10.0 Musculoskeletal and joint diseases

10.1.1 Non-steroidal anti-inflammatory drugs (NSAIDs)

First line treatment

GREEN Ibuprofen

tablets 200mg, 400mg, 600mg

syrup 100mg/5mL

GREEN Naproxen

tablets 250mg, 500mg

Gastrointestinal toxicity and cardiovascular toxicity are the two most important safety concerns for

non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors (coxibs). Clinical trial and

epidemiological data have given important information on the level of risk with individual

medicines. However, these data are complex and there are no robust comparisons for many

NSAIDs. Most evidence relates to the coxibs, naproxen, ibuprofen, and diclofenac. The National

Prescribing Centre (NPC) has summarised up-to-date prescribing advice and information in relation

to NSAIDs, which is available through their website (www.npc.nhs.uk).

Thrombotic risks

In October 2006, the Commission on Human Medicines (CHM) gave advice on the latest evidence for

cardiovascular thrombotic risks:

> Diclofenac 150 mg daily has a thrombotic risk profile similar to that of at least one coxib

(etoricoxib) and possibly others

> Naproxen 1000 mg daily has a lower thrombotic risk than coxibs and, overall, epidemiological

data do not suggest an increased risk of myocardial infarction

> For ibuprofen at high doses (eg, 2400 mg daily) there may be a small thrombotic risk, but at

lower doses (eg, 1200 mg daily or less) epidemiological data do not suggest an increased risk

of myocardial infarction

Less evidence is available for other NSAIDs, but they may be associated with a small risk of thrombotic

events, especially with long duration of treatment and high doses.

Cardiovascular risks

Results of two recently published epidemiological studies lend support to the view that some increase in

thrombotic cardiovascular risk may apply to all NSAID users, irrespective of their baseline risk, and not

only to chronic users. The absolute increase in risk for 'healthy' users is very low. Current advice

remains that patients should use the lowest effective dose and the shortest duration of treatment

necessary to control symptoms. Overall evidence continues to indicate that naproxen is associated with

a lower thrombotic risk than coxibs. For ibuprofen, no significant increase in risk has been identified

for doses of up to 1200mg daily.

Reference: Drug Safety Update, Volume 2 Issue 7, February 2009.

Gastrointestinal risks

The Committee on Safety of Medicines (now the Commission on Human Medicines) has reviewed the

relative gastrointestinal risks of NSAIDs on several occasions. Recently, we have highlighted the high

gastrointestinal risks with piroxicam, ketoprofen, and ketorolac. Of the traditional NSAIDs, low-dose

ibuprofen offers the lowest risk. Coxibs are associated with reduced gastrointestinal risk relative to

most NSAIDs at equivalent doses. However, coxibs (like NSAIDs) may vary in their effects, and evidence

for a reduction in the most clinically important gastrointestinal risks for etoricoxib is weak. Proton

pump inhibitors reduce the gastrointestinal risks associated with NSAIDs, and may reduce the risks to a

similar level as use of a coxib alone.

Other NSAIDs

GREEN Diclofenac

injection 25mg/mL

suppositories 12.5mg, 25mg, 50mg, 100mg

GREEN Mefenamic acid

capsules 250mg

tablets 500mg

Indometacin is usually recommended only for ankylosing spondylitis and gout.

GREEN Indometacin

capsules 25mg, 50mg

suppositories 100mg

Patients over 65 years who are in high risk groups for developing ulcers (history of peptic ulcer or

bleeding, cardiovascular disease) should be given protection for the stomach when prescribed NSAIDs.

NSAIDs and PPIs (Section 1.3.5) are often used together for these at risk patients.

Cox IIs (cyclo-oxygenase II selective inhibitors)

The MHRA has issued the following general advice concerning all selective COX-2 inhibitors (Feb-05):

> Patients with established ischaemic heart disease, cerebrovascular disease or peripheral

arterial disease should be switched to alternative treatment

> For all patients the balance of gastrointestinal and cardiovascular risk should be

considered before prescribing a COX-2 inhibitor, particularly for those with risk

factors for heart disease and those taking low dose aspirin, for whom gastrointestinal benefit

has not been clearly demonstrated.

