10.1.1 NSAIDs
10.1.2.2 Local steroid injections
10.1.3 Drugs which suppress rheumatoid disease
10.1.4 Gout and cytoxic-induced
hyperuricaemia
10.2.1Neuromuscular transmission
10.2.2 Skeletal muscle relaxants
10.3.1 Enzymes
10.3.2 Rubefacients and other topical
antirheumatics
Link to GP Formulary
10.1 Rheumatic diseases and gout
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10.1.1 NSAIDs
Pain relief is necessary in most rheumatic diseases. For degenerative joint
disease (osteoarthritis) or soft-tissue lesions, paracetamol should be
used first, either alone or combined with a low dose of an opioid analgesic, eg
co-codamol 8/500 or co-dydramol 10/500. Nonsteroidal
anti-inflammatory drugs (NSAIDs) are indicated for the pain and stiffness of
inflammatory rheumatic diseases.
NSAIDs vary in chemical structure but this is not of major clinical importance.
In single dose they have analgesic activity and taken regularly they have
lasting analgesic and anti- inflammatory effects.
There is wide variation in individual response to NSAIDs despite similar
anti-inflammatory properties. About 60% of patients will respond to any; others
who do not respond to one may benefit from another. If used purely for
analgesia NSAIDs should be changed after a week if there is no benefit; if used
for anti-inflammatory effect they should be changed after 3 weeks if there is
no benefit. Caution: Patients should not receive more than one
oral NSAID at any one time. Low risk NSAIDs, such as ibuprofen, should be used
as first choice, and should be started at the lowest recommended dose.
NSAIDs should not be prescribed to patients taking warfarin or other oral
anticoagulants. NSAIDs should be used with care in pregnancy, in those with
cardiac or hepatic impairment, allergies, particularly salicylate
hypersensitivity and in those with asthma, which may worsen. Renal impairment
may deteriorate to the point of severe renal failure so serum creatinine should
be monitored, especially if patient is also taking a diuretic.
NSAIDs should not be used if there is active peptic ulceration. With a previous
history of peptic ulcer, and in the elderly, they should be given only if other
treatments are unsuitable.
NSAIDs with shorter half lives (t½) are liable to cause fewer side effects,
especially in the elderly in who doses and duration of treatment should be kept
to a minimum.
When to prescribe a PPI
NICE guidance on osteoarthritis and rheumatoid arthritis recommends
co-prescribing of PPI with NSAID or COX-2 inhibitors for all patients,
regardless of risk factor status. This recommendation was discussed by the
Effective Practice Committee who considered that the evidence for patients at
low risk of gastrointestinal events was not sufficiently robust to warrant
co-prescription of PPI with NSAID or COX-2 inhibitor for this group of
patients. Prescribers are advised to follow local advice.
Local advice is to consider co-prescription of a PPI with a NSAID or COX-2
based upon assessment of the patient’s baseline risk factors for an adverse GI
event. Patients at higher risk who should receive a PPI include those: aged
over65 years, past history of relevant GI pathology, concomitant use of other
medications which increase the likelihood of upper GI complications (e.g.
steroids, anticoagulants), serious co-morbidity (cardiovascular disease, renal
or hepatic impairment, diabetes, hypertension).
Propionic acid derivatives
Ibuprofen (t½ 2hrs) is analgesic and antipyretic, it has fewer side
effects than other NSAIDs but its anti-inflammatory properties are weaker. Naproxen
(t½ 13hrs) has emerged as one of the first choices as it combines
good efficacy with a low incidence of side-effects and administration is only
twice daily.
First Choice: Ibuprofen tabs: 200mg [21 tabs 42p]; 400mg [21 tabs 46p]. Dose:
initially 200-400mg 3 times daily after meals, increased if needed to a max of
2.4g daily in divided doses.
Ibuprofen syrup: 100mg in 5ml [420ml £6.34].
Also:
Naproxen tabs: 250mg [14 tabs £1.13]. Dose: 250-500mg twice daily
after meals; max daily dose 1g.
Acetic acid derivatives
Diclofenac (t½ 2hrs) is similar to naproxen for efficacy and side
effects. Diclofenac suppositories are particularly useful for post-op
analgesia.
First choice: Diclofenac EC tabs: 25mg [21 tabs 29p]; 50mg [21
tabs 33p]. Dose: 25-50mg 3 times daily after meals; max daily dose
150mg.
