Drug reference
Treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP) in patients with stage 1 symptomatic polyneuropathy to delay peripheral neurological impairment (initiated under specialist supervision) ▶BY MOUTH ▶Adult: 20 mg once daily
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Tafamidis should be prescribed in addition to standard treatment, but before liver transplantation; it should be discontinued in patients who undergo liver transplantation.
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▶Common or very common Abdominal pain upper. diarrhoea . increased risk of infection
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Exclude pregnancy before treatment and ensure effective contraception during and for one month after stopping treatment.
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Avoid (toxicity in animal studies).
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Avoid—present in milk in animal studies.
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Manufacturer advises caution in severe impairment (no information available).
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There can be variation in the licensing of different medicines containing the same drug. Capsule CAUTIONARY AND ADVISORY LABELS 25 ▶Vyndaqel (Pfizer Ltd) A Tafamidis 20 mg Vyndaqel 20mg capsules | 30 capsule P £10,685.00 (Hospital only) 4.2 Parkinson’s disease Parkinson’s disease Description of condition Parkinson’s disease is a progressive neurodegenerative condition resulting from the death of dopaminergic cells of the substantia nigra in the brain. Patients with Parkinson’s disease classically present with motor-symptoms including hypokinesia, bradykinesia, rigidity, rest tremor, and postural instability. Non-motor symptoms include dementia, depression, sleep disturbances, bladder and bowel dysfunction, speech and language changes, swallowing problems and weight loss. g Patients with suspected Parkinson’s disease should be referred to a specialist and reviewed every 6 to 12 months. When Parkinson’s disease diagnosis is confirmed, patients should be advised to inform the DVLA and their car insurer. h Aims of treatment Parkinson’s disease is an incurable progressive condition, and the aim of treatment is to control the symptoms and to improve the patient’s quality of life. Non-drug treatment g Parkinson’s disease patients should be offered physiotherapy if balance or motor function problems are present, speech and language therapy if they develop communication, swallowing or saliva problems, and occupational therapy if they experience difficulties with their daily activities. Dietitian referral should be considered. h Drug treatment Drug management of motor symptoms in Parkinson’s disease First-line treatment g In early stages of Parkinson’s disease, patients whose motor symptoms decrease their quality of life should be offered levodopa combined with carbidopa (co-careldopa p. 434) or benserazide (co-beneldopa p. 433). Parkinson’s disease patients whose motor symptoms do not affect their quality of life, could be prescribed a choice of levodopa, non-ergot-derived dopamine-receptor agonists (pramipexole p. 442, ropinirole p. 444 or rotigotine p. 445) or monoamine-oxidase-B inhibitors (rasagiline p. 446 or selegiline hydrochloride p. 447). Before starting antiparkinsonian treatment, the patient’s individual circumstances, including symptoms, comorbidities and preferences, should be discussed together with the potential benefits and harms from the different drugs available. Patients and their carers should be informed about the risk of adverse reactions from antiparkinsonian drugs, including psychotic symptoms, excessive sleepiness and sudden onset of sleep with dopamine-receptor agonists, and impulse control disorders with all dopaminergic therapy (especially dopamine-receptor agonists). For further information see Impulse control disorders. h Levodopa treatment is associated with motor complications, including response fluctuations and dyskinesias. Response fluctuations are characterised by large variations in motor performance, with normal function during the ‘on’ period, and weakness and restricted mobility during the ‘off’ period. ‘End-of-dose’ deterioration with progressively shorter duration of benefit can also occur. Modified-release preparations may help with ‘end-of-dose’ deterioration or nocturnal immobility. The overall improvement in motor performance is more noticeable with levodopa than with dopamine-receptor Nervous system agonists, and motor complications are less likely to occur with dopamine-receptor agonists when used alone long-term. Conversely, excessive sleepiness, hallucinations, and impulse control disorders are more likely to occur with dopamine-receptor agonists than with levodopa. g To avoid the potential for acute akinesia or neuroleptic malignant syndrome, antiparkinsonian drug concentrations should not be allowed to fall suddenly due to poor absorption or abrupt withdrawal. h Adjuvant therapy g If a patient with Parkinson’s disease develops dyskinesia or motor fluctuations, specialist advice should be sought before modifying antiparkinsonian drug therapy. Patients who develop dyskinesia or motor fluctuations despite optimal levodopa therapy should be offered a choice of non-ergotic dopamine-receptor agonists (pramipexole, ropinirole, rotigotine), monoamine oxidase B inhibitors (rasagiline or selegiline hydrochloride) or COMT inhibitors (entacapone p. 432 or tolcapone p. 432) as an adjunct to levodopa. An ergot-derived dopamine-receptor agonist (bromocriptine p. 439, cabergoline p. 440 or pergolide p. 441) should only be considered as an adjunct to levodopa if symptoms are not adequately controlled with a non-ergot-derived dopamine- receptor agonist. If dyskinesia is not adequately managed by modifying existing therapy, amantadine hydrochloride p. 437 should be considered. h Drug management of non-motor symptoms in Parkinson’s disease Daytime sleepiness and sudden onset of sleep g Patients who experience daytime sleepiness or sudden onset of sleep, should have their Parkinson’s drug treatment adjusted under specialist medical guidance. If reversible