> The lowest effective dose of COX-2 inhibitor should be used for the shortest necessary

period. Periodic re-evaluation is recommended, especially for osteoarthritis patients who may

only require intermittent treatment.

> Gastro-protective agents should be considered for patients switched to non-selective

NSAIDs

GREEN Celecoxib

capsules 100mg, 200mg

GREEN Meloxicam

tablets 7.5mg, 15mg

AMBER Etoricoxib (Rheumatology initiation only)

tablets 60mg, 90mg, 120mg

Osteoarthritis - NICE Clinical Guideline 177 February 2014

Treatment and management

Core treatment:

There are three core interventions which should be considered for every person with osteoarthritis:

> access to appropriate patient information sources,

> activity and exercise,

> interventions to achieve weight loss if person is overweight or obese.

If further treatment is required then adjunctive treatments should be considered;

Pharmacological:

> Paracetamol (regular dosing may be required). AND/OR

> Topical non steroidal anti-inflammatory drugs (NSAIDs) or topical capsaicin for knee or hand

osteoarthritis

If above agent/s are ineffective or insufficient then consider;

> Substitution or addition of an oral NSAID or COX-2 inhibitor (but NOT eterocoxib) OR

> Opioid analgesics

Consider intra-articular corticosteroid injections if pain is moderate to severe.

Treatment with oral NSAIDs/COX-2 inhibitors:

All oral NSAIDs/COX-2 inhibitors have similar analgesic effects but vary in their gastrointestinal, liver and

cardio-renal toxicity. This should be taken into account when choosing the drug and dose for an

individual patient.

Treatment with oral NSAIDs/COX-2 inhibitors:

> Prescribe the lowest effective dose for the shortest possible period of time,

> ALWAYS co-prescribe a proton pump inhibitor (PPI) - choose one with the lowest cost.

> Assess patient risk factors for gastrointestinal, liver and cardio-renal toxicity,

> Consider ongoing monitoring of patient risk factors,

> Use an alternative analgesic if patient is taking low-dose aspirin.

Treatment with opioids:

> Consider the risks and benefits particularly in elderly people.

> Adverse effects: constipation, nausea, itchiness, drowsiness and confusion

Non-pharmacological:

> Application of heat or cold to the site of pain.

> Transcutaneous electrical nerve stimulation (TENS).

> Manipulation and stretching, particularly for hip osteoarthritis.

> Assessment for bracing/joint supports/insoles for people with biomechanical joint pain or

instability.

> Assistive devices (for example, walking sticks and tap turners) for people with specific

problems with daily activities. Expert advice may be required.

Treatments not recommended

> rubefacients

> intra-articular hyaluronan injections

> electro-acupuncture

> chondroitin or glucosamine products

10.1.2 Corticosteroids

10.1.2.2 Local corticosteroid injections

These are given by intra-articular injection or by injection into soft tissue or the tendon sheath and

should be considered as an adjunct to core treatments for the relief of moderate to severe pain

in people with osteoarthritis.

GREEN Hydrocortisone acetate injection 25mg/mL

GREEN Methylprednisolone injection 40mg/mL

GREEN Triamcinolone acetonide injection 40mg/mL

RED Triamcinolone acetonide injection 10mg/mL

RED Triamcinolone hexacetanide 20mg/mL (Lederspan®) – unlicensed import for use in chronic

juvenile arthritis only.

10.1.2.3 Other local injections

Hyaluronan injections for osteoarthritis- Updated Feb 2014 CG177

NICE states ‘ Do not offer intra-articular hyaluronan injections for the management of osteoarthritis'

BLACK - Hyaluronan injections.

10.1.3. Drugs which suppress the rheumatic disease process

These are sometimes called disease modifying anti-rheumatic drugs (DMARDs). They are used when

NSAIDs alone are not sufficient and they should only be initiated by a specialist. They require 4-6

months of treatment for a full response. If there is no benefit after 6 months they should be

discontinued on specialist advice.

AMBER SHARED CARE Azathioprine tablets 25mg, 50mg

AMBER SHARED CARE Ciclosporin (Neoral®)

capsules 25mg, 100mg

oral solution 100mg/mL

RED Cyclophosphamide injection 500mg, 1g

AMBER Hydroxychloroquine tablets 200mg - see Prescriber Information Sheet

AMBER SHARED CARE Leflunomide tablets 10mg, 20mg

RED Leflunomide tablets 100mg (used for initial loading doses only)

Secondary care will prescribe and supply leflunomide for the first three months, the primary care prescriber

may then take over prescribing and the associated monitoring.

