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Two newly funded medicines for Chronic Obstructive Pulmonary Disease (COPD)
Recommended treatments for COPD include long-acting muscarinic antagonists (LAMA), such as tiotropium, which act on a subtype of cholinergic receptor,
and long-acting beta agonists (LABA) such as salmeterol and formoterol fumarate. As of 1 November, 2014, two additional medicines in these classes are now
fully subsidised: glycopyrronium, a LAMA, and indacaterol, a LABA. This offers a wider range of treatment options for patients with COPD. Glycopyrronium
subsidy is subject to Special Authority approval, with a number of restrictions. Indacaterol is subsidised without restriction.
The exact prevalence of COPD in New Zealand is unknown, but it has been estimated to affect approximately 14% of people
aged 40 years and older.1 Smoking is the main risk factor.2 Primary care clinicians have an important role in identifying
patients at risk of COPD, diagnosing COPD, referring patients to respiratory specialists and providing ongoing management.
Long-acting muscarinic antagonist (LAMA) or beta-agonist (LABA) inhalations are the recommended first-line treatment
for many patients with COPD.3 These include formoterol (also known as eformoterol), tiotropium and salmeterol, which were
already fully or partly subsidised, and the newly subsidised glycopyrronium and indacaterol. Other treatment options include
short-acting medicines such as salbutamol (a short-acting beta-agonist) and ipratropium bromide (a short-acting muscarinic
antagonist), both of which are fully subsidised.
COPD is a progressive condition and stopping smoking in those patients who still smoke is one of the main interventions
to improve survival, particularly as many patients will die of cardiac disease rather than respiratory complications.2,
Access and funding criteria
Glycopyrronium is fully subsidised, subject to Special Authority approval. Initial applications and renewals can be
applied for by general practitioners, and both are valid for two years.
A number of restrictions for the initiation of glycopyrronium are in place, including that the patient must have:
- Previously trialled ipratropium bromide for one month
- Grade 4 or 5 breathlessness according to the Medical Research Council (UK) dyspnoea scale*
- A FEV1 of below 60% of predicted FEV1
* Grade 4 breathlessness under the MRC dyspnoea scale means stopping for breath after about 100 metres or after walking
for a few minutes on the level, and Grade 5 means being too breathless to leave the house, or breathless when dressing
Patients should also not be smokers, or alternatively have been offered smoking cessation advice, and they must have
been offered an up-to-date influenza vaccination. The same Special Authority criteria apply to tiotropium, and patients
can be switched between these two medicines without the need to reapply for Special Authority. However, funding is only
for one of these medicines at a time and tiotropium and glycopyrronium should not be used together.
For renewal of Special Authority applications, patients must be compliant with medicine use and show benefit from glycopyrronium.
Indacaterol is available, fully subsidised, without the need for Special Authority approval.
How do these medicines work?
Glycopyrronium is an inhaled long-acting muscarinic receptor antagonist (LAMA), which acts as a bronchodilator and is
indicated for use in patients with COPD. Glycopyrronium is administered as a 50 microgram dose, once daily, via inhalation
of dry powder using the inhaler device; each dose (supplied as a blister-packed capsule) must be loaded into the inhaler
device immediately before use. Patients will need to be instructed on how to use the inhaler. It is designed to give feedback
when a dose is taken correctly, with an audible whirring noise after dose delivery, and patients are able to check that
the delivery capsule is empty. It is rapidly absorbed and reaches peak plasma levels five minutes after administration.
Based on data from clinical trials, the expected benefit is likely to be in the range of a 100 mL increase in forced expiratory
volume (FEV1).6 The result for patients therefore is an improvement in breathlessness and exercise tolerance.
