In-depth: Codeine regulation – a tussle between pain relief and addiction
Whether a pharmacist suggests it for treating headaches or whether a doctor prescribes it for managing post-surgical pain, chances are good that at some point you’ve taken a pain pill containing the opioid codeine. Products like Gen-payne, Myprodol, and Stopayne all contain small amounts of codeine – typically in combination with other painkillers such as paracetamol or ibuprofen.
In recent years, however, the regulation of codeine has become something of a headache.
On the one hand, codeine is a powerful and effective painkiller that can bring relief to many. On the other, abuse or misuse of the drug can lead to dependence and addiction. Finding the right balance between an outright ban and a free-for-all is not straightforward.
Addiction and withdrawal
That codeine misuse poses serious health risks is not disputed and in most countries, access to the drug is at least partially restricted through regulation.
Whether taking it [codeine] as pain relief or to get high, over time there is a risk of addiction.
Dr Shaquir Salduker, a member of the South African Society of Psychiatrists, says there are two types of problems associated with codeine misuse or abuse. The first is when patients with pain take increasing amounts of codeine-containing pills or capsules over time or take higher doses. He says these patients are essentially dependent on codeine without realising it.
The second is when people use codeine pills without having any pain and instead use them for their sedative and ‘feel-good’ properties. Bhekisisa recently reported on the use of codeine in a drink called ‘lean’ – made by mixing codeine-containing cough syrup with a fizzy drink.
Whether taking it as pain relief or to get high, over time there is a risk of addiction.
Salduker describes addiction as a state where a person becomes tolerant of the effects of a drug so that they require higher and higher doses to get the same effect as previously and where a person experiences withdrawal symptoms when they stop using the drug. The withdrawal symptoms with codeine, he says, can be severe.
“You can have a very serious clinical syndrome or withdrawals, which ranges from physical symptoms like nausea, vomiting, excessive sweating, increase heart rate, and blood pressure fluctuations to very serious symptoms like seizures, confusion, and psychosis where you start hallucinating and believing things that are not there,” he says.
For medicines to be marketed in South Africa, they first have to be registered by the South African Health Products Regulatory Authority (SAHPRA). Registered medicines are placed into different categories (called schedules) according to the risks associated with the product. Schedule 0 can be sold off the shelf, schedule 1 and 2 is over-the-counter (which means you have to ask a pharmacist for it), and schedule 3 and up require prescriptions.
Andy Gray, a senior lecturer at the University of KwaZulu-Natal, explains that products containing codeine fall into several different schedules, depending on factors such as the amount of codeine in the product, whether it is combined with another active ingredient, the package size, and whether it is for export.
Codeine-containing products fall into Schedule 2 when codeine is combined with another active ingredient, has a maximum of 10mg of codeine per pill or capsule, or a maximum of 5ml of codeine in syrups or suspensions. A Schedule 2 can have a maximum dosage of 80mg or less per day and a package size that allows for no more than 5 days’ treatment. Anything above that, for a combined product of codeine and another active ingredient, is Schedule 3 and thus requires a prescription from a doctor.
Unlike Schedule 1, the sale of a Schedule 2 product has to be documented by the dispensing pharmacist by capturing the patient’s identity and address. In theory, this should allow for repeat purchasing to be detected. However, as Gray explains, it doesn’t stop patients from visiting multiple pharmacies or seeing multiple prescribers, nor does it address criminal activity.
When codeine is not combined with another active ingredient, it falls into Schedule 6, regardless of dosage or strength. Schedule 6 medicines can be subscribed for a maximum of 30 days and no repeat prescriptions are allowed.
there are two sides to the problem of codeine abuse or addiction. The first is the inappropriate sale of codeine-containing medicines by pharmacists or inappropriate prescription by authorised prescribers. The second is codeine-containing substances being diverted into unregulated distribution channels through theft or illegal sale by “unscrupulous practitioners”
Where things go wrong
Gray suggests there are two sides to the problem of codeine abuse or addiction. The first is the inappropriate sale of codeine-containing medicines by pharmacists or inappropriate prescription by authorised prescribers. The second is codeine-containing substances being diverted into unregulated distribution channels through theft or illegal sale by “unscrupulous practitioners”.
In relation to the prior, Gray says, “The dangers of codeine-containing medicines are well known and should be familiar to most health professionals. However, it is unclear whether they are exercising the necessary care in respect of these products, and adequately informing patients of the risks.”
Salduker has similar concerns.
He says patients are not being adequately informed of the risk of addiction. If pain has a specific cause like a car accident or surgery, then of course medication like codeine should be given to help manage it. But something like a persistent headache possibly caused by stress shouldn’t be treated in the long term with a medication that contains codeine because it is not solving the root cause. “It’s one of those things where we’re saying it’s good, but only in certain circumstances. In others it’s bad. So, it can be a good drug, which does bad things,” he says.
It is unclear to what extent pharmacists are helping patients make informed choices about codeine use.
Pharmacists answer to the South African Pharmacy Council (SAPC) and not to SAHPRA. As Gray explains, the SAPC doesn’t regulate medicines per se, but has a role in regulating the professional conduct of pharmaceutical personnel. “It can investigate complaints of unprofessional action and take disciplinary steps where needed,” he says.
The dangers of codeine-containing medicines are well known and should be familiar to most health professionals. However, it is unclear whether they are exercising the necessary care in respect of these products, and adequately informing patients of the risks.
Vincent Tlala, Registrar and CEO of the SAPC, confirms that pharmacists are responsible for educating patients on the proper usage and storage of medications, including codeine-containing medicines.