Methotrexate

All new patients started on methotrexate will be supplied with 2.5mg tablets only. Prescribers are

reminded to follow the monitoring guidance outlined in the shared care protocol available here .

AMBER SHARED CARE Methotrexate tablets 2.5mg only

RED Methotrexate injection, for s/c or i/m use (Metoject®, Ebetrex®)

Methotrexate should be prescribed once weekly as a single dose on the same day each week.

Folic acid 5mg should normally be taken the day after methotrexate dosing.

AMBER SHARED CARE Penicillamine tablets 125mg, 250mg

AMBER SHARED CARE Sodium aurothiomalate injection 10mg, 20mg, 50mg

AMBER SHARED CARE Sulfasalazine tablets e/c 500mg

Cytokine modulators

These drugs should be prescribed by specialists only, and in line with any relevant NICE guidance.

Certolizumab, rituximab and tocilizumab (inc. Abatacept, Adalimumab, Etanercept, Golimumab and

Infliximab) - NICE guidance for rheumatoid arthritis (TAG 130, 186, 195, 198, & 225).

Treatment pathways for highly active rheumatoid arthritis in adults who have failed to respond to at

least two standard disease modifying anti-rheumatic drugs (DMARDs) including methotrexate. These

drugs should be prescribed according to the guidelines of the British Society for Rheumatology under

the supervision of consultant rheumatologist.

Please refer to the full guidelines for further information.

Etanercept - NICE guidance for juvenile idiopathic rheumatoid arthritis (TAG 35)

For children aged 4 to 17 years who have active JIA in at least five joints and whose condition has not

responded adequately to or have been unable to tolerate treatment with methotrexate. Only a

consultant who regularly sees children and young adults with JIA and who runs specialised paediatric

rheumatology clinics should prescribe etanercept.

Please refer to full guidelines for further information.

Secukinumab is recommended, within its marketing authorisation, 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) as per NICE TA407

RED Secukinumab solution for injection 150mg/1mL

Adalimumab, Certolizumab pegol , Etanercept, Golimumab and Infliximab - in line with NICE Guidance

for Ankylosing spondylitis and non-radiographic axial spondyloarthritis (NICE TA383).

(Replaces NICE technology appraisal guidance on adalimumab, etanercept and infliximab for ankylosing

spondylitis (TA143) and golimumab for the treatment of ankylosing spondylitis (TA233).

These drugs are for people with severe active ankylosing spondylitis or severe non‑radiographic axial

spondyloarthritis who have tried non‑steroidal anti‑inflammatory drugs (NSAIDs), but they have not

worked.

RED Adalimumab pre-filled pen/syringe 40mg

RED Certolizumab pegol pre-filled syringe 200mg

RED Etanercept vial for injection 25mg

pre-filled pen/syringe 25mg, 50mg

RED Golimumab pre-filled pen/syringe 50mg,100mg

RED Infliximab vial for infusion 100mg

Golimumab for severe non-radiographic axial spondyloarthritis.

This drug is for adults who have tried nonsteroidal anti-inflammatory drugs (NSAIDs),

but they have not worked. Recommended as an option, within its marketing authorisation, as an

option in NICE TA497

RED Golimumab 50 mg solution for injection in pre-filled pen (Simponi®)

CCG Commissioned - BlueTeq Form

Adalimumab, Etanercept, Infliximab, Certolizumab pegol, Golimumab, tocilizumab and abatacept -

NICE Guidance for Rheumatoid arthritis not previously treated with DMARDS or after conventional

DMARDS only have failed are recommended as an option by NICE. NICE TA375.

Please refer to full guidelines for further information.

Belimumab is recommended as an option as add-on treatment for active autoantibody-positive

systemic lupus erythematosus in adults as per NICE TA397

RED Belimumab ( Benlysta®)

powder for concentrate for solution for infusion 120mg, 400mg

Adalimumab, Etanercept, Golimumab and Infliximab - NICE guidance for psoriatic

arthritis (NICE TAG199 & 220)

Treatment options for adults with severe active psoriatic arthritis who:

> have peripheral arthritis with three or more tender joints, and

> three or more swollen joints, and

> other disease modifying anti-rheumatic drugs (DMARDs) administered individually or in

combination have not worked.

