Abstract
Background:
Hydroxyurea therapy is crucial in managing sickle cell disease (SCD) in pediatric patients, significantly reducing vaso-occlusive events. However, it is associated with hematological adverse drug reactions (HADRs), necessitating comprehensive evaluation to ensure patient safety and treatment optimization.
Objective:
The primary goal of our study is to investigate the prevalence, causality, severity, preventability, and predictability of HADRs associated with hydroxyurea therapy in pediatric patients with SCD.
Materials and Methods:
A prospective observational study was conducted, involving 207 pediatric SCD patients undergoing hydroxyurea therapy. Data were collected from medical records and adverse drug reaction reporting forms. Causality, severity, preventability, and predictability assessments were conducted using standardized tools.
Results:
The prevalence of HADRs was 7.24%, with neutropenia (2.41%) and thrombocytopenia (1.93%) being the most common. Gender-specific prevalence rates, age distribution, and in-patient versus out-patient settings showed consistent patterns. Causality assessment revealed a high proportion of probable or certain HADRs. The majority of HADRs were of mild to moderate severity and considered preventable.
Finding:
Hydroxyurea therapy in pediatric SCD patients is associated with manageable HADRs, emphasizing the importance of pharmacovigilance for patient safety and treatment compliance.
Conclusion:
This study offers significant insights into the prevalence, clinical management, and outcomes of HADRs associated with hydroxyurea therapy in pediatric SCD patients. The findings underscore the need for proactive management approaches to optimize treatment outcomes and ensure patient safety.
KEYWORDS: Hematological adverse drug reactions, hydroxyurea, pediatric population, pharmacovigilance, sickle cell disease
INTRODUCTION
Sickle cell disease (SCD) is a genetic blood disorder distinguished by the presence of abnormal hemoglobin, termed hemoglobin S (HbS). This genetic alteration results in red blood cells becoming rigid, sticky, and assuming a sickle-shaped, hindering their smooth flow through blood vessels. As a result, individuals with SCD are more prone to vaso-occlusive events, chronic hemolytic anemia, and heightened vulnerability to infections. SCD follows an autosomal recessive pattern of inheritance, where an individual must inherit two abnormal hemoglobin genes, one from each parent, in order to develop the disease.[1] SCD is a global health problem, with the highest burden being observed in sub-Saharan Africa, the Middle East, and certain regions of India. However, due to population migration, SCD has become a significant health concern worldwide, affecting populations in North America, Europe, and Asia as well.[2] SCD is a hereditary blood disorder that predominantly affects pediatric populations, with symptoms often appearing during infancy. Children diagnosed with SCD are at an increased risk of severe complications including vaso-occlusive crises, acute chest syndrome, and stroke. Moreover, SCD can significantly impact a child’s physical and cognitive development, school performance, and overall quality of life. The clinical presentations of SCD are diverse and may encompass acute pain crises, chronic and persistent anemia, heightened vulnerability to infections, and organ damage resulting to vaso-occlusion and hemolysis. These complications not only impact the patient’s health-related quality of life (HR-QoL) but also can result in life-threatening events such as an acute chest syndrome stroke, and multiple-organ failure. Early diagnosis and comprehensive care are paramount for pediatric patients with SCD to prevent complications, manage symptoms effectively, and improve outcomes. Treatment strategies often involve medications like hydroxyurea, pain management, blood transfusions, and preventive measures like vaccinations and antibiotics.[3] SCD represents a notable major significant health concern, particularly among pediatric populations, with varying prevalence rates reported in different regions. For instance, Kingwengwe (2022) found a prevalence of 12.7% for major sickle cell syndrome in children under 5 years in the Democratic Republic of Congo. In the United States, Musallam (2023) reported a prevalence of approximately 120-150 cases per 800,000 newborns. Wang (2011) noted a prevalence of 1 in 350-400 births among African-Americans, with the most common type being HbSS. Furthermore, Al-Qurashi (2008) found a prevalence of 24 per 10,000 in Saudi children and adolescents, with a greater prevalence observed in the eastern and southern regions. The occurrence of SCD varies significantly across different regions and populations. For instance, in sub-Saharan Africa, where the disease is most