|Year : 2022 | Volume
| Issue : 3 | Page : 218-223
Drug Utilization Pattern in the Treatment of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV 2) Patients at Dedicated COVID Tertiary Care Teaching Hospital: An Observational Study
Shubha Singhal1, Sumit Bansal2, Ankita Negi3, Bhupinder S Kalra3, Lalit Gupta4, Sandeep Garg5, Sumit Sural6, Seema Kapoor7, Shalini Chawla3
1 Department of Pharmacology, AIIMS, Rajkot, Gujarat, India
2 Department of Anaesthesiology, Max Super speciality Hospital, Patparganj, New Delhi, India
3 Department of Pharmacology, MAMC and L.N. Hospital, New Delhi, India
4 Department of Anaesthesiology, MAMC and L.N. Hospital, New Delhi, India
5 Department of Medicine, MAMC and L.N. Hospital, New Delhi, India
6 Department of Orthopedics, MAMC and L.N. Hospital, New Delhi, India
7 Department of Pediatrics, MAMC and L.N. Hospital, New Delhi, India
|Date of Submission||10-Sep-2022|
|Date of Acceptance||26-Oct-2022|
|Date of Web Publication||07-Dec-2022|
Bhupinder S Kalra
Department of Pharmacology, MAMC and L.N. Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Background and aims: Coronavirus disease of 2019 (COVID-19) has emerged as a pandemic and increasing numbers of patients are being admitted to dedicated COVID hospitals in a city. Since patients were being prescribed investigational, off label, and some approved drugs, it is important to understand and document prescription and drug utilization patterns. Material and methods: A prospective observational study was conducted on 1164 RT-PCR positive COVID-19 patients admitted to a dedicated COVID-19 tertiary care hospital. Treatment given to patients with COVID-19 was recorded and evaluated with respect to the place of admission, that is, wards or Intensive Care Unit (ICU). Descriptive statistics were used for the evaluation of data. Results: Among the 1164 patients, 670 (57.5%) patients were admitted to the wards while 494 (42.4%) patients were admitted to the ICU. The mortality rate of study participants was 4.1%. Ceftriaxone (39.27%) was the most commonly prescribed antibiotic in the ICU patients while azithromycin (79.10%) was the most prescribed antibiotic in wards patients. 242 (48.98%) patients received dexamethasone whereas methylprednisolone was administered to 88 (17.81%) patients. Remdesivir was administered to 48% of the patients in our study. Conclusion: We observed high rates of mortality in patients with one or more comorbidities having SpO2 less than 65. Concordance and adherence to the line of treatment as recommended by Ministry of Health and Family Welfare/ICMR guidelines were discerned. Rational use of antimicrobials is warranted to curb antibiotic resistance and opportunistic infections since most of the patients received empirical therapy.
Keywords: anticoagulants, comorbidity, coronavirus, drug utilization, SARS-CoV- 2
|How to cite this article:|
Singhal S, Bansal S, Negi A, Kalra BS, Gupta L, Garg S, Sural S, Kapoor S, Chawla S. Drug Utilization Pattern in the Treatment of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV 2) Patients at Dedicated COVID Tertiary Care Teaching Hospital: An Observational Study. MAMC J Med Sci 2022;8:218-23
|How to cite this URL:|
Singhal S, Bansal S, Negi A, Kalra BS, Gupta L, Garg S, Sural S, Kapoor S, Chawla S. Drug Utilization Pattern in the Treatment of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV 2) Patients at Dedicated COVID Tertiary Care Teaching Hospital: An Observational Study. MAMC J Med Sci [serial online] 2022 [cited 2023 Feb 1];8:218-23. Available from: https://www.mamcjms.in/text.asp?2022/8/3/218/362899
| Introduction|| |
Coronavirus disease of 2019 (COVID-19) has emerged as a pandemic and increasing numbers of patients were being admitted to dedicated COVID hospitals in Delhi. COVID-19 is caused by severe acute respiratory syndrome coronavirus −2 (SARS CoV-2), a beta coronavirus which is an enveloped positive-sense, single-stranded RNA virus.. As on October 7, 2020, 9 lakh people (mortality rate 1.55%) were infected with COVID in India out of which Delhi had 22,000 patients. Globally, there have been 3,53,47,404 confirmed cases of COVID-19, including 10,39,406 deaths as reported to WHO in 2019 to 2020.