Indacaterol is a long-acting beta-agonist (LABA) for the treatment of patients with COPD. It is taken by inhalation
as a once daily dose of 150 micrograms or 300 micrograms. Indacterol is also administered by loading a capsule containing
the dry powder dose into the inhaler device, and patients will need to be instructed in its use. Meta-analyses of trials
including patients taking indacaterol for the treatment of COPD report that patients experience an improvement in respiratory
symptoms to a similar or slightly greater extent than with other bronchodilators such as tiotropium, salmeterol or formoterol.7,
8 Overall efficacy in terms of improvements in FEV1 scores appears similar to treatment with these comparator medicines.7,
8 For patients with stable COPD, maximal benefit is likely to be gained at a 150 microgram, once daily, dose.7
The most frequently reported adverse effect of glycopyrronium is dry mouth, related to its antimuscarinic action. Other
adverse effects include dyspepsia and gastroenteritis, insomnia, irritation affecting the nasal and throat passages, rhinitis
and sinusitis.9, 10 Given its anticholinergic effects, glycopyrronium should be used with caution in patients with narrow-angle
glaucoma or urinary retention, as well as in patients with renal impairment.10 The European Medicines Authority has recommended
that post-marketing studies include more detailed assessments of possible cardiovascular adverse effects, after higher
rates of atrial fibrillation were observed in one clinical trial.6, 9
Adverse effects of indacaterol include nasopharyngitis and headache, insomnia, tachycardia and muscle cramps.7,
8, 11 ,12 Indacaterol does not protect against exacerbations of COPD, nor worsening of symptoms.8 Beta-agonists may cause potential
systemic effects such as tachycardia, and should be used with caution in patients with cardiovascular disease, or thyrotoxicosis
where tachycardia is already present and the patient has possible increased sensitivity to beta agonists.13
A combination indacaterol/glycopyrronium inhaled powder has been investigated for effectiveness in the treatment of
patients with COPD and shows some benefit over either treatment alone. 14, 15 It is possible that this preparation may
also be subsidised on the Pharmaceutical Schedule in the future.
For further information on managing patients with COPD, see:
N.B. An update on COPD management is planned for Best Practice Journal in 2015.
- Shirtcliffe P, Weatherall M, Marsh S, et al. COPD prevalence in a random population survey: a matter of definition.
Eur Respir J 2007;30:232–9.
- Postma DS, Bush A, van den Berge M. Risk factors and early origins of chronic obstructive pulmonary disease. Lancet
2014;[Epub ahead of print].
- Global initiative for chronic obstructive lung disease (GOLD). Global strategy for diagnosis, management and prevention
of COPD. GOLD, 2014. Available from:
www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html (Accessed Nov, 2014).
- Chang CL, Hancox RJ, Beckert L. Reading between the COPD audits: have current GOLD standards lost their lustre? N
Z Med J 2013;126:5–8.
- Bestall JC, Paul EA, Garrod R, et al. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure
of disability in patients with chronic obstructive pulmonary disease. Thorax 1999;54:581–6.
- National Institute for Health and Care Excellence (NICE). NICE Evidence Summary ESNM9: Chronic obstructive pulmonary
disease: glycopyrronium bromide. NICE, 2013. Available from:
www.nice.org.uk/advice/esnm9 (Accessed Nov, 2014).
- Jiang F-M, Liang Z-A, Zheng Q-L, et al. Safety and efficacy of 12-week or longer indacaterol treatment in moderate-to-severe
COPD patients: a systematic review. Lung 2013;191:135–46.
- Chung VCH, Ma PHX, Hui DSC, et al. Indacaterol for chronic obstructive pulmonary disease: systematic review and meta-analysis.
PloS One 2013;8:e70784.
- European Medicines Agency (EMA). Seebri Breezhaler. Glycopyrronium bromide. EMA, 2014. Available from:
www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002430/human_med_001580.jsp&mid=WC0b01ac058001d124 (Accessed Nov, 2014).
- Novartis New Zealand Limited. Seebri Breezhaler. Glycopyrronium bromide. New Zealand Data Sheet. 2014. Available
www.medsafe.govt.nz/Profs/Datasheet/s/seebricap.pdf (Accessed Nov, 2014).