Please refer to the full guidelines for further information.

Belimumab is recommended as an option as add-on treatment for active autoantibody-positive

systemic lupus erythematosus in adults as per NICE TA397

RED Belimumab ( Benlysta®)

powder for concentrate for solution for infusion 120mg, 400mg

Abatacept (Orencia), adalimumab (Humira), etanercept (Enbrel) and tocilizumab (RoActemra) are

recommended as possible treatments for people with polyarticular juvenile idiopathic arthritis. Full

guidance - NICE TA373

> 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

Abatacept

Abatacept may be considered as a second line option for rheumatoid arthritis if either rituximab or

methotrexate is contraindicated or an adverse reaction has been experienced (see NICE guidance).

Infusion to be administered in hospital. (NICE TA195)

Abatacept for treating Rheumatoid Arthritis after failure of conventional disease modifying anti-

rheumatic drugs (NICE TAG280) (rapid review of TAG234) - recommended as an option by NICE in adults

whose disease has responded inadequately to two conventional DMARD's including methotrexate if

used in accordance with recommendations for other biologicals (TAG130) and PAS is provided

RED Abatacept vial for infusion 250mg

RED Abatacept pre-filled pen/syringe 125mcg

Adalimumab

Adalimumab is recommended either alone or in combination for the treatment of psoriatic arthritis

and ankylosing spondylitis. It is also a treatment option for rheumatoid arthritis (see NICE guidance).

Patients should be trained to self administer the injection.

RED Adalimumab pre-filled pen/syringe 40mg

Apremilast - NICE TA433 (relaces TA372) CCG Commissioned

Apremilast, alone or in combination with disease-modifying antirheumatic drugs (DMARDs), is

recommended as an option for treating active psoriatic arthritis in adults only if:

¤ they have peripheral arthritis with 3 or more tender joints and 3 or more swollen joints and

¤ their disease has not responded to adequate trials of at least 2 standard DMARDs, given either

alone or in combination and

¤ the company provides apremilast with the discount agreed in the patient access scheme

RED Apremilast tablets 10mg, 20mg, 30mg (Otezla®)

Certolizumab

Certolizumab pegol in combination with methotrexate is indicated for the treatment of moderate

to severe, active rheumatoid arthritisin adult patients when the response to conventional disease

modifying anti-rheumatic drugs (DMARDs) including methotrexate, has been inadequate (see NICE

guidance). Patients should be trained to self administer the injection.

RED Certolizumab pre-filled syringe 200mg

Certolizumab and Secukinumab as per NICE TA445 CCG Commissioned

The response to certolizumab pegol and secukinumab should be assessed after 12 weeks and 16 weeks of

treatment respectively and should only be continued if there is clear evidence of response as in NICE TA445.

Certolizumab pegol alone, or in combination with methotrexate, is recommended as an option for

treating active psoriatic arthritis in adults only if:

> it is used as described in the NICE technology appraisal guidance on on etanercept, infliximab

and adalimumab for the treatment of psoriatic arthritis (recommendations 1.1 and 1.2) or

> the person has had a tumour necrosis factor (TNF)-alpha inhibitor but their disease has

stopped responding after the first 12 weeks.

Certolizumab pegol is only recommended if the company provides it as agreed in the patient access

Secukinumab alone, or in combination with methotrexate, is recommended as an option for treating

active psoriatic arthritis in adults only if:

> it is used as described in the NICE technology appraisal guidance on etanercept, infliximab

and adalimumab for the treatment of psoriatic arthritis (recommendations 1.2 and 1.2) or

> the person has had a TNF‑alpha inhibitor but their disease has not responded within the first

12 weeks or has stopped responding after 12 weeks or

> TNF‑alpha inhibitors are contraindicated but would otherwise be considered (as described in

NICE technology appraisal guidance on etanercept, infliximab and adalimumab for the

treatment of psoriatic arthritis).

Secukinumab is only recommended if the company provides it as agreed in the patient access

scheme.