Diclofenac dispersible tabs: 50mg [21 tabs £6.19]. Dose: 50mg 3
times daily.
Diclofenac SR tabs: 100mg [10 tabs £2.93]. Dose: 100mg once daily
after meals.
Diclofenac suppositories: 12.5mg [21 supps £1.22], 25mg [21 supps
£2.16], 50mg [21 supps £3.57], 100mg [10 supps £3.40]. Dose: 75 to 150mg
daily in divided doses.
Salicylic acid derivatives
Aspirin (t½ 5hrs) is useful but has been superseded to some degree
by other NSAIDs that are better tolerated and more convenient.
Caution: Aspirin should be avoided in those with asthma.
First choice: Aspirin dispersible tabs: 300mg [56 tabs £1.72]. Dose:
300-900mg every 4hrs after meals.
Aspirin EC tabs: 300mg [56 tabs 3.48].
Oxicam derivatives
Perioperative use only
Piroxicam orodispersible tabs: 20mg (Feldene® Melt) [1 tab
35p]. Dose: 20 to 40mg as a single dose preferably one hour prior to
surgery. (NB Feldene® Melt was previously licensed for
peri-operative use but no longer).
Cox II selective inhibitors
COX-2 inhibitors are indicated for
the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis
and gout (etoricoxib only) where inadequate response to NSAIDS or NSAIDs are
not suitable on the basis of patient risk factors (eg patient at a particularly
high risk of developing ulceration or bleeding). COX-2 can also be prescribed for patients
where a PPI is not tolerated or contraindicated.
Patients with Cardiovascular Risks
In patients with established cardiovascular disease and those at increased risk
of developing cardiovascular, low dose ibuprofen or naproxen are an appropriate
choice. Patients with significant risk factors
for cardiovascular disease (eg hypertension, diabetes, smoking, elevated
cholesterol levels) should only be treated with COX-2 inhibitors after careful
consideration (NB etoricoxib is contraindicated in patients with poorly
controlled hypertension). The greatest
concern relates to chronic use of high-doses of NSAIDs, especially diclofenac
and COX-2 inhibitors. Co-prescription
with aspirin should be avoided unless absolutely essential.
Patients with Gastrointesinal Risks
The risk of gastrointestinal toxicity with NSAIDs increases with increase in
dose. Low dose ibuprofen has the lowest
gastrointestinal risk of the formulary NSAIDs. Naproxen and diclofenac are
associated with an intermediate risk of gastrointestinal events with naproxen
having a slightly higher risk than diclofenac.
COX-2 inhibitors are associated with a lower gastrointestinal risk
relative to most NSAIDS at equivalent doses.
However, evidence for a reduction in most clinically important
gastrointestinal risks (eg bleeding from ulcer) with etoricoxib is weak.
First Choice: Celecoxib caps: 100mg [14 caps £5.03]; 200mg [14 caps £10.06]. Dose: 100mg twice a day, increased if
necessary to a maximum of 200mg twice daily.
Discontinue if no improvement after 2 weeks on the maximum dose.
Also
Etoricoxib tabs: 30mg [7 tabs
£3.50]; 60mg [7 tabs £5.03]; 90mg [7 tabs £5.74]; 120mg [7 tabs £6.03]. Dose:
osteoarthritis 30mg once daily, increased if necessary to 60mg once daily, rheumatoid arthritis and ankylosing
spondylitis 90mg once daily, acute
gout 120mg once daily for a maximum of 8 days.
10.1.2 Corticosteroids
10.1.2.1 Systemic steroids
The actions and uses of systemic steroids are described in section 6.3. Steroid treatment in rheumatic diseases should be started only after specialist input.
10.1.2.2 Local steroid injections
Steroids, sometimes mixed with local anaesthetic such as lidocaine 1%, are
injected into inflamed, non-infected joints using an aseptic technique. In
rheumatoid arthritis intra-articular steroids reduce the degree of synovitis
with a subsequent reduction in pain and stiffness. There is no agreed limit on
the number of times a joint can be injected, but generally they should not be
injected more than 3 times in a year without specialist advice. Facial flushing
may occur after intra-articular steroids and diabetes may worsen. Small doses
of steroid are injected into periarticular and soft tissues to relieve
compression neuropathies and enthesopathies such as tennis or golfer's elbow.
