Department of Pharmacology Chandigarh, India
Received date: 06/12/2021; Accepted date: 20/12/2021; Published date: 27/12/2021
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COVID-19 pandemic caused by the SARS-Cov-2 virus, has become a serious public health concern worldwide which spread across more than 200 countries in a matter of months. Amidst a deadly second COVID wave in India, the resources and the health infrastructure required to handle the situation was stretched to their limits. Furthermore, due to the non-specific nature of the disease and the plethora of symptoms and complications it presents, the medical management of COVID-19 became complicated and uncertain. Such a grim scenario evokes fear and panic among the citizens, leading to questionable and unnecessary practices such as stocking of medicines, hoarding oxygen cylinders and most importantly, selfmedication with over-the-counter drugs, dietary supplements (so-called immune boosters), prescription-only drugs, along with combining the use of alternative systems of medicine. Due to all these reasons, the practice of ‘polypharmacy’ is becoming rampant among the general population, which in most cases is inappropriate and even harmful. This review summarizes the various patient and physician associated factors promoting polypharmacy, along with examples of the common drugs being prescribed and/or self-administered, and the various steps that can be taken to prevent such futile practices.
SARS-Cov-2 virus; Pharma health infrastructure; Medications
COVID-19 is a viral disease, caused by SARS-CoV-2 virus, with symptoms ranging from flu-like illness to acute respiratory distress syndrome (ARDS), venous thromboembolism, multi-organ failure, and eventual death . COVID-19 has taken the whole world by storm, with India currently overcoming the heaviest brunt of the pandemic since it began in 2020. In the deadliest wave yet, India witnessed about 3-4 lakh cases of COVID-19, with over 3000 deaths per day .
It has been over one year since our descent into the pandemic, and we still lack a thorough understanding of all the aspects of this disease, one of the major reasons being the rapid evolution of the virus with multiple mutations and new strains, making not only the management but even the diagnosis tricky and uncertain. The US CDC has classified 5 COVID strains as variants of concern (VOCs), including the UK, South African, Japanese/Brazilian and Californian strains . Apart from these the ‘double mutant or delta’, and the ‘N440K’ variant of COVID-19, which is noted to be behind the unprecedented surge in some states in India, has added to the severity of the disease .
Due to the paucity of well-established evidence-based therapeutics for its prevention and cure, most COVID guidelines advocate a supportive treatment approach, with antivirals, steroids and monoclonal antibodies reserved for moderate-severe disease, with advanced lung involvement and risk of further worsening.
However, it is being observed that to a variety of reasons, people are consuming multiple medications, even for mild to moderate cases of COVID-19, most of which are not required, thus leading to inappropriate polypharmacy . ‘Polypharmacy’ as a word in medical science, was first coined about 150 years ago, and is defined as the consumption of 5 or more medicines at a time. It often is related to the consumption of multiple medicines which may lack scientific grounds, or evidence-based practice . While, polypharmacy is discussed more commonly with reference to the at-risk and the elderly population, in the current pandemic it is becoming increasingly evident among all age groups. Data shows that >80% of COVID cases are mild in nature, with <5% patients progressing onto severe disease and needing ventilator support. Thus, in most COVID cases the use of multiple medicines is irrational, unnecessary, and may even be counter-productive, thereby increasing the risk of adverse events and adding to the patient’s financial burden. It becomes important to understand and explain to the patients, the demerits of consuming multiple drugs at once because such practices can have many short-term and long-term repercussions  (Tables 1 and 2).