RED Certolizumab pre-filled syringe 200mg

RED Secukinumab pre-filled syringe 150mg/1mL

Certolizumab

Certolizumab is recommended for the treatment of adults withactive and progressive psoriatic arthritis

in line with NICE TA199, that is when the person has peripheral arthritis with three or more tender

joints and three or more swollen joints and their psoriatic arthritis has not responded to adequate trials

of at least two standard disease-modifying antirheumatic drugs, administered either individually or in

combination.

Certolizumab should be used in combination with methotrexate where possible, however can be given

as monotherapy in the case of intolerance to methotrexate or when continued treatment with

methotrexate is inappropriate

RED Certolizumab pre-filled syringe 200mg

Certolizumab

An option as as a second line anti-TNF (tumour necrosis factor) in psoriatic arthritis (PsA) following

discontinuation of first anti-TNF due to an adverse event or primary or secondary inefficacy.

RED Certolizumab pre-filled syringe 200mg

Certolizumab

Certolizumab pegol is licensed for the treatment of adults with severe active ankylosing spondylitis

who have had an inadequate response to, or are intolerant to non-steroidal anti-inflammatory

drugs (NSAIDs) (in line with NICE TA143)

RED Certolizumab pre-filled syringe 200mg

Certolizumab

Certolizumab pegol is recommended as an option for treating rheumatoid arthritis after inadequate

response to a TNF-alpha inhibitor - NICE TA415

RED Certolizumab pre-filled syringe 200mg CCG commissioned

Etanercept

Etanercept is recommended either alone or in combination with methotrexate for the treatment of

active polyarticular juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis. It is also a

treatment option for rheumatoid arthritis (see NICE guidance). Patients should be trained to self

administer the injection.

RED Etanercept vial for injection 25mg

pre-filled pen/syringe 25mg, 50mg

Golimumab

Treatment option for adults with severe active psoriatic arthritis only if used as described for other

tumour necrosis factor (TNF) inhibitors and the manufacturer provides the 100mg dose of Golimumab

at the same cost as the 50mg dose.

Please refer to the full guidelines for further information.

RED Golimumab pre-filled pen/syringe 50mg,100mg

Infliximab

Infliximab may be considered as an option to treat rheumatoid arthritis where:

> certolizumab, adalimumab and etanercept are contraindicated, or

> methotrexate is contraindicated or not tolerated, or

> the patient cannot self inject (see NICE guidance).

It is also a treatment option for psoriatic arthritis. Infusion to be administered in hospital.

RED Infliximab vial for infusion 100mg

Rituximab

Rituximab in combination with methotrexate is recommended as a second line option for the treatment

of adults with severe active rheumatoid arthritis who have had an inadequate response to, or are

intolerant of, other disease modifying anti-rheumatic drugs (DMARDs), including at least one tumour

necrosis factor (TNF) inhibitor. Treatment with rituximab should be given no more frequently than

every 6 months (see NICE guidance). Infusion to be administered in hospital.

Pre-medication 30-60 minutes before hand with methylprednisolone is necessary to reduce infusion-

related reactions. Rituximab should be prepared by a pharmacist or healthcare professional observing

aseptic techniques. As per BSR guidelines for anti-TNFs, treatment should be withdrawn following

adverse events or where there is an inadequate response at 3 months following initiation of treatment.

Rituximab should be funded via 'pass through funding' under payment by results, booked out to

individual patients in pharmacy and recharged directly to the PCTs. A New Drug review for rituximab

in rheumatoid arthritis is available - click here.

RED Rituximab vial for infusion 100mg, 500mg

Sarilumab - NICE guidance for moderate to severe rheumatoid arthritis (TA485)

Sarilumab with methotrexate , is recommended as an option for treating active rheumatoid arthritis in

adults whose disease has responded inadequately to intensive therapy with a combination of

conventional disease- modifying antirheumatic drugs (DMARDs) - as per NICE TA485

CCG Commissioned (Blue Tec form required)

Tocilizumab

Tocilizumab in combination with methotrexate is recommended third line for the treatment of

moderate to severe active rheumatoid arthritis in people whose condition (NICE TA198):

> has responded inadequately to one or more tumour necrosis factor alpha (TNFα)

inhibitors; and

> has responded inadequately or are contraindicated to rituximab, or when rituximab is

withdrawn because of an adverse effect as per NICE guidance.