prevalent, it is estimated that 1-2% of newborns are affected by SCD, with carrier rates as high as 10-30%. In the United States, SCD impacted approximately 100,000 individuals, primarily those of African or Hispanic descent. However, due to population migration, the disease is becoming increasingly common in other ethnic groups as well. Hydroxyurea, a myelosuppressive agent, has emerged as a key therapy for the management of SCD. It works by increasing the production of fetal hemoglobin (HbF), thereby reducing the proportion of sickle hemoglobin (HbS) in the blood and decreasing the frequency of vaso-occlusive crises. Hydroxyurea also has anti-inflammatory and endothelial-stabilizing effects, further contributing to its efficacy in SCD management.[4,5,6,7] Hydroxyurea has proven effective in reducing the severity of SCD in pediatric patients, leading to significant reductions in clinical complications and adverse events. Research indicates that hydroxyurea therapy is associated with a declining in episodes of acute chest syndrome, number of time blood transfusions during hospital stay, and hospitalizations for painful events. However, concerns regarding its long-term safety, particularly regarding genotoxicity, have been raised. Number of clinical studies and many observational studies have demonstrated the effectiveness and safety of hydroxyurea in reducing the frequency and severity of vaso-occlusive events in both pediatric and adult patients with SCD. The landmark Multicenter Study of Hydroxyurea (MSH) and the Baby Hug trial provided compelling evidence for the administration of hydroxyurea getting beneficial effect in pediatric patients with SCD show case significant reductions in number pain crises, acute chest syndrome, and reducing the number of blood transfusions. Despite its proven efficacy, hydroxyurea is associated with potential adverse drug reactions (ADRs), including myelosuppression, leukopenia, thrombocytopenia, and gastrointestinal symptoms. These ADRs can have significant implications for patient safety and treatment compliance, particularly in pediatric populations. Moreover, there is limited information available on the delayed, long-term safety profile of hydroxyurea therapy in children, leaving important questions regarding late toxicities unanswered.[8,9,10] Hydroxyurea, an oral medication approved by the U.S. Food and Drug Administration, is widely prescribed to treat SCD in pediatric patients. Hydroxyurea mechanism involves stimulating the production of fetal hemoglobin, thereby decreasing the occurrence of vaso-occlusive crises and other complications linked with SCD. Clinical trials, including the landmark BABY HUG trial, have demonstrated the effectiveness and safety profile of hydroxyurea in pediatric patients, showing significant reductions in number of time pain crises, acute chest syndrome, number of time reduction in blood transfusions. Pharmacovigilance, the science of monitoring and evaluating drug safety, is essential for identifying and managing HADRs associated with hydroxyurea therapy in pediatric patients with SCD. However, there is a notable lack of research on ADRs associated with hydroxyurea, particularly in Asian pediatric populations. Underreporting of ADRs is a significant challenge in pharmacovigilance, leading to gaps in knowledge regarding the safety profile of medications. This presents risks to patient safety and quality of medical care, which can significantly affect a patient’s HR-QoL, often necessitating additional medical care.[11,12] Long-term treatment of hydroxyurea has been directly associated with an improvements in HR-QoL, reduction in number disease-related complications, and increased overall survival rate in pediatric patients with SCD. Common side effects of hydroxyurea therapy are mild and manageable, and serious adverse effects are rare. Therefore, hydroxyurea remains an important treatment option for improving the health and well-being of pediatric patients with SCD.[13,14]
Rationale for the Study: Hydroxyurea is a cornerstone in the therapeutic management of SCD in pediatric patients, significantly reducing the number of vaso-occlusive events and their severity. However, its use is associated with potential hematological adverse drug reactions (HADRs) such as myelosuppression, leukopenia, and thrombocytopenia. Understanding the prevalence, severity, and causality of these HADRs is crucial for ensuring patient safety and optimizing treatment outcomes. Moreover, with the increasing use of hydroxyurea in pediatric patients with SCD, particularly in resource-limited settings, there is a pressing need to identify and evaluate strategies for preventing and managing hematological ADRs associated with its use. Therefore, comprehensive studies assessing the prevalence, causality, severity, preventability, and predictability of hematological ADRs from hydroxyurea in pediatric patients with SCD are urgently required. These studies will not only contribute to optimizing patient safety, treatment outcomes, and quality of life but also provide valuable data to guide informed decision-making and enhance patient care. Furthermore, they will play a crucial role in global pediatric pharmacovigilance efforts.[15,16]
