Medicines and Healthcare products Regulatory Agency (MHRA) announces that there are new recommendations following a review of the risks of dependence and addiction associated with prolonged use of opioid medicines (opioids) for non-cancer pain.
Considerable concern has been raised regarding prescribing rates of opioids in the United Kingdom and the awareness of healthcare professionals and patients of the risks of dependence and addiction. In 2019, the Commission on Human Medicines (CHM) convened an Expert Working Group to examine the benefits and risks of opioids in the relief of non-cancer pain, including information available to healthcare professionals and patients about the risks of dependence and addiction. Following this review, CHM has made recommendations to improve information for prescribers and patients about these risks to protect public health.
To make it clear that a medicine contains an opioid and that there is a risk of addiction (a recognised term by patients) with prolonged use, CHM recommended that the packaging for all opioid medicines in the United Kingdom carries the warnings ‘Can cause addiction’ and ‘Contains opioid’. The CHM also recommended including further information on the risk of tolerance, dependence and addiction in the product information. The changes apply to the following opioids: alfentanil, buprenorphine, codeine, diamorphine, dihydrocodeine, dipipanone, fentanyl, hydromorphone, meptazinol, methadone, morphine, opium, oxycodone, papaveretum, pentazocine, pethidine, remifentanil, tapentadol, tramadol.
Product information for opioids in the United Kingdom will include consistent warnings of the risks of tolerance and dependence and addiction. Patients may find that treatment is less effective with long-term use and express a need to increase the dose to obtain the same level of pain control as initially experienced. This could indicate that the patient is developing tolerance and dependence. For all patients, prolonged use of opioids may lead to drug dependence (and in some patients addiction/opioid use disorder), even at therapeutic doses. The risks are increased in individuals with current or past history of substance use disorder (including alcohol misuse) or mental health disorder (for example, major depression). Additional support and monitoring may be necessary when prescribing for patients at risk of opioid misuse.
Typical signs of addiction are expression of craving for the drug, even if it is causing adverse effects on overall health; expression of a need for more, or reporting additional use of other pain-relief medicines; taking medicines for reasons other than pain relief, experiencing withdrawal side effects when opioids are stopped suddenly.
Dependence and addiction to opioids are associated with adverse reactions of withdrawal upon sudden cessation of treatment that make it harder to stop taking these medicines. CHM has therefore recommended that before prescribing an opioid a discussion should be held with the patient, to put in place a withdrawal strategy for ending treatment with their opioid medicine. Withdrawal from an opioid is characterised by shivers, diarrhoea, difficulty sleeping (insomnia), sweating, body aches (myalgia), widespread or increased pain, irritability and agitation, and nausea and vomiting. Other signs and symptoms include restlessness, lacrimation, rhinorrhoea, yawning, mydriasis, palpitations, anxiety, hyperkinesia, tremor, weakness, anorexia, abdominal cramps, and increased blood pressure, respiratory rate, and heart rate. To minimise the risk of withdrawal reactions, the dose of opioid should be tapered slowly at the end of treatment. This can take weeks or months, depending on individual response and the dose taken. Healthcare professionals should advise patients not to stop suddenly taking their medicines or try to self-medicate to overcome withdrawal effects. Self-medication with opioids can result in overdose and potentially death.
Some patients can develop hyperalgesia (increased sensitivity to pain) with long-term use of opioids. This might be qualitatively and anatomically distinct from pain related to disease progression or to breakthrough pain resulting from development of opioid tolerance. These symptoms may resolve with a gradual reduction in opioid dose.
Opioids readily cross the placenta, therefore if used during pregnancy neonates may become dependent and experience neonatal abstinence syndrome at birth. Extra vigilance is required and appropriate treatment should be made available.
Advice for healthcare professionals:
- Opioid medicines (opioids) provide relief from serious short-term pain; however long-term use in non-cancer pain (longer than 3 months) carries an increased risk of dependence and addiction.
- Discuss with patients that prolonged use of opioids may lead to drug dependence and addiction, even at therapeutic doses – warnings have been added to the labels (packaging) of United Kingdom opioid medicines to support patient awareness.
- Before starting treatment with opioids, agree with the patient a treatment strategy and plan for end of treatment.
- Explain the risks of tolerance and potentially fatal unintentional overdose, and counsel patients and caregivers on signs and symptoms of opioid overdose to be aware of.
- Provide regular monitoring and support especially to individuals at increased risk, such as those with current or past history of substance use disorder (including alcohol misuse) or mental health disorder.
- At the end of treatment, taper dosage slowly to reduce the risk of withdrawal effects associated with sudden cessation of opioids; tapering from a high dose may take weeks or months.
- Consider the possibility of hyperalgesia if a patient on long-term opioid therapy presents with increased sensitivity to pain.
- Consult the latest advice and warnings for opioids during pregnancy in the product information and in clinical resources.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/opioids-risk-of-dependence-and-addiction
In Hong Kong, there are registered pharmaceutical products containing alfentanil (1 product), buprenorphine (8 products), codeine (357 products), dihydrocodeine (11 products), fentanyl (13 products), methadone (2 products), morphine (20 products), opium (17 products), oxycodone (25 products), pethidine (4 products), remifentanil (8 products), tapentadol (8 products) and tramadol (50 products). These products are drugs under supervised sales or prescription-only medicines. There is no registered pharmaceutical product containing diamorphine, dipipanone, hydromorphone, meptazinol, papaveretum and pentazocine.
So far, the Department of Health (DH) has received adverse drug reaction related to codeine (4 cases), fentanyl (1 case), methadone (4 cases), morphine (8 cases), oxycodone (2 cases), pethidine (3 cases) and tramadol (4 cases). The DH has not received any case of adverse drug reaction related to alfentanil, buprenorphine, dihydrocodeine, opium, remifentanil and tapentadol.
News related to the safe and appropriate use of opioid analgesics was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 11 Sep 2013, with the latest update posted on 23 Aug 2019. Letters to inform local healthcare professionals were issued by the DH on 11 Sep 2013. The Registration Committee of the Pharmacy and Poisons Board discussed the matter in Feb 2015. Currently, pharmaceutical products which are controlled-release, extended-release or long-acting opioid analgesics (containing hydromorphone, morphine, oxycodone, tapentadol, fentanyl, buprenorphine and methadone) should include safety information about the risks of addiction, abuse, misuse, overdose and death, and limitations of use in patients with severe pain for which alternative treatment options are inadequate.
The risk of tolerance, dependence and withdrawal symptoms associated with the use of opioid analgesics are documented in overseas reputable drug references such as the “Martindale: The Complete Drug Reference”. The DH will remain vigilant on safety update of the drugs issued by other overseas drug regulatory authorities for consideration of any action deemed necessary.
Ends/Thursday, Sep 24, 2020
Issued at HKT 18:00
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