Drug reference
Spasticity associated with multiple sclerosis or spinal cord injury or disease ▶BY MOUTH ▶Adult: Initially 2 mg daily, then increased in steps of 2 mg daily in divided doses, increased at intervals of at least 3–4 days and adjust according to response; usual dose up to 24 mg daily in 3–4 divided doses; maximum 36 mg per day
PDF page 1214
Elderly
PDF page 1214
→Appendix 1: tizanidine
PDF page 1214
▶Common or very common Arrhythmias. dizziness. drowsiness. dry mouth. fatigue. hypotension. rebound hypertension ▶Rare or very rare Gastrointestinal disorder. hallucination. hepatic disorders. muscle weakness. nausea. sleep disorders ▶Frequency not known Abdominal pain. accommodation disorder. anxiety. appetite decreased. confusion. headache. QT interval prolongation. skin reactions. vomiting. withdrawal syndrome SIDE-EFFECTS, FURTHER INFORMATION Treatment should be discontinued if liver enzymes are persistently raised— consult product literature.
PDF page 1214
Avoid (toxicity in animal studies).
PDF page 1214
Avoid (present in milk in animal studies).
PDF page 1214
Manufacturer advises avoid in significant impairment.
PDF page 1214
Manufacturer advises caution.
PDF page 1214
Monitor liver function monthly for first 4 months for daily doses of 12 mg or higher, and in those who develop unexplained nausea, anorexia or fatigue.
PDF page 1214
There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: oral suspension, oral solution Tablet CAUTIONARY AND ADVISORY LABELS 2, 8 ▶Tizanidine (Non-proprietary) Tizanidine (as Tizanidine hydrochloride) 2 mg Tizanidine 2mg tablets | 120 tablet P £28.89 DT = £17.16 Tizanidine (as Tizanidine hydrochloride) 4 mg Tizanidine 4mg tablets | 120 tablet P £40.07 DT = £40.05 Pain and inflammation in musculoskeletal disorders Low back pain and sciatica Description of condition Low back pain is pain in the lumbosacral area of the back. It can be described as non-specific, mechanical, musculoskeletal or simple (if it is not associated with serious or potentially serious causes). Episodes of back pain do not usually last long, with rapid improvements in pain and disability seen within a few weeks to months. Sciatica (radicular pain or radiculopathy) is neuropathic leg pain secondary to compressive lumbosacral nerve root pathology. Non-drug treatment g Exercise programmes, manual therapy, and psychological therapies should be considered for managing low back pain with or without sciatica. Spinal decompression may be considered in patients with sciatica when pain and function has not improved with non- surgical treatment (including drug treatment). h Drug treatment g An oral NSAID (see Non-steroidal anti-inflammatory drugs p. 1193) should be considered for managing acute low back pain, taking into consideration the gastro-intestinal, cardio-renal and hepatic risks associated with NSAIDs; as well as the need for continued monitoring, and the possible need for gastroprotective treatment (see Peptic ulcer disease p. 76). A weak opioid, either alone or with paracetamol p. 465, can be used to manage acute low back pain only if an NSAID is contra-indicated, not tolerated or ineffective (see Opioid analgesics under Analgesics p. 462). Paracetamol alone is ineffective for managing low back pain. h g Benzodiazepines are sometimes used to manage acute low back pain (particularly in loss of lordosis); however evidence to support their use is very weak. l g In patients with chronic low back pain who have had an inadequate response to non-drug treatment, NSAIDs should be considered as first-line therapy. Opioids should be the last treatment option considered and should be considered only in patients for whom other therapies have failed and only if the potential benefits outweigh the risks for individual patients. If indicated, opioids should only be prescribed for a limited period of time. Long term opioid therapy should be avoided. Selective serotonin re-uptake inhibitors (SSRIs), serotonin and noradrenaline re-uptake inhibitors (SNRIs), tricyclic antidepressants, and antiepileptic drugs should not be offered for managing low back pain. When non-surgical treatment is ineffective in patients with moderate and severe localised back pain arising from structures supplied by the medial branch nerve, radiofrequency denervation can be considered. h Sciatica Patients with sciatica may require specific treatment for Neuropathic pain p. 505. g Patients with acute and severe sciatica may benefit from treatment with epidural injections of local anaesthetic and/or corticosteroid. h Useful Resources Low back pain and sciatica. National Institute for Health and Care Excellence. Clinical guideline NG59. November 2016. www.nice.org.uk/guidance/ng59 Non-steroidal anti-inflammatory drugs Therapeutic effects In single doses non-steroidal anti-inflammatory drugs (NSAIDs) have analgesic activity comparable to that of paracetamol p. 465, but paracetamol is preferred, particularly in the elderly. In regular full dosage NSAIDs have both a lasting analgesic and an anti-inflammatory effect which makes them particularly useful for the treatment of continuous or regular pain associated with inflammation. Therefore, although paracetamol often gives adequate pain control in osteoarthritis, NSAIDs are more appropriate than paracetamol or the opioid analgesics in the inflammatory arthritides (e.g. rheumatoid arthritis) and in some cases of advanced osteoarthritis. NSAIDs can also be of benefit in the less well defined conditions of