From this module on codeine use you will learn:
- The efficacy and function of codeine
- The tolerance and addiction associated with this medicine
- The SOPs and training needed for OTC codeine sales
Download this module - this includes the 5-minute test - here.
All pharmacists will know the information the Medicines and Healthcare products Regulatory Agency (MHRA) requires to be printed on all over-the-counter (OTC) codeine packaging. This ensures the following warnings are prominently displayed on the front of the pack:
- can cause addiction
- for three days’ use only.
It also requires the following wording to be included on the back of the pack:
- for the short-term treatment of acute moderate pain when other painkillers have not worked
- do not take less than four hours after taking other painkillers.
But even though this information is familiar to pharmacists, how often is it passed on to patients by pharmacy staff?
This module looks at how the whole pharmacy team can work together to provide the best advice and support for patients requiring codeine for the management of mild to moderate pain.
What is codeine?
Codeine is a weak opioid that can be used to treat: mild to moderate pain; coughs, although there is limited evidence for this; and, to a lesser extent, diarrhoea.
For the management of mild to moderate pain, OTC codeine is available as a combination product, for example with paracetamol (co-codamol) 8mg/500mg, with aspirin 8mg/400mg or 500mg, and with ibuprofen 12.8mg/200mg.
It is also available on prescription, in strengths of 15mg, 30mg or 60mg as a single constituent, or in combination with paracetamol 500mg with 15mg or 30mg.
Codeine is metabolised to morphine in the liver and this binds to opioid receptors in the brain. This increases the tolerance to pain, but does not remove the cause of the pain. As a result of this metabolism to morphine, there are positive side effects, such as feelings of warmth, wellbeing, relaxation and sleepiness. As such, codeine has a tendency to be abused.
However, other side effects that are less desired include drowsiness, constipation, nausea, vomiting and confusion.
Efficacy of codeine
The National Institute for health and Care Excellence (Nice) guidelines for mild to moderate pain recommend codeine as one of the weak opioid options to be prescribed to those who have an inadequate response to paracetamol or a non-steroidal anti-inflammatory drug (NSAID), either alone or in combination. However, you should be aware that these guidelines refer to a 30-60mg dose of codeine taken four times a day.
The evidence used in the guidance finds that a combination analgesic of codeine 8mg plus paracetamol 500mg is no more effective than paracetamol alone. In addition, it can cause opioid adverse effects, such as constipation.
Despite Nice guidance, codeine prescriptions are on the rise, and co-codamol appeared in the top 20 most prescribed items list in 2015.
This could be due to conflicting evidence on the risks and efficiacy of opioid alternatives. These include: the links between NSAIDs and gastric irritation; the links between NSAIDS and cardiac risks; and the 2016 Cochrane review of the efficacy of paracetamol for lower back pain, which suggested it is no more efficient than a placebo. Perhaps it is unsurprising co-codamol is often considered the easiest option for patients and prescribers.
Tolerance and addiction
Although codeine has its uses in acute pain relief, it can only be used for a few days before tolerance to the steady dose occurs. Tolerance describes a person's diminished response to a drug, which occurs when the drug is used repeatedly and the body adapts to its continued presence.
Therefore the regular or original dose of codeine will no longer be effective in controlling pain, and increasingly higher doses are required to achieve the same therapeutic effect.
There are two pharmacodynamic theories – ie relating to how a drug affects an organism – for opioid tolerance. One is that opioid receptor down-regulation is a factor, and the other is that the receptors undergo change or desensitisation with prolonged exposure.
As a patient’s tolerance of codeine increases, they develop a physical dependency – recognised as addiction – due to a change in receptors. This means that if the patient stops taking the drug, they will experience withdrawal effects. These effects are often initially confused with flu symptoms, and include:
- runny nose
- muscle cramps.
If tolerance has developed and the patient is misusing combination OTC products by taking higher doses than recommended, they are at risk of potentially fatal effects, such as:
- paracetamol toxicity, with a risk of liver damage or kidney failure
- ibuprofen overdose, which could result in a gastric bleed.
Pharmacies have shelves full of OTC combination codeine products, all marketed for different forms of pain, including headaches. However, Nice guidance for the management of all types of headaches does not actually support routine use of codeine or any other type of opioids. This is due to their potential to cause painkiller overuse headaches and the possible opioid side effect of nausea, which could be as bad as that of the migraine being treated.
Nice recommends the use of triptans, paracetamol, aspirin, NSAIDs or acupuncture therapy – used separately or in combination, depending on the type of headache.
Even with non-opioid drugs, there is a potential for medication overuse headache, normally occurring after 15 days or more prolonged use. The only cure is to abruptly stop treatment for one month, before reintroducing the drug. With codeine, abrupt withdrawal could be dangerous and therefore a much more cautious withdrawal programme is required.
