Download chapter 10 - Eastbourne, Hailsham and Seaford CCG

CHAPTER 10
MUSCULOSKELETAL AND JOINT DISEASES
First line drugs – drugs
recommended in both
primary and secondary care
Second line drugs – alternatives
(often in specific conditions) in
both primary and secondary care
Specialist drugs – Drugs
where a specialist input is
needed (see introduction for
definition)
Specialist only drugs –
prescribing within
specialist service only.
Page:
10.1
Drugs used in rheumatic diseases and gout
3
10.2
Drugs used in neuromuscular disorders
11
10.3
Drugs for the relief of soft-tissue inflammation
12
Date
10/10
Revision
10.1.3 (NICE guidance, Biologics treatment pathway)
09/11
05/12
11/12
12/12
07/13
02/14
06/14
11/14
03/15
09/15
03/16
04/16
07/16
01/17
04/17
10.1.3 (NICE guidance)
10.3 (drug addition); 10.1.3 (NICE guidance)
10.1.4 (minor amendment)
10.1.3 (drug deletion, strength deletion)
10.1 (MHRA update); (NICE guidance)
10.1, 10.3 (NICE guidance)
10.1.3 (MHRA safety update)
10.2 (NICE guidance)
10.1 (Minor amendment)
10.1(NICE guidance), (minor amendments)
10.1.3 ( New formulation), (NICE guidance)
10.1 (NICE guidance)
10.1 (NICE guidance)
10.1 (NICE guidance)
10.1 (minor amendment)
First line drugs
Second line drugs
Contributors
Dr A Pool, Dr S Panthalakam, W Inman,
J Heath, G Ells
G Ells
G Ells
G Ells
A Luck
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 1 of 13
Specialist only drugs
NICE Clinical guideline 79: the management of rheumatoid arthritis in adults (February 2009) updated Dec15
Pharmacological management
Disease-modifying and biological drugs DMARDs
1. In people with newly diagnosed active RA, offer a combination of DMARDs (including methotrexate and at least
one other DMARD, plus short-term glucocorticoids) as first-line treatment as soon as possible, ideally within
3 months of the onset of persistent symptoms.
2. Consider offering short-term treatment with glucocorticoids (oral, intramuscular or intra-articular) to rapidly
improve symptoms in people with newly diagnosed RA if they are not already receiving glucocorticoids as part of
DMARD combination therapy.
3. In people with recent-onset RA receiving combination DMARD therapy and in whom sustained and satisfactory
levels of disease control have been achieved, cautiously try to reduce drug doses to levels that still maintain
disease control.
4. In people with newly diagnosed RA for whom combination DMARD therapy is not appropriate, start DMARD
monotherapy, placing greater emphasis on fast escalation to a clinically effective dose rather than on the choice
of DMARD.
5. In people with established RA whose disease is stable, cautiously reduce dosages of disease-modifying or
biological drugs. Return promptly to disease-controlling dosages at the first sign of a flare.
6. When introducing new drugs to improve disease control into the treatment regimen of a person with established
RA, consider decreasing or stopping their pre-existing rheumatological drugs once the disease is controlled.
7. In any person with established rheumatoid arthritis in whom disease-modifying or biological drug doses are being
decreased or stopped, arrangements should be in place for prompt review.
Glucocorticoids
1. Offer short-term treatment with glucocorticoids for managing flares in people with recent-onset or established
disease to rapidly decrease inflammation.
2. In people with established RA, only continue long-term treatment with glucocorticoids when:
 the long-term complications of glucocorticoid therapy have been fully discussed, and
 all other treatment options (including biological drugs) have been offered.
Biological drugs
1. On the balance of its clinical benefits and cost effectiveness, anakinra is not recommended for the treatment of
RA, except in the context of a controlled, long-term clinical study.
2. Patients currently receiving anakinra for RA may suffer loss of wellbeing if their treatment were discontinued at a
time they did not anticipate. Therefore, patients should continue therapy with anakinra until they and their
consultant consider it is appropriate to stop.
3. Do not offer the combination of tumour necrosis factor-α (TNF-α) inhibitor therapy and anakinra for RA.
Symptom control
1. Offer analgesics (for example, paracetamol, codeine or compound analgesics) to people with RA whose pain
control is not adequate, to potentially reduce their need for long-term treatment with non-steroidal antiinflammatory drugs (NSAIDs) or cyclo-oxygenase-2 (COX-2) inhibitors.
2. Oral NSAIDs/COX-2 inhibitors should be used at the lowest effective dose for the shortest possible period of
time.
3. When offering treatment with an oral NSAID/COX-2 inhibitor, the first choice should be either a standard NSAID
or a COX-2 inhibitor. In either case, these should be co-prescribed with a proton pump inhibitor (PPI), choosing
the one with the lowest acquisition cost.
4. All oral NSAIDs/COX-2 inhibitors have analgesic effects of a similar magnitude but vary in their potential