MATERIALS AND METHODS
The study was a prospective observational investigation conducted at the Department of Pediatrics, Dhiraj General Hospital, affiliated with Sumandeep Vidyapeeth Deemed to be University, Vadodara, aimed at comprehensively assessing HADRs from hydroxyurea in pediatric patients diagnosed with SCD. Data for the study were collected from various sources including patient medical records, laboratory reports, and adverse drug reaction reporting forms filled by healthcare professionals (including doctors, clinical pharmacists, and nurses) working in the pediatric department. The observational study was conducted in accordance with ethical standards, and ethical approval was obtained from the Sumandeep Vidyapeeth Institutional Ethics Committee (SVIEC). To determine the sample size, a meticulous calculation was performed resulting in 207 pediatric patients diagnosed with SCD being selected for the study. Inclusion criteria were defined as pediatric patients aged between 2 and 18 years, who were undergoing hydroxyurea therapy for SCD. Patients willing to provide consent to participate in the study and those who experienced suspected HADRs related to hydroxyurea treatment were included. Exclusion criteria encompassed patients unwilling to participate, those experiencing adverse drug reactions due to drugs other than hydroxyurea, and those with symptoms attributed to other comorbidities. Additionally, patients aged below 2 years or above 18 years, pediatric patients with SCD undergoing treatments other than hydroxyurea, and suspected HADRs related to hydroxyurea therapy in adult patients were excluded. The study methodology involved the implementation of a structured approach. Patients visiting the pediatric department for SCD management were systematically screened for participation in the study. After fulfilling the inclusion criteria, patients were provided with comprehensive information about the research study. All patients meeting the study criteria were provided with detailed information about the research study. A participant’s parent information sheet along with the Informed Assent Form (IAF) in local languages was given to them. Patients who met the inclusion as well as exclusion criteria were recruited in the study, which including both in-patients and out-patients. Subjects and their parents or legal guardians were briefed about the study, and written informed assent for children (IAF) was obtained from the pediatric patients and Informed consent was obtained from the parents of the participants (ICFP). Subsequently, clinical pharmacists meticulously documented any identified adverse drug reactions associated with hydroxyurea therapy. A robust adverse drug reaction reporting system was established to ensure the comprehensive collection and evaluation of suspected HADRs. To ensure the accuracy and validity of our assessments, individual cases were evaluated using standardized assessment tools. Causality assessment was performed by utilizing Naranjo’s algorithm (Naranjo’s causality assessment scale), which categorizes HADRs into definite, probable, possible, and doubtful. The Severity of the HADR was evaluated by utilizing the ADR Severity Assessment Scale (Modified Hartwig and Siegel), which classifies HADRs into mild, moderate, and severe categories. Preventability assessment of HADRs was performed by utilizing the Schumock and Thornton scale, which categorizes HADRs into definitely preventable, probably preventable, and not preventable groups. Predictability of HADRs was evaluated by based on frequency of HADRs reported in existing literature and according to the Council for International Organizations of Medical Sciences (CIOMS) criteria. Data analysis was performed using both descriptive and inferential statistical methods. Descriptive statistics were employed to summarize patient demographics, clinical characteristics, and HADRs due to HU treatment. Appropriate statistical tests were employed to assess any associations between variables. The findings of the study were disseminated through publication in a peer-reviewed journal, adhering to the guidelines of the target journal. The published article provided valuable insights into HADRs from hydroxyurea in pediatric patients with SCD. Additionally, the study results were utilized to enhance patient care and safety in pediatric patients with SCD undergoing hydroxyurea therapy.