- Donohue JF, Singh D, Kornmann O, et al. Safety of indacaterol in the treatment of patients with COPD. Int J Chron
Obstruct Pulmon Dis 2011;6:477–92.
- Novartis New Zealand Limited. New Zealand Data Sheet. Onbrez Breezhaler. Indacaterol maleate. 2013. Available from:
www.medsafe.govt.nz/profs/datasheet/o/onbrezcap.pdf (Accessed Nov, 2014).
- Devereaux D, Tewelde SZ. Hyperthyroidism and thyrotoxicosis. Emerg Med Clin North Am 2014;32:277–92.
- Rodrigo GJ, Plaza V. Efficacy and safety of a fixed-dose combination of indacaterol and glycopyrronium for the treatment
of COPD: a systematic review. Chest 2014;146:309–17.
- European Medicines Agency (EMA). Ultibro Breezhaler. Indacaterol/glycopyrronium. London: European Medicines Agency, 2013.
Rivastigmine patches (Exelon) now funded for patients with dementia
On 1 November, 2014, rivastigmine patches were newly funded on the national Pharmaceutical Schedule for the management of
patients with dementia. Two strengths of patches are now funded as a second-line treatment for dementia, subject to Special Authority
criteria. Patients first must have tried oral donepezil but have experienced intolerable nausea and vomiting. Rivastigmine is equally
effective as donepezil.
Approximately 30,000 people in New Zealand are estimated to be living with Alzheimer’s disease,1 the primary cause of
dementia, and general practitioners are often the first point of contact for patients or their family members who may
have concerns over memory problems or behaviour changes.
International guidelines recommend that initial evaluations for the diagnosis of dementia include an assessment of patient
history, with information from family members and people familiar with the patient, as well as some form of cognitive
test, such as the Mini Mental State Examination.2, 3 Investigations such as complete blood count, renal and liver function
tests, thyroid-stimulating hormone, electrolytes, calcium, glucose, folate and vitamin B12 levels may be considered, as
these can help to exclude other differential diagnoses or additional causes of cognitive impairment.2, 3 Patients with
suspected dementia are likely to require referral to a geriatrician or psychiatrist to confirm a diagnosis as other tests
and imaging may be required.
There are no medicines or lifestyle interventions which have been shown to reverse or cure dementia. As dementia influences
many aspects of a person’s daily life, and in turn the lives of those around them, care of patients with dementia and
their families revolves around the provision of support services, including counselling to promote independence in activities
of daily living and to provide psychological support.3 Medicines indicated for the treatment of dementia are not a cure,
and act only to improve or delay symptoms. In New Zealand, the acetylcholinesterase inhibitor donepezil, taken orally,
is fully funded as a first-line treatment for dementia. Rivastigmine patches are a second-line treatment if donepezil
tablets are not tolerated. Galantamine and memantine are also indicated for the management of dementia in patients with
Alzheimer’s disease, but are not subsidised.
Access and subsidy criteria for rivastigmine patches
The approved indication for rivastigmine is for the management of patients with dementia due to Alzheimer’s disease.
Its use in patients with dementia due to other causes such as Parkinson’s disease or Lewy body dementia is an unapproved
indication, however, these patients may benefit from rivastigmine treatment,4 and the Special Authority criteria do not
limit access to specific causes of dementia.
Rivastigmine patches at two strengths, 4.6 mg/24 hours (5 cm2 patch) and 9.5 mg/24 hours (10 cm2 patch), are fully subsidised
subject to Special Authority criteria for use in patients intolerant to the gastrointestinal side effects of donepezil.
Applicants will need to confirm the patient has dementia and has experienced intolerable nausea and/or vomiting from donepezil
tablets, which is estimated to occur in approximately 15% of patients.4 Initial applications are valid for six months
and renewal applications can be made if the patient shows benefit, and are valid for another 12 months.
How does rivastigmine work?