gastrointestinal, liver and cardio-renal toxicity; therefore, when choosing the agent and dose, healthcare
professionals should take into account individual patient risk factors, including age. When prescribing these
drugs, consideration should be given to appropriate assessment and/or ongoing monitoring of these risk factors.
5. If a person with RA needs to take low-dose aspirin, healthcare professionals should consider other analgesics
before substituting or adding an NSAID or COX-2 inhibitor (with a PPI) if pain relief is ineffective or insufficient.
6. If NSAIDs or COX-2 inhibitors are not providing satisfactory symptom control, review the disease-modifying or
biological drug regimen.
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 2 of 13
Specialist only drugs
10.1 Drugs used in rheumatic diseases and gout
In osteoarthritis and soft-tissue disorders, paracetamol taken regularly and/or topical NSAIDs should be considered
ahead of oral NSAIDS (CG177 Feb 2014).
NICE CG177 does not recommend the use of intra-articular hyaluronan injections for the management of
osteoarthritis
Only prescribe a Non Steroidal Anti-Inflammatory Drug if the benefits of treatment clearly outweigh the risks
and a need for an anti-inflammatory agent is identified.
Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and adverse events
1. NSAIDs are the drugs most often reported to the Committee on Safety of Medicines (CSM) as being responsible
for adverse effects. These effects fall into the following categories:
 Upper gastrointestinal
 Skin reactions
 Cardiovascular
 CNS
 Renal
Please Note: Gastrointestinal damage is a systemic effect of NSAIDs as well as a local effect. Symptoms such
as dyspepsia are only partially reduced by the use of enteric-coated tablets or suppositories.
2. All NSAIDS, including COX-II selective inhibitors, are associated with adverse events and should only be
prescribed when there is a demonstrable clinical need. Paracetamol should be used wherever possible with
NSAIDs being reserved for inflammatory conditions.
3. Gastro-intestinal side effects: CSM advice: NSAIDs associated with low gastro-intestinal risk e.g. ibuprofen are
generally preferred; start at the lowest recommended dose; do not to use more than one NSAID at a time.
4. Low dose aspirin alone does not significantly increase ulcer incidence but the combination of an NSAID and lowdose aspirin may increase the risk of gastro-intestinal side effects; this combination should only be used if
absolutely necessary and the patient monitored closely.
5. All NSAIDs, including COX-II agents are contra-indicated in patients with active peptic ulceration. The CSM also
contra-indicates non-selective NSAIDs in patients with a history of peptic ulceration.
6. Serious thrombotic events: Rofecoxib was withdrawn as trial results showed an increased risk of confirmed
serious thrombotic events, including myocardial infarction and stroke, compared to placebo, following long-term
use. Caution should be used when using other COX-II agents in patients at risk of cardiovascular disease and
should not be used in preference to non-selective NSAIDs, except where specifically indicated for patients who at
particularly high risk of developing gastroduodenal ulceration, perforation or bleeding and after an assessment of
cardiovascular risk.
7. When used at high doses for long-term treatment, non-selective NSAIDs may also be associated with a small
increased risk of thrombotic events. Diclofenac is associated with an increased risk similar to etoricoxib, whereas
naproxen is associated with a lower risk. There may be a small risk with high doses of ibuprofen (2.4g daily) but
lower doses (1.2g daily or less) are not associated with an increased risk.
8. NSAIDS are contra-indicated in patients with a history of hypersensitivity to aspirin or any other NSAID.
9. CSM Warning: any degree of worsening of asthma may be related to the ingestion of NSAIDs, either prescribed
or purchased over the counter.
Choosing a standard NSAID
1. 60% of patients will respond to any NSAID, but the remaining 40% will need to try several different drugs before
the most suitable agent for that particular individual is found (MeRec 1994, Vol 5, No 12).
2. Differences in anti-inflammatory activity between different NSAIDs are small; pain relief starts soon after taking
the first dose and full analgesia is normally obtained within one week; anti-inflammatory effects may take 3 weeks
to achieve. If an inadequate response is obtained within these time intervals, a different NSAID should be tried.
3. Short acting NSAIDs are preferred for the majority of patients as they allow flexible dosing leading to better
control of symptoms using lower daily doses.
4. Long acting NSAIDs may be required in patients with established rheumatoid arthritis and other conditions
where morning stiffness is a major component of the disease.
10.1.1 Non-steroidal anti-inflammatory drugs
Ibuprofen


