Opioid Analgesics
General principles and management of cancer pain in adults
Step II opioids: tramadol, codeine or low-dose morphine
Step III opioids: morphine and other strong opioids
Myths about morphine that may limit its use
Alternative systemic routes of opioid administration
Changing from one opioid to another
Treatment of opioid-related side effects
Use of opioids in renal failure
Use of opioids in hepatic failure
Use of opioids in patients with HIV and AIDS
Step II opioids: tramadol, codeine or low-dose morphine
Patients with moderate pain whose pain is not adequately controlled with regular doses of NSAIDs or paracetamol may experience good pain relief with the addition of a weak opioid (tramadol or codeine).11
Side effects of tramadol include nausea/vomiting, constipation, drowsiness, dizziness and seizures.19 Because it lowers the seizure threshold, tramadol should be used with caution in patients with epilepsy. When tramadol is used in combination with antidepressants there is an increased risk of seizures and serotonin syndrome. Therefore this combination should be used with caution and the patient must be closely monitored.
Codeine is not usually available on its own, but is often contained in combination products with other analgesics, such as paracetamol. The codeine dose in these preparations is often low and subtherapeutic (e.g., 8-10 mg), where the recommended adult dose sufficient for analgesia is 30-60 mg 4 hourly (Table 1). The analgesic effect of codeine is due to metabolism to morphine. A small proportion of patients (<10%) is unable to convert codeine to morphine and analgesia will be inadequate in these individuals.9 Young children have inadequate amounts of the enzyme required for the conversion and use of codeine is not recommended in this population, where low dose morphine is effective with fewer side effects.16
Usual starting doses are listed in Table 1. An alternative to codeine or tramadol at step II is to start with a low dose of a more potent opioid (morphine or oxycodone).11
Step III opioids: morphine and other strong opioids
Potent opioids include morphine, oxycodone, hydromorphone and fentanyl, which, at equipotent doses are similar in efficacy, tolerability and safety.11 Morphine is recommended as a first choice, because it is inexpensive and is often the only strong opioid available for pain management. It is available in oral immediate and slow-release forms and as an injectable. An oral liquid is easily prepared from morphine sulphate powder into different strengths and proportions as required. Immediate-release morphine has a rapid onset of effect (within 20 minutes), but its half-life of 2-4 hours means that it must be administered 4 hourly for effective continuous pain relief. It is metabolised by the liver.
| Table 1: Starting and Usual Maintenance Oral Doses of Opioid Analgesics in Adults9,16,22,40,60 | ||
| Starting Dose | Maximum Daily Dose | |
| Codeine | 30-60 mg q4-6h | 240 mg |
| Dihydrocodeine | 30 mg q6h | 240 mg |
| Tramadol | 50-100 mg q6h | 400 mg |
| Morphine | 2.5-10 mg q4h (IR) Patients switching from a regular step II opioid should start on 5-10 mg q4h Frail/ elderly patients should start at 2.5 mg q6-8h due to the likelihood of impaired renal function 20-30 mg q12h (CR) |
There is no ceiling or maximum dose, but the dose should be increased gradually |
| Hydromorphone (extended-release tabs)* | 4-8 mg once daily | |
| Oxycodone | 5 mg q4-6h (IR) 10 mg q12h (CR) |
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| IR: immediate-release; CR: continuous-release; *Manufacturer’s recommendation. Opioids should be initiated at lower doses in patients with severe renal impairment. Patients with HIV may require lower doses of opioids. |
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Titration of immediate-release morphine should always be used initially to establish control of pain, usually with dose adjustments every 24 hours, unless the pain is more severe, requiring earlier titration. Only thereafter may a slow-release preparation or another opioid (e.g., fentanyl) be used for maintenance of analgesia. Breakthrough pain should be managed with immediate-release morphine as required.