The biological processes that lead to dementia in Alzheimer’s disease are not entirely understood, but alterations are
seen in key synaptic pathways using the neurotransmitter acetylcholine.5 Medicines which increase acetylcholine levels
have been shown to improve cognitive performance in patients with dementia.6–8 Rivastigmine is a cholinesterase inhibitor
that blocks the enzymes involved in acetylcholine degradation, and primarily acts in the central nervous system.9 Clinical
trials of rivastigmine have reported that in patients with dementia it can improve assessments of cognitive function compared
with placebo, as well as improvements in daily living activities.7 Data from clinical trials show that cognitive measures
improve gradually over the course of months.7 Caregivers report a preference for rivastigmine patches rather than oral
tablets in countries where both oral rivastigmine and patches have been available, due to factors such as ease of use
and low interference with daily living.10, 11
How are rivastigmine patches given?
Rivastigmine patches are applied to the skin once daily, and should be removed and changed for a new patch after 24
hours. Because of the potential for skin site reactions, patches should be reapplied to a different area of skin, although
this may be in the same anatomical region (e.g. back), avoiding the same area for the following 14 days. Patches may be
worn during everyday activities such as bathing, but prolonged exposure to external heat sources should be avoided, e.g.
direct sun or heaters.
Dosing should begin with the smaller 5 cm2 patch, which delivers 4.6 mg over 24 hours, and increase to the larger 10
cm2 (9.5 mg/24 hour) patch after four weeks if the lower dose was tolerated.12 The higher dose patch is regarded as the
target dose, with the lower dose patch used for titration.4 If patients have previously been taking oral donepezil, those
taking 5 mg orally per day may be switched to the lower dose transdermal patch (4.6 mg) and those usually taking 10 mg
orally per day and tolerating this dose may be switched to a 9.5 mg patch.13
Adverse effects are to be expected but are usually not serious
The majority of patients taking rivastigmine experience adverse effects; most often these are application site reactions,
but also include gastrointestinal symptoms such as nausea, vomiting and diarrhoea, as well as anorexia, headache, syncope,
dizziness, falls and extrapyramidal symptoms.7, 13, 14 Serious adverse effects are rare.7, 14 Patients taking rivastigmine
via transdermal patches show lower rates of gastrointestinal adverse effects than those taking rivastigmine capsules,14
and therefore patients who have experienced gastrointestinal adverse effects while taking donepezil may find transdermal
rivastigmine more tolerable.
Rivastigmine should be used cautiously in patients with hepatic impairment, as this may reduce drug clearance and result
in more adverse effects; adverse effects may also be more prevalent in patients weighing less than 50 kg. As rivastigmine
can have cholinergic effects, it should also be used cautiously in patients at risk of urinary obstruction, gastric ulceration
or seizures, with COPD or asthma or with defects of cardiac conduction.12
In all patients, rivastigmine treatment should be stopped if gastrointestinal adverse effects occur or there are extrapyramidal
effects, but treatment can continue once these resolve.12 If symptoms reappear, it may be necessary to reduce the dose.
Adverse effects are more likely to occur if a carer or the patient does not remove the previous patch prior to applying
another.12 Practical reminders may be helpful such as a note placed on the medicine box, or establishing a routine of
always throwing out the discarded pouch from the new patch with the previous day’s removed patch inside it.
For further information of the use of donepezil in patients with Alzheimer’s disease,
- Tobias M, Yeh L-C, Johnson E. Burden of Alzheimer’s disease: population-based estimates and projections for New Zealand,
2006-2031. Aust N Z J Psychiatry 2008;42:828–36.
- Sorbi S, Hort J, Erkinjuntti T, et al. EFNS-ENS Guidelines on the diagnosis and management of disorders associated
with dementia. Eur J Neurol 2012;19:1159–79.
- NICE. Dementia: supporting people with dementia and their carers in health and social care. NICE 2006.
(Accessed Nov, 2014).
- Minutes of the Mental Health Subcommittee of PTAC, 21 June 2010 meeting. 2010. Available from:
https://pharmac.govt.nz/assets/ptac-mental-health-subcommittee-minutes-2010-06.pdf (Accessed Nov, 2014).