Triamcinolone hexacetonide, a powerful synthetic steroid, is used for
large joints: wrist, elbow, shoulder and knee. Caution: There is risk of
muscle wasting, skin atrophy and depigmentation if it leaks back along the
needle track.
Hydrocortisone acetate, is used for metacarpophalangeal and other small
joints, and for soft tissues. For tendonitis the injection should be made into
the tendon sheath, not directly into the tendon, to avoid risk of rupture.
Hydrocortisone acetate injection: 25mg in 1ml [£5.72]. Dose:
usually 25mg to site of injection.
Methylprednisolone acetate depot injection: 40mg in 1ml [£2.87]; 80mg in
2ml [£5.15]. Dose: by
intra-articular or intrasynovial injection (for details consult product literature)
4 to 80mg according to size; where appropriate may be repeated at intervals of
7-35days.
Methylprednisolone acetate with lidocaine1% depot injection: 40mg in 1ml
[£3.28]; 80mg in 2ml [£5.88]. Dose: by
intra-articular or intrasynovial injection (for details consult product
literature) 4 to 80mg according to size; where appropriate may be repeated at
intervals of 7-35days.
Triamcinolone acetonide injection: (Acortyl®) 10mg in 1ml
[1ml amp £0.89, 5ml vial £3.63]. Dose: by intra-articular or intrasynovial
injection: 2.5 to 15mg according to size (for larger doses use Kenalog®).
By intrademal injection 2 to 3mg; max 5mg at any one site (total max 30mg).
Triamcinolone acetonide injection: (Kenalog®) 40mg in 1ml
[1ml vial £1.49]. Dose: by intra-articular or intrasynovial injection: 5
to 40mg according to size; total max 80mg.
10.1.3 Drugs which suppress rheumatoid disease
Patients with definite rheumatoid arthritis should be considered sooner
rather than later for disease modifying drugs such as sulfasalazine, gold,
penicillamine, hydroxychloroquine and methotrexate. Their effect tends to
become apparent only after 3-4 months and they may be very toxic. Specialist
advice should be sought.
All drugs in this section should only be used under specialist supervision as
regular monitoring is essential as specified in the relevant Shared Care
Guideline.
Forexpert use:
Penicillamine.
Penicillamine tabs: 125mg [14 tabs £4.14]; 250mg [14 tabs £6.64]. Dose:
125-250mg daily 1hr before meals for the first month, increased by this amount
every 4-12 weeks until remission occurs; maintenance usually 500-750mg daily.
It should be discontinued if there is no improvement within 1 year.
Link to Shared Care
Guideline.
Antimalarials.
Hydroxychloroquine sulphate tabs: 200mg [14 tabs £1.20]. Dose:
Initially 400mg daily in divided doses; maintenance 200-400mg daily; max
6.5mg/kg/day.
Link to Shared Care
Guideline.
Drugs Affecting the Immune Response.
Azathioprine tabs: 25mg [14 tabs £1.69]; 50mg [14 tabs £1.29]. (see 8.2). Dose:
according to expert advice, 1.5-2.5mg/kg/day in divided doses.
Link to Shared Care
Guideline.
Ciclosporin caps (Neoral®): 10mg [14 caps £4.31]; 25mg
[14 caps £8.68]; 50mg [14 caps £16.99]; 100mg [14 caps £32.25]; 100mg per ml
oral solution [50ml £117.00]. Dose: initially 2.5mg/kg daily in two
divided doses, if necessary increased gradually after 6 weeks; max 4mg/kg
daily.
Link to Shared Care
Guideline.
Leflunomide tabs (Arava®): 10mg [7tabs £11.93]; 20mg [7tabs
£11.93]. Dose: 10 to 20mg once daily.
Link to Shared Care
Guideline.
Methotrexate tabs: 2.5mg [4 tabs 30p]. (see 8.1.3). Dose:
according to expert advice, 7.5mg weekly as a single dose; increased if needed
to a max of 15mg or rarely 20mg weekly.
Link to Shared Care
Guideline.
Gold.
Sodium aurothiomalate inj: 10mg [£3.80]; 50mg [£11.23]. Dose: by
deep im injection on expert advice.
Link to Shared Care
Guideline.