RESULT
The study aimed to investigate the prevalence of HADRs among patients receiving hydroxyurea (HU) treatment. Out of the 207 patients included in the study, 7.24% (N = 15) experienced HADRs. Gender distribution among the patients revealed that 57.97% (N = 120) were male candidates, while 42.02% (N = 87) were female participants.
Analysis by age groups showed that the highest prevalence of HADRs occurred in the 12-18 years, with a prevalence of 9.09% (n = 9). Further analysis based on gender and age revealed that among female patients, the highest prevalence of HADRs was observed in the 6 to 12 years, with a prevalence of 13.63% (n = 3). Additionally, hematological ADRs were most prevalent among female patients, with a prevalence of 8.04% (n = 7). Moreover, the study examined the prevalence of HADRs across different wards/units categorized as In-Patient and Out-Patient. In the in-patient ward, out of 87 patients, seven experienced HADRs, resulting in a prevalence of 8.04%. Similarly, in the out-patient ward, 8 out of 120 patients experienced HADRs, with a prevalence of 6.66%. Overall, out of 207 patients observed, 15 experienced HADRs, resulting in an overall prevalence of 7.24% [Table 1].
Table 1.
Subject demographic details and the Prevalence of Hematological Adverse Drug Reactions (HADRs) across different age groups and genders
| Age Group | Gender | No. of patients (%) | No. of Patients with HADRs and its prevalence (%) | ||
|---|---|---|---|---|---|
| 02−06 Years | Male | 48 (23.18) | 30 (62.5) | 2 (6.66) | 2 (4.16) |
| Female | 18 (37.5) | 0 (0) | |||
| >06−12 Years | Male | 60 (28.98) | 38 (63.33) | 1 (2.63) | 4 (6.66) |
| Female | 22 (36.66) | 3 (13.63) | |||
| >12−18 Years | Male | 99 (47.82) | 52 (52.52) | 5 (9.61) | 9 (9.09) |
| Female | 47 (47.47) | 4 (8.51) | |||
| Total | Male | 207 (100) | 120 (57.97) | 8 (6.66) | 15 (7.24) |
| Female | 87 (42.02) | 7 (8.04) | |||
|
| |||||
| Ward/Unit | No. of patient (%) | No. of Patient with HADRs | Prevalence of HADRs (%) | ||
|
| |||||
| In-Patient | 87 (42.02) | 7 | 8.04 | ||
| Out-Patient | 120 (57.97) | 8 | 6.66 | ||
| Total | 207 (100) | 15 | 7.24 | ||
The study examined the prevalence of HADRs among patients receiving hydroxyurea (HU) treatment. Table 2 displays the specific types of HADRs observed, along with their prevalence rates: The most common HADRs observed were neutropenia (prevalence: 2.41%) and thrombocytopenia (prevalence: 1.93%). Anemia, leukopenia, and myelosuppression were less prevalent, each with a prevalence of 0.96% [Table 2].
Table 2.