The systemic bioavailability of oral morphine is poor with wide variation between individuals. Therefore dosing should be individualised. There is no ceiling or maximum dose of morphine and the dose should be increased gradually to an appropriate level that controls the patient’s pain.9,12,16
Usual starting and maintenance doses of commonly used opioids are listed in Table 1. Undesirable effects of opioids and potential intolerable effects of morphine are listed in Tables 2 and 3, respectively.
| Table 2: Undesirable Effects of Opioids When Used for Analgesia 40 | |
| Common initial - Nausea and vomiting - Drowsiness - Light-headedness/ unsteadiness - Delirium (acute confusional state) Common ongoing - Constipation - Dry mouth Possible ongoing - Suppression of hypothalamic-pituitary axis |
Less common - Neurotoxicity - Hyperalgesia - Allodynia - Myoclonus - Cognitive failure/ delirium - Hallucinations - Sweating - Urinary retention - Postural hypotension - Pruritus Rare - Respiratory depression - Psychological dependence |
Myths about morphine that may limit its use 16,17
When initiating opioids, it is necessary to discuss treatment with the patient and their family and address misguided concerns, including:
Physical dependence
Physical dependence, resulting in withdrawal symptoms when a drug is abruptly discontinued, is a normal physiological response to chronic opioid therapy as well as long-term use of various other medications. It does not prevent withdrawal of medication as long as the patient is weaned from the drug slowly. Dependence differs from addiction in that the patient remains compliant with changes in opioid prescription.
Psychological dependence on analgesia may result from fear of pain recurrence or incomplete pain relief and may be associated with requests for increased use of opioids.
Although psychological dependence may also be confused with addiction, it differs in that requests for medication decrease with the establishment of adequate analgesia.
Sedation and respiratory depression
Because pain causes sleep deprivation, effective analgesia may initially be associated with sleep. However, thereafter, if dose is titrated against pain, with an appropriate drug given at the appropriate time by the appropriate route, opioid therapy is not associated with either profound sedation or respiratory depression. In palliative care, low doses of morphine may be used in patients with end-stage chronic obstructive airways disease, lung cancer or severe dyspnoea and makes breathing more comfortable. Nevertheless, sedation is a side effect of opioids that occurs especially when starting treatment and tolerance to the sedating effects develops within a few days.
Pain is a physiological antagonist to the respiratory depressant effects of opioids and respiratory depression is rare if dose is titrated upwards against pain.
Tolerance
Tolerance is defined as a reduced effect for the equivalent analgesic dose, or requirement of increased dose to attain the same effects. It may occur to both analgesia and unwanted side effects, such as nausea, vomiting, sedation and respiratory depression. In palliative care, tolerance to analgesia is uncommon and requirement for increasing doses of morphine is usually related to disease progression. There is no maximum dose of opioid analgesia and dose should be titrated according to the level of pain relief required. Because of the phenomenon of ‘incomplete cross-tolerance’, switching to another opioid may provide adequate analgesic efficacy when tolerance to current therapy has occurred. Furthermore, non-opioid co-analgesics may also be prescribed to limit the dose of opioid required to achieve the same level of analgesia.
Addiction
Addiction is rare in palliative care when opioids are prescribed at appropriate doses to relieve pain. Drug seeking behaviours such as drug hoarding, requests for additional prescriptions or increased doses occurring in patients with a poor response to certain opioids or low-dose opioids is termed ‘pseudoaddiction’. These behaviours may be mistaken as signs of addiction, but occur in an attempt to obtain better pain relief and cease when pain is controlled.
The perception that opioids are only used at end of life and hasten death
Opioids are frequently used for many different conditions associated with severe pain. In some patients they may safely be used for months or years for prolonged analgesia and they significantly improve quality of life.