Tocilizumab in combination with methotrexate is recommended for some children with juvenile

idiopathic arthritis where all other treatments have failed (NICE TA238).

Infusion to be administered in hospital.

RED Tocilizumab vial for infusion 80mg, 200mg, 400mg

Subcutaneous Tocilizumab is recommended for use as an alternative to intravenous Tocilizumab

providing the patient meets the prescribing criteria as set out in NICE technology appraisals for

1st, 2nd and 3rd line use to treat active rheumatoid arthritis (RA) and the agreed Lancashire

Rheumatology Alliance flex for use as monotherapy. CLICK here to link to the recommendation.

RED Tocilizumab injection 162mg pre-filled syringe

Tocilizumab is recommended as an option in treating Giant Cell Arteritis by NICE TA518, when used with

a tapering course of glucocoticoids (and when used alone after glucocorticoids) only if:

> they have relapsing or refractory disease

> they have not already had

> tocilizumab is stopped after 1 year of uninterrupted treatment at most and

> the company provides it with the discount agreed in the patient access scheme

RED Tocilizumab concentration for solution for infusion (RoActemra®)

(NHS England Commissioned)

Tofacitinib - Moderate to severe rheumatoid arthritis NICE TA480

Tofacitinib, with methotrexate, is recommended as an option for treating active rheumatoid arthritis in

adults whose disease has responded inadequately to intensive therapy with a combination of

conventional disease-modifying anti-rheumatic drugs (DMARDs), only if:

> disease is severe (a disease activity score [DAS28] of more than 5.1) and

> the company provides tofacitinib with the discoiunt agreed in the patient access scheme

Tofacitinib with methotrexate, is recommended as an option for treating active rheumatoid arthritis in

adults whose disease has responded inadequately to, or who cannot have, other DMARDs, including at

least 1 biological DMARD, only if:

> disease is severe (a DAS28 of more than 5.1) and

> they cannot have rituximab

> the company provides tofacitinib with the discount agreed in the patient access scheme

Tofacitinib can be used as monotherapy for adults who cannot take methotrexate because it is

contraindicated or because of intolerance, when the criteria in sections 1.1 and 1.2 are met.

RED Tofacitinib

tablets 5mg (Xeljanz®) (CCG Commissioned - Blue Teq form required)

10 Gout Management Prescribing Guidance v1.1 [pdf / 702KB] Gout Management Prescribing Guidance

10.1.4 Gout and cytotoxic-induced hyperuricaemia

Acute attacks of gout

High doses of NSAIDs are usually used.

Colchicine is an alternative. The BNF dose of colchicine is known to cause gastrointestinal side effects,

particularly in patients with impaired renal function. Local rheumatologists recommend colchicine be given at

a dose of 500micrograms twice daily for acute gout.

GREEN Colchicine tablets 500 micrograms

Long term control of gout

Long term control to reduce formation of uric acid can be achieved with allopurinol. It should not be started

during an acute attack. For approximately the first 6 weeks of therapy NSAIDs or colchicine should also be

given.

GREEN Allopurinol tablets 100mg, 300mg

Febuxostat

NICE TA164 advises febuxostat, within its marketing authorisation, as 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 as appropriate within its marketing

authorisation. Annual treatment costs for febuxostat are approximately £318 while for allopurinol they are approximately £16.

Drug Safety Update July 2019 advises avoiding treatment with febuxostat in patients with pre-existing major

cardiovascular disease (for example, myocardial infarction, stroke or unstable angina), unless no other

therapy options are appropriate.

AMBER Febuxostat tablets 40mg, 80mg

Hyperuricaemia associated with cytotoxic drugs

RED Rasburicase 1.5mg (Consultant Haematologist use only)

10.2.1 Drugs which enhance neuromuscular transmission

The anticholinesterases are used as first line treatment in myasthenia gravis. Edrophonium has brief action and is used

in diagnosis.

RED Edrophonium injection 10mg/mL

AMBER Pyridostigmine tablets 60mg

Acetylcholine-release enhancer, 3, 4 diaminopyridine (an orphan drug) has been approved for use in the treatment of

Lambert-Eaton myasthenic syndrome (LEMS), a rare disorder of neuromusculsr transmission.

