Guideline for the management of knee and hip osteoarthritis

Recommendations

Oral analgesics

Guideline for the management of knee and hip osteoarthritis
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  3. Figures and tables
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Pharmacological interventions

Oral analgesics


 

Intervention: Paracetamol – Knee and/or hip

Recommendation

We are unable to recommend either for or against the use of paracetamol for people with knee and/or hip osteoarthritis (OA). However, it might be reasonable to trial paracetamol for a short period and then discontinue use if it is not effective. Clinicians also need to monitor and capture adverse events that may be associated with its use.

Strength of recommendation

Conditional (neutral) recommendation

Quality of evidence

Very low

What is it? 

Paracetamol, also known as acetaminophen, is typically used to treat mild-to-moderate pain and fever. Unlike other common analgesics (eg nonsteroidal anti-inflammatory drugs [NSAIDs], aspirin, ibuprofen), paracetamol is generally considered to be a weak inhibitor of the synthesis of prostaglandins (PGs), but does not have a significant anti-inflammatory activity.

Rationale 

While paracetamol has long been considered first-line therapy for OA, this has mainly reflected its relative safety, availability and cost, compared with other pharmacological options (eg NSAIDs, opioids). Current evidence from a systematic review of randomised controlled trials (RCTs) suggests that, on average, the reduction in OA pain achieved with paracetamol is too small to be of clinical relevance.95 Moreover, paracetamol is associated with infrequent potential for significant harms, both short-term excess dosing and long-term regular use. 96

Many people will have tried paracetamol prior to seeking advice from a health professional. In those who have experienced a clear benefit that outweighs any potential for harm, it is reasonable to continue paracetamol in the lowest effective dose. Given the variable natural history of OA symptoms, periodic trials of withdrawal are recommended. In people who have not previously trialled paracetamol in an appropriate dose, a short-term trial may be considered, with cessation of the drug in those who do not respond. Repeated trials of paracetamol in those for whom it has not been effective are probably not warranted. 

Practitioners should discuss a cessation strategy with people who regularly use paracetamol without clear benefit. Importantly, it should be emphasised that the replacement of paracetamol with another analgesic drug may not be necessary or appropriate, and that non-pharmacological approaches to management should be optimised. 

Harms 

There is no significant increase of adverse events with the use of paracetamol, compared with placebos. However, clinicians should be cautious that paracetamol is more likely to increase the risk of abnormal liver functions, and side effects are multiplied when combined with alcoholic drinks.

Intervention: Oral NSAIDs including cyclooxygenase-2 (COX-2) inhibitors – Knee and/or hip

Recommendation

It may be appropriate to offer oral NSAIDs for some people with knee and/or hip OA. 

It might be reasonable to trial oral NSAIDs at the lowest effective dose for a short period, then discontinue use if not effective. Clinicians also need to inform individuals about, monitor and capture adverse events, especially gastrointestinal, renal and cardiovascular, which may be associated with use of NSAIDs.

Strength of recommendation

Conditional for recommendation

Quality of evidence

Moderate

What is it? 

NSAIDs are anti-inflammatory and analgesic agents commonly used for OA. NSAIDs are effective anti-inflammatory and analgesic drugs by virtue of their ability to inhibit biosynthesis of PGs at the level of the COX. It is thought that inhibiting COX-2 leads to the anti-inflammatory, analgesic and antipyretic effects, and those NSAIDs also inhibiting COX-1 may cause gastrointestinal bleeding and ulcers in large doses. 97

Rationale 

On average, the use of NSAIDs result in small but clinically relevant improvements in pain and function in individuals with knee and/or hip OA, and are likely to be more effective than paracetamol for most people (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). The direct costs of NSAIDs are relatively low. 

Evidence for effectiveness is derived from trials of relatively short duration, so the relative benefits versus harms of long-term NSAID therapy are unknown. It is likely that the risk of harms increases with duration of therapy; therefore, the balance of benefits and harms may become less favourable with time. Given the variable natural history of OA symptoms, periodic trials of drug withdrawal are recommended. 