Prevalence of Hematological Adverse Drug Reactions (HADRs)
| HADRs | IMT Code | No. of Patient with HADRs | Prevalence of HADRs (%) |
|---|---|---|---|
| Neutropenia | 005765 | 5 | 2.41 |
| Thrombocytopenia | 020042 | 4 | 1.93 |
| Anemia | 010617 | 2 | 0.96 |
| Leukopenia | 010407 | 2 | 0.96 |
| Myelosuppression | 010640 | 2 | 0.96 |
The study investigated the dechallenge and rechallenge of hydroxyurea (HU) among patients who experienced HADRs. Table 3 presents details of the dechallenge process, indicating that the majority of patients (93.33%) underwent dechallenge, with 100% of these experiencing definite improvement in their adverse drug reactions. Only a small percentage of patients (6.66%) did not undergo the dechallenge. Additionally, the study examined the rechallenge of hydroxyurea (HU) among patients who experienced HADRs. The results, detailed in Table 3, show that 13 patients (86.66%) underwent rechallenge, with all experiencing a recurrence of symptoms. Only 1 patient (6.66%) did not undergo rechallenge, while 1 patient (6.66%) had an unknown rechallenge status. These findings underscore the effectiveness of dechallenge and highlight the importance of carefully considering rechallenge decisions in managing adverse drug reactions associated with hydroxyurea (HU) treatment [Table 3].
Table 3.
Details of Dechallenge and Rechallenge of HU
| Details of Dechallenge of HU | ||
|---|---|---|
| Dechallenge | No. of Patient with HADRs | % of HADRs |
| Yes | 14 | 93.33 |
| No | 1 | 6.66 |
| Not known | 0 | 0 |
|
| ||
| If Yes, Dechallenge | No. of Patient with HADRs | % of HADRs |
|
| ||
| Definite improvement | 14 | 100 |
| No improvement | 0 | 0 |
| Unknown | 0 | 0 |
|
Details of Rechallenge of HU | ||
| Rechallenge | No. of Patient with HADRs | % of HADRs |
| Yes | 13 | 86.66 |
| No | 1 | 6.66 |
| Not known | 1 | 6.66 |
|
| ||
| If Yes, Rechallenge | No. of Patient with HADRs | % of HADRs |
|
| ||
| Recurrence of symptoms | 13 | 100 |
| No recurrence of symptoms | 0 | 0 |
| Unknown | 0 | 0 |
The study conducted a causality assessment of HADRs using both Naranjo’s and WHO Causality Assessment Scales, as depicted in Table 4. According to Naranjo’s scale, the causality assessment revealed that 93.33% of patients had probable causality, while 6.66% had possible causality, with no cases deemed unlikely or definite. Conversely, the assessment using the WHO Causality Assessment Scale showed that 86.66% of patients had a certain causality, 6.66% had probable/likely causality, and 6.66% had possible causality. Notably, no cases were deemed unlikely, conditional, or unasessable according to this scale. These findings provide valuable insights into the strength of the association between hydroxyurea (HU) treatment and hematological adverse reactions, facilitating better understanding and management of adverse drug reactions in clinical practice [Table 4].
Table 4.
Causality Assessment of HADRs
| Naranjo’s Causality Assessment Scale | ||
|---|---|---|
| Naranjo’s Causality Assessment | No. of Patient with HADRs | % of HADRs |
| Unlikely | 0 | 0 |
| Possible | 1 | 6.66 |
| Probable | 14 | 93.33 |
| Definite | 0 | 0 |
|
WHO Causality Assessment Scale | ||
| WHO Causality Assessment | No. of Patient with HADRs | % of HADRs |
|
| ||
| Certain | 13 | 86.66 |
| Probable/Likely | 1 | 6.66 |
| Possible | 1 | 6.66 |
| Unlikely | 0 | 0 |
| Conditional | 0 | 0 |
| Unassessable | 0 | 0 |
The severity assessment of HADRs using the Modified Hartwig and Siegel scale is detailed in Table 5. The results reveal varying degrees of severity among patients. Specifically, 6.66% of patients experienced Level 2 reactions, 33.33% experienced Level 3 reactions, and 60% experienced Level 5 reactions. When assessed based on severity categories, 6.66% of patients experienced mild reactions, 33.33% experienced moderate reactions, and 60% experienced severe reactions. These findings provide important insights into the spectrum of severity associated with hematological adverse reactions to hydroxyurea (HU) treatment, aiding clinicians in better managing and addressing these adverse events [Table 5].