Tablets 200mg, 400mg
Suspension SF 100mg / 5 ml
Naproxen

Tablets 250 mg, 500 mg
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 3 of 13
Specialist only drugs
Diclofenac sodium





Tablets 25mg, 50mg
Sustained release caps 75mg, 100mg
Dispersible tablets 50mg
Suppositories 12.5mg, 25mg, 50mg, 100mg
Injection 75mg in 3ml
Notes:
1. Ibuprofen remains the first line NSAID. If a patient says that they have tried ibuprofen check that they have
taken an anti-inflammatory dose i.e. at least 400 mg TDS, regularly. Higher doses are not recommended as they
are likely to be associated with a higher risk of gastrointestinal side effects. When ibuprofen 400mg TDS is not
effective, consider switching to naproxen or diclofenac.
2. Naproxen is one of the first choices because it combines good efficacy with a low incidence of side effects. It is
particularly useful where a sustained effect is required because it has a half-life of 14 hours i.e. BD dose. Gastrointestinal side effects are similar to diclofenac but naproxen is more cost-effective.
3. Naproxen is also associated with a lower risk of thrombotic events compared with diclofenac.
4. Sustained release formulations are not normally needed for the management of acute pain.
5. MHRA drug Safety Update (June 2013): Diclofenac is now contraindicated in patients with established:
 ischaemic heart disease
 peripheral arterial disease
 cerebrovascular disease
 congestive heart failure (New York Heart Association [NYHA] classification II–IV).
6. Diclofenac treatment should only be initiated after careful consideration for patients with significant risk factors for
cardiovascular events (eg, hypertension, hyperlipidaemia, diabetes mellitus, smoking) 7. Diclofenac suppositories are preferred to diclofenac injection (which may be painful when given IM) for the
acute relief of pain e.g. biliary colic.
8. Diclofenac by intravenous infusion is used in the hospital setting only, for peri-operative pain management.
9. GPs should take care to ensure that diclofenac potassium is not selected in error, as this orodispersible
formulation is considerably more expensive.
10. NSAIDs are an important adjuvant analgesic in palliative care, especially in patients with bone metastases. It is
important to use them regularly in full doses (see Adult Palliative Care Guidance 2nd Edition 2006 Sussex Cancer
Network)).
11. Treatment of dysmenorrhoea: Three systematic reviews and one subsequent RCT found that all NSAIDs used
for the treatment of dysmenorrhoea reduced pain compared to placebo. One systematic review found that all
NSAIDs reduced restriction of daily activities, absence from work/school, and the need for additional analgesia
compared with placebo. No comparative data exists to determine whether any NSAID is more effective than
another. Ibuprofen and naproxen are indicated for the use of dysmenorrhoea.
12. Treatment of menorrhagia: NSAIDs significantly reduce menstrual blood loss compared with placebo. There
is no significant difference between mefenamic acid and naproxen, or between NSAIDs and oral progestogens
given in the luteal phase.
13. Treatment of premenstrual syndrome: RCTs have found benefit from NSAIDs compared to placebo for a
range of premenstrual symptoms. No systematic reviews have been found, but two small RCTs show naproxen
to significantly reduce pain and physical symptoms of premenstrual syndrome.
14. Indometacin is the first-line NSAID in the management of gout (see section 10.1.4). Its use is limited by high
incidence of side effects such as headache and dizziness.
13. Where gastroprotection is considered necessary and there is no alternative to prescribing an NSAID, omeprazole
capsules 20mg or lansoprazole 15mg capsules should be chosen.
Cyclo-oxygenase (COX) II Selective Inhibitors
Only included when prescribed in accordance with NICE guidance. In all other cases standard NSAIDs should be
used.
Celecoxib

Capsules 100mg, 200mg

Tablets 30mg, 60mg, 90mg, 120mg
Notes:
1. COX-II agents are contraindicated in ischaemic heart disease, cerebrovascular disease, peripheral arterial
disease, moderate or severe heart failure and should be used with caution with a history of cardiac failure, left
ventricular dysfunction, hypertension, oedema for any other reason and risk factors for developing heart disease.
2. Serious thrombotic events: Rofecoxib was withdrawn as trial results showed an increased risk of confirmed
serious thrombotic events, including myocardial infarction and stroke, compared to placebo, following long-term
use. Caution should be used when using other COX-II agents in patients at risk of cardiovascular disease and
should not be used in preference to non-selective NSAIDs, except where specifically indicated for patients who at
particularly high risk of developing gastroduodenal ulceration, perforation or bleeding and after an assessment of
Etoricoxib
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 4 of 13
Specialist only drugs
cardiovascular risk. There is evidence that COX-II agents have similar cardiovascular toxicity to diclofenac; hence
the recommendation to use naproxen in preference to diclofenac.
3. It should be noted that the SPCs for the COX-II agents state that they are contraindicated in patients with active
peptic ulceration or gastrointestinal bleeding. For such patients where there is no alternative to prescribing an
NSAID, ibuprofen, naproxen or diclofenac with omeprazole capsules 20mg or lansoprazole 15mg capsules should
be chosen.
4. Low dose aspirin alone does not significantly increase ulcer incidence. However addition of a Cox-2 selective
inhibitor to low dose aspirin increases ulcer incidence to a rate similar to NSAIDs alone. Gastroenterology. 2004
Aug; 127(2): 395-402
10.1.2 Corticosteroids
10.1.2.2 Local corticosteroid injections
Methyl-prednisolone acetate
 Depo-Medrone® injection
40mg in 1ml, 80mg in 2ml, 120mg in 3ml
 Depo-Medrone® with Lidocaine injection
40mg+10mg in 1ml. 80mg+20mg in 2 ml
 Adcortyl ® Injection 50mg in 5 ml
Triamcinolone acetonide
10.1.3 Drugs which suppress the rheumatic disease process
Notes:
1. In general, disease-modifying antirheumatic drugs (DMARDs) should only be initiated by a specialist. GPs can take
over prescribing once the patient has been stabilised on a therapeutic dose (approximately 3 months). Shared care
guidelines can be searched for here (requires N3 connection).
2. The choice of DMARD will depend on patient preference and co-morbidity.
3. Sulfasalazine, methotrexate, intramuscular gold and penicillamine are similar in efficacy.
4. Sulfasalazine or methotrexate are often used first as they may be better tolerated.
5. The antimalarial hydroxychloroquine is also used to treat rheumatoid arthritis of moderate inflammatory activity.
Gold

Sodium Aurothiomalate
Injection 10mg amp, 20mg
amp, 50mg amp
Notes:
Auranofin is less effective than parenteral gold and should be discontinued if there is no response to treatment after 6
months

Tablets 125mg, 250mg
Penicillamine

Tablets 200ng
Azathioprine

Tablets 25 mg, 50mg
Ciclosporin (Neoral®)