back pain and soft-tissue disorders. Choice Differences in anti-inflammatory activity between NSAIDs are small, but there is considerable variation in individual response and tolerance to these drugs. About 60% of patients will respond to any NSAID; of the others, those who do not respond to one may well respond to another. Pain relief starts soon after taking the first dose and a full analgesic effect should normally be obtained within a week, whereas an anti-inflammatory effect may not be achieved (or may not be clinically assessable) for up to 3 weeks. If appropriate responses are not obtained within these times, another NSAID should be tried. NSAIDs reduce the production of prostaglandins by inhibiting the enzyme cyclo-oxygenase. They vary in their selectivity for inhibiting different types of cyclo-oxygenase; selective inhibition of cyclo-oxygenase-2 (COX-2) is associated with less gastro-intestinal intolerance. Several other factors also influence susceptibility to gastrointestinal effects, and a NSAID should be chosen on the basis of the incidence of gastro-intestinal and other side-effects. Ibuprofen p. 1203 is a propionic acid derivative with anti- inflammatory, analgesic, and antipyretic properties. It has fewer side-effects than other non-selective NSAIDs but its anti-inflammatory properties are weaker. It is unsuitable for conditions where inflammation is prominent, such as acute gout. Dexibuprofen p. 1196 is the active enantiomer of ibuprofen. It has similar properties to ibuprofen and is licensed for the relief of mild to moderate pain and inflammation. Other propionic acid derivatives: Naproxen p. 1211 is one of the first choices because it combines good efficacy with a low incidence of side-effects (but more than ibuprofen). Flurbiprofen p. 1203 may be slightly more effective than naproxen, and is associated with slightly more gastro- intestinal side-effects than ibuprofen. Ketoprofen p. 1207 has anti-inflammatory properties similar to ibuprofen and has more side-effects. Dexketoprofen p. 1197, an isomer of ketoprofen, has been introduced for the short-term relief of mild to moderate Musculoskeletal system pain. Tiaprofenic acid p. 1215 is as effective as naproxen; it has more side-effects than ibuprofen. Drugs with properties similar to those of propionic acid derivatives: Diclofenac sodium p. 1198 and aceclofenac p. 1194 are similar in efficacy to naproxen. Etodolac p. 1201 is comparable in efficacy to naproxen; it is licensed for symptomatic relief of osteoarthritis and rheumatoid arthritis. Indometacin p. 1206 has an action equal to or superior to that of naproxen, but with a high incidence of side-effects including headache, dizziness, and gastro-intestinal disturbances. Mefenamic acid p. 1208 has minor anti-inflammatory properties. It has occasionally been associated with diarrhoea and haemolytic anaemia which require discontinuation of treatment. Meloxicam p. 1209 is licensed for the short-term relief of pain in osteoarthritis and for long-term treatment of rheumatoid arthritis and ankylosing spondylitis. Nabumetone p. 1210 is comparable in effect to naproxen. Phenylbutazone is licensed for ankylosing spondylitis, but is not recommended because it is associated with serious side-effects, in particular haematological reactions; it should be used only by a specialist in severe cases where other treatments have been found unsuitable. Piroxicam p. 1212 is as effective as naproxen and has a long duration of action which permits once-daily administration. However, it has more gastro-intestinal side- effects than most other NSAIDs, and is associated with more frequent serious skin reactions. Sulindac p. 1213 is similar in tolerance to naproxen. Tenoxicam p. 1214 is similar in activity and tolerance to naproxen. Its long duration of action allows once-daily administration. Tolfenamic acid p. 497 is licensed for the treatment of migraine. Ketorolac trometamol p. 1242 and the selective inhibitor of cyclo-oxygenase-2, parecoxib p. 1413, are licensed for the short-term management of postoperative pain. The selective inhibitors of COX-2, etoricoxib p. 1201 and celecoxib p. 1195, are as effective as non-selective NSAIDs such as diclofenac sodium and naproxen. Although selective inhibitors can cause serious gastro-intestinal events, available evidence appears to indicate that the risk of serious upper gastro-intestinal events is lower with selective inhibitors compared to non-selective NSAIDs; this advantage may be lost in patients who require concomitant low-dose aspirin. Celecoxib and etoricoxib are licensed for the relief of pain in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis; etoricoxib is also licensed for the relief of pain from acute gout. Aspirin p. 130 has been used in high doses to treat rheumatoid arthritis, but other NSAIDs are now preferred. Dental and orofacial pain Most mild to moderate dental pain and inflammation is effectively relieved by NSAIDs. Those used for dental pain include ibuprofen, diclofenac sodium, and diclofenac potassium p. 1197. Considerations in the elderly The use of NSAIDs in elderly patients is potentially inappropriate (STOPP criteria) if prescribed: . with a vitamin K antagonist, direct thrombin inhibitor or factor Xa inhibitor in combination (risk of major gastrointestinal bleeding); . with concurrent antiplatelet agent(s) without proton pump inhibitor (PPI) prophylaxis (increased risk of peptic ulcer disease); . in a history of peptic ulcer disease or