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Olanzapine parenteral prolonged release

Presentation

Prolonged release suspension for injection formulation of olanzapine.

Olanzapine embonate is the INN for olanzapine pamoate monohydrate.

Drugs List

  • olanzapine 210mg powder for prolonged release injection suspension
  • olanzapine 300mg powder for prolonged release injection suspension
  • olanzapine 405mg powder for prolonged release injection suspension
  • ZYPADHERA 210mg powder for prolonged release injection suspension
  • ZYPADHERA 300mg powder for prolonged release injection suspension
  • ZYPADHERA 405mg powder for prolonged release injection suspension
  • Therapeutic Indications

    Uses

    Maintenance treatment of schizophrenia

    Dosage

    Patients should be treated initially with oral olanzapine before administering olanzapine embonate for prolonged release suspension for injection, to establish tolerability and response.

    Patients should be monitored carefully for signs of relapse during the first one to two months of treatment.

    Adults

    In order to identify the first olanzapine embonate dose for all patients, the following scheme should be used:

    For patients on a target oral olanzapine dose of 10 mg/day
    Recommended starting dose: 210 mg/2 weeks or 405 mg/4 weeks.
    Maintenance dose after 2 months of olanzapine embonate prolonged release suspension for injection treatment: 150 mg/2 weeks or 300 mg/4 weeks.

    For patients on a target oral olanzapine dose of 15 mg/day
    Recommended starting dose: 300 mg/2 weeks.
    Maintenance dose after 2 months of olanzapine embonate prolonged release suspension for injection treatment: 210 mg/2 weeks or 405 mg/4 weeks.

    For patients on a target oral olanzapine dose of 20 mg/day
    Recommended starting dose: 300 mg/2 weeks.
    Maintenance dose after 2 months of olanzapine embonate prolonged release suspension for injection treatment: 300 mg/2 weeks.

    Elderly

    Olanzapine is not recommended for treatment in the elderly population (greater than 65 years) unless a well-tolerated and effective dose regimen using oral olanzapine has been established. A lower starting dose (150 mg/4 weeks) is not routinely indicated, but should be considered for those 65 and over when clinical factors warrant.

    Not recommended to be started in patients aged older than 75 years.

    Patients with Renal Impairment

    A lower starting dose (150 mg every 4 weeks) should be considered for patients with renal impairment.

    Patients with Hepatic Impairment

    A lower starting dose (150 mg every 4 weeks) should be considered for patients with hepatic impairment.

    In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh class A or B), the starting dose should be 150 mg every 4 weeks and only increased with caution

    Additional Dosage Information

    Patients should be monitored carefully for signs of relapse during the first one to two months of treatment. During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks. Patients should be closely monitored during this period. During treatment, dose may subsequently be adjusted on the basis of individual clinical status.

    Supplementation with oral olanzapine was not authorised in double-blind clinical studies. If oral olanzapine supplementation is clinically indicated, then the combined total dose of olanzapine from both formulations should not exceed the corresponding maximum oral olanzapine dose of 20 mg/day.

    Administration

    For intramuscular use only by deep intramuscular gluteal injection by a healthcare professional trained in the appropriate injection technique and in an environment where post-injection observation and access to appropriate medical care in the case of overdose can be assured.

    Contraindications

    Children under 18 years
    Predisposition to narrow angle glaucoma
    Breastfeeding
    Dementia
    Long QT syndrome
    Torsade de pointes

    Precautions and Warnings

    Family history of long QT syndrome
    Patients over 65 years
    Predisposition to venous thromboembolism
    Tobacco smoking
    Benign prostatic hyperplasia
    Cardiac hypertrophy
    Congestive cardiac failure
    Diabetes mellitus
    Disorder of lipid metabolism
    Electrolyte imbalance
    Elevated serum transaminases
    Hepatic cirrhosis
    Hepatic impairment
    Hepatitis
    History of myelosuppression
    History of seizures
    History of torsade de pointes
    Hypereosinophilic disorder
    Leucopenia
    Myeloproliferative disorder
    Myelosuppression
    Neutropenia
    Paralytic ileus
    Parkinson's disease
    Pregnancy
    Renal impairment

    Correct electrolyte disorders before treatment
    Reduce dose in patients with hepatic impairment
    Reduce dose in patients with renal impairment
    Advise ability to drive/operate machinery may be affected by side effects
    Monitor blood pressure in elderly
    Monitor ECG in patients at risk of QT prolongation
    Monitor patient for 3 hours after treatment
    Monitor patient's weight
    Monitor patients with existing or tendency towards diabetes mellitus
    Monitor serum electrolytes
    Monitor serum lipids
    Risk of narrow angle glaucoma
    Consider discontinuation if signs of tardive dyskinesia occur
    Discontinue if hepatitis develops
    Discontinue treatment if DRESS is suspected
    Increased risk for venous thromboembolism - take preventive measures
    May cause postural hypotension especially in elderly
    To discontinue, reduce dose gradually
    Discontinue if patient develops neuroleptic malignant syndrome
    Discontinue if severe skin reaction occurs
    Dose adjustment required if patient starts/stops smoking during therapy
    Slower metabolisers with 2+ factors(female,elderly,non-smoke):modify dosing
    Advise patient to avoid alcohol during treatment
    Advise patients to report skin rash

    Post-injection syndrome including reactions presenting with signs and symptoms consistent with olanzapine overdose were reported in patients following an olanzapine injection. The majority of these reactions were reported to be of mild to moderate severity. Patients should be observed for 3 hours in a healthcare facility each time olanzapine is administered.