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Table 3: Potential Intolerable Effects of Morphine 40
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| Effects | Initial Action | Comment |
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Gastric stasis
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| Epigastric fullness, flatulence, anorexia, hiccup, persistent nausea | Prescribe prokinetic; e.g., metoclopramide 10-20 mg q6-8h |
If the problem persists, change to an alternative opioid with less impact on the GI tract. |
| Sedation | ||
| Intolerable persistent sedation |
Reduce dose of morphine, consider a psychostimulant, e.g., methylphenidate 5 mg q12h | Sedation may be caused by other factors; stimulant is rarely appropriate |
| Cognitive failure | ||
| Agitated delirium with hallucinations |
Prescribe an antipsychotic; e.g., haloperidol 1 mg stat and q2h prn; reduce dose of morphine and, if no improvement, switch to an alternative opioid |
Some patients develop intractable delirium with one opioid, but not with an alternative opioid. |
| Myoclonus | ||
| Multifocal twitching +/- jerking of limbs |
Prescribe a benzodiazepine; e.g., diazepam / midazolam 5 mg or lorazepam 500 mcg stat and q1h prn; reduce dose of morphine, but increase again if pain recurs | Uncommon with typical doses of oral morphine; more common with high dose IV and spinal morphine |
| Neurotoxicity | ||
| Abdominal muscle spasms, symmetrical jerking of legs; whole body allodynia, hyperalgesia (manifests as excruciating pain) |
Prescribe a benzodiazepine; e.g., diazepam / midazolam 5 mg or lorazepam 500 mcg stat and q1h prn; reduce dose of morphine; consider changing to an alternative opioid | An uncommon syndrome in patients receiving intrathecal or high dose IV morphine; occasionally seen with typical oral and SC doses |
| Vestibular stimulation | ||
| Movement-induced nausea and vomiting | Prescribe an antihistaminic antimuscarinic anti-emetic; e.g., cyclizine 25-50 mg q6-8h | If intractable, switch to an alternative opioid |
| Pruritus | ||
| Whole body itch with systemic morphine; localised to upper body or face/nose with spinal morphine |
With systemic opioids, prescribe oral H1-antihistamine (e.g., chlorphenamine 4-8 mg stat; if beneficial continue with 4 mg q8h or prn for 2-3 days). Possibly switch opioids; e.g., morphine to oxycodone Most patients receiving spinal analgesia are not opioid naive, so the probability of pruritus is reduced. If it does occur, possibly switch opioids. |
Pruritus after systemic opioids is uncommon. Sometimes caused by cutaneous histamine release and self-limiting, but most are chronic and antihistamine-resistant. Centrally-acting opioid antagonists relieve the pruritus, but also antagonise analgesia. |
| Histamine release | ||
| Bronchoconstriction and breathlessness |
Treat as for anaphylaxis; change to a chemically distinct opioid immediately. Seek specialist advice | Uncommon |
Methadone
Methadone is a potent opioid with complicated pharmacokinetics and considerable inter-individual variation. It requires careful monitoring and is not recommended for routine use in the management of cancer pain. It should only be used by experienced pain management specialists.9,11
Opioid titration
The usual starting dose of oral immediate-release morphine is 5-10 mg four hourly in young and middle-aged people and 2.5-5 mg in elderly patients. Starting therapy with an immediate-release preparation allows more rapid analgesia. The dose may be adjusted according to pain control, degree of side effects and total amount of opioid required, including breakthrough doses. For example, a patient receiving oral morphine 10 mg four hourly and requiring rescue doses for breakthrough pain (10 mg) three times daily, will be converted to a new daily dose as follows:
(maintenance: 10 mg x 6) + (breakthrough: 10 mg x 3) = 90 mg daily
Once pain control is stable, this dose may be administered as:
- immediate-release oral morphine 15 mg every 4 hours, or
- an equivalent dose of 12 hourly modified-release morphine twice daily plus appropriate doses of immediate-release morphine for breakthrough pain (see Breakthrough Pain)
Alternatively, an empiric increase of 30-50% of the previous daily dose is a useful rule of thumb in settings where breakthrough pain is not well monitored or treated.
Once analgesia is stabilised, there is no significant difference between pain control with 4 hourly immediate-release, 12 hourly modified-release, or once daily modified-release opioid preparations administered as appropriate. Modified-release preparations have a slow onset and time to reach peak concentrations, so they do not allow rapid titration for patients who are in severe pain. They are most appropriate for maintenance of analgesia once pain control is stabilised and have been shown to improve compliance and reduce sleep disturbance. Therefore, the following is recommended:
- Patients with stable pain on oral morphine should be prescribed a once or twice daily modified-release preparation.9
- Patients with stable pain on oral oxycodone should be prescribed a twice daily modified-release preparation.9
The following intervals should be observed before increasing the maintenance dose of opioid:
- Allow 24 hours of regular and breakthrough dosing before increasing the dose of immediate-release opioid
- Allow 48 hours of regular and rescue dosing before increasing the dose of sustained-release morphine, hydromorphone and oxycodone preparations
- Allow 72 hours before considering increasing the strength of a transdermal fentanyl or buprenorphine patch 23
Care should be taken when calculating a new opioid dose for patients who are pain free at rest, but who have pain on movement. If incident pain is confused with breakthrough pain when calculating the new dose, patients may experience opioid-related adverse effects, including excessive nausea, sedation and confusion.9 Alternative methods for limiting pain on movement should be considered. Activities that may be associated with pain (e.g., bathing, dressing wounds) should be scheduled for one hour after the last dose of morphine or a breakthrough dose should be administered 1 hour before the event.