gastrointestinal Musculoskeletal system bleeding, unless with concurrent PPI or H2-receptor antagonist (risk of peptic ulcer relapse)—not including COX-2 selective NSAIDs; . with concurrent corticosteroids without PPI prophylaxis (increased risk of peptic ulcer disease); . in patients with an eGFR less than 50 mL/minute/1.73 m2 (risk of deterioration in renal function); . in severe hypertension or severe heart failure (risk of exacerbation); . for long-term (longer than 3 months) symptom relief of osteoarthritis pain where paracetamol has not been tried (simple analgesics are preferable and usually as effective for pain relief); . for chronic treatment of gout where there is no contra- indication to a xanthine-oxidase inhibitor (xanthine- oxidase inhibitors are first choice prophylactic drugs in gout); . a COX-2 selective NSAID in concurrent cardiovascular disease (increased risk of myocardial infarction and stroke). For further information, see STOPP/START criteria in Prescribing in the elderly p. 33. Asthma Any degree of worsening of asthma may be related to the ingestion of NSAIDs, either prescribed or (in the case of ibuprofen and others) purchased over the counter. NSAIDs and cardiovascular events All NSAID use (including COX-2 selective inhibitors) can, to varying degrees, be associated with a small increased risk of thrombotic events (e.g. myocardial infarction and stroke) independent of baseline cardiovascular risk factors or duration of NSAID use; however, the greatest risk may be in those receiving high doses long term. COX-2 selective inhibitors, diclofenac (150 mg daily) and ibuprofen p. 1203 (2.4 g daily) are associated with an increased risk of thrombotic events. Although there are limited data regarding the thrombotic effects of aceclofenac below, treatment advice has been updated in line with diclofenac, based on aceclofenac’s structural similarity to diclofenac and its metabolism to diclofenac. The increased risk for diclofenac is similar to that of licensed doses of etoricoxib p. 1201. Naproxen p. 1211 (1 g daily) is associated with a lower thrombotic risk, and low doses of ibuprofen (1.2 g daily or less) have not been associated with an increased risk of myocardial infarction. The lowest effective dose of NSAID should be prescribed for the shortest period of time to control symptoms and the need for long-term treatment should be reviewed periodically. NSAIDs and gastro-intestinal events All NSAIDs are associated with serious gastro-intestinal toxicity; the risk is higher in the elderly. Evidence on the relative safety of non-selective NSAIDs indicates differences in the risks of serious upper gastro-intestinal side-effects— piroxicam p. 1212, ketoprofen p. 1207, and ketorolac trometamol p. 1242 are associated with the highest risk; indometacin p. 1206, diclofenac, and naproxen are associated with intermediate risk, and ibuprofen with the lowest risk (although high doses of ibuprofen have been associated with intermediate risk). Selective inhibitors of COX-2 are associated with a lower risk of serious upper gastro-intestinal side-effects than non-selective NSAIDs. Recommendations are that NSAIDs associated with a low risk e.g. ibuprofen are generally preferred, to start at the lowest recommended dose and not to use more than one oral NSAID at a time. The combination of a NSAID and low-dose aspirin can increase the risk of gastro-intestinal side-effects; this combination should be used only if absolutely necessary and the patient should be monitored closely. While it is preferable to avoid NSAIDs in patients with active or previous gastro-intestinal ulceration or bleeding, and to withdraw them if gastro-intestinal lesions develop, nevertheless patients with serious rheumatic diseases (e.g. rheumatoid arthritis) are usually dependent on NSAIDs for effective relief of pain and stiffness. Patients at risk of gastro-intestinal ulceration (including the elderly), who need NSAID treatment should receive gastroprotective treatment. Systemic as well as local effects of NSAIDs contribute to gastro–intestinal damage; taking oral formulations with milk or food, or using enteric-coated formulations, or changing the route of administration may only partially reduce symptoms such as dyspepsia. NSAIDs and alcohol Alcohol increases the risk of gastro-intestinal haemorrhage associated with NSAIDs. Specialist sources recommend that concurrent use need not be avoided with moderate alcohol intake, but greater caution is warranted in those who drink more than the recommended daily limits. Some cases of acute kidney injury have been attributed to use of NSAIDs and acute excessive alcohol consumption. Advanced Pharmacy Services Patients taking NSAIDs may be eligible for the Medicines Use Review service provided by a community pharmacist. For further information, see Advanced Pharmacy Services in Medicines optimisation p. 18. Other drugs used for Pain and inflammation in musculoskeletal disorders Tramadol with dexketoprofen, p. 494 ANALGESICS › NON-STEROIDAL ANTI- INFLAMMATORY DRUGS
PDF pages 1214, 1215, 1216
Avoid abrupt withdrawal (risk of rebound hypertension and tachycardia); to minimise risk, discontinue gradually and monitor blood pressure.
PDF page 1214
Driving and skilled tasks Drowsiness may affect performance of skilled tasks (e.g. driving); effects of alcohol enhanced.
PDF page 1214
Initially 2 mg daily, then increased in steps of
First-line fragment. Read the complete Indications and Dose section above.
PDF page 1214