- Contestabile A. The history of the cholinergic hypothesis. Behav Brain Res 2011;221:334–40.
- Hansen RA, Gartlehner G, Webb AP, et al. Efficacy and safety of donepezil, galantamine, and rivastigmine for the
treatment of Alzheimer’s disease: a systematic review and meta-analysis. Clin Interv Aging 2008;3:211–25.
- Birks J, Grimley Evans J, Iakovidou V, et al. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev 2009;2:CD001191.
- Rodda J, Carter J. Cholinesterase inhibitors and memantine for symptomatic treatment of dementia. BMJ 2012;344:e2986–e2986.
- Kennedy JS, Polinsky RJ, Johnson B, et al. Preferential cerebrospinal fluid acetylcholinesterase inhibition by rivastigmine
in humans. J Clin Psychopharmacol 1999;19:513–21.
- Reñé R, Ricart J, Hernández B, et al. From high doses of oral rivastigmine to transdermal rivastigmine patches: user
experience and satisfaction among caregivers of patients with mild to moderate Alzheimer disease. Neurologia 2014;29:86–93.
- Gauthier S, Robillard A, Cohen S, et al. Real-life effectiveness and tolerability of the rivastigmine transdermal
patch in patients with mild-to-moderate Alzheimer’s disease: the EMBRACE study. Curr Med Res Opin 2013;29:989–1000.
- Novartis New Zealand Limited. New Zealand Data Sheet. Exelon; Rivastigmine transdermal patch. Auckland, NZ: 2014. Available from:
www.medsafe.govt.nz/profs/datasheet/e/Exelonpatch.pdf (Accessed Nov, 2014).
- New Zealand Formulary (NZF). NZF v29. 2014. Available from:
www.nzf.org.nz (Accessed Nov, 2014).
- Sadowsky CH, Farlow MR, Meng X, et al. Safety and tolerability of rivastigmine transdermal patch compared with rivastigmine
capsules in patients switched from donepezil: data from three clinical trials. Int J Clin Pract 2010;64:188–93.
Access to medicines for people with multiple sclerosis has changed
From 1 November 2014, people diagnosed with relapsing-remitting multiple sclerosis (MS) were able to be initiated on
two new fully-subsidised, disease-modifying medicines, at an earlier stage in the disease process. These medicines are:
- Fingolimod capsules – initiated in secondary care (see below) and dispensed from community pharmacies
- Natalizumab intravenous infusions – administered in secondary care
Fingolimod and natalizumab are now effectively the first-line treatments for people with relapsing-remitting MS. The
“ABC medicines” – interferon beta-1a (Avonex), interferon beta-1b (Betaferon) and glatiramer acetate (Copaxone) – will
still be fully subsidised, but only as second-line treatments if fingolimod and natalizumab are not tolerated, or are
not clinically appropriate. However, the “ABC” medicines will continue to be subsidised for people who were receiving
one of these treatments prior to 1 November 2014; therefore these people do not need to switch treatment unless they wish
People with multiple sclerosis now have earlier access to treatment
The entry criteria that people must meet to receive fully-subsided treatment for relapsing-remitting MS has been changed.
Natalizumab and fingolimid can now be initiated earlier in the disease process and there is no longer a need for the person
to experience frequent relapses before qualifying for subsided treatment. Fingolimod and natalizumab are now subsidised:
- From the first confirmed diagnosis of definitive relapsing-remitting MS for people with an Expanded Disability Status
Scale (EDSS)* score of 0 – 4.0 who meet the subsidy criteria
- For people with MS with one significant relapse in the previous 12 months, or two significant relapses in the previous
24 months. Treatment can be initiated once the diagnosis of MS has been confirmed. Previously, people with
MS had to display frequent relapses and significant residual disability to qualify for subsidised treatment.
* The Kurtzke EDSS is a method of quantifying disability in patients with MS. The assessment is undertaken in secondary
care and is used to measure and assess disability and disease progression in patients with MS.