Alternative systemic routes of opioid administration
Because it is effective and simple, the oral route is preferred in the majority of patients receiving opioids.9 However, alternative routes of administration (intravenous, transdermal, subcutaneous or rectal) may be necessary in patients with nausea or vomiting, those who cannot swallow and patients near the end of life who are weak or debilitated. Once they reach steady state, intravenous (IV) and subcutaneous (SC) continuous infusions of morphine are equianalgesic with similar side effect profiles.
The following recommendations apply:9,11
- Opioids should be administered orally as far as practical and feasible.
- Transdermal patches (e.g., fentanyl, buprenorphine) have a long duration of action and are useful alternatives to oral morphine. However, because of their slow onset of action and long time to reach steady state, they should only be initiated in patients whose pain has already been stabilised with oral morphine. The initial patch strength is calculated from the average 24 hour oral morphine dose required to control pain. Breakthrough doses of oral morphine may still be administered and patch strength should be titrated if necessary based on the average opioid requirement during the previous 72 hours.
- In patients unable to achieve adequate analgesia with oral and transdermal administration, continuous SC administration of morphine is simple and effective and the next preferable choice.
- SC opioids may be administered by patient controlled analgesia (PCA) pump, syringe driver, or disposable PCA device.
- Care should be taken when administering SC drugs with a syringe driver as the small volumes used means that the drugs delivered are often very concentrated, increasing the danger of drug incompatibilities and irritation of the SC site. Drug solutions for SC administration should be diluted to the maximum allowed by the administration device.
- Consider IV infusion when subcutaneous administration is contraindicated (e.g., peripheral oedema, coagulation disorders, poor peripheral circulation, need for high doses and volumes).
- When switching from oral to IV or SC opioids, the relative analgesic potency is the same for both routes and is between 3:1 and 2:1 (see Dose conversion ratios).
- IV administration should be used for opioid titration when rapid pain control is required. However, patients must be closely monitored for respiratory depression.
- PCA may be used with IV or SC opioid infusions for patients who are willing and able to be in control of doses for breakthrough pain.
- Rectal administration is not acceptable to many patients and is not a preferred route of administration. However, it may be preferable to IV administration when SC is not available.
- Diamorphine, oxycodone and hydromorphone are not available for parenteral administration in South Africa.
Changing from one opioid to another
A minority of patients may experience inadequate pain relief or persistent unacceptable side effects at step III of the analgesic ladder. In such cases, switching to another opioid to optimise the balance between pain control and side effects may be appropriate after consideration of the following:9,11
- Other pain control strategies must be optimised.
- Presumed adverse effects must be carefully differentiated from similar symptoms related to the patient’s illness or adverse effects of other co-administered medications.
- Opioid-related side effects may be addressed with temporary reduction of opioid dose followed by slower titration.
- Additional medication may be used to control predictable side effects.
- Symptoms such as nausea or drowsiness may occur after switching to a potent opioid or increasing the dose. These side effects usually resolve within days and do not necessitate changing to another opioid.