Harms 

The potential harms of NSAIDs are well recognised, and include gastrointestinal, renal and cardiovascular adverse effects. Older persons, who are at higher risk for OA, may also be at higher risk of adverse effects from NSAIDs, so this class of medication should be used with caution. Formal estimation of cardiovascular risk may be worthwhile using a validated tool (eg www.cvdcheck.org.au). 

In individuals at low absolute risk of harms, a judicious trial of NSAIDs may be considered, aiming for the lowest effective dose. Co-prescription of a proton-pump inhibitor (PPI) or the use of a COX-2 inhibitor should be considered in people at risk of gastrointestinal adverse effects. The balance of benefits and risks may vary between NSAIDs and between individuals; however, no particular drug is likely to be superior to others, nor is any NSAID free from the potential for harm.

Intervention: Oral opioids – Knee and/or hip

Recommendation

We do not recommend offering oral opioids for people with knee and/or hip OA.

Strength of recommendation

Strong against recommendation

Quality of evidence

Low (knee)
Very low (hip)

What is it? 

Opioids, including morphine, are substances derived from opium. Opioids act on binding opioid receptors, which are principally found in the central and peripheral nervous system, and gastrointestinal tract. Medically, opioids are conceived as powerful pain-relieving substances, and have been shown to be effective for acute pain.

Rationale

Opioid prescription for chronic non-cancer pain (including OA) has increased in recent years despite a lack of high-quality evidence demonstrating benefit, particularly with long-term use. Evidence for the efficacy of opioids in the treatment of OA is mostly derived from short-term trials. There is moderate-quality evidence from trials that improvement in pain and function with opioids is of marginal clinical significance at best, and is offset by the risk of harms (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). Given opioids results in little to no effect on OA pain, and is associated with a risk of serious medical and social harms, we strongly recommend against the use of any opioid preparation for the treatment of knee and/or hip OA. People who are already using opioids for OA pain should be monitored closely. The lowest effective dose should be sought, and opportunities for reduction in dose or cessation should be regularly sought, in conjunction with optimisation of non-pharmacological management. 

Harms 

Common harmful effects may occur in the short-term (eg gastrointestinal disturbance, cognitive dysfunction), leading to a discontinuation of the drug in a significant proportion of individuals. The risk of additional adverse effects may accumulate with long-term use, including dependence, adverse effects on bone health, endocrine and immune function, and possible potentiation of chronic pain mechanisms. Deliberate misuse of opioids is an uncommon but serious risk associated with opioid prescription. Opioid use is associated with a risk of both non-fatal and fatal overdose. Observational data in those using opioids for chronic non-cancer pain suggest a risk of death from opioid-related causes as high as one in 550 individuals.98

Intervention: Transdermal opioids – Knee and/or hip

Recommendation

We do not recommend offering transdermal opioids for people with knee and/or hip OA.

Strength of recommendation

Strong against recommendation

Quality of evidence

Low

What is it? 

Transdermal opioid patch is a long-acting formulation with a delayed onset of effect initially and a prolonged duration of action and, as such, these are best reserved for opioid-tolerant individuals with stable opioid requirements. Transdermal opioid delivery avoids first-pass metabolism by the liver, increasing bio-availability and limiting variation in plasma concentration.99

Rationale 

Evidence is mostly derived from two short-term trials of transdermal opioids: buprenorphine and fentanyl. Similar to oral opioid, the low-quality evidence demonstrated the improvements in pain and function are of marginal clinical significance at best, and is offset by the risk of harms (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). Therefore, we are strongly against the use of any opioid preparation for the treatment of OA of the knee or hip. 

Harms 

Compared with oral opioid, transdermal patches increase drug bio-availability, which enables the use of lower drug doses, thus reducing the incidence of adverse events. However, from the evidence, the risk of adverse effects significantly increased after administration of opioids, regardless of the delivery methods. Other potential risks, such as deliberate misuse, are also not different from oral opioids.

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