The disease pattern varied from asymptomatic to mild, moderate, and severe categories depending upon respiratory signs and symptoms like oxygen saturation, pneumonia, tachypnoea, fever, etc. It has been reported that the majority of patients fall under the asymptomatic to the mild category where the disease is self-limiting and medications like antipyretics and antihistamines are only required. Patients with moderate to severe category require hospitalization and were prescribed hydroxychloroquine, steroids, unfractionated heparin, or low molecular weight heparin, remdesivir, toclizumab, etc. depending upon the severity of the disease. These patients were administered multivitamins and minerals like ascorbic acid, zinc, vitamin D as supportive therapy.,
Monitoring the effect of these drugs is pertinent as most of them are repurposed or off label medications. Data with regard to their efficacy for treating COVID-19 is limited. Moreover, these drugs can lead to adverse effects and some drug–drug interactions, for example, hydroxycloroquine is prone to cause QT prolongation and when given along with azithromycin, risk for QT prolongation increases. Investigational drugs like remdesivir, tocilizumab, favipiravir, etc. were used for the management of COVID-19. There is scarcity of literature with regard to its efficacy in the treatment of COVID-19. Moreover, adverse effects of these drugs like hepatotoxicity, neutropenia, etc. needs to be reported and monitored.,
COVID-19 patients are and were managed at teaching tertiary care and dedicated COVID hospital in with 2000 plus bed capacity. Since patients were being prescribed with approved, investigational, and some off label drugs, it is important to understand and document prescription and drug utilization pattern.
| Material and methods|| |
After receiving approval from the Institutional Ethics Committee, an observational, prospective study was carried out on 1164 patients admitted to wards and the Intensive Care Unit (ICU) of a dedicated COVID tertiary care teaching hospital. Written informed consent was taken from patients or their relatives prior to their enrollment in the study. Prior to initiation of the study, a study was registered with the Clinical trial registry of India (CTRI) (CTRI/2020/12/029463 Registered on: 01/12/2020). The total duration of the study was 3 months from December 2020 to March 2021.
All patients irrespective of gender and age group with a confirmed diagnosis of COVID-19 with RT-PCR and on treatment for the same were included in the study. Suspect cases of COVID-19 infection were excluded from the study.
Treatment given to patients of COVID-19 was recorded and evaluated with respect to the place of admission (Wards or ICU). Patients’ demographic, details about patients’ disease, concomitant illness, and treatment details were recorded from the prescription.
Additionally, patients were also monitored for severity of signs and symptoms, investigation carried out during the stay of patient in hospital, percentage (%) of drugs prescribed by generic name, percentage (%) of prescription with antibiotics, average number of drugs per patient, percentage (%) of off label and Investigational drug prescribed.
The primary outcome of the study was to analyze prescription patterns for the treatment of COVID patients in line with Ministry of Health and Family Welfare (MoHFW) & ICMR guidelines. The secondary outcome was the evaluation of drugs prescribed to COVID patients with regard to the severity of the disease.
Data was compiled in MS Excel sheet. A presumptive sample size of 1000 was proposed since it was a short duration study with keeping in view the footfall of inpatients. Descriptive statistics were used for the evaluation of data.
| Results|| |
A total of 1164 patients diagnosed with SARS CoV-2 were recruited in the study. Among the 1164 patients, 670 (57.5%) patients were admitted to the wards while 494 (42.4%) patients were admitted to the intensive care unit (ICU). The mean age of the study participants was 48 ± 17.98. A total of 828 (71.13%) males and 336 (28.86%) females were included in the study [Table 1].
48.79% of the patients developed mild symptoms whereas 44% of the patients were admitted to the ICU who fall under the moderate to severe category. The mortality rate of study participants was 4.1%. These casualties were mainly observed in the patients who were admitted with SpO2 <65. The demographic details of study participants have been represented in [Table 1].
The majority of the patients admitted to the hospital presented with complaints of fever (45%), shortness of breath (43.47%), and cough (41%). Loss of taste sensation was reported in 1% of patients. Shortness of breath (74%) was the most common symptom among ICU patients while fever (44.4%) was the most common symptom among ward patients. Mean SpO2 was found to be 87 ±7.01 in ICU patients and 95.4 ± 5.49 in the patients admitted in wards. All laboratory parameters including RBS, CRP, ferritin, and IL-6 were found to profoundly deranged among ICU patients as compared to ward patients [Table 2].