Dose conversion ratios
Equivalent doses of opioids need to be calculated when
- stepping up from a weak opioid to morphine, or
- the need arises to switch to an alternative potent opioid
Equianalgesic doses and dose ratios are listed in Table 4. These dose conversions are specific for patients with a satisfactory response to the first opioid. Therefore, in patients with inadequate analgesia and/or unacceptable side effects from the first opioid, the starting dose should be lower than that listed. In all cases, the dose must be titrated according to clinical response.9
It should be noted that there is a wide range of equianalgesic dose ratios listed in the literature and care should be taken with individual patients.
| Table 4: Suggested Dose Conversion Ratios9,11 | ||
| Current opioid (converting from:) | New opioid or new route of administration (converting to:) | Divide 24 hour dose of current opioid (column 1) by relevant figure below to calculate initial 24 hour dose of new opioid and/or new route (column 2) (the same units for both drugs must be used; e.g., mg) |
| Example: 120 mg oral morphine in 24 hours |
SC morphine | Divide by 3 (120 mg / 3) = 40 mg SC morphine in 24 hours |
| Oral to Oral Route Conversions | ||
| Oral codeine | Oral morphine | Divide by 10 |
| Oral tramadol | Oral morphine | Divide by 5 |
| Oral morphine | Oral oxycodone | Divide by 2 |
| Oral morphine | Oral hydromorphone | Divide by 7.5 |
| Oral oxycodone | Oral hydromorphone | Divide by 4 |
| Oral to Subcutaneous Route Conversions | ||
| Oral morphine | SC morphine | Divide by 2-3 |
| Oral oxycodone | SC morphine | No change |
| Oral oxycodone | SC oxycodone | Divide by 2 |
| Oral to Transdermal Route Conversions (see Transdermal opioids) | ||
| Oral morphine | Transdermal fentanyl | See Table 5 |
| Oral morphine | Transdermal buprenorphine | Seek specialist palliative care advice (Table 6) |
| Other Route Conversions (Rarely Used in Palliative Medicine) | ||
| SC or IM morphine | IV morphine | No change |
| Oral morphine | IV morphine | Divide by 2-3 |
| IV morphine | Oral morphine | Multiply by 2 |
| Oral morphine | IM morphine | Divide by 2 |
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SC: subcutaneous; IM: intramuscular; IV: intravenous. Note: These dose conversions are specific for patients with a satisfactory response to the first opioid. Therefore, in patients with inadequate analgesia and/or unacceptable side effects from the first opioid, the starting dose should be lower than that listed. In all cases, the dose must be titrated according to clinical response. Active metabolites are not usually considered in studies and because of the role of metabolites that take longer to reach steady state, the applicability of these ratios to chronic opioid administration is questionable. Bioavailability may differ between individuals for the same and for different opioids.9
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Transdermal opioids
Due to costs and dosing complications, it may be appropriate to seek specialist advice before starting therapy with transdermal opioids.
Transdermal fentanyl
Fentanyl patches may be appropriate for patients with stabilised severe pain (step III) who cannot tolerate oral therapy, or who express a preference for the patch. The transdermal system enables slow increase of drug plasma concentrations with a long half-life and provides continuous delivery of fentanyl for 72 hours.
- After initiating therapy or changing the dose there is a long latent period before steady state and analgesia are achieved, so dose titration is slow. Therefore, dose titration intervals should be at least 3 days.
- Starting a patch or titrating the dose must be accompanied by frequent reassessment and an appropriate immediate-release opioid for breakthrough pain.
- If dose titration is required to achieve pain control, the strength (opioid dose) of the patch may be increased, or a combination of lower strength patches may be applied at different places to achieve pain control.
- After patch removal, a subcutaneous depot of fentanyl remains and up to 24 hours may be required for fentanyl to clear from the system. Consequently caution must be applied when converting from the patch to another opioid.
Table 5 lists dose conversion ratios for switching from a strong opioid to a fentanyl patch.