Ciclosporin capsules 10mg, 25mg,
Hydroxychloroquine sulphate
Drugs affecting the immune response
(prescribe by brand name)
50mg, 100mg
Leflunomide

Methotrexate



Tablets 10 mg, 20 mg
Tablets 2.5 mg
Tablets 10mg
Injection pre-filled syringe 50mg/ml
7.5mg, 10mg, 15mg, 20mg, 25mg doses
(Metojet®)
Notes:
1. Ciclosporin (Neoral®) is licensed for severe active RA when conventional second-line therapy is inappropriate or
ineffective. It is contraindicated in abnormal renal function, uncontrolled hypertension, uncontrolled infections and
malignancy. Monitor hepatic function if concomitant NSAIDs given. Prescribe by the brand name Neoral®.
2. CSM Advice – Methotrexate: In view of reports of blood dyscrasias (including fatalities) and liver cirrhosis with
low-dose methotrexate, the CSM has advised:
 full blood count and renal and liver function tests before starting treatment and repeated weekly until therapy
stabilised, thereafter patients should be monitored every two to three months.
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 5 of 13
Specialist only drugs
 patients should be advised to report all symptoms and signs suggestive of infection, especially sore throat.
Treatment with folinic acid (as calcium folinate, section 8.1) may be required in acute toxicity.
3. The CSM has received reports of prescription and dispensing errors with methotrexate, including fatalities.
Attention should be paid to the strength of methotrexate tablets prescribed and the frequency of dosing.
4. Errors tend to occur due to confusion between the 2.5mg and 10mg tablets and often occur following a change of
dose. Prescribers should pay particular attention to dose changes. The dose should be clearly specified by
secondary care when communicating with GPs and GPs should clearly specify the strength and number of tablets
to be taken on prescriptions.
5. To avoid errors it is recommended that patients be carefully advised of the dose, strength of tablets and
frequency of dosing. Only one strength should be prescribed and dispensed i.e. avoid combinations of 10mg and
2.5mg tablets. Patients should be warned to report immediately the onset of signs of blood disorders, liver toxicity
and respiratory effects (see BNF).
6. Pharmacists should also be particularly vigilant due to the potential for serious untoward events if the wrong
strength is dispensed. Pharmacists should communicate verbally any dose changes to the patient/carer to ensure
changes are understood. The dispensing label should clearly show the strength, dose and frequency of
administration.
7. In the treatment of non-cancer conditions (e.g. rheumatology and dermatology), methotrexate must be given once
a week or once a month. Staff must ensure the correct dosing interval is given.
8. Please note: special waste disposal arrangements for methotrexate are required by law.
9. Folic acid 5mg supplements are advisable. There is little evidence with regard to the use and dose. 5-10mg is
frequently used, with a gap of 24-48 hours between methotrexate and folic acid doses.
10. Folic acid should be prescribed generically.
11. Methotrexate-induced mucositis or myelosuppression: folinic acid (given as calcium folinate) is used to counteract
the folate-antagonist action of methotrexate and so facilitate recovery from methotrexate-induced mucositis or
myelosuppression.
12. Methotrexate and NSAIDs: if aspirin or other NSAIDs are given concurrently, the dose of methotrexate should be
carefully monitored. Patients should be advised to avoid self-medication with over-the-counter aspirin or ibuprofen.
13. Mycophenolate is recommended locally for lupus, scleroderma, overlap syndrome, myositis and general
connective tissue disorders. These are unlicensed uses and should only be prescribed in primary care under
shared care arrangements agreed by each individual GP. The MHRA has recently issued a warning regarding
reports of pure red blood cell aplasia associated with mycophenolate use hence responsibilities for monitoring
should be made clear within the shared care arrangements.
SUPPORTING INFORMATION ON THE PRESCRIBING OF METHOTREXATE
Please refer to:


National Patient Safety Agency (NPSA): Reducing the harm caused by oral methotrexate
Guidelines on monitoring drugs in primary care
 British National Formulary (most recent issue)
Background
Methotrexate is a disease-modifying drug used in the treatment of moderate to severe rheumatoid arthritis, including
juvenile arthritis and severe uncontrolled psoriasis, unresponsive to conventional therapy; and steroid
dependent/refractory Crohn’s Disease.
50,000 prescriptions for oral methotrexate are written in the NHS each year. It is a safe and effective medication if
taken at the right dose and with appropriate monitoring. However, the NPSA is aware of 137 patient safety incidents
over the last 10 years in England alone due to problems with taking methotrexate. This included 25 patient deaths and
26 cases of serious harm.
Preparations
Methotrexate is available as tablets containing the equivalent of 2.5mg and 10mg of methotrexate. Injection forms are
available.
Care needs to be taken by prescribers and pharmacists to ensure the correct strength is prescribed and dispensed. All
dose changes must be clearly communicated with patients / carers.
Recommended dosage and administration
Psoriasis
10mg - 25mg orally once weekly
Rheumatoid Arthritis
7.5mg - 25mg orally once weekly
The maximum total weekly dose of methotrexate is usually 20mg, however, there may be
specific situations where the specialist will advise of the need for a higher dose.
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 6 of 13
Specialist only drugs
Side effects
The toxicity profile when methotrexate is given in weekly low doses is different from when given at high doses for
neoplastic disease. The most common side effects include:
GI toxicity – nausea, diarrhoea, ulcerative stomatitis
CNS effects – headaches, drowsiness, blurred vision
Folic acid may help reduce the frequency of mucosal or gastrointestinal side effects.
Serious side effects can occur acutely at any time during treatment, in particular:
Blood count
Haematopoietic suppression may occur abruptly; factors likely to increase toxicity include
advanced age, renal impairment and concomitant administration of another anti-folate drug. Any
profound drop in white cell or platelet count calls for immediate withdrawal of methotrexate and
introduction of supportive therapy.
Liver toxicity
Treatment should not be started or should be discontinued if any abnormality of liver function
tests or liver biopsy is present or develops during therapy. Abnormalities may return to normal
within 2 weeks after which treatment may be recommenced if judged appropriate.
Pulmonary
Pulmonary toxicity may be a special problem in rheumatoid arthritis – patient should seek
toxicity
medical attention if dyspnoea, cough or fever. Monitor for symptoms at each visit and refer back
to the specialist if present. Discontinue if pnemonitis suspected.
Drug interactions
The following classes/drugs have a potentially serious interaction with methotrexate and caution must be used when
prescribing concurrently: [Refer to BNF for further information]
 Antibacterials
 Ciclosporin
 Cisplatin
 Corticosteroids
 NSAIDs
 Omeprazole
 Phenytoin
 Probenecid
 Pyrimethamine
 Theophylline
Avoid concomitant use of methotrexate with:
 Acitretin
 Clozapine
 Nitrous oxide
Aspirin and other NSAIDs:
If aspirin or other NSAIDs are given concurrently the dose of methotrexate should be carefully monitored. Patients
should be advised to avoid self-medication with over-the-counter aspirin or ibuprofen.
Contra-indications
 Hepatic impairment
 Pregnancy ~ following administration to a woman or a man, avoid conception for at least 3 months after stopping.
Female patients of childbearing age should be offered contraception.
 Breast feeding
 Active infection and immunodeficiency syndromes
Cautions
 Blood disorders ~ avoid in macrocytosis and cytopenias. Investigate appropriately before starting methotrexate
treatment.
 Renal impairment ~ avoid in moderate to severe (GFR <20ml/minute; serum creatinine > 300micromol/L)
 Peptic ulceration, ulcerative colitis, diarrhoea and ulcerative stomatitis ~ withdraw if stomatitis
 Risk of accumulation in pleural effusion or ascites ~ drain before treatment
 Porphyries
 Patients should exercise restraint from alcohol whilst taking methotrexate, as concomitant alcohol consumption
may increase the risk of liver damage.
 Patients should be made aware of, and report sore throats, fever or chills, nose bleeds, severe skin rash or
bruising, ulceration of mucous membranes, or any unexplained illness that occurs, including nausea or
diarrhoea. An urgent full blood count and liver function tests should be performed.
 Patients experiencing any pulmonary symptoms (chest pain, difficulty breathing or a persistent cough) should be
investigated urgently with chest x-ray to exclude pneumonitis.
 Patients should check with their doctor or pharmacist before taking any other medicines and before having any
vaccinations.
Shared care guidelines
Shared care guidelines including monitoring requirements can be searched for here (accessible by N3 connection
only)
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 7 of 13
Specialist only drugs
Further information
Why do health professionals make mistakes?
The once weekly dosage is very unusual. Only a tiny proportion of medicines administered in the UK are taken at
this frequency. Whilst drug packaging includes reminders of the correct dose, in practice these prompts are not
sufficiently eye-catching to prevent mistakes. In addition, the packaging for the 10mg strength tablet looks very
similar to the 2.5 mg strength tablet.
Why do carers make mistakes?
The drug is packaged in packs of 28 or 100. When patients are prescribed smaller quantities, the dose warning
information is often separated from the tablets. In addition folic acid is often prescribed with methotrexate. As these
tablets are taken daily this can add to the confusion. There is evidence that even when patients are given clear
written information that they should take this drug on a weekly basis, they can assume that this must be incorrect.
For this reason verbal communication with patients is essential.
In addition methotrexate is a powerful drug. Patients and carers are not always sufficiently informed of the symptoms
they should look out for that would indicate toxicity.
Patient information
Patients should be given information about oral methotrexate and allowed time to understand it or discuss it with
their families, before embarking on treatment. The weekly dosing regime and the importance of monitoring must be
stressed.
Once treatment has been commenced, the patient should be given a “patient-held monitoring and dosage record”.
Prescriptions
All prescriptions should avoid the use of “as directed” in prescribing; a specific dose must be applied to each
prescription. Patients often understand their dose by number of tablets rather than “mg”; quantity and frequency of
dose should be regularly discussed with the patient.
Patient held monitoring booklets
It is important that the monitoring booklet held by the patient is completed after each blood test to provide a
complete record that can be seen by any practitioner who is seeing the patient.

Sulfasalazine
Tablets E/C 500 mg,
SUPPORTING INFORMATION ON THE PRESCRIBING OF SULFASALAZINE
Please refer to BRITISH NATIONAL FORMULARY (most recent issue)
Background
Sulfasalazine has a beneficial effect in suppressing the inflammatory activity of rheumatoid arthritis.
Preparations
Sulfasalazine is available as enteric-coated tablets or film coated tablets in a strength of 500mg.
Recommended dosage and administration (unless otherwise indicated)
500mg DAILY, increased by 500mg intervals of 1 week to a maximum of 2g – 3g DAILY in divided doses.
Side effects

General ~ slow acetylator patients are more likely to experience nausea, headache, rash, loss of appetite and
raised temperature.