RED 3, 4 Diaminopyridine tablets 10mg

RED Nusinersen: solution for injection 2.4 mg per 1 ml (Spinraza®) NHS England commissioned

NICE TA588 Nusinersen is recommended as an option for treating 5q spinal muscular atrophy (SMA) only if:

> people have pre-symptomatic SMA, or SMA types 1,2 or 3 and

> the condition is in the managed access agreement are followed.

10.2.2 Skeletal muscle relaxants

Used for the relief of chronic muscle spasm or spasticity acting principally on the CNS.

GREEN Baclofen

tablets 10mg,

liquid 5mg/5mL

GREEN Diazepam

tablets 2mg, 5mg, 10mg,

syrup 2mg/5mL

GREEN Tizanidine

tablets 2mg, 4mg

Sativex® Delta-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex®) - Management of spasticity

associated with MS.

In line with NICE CG 186 October 2014 Sativex should no longer be offered as an option to MS patients to treat

spasticity. This does not affect people who have already started treatment with Sativex in the NHS who should be able

to continue treatment until they and their NHS clinician think it appropriate to stop. Clinicians are reminded for

existing patients that Sativex® should only be used strictly within its UK licence for the treatment of spasticity

unresponsive to a variety of available alternatives (including tricyclic antidepressants, gabapentin & baclofen). For

existing patients on this traetment Sativex® should only be prescribed by the two specialists in the treatment of

neuropathic pain associated with multiple sclerosis - Dr Tidswell & Dr Shaunak (Consultant Neurologists).

GPs should not be asked to prescribe Sativex® and should be aware of the updated guidance.

Patients who commenced treatment before NICE guidance

RED Cannabis extract (Sativex®)

All other patients

BLACK Cannabis extract (Sativex®)

10.3.1 Enzymes

[Collagenase clostridium hystolyticum Discontinued by manufacturer]

Collagenase Clostridium histolyticum 900mcg (Xiapex®) *

* Xiapex® - Sobi has discontinued commercialisation of this product at the end of 2019 - see attached information

Hyaluronidase

Used to render tissues more easily permeable to injected fluids i.e. in hypodermoclysis.

AMBER Hyaluronidase injection 1500 unit

10.3.2 Rubefacients and other topical anti-rheumatics

Topical non-steroidal anti-inflammatory drugs (NSAIDs) are recommended by NICE as a first line treatment with or

without regular paracetamol for the management of osteoarthritis.

GREEN Ibuprofen gel 5%

GREEN Ketoprofen gel 2.5% (licensed for up to 7 days use only)

Prescribers are reminded that photosensitivity reactions are an important side effect of Ketoprofen gel. Before

prescribing

> Verify that the patient does not have any phototoxicity- or photoallergy-related contraindications.

> explain to patients the steps they need to take to minimise the risk of photosensitivity reactions

> check that patients understand the risk of photosensitivity and the steps they need to take to minimise this

risk. A prescriber checklist is available here

Capsaicin

If above agent/s are ineffective or insufficient then alongside other options (such as oral NSAIDs, oral opioids or

intra-articular injections) consider substitution or addition of topical capsaicin for hand/knee osteoarthritis.

Cautions

Avoid contact with eyes, and inflamed or broken skin. Hands should be washed immediately after use. Not for use

under tight bandages. Avoid taking a hot shower or bath just before or after applying capsaicin - burning sensation

enhanced.

Side-effects

Transient burning sensation can occur during initial treatment, particularly if too much cream is used, or if the

frequency of administration is less than 3–4 times daily.

GREEN Capsaicin cream 0.025% [Zacin®] (for osteoarthritis of the hand and knee only- NOT for back pain)

For general musculoskeletal pain advise to purchase a rubefacient product] [Consider OTC/Self care]

AMBER Capsaicin cream 0.075% [Axsain®] (for post herpetic neuralgia & painful diabetic neuropathy)

For the use in specialist services, Transvasin® cream has been approved for off-licence use to improve the blood

flow of the ear lobe prior to measuring capillary ear lobe blood gases.

RED Transvasin® cream

Information about changes to medicines or treatments on the NHS: Changes to rubefacients prescribing: Patient Information Leaflet