A Johannesburg man who suffered four tendon ruptures has accused Cipla Medpro of deliberately not disclosing adverse events associated with an antibiotic it markets in this country, raising the issue of patients' rights to be adequately informed about the risks associated with medicines they are prescribed.
The warnings, he says, should have been spelt out in the leaflet within the medicine’s box.
The company’s defence, however, is that the warnings were posted online, on the website South African Health Products Regulatory Authority (SAHPRA), which has said it was satisifed that the company had complied with its requirements.
But in an unrelated analysis on the GroundUp site, Dr Andy Gray, senior lecturer at the University of KwaZulu-Natal and co-director of the WHO Collaborating Centre on Pharmaceutical Policy and Evidence Based Practice, said the rights and duties of users and healthcare providers are clearly described under the National Health Act, and should be enforceable – and everyone has the right to know about the medicine they take and the potential risks thereof.
Anton van den Heever, an outdoor enthusiast and polo-cross player in his 40s, is now looking at his legal options after enduring four tendon ruptures after he was prescribed Cipla’s Tavaloxx (fluoroquinolone), a drug which treats sinus, urinary tract and respiratory infections.
He was prescribed the drug by his doctor after developing an infection linked to a kidney stone removal procedure in 2018.
“I didn’t know this drug was going to change my life forever … a couple of weeks after recovering from the infection I was back in the routine of my life and exercising,” he said.
But then one day, while taking a breather after exercise, his right elbow collapsed without warning.
“My right bicep suddenly ruptured – a huge shock. I consulted a surgeon and had surgery,” he said. After the operation, he was told to wear a sling.
After a few weeks of light exercises, however, his left bicep ruptured.
“This was incredible … again back to the surgeon, who said that in this case the tendon was so poor they would need to add cowhide to fix the rupture. Now [I have] two arms in slings,” he said.
Warnings of ruptures
Between 2015 and 2018, the US Food and Drug Administration (FDA) had issued numerous warnings that fluoroquinolone’s possible toxic side effects could range from tendon ruptures to aortic aneurysms.
In 2015, the FDA called for a black box warning, the agency’s strongest, for all fluoroquinolones.
Pharmaceutical company Johnson & Johnson, which faced an $800m class lawsuit from flouroquinolone users who suffered severe adverse reactions, settled hundreds of the cases.
In January 2019, Cipla was one of the pharmaceutical companies that signed “important medical safety information” that TimesLIVE Premium has seen, which advised medical practitioners not to prescribe the drug for “non-bacterial (chronic) prostatitis for mild to moderate infections, including uncomplicated cystitis and acute exacerbation of chronic bronchitis, among others”.
The letter issued in collaboration with SAHPRA stated that “healthcare professionals are advised that for the indications listed, only to prescribe quinolone/fluoroquinolone antibiotics where other antimicrobials are considered not to be an appropriate treatment option, have failed, are contraindicated, or not tolerated”.
Doctors were advised not to prescribe the drug for “treating non-severe or self-limiting infections (such as pharyngitis, tonsillitis and acute bronchitis), preventing travellers’ diarrhoea or recurrent lower urinary tract infections, and non-bacterial infections”.
Despite this warning and commitments to update insert packaging leaflets, Cipla’s package insert inside Tavaloxx’s box does not contain warnings about some of the latest side effects.
The insert package found in the Tavaloxx box was published in October 2007, and had not been revised.
Cipla spokesperson Fidelia van der Linde said the updated package leaflet can be found on the SAHPRA website. She also confirmed that the company signed the January 2019 letter to alert healthcare professionals of the adverse side effects and warnings related to the drug.
“Therefore doctors and pharmacists are aware of the updates. Please note Cipla has been in constant engagement with SAHPRA regarding this matter. SAHPRA has recommended we do an over-label, referencing the latest package inserts/leaflet information on the SAPHRA site,” she said.
‘Unsubstantiated allegations’ – CIPLA
On why the warning was not on the package insert inside the box, she said: “We have over-labelled all Tavaloxx product on hand accordingly. The over-label refers patients and healthcare professionals to the SAHPRA website for the latest package insert and leaflet information.”
She said all healthcare professionals “are well aware of these … changes and should ensure they take the necessary precautions for this class of medicine”.
SAHPRA spokesperson Yuven Gounden said based on an “approved package insert dated 16 August 2020 for Tavaloxx, Cipla Medpro has complied with SAHPRA’s requirements”.
Gounden said the regulator takes the necessary steps to ensure all products meet the criteria of safety, quality and efficacy.
“If SAHPRA is aware of any violation of the Medicines and Related Substances Act, then it can take action. However, in this instance, this is not relevant for Cipla Medpro,” he added.