“At the level of the pharmacy, counselling on safe usage and storage is provided in line with Good Pharmacy Practice,” he says. “Further to this, pharmacy professionals also observe pharmacovigilance – this process ensures that any unexpected side effects reported by the patient, including dependency, are noted, addressed, and reported in line with relevant protocols.”
He says the Schedule 2 register is audited at every inspection of a pharmacy by the SAPC and the council undertakes monitoring and disciplinary inspections to “ensure pharmacies adhere to good practice and are not engaging in practices that may endanger the lives of patients”. Additionally, he says, they “investigate and institute disciplinary action when members of the public report alleged misconduct of any kind by those we regulate”.
Dealing with diversion
The second problem identified by Gray is the diversion of codeine-containing substances into unregulated distribution channels through theft or illegal sale.
“There is evidence of large quantities of codeine-containing cough mixtures being sold in markets, from retail outlets such as hairdressers, and also moved across borders into neighbouring states. The origin of those diverted stocks has not been identified,” he says. “There is also evidence that some pharmacies and dispensing practices are procuring large volumes from wholesalers. None have yet been prosecuted.”
Here we are back in SAHPRA’s territory.
Mokgadi Fafudi, the manager of SAHPRA’s Regulatory Compliance unit, which is responsible for the management of narcotics and psychotropic substances, says codeine falls under narcotic substances and thus under the unit’s jurisdiction. She says that the unit is tasked with market surveillance, detecting and responding to sub-standard products or falsified products, and ensuring that the production, sale, or distribution of all medicines and health substances are in compliance with the law, including imported products.
There is also evidence that some pharmacies and dispensing practices are procuring large volumes from wholesalers. None have yet been prosecuted.
According to Fafudi, SAHPRA’s oversight starts at the very beginning, with the manufacture of codeine-containing substances, and spans the entire pharmaceutical supply chain. This includes annually pre-determining estimates of how much of each codeine-containing product will be manufactured by suppliers, keeping track of the different pill, capsule, and syrup formulations, and estimating how much waste and consumption will occur at the end of the manufacturing process. They also have to give the green light before expired or wasted medicines may be destroyed.
“We got oversight from birth to death of these substances throughout the supply chain just to monitor there is no illicit channel of these substances,” she says.
She adds that regular meetings with manufacturers and sellers of codeine are being conducted to monitor the production and consumption of codeine as a way of oversight. “We’ve got regular meetings with them [the manufacturers] where they need to justify why they need to produce that much… [for sellers] why are you selling this much? So, we have got those monitoring, discussions, and engagement with them,” she says.
In response to these various challenges, there have been some changes to how codeine is regulated in recent years.
“The first step was to tighten the schedule inscription, reducing the strength and quantity sold, making it possible to only sell one pack per patient,” says Gray. Schedules were also amended so that codeine products for export and products containing no other active ingredients besides codeine all fall into Schedule 6.
“The next step was to request a full accounting of production volumes and sales from manufacturers and wholesalers in an attempt to identify which products were moving where. That has been followed by enhanced compliance monitoring by SAHPRA inspectors. At the moment, the professional information and patient information leaflets are being updated,” Gray says. He adds that the option to further restrict the use of codeine in children is being explored in the country and, if achieved, will be done through labelling changes in the Professional Information and Patient Information Leaflets.
Another response to codeine abuse was the launch of the Codeine Care Initiative in 2013 by the Community Pharmacy Sector and the Pharmacy Society of South Africa. In pharmacies that have signed up for the Initiative, when a patient puts in a request for a medication that contains codeine, either via a prescription or request at a pharmacy, their details are recorded in the dispensing programme which allows the Codeine Care Initiative’s software to link that patient’s identification number, either ID number or passport number, to the database of other pharmacies that have signed up for the Initiative. The system can thus flag if someone has recently purchased a codeine-containing product and may be at risk of addiction or abuse.
But, as explained by Dr Mariet Eksteen, who has an area of expertise in professional development and support at the Pharmaceutical Society of South Africa, it is currently a voluntary programme and it has only been implemented in community pharmacies in the private healthcare sector. To assist pharmacists in detecting and reporting abuse of medications that contain codeine, Eksteen says a nationwide implementation of the initiative must be mandated by the relevant regulators, stakeholders, and authorities. “And secondly,” she says, “the whole supply chain from manufacturing and importing to the point of dispensing must be monitored. If any of these components are not fully adopted and optimised, it will result in an ineffective initiative that will not achieve the desired outcomes.”
Should codeine-containing products be up-scheduled?
One option that Fafudi says SAHPRA is having discussions on is whether access to codeine should be further restricted by up-scheduling some codeine-containing products. A shift from Schedule 2 to Schedule 3, for example, would mean that products that can now be purchased over the counter would require a prescription. Salduker is of the view that up-scheduling medicines that contain codeine will help solve the addiction and abuse problem.
But Tlala argues that the up-scheduling of codeine-containing medicines has not worked in other countries. He says countries that have up-scheduled codeine have reported a reduction in legal sales but that it has not translated into reduced codeine abuse. “The only persons who seem to suffer from such bans are legitimate patients who have to endure pain or fork [out] more money for stronger painkillers than those which are available over-the-counter,” he says. “Up-scheduling low-strength codeine products will increase the cost of care for legitimate patients who are managing chronic or acute pain as they would then be required to add the cost of a prescription for accessing their medicines.”
Fafudi says SAHPRA will continue to consider the issue.
“We cannot up-schedule until we get to the core of the problem,” she says. There needs to be a balance struck between restricting access to codeine to limit abuse or misuse and ensuring that people who need it are still able to access it, she says. To find this balance, she suggests more data is needed about codeine abuse and addiction. She says that research and consultations are ongoing and a clear path forward should emerge in the next six months.