    Prior to giving the injection, the healthcare professional should find out whether the patient is travelling alone to their destination. After observation for 3 hours in a healthcare facility, it should be confirmed that the patient is alert, orientated, and absent of signs and symptoms of overdose. Furthermore, the patient should be advised to be vigilant for signs and symptoms of overdose secondary to post-injection adverse reactions.

    Pregnancy and Lactation

    Pregnancy

    Olanzapine should be used with caution during pregnancy.

    The data available suggest that the risk associated with olanzapine treatment during pregnancy is low for both mother and foetus (Briggs, 2011). Reports on over 200 pregnancies exposed to olanzapine indicated no teratogenicity (Schaefer, 2007). Reproductive studies in rats and rabbits at doses up to 9 and 30 times the maximum dose respectively showed no evidence of teratogenicity.

    The data available suggest that the risk associated with olanzapine treatment during pregnancy is low for both mother and foetus (Schaefer, 2007).

    UK licensed product information notes that neonates exposed to antipsychotics during the third trimester are at a risk of adverse reactions including extrapyramidal and/or withdrawal symptoms which may vary in severity and duration following delivery. The effects include agitation, hypertonia, hypotonus, tremor, somnolence, respiratory distress and feeding disorders.

    NICE advises prescribers to take into account risk factors for gestational diabetes and weight gain if they are considering giving olanzapine to a woman who is pregnant. Risk assessment should also encompass family history, existing weight and ethnicity.

    When neuroleptics have been used up to delivery, observation of the neonate for at least 2 days is recommended. In order to prevent neonatal adaptation disorders, prescribers are advised to reduce the dose or even interrupt treatment in the days immediately preceding delivery.

    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 14-17 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

    Olanzapine is contraindicated during breastfeeding.

    The amount of olanzapine that can be absorbed from breast milk is very low and evidence indicates that the majority of nursing infants do not suffer side effects. However, sedation in infants has occurred. Further, the long-term potential for neurodevelopment toxicity in the infant should be considered before olanzapine is prescribed during lactation.

    NICE advises that Infants of mothers who are breastfeeding while taking psychotropic medication should be monitored for adverse reactions.

    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

    Aggression
    Agitation
    Akathisia
    Allergic reaction
    Alopecia
    Amenorrhoea
    Anaphylactic reaction
    Anticholinergic effects
    Asthenia
    Ataxia
    Bradycardia
    Breast enlargement
    Coma
    Confusion
    Constipation
    Convulsions
    Creatine phosphokinase increased
    Deep vein thrombosis (DVT)
    Delirium
    Disorientation
    Dizziness
    Drug rash with eosinophilia and systemic symptoms (DRESS)
    Dry mouth
    Dysarthria
    Dyskinesia
    Dystonia
    Elevated triglyceride levels
    Eosinophilia
    Erectile dysfunction
    Erythema
    Erythema at injection site
    Exacerbation of diabetes
    Extrapyramidal effects
    Falls
    Fatigue
    Gait abnormality
    Glucosuria
    Gynaecomastia
    Hallucinations
    Hepatitis
    Hyperglycaemia
    Hypersomnia
    Hypertension
    Hypothermia
    Increase in alkaline phosphatase
    Increase in plasma cholesterol
    Increase of liver transaminases
    Increased appetite
    Increased prolactin
    Injection site reactions
    Ketoacidosis
    Lethargy
    Leucopenia
    Local pain (injection site)
    Neuroleptic malignant syndrome
    Neutropenia
    Nodules (injection site)
    Oculogyric crisis
    Oedema
    Orthostatic hypotension
    Pancreatitis
    Parkinsonism
    Photosensitivity
    Pneumonia
    Priapism
    Prolongation of QT interval
    Pulmonary embolism
    Rash
    Reduced libido
    Rhabdomyolysis
    Rise in body temperature
    Sedation
    Seizures
    Serum bilirubin increased
    Somnolence
    Speech disturbances
    Stroke
    Sudden cardiac death
    Tardive dyskinesia
    Thrombocytopenia
    Thromboembolism
    Transient ischaemic attack
    Urinary hesitancy
    Urinary incontinence
    Urinary retention
    Ventricular fibrillation
    Ventricular tachycardia
    Weakness
    Weight gain

    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: June 2013

    Reference Sources

    British National Formulary, 65th Edition (March - September 2013) Pharmaceutical Press, London.

    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.

    Summary of Product Characteristics: Zypadhera 210 mg, 300 mg, and 405 mg, powder and solvent for prolonged release suspension for injection. Eli Lilly & Co Ltd. Revised February 2013.

    The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

    Antenatal and postnatal mental health. Clinical management and service guidance (Dated April 2007).
    National Institute for Health and Care Excellence (NICE)
    Available at: https://www.nice.org.uk/nicemedia/pdf/CG045NICEGuidelineCorrected.pdf
    Last accessed: June 7, 2013

    Specialist Pharmacy Service (SPS)
    Available at: https://www.sps.nhs.uk/
    What are the clinically significant drug interactions with tobacco smoking? Last revised: July 2020
    Last accessed: 07 December 2020

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