|Various medications being prescribed for COVID-19 in India|
|Name||Recommendation by ICMR1||Recommendation by US-CDC5|
|Paracetamol||Mild, moderate, severe disease||Mild, moderate, severe disease|
|NSAIDs||Mild disease||Mild disease|
|NSAIDs+/- paracetamol Fixed Drug Combinations (FDC)||Not recommended||Not recommended|
|Esomeprazole/Omeprazole||Not recommended||Not recommended|
|Domperidone||Not recommended||Not recommended|
|Antacids||Not recommended||Not recommended|
|Probiotics||Not recommended||Not recommended|
|Respiratory system agents|
|Cough syrup||Mild to moderate disease|
|Montelukast+levocetrizine fixed drug combination (FDC)||Not recommended||Not recommended|
|Antihistaminics (eg. Hydroxyzine)||Not recommended||Not recommended|
|Betadine/chlorhexidine (for gargles)||Not recommended||Not recommended|
|Vitamin C tablets||Not recommended||Insufficient data to recommend for/against|
|Vitamin D tablets||Not recommended||Insufficient data to recommend for/against|
|Zinc+/- multivitamins||Not recommended||Insufficient data to recommend for/against|
|Multivitamin capsules/syrup||Mild disease||Insufficient data to recommend for/against|
|Ivermectin||Mild disease (low certainty of evidence)||Insufficient data to recommend for/against|
|Hydroxychloroquine||Mild disease (low certainty of evidence)||Not recommended|
|Favipiravir||Not recommended||Not recommended|
|Remdesivir||Moderate to severe disease (EUA)||USFDA approved for hospitalised patients|
|Azithromycin||Moderate to severe (As per antibiogram)||Not recommended unless indicated|
|Doxycycline||Moderate to severe disease (As per antibiogram)||Not recommended unless indicated|
|Amoxicillin+clavulanic acid||Moderate to severe disease (As per antibiogram)||Not recommended unless indicated|
|Cephalosporins||Moderate to severe disease (As per antibiogram)||Not recommended unless indicated|
|Antifungals (Amphotericin B)||Superimposed mucormycosis||Not recommended unless indicated|
|Topical steroids||Not recommended (Superimposed candidiasis only)||Not recommended unless indicated|
|Inhalational steroids (budesonide)||Mild disease (low certainty of evidence)||Not recommended|
|Oral steroids (dexamethasone/methylprednisolone)||Moderate disease||Recommended in hospitalised patients who require supplemental Oxygen|
|Intravenous steroids (dexamethasone/methylprednisolone)||Moderate to severe disease||Recommended in hospitalised patients who require supplemental Oxygen|
|Tofacitinib||Not recommended||Not recommended|
|Tocilizumab||Severe disease (EUA)||Recommended in hospitalised patients, requiring oxygen|
|Aspirin||Not recommended||Not recommended|
|Apixaban||Not recommended||Not recommended|
|Clopidogrel||Not recommended||Not recommended|
|Enoxaparin injection/Dalteparin injection||Moderate to severe disease||Insufficient data to recommend for/against|
|Alprazolam||Not recommended||Not recommended|
|Zolpidem||Not recommended||Not recommended|
|Selective Serotonin Reuptake Inhibitors (SSRIs)||Not recommended||Not recommended|
Note: CDC5 and ICMR1: Indicate the latest version of the CDC5 and ICMR1 COVID guidelines,
Table 1. Few examples of drugs being commonly prescribed for COVID-19 in India, along with their ICMR and US-CDC recommendations.
|Considerations to limit polypharmacy|
|DOs for patients
||DON'Ts for patients
|DOs for physicians
||DON’Ts for physicians
Table 2. Considerations for patients and physicians to avoid inappropriate polypharmacy.
The literature search for this review was performed by searching various bibliographic databases (Google Scholar, PubMed, Research Gate). We principally utilized the articles which were open access, since this research is not funded by any source. The search terms used were: “COVID-19”, “Polypharmacy”, “COVID treatment guidelines”, “Doctor-shopping”, “self-medication”, “steroids”, “multivitamins”, and “public health”, followed by cross-referencing across other reputed journals. Articles with full text and those written in English were included. The latest version of the CDC5 and ICMR1 COVID guidelines, as dated prior to the submission of this manuscript have been included. As this is a narrative review focusing on the current and evolving polypharmacy trends in the Indian scenario, we have included numerous recent newspaper articles, which have helped corroborate our observations with the already prevalent self-medication habits in India, along with providing insight into the current and evolving therapeutic practices. The table listing the examples of drugs being commonly used and abused during COVID pandemic in India was compiled after referencing multiple newspaper and journal articles, along with the clinical observations of the authors (Figure 1).
Patient associated factors
The second COVID wave has been brutal, and have stretched the entire health infrastructure to its limits, leading to an acute shortage of resources. Thus, many people have turned to various unhelpful practices such as stockpiling of medicines and oxygen cylinders, along with rampant use of dietary supplements, antibiotics, antivirals and even steroids, both for therapeutic and prophylactic purposes, without regard or knowledge of the consequences they may face.
