)
• Quetiapine 300 Teva (Teva Pharmaceuticals)
• Quetiapine Biotech (Biotech)
• Serez (Adcock)
• Seroquel (AstraZeneca) originator
• Sizocam 300mg (Alkem Laboratories)
• Sizonorm (Ranbaxy)
• Spec Quetiapine fct (Specpharm)
• Truvalin (AstraZeneca)
• Zimbiquet (Zimbili Pharma)

Tablet xr 50mg

• Aroquet XR 50mg (Accord Healthcare)
• Quero XR 50mg (Pharma Dynamics)
• Seroquel XR (AstraZeneca) originator
• Truvalin XR (AstraZeneca)

Tablet xr 150mg

• Aroquet XR 150mg (Accord Healthcare)
• Quero XR 150mg (Pharma Dynamics)
• Quesara XR 150mg (Macleods Pharmaceuticals SA)
• Seroquel XR (AstraZeneca) originator
• Truvalin XR (AstraZeneca)

Tablet xr 200mg

• Aroquet XR 200mg (Accord Healthcare)
• Quero XR 200mg (Pharma Dynamics)
• Quesara XR 200mg (Macleods Pharmaceuticals SA)
• Seroquel XR (AstraZeneca) originator
• Truvalin XR (AstraZeneca)

Tablet xr 300mg

• Aroquet XR 300mg (Accord Healthcare)
• Quero XR 300mg (Pharma Dynamics)
• Quesara XR 300mg (Macleods Pharmaceuticals SA)
• Seroquel XR (AstraZeneca) originator
• Truvalin XR (AstraZeneca)

Tablet xr 400mg

• Aroquet XR 400mg (Accord Healthcare)
• Quero XR 400mg (Pharma Dynamics)
• Quesara XR 400mg (Macleods Pharmaceuticals SA)
• Seroquel XR (AstraZeneca) originator
• Truvalin XR (AstraZeneca)