| Table 5: Conversion Ratios From Oral Morphine to Fentanyl Patch9 | |
| Oral 24-Hour Morphine (mg/day) | Transdermal Fentanyl Patch (mcg/h)* |
| <90 | 25 |
| 90-134 | 37 (if available, otherwise 25) |
| 135-189 | 50 |
| 190-224 | 62 (if available, otherwise 50) |
| 225-314 | 75 |
| 315-404 | 100 |
| 405-494 | 125 |
| 495-584 | 150 |
| 585-674 | 175 |
| 675-764 | 200 |
| 765-854 | 225 |
| 855-944 | 250 |
| 945-1034 | 275 |
| 1035-1124 | 300 |
| *Patches are available in the following strengths (mcg/h): 12, 25, 50, 75, 100. The doses listed are conservative for conversion from oral morphine to transdermal fentanyl. When converting from transdermal fentanyl to oral morphine, reduce the dose by one third. Particular attention to monitoring and dose titration up or down is required when switching between high-dose opioids, or after a recent rapid escalation of the dose of the first opioid. |
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| Frequency of Oral Opioid Before Switch | After Initiating Patch |
| 4 hourly | Continue oral opioid for 12 hours |
| 12 hourly | Give last dose when first transdermal patch is applied |
| 24 hourly | Apply transdermal patch 12 hours after last dose |
Because they contain an equal distribution of drug, some matrix fentanyl patches may be cut, meaning that it is possible to administer 37.5 mcg/h by using one full and one half 25 mcg patch. However, clinicians should confirm that it is appropriate to cut a particular patch before doing so.
Transdermal buprenorphine
Transdermal buprenorphine is available in three dosage forms from 5 to 20 mcg/hour. Patches are applied weekly and a second patch may be added after 3-5 days if pain relief is inadequate.
Table 6 lists dose conversion ratios for switching from a strong opioid to a buprenorphine patch.
| Table 6: Conversion Ratios From Oral Morphine to Buprenorphine Patch16 | |
| Oral 24-Hour Morphine (mg/day) | Transdermal Buprenorphine Patch (mcg/h)* |
| 10 | 5 |
| 15 | 10 |
| 30 | 20 |
| 60 | 35 |
| 90 | 52.5 |
| 120 | 70 |
| 180 | 105 |
| 240 | 140 |
| *Patches are available in the following strengths (mcg/h): 5, 10, 20. Seek specialist advice before converting from an oral opioid to transdermal buprenorphine |
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Breakthrough pain
Breakthrough pain (BTP) is common in patients with cancer pain. It is a transient exacerbation of pain occurring in a patient receiving chronic opioid therapy and with otherwise stable pain.18 Characteristically, BTP has a rapid onset (peaks within 1-3 minutes) and may last from minutes to hours (median 30 minutes; range 1-240 minutes). It may be spontaneous (sudden and unexpected) or incident, related to an action, such as movement, cough, micturition, respiration or swallowing, in which case it may be anticipated.
BTP must be distinguished from ‘end of dose failure’ of regular analgesia, which has a gradual onset and longer duration than incident or spontaneous BTP.
Recommendations of management of BTP are as follows:9,11,12,18
- BTP should be treated with an orally administered immediate-release opioid.
- Oxycodone and morphine have similar analgesic and side effect profiles, but because morphine is less expensive than oxycodone, morphine is recommended as first-line choice for BTP.
- An appropriate dose of immediate-release oral opioid for BTP is equivalent to one sixth the total 24 hour dose of the around-the-clock opioid (i.e., one four-hourly dose).
- Use of BTP doses will dictate adjustment of the maintenance (around-the-clock) opioid dose: the 24 hour maintenance opioid dose should be up-titrated by adding the total BTP doses used in the preceding 24 hours to the current maintenance dose, which will indicate the new 24-hour maintenance dose to be administered.
- BTP doses should be increased in proportion (1:6) as the maintenance dose is increased.
- Predictable episodes of BTP may be pre-emptively treated with an immediate-release,short-acting opioid 20-30 minutes prior to the provoking activity.
For example, a patient receiving oral morphine 10 mg four hourly and requiring breakthrough doses (10 mg) three times daily, will be converted to a new daily dose as follows:
(maintenance: 10 mg x 6) + (breakthrough: 10 mg x 3) = 90 mg daily
New daily dosage = 15 mg q4h plus 15 mg for breakthrough pain
Treatment of opioid-related side effects
Up to 40% of patients receiving opioids will experience treatment-related nausea and vomiting. Because this side effect may be dose-limiting, effective management is essential.
- Patients should be advised that nausea and/or vomiting may occur when starting or increasing the dose of an opioid, but that it is likely to be transient and improve after 5-7 days.
- General recommendations that may assist to reduce nausea include not administering medication close to meals and avoiding fatty or spicy foods.