Unregulated sale and consumption of dietary supplements
COVID-19 has fortified the community to an important lesson that ‘prevention is better than cure’, but the quest for prevention is making people frantically consume multiple medicines and dietary supplements, thereby promoting the inadvertent practice of polypharmacy during these COVID times. Many of these dietary supplements or nutraceuticals such as, vitamins, minerals like zinc, iron etc., herbal supplements like haldi (turmeric) capsules, protein supplements etc. are being consumed left and right, without prescription or doctor’s advice, with the prevailing myth that they act as ‘immune boosters’ and lack any potential side effects even if consumed in large quantities and for long durations. Since the start of the pandemic in 2020, internet has been flooded with a wide range of nutritional information, from a variety of sources on how to prevent or cure COVID-19, however, this information may be confusing and non-evidence-based speculation .
While, the ICMR guidelines recommends consumption of multivitamins in COVID-19 patients, their exact role in the alteration of disease process is unknown. Renowned doctors all over the country have cautioned against these ‘immune boosters’, stating explicitly that there are no magic pills for boosting immunity, and good diet and adequate sleep is enough for protecting oneself against infectious diseases Multiple studies, evaluating the roles of vitamin C, D, zinc and selenium, have been conducted or are ongoing. However, none of the studies conducted so far show prevention or decrease in severity of COVID-19. The US-CDC COVID-19 treatment guidelines also explicitly states that there is insufficient evidence to recommend for or against vitamins C and D, and zinc in the treatment and prevention of COVID-19 (Table 1) [9-11].
Other potential risks with dietary supplements:
•tentional/unintentional adulteration or contamination
• Misreporting of the claimed content by manufacturers
• Presence of an undeclared substance
• Deviation from recommended level
• Hypervitaminosis syndrome
The role of zinc was postulated in various studies as an immune booster, but none concluded any significant improvement in the severity and course of the disease Still, zinc was one of the most widely bought and consumed dietary supplement in the pandemic, with people consuming zinc tablets for months on end . In fact, the role of zinc supplementation is now being evaluated for the spread and increase in severity of mucormycosis, which is an opportunistic fungal infection, now reaching epidemic proportions in India . Zinc is required for the life cycle and survival of the fungus, and in vitro studies have evaluated the role of zinc chelators as a treatment option in patients of mucormycosis .
To summarise, while vitamins, minerals and antioxidants are vital for one’s immune system and various physiological processes, and may be rational for use anaemia, protein deficiencies, malnutrition syndromes, eating disorders, malabsorption syndromes, pregnant women, etc.
It is always preferable to obtain said nutrients from food, rather than from supplements. A healthy and balanced diet can decrease the risk of contracting the infection, and also improve control of diabetes, hypertension, obesity, etc. which are all co-morbidities, adding to the risk of COVID complications.
The key message regarding nutritional supplements is that, while they may be prescribed for COVID positive patients, individuals should not rely on supplements to prevent COVID infection. Irrational and unwarranted consumption of such supplements should be curtailed, and instead one should focus on consuming a healthy diet and exercise regularly.
Self-medication with antimicrobials and steroids in COVID-19
As per the World Health Organization (WHO), Self-Medication (SM) is the selection and consumption of medicines to treat self-recognized symptoms or ailments without consulting a clinician . It also includes the utilization of previously prescribed or unused drugs, direct purchasing of prescription drugs from pharmacies without consultation, and irrational and unrecommended usage of Over-The-Counter (OTC) medicines .
Self-medication habits are particularly common in developing countries, like India, where not only dietary supplements, but even with antibiotics and steroids, are sold as OTC drugs, i.e. without a valid prescription. Such practices are a major cause for polypharmacy, since people end up consuming unnecessary medications for prolonged periods. Several studies have been carried out over the years in various parts of India to estimate the prevalence of self-medication habits. In the study conducted by Rajendran et al. in Thrippunithura municipality, Kerala, in a sample size of 755 adults, it was observed that 3.31% of population practiced self-medication with antibiotics . The most common ailment was sore throat (25%), with azithromycin as the most common antibiotic (39%) self-prescribed for the same. In another study conducted by Kaushal et. al. in Rohtak district of Haryana it was observed that out of 100 households that were interviewed, 73% households practiced self-medication with some or the other class of drugs. Out of the drugs surveyed, the most common classes were analgesics (81%), antacids (44%), antibiotics (33%0, nutritional supplements (23%), cough syrups (16%), antispasmodics (14%), topical applications (34%) and others .