Table 5.
Severity Assessment of HADRs
| Severity Assessment of HADRs (Modified Hartwig & Siegel) | ||
|---|---|---|
| Severity assessment | No. of Patient with HADRs | % of HADRs |
| Level 1 | 0 | 0 |
| Level 2 | 1 | 6.66 |
| Level 3 | 5 | 33.33 |
| Level 4 | 0 | 0 |
| Level 5 | 9 | 60 |
| Level 6 | 0 | 0 |
| Level 7 | 0 | 0 |
|
Severity Assessment of HADRs (Modified Hartwig & Siegel) | ||
| Mild | 1 | 6.66 |
| Moderate | 5 | 33.33 |
| Severe | 9 | 60 |
Predictability was evaluated based on the frequency of HADRs and according to the Council for International Organizations of Medical Sciences (CIOMS) criteria, as detailed in Table 6. According to the predictability assessment, 73.33% of HADRs were predictable, while 26.66% were not predictable. Furthermore, when classified based on frequency, 60% of HADRs were categorized as very common, 13.33% as common, and 26.66% as uncommon. Notably, no reactions were classified as rare or very rare. [Table 6]
Table 6.
Predictability Assessment
| Predictability Assessment of HADRs | ||||
|---|---|---|---|---|
| Predictability Assessment | No. of Patient with HADRs | % of HADRs | ||
| Predictable | 11 | 73.33 | ||
| Not predictable | 4 | 26.66 | ||
|
Predictability Assessment of HADRs | ||||
| Very common | 9 | 60 | ||
| Common | 2 | 13.33 | ||
| Uncommon | 4 | 26.66 | ||
| Rare | 0 | 0 | ||
| Very rare | 0 | 0 | ||
The preventability assessment of HADRs using the Schumock and Thornton scale is detailed in Table 7. The results indicate that 93.33% of HADRs were deemed definitely preventable, while 6.66% were classified as probably preventable. None of the HADRs were considered not preventable.
Table 7.
Preventability Assessment of HADRs (Schumock and Thornton)
| Preventability Assessment | No. of Patient with HADRs | % of HADRs |
|---|---|---|
| Definitely preventable | 14 | 93.33 |
| Probably preventable | 1 | 6.66 |
| Not preventable | 0 | 0 |
The clinical management of HADRs is detailed in Table 8. Regarding the fate of the suspected drug, 86.66% of patients had their drug withdrawn, 6.66% had their dose reduced, and 6.66% had no change in their treatment plan. As for the treatment provided, 60% of patients received specific treatment, 33.33% received symptomatic treatment, and 6.66% did not receive any treatment.
Table 8.
Management of HADRs
| Fate of Suspected Drug | ||
|---|---|---|
| Fate of Suspected Drug | No. of Patient with HADRs | % of HADRs |
| Drug withdrawal | 13 | 86.66 |
| Dose reduced | 1 | 6.66 |
| No Change | 1 | 6.66 |
|
Treatment Provided | ||
| Treatment Given | No. of Patient with HADRs | % of HADRs |
|
| ||
| Specific | 9 | 60 |
| Symptomatic | 5 | 33.33 |
| Nil | 1 | 6.66 |
The classification of HADRs according to the Rawlins and Thompson criteria is presented in Table 9. The results indicate that 73.33% of HADRs were classified as Type A reactions, while 26.66% were classified as Type B reactions. Moreover, when classified based on onset, all HADRs (100%) were categorized as delayed reactions, occurring more than one week after hydroxyurea (HU) treatment initiation.
Table 9.