General practitioners are encouraged to review the treatment of all patients with an existing diagnosis of MS who potentially
meet the new funding criteria. It is important that general practitioners refer patients with symptoms suggestive of MS
early to a neurologist for assessment. Earlier access to disease-modifying medicines may slow progression of MS and result
in reduced disability for some people (see below).
Specific details about eligibility criteria for MS treatments, and other information, can be found in the Questions
and Answers on the PHARMAC MS treatments webpage at:
Relapsing-remitting multiple sclerosis
A relapsing-remitting pattern of disease is seen in 85% of people with early stage MS.1 This is characterised by recurrent
acute neurological episodes, with residual symptoms increasing or new symptoms developing. On average, people with MS
have approximately one relapse every two years, however, the frequency and severity of these can vary widely.2 A high
frequency of relapses during the first two years of the disease increases the risk that the person with MS will progress
to secondary progressive MS and long-term disability.2
For further information, see:
“Multiple sclerosis: Managing shades of grey”, BPJ 54 (Aug, 2013).
General practitioners may be required to prescribe fingolimod
General practitioners may be requested to provide repeat prescriptions for fingolimod following approval of the initial
treatment application by the Multiple Sclerosis Treatment Advisory Committee (MSTAC). Fingolimod is available in 500 microgram
capsules, which are taken once daily.
Compared with the injectable “ABC” MS treatments, fingolimod has a wider-ranging immunosuppressant action.3 It inhibits
leukocyte migration across the blood-brain barrier and therefore reduces inflammation in the central nervous system.4
This occurs through an agonist action at sphinogosine-1-phosphate receptors.3 A two-year trial reported that, in comparison
to placebo, fingolimod more than halved the rate of relapse in people with relapsing-remitting MS.3 A possible decrease
in disease progression was also noted.3 Compared with once-weekly subcutaneous injections of interferon beta-1b, fingolimod
is reported to reduce the annual rate of relapse in people with relapsing-remitting MS.3
Fingolimod is contraindicated in people who are undergoing immunosuppressant treatment, have active infection or an
active malignancy (other than basal cell carcinoma).5 Fingolimod is not recommended for people with an increased cardiovascular
risk as it may cause bradycardia and heart block due to its effects on the sphinogosine-1-phosphate receptors on the heart.5
Fingolimod may also not be appropriate for people with other cardiac conditions (see NZF for more details).
Discussion with a cardiologist is strongly recommended prior to starting fingolimod in a patient with a history of cardiovascular
issues. The clinician managing the patient’s treatment for MS should be informed if the patient develops any clinically
significant cardiovascular symptoms while taking fingolimod.
Patients will require intensive cardiac monitoring in a secondary care setting the first time they take fingolimod.
All patients should have an ECG performed prior to dosing and continuously for the first six hours after treatment initiation.5,
6 If any cardiac effects are observed, extended monitoring (at least overnight) will be required.5 Hourly blood pressure
and heart rate measurements should also be taken for the first six hours of treatment.5, 6
It is recommended that people who do not have a validated history of varicella or a documented full course of varicella
vaccine undergo varicella zoster antibody testing prior to starting fingolimod.5 A full course of varicella vaccine should
be administered in patients who are varicella antibody-negative and the initiation of fingolimod treatment delayed for
one month to allow the vaccine to reach full effectiveness.