Multiple reports of self-medication practices have been published as newspaper and journal articles from prominent hospitals across India, citing incidences where patients land up in complications after consuming the so-called ‘popular’ or ‘known COVID drugs’ like ivermectin, hydroxychloroquine, doxycycline and dexamethasone, to ‘prevent severe disease’. The vast pool of knowledge available online, through news or social media is becoming a major factor in spreading misconceptions about all these drugs. They have several contraindications and warnings, and are leading on to complications at a later stage which are adding to the burden of an already saturated healthcare infrastructure.
Presently, many people are self-medicating with broad spectrum antibiotics like azithromycin, cephalosporins, doxycycline etc. right from day 1 of fever onset, without even getting themselves tested for COVID or waiting for experts’ recommendation. They end up consuming these prescription drugs (often sold as over-the-counter medications in India), for days or weeks on end, without regard to their indication or adverse effects. This is also a major factor contributing further to the spread of antimicrobial resistance, which is already a major public health concern [19-21].
Antivirals like favipiravir and Remdesivir are being used for mild-moderate and moderate-severe COVID infection, respectively. While, Remdesivir requires intravenous administration and under close monitoring in hospital settings, favipiravir is being marketed as oral tablets and is readily available. So, self-medication with favipiravir is also common, with patients procuring the same directly from pharmacists, even though its approval mandates a prescription from a registered medical practitioner.
However, the most dangerous example of self-medication is the consumption of steroids. Doctors have repeatedly warned against the use of steroids without medical consultation because they have a plethora of short-term and long-term side effects, and are only to be taken under specific conditions, and under strict supervision of the consulting physician . Multiple case reports and newspaper reports are available describing a variety of complications and deterioration of patients’ condition because they began self-administering steroids in the early stages of illness and/or without medical advice . Besides suppressing one’s immune system, some common risks of steroid consumption include, weight gain, fluid retention, hormonal imbalance, anxiety and disturbed sleep, while some uncommon and dangerous complications include hemorrhagic events, visual defects, uncontrolled diabetes, reactivation of latent infections and opportunistic infections like candidiasis and mucormycosis .
As per the ICMR guidelines, oral steroids are indicated only in moderate or severe cases, with the possibility of further deterioration as it becomes crucial to balance pro- and anti-inflammatory mediators, to curtail multi-organ damage (specifically lung fibrosis), and/or prevent cytokine storm.
Another common practice involving self-medication, is sharing of prescriptions among patients, via social media (e.g. WhatsApp) or telephonically. The sudden rise in cases during the second wave of COVID-19 has led to an acute shortage of resources, including long waiting periods for RT-PCR testing and delays in booking tele-consultation appointments. Due to all these issues some people are preferring to skip getting themselves tested, assuming they have COVID, and are straightaway starting medications by borrowing someone else’s prescription or using the ones being circulated on social media, many of which are fake.
Mental health issues due to COVID-19 pandemic
The concept of health is incomplete without taking one’s mental health into consideration. In fact, mental health is still one of the most neglected and undertreated healthcare concerns in the present-day scenario, especially owing to the dire effects of the current pandemic adversely affecting the psychological profile of most, if not all individuals. The anxiety of contracting COVID is multiplied manifold by the isolation norms, social distancing, lockdown/curfew measures, closure of educational institutes, workplaces, lack of entertainment options, travel ban, etc. All of these measures, along with the grief and fear of losing one’s life or that of someone close, are all playing havoc on the mental and social health of people worldwide, and have led to additional problems such as generalized anxiety disorder, depression, insomnia, panic attacks etc., for which long term medications are now being prescribed or are more frequently being self-consumed against the better judgement of the medical fraternity . The most common self-employed strategies include, alcohol consumption, nicotine, recreational drugs like marijuana, amphetamines etc., and prescription medicines like pain killers, including NSAIDs and opioids. In a cross-sectional study conducted by Chopra online survey was carried out using self-rating anxiety scale, validated COVID-19 Anxiety Inventory Items and self-medication practices during COVID-19 pandemic . Out of 1100 responses received, prevalence of mild-to-moderate, moderate-to–severe, and severe anxiety cases were 23.1%, 4.7%, and 0.54%, respectively. Among the most commonly reported self-medications were with NSAIDS, anti-ulcer drugs, anti-histaminics and benzodiazepines.