‘The right to be informed’
UKZN’s Gray, meanwhile, who is also a member of South Africa’s National Essential Medicines List Committee and co-chairs its Expert Review Committee, said the right to be informed should be recognised as a human right, but in practise, there are barriers in both the public and private sectors.
Writing in GroundUp, he said this right is already included in law when it comes to our health. Chapter 2 of the National Health Act 2003 deals with the rights of healthcare users and duties of healthcare providers and workers.
Section 6, headed: User to have full knowledge, requires “every healthcare provider to inform a user of –
• (a) the user’s health status except in circumstances where there is substantial evidence that the disclosure … would be contrary to the best interests of the user;
• (b) the range of diagnostic procedures and treatment options generally available;
• (c) the benefits, risks, costs and consequences generally associated with each option; and
• (d) the user’s right to refuse health services and explain the implications, risks, obligations of such refusal.”
This information must also be conveyed in a language the user understands “and which takes into account the user’s level of literacy”.
A healthcare provider must also take all reasonable steps to obtain the user’s informed consent – meaning the user has consented to the treatment or health service.
The point is hammered home in section 8, Gray writes: “A user has the right to participate in any decision affecting his or her personal health and treatment.”
The rights and duties of users and healthcare providers are clearly described and should be enforceable, he adds, yet while the Patient Rights Charter may well be posted on hospital walls, like the faded Batho Pele posters, it has become merely part of the décor, he added
The right to know
Medicines should be included in the range of treatment options disclosed to patients, with their associated “benefits, risks, costs and consequences”, but patients, parents and caregivers may also access information about medicines from many other sources, including marketing materials published by the manufacturers and sellers of these products.
The Medicine Act’s regulations limit advertising. The only medicines that can be advertised directly to consumers are those containing substances in Schedule 0 (which can be sold in any retail outlet, eg paracetamol) and Schedule 1 (which can only be sold in a pharmacy, eg ibuprofen gel).
Medicines containing substances in Schedules 2 (also pharmacist-initiated) and Schedules 3 to 6 (prescription-only medicines) may only be advertised to healthcare workers and practitioners.
Every medicine registered by SAHPRA has to have an approved professional information (PI) as well as a patient information leaflet (PIL).
The PI is written in technical language for professionals, whereas a patient should be able to read the PIL.
In September last year, the Minister issued a proposed amendment to the regulations for comment, allowing the PIL to be printed in English only, but also requiring that it be provided in any of the other official languages in electronic format.
Is restricting advertising justifiable, and enforced?
Only the US and New Zealand allow direct-to-consumer advertising of prescription-only medicines.
Restricting advertising of prescription-only medicines is justified on the basis that it reduces inappropriate use of such medicines, influenced by patient demands.
But is this enough, asks Gray. Does South Africa’s medicine legislation meet the right to be informed?
Patients may want more information, even after being prescribed a medicine. Being verbally informed of the risks and benefits of a medicine by a pharmacist or doctor may not be enough; a patient may need to read the PIL.
The PIL should be accessible in languages other than English, but if these are only available electronically, it might be tricky to access it. A link or QR code included on the packaging of the medicine may make this easier.
Although the SAHPRA website provides a repository of PIs and PILs, it does not restrict access to the former to health professionals only.
There are also implementation issues. No approved translations of these documents are accessible, and the resource appears to be incomplete.
Also, the existing regulation of advertising is severely limited because it fails to take account of the many other channels by which information is disseminated, including websites and social media.
Medicines might be advertised directly to people using these channels, but the quality of this information may be poor, or inappropriate for particular patients.
Manufacturers’ websites may include navigation options to consumer and professional versions, but these are difficult to enforce. Those that are provided to a US market are easily accessed outside that country.
Also, where the use of medicines is promoted by influencers on social media, this may well be beyond the reach of existing regulatory systems.
The Covid pandemic provided an instructive case study, where many websites and public figures promoted the use of Ivermectin for both prevention and treatment, despite the lack of evidence.
Misinformation about medicines is reaching the public, despite the law, and while the “right to be informed” certainly applies to medicines, and the rights and duties of users and healthcare providers are clearly described in law, the reality is that existing attempts to regulate the marketing or promotion of medicines are not enough to protect the public, Gray adds.
GroundUp article – These are our rights when we use medicines (Creative Commons Licence)
See more from MedicalBrief archives:
ASA rules on ‘uncomfortable’ medical advertising
Medical influencers come with serious side effects
More than 25% of YouTube videos on Covid-19 contain misinformation
EMA recommends restrictions on fluoroquinolone and quinolone
Joint SA pharma advisory on risks with quinolone and fluroquinolone
SA medical regulator warns of ‘disabling’ effect of two antibiotics