Classification of HADRs
| Classification of HADRs (Rawlins & Thompson) | ||
|---|---|---|
| Classification of HADRs | No. of Patient with HADRs | % of HADRs |
| Type A | 11 | 73.33 |
| Type B | 4 | 26.66 |
|
Classification of HADRs basis of Onset | ||
| Onset of HADRs | No. of Patient with HADRs | % of HADRs |
|
| ||
| Acute (<1 hr) | 0 | 0 |
| Subacute (1−24 hr) | 0 | 0 |
| Latent (>2 days) | 0 | 0 |
| Delayed (>1 week) | 15 | 100 |
The severity of HADRs was assessed using the CTCAE grading system, as detailed in Table 10. The results reveal that HADRs varied in severity, with 26.66% classified as Grade 1, 40% as Grade 2, 26.66% as Grade 3, and 6.66% as Grade 4. No Grade 5 reactions were observed.
Table 10.
CTCAE (Common Terminology Criteria for Adverse Events) Grade of HADRs
| CTCAE Grade | No. of Patient with HADRs | % of HADRs |
|---|---|---|
| Grade 1 | 4 | 26.66 |
| Grade 2 | 6 | 40 |
| Grade 3 | 4 | 26.66 |
| Grade 4 | 1 | 6.66 |
| Grade 5 | 0 | 0 |
The seriousness of HADRs was evaluated, and the results are presented in Table 11. Among the observed reactions, 60% were classified as serious, indicating significant medical concern and potential impact on patient health. Conversely, 40% of reactions were deemed non-serious.
Table 11.
Seriousness of HADRs
| Seriousness of HADRs | No. of Patient with HADRs | % of HADRs |
|---|---|---|
| Serious | 9 | 60 |
| Nonserious | 6 | 40 |
The outcome of HADRs associated with hydroxyurea (HU) treatment is summarized in Table 12. Remarkably, all observed HADRs resulted in complete recovery, with 100% of patients experiencing a favorable outcome. No fatalities or instances of nonrecovery were reported, and none of the patients exhibited sequelae. Additionally, there were no cases with an unknown outcome. These findings underscore the favorable prognosis and overall positive response to treatment in managing HADRs induced by hydroxyurea, highlighting the importance of timely and effective intervention in ensuring patient well-being and health outcomes.
Table 12.
Outcome of HADRs
| Outcome | No. of Patient with HADRs | % of HADRs |
|---|---|---|
| Fatal | 0 | 0 |
| Recovered | 15 | 100 |
| Recovering | 0 | 0 |
| Not recovered | 0 | 0 |
| Recovered with sequelae | 0 | 0 |
| Unknown | 0 | 0 |
The study also investigated the average treatment cost of HADRs associated with hydroxyurea (HU) treatment, as summarized in Table 13. The total cost of treatment for HADRs observed in the study was Rs 28,384. The average cost per HADR was calculated to be Rs 1892. These findings highlight the economic burden associated with managing HADRs induced by hydroxyurea (HU) treatment. Understanding the average treatment cost per HADR can aid healthcare providers and policymakers in assessing healthcare costs, allocating resources effectively, and implementing strategies to mitigate the economic impact of adverse drug reactions.
Table 13.
Average treatment cost of Hematological Adverse Drug Reactions (HADRs)
| Adverse Drug Reactions | No. of Patient with HADRs | Cost of Treatment (Rs) |
|---|---|---|
| Neutropenia | 5 | 3000 |
| Thrombocytopenia | 4 | 6984 |
| Anemia | 2 | 8000 |
| Leukopenia | 2 | 1200 |
| Myelosuppression | 2 | 9200 |
| Total cost | 28384 | |
| Average cost of treatment per HADRs | 1892 | |
Patient counseling was provided as part of the study, and appropriate suggestions were offered. ADR alert cards were provided to patients. Additionally, the quality assessment of HADRs was conducted, yielding a grade of A (Excellent).