Sulfasalazine.
Sulfasalazine enteric coated tabs: 500mg [28 tabs £3.62]. Dose:
Initially 500mg daily, increased by 500mg at intervals of 1 week to a maximum
of 2-3g daily in divided doses.
Link to Shared Care
Guideline.
10.1.3.1 Cytokine inhibitors
Adalimumab, certolizumab, etanercept and infliximab inhibit the activity of
tumour necrosis factor. They should only be prescribed by a specialist in
accordance with NICE guidance.
For Consultant Rheumatologist Use Only
Adalimumab inj: 40mg [prefilled syringe £352.14]. Dose: see BNF.
Certolizumab inj: 200mg [prefilled
syringe £357.50]. Dose: see BNF.
Etanercept inj: 25mg [prefilled syringe £89.38]; 50mg [prefilled syringe
£178.75]. Dose: see BNF.
Infliximab inj: 100mg [vial £419.62]. Dose: see BNF.
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Links to NICE guidance |
Acute gout
Acute gout is usually treated with high doses of NSAIDs such as naproxen or
diclofenac. Colchicine is occasionally used instead but it has a
high incidence of side effects. Aspirin and the prophylactic treatments
for gout, such as allopurinol, are contra-indicated in the acute attack,
which they may worsen.
First choice: Naproxen tabs: 250mg. Dose: 750mg initially, then
250mg every 8hrs after meals until the attack has passed [28 tabs £1.26].
Also:
Diclofenac tabs: 50mg [28 tabs 44p]. Dose: 50mg 3 times daily after
meals.
For expert use:
Colchicine tabs: 500microgram[12 tabs £3.61].Dose: acute gout: 500 micrograms three times a day.
Maximum total dose of 6mg per course; the course should not be repeated within
3 days; prevention of gout attacks during
initial treatment with allopurinol or uricosuric drugs: 500 micrograms
twice daily.
MHRA Drug Safety Update – Nov 2009
Colchicine has a narrow therapeutic index and is extremely toxic in
overdose. Patients at particular risk of
toxicity are those with renal or hepatic impairment, gastrointestinal or
cardiac disease, and patients at extremes of age. The symptoms of overdose are often
delayed. All patients, even in the absence
of early symptoms, should be referred for immediate medical assessment.
Please be aware, serious reactions can
occur when colchicine is given with clarithromycin, erythromycin,
verapamil, diltiazem, amiodarone and fluconazole.
Chronic gout
Chronic gout is treated by reducing serum urate levels with the xanthine
oxidase inhibitor, allopurinol. NICE has
appoved febuxostat as an
option for the management of chronic hyperuricaemia in gout only for patients
who are intolerant of allopurinol or for whom allopurinol is
contra-indicated. For the purposes of
this guidance, intolerance of allopurinol is defined as adverse effects that
are sufficiently severe to warrant discontinuation, or to prevent full dose
escalation for optimal effectiveness.
First choice: Allopurinol tabs: 100mg [7 tabs 30p]; 300mg [7 tabs 32p]. Dose:
initially 100mg daily as a single dose after food, gradually increased over 1-3
weeks according to serum urate to about 300mg daily; maintenance usually
200-600mg daily (doses over 300mg daily should be divided).
Also:
Febuxostat tabs: 80mg [7 tabs £6.09]; 120mg [7 tabs £6.09]. Dose: 80mg once daily, if after 2 to 4
weeks serum uric acid greater than 6mg/100ml increase to 120mg once daily.
10.1.4.1 Hyperuricaemia associated
with cytotoxic drugs
Rasburicase is licensed for the prophylaxis and treatment of acute hyperuricaemia,
before and during initiation of chemotherapy, in patients with haematological
malignancy and high tumour burden at risk of rapid lysis.
Rasburicase injection: (Fasturtec®)1.5mg
[vial £57.89]; 7.5mg [vial £241.20]. Dose:
by iv infusion, 200 micrograms/kg
once daily for up to 7 days according to plasma uric acid concentration.
10.2 Neuromuscular disorders
10.2.1Neuromuscular transmission
Anticholinesterases are used for myasthenia gravis Their muscarinic side
effects, including bradycardia and an increase in sweating, salivary and
gastric secretion and gastrointestinal and uterine motility, are all
antagonised by atropine.