Doctor Shopping’ in India
Another unique practice in our country is that of ‘doctor shopping’, which is the tendency of patients to receive care from multiple doctors. Since India lacks the referral system in healthcare, one patient can visit numerous doctors, of same/different specialties, for the same illness. There exists a lack of trust between the patient and physician on most occasions, which leads them to consult multiple doctors. This is becoming very common in COVID times, also because remote or tele-consultation service makes it easier for one patient to confer with multiple physicians, and as a result they end up with multiple prescriptions. While, it is any patient’s right to take different opinions, especially in a high panic state like the current pandemic, the old saying that too many cooks spoil the broth, holds true in such a scenario. This is because, consulting multiple physicians creates more confusion and it not only promotes polypharmacy but can also lead to repetition or increase/decrease in the dose and frequency of same medicine, which lead to over/under dosage, adding to side effect profile and toxicity of the drugs.
Since there is a wide clinical spectrum for COVID illness, every case has to handled differently, keeping in mind co-morbidities, age, previous drug intake, severity, etc. Besides, every clinician has a unique approach to medical management, based on their knowledge and experience. Even if a second opinion is warranted it should be taken only on physician’s referral, from a senior doctor, who may be more experienced and/or a specialist, like a pulmonologist. Also, since the present healthcare infrastructure is already overwhelmed, with over-burdened doctors and hospitals running on full capacity, it becomes extremely wasteful to unnecessarily utilize resources and most importantly waste money and time on such a practice like ‘doctor shopping’.
Physician associated factors
Due to the wide spectrum of COVID-19, targeting multiple organ systems and physiological processes, physicians have to keep a broad prospective, and adopt a multi-system approach to tackle the infection. The COVID treatment guidelines are still evolving, with minor and major changes happening every few months. It becomes tough for physicians to keep up with this overload of information, when they are already heavily burdened with patient care.
Also, since many patients present with co-morbidities which are known to worsen due to COVID-19, or they may add to the severity of COVID illness, so along with supportive measures and symptomatic treatment, most patients now require additional drugs such as, anti-coagulants, steroids, insulin etc., thus leading to unavoidable polypharmacy.
However, irrational prescriptions are still one of the major causes of polypharmacy and there are many situations in which multiple medicines are not needed, and their unreasonable use can be prevented.
With respect to dietary supplements, no vitamin or mineral has so far shown any concrete evidence for prevention or cure of COVID-19, hence, their widespread prescription and use, lacks scientific basis. Without consideration of the micronutrient requirements of the patient, multivitamins, vitamin C, vitamin D and zinc are being prescribed all at once, when none of these micronutrients have any well-defined roles in the treatment of COVID-19 so far.
The latest ICMR/AIIMS guidelines1, clearly specifies that antibiotics are only to be used in COVID management, if there exists a clear indication of a superimposed bacterial infection. However, most physicians are prescribing azithromycin, doxycycline, amoxicillin, cephalosporins, etc., even in mild cases, having no indication of bacterial infection at all. This practice can rapidly lead to the worsening of antibiotic resistance, and if not curtailed, we might be looking at a bacterial pandemic next, which may prove to be much more devasting, than the viral pandemic we currently face.
Apart from antibiotics, antivirals also have a limited role so far, with definite evidence of their benefits still lacking. Remdesivir has been approved by the USFDA for COVID-19, but in India it is still under Emergency Use Authorization (EUA) by the Drugs Controller General of India (DCGI), citing lack of sufficient evidence for its full approval. It is only to be prescribed in selected moderate-severe hospitalized COVID patients, receiving supplemental oxygen and is to be prescribed within 10 days of disease onset. Favipiravir, on the other hand has not received any reference in ICMR1, CGHS54, or US-CDC5 guidelines and is currently being used as an off-label oral therapy for mild to moderate COVID cases, after marketing approval by the DCGI, in June 2020; however, unequivocal role of favipiravir is still largely lacking. Hence, antivirals such as favipiravir and remdesivir should be used only if the situation mandates, as per the COVID guidelines, with continuous monitoring of the patient, and should not be prescribed indiscriminately.