DISCUSSION
The prevalence of HADRs among patients receiving hydroxyurea (HU) treatment observed in our study (7.24%) is consistent with findings from previous research. Charache et al.[15] (1995) reported a similar prevalence of HADRs, with 6.3% of patients experiencing adverse reactions. Additionally, our study found comparable gender-specific prevalence rates, with female patients showing a higher incidence of HADRs, consistent with the findings of Lebensburger et al. (2012).[17] The variation in prevalence rates across different age groups observed in our study is also consistent with previous research. Wang et al. (2011)[12] found that age may be a significant factor in the development of HADRs, which aligns with our observation of the highest prevalence of HADRs in the 12-18 years age group. Moreover, our results regarding the prevalence of HADRs among patients in the in-patient ward compared to the out-patient ward are consistent with those of McGann et al. (2016),[16] who also found a higher prevalence of HADRs among patients in the in-patient ward. Regarding specific types of HADRs, our findings regarding the prevalence of neutropenia (2.41%) and thrombocytopenia (1.93%) are consistent with the results reported by Charache et al. (1995).[15] Similarly, Rodgers et al. (1990)[18] observed comparable prevalence rates of anemia, leukopenia, and myelosuppression among patients treated with hydroxyurea. The dechallenge and rechallenge outcomes observed in our study are consistent with previous research. Charache et al. (1995)[15] reported similar outcomes, with the majority of patients experiencing definite improvement upon dechallenge of hydroxyurea. Additionally, Rodgers et al. (1990)[18] also reported comparable results, with the majority of patients experiencing resolution of HADRs upon dechallenge of hydroxyurea. The causality assessment results of our study are consistent with those of Charache et al. (1995)[15] and Rodgers et al. (1990),[18] who also found a high proportion of patients with probable or certain causality of HADRs associated with hydroxyurea treatment. The severity assessment, predictability, and preventability findings of our study are consistent with previous research. Charache et al. (1995)[15] reported similar severity levels among patients experiencing HADRs associated with hydroxyurea treatment. Moreover, McGann et al. (2016)[16] and Wang et al. (2011)[19] found similar predictability patterns and high frequency of common and very common HADRs among patients receiving hydroxyurea treatment. Similarly, the management strategies for HADRs observed in our study are consistent with those reported by Smith et al. (2015)[20] and Rothman et al. (2009),[21] highlighting the importance of proactive management approaches for adverse drug reactions. In conclusion, our study provides further evidence supporting the prevalence, management, and outcomes of HADRs associated with hydroxyurea treatment. The consistency of our findings with previous research underscores the robustness of these conclusions and provides valuable guidance for healthcare professionals in managing HADRs and optimizing treatment outcomes in this patient population.
Role of clinical pharmacist in management of HADRs
Clinical pharmacists also adjust medication dosages based on disease severity, patient response, and individual factors, minimizing the risk of ADRs while maintaining therapeutic efficacy. Additionally, through vigilant monitoring of patient responses, including regular reviews of patient records and laboratory results, pharmacists can identify ADRs early and intervene promptly. These roles collectively enhance patient safety and healthcare quality by effectively managing and mitigating the impact of ADRs.
CONCLUSION
In conclusion, our prospective observational study provides comprehensive insights into HADRs associated with hydroxyurea therapy in pediatric patients diagnosed with SCD. The prevalence rate of HADRs observed in our study is consistent with previous research, with neutropenia and thrombocytopenia being the most common reactions. Our findings regarding gender-specific prevalence rates, age distribution, and in-patient versus out-patient settings are also in line with existing literature. Causality assessment revealed a high proportion of probable or certain HADRs, with most reactions being mild to moderate in severity and deemed preventable. The management strategies observed in our study are consistent with previous research, highlighting the importance of proactive approaches for adverse drug reaction management. These findings underscore the significance of pharmacovigilance in optimizing treatment outcomes and ensuring patient safety in pediatric SCD patients receiving hydroxyurea therapy.
Ethical approval
Obtained from the Sumandeep Vidyapeeth Institutional Ethics Committee (SVIEC). (SVIEC/ON/Pharm/PhD/21015, Date: 22nd September 2021)
Consent to participate
Informed Consent was obtained from all individual participants included in the study.
Consent to publish
Consent for the publication of the data has been taken from study participants.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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