186 (15.97%) of the patients had diabetes as comorbidity whereas hypertension as a comorbidity was associated in 175 (15.03%) among the surveyed COVID-19 patients. Chronic kidney disease and chronic lung disorder were reported in 48 (4.12) and 77 (6.61) admitted patients [Table 3].
A total of 1484 antibiotics were prescribed for 1164 COVID-19 patients. The majority of the antibiotics were prescribed by brand name [Table 4].
Ceftriaxone (39.27%) was the commonly prescribed antibiotic in the ICU patients while azithromycin, levofloxacin, and tazobactam were administered to 37%, 32.79%, and 31.57% ICU patients respectively. Antibiotics including meropenem, clindamycin, metronidazole, amikacin, vancomycin, teicoplanin, tigecycline, colistin, amoxiclav, linezolid were used only in ICU patients [Table 4]. 242 (48.98%) patients received dexamethasone whereas methylprednisolone was administered to 88 (17.81%) patients. The prescriptions were written with the generic name of steroids. More than 60% of ICU patients, 306 (61.94%) received anticoagulant enoxaparin and it was prescribed by brand name. Among the off label and investigational drugs, Ivermectin was administered to 272 (55.06%) patients and remdesivir was received by 184 (37.24%) patients. Convalescent plasma therapy (CPT) was given to 6.8% of the ICU patients [Table 5].
In contrast, the patients admitted to wards with mild to moderate symptoms were prescribed azithromycin (79.10%) and ceftriaxone (23.88%). The requirement for levofloxacin (2.98%) and tazobactam (1.79%) was limited as compared to ICU patients. 78 (11.64%) of the patients were administered with remdesivir who fell under moderate category. Ivermectin was prescribed in 28 (4.17%) patients presenting with mild to moderate severity. Among steroids, dexamethasone was administered to 142 (21.19%) patients. Enoxaparin was received by 140 (20.89) patients [Table 5].
Vitamins and antioxidants including vitamin C, vitamin E, vitamin D, zinc, calcium was prescribed to both ward and ICU patients. However, the use of vitamins was found to be more in wards patients as compared to ICU patients [Table 5]. Vitamin C (80.41%) was the most prescribed antioxidant followed by zinc sulfate (74%). The majority of them were prescribed by generic names. Paracetamol was the only antipyretic which was used in surveyed COVID-19 patients. 61.9% of wards patients and 8% of ICU patients received paracetamol. Levocetirizine (25.7%) was the most common prescribed antihistaminic followed by montelukast (9%). Bromhexine (2.9%) and noscapine (0.5%) were also prescribed in a smaller number of patients. The majority of the levocetirizine (99.3%) and montelukast (93%) were prescribed by generic name.
Pantoprazole was prescribed in 54% of ward patients and in 22.26% of ICU patients. Consumption of ondansetron was less as compared to pantoprazole. Ondansetron was prescribed in 21% ward patients and 8% in ICU patients. Both the drugs were prescribed by brand names only [Table 5].
Forty eight causalities were reported during this study period. These patients were being treated in ICU and 98% of them have one or more comorbid conditions. The mean age of patients who died was found to be 61 ± 12.36 and the mean SpO2 at the time of admission was 84.3 ± 3.27.81. 2% of patients were administered with both enoxaparin and ivermectin. 64.5% of patients received steroids and 45.8% were administered with a piperacillin/tazobactum combination. Among 48 causalities, remdesivir was given to 10 (20.8%) and convalescent plasma therapy was administered to 6 (12.5%) of these patients.
We observed that medicines like ceftriaxone, piperacillin/tazobactum, meropenem, enoxapain, pantaprazole, and ondensetron were primarily prescribed with generic name whereas generic names were used in most of the prescriptions for vitamins, steroids, ivermectin, and metronidazole.
| Discussion|| |
In our study, we observed that majority of the patients who required hospitalization were middle-aged men. Predominant clinical features are cough, shortness of breath, and fever. Our findings with regard to age, gender, and symptoms were consistent with previously published studies.,, Anosmia was reported by less than 1% of the patients. Diabetes and hypertension were the most common comorbid conditions observed in these patients. In the majority of patients admitted to ICU, D dimer, IL-6, and Ferritin were found to be markedly raised. D dimer being fibrin degradation product and has utility in the diagnosis and management of thrombotic disorders. It has prognostic value in COVID and high levels are associated with mortality.