Similarly, while inhalational steroids are now indicated for mild COVID cases, systemic steroids are to be used judiciously and with great caution, since their misuse can lead to multiple side effects, including opportunistic infections like candidiasis and mucormycosis. Steroids are considered as life-saving drugs for severe cases of COVID, but they should be considered as a double-edged sword, especially if their timing, dosage or duration is wrongly determined.
Impact of polypharmacy
Consuming numerous medicines at once may be a necessary evil for some, specially those suffering from multiple illnesses and those having long term sequelae, but in these uncertain times, it is important for us to understand the implications of, and curtail the practice of inappropriate polypharmacy.
Some schools of thought refer to polypharmacy as a part of Potentially inappropriate prescribing (PIP), which in turn may cause adverse clinical outcomes due to multiple drug interactions and side effects, all of which eventually leads to worsening of one’s condition and increased healthcare costs .
Multiple drug intake is a major risk factor for drug-drug, drug-food and drug-disease interactions, all of which are important to know and suspect timely. Physicians should take a detailed history of the various medications being consumed by the patient (allopathic, homeopathic, ayurvedic, etc.), their dose, duration and route of administration, along with any co-morbidities, drug allergies, history of substance abuse, etc., all of which need to be correlated with one’s COVID positive diagnosis; identifying and amending any predisposing factors that may lead to further complications and/or add to the severity of the infection. This also why patients should never take medicines (including dietary supplements), without a proper prescription, and disclose any and all medications they may have consumed on their own.
Each individual is unique and has varied metabolism and dietary requirements. Hence, although vitamin supplements may be indicated during the course of COVID-19, as per ICMR guidelines1, but they are usually not required unconditionally or for prolonged duration. One of the reasons for indiscriminate use of vitamins is their easy availability, and the myth that they do not cause harm, but this is not true. Hypervitaminosis is an entity that is described due to over consumption of vitamin supplements58. Vitamin C is being widely promoted as an immunity booster, but excess intake may cause gastric upset, nausea, kidney stones and disrupt antioxidant balance of the body. Vitamin D toxicity can lead to seizures, depression, dental problems, brittle bones etc. Excess vitamin K can lead to thrombi formation as it plays a vital role in blood clotting. Likewise, other vitamins can also have detrimental effects on one’s health if not taken as per the body’s requirement. In fact, indiscriminate use of zinc is now being implicated as one of the contributing factors for mucormycosis, even in recovered patients of COVID-19 .
Another pressing concern is the emergence of antibacterial resistance (AMR), which is already rampant worldwide, and is being overlooked in the COVID pandemic, owing to the indiscriminate use of broad-spectrum antibiotics like azithromycin by patients and physicians alike. It is vital for everyone to understand that antibiotics are not to be taken in any undetermined bacterial infection, and are definitely not indicated prophylactically for mild COVID infection [28,29].
COVID-19 has a complex clinical spectrum, to say the least. It has been almost 2 years since it first began, and our knowledge of its prevention, management and prognosis is still evolving. Numerous medications have been tried and are undergoing trials for the same, but no drug has emerged as first-line, or treatment-of-choice for COVID-19. All these uncertainties and limitations have resorted both patients and physicians, to the habit of consuming and prescribing multiple drugs, respectively, leading to the inadvertent practice of polypharmacy. Notwithstanding the glaring absence of clear evidence of clinical efficacy and safety, broad spectrum antibiotics and dietary supplements are widely being used as off-label therapies for prophylaxis and treatment of COVID-19. The rationale behind their prescription is still obscure, and their widespread use is at odds with rational pharmacotherapeutics, which is the cornerstone of the principles of pharmacotherapy, as first advised by the World Health Organization (WHO) back in 1985.
Thus, mindlessly consuming or prescribing medicines is never the solution or the cure. Dubious practices such as, self-medication, prescription-sharing, doctor-shopping, etc. must be discouraged. Physicians also must be extremely cautious of what drugs they advise in these uncertain times, and must individualize prescriptions as per patient condition, severity, co-morbidities and clinical history.