In a major setback to Indian drug makers like Zydus Cadila and IPCA Laboratories, the US biomedical research agency National Institute of Health (NIH) and the European Union drug regulator European Medicines Agency (EMA) have warned health professionals to restrict and monitor the usage of anti-malarial drug hydroxychloroquine (HCQ) owing to potential side effects. Zydus and IPCA are the world's largest producers of HCQ, which has been hyped as a 'cure' for COVID-19.
EMA said recent studies have reported serious, in some cases fatal, heart rhythm problems with chloroquine or hydroxychloroquine, particularly when taken in high doses or in combination with the antibiotic azithromycin. "In the context of COVID-19, these medicines should only be used as part of clinical trials or in line with nationally agreed protocols. They must not be used without a prescription and without supervision by a doctor," said the EMA.
Sources said a study by the Universities of Virginia and South Carolina, along with the VA system of Columbia among 368 male COVID-19 patients in the US - with 97 receiving hydroxychloroquine, 113 receiving a combination of hydroxychloroquine and azithromycin, and 158 not receiving any hydroxychloroquine - showed that 27 per cent treated with hydroxychloroquine and 22 per cent with the combination therapy died. The group not treated with the drugs showed a mortality rate of 11.4 per cent.
The US Department of Health and Human Services' National Institute of Health (NIH), the largest biomedical research agency in the world, have said there are insufficient clinical data to recommend either for or against using hydroxychloroquine for the treatment of COVID-19. "If used, clinicians should monitor the patient for adverse effects, especially prolonged heart rhythm interval", the NIH says in its COVID-19 treatment guidelines.
Hydroxychloroquine is used for the treatment of malaria and certain autoimmune diseases like Lupus and Rheumatoid Arthritis.
In addition to side effects affecting the heart, hydroxychloroquine is known to potentially cause liver and kidney problems, nerve cell damage that can lead to seizures, and low blood sugar (hypoglycaemia).
The drug was found to be effective in smaller group studies on COVID-19 patients in France and multicenter clinical trials conducted in China.
The drug got global publicity after US President Donald Trump termed HCQ as a 'game changer' in the fight against coronavirus and warned India of 'consequences' if it denied adequate quantities of supply to the US. Zydus, IPCA, and numerous other Indian manufacturers supply 70 per cent of the global requirement of HCQ worth $300-400 million, an old cheap molecule discarded by multinational drugmakers. Following this, manufacturers like Zydus and IPCA had enhanced their manufacturing capacities by many times.
Currently, large trials of the drug have been initiated by the World Health Organisation (WHO) under the 'solidarity trial' in 100 countries and 600 hospitals, along with four other medicines - remdesivir, lopinavir and ritonavir, and Interferon beta-1a. The Indian Council of Medical Research (ICMR), which along with the Drug Controller General of India (DCGI) had allowed restricted use of HCQ in COVID-19 patients in India, is also conducting its own large trials among coronavirus patients in India, as part of the WHO trial.
"These medicines are being used in the context of the ongoing pandemic for treating patients with COVID-19 and investigated in clinical trials. However, clinical data are still very limited and inconclusive, and the beneficial effects of these medicines in COVID-19 have not been demonstrated. Results from large, well-designed studies are needed to make any conclusions," said EMA. The advisory was issued by the COVID-19 EMA pandemic Task Force (COVID-ETF) in consultation with EMA's Pharmacovigilance Risk Assessment Committee (PRAC).
EMA said some clinical trials currently investigating the effectiveness of hydroxychloroquine in treating COVID-19 use higher doses than recommended levels. While serious side effects can occur with recommended doses, higher doses can increase the risk of these side effects, including abnormal electrical activity that affects the heart rhythm (QT-prolongation). EMA and national competent authorities are monitoring the situation closely and have enhanced their safety monitoring of medicines used in the treatment of COVID-19 in order to take timely action when necessary, it said.
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