• No results found

STUDY OF ADVERSE DRUG REACTIONS IN ANTIRETROVIRAL THERAPY

N/A
N/A
Protected

Academic year: 2020

Share "STUDY OF ADVERSE DRUG REACTIONS IN ANTIRETROVIRAL THERAPY"

Copied!
7
0
0

Loading.... (view fulltext now)

Full text

(1)

STUDY OF ADVERSE DRUG REACTIONS IN ANTIRETROVIRAL

THERAPY

1

*C S Manju, 2Muhammed Shajeel P, 3Dr. Aquil Kalanad and 4B. Athira

1

Assistant Professor in Pharmacy, College of Pharmaceutical Sciences, Govt. Medical

College, Kozhikode, Kerala, India.

2

M. Pharm Student, College of Pharmaceutical Sciences, Govt. Medical College, Kozhikode,

Kerala, India.

3

Department of Medicine, Govt. Medical College, Kozhikode, Kerala, India

4

M.Pharm Student, College of Pharmaceutical Sciences, Govt. Medical College, Kozhikode,

Kerala, India.

ABSTRACT

Human immune deficiency virus infection is one of the most serious

challenges in health care. Highly Active Anti Retroviral Therapy

(HAART) is the name given to the aggressive treatment regimen. Anti

retro viral therapy exhibit greater level of efficacy with satisfactory

degree of toxicity. Adverse reactions to therapy lead to decrease in

patient compliance and adherence. The present work was a prospective

observational study used to evaluate the adverse drug reactions

associated with the use of antiretroviral drugs used in a tertiary care

hospital. The total incidence rate for Adverse Drug Reactions (ADRs)

was observed to be 40.50% in clinical settings of this study.

Tuberculosis was the most common Opportunistic Infection followed

by Candidiasis and skin infections. Incidence of ADRs was

significantly higher in Females. Gastrointestinal system involvement was the commonest

ADR encountered. Zidovudine + Lamivudine +Nevirapine were responsible for majority of

ADRs. Causality assessment between the ADR and suspected drug therapy were assessed

using the Naranjo probability scale. The severity of reaction was determined according to

modified Hartwig and Siegel scale and preventability by modified Schumock and Thornton

scale. Majority of the ADRs were probable, mild and preventable. The risk factors to ADRs

observed in this study are CD4 less than 200 cells/μL, female gender, tuberculosis,

Volume 5, Issue 01, 1226-1232. Research Article ISSN 2277– 7105

*Correspondence for

Author

C S Manju

Assistant Professor in

Pharmacy, College of

Pharmaceutical Sciences,

Govt. Medical College,

Kozhikode, Kerala, India. Article Received on 08 Nov 2015,

(2)

candidiasis and polypharmacy. In spite of high ADRs, HAART is the only answer to

HIV/AIDS; thus, management requires a highly precise balance between benefits of durable

HIV suppression and the risks of drug toxicity to achieve the therapeutic goals.

KEYWORDS : Adverse drug reactions, HAART therapy, opportunistic infections, poly pharmacy, causality, severity, preventability.

INTRODUCTION

One of the most formidable challenges in health sector is human immune deficiency virus

(HIV). Once infected the human body cannot clear out this virus. Highly active antiretroviral

therapy (HAART) is the name given to the treatment regimen to suppress HIV replication

and progression which has lead to a remarkable reduction in the morbidity and mortality.[1] Up to 25% of patients discontinue their HAART regimen because of treatment failure, toxic

effects and noncompliance with in the initial months of therapy. These medicines are

associated with significant safety concerns including serious Adverse Drug Reactions

(ADRs) with short and long term effects. Studies on incidence of ADRs reported that

incidence rate is 10 to 40%.[2] The pattern and incidence of ADRs may vary due to economic restrictions, co morbid