Standard operating procedures (SOPs) and training
Community pharmacies will have SOPs in place to support all pharmacy staff. These should cover not only the sale of medicines when requested by brand or as a response to symptoms, but also the safe supply of OTC drugs that are vulnerable to abuse, such as codeine.
Staff should all be trained to be aware of the risks of codeine, to identify customers who may potentially be purchasing it for abuse or misuse, and to refer these individuals to a pharmacist as appropriate (see Pharmacy interventions, below). Signs to look out for can include:
- repeated requests from the same customer over a short time frame
- patients who already collect a prescription for a strong opioid from your pharmacy or have done so in the past
- lack of eye contact
- irritability on questioning
- nervous demeanour
- having excuses at the ready
- having exactly the right change for the product, despite claiming it is “the first time” they are using it.
It may a good idea to check a patient’s medication record to see how long they have been taking the medication. Many addicts will not identify that they have a problem, or may feel there is a stigma attached to seeking support for this.
Codeine OTC sales are restricted to one pack per customer and a maximum of 32 tablets, for either effervescent or non-effervescent forms. When dispensing or selling effervescent products to hypertensive patients, you should highlight their high salt content.
Codeine is also only for sale to adults over 18 years. This follows the European Medicines Agency (EMA) safety review and Commission on Human Medicines (CHM) guidance of 2013. This came about after it was found that genetic variations had resulted in the death of some children who were ultra-rapid metabolisers of codeine to morphine, and experienced toxicity from a standard dose.
This ultra-rapid metabolism is due to extra copies of the enzyme (CYP2D6), resulting in faster than normal breakdown. Approximately 3% of Europeans have this genotype.
Codeine was contraindicated in breastfeeding by the MHRA and EMA in 2013. This followed the death of a 12-day-old baby, where the mother took codeine (previously considered safe in breastfeeding) for her episiotomy – a surgical cut in the muscular area between the vagina and the anus – pain. As she was an ultra-rapid metaboliser of codeine and the baby was not, it resulted in morphine toxicity in the baby.
Codeine is also contraindicated in an acute asthma attack, due to the risk of respiratory depression.
Training for staff should cover the essential printed information of:
- a maximum three-day use
- risk of addiction
- rebound headaches
- other relevant restrictions. For example, it’s illegal in England and Wales to drive with legal drugs in your body if they impair your driving.
In addition, staff should be able to signpost potential codeine addicts to the appropriate support service available, and help them to understand why they need this help.
Pharmacists should also consider that codeine is not appropriate for all patients, for example in those with a previous allergic reaction to codeine, in those with pre-existing kidney or liver problems and in those who are pregnant or breastfeeding.
There is also a high risk that the patient may move on to the procurement of stronger opioids, illegally.
There have been several stories in the news of patients becoming addicted to OTC codeine products, following the drug being recommended to them by their GP, and the patient viewing it as a ‘safe option’ as no prescription is required. By the time they finally realise they have a dependency problem, they require an arduous weaning programme – sometimes involving daily doses of methadone – to reduce or stop their medication.
How you approach customers about a codeine sale refusal needs to be thought out, as people can act unexpectedly. While there are often strong words, the risk of a physical response from someone who is addicted – and will do anything to try to get their painkiller – is always there. This potential situation should make you reflect on how you deal with repeated codeine requests, as it is essential you do not turn a blind eye for fear of intimidation.
Your consultations with repeat requesters should begin with empathy, to avoid the customer taking a defensive approach. To start with, you should ensure your body language remains open and friendly, so they are engaged in conversation with you.
You can use the medicine’s box to talk through the risks of side effects and delve into why they require the medication. It is worth having a good overview of each of the Nice guidelines for pain and headache management. It helps to have this guidance printed in an easily accessible form, so you can illustrate your advice when you talk it through with the patient.
Signposting them to their GP as a first port of call to discuss a weaning programme is essential. If the individual is not prepared to see their GP due to embarrassment, then the website talktofrank.com contains a search option for support in their area.
Although pharmacists may find it hard to identify opportunities to engage with prescribers about their prescribing choices, their role as medicine experts is to have exactly this kind of conversation – so they should not shy away from it. The new General Pharmaceutical Council standards for pharmacy professionals even declare pharmacists must “speak up when they have concerns”.
Once the patient has agreed to a pharmacological tapering protocol for their codeine use, they will need psychological support in the form of cognitive behavioural therapy or group therapy, in addition to a withdrawal plan.
The patient must decide over what period they wish to withdraw. This could involve, for example, reducing the dose by one tablet per week, or half a tablet twice a week or less, depending on how they find the withdrawal symptoms.
If they go ‘cold turkey’, the withdrawal symptoms peak in the first week, then will be gone after a month. However, some of the psychological effects that can occur in the first week of sudden withdrawal include suicidal thoughts, so this should be kept in mind when discussing the options with the patient, especially if they have any mental health issues.