Neostigmine has a therapeutic effect for up to 4hrs but marked
muscarinic action. Pyridostigmine is less powerful and slower in onset
but is preferable to neostigmine because of its smoother and longer duration of
action. Edrophonium has a very brief action and is only used for the
diagnosis of myasthenia.
First choice: Pyridostigmine tabs: 60mg [42 tabs £9.52]. Dose:
30-120mg at intervals throughout the day when strength is needed. The effective
action is usually 3-4hrs during the day but may be prolonged to 6hrs with the
dose taken before bed. The total dose is usually 30-720mg daily but higher
doses may be taken on expert advice.
Also:
Neostigmine tabs: 15mg [56 tabs £22.44]. Dose: 15-30mg at intervals
throughout the day; total dose 75-180mg daily, or more on expert advice.
Neostigmine injection: 2.5mg in 1ml [58p]. Dose: 1-2.5mg by sc or
im injection at intervals throughout the day; total dose usually 5-20mg daily.
Edrophonium chloride injection: 10mg in 1ml [£8.65]. Dose: for
the diagnosis of myasthenia gravis 2mg by iv injection, followed after 30secs
by 8mg if there has been no response or adverse reaction; in adults without
suitable veins, 10mg by im injection. Caution: atropine injection
600microgram-1mg (see 2.3.2)
should be available to treat severe cholinergic reactions and may be given
beforehand to prevent them.
10.2.2 Skeletal muscle relaxants
Baclofen and dantrolene are used to relieve chronic muscle
spasm and spasticity but may reveal or aggravate underlying weakness. They are
not used for minor injuries. Baclofen inhibits transmission at spinal
level and also depresses the CNS so the dose should be increased slowly to
avoid sedation and hypotonia. Dantrolene acts directly on skeletal
muscle and causes less sedation but liver damage may occur. Diazepam may
improve spasticity at anxiolytic doses (see 4.1.2) but it also causes
sedation and occasionally extensor hypotonus.
First choice: Baclofen tabs: 10mg [21 tabs 41p]. Dose: 5mg 3
times daily after meals, gradually increased to a max of 100mg daily in divided
doses.
Baclofen Syrup: 5mg in 5ml [210ml £6.52].
Also:
Dantrolene caps: 25mg [28 caps £4.72]; 100mg [28 caps £12.06]. Dose:
initially 25mg daily, increased at weekly intervals if needed to a max of 100mg
four times daily.
For consultant neurologist use only:
Tizanidine may be prescribed for patients with spasticity who have been
tried on baclofen but are unable to tolerate the adverse effects.
Tizanidine tabs: 2mg [21 tabs 97p]; 4mg [21 tabs £1.21]. Dose:
initially 2mg daily as a single dose increased according to response at
intervals of at least 3-4 days on steps of 2mg daily (and given in divided
doses) usually up to 24mg daily in 3-4 divided doses; max 36mg daily.
Hyaluronidase renders tissues more permeable to fluids given by
subcutaneous infusion but it is not usually needed unless more than 2 litres
are given in 24hrs. Supplies to the hospital are sometimes delayed.
Hyaluronidase injection: 1500 units [£7.60]. Dose: for
subcutaneous infusion, 1500 units mixed with the infusion fluid or injected
into the site before the infusion is given.
10.3.2 Rubefacients and other topical antirheumatics
Rubefacients act by counter-irritation which is comforting for nonarticular
rheumatism and painful lesions of muscles, tendons and joints. Topical NSAIDs
may provide some pain relief for musculoskeletal conditions but can aggravate
asthma. Contact with eyes, mucous membranes and inflamed or broken skin should
be avoided.
Creams
First choice: Algesal® cream: [50g £1.21]. Dose:
apply 3 times daily to the affected area, massaging until cream is fully
absorbed.
Gels:
Ibuprofen gel: 5% [100g £5.64]. Dose: apply up to 3 times daily.
Ketoprofen gel: 2.5% [100g £2.72]. Dose: apply two to four times a day for
up to 7 days (usual max 15g daily).
MHRA caution:
Patients should ensure that treated areas are protected from sunlight during
the whole period of topical ketoprofen treatment and for 2 weeks after stopping
treatment; they should also carefully wash the their hands after every
application.
Patients should stop treatment immediately if they develop any skin reaction
and seek their doctor’s advice.