Apomorphine parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Solution for infusion or injection containing apomorphine
Drugs List
Therapeutic Indications
Uses
Parkinson's. Motor fluctuations inadequately controlled by dopaminergics
Dosage
Treatment with apomorphine should only start once the patient's treatment with levodopa, with or without dopamine agonists, has been optimised.
The optimal dosage of apomorphine should be determined on an individual patient basis.
Patients using apomorphine should be capable of recognising the onset of hypokinetic ("off") episodes and be capable of injecting themselves or have a carer able to inject them when required.
Adults
Intermittent injections
Determination of threshold dose by incremental dosing schedule:
Initially 1mg of apomorphine hydrochloride (approximately 15 to 20micrograms/kg) is injected subcutaneously during a hypokinetic period and the patient observed over 30 minutes for a motor response.
If there is no response, or the response is inadequate, a second dose of 2mg is injected subcutaneously after at least 40 minutes, and the patient observed for an adequate response for a further 30 minutes.
The dosage may be increased by incremental injections with at least a 40 minute interval between succeeding injections, until a satisfactory response is obtained (not exceeding the maximum for a single injection of 10mg or maximum total daily dose of 100mg).
Establishment of treatment:
Once the appropriate dose is determined a single subcutaneous injection may be given, into the lower abdomen or outer thigh, at the first sign of a hypokinetic episode and the patient observed for the next hour. Alterations in dosage may be made according to patient response, but once the dose is established for an individual patient it remains relatively constant.
Precautions for continuing treatment:
The daily dose varies widely between individual patients and is typically within the range 3 to 30mg daily in 1 to 12 divided doses (maximum single bolus dose 10mg, maximum total daily dose 100mg).
Once treatment is established it may be possible to reduce the dose of any concomitant levodopa. Due to variation in patient response this reduction needs to be managed by an experienced physician. The dose of domperidone may also be gradually reduced, but successfully discontinued in only a few patients without any vomiting or hypotension.
Continuous infusion:
Patients who have shown a good "on" response during the initiation phase, but whose overall control remains unsatisfactory using bolus injections, or who require more than 10 injections daily; may be started on, or transferred to, continuous subcutaneous infusion using a minipump or syringe driver. Infusions sites should be changed every 12 hours and be run during waking hours only unless the patient is experiencing severe night time problems.
Tolerance to the therapy does not seem to occur as long as there is an overnight period without treatment of at least 4 hours.
Initially the infusion should be started at a rate of 1mg apomorphine hydrochloride per hour and then increased according to individual response each day at a rate not exceeding 0.5 mg per hour at intervals of not less than 4 hours. Hourly infusion rates may vary between 1mg and 4mg (0.014 to 0.06mg/kg/hour), and may need supplementing with intermittent bolus boosts via the pump system as necessary.
Additional intermittent bolus doses may be required in some patients. A reduction in dosage of concomitant dopamine agaonist may be considered.
Contraindications
Children under 18 years
Dementia
Hepatic impairment
Long QT syndrome
Psychosis
Respiratory depression
Torsade de pointes
Precautions and Warnings
Debilitation
Elderly
Family history of long QT syndrome
Predisposition to nausea and vomiting
Predisposition to orthostatic hypotension
Breastfeeding
Cardiovascular disorder
Congestive cardiac failure
Electrolyte imbalance
History of torsade de pointes
Neuropsychiatric disorders
Postural hypotension
Pregnancy
Pulmonary disease
Renal impairment
Advise patient/carer risk of dopamine dysregulation syndrome (DDS)
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Advise patient not to drive until they know how the medicine affects them
Advise patient that sudden onset sleep episodes may affect ability to drive
Advise patient this medicine may be subject to driving restrictions
Treatment to be initiated and supervised by a specialist
Some brands contain metabisulfite, may cause bronchospasm/allergies
Do not use if the solution is green
Domperidone prophylaxis required for at least 2 days before first use
For subcutaneous use only
Rotate injection sites to minimise the risk of hypertrophy
Perform ECG before and during treatment
Monitor haematological parameters periodically
Monitor regularly for frequency or severity of adverse events
Monitor serum electrolytes
Review treatment if impulse control disorders symptoms occur
Advise patient to report any signs of cardiac arrhythmias
Dopamine agonists have been associated with pathological gambling
Monitor for haemolytic anaemia: When used in combination with levodopa
Avoid abrupt withdrawal
Reduce dose or discontinue if sudden onset of sleep during daily activities
Advise patient/carer about symptoms of impulse control disorders
Treatment may have the potential for QT prolongation, particularly during concomitant treatment with domperidone. An ECG should be performed prior to initiating domperidone, during the treatment initiation phase and as clinically indicated thereafter. Re-assess risk factors for QT prolongation at each medical visit.
Use caution in patients with concomitant neuropsychiatric disorders as they may be exacerbated by use of apomorphine.
Pregnancy and Lactation
Pregnancy
Use apomorphine with caution during pregnancy.
Animal studies do not indicate teratogenic effects but potential risk to humans is unknown. The manufacturers state apomorphine should only be used during pregnancy if clearly necessary.
Lactation
Use apomorphine with caution during breastfeeding.
It is not known whether apomorphine is excreted in breast milk. A decision on whether to continue/discontinue breastfeeding or continue/discontinue therapy should be made, taking into account the benefit of breastfeeding to the child and the benefit of apomorphine to the mother.
Effects on Ability to Drive and Operate Machinery
This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them.
Side Effects
Aggression
Agitation
Allergic reaction
Anaphylaxis
Breathing difficulties
Bronchospasm
Bruising
Cognitive impairment
Confusion (transient)
Drowsiness
Dyskinesia
Eosinophilia
Erythema at injection site
Euphoria
Falls
Haemolytic anaemia
Hallucinations
Hypersalivation
Hypersexuality
Increased libido
Induration (injection site)
Irritation (localised)
Itching sensation (local)
Light-headedness
Nausea
Necrosis (injection site)
Neuropsychiatric disturbances
Nodules (injection site)
Pain
Panniculitis
Pathological gambling
Peripheral oedema
Personality change
Perspiration
Positive Coombs test
Postural hypotension
Postural instability
Pruritus
Rash
Restlessness
Sedation
Somnolence
Syncope
Tachycardia
Tachypnoea
Tenderness (injection site)
Thrombocytopenia
Tremor
Ulceration (injection site)
Vomiting
Yawning
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: December 2018
Reference Sources
Summary of Product Characteristics: APO-Go PFS 5 mg/ml Solution for Infusion in Pre-filled Syringe. Britannia Pharmaceuticals Limited. Revised February 2018.
Summary of Product Characteristics: APO-Go ampoules 10 mg/ml for injection or infusion. Britannia Pharmaceuticals Limited. Revised February 2018.
Summary of Product Characteristics: APO-Go Pen 10 mg/ml Solution for Injection. Britannia Pharmaceuticals Limited. Revised February 2018.
Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 6 January 2015 New drug driving offence implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 6 January 2015
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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