Specific ~ The risk of blood disorders are substantially higher in patients treated for rheumatoid arthritis.

Hypersensitivity reaction ~ including exfoliative dermatitis, epidermal necrolysis, pruritus, photsensitization,
anaphylaxis, serum sickness.

Gastro-intestinal reactions ~ Stomatitis, parotitis, pancreatitis, hepatitis.

CNS reactions ~ Vertigo, tinnitus, peripheral neuropathy, aseptic meningitis, ataxia, convulsions, insomnia,
mental depression and hallucinations.

Fertility ~ Oligospermia, reversible when drug discontinued.

Renal Reactions ~ Crystalluria, haematuria, proteinuria and nephritic syndrome. An acute attack may be
precipitated in patients with porphyria.
Drug interactions
The following drugs interact with sulfasalazine and caution must be used when prescribing concurrently:
[Refer to BNF for further information]
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 8 of 13
Specialist only drugs

Sulfasalazine possibly reduces absorption of digoxin and folic acid

Possible increased risk of leucopenia with azathioprine and mercaptopurine
Cytokine Modulators
Abatacept

Orencia® 125mg, 250mg vial, 125mg prefilled pen, syringe
IV infusion
Subcutaneous injection
Adalimumab

Humira® 40mg pre-filled syringe, 40mg prefilled pen, 40mg vial
Subcutaneous injection
Certolizumab pegol

Cimzia® pre-filled syringe, 200mg
Subcutaneous injection
Etanercept

Benepali®▼ 50mg prefilled pen, 50mg
prefilled syringe
1st choice for new initiations

Enbrel®10mg, 25mg vial; 25mg,50mg prefilled syringe; 25mg, 50mg pre-filled pen
Subcutaneous injection
Golimumab

Simponi® 50mg, 100mg pre-filled pen
Subcutaneous injection
Infliximab

Inflectra®▼ 100mg vial
Biosimilar – 1st choice

Remicade® 100mg vial
Infliximab must be prescribed by
brand

Remsina®▼ 100mg vial
Biosimilar – 1st choice.

MabThera®, 500mg vial
Prescribe rituximab by brand

Truxima®▼, 500mg vial
Secukinumab▼

Cosentyx® 150mg pre-filled syringe; 150mg
pre-filled pen
Subcutaneous injection
Tocilizumab

RoActemra® 80mg,200mg, 400mg vial,
162mg pre-filled syringe
IV infusion
Stelara ® 45mg vial; 45mg, 90mg pre-filled
syringe
Subcutaneous injection
Rituximab
Ustekinumab

Prescribe by brand
Biosimilar – 1st choice.
Subcutaneous injection
Two biosimilar versions of infliximab are now available. They originate from the same manufacturer hence
either can be used when a biosimilar version of infliximab has been prescribed.
MHRA drug safety update (April 2014): There is an increased risk of tuberculosis, or reactivation of latent
tuberculosis, during treatment with tumour necrosis factor alpha (TNF-alpha) inhibitors. TNF-alpha inhibitors
are contraindicated in patients with active tuberculosis or other severe infections. Patients should be screened
patients for active and latent tuberculosis before starting treatment with a TNF-alpha inhibitor and monitored
closely for infectious diseases including tuberculosis before, during, and after treatment.
NICE TA 375: Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and
abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs
only have failed (Jan 2106) replaces NICE technology appraisal guidance on:
adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis (TA130), certolizumab pegol for
the treatment of rheumatoid arthritis (TA186), golimumab for the treatment of methotrexate-naive rheumatoid
arthritis (TA224) and abatacept for treating rheumatoid arthritis after the failure of conventional diseasemodifying anti-rheumatic drugs (TA280). It partially updates golimumab for the treatment of rheumatoid arthritis
after the failure of previous disease-modifying anti-rheumatic drugs (TA225) and tocilizumab for the treatment
of rheumatoid arthritis (TA247).
Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept, all in
combination with methotrexate, are recommended as options for treating rheumatoid arthritis, only if:
 disease is severe, that is, a disease activity score (DAS28) greater than 5.1 and
 disease has not responded to intensive therapy with a combination of conventional disease‑ modifying
antirheumatic drugs (DMARDs)
and
 the companies provide certolizumab pegol, golimumab, abatacept and tocilizumab as agreed in their
patient access schemes.
Adalimumab, etanercept, certolizumab pegol or tocilizumab can be used as monotherapy for people who
cannot take methotrexate because it is contraindicated or because of intolerance, when the criteria above are
met.
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 9 of 13
Specialist only drugs
NICE TA 415: Certolizumab pegol for treating rheumatoid arthritis after inadequate response to a TNFalpha inhibitor (Oct 2016)
Certolizumab pegol, in combination with methotrexate, is recommended as an option for treating rheumatoid
arthritis in adults whose disease has responded inadequately to, or who cannot tolerate, other diseasemodifying antirheumatic drugs (DMARDs) including at least 1 tumour necrosis factor‑ alpha (TNF‑ alpha)
inhibitor, only if:

disease activity is severe and

rituximab is contraindicated or not tolerated
Continue treatment only if there is a moderate response measured using European League Against
Rheumatism (EULAR) criteria at 6 months after starting therapy.
After initial response within 6 months, withdraw treatment if a moderate EULAR response is not maintained.
If more than one treatment is suitable, the least expensive (taking into account administration costs
and patient access schemes) should be chosen.
Anakinra is not commissioned for the treatment of rheumatoid arthritis in East Sussex.
NICE Guidance TA 199: Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis
(Aug 2010)
Etanercept, infliximab and adalimumab are all recommended for the treatment of active and progressive
psoriatic arthritis, based on specific criteria. Treatment choice should be started with the least expensive drug
(taking into account drug administration costs, required dose and product price per dose).
The guidance recommends that treatment should be discontinued if people’s disease does not show an
adequate response on the Psoriatic Arthritis Response Criteria (PsARC) at 12 weeks. Healthcare professionals
should also
consider continuing treatment if people’s skin disease has a Psoriasis Area and Severity Index (PASI) 75
response
at 12 weeks in the absence of an adequate PsARC response. This assessment should be done by a
dermatologist
to determine whether continued treatment is appropriate on the basis of the skin response alone.
NICE Guidance TA 220: Golimumab for the treatment of Psoriatic Arthritis (April 2011)
Golimumab is recommended as a treatment option for psoriatic arthritis in accordance with TA 199 above.
Note: NICE reported that their review of the evidence suggested that golimumab may not be as effective at
controlling the joint manifestations of psoriatic arthritis and that of all the treatments, etanercept is the most cost
effective. Etanercept should therefore be considered as the first-line treatment option for psoriatic arthritis.
NICE Guidance TA 340: Ustekinumab for treating active psoriatic arthritis (rapid review of technology
appraisal guidance 313) (June 2015)
Ustekinumab is recommended for treating active psoriatic arthritis when patients have failed treatment with
TNF-alpha inhibitors or where TNF-alpha inhibitors are contraindicated.
NICE guidance TA 383: TNF-alpha inhibitors for ankylosing spondylitis and non-radiographic axial
spondyloarthritis (Feb 2016) replaces NICE technology appraisal guidance on adalimumab, etanercept and
infliximab for ankylosing spondylitis (TA143) and golimumab for the treatment of ankylosing spondylitis
(TA233).
In severe active ankylosing spondylitis:

Adalimumab, certolizumab pegol, etanercept, golimumab and infliximab are recommended in adults
whose disease has responded inadequately to, or who cannot tolerate, non steroidal anti inflammatory
drugs.

Infliximab is recommended only if treatment is started with the least expensive infliximab product. In
the East Sussex local health economy, this is currently the biosimilar Inflectra®
In severe non-radiographic axial spondyloarthritis (nrAS):

Adalimumab, certolizumab pegol and etanercept are recommended within their marketing
authorisations in adults whose disease has responded inadequately to, or who cannot tolerate, non
steroidal anti inflammatory drugs
If more than one treatment is suitable, the least expensive (taking into account administration costs
and patient access schemes) should be chosen.
The response to TNF-alpha inhibitor treatment should be assessed 12 weeks after the start of treatment and
should only be continued if there is clear evidence of response, defined as:

a reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score to 50% of the
pre‑ treatment value or by 2 or more units
and
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 10 of 13
Specialist only drugs

a reduction in the spinal pain visual analogue scale (VAS) by 2 cm or more.
Treatment with another TNF‑ alpha inhibitor is recommended for people who cannot tolerate, or whose
disease has not responded to, treatment with the first TNF‑ alpha inhibitor, or whose disease has stopped
responding after an initial response.
NICE guidance TA 407: Secukinumab for active ankylosing spondylitis after treatment with nonsteroidal anti-inflammatory drugs or TNF-alpha inhibitors (Sept 2016)
Secukinumab is recommended as an option for treating active ankylosing spondylitis in adults whose disease
has responded inadequately to conventional therapy (non-steroidal anti-inflammatory drugs or TNF alpha
inhibitors)
NICE Guidance TA 373: Abatacept, adalimumab, etanercept and tocilizumab for treating juvenile
idiopathic arthritis (December 2015)
Abatacept (Orencia), adalimumab (Humira), etanercept (Enbrel) and tocilizumab (RoActemra) are
recommended as possible treatments for people with polyarticular juvenile idiopathic arthritis.
Adalimumab and etanercept are recommended as possible treatments for people with enthesitis-related
juvenile idiopathic arthritis.
Etanercept is recommended as a possible treatment for people with psoriatic juvenile idiopathic arthritis.
10.1.4 Gout and cytotoxic-induced hyperuricaemia
Acute attacks of gout
Indometacin
 Capsules 25 mg, 50 mg
 Suppositories 100 mg
Dose: 150-200mg daily in divided doses
Naproxen
 Tablets 250 mg, 500 mg
Dose: 750mg initially, then 250mg every 8 hours
until attack has passed
Diclofenac

Tablets 25 mg, 50 mg
 Dispersible tablets 50 mg
 Suppositories 12.5 mg, 25 mg, 50 mg,
100 mg