- Exclude other causes of nausea and vomiting
- If nausea persists, consider prescribing and optimising antiemetic therapy (e.g., haloperidol, metoclopramide) before switching to a more potent opioid or increasing the dose.
- Other management strategies include discontinuing or reducing the dose of opioid (including using non-opioid analgesia for opioid-sparing effects), switching to another opioid or to another route of administration.
Complications of constipation include pain, overflow diarrhoea, bowel obstruction and urinary retention.
- Patients should be advised that constipation is common with all opioids.
- Laxatives should routinely be prescribed for prophylaxis of opioid-associated constipation, to be taken regularly at an effective dose.
- There is no evidence to recommend one laxative in preference to another.
- A combination of laxatives with different modes of action (e.g., stool softener and bowel stimulant) is more effective than a single agent.
- Patients should be advised that laxatives take time to work and adherence is important.
- Manual removal should never be attempted without sedation and pain control.
Drowsiness and other CNS symptoms11,12
Drowsiness is defined as ‘decreased level of consciousness characterised by sleepiness and difficulty in remaining alert, but with easy arousal by stimuli’.
Opioids may be associated with sedative effects ranging from mild sleepiness to severe drowsiness or coma. Sedation may be accompanied by hallucinations, cognitive impairment, agitation, myoclonus, respiratory depression and delirium.
- Patients should be advised that drowsiness may occur when starting or increasing the dose of an opioid, but that it is likely to be transient, and that it may impair their ability to perform manual tasks (including driving).
- In patients with persistent or moderate-severe central nervous system side effects, if pain is controlled, consider dose reduction. If pain is uncontrolled, switch to another opioid.
- IV morphine should be used with caution in patients who are at risk of respiratory depression.
Use of opioids in renal failure10,11,62
- Accumulation of opioids and their metabolites may occur in patients with severe renal impairment. Therefore, in patients with severe renal impairment (glomerular filtration rate <30 ml/min), opioids should be used with caution.
- Where they are available, the opioids of first choice are fentanyl or buprenorphine administered at a low starting dose, followed by careful titration.
- Dose reduction of buprenorphine is not necessary in patients with renal impairment or undergoing haemodialysis treatment.
- An alternative short-term strategy is to reduce the dose or frequency of administration of morphine.
- Tramadol is recommended with caution.
Use of opioids in hepatic failure62
- Hepatic dysfunction may be associated with accumulation of opioids and their metabolites. Therefore, opioids should be used and titrated with care in patients with liver disease.
- Opioids that may be appropriate in these patients include fentanyl (recommended), or alternatively morphine, hydromorphone, oxycodone or codeine (recommended with caution).
Use of opioids in patients with HIV and AIDS16,63
- In addition to cancers, patients with HIV and AIDS may experience various conditions associated with both nociceptive and neuropathic pain.
- Pain management should follow the SHIP stepwise approach.
- Some antiretroviral medications have important drug interactions and contraindications that necessitate caution, dose changes or selection of an alternative medication when considering co-prescription. Particular care should be taken with anticonvulsants, corticosteroids and antidepressants.
- There is anecdotal evidence that HIV/AIDS patients may respond to lower doses of opioids and starting doses may need to be reduced.
Patients with porphyria
Caution is needed when prescribing medication for patients with porphyria and specialist advice should be sought where necessary. Some medications that may be used are listed in Table 7. For a complete list of drugs that may be used safely, or which should be avoided in patients with porphyria, refer to Porphyria South Africa; Universities of Cape Town and KwaZulu Natal: http://www.porphyria.uct.ac.za/professional/prof-home.htm.
| Table 7: Use of Medications in Patients with Porphyria64 | ||
| Use | Use, But With Caution | Use Only With Extreme Caution, And Only If No Other Alternative Is Available |
| Ibuprofen | Clonidine | Diclofenac |
| Indomethacin | Tramadol | Venlafaxine |
| Naproxen | Metoclopramide | Amitriptyline |
| Gabapentin | Tilidine | |
| Dexamethasone | ||
| Prednisone | ||
| Prednisolone | ||
| Zoledronic acid | ||
| Buprenorphine | ||
| Codeine | ||
| Dihydrocodeine | ||
| Fentanyl | ||
| Morphine | ||