Other adverse effects associated with fingolimod include: diarrhoea, weight loss, abnormal liver function tests, hypertension,
cough, dyspnoea, depression, malaise, headache, dizziness, paraesthesia, influenza, bronchitis, sinusitis, gastroenteritis,
tinea infections, back pain, asthenia, blurred vision, eye pain, eczema, alopecia and pruritus.5 As expected with an immunosuppressive
treatment, people taking fingolimod have an increased risk of infectious complications, particularly due to herpes zoster,
skin cancer and other neoplasms.3 Due to the increased risk of macular oedema, patients should undergo an ophthalmic examination
before beginning treatment and regularly thereafter.3 Pregnancy is an absolute contraindication to the use of fingolimod
and should be excluded.3 Effective contraception should be used until at least two months after treatment has finished.3
Natalizumab infusions are administered in secondary care
Natalizumab is an intravenous infusion, given every four weeks in secondary care for the treatment of people with relapsing-remitting
MS. It is available as a 300 mg/15 mL formulation. General practitioners are unlikely to be involved in prescribing natalizumab,
but will be involved in monitoring patients for adverse effects. Community pharmacists are unlikely to dispense natalizumab
directly to the patient as this will generally be arranged by the hospital pharmacy.
Health professionals who are involved in the prescribing or dispensing of natalizumab will be required to undergo training
provided by the manufacturer (the Tysabri Australasian Prescribing Programme). This is due to the potential for
patients to develop progressive multifocal leucoencephalopathy (PML), which has a 20% fatality rate in people
Natalizumab may be the most effective medicine available for treating relapsing-remitting MS.3 It is a humanised monoclonal
antibody that blocks receptors on the surface of phagocytic mononuclear cells, preventing them from migrating from peripheral
circulation into the central nervous system.3 A review of three studies, one placebo-controlled study (942 patients) and
two studies involving adjunctive treatment with either glatiramer acetate (110 patients) or interferon beta-1b (1171 patients),
found robust evidence of a reduction in relapses and disability in patients with MS after two years.4 It is important
that general practitioners discuss any concerns they have about the effectiveness of MS treatments that a patient is taking
with the clinician managing the patient’s treatment for MS, as patients that are not responding to other medicines may
be eligible for treatment with natalizumab.
Natalizumab is contraindicated in: people with PML or active infection, people who are concurrently taking interferon
beta-1b or glatiramer acetate, people who are immunosuppressed, or people who have active malignancies other than basal
Patients may experience infusion-related adverse effects following administration of natalizumab, e.g. nausea, vomiting,
headaches, dizziness, fatigue, fever, or hypersensitivity reactions including anaphylaxis.5 Patients should be monitored
for these symptoms during the infusion and for one hour after.5
Progressive multifocal leucoencephalopathy (PML)
PML is a rare, and usually fatal, viral disease characterised by progressive damage or inflammation of the white matter
of the brain at multiple locations. PML occurs almost exclusively in people with a severe immune deficiency. It is caused
by the John Cunningham (JC) virus and is characterised by muscle weakness, sensory deficit, cognitive dysfunction, language
impairment – and coordination and gait difficulties. The risk of a patient with MS having PML is approximately 1% if they
have a detectable titre for JC virus.3 This risk may be increased in patients who have previously used immunosuppressant
medicines.3 The risk of PML is an order of magnitude lower in patients without a detectable titre for JC virus.3
People taking natalizumab also have an increased risk of PML, which increases after two years of treatment.5 A MRI scan
is recommended before starting natalizumab treatment and annually thereafter. Patients taking natalizumab should be monitored
for symptoms of PML. If PML is suspected, natalizumab should be permanently discontinued.5
For further information on PML see:
- Simon C. Multiple sclerosis. InnovAiT 2009;2:205–12.
- Scalfari A, Neuhaus A, Degenhardt A, et al. The natural history of multiple sclerosis: a geographically based study
10: relapses and long-term disability. Brain J Neurol 2010;133:1914–29.
- Carrithers MD. Update on disease-modifying treatments for multiple sclerosis. Clin Ther 2014;[Epub ahead of print].
- Pucci E, Giuliani G, Solari A, et al. Natalizumab for relapsing remitting multiple sclerosis. Cochrane Database Syst
- New Zealand Formulary (NZF). NZF v29. 2014. Available from: www.nzf.org.nz (Accessed
- Novartis New Zealand Limited. Gilenya. Fingolimod. New Zealand Data Sheet. 2014 .Available from:
(Accessed Nov, 2014).