Tablets 500 micrograms
Allopurinol

Tablets 100 mg, 300 mg
Febuxostat

Adenuric® Tablets 80mg, 120mg
Colchicine
Long-term control of gout
1. High doses of NSAIDs such as indomethacin, diclofenac or etoricoxib, or colchicine may be used for the
treatment of acute attacks of gout.
2. Caution: toxicity in high risk, especially older, patients.
3. Colchicine is probably as effective as NSAIDs and is of value for patients with heart failure since, unlike NSAIDs,
it does not induce fluid retention. It can also be given to patients receiving anticoagulants.
4. The dose of colchicine in acute gout is 1mg initially followed by 500micrograms every 4 hours until relief of pain is
obtained or vomiting or diarrhoea occurs or until a total dose of 6mg (12 tablets) has been reached. The course
should not be repeated within 3 days.
5. Allopurinol is indicated for gout prophylaxis but it should never be started during, or within one month of, an
acute attack. Colchicine or NSAIDs should be used as a prophylactic and continued for at least one month after
the hyperuricaemia has been corrected.
6. The dose of allopurinol should be reduced in patients with renal failure.
7. Febuxostat is an option for the management of chronic hyperuricaemia in gout only for people who are intolerant
of allopurinol or for whom allopurinol is contraindicated. Intolerance of allopurinol is defined as adverse effects that
are sufficiently severe to warrant its discontinuation, or to prevent full dose escalation for optimal effectiveness.
NICE TA 164: Febuxostat for the treatment of hyperuricaemia (July 2008)
10.1.5 Other drugs for rheumatic diseases
1. Prescribing of glucosamine and chondroitin is not recommended within East Sussex. The evidence of benefit
in osteoarthritis is inconsistent and variable. NICE guidance CG177 Feb 2014 states that the use of glucosamine or
chondroitin products is not recommended for the treatment of osteoarthritis.
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 11 of 13
Specialist only drugs
2. Patients wishing to use these treatments should be advised to purchase them.
3. Whilst evidence of benefit is minimal, there is little evidence of harm, although the MHRA recommend that patients
on warfarin should not take glucosamine supplements since the combination may increase the likelihood of
bleeding.
10.2 Drugs used in neuromuscular disorders
10.2.1 Drugs which enhance neuromuscular transmission
Pyridostigmine
 Tablets 60 mg
Neostigmine
 Tablets 15mg
Edrophonium chloride
 Injection 10 mg in 1 ml
Notes:
1. Pyridostigmine and neostigmine are included for the treatment of myasthenia gravis diagnosed by a Specialist.
2. Edrophonium is used as a diagnostic agent for myasthenia gravis.
10.2.2 Skeletal muscle relaxants
Baclofen
 Tablets 10 mg
 Liquid SF 5 mg in 5 ml
Dantrolene

Capsules 25mg, 100mg
Tizanidine

Tablets 2mg, 4mg
Notes:
For guidance on the treatment of spasticity in Multiple Sclerosis see NICE CG 186 (October 2014)
1. The underlying cause of spasticity should be treated and any aggravating factors (e.g. pressure sores, infection)
treated.
2. Dantrolene acts directly on skeletal muscle and produces fewer central adverse effects making it a drug of choice.
3. Baclofen inhibits transmission at spinal level and also depresses the central nervous system.
4. Doses for dantrolene and baclofen should be increased slowly.
5. Tizanidine is an alpha2-adrenoceptor agonist indicated for spasticity associated with multiple sclerosis or spinal
cord injury. It should only be initiated by a specialist for patients unable to tolerate dantrolene or baclofen.
6. Diazepam (section 4.1.2) may also be used. Sedation and, occasionally, extensor hypotonus are disadvantages.
Nocturnal leg cramps
 Tablets 200 mg, 300 mg
Quinine Sulphate
1. Quinine salts are effective in reducing the frequency of nocturnal leg cramps by about 25% in ambulatory patients.
2. It may take up to 4 weeks for improvement to become apparent and it is then given on a continuous basis if there
is a benefit.
3. Treatment should be interrupted at intervals of approximately 3 months to assess the need for further quinine
treatment.
4. Patients should be monitored closely during the early stages for adverse effects as well as for benefit.
5. Quinine is very toxic in over dosage and accidental fatalities have occurred in children.
Refer to current BNF for information on cautions, contraindications and side effects.
10.3
Drugs for the relief of soft-tissue inflammation
10.3.1 Enzymes
Hyaluronidase
Hyalase® powder for reconstitution 1,500 units
10.3.2 Rubefacients and other topical antirheumatics
Algesal®
 Cream containing diethylamine salicylate 10%
Ibuprofen
 Gel 5%
Ketoprofen
 Gel 2.5%
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 12 of 13
Specialist only drugs
Piroxicam
 Gel 0.5%
Capsaicin (Zacin®)
 Cream containing 0.025% capsaicin
1. NICE clinical guidelines for Osteoarthritis CG177 Feb 2014 recommend topical NSAIDs for pain relief in
osteoarthritis but not topical rubefacients.
2. The term topical NSAID included salicylate and benzydamine compounds, and therefore, the formulary
supports the use of Algesal® first line.
3. The Drug Tariff price of different topical NSAID preparations fluctuates greatly and the hence a prescribers product
of choice should be reviewed regularly.
4. Generally, foam, spray and patch formulations are more expensive and hence should not be prescribed.
5. Topical capsaicin cream is a treatment option for knee and hand osteoarthritis but please note only the 0.025%
formulation (Zacin®) is licensed for symptomatic relief in osteoarthritis. The 0.075% cream (Axsain®) is only
licensed for post-herpetic neuralgia and painful diabetic neuropathy.
First line drugs
Second line drugs
Specialist drugs
Adapted from Plymouth Area Joint Formulary
Chapter 10 Musculoskeletal and joint diseases. Page 13 of 13
Specialist only drugs