pharmacological and physical causes have been excluded, modafinil p. 514 should be considered to treat excessive daytime sleepiness, and treatment should be reviewed at least every 12 months. Patients with Parkinson’s disease who have daytime sleepiness or sudden onset of sleep should be advised not to drive, to inform the DVLA about their symptoms, and to think about any occupational hazards. h Nocturnal akinesia g When treating nocturnal akinesia in patients with Parkinson’s disease, levodopa or oral dopamine-receptor agonists should be considered as first-line options and rotigotine p. 445 as second-line (if both levodopa or oral dopamine-receptor agonists are ineffective). h Postural hypotension g Patients with Parkinson’s disease who develop postural hypotension should have their drug treatment reviewed to address any pharmacological cause. If drug therapy is required, midodrine hydrochloride p. 199 should be considered as the first option and fludrocortisone acetate p. 713 [unlicensed indication] as an alternative. h Depression See Antidepressant drugs p. 376. Psychotic symptoms g Hallucinations and delusions need not be treated if they are well tolerated. Otherwise, the dosage of any antiparkinsonism drugs that might have triggered hallucinations or delusions should be reduced, taking into account the severity of symptoms and possible withdrawal effects. Specialist advice should be sought before modifying drug treatment. In Parkinson’s disease patients with no cognitive impairment, quetiapine p. 419 [unlicensed indication] can be considered to treat hallucinations and delusions. If standard treatment is not effective, clozapine p. 414 should be offered to treat hallucinations and delusions in patients with Nervous system Parkinson’s disease. h It is important to acknowledge that other antipsychotic medicines (such as phenothiazines and butyrophenones) can worsen the motor features of Parkinson’s disease. Rapid eye movement sleep behaviour disorder g Clonazepam p. 354 [unlicensed indication] or melatonin p. 511 [unlicensed indication] should be considered to treat rapid eye movement sleep behaviour disorder in Parkinson’s patients once possible pharmacological causes have been addressed. h Drooling of saliva g Drug treatment for drooling of saliva in patients with Parkinson’s disease should only be considered if non-drug treatment such as speech and language therapy is not available or is ineffective. Glycopyrronium bromide p. 1405 [unlicensed indication] should be considered as first-line treatment and botulinum toxin type A p. 425 [unlicensed indication] as second-line. Other antimuscarinic drugs, should only be considered if the risk of cognitive adverse effects is thought to be minimal; topical preparations, such as atropine [unlicensed indication], should be used if possible to reduce the risk of adverse events. h Parkinson’s disease dementia g An acetylcholinesterase inhibitor should be offered to patients with mild-to-moderate Parkinson’s disease dementia and considered for patients with severe Parkinson’s disease dementia [unlicensed indications apart from rivastigmine capsules and oral solution p. 318 for the treatment of mild-to-moderate dementia in patients with Parkinson’s disease]. If acetylcholinesterase inhibitors are not tolerated or contra-indicated, memantine hydrochloride p. 320 [unlicensed indication] should be considered. h For further information see Dementia p. 315 Advanced Parkinson’s disease g Patients with advanced Parkinson’s disease can be offered apomorphine hydrochloride p. 438 as intermittent injections or continuous subcutaneous infusions. h To control nausea and vomiting associated with apomorphine, the manufacturers recommend that administration of domperidone p. 451 [unlicensed in those weighing less than 35 kg] will usually need to be started two days before apomorphine therapy, and then discontinued as soon as possible. To reduce the risk of serious arrhythmia due to QT prolongation associated to the concomitant use of domperidone p. 451 and apomorphine hydrochloride p. 438, the MHRA and CHM (2016) recommend an assessment of cardiac risk factors and ECG monitoring and to ensure that the benefits outweighs the risks when initiating treatment. In addition, the MHRA and CHM (2019) have released important safety information and restrictions regarding the use of domperidone for nausea and vomiting in those weighing less than 35 kg, and a reminder of contra- indications. For further information, see Important safety information for domperidone p. 451. Levodopa-carbidopa intestinal gel is used for the treatment of advanced levodopa-responsive Parkinson’s disease with severe motor fluctuations and hyperkinesia or dyskinesia. The gel is administered with a portable pump directly into the duodenum or upper jejunum. g Deep brain stimulation should only be considered for patients with advanced Parkinson’s disease whose symptoms are not adequately controlled by best drug therapy. h Impulse control disorders Impulse control disorders (compulsive gambling, hypersexuality, binge eating, or obsessive shopping) can develop in a person with Parkinson’s disease who is on any dopaminergic therapy at any stage in the disease course particularly if the patient has a history of previous impulsive behaviours, alcohol consumption, or smoking. g Patients should be informed about the different types of impulse control disorders and that dopamine-receptor agonist therapy may be reduced or stopped if problematic impulse control disorders develop. When managing impulse control disorders, dopamine- receptor agonist doses should be reduced gradually and patients should be monitored for symptoms of dopamine agonist withdrawal. Specialist cognitive behavioural therapy should be offered if modifying dopaminergic therapy is not effective. h Useful Resources Parkinson’s disease in adults. National Institute for Health and Care Excellence. NICE guideline 71. July 2017. www.nice.org.uk/guidance/NG71 ANTIMUSCARINICS
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20 mg once daily
First-line fragment. Read the complete Indications and Dose section above.
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