Whether a pharmacist suggests it for treating headaches or whether a doctor prescribes it for post-surgical pain, chances are that at some point you’ve taken a pain pill containing the opioid codeine. However, regulating codeine has become something of a headache, writes Elri Voigt for Spotlight.
Products like Gen-payne, Myprodol and Stopayne all contain small amounts of codeine – typically in combination with other painkillers such as paracetamol or ibuprofen. On one hand, it is a powerful, effective painkiller that can bring relief to many. On the other, abuse or misuse 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.
Dr Shaquir Salduker of the South African Society of Psychiatrists says there are two problems associated with codeine misuse/abuse. One is when patients with pain take increasing amounts of codeine-containing pills or capsules over time or take higher doses: 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. MedicalBrief recently reported on a Bhekisisa story about 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’s a risk of addiction.
Salduker said withdrawal symptoms with codeine can be severe. “You can have a very serious clinical syndrome or withdrawals, from physical symptoms like nausea, vomiting, excessive sweating, increased heart rate, and blood pressure fluctuations to very serious symptoms like seizures, confusion, and psychosis,” he says.
Current schedules
For medicines to be marketed in SA, they have to be registered by the South African Health Products Regulatory Authority (SAHPRA) and placed into different schedules according to the risks associated with the product.
Andy Gray, a senior lecturer at the University of KwaZulu-Natal, said 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, 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/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 allowing for no more than 5 days’ treatment. Anything above that, for a combined product of codeine and another active ingredient, is schedule 3, requiring a doctor’s prescription.
Unlike schedule 1, the sale of a schedule 2 product must be documented by the dispensing pharmacist by capturing the patient’s identity and address. Theoretically, this should allow repeat purchasing to be detected. However, as Gray adds, 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.
Where things go wrong
Gray said there are two sides to the problem of codeine abuse or addiction. The first is the inappropriate sale of these 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”.
Regarding the former, he says: “The dangers of codeine-containing medicines are well known. However, it is unclear all health professionals exercise the necessary care in respect of these products, and adequately inform patients of the risks.”
Salduker has similar concerns, saying patients are not being properly educated about the addiction risk. If pain has a specific cause like a car accident or surgery, then medication like codeine should be given to help manage it. But a persistent headache possibly caused by stress shouldn’t be treated in the long term with codeine medication because it is not solving the root cause.
It is unclear to what extent pharmacists help 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,” he says.
Vincent Tlala, Registrar and CEO of the SAPC, confirms pharmacists are responsible for educating patients on the proper usage and storage of medications, including codeine-containing medicines.
“Counselling on usage and storage is provided in line with Good Pharmacy Practice,” he says. “Pharmacists also observe pharmacovigilance – ensuring any unexpected side effects reported, including dependency, are noted, addressed and reported.”
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. Additionally, they “investigate and institute disciplinary action when the public reports 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.
“Large quantities of codeine-containing cough mixtures are sold in markets such as retail outlets like hairdressers, and also moved across borders into neighbouring states. The origin of those diverted stocks has not been identified. Some pharmacies and dispensing practices are also procuring large volumes from wholesalers. None has yet been prosecuted.”
Here we are back in SAHPRA’s territory.
Mokgadi Fafudi, 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. The unit is tasked with market surveillance, detecting and responding to sub-standard products or falsified products, and ensuring the production, sale, or distribution of all medicines/health substances are in compliance with the law.
SAHPRA’s oversight starts at the 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 have oversight from birth to death of these substances throughout the supply chain just to monitor there is no illicit channel,” she says.
Regular meetings with manufacturers and sellers of codeine are conducted to monitor the production and consumption as a way of oversight. “They need to justify why they need to produce that much… (for sellers) why are you selling this much? So, we have monitoring, discussions, and engagement with them,” she says.
Regulatory changes
In recent years, there have been some changes to how codeine is regulated.
“The first step was tightening 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 requesting a full accounting of production volumes and sales from manufacturers and wholesalers so as to identify which products were moving where. That is followed by enhanced compliance monitoring by SAHPRA inspectors. Currently, the professional information and patient information leaflets are being updated.”
Gray adds that the option to further restrict the use of codeine in children is being explored 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 containing codeine, either via a prescription or request at a pharmacy, their details are recorded in the dispensing programme allowing 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, says 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 help pharmacists detect and report abuse of codeine-containing medications, Eksteen says a nationwide implementation of the initiative must be mandated by regulators, stakeholders, and authorities. “Also,” she says, “the whole supply chain from manufacturing and importing to the point of dispensing must be monitored. If any of these is not fully adopted and optimised, it will result in an ineffective initiative that won’t achieve the desired outcomes.”
Should codeine-containing products be up-scheduled?
Fafudi says SAHPRA is discussing whether access to codeine should be further restricted by up-scheduling some products. Shifting from schedule 2 to schedule 3, for example, would mean products now bought over the counter would require a prescription. Salduker believes this could help solve the addiction and abuse problem.
But Tlala argues this has not worked in other countries. Those that have up-scheduled codeine have reported a reduction in legal sales but it has not reduced codeine abuse. “The only people affected from such bans are legitimate patients who must endure pain or fork (out) more money for stronger painkillers than those available over-the-counter,” he says. “Up-scheduling low-strength codeine products will increase costs for legitimate patients managing chronic or acute pain as they then have 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 between restricting access to codeine to limit abuse or misuse and ensuring people who need can still access it, she says. She suggests more data are needed about codeine abuse and addiction, that research and consultations are ongoing and a solution should emerge in the next six months.
See more from MedicalBrief archives:
Cheap, over-the-counter codeine fuels SA schoolchildren’s addiction
SAHPRA review: Pain meds with codeine may be prescription only
Medicines regulator may restrict codeine to prescription only
Lean – South Africa’s codeine addiction crisis
Nigeria legislates to ban codeine in cough syrup