Hydroxychloroquine was not administered to any patient as was being done in 2019 at our institution. Discontinuation of HCQ in COVID patients was a result of findings in solidarity trial, the UK’s Recovery trial, and a Cochrane review of other evidence wherein hydroxychloroquine conclusively showed no reduction in deaths among hospitalized COVID-19 patients. Based on this information, WHO decided to abandon the Solidarity Trial’s hydroxychloroquine arm in June 2020.
Ivermectin, off label use, was prescribed in nearly 59% of the patients. Ivermectin has exhibited antiviral activity against a wide range of RNA and some DNA viruses, for example, Zika, dengue, yellow fever, and others. The mechanism of action postulated is blocking the nuclear import of viral proteins which suppress normal immune responses. Later, the national task force on COVID-19, constituted by Indian Council of Medical Research (ICMR) excluded both Hydroxychloroquine (HCQ) and ivermectin due to a lack of evidence from the management of COVID guidelines in August 2021.
Repurposing of both HCQ and ivermectin was not found to be useful in the treatment of COVID-19. With regard to antimicrobials, azithromycin and ceftriaxone were extensively used in the wards and piperacillin/tazobactum combination, ceftriaxone, azithromycin, and levofloxacin were commonly administered in patients admitted to ICU. These findings are in agreement with previously published studies., Since in most of the cases antibiotics were given empirically, the need is to monitor therapy for effectiveness and antibiotic-related ADRs. SARS-CoV-2 infection leads to an inflammatory response due to the release of various mediators like chemokines, cytokines, etc. and a dysregulated macrophage response also contributes to visceral inflammation. To control the inflammatory response, corticosteroids are being prescribed in the form inhalational budesonide for mild cases and systemic steroids are reserved for moderate to severe cases.
We observed that, 60% of the admitted patients were given dexamethasone or methylprednisolone during their stay in hospital. Usage of corticosteroids was found to be 54.7% in a California hospital setting which is line with our study. The management of SARS CoV 2 patients was in line with guidelines issued by MoHFW & ICMR recommendation. ICMR recommends use of methylprednisolone 0.5 to 2 mg/kg in two divided doses for 5 to 10 days for moderate to severe cases.
Anticoagulation is considered key to suppress thrombotic events associated with COVID infection. Inflammatory cytokines may lead to activation of coagulation cascade. Cytokines and viral particles activate endothelial cells which produce monocyte chemoattractant and adhesion molecules. Tissue factor exposed on endothelial cells as a result of endothelial damage caused by the virus. Tissue factor expressed by activated monocytes, monocyte-derived micro vesicles, and endothelial cells activates the extrinsic coagulation pathway, leading to fibrin deposition and blood clotting. Enoxaparin was prescribed in 80% of the patients in patients with moderate to severe category. This was in contrast to previously published study where its usage was found to be 40%.
An antiviral drug like remdesivir has very limited evidence in the management of COVID and is being used as an Investigational off label drug. Remdesivir was administered to 48% of the patients in our study and this finding is in concordance with a previously published study where it was found to be 62.5%. Presently as per ICMR guidelines, it is to be used under special circumstances for moderate to severe presentation who are on supplemental oxygen. Convalescent plasma therapy was administered to 6.8% of patients as part of a clinical trial and the outcome remained inconclusive. WHO in its living guideline dated Dec 7, 2021 strongly recommended against the use of convalescent plasma in patients with non-severe illness, and a recommendation against its use in patients with severe and critical illness, except in the context of a randomized controlled trial (RCT).
Antioxidants, vitamins, and antihistaminics were prescribed to almost all patients. Vitamin C, E, and zinc were administrated orally during their stay in the hospital. Although there is no substantial evidence to suggest a role of vitamins and antioxidants in decreasing the severity or duration of hospitalization, these drugs were prescribed to almost all patients.
This drug utilization study in COVID patients conducted at dedicated tertiary care covid hospital is the first study in India to the best of our knowledge. This study may help administrators to look into procurement of drugs based on disease and prescription pattern. Variation in dosing and duration of drugs and antioxidants need to be streamlined. Limitation of this study is lack of Adverse drug reaction (ADR) monitoring which we were not able to carry out because of limited resources.
| Conclusion|| |
We observed high rates of mortality in patients with one or more co morbidities having SpO2 less than 65. Concordance and adherence to the line of treatment as recommended by Ministry of Health and Family Welfare/ICMR guidelines were discerned. We recommend rational use of antimicrobials to be practiced in ICU patients to curb antibiotic resistance and opportunistic infections since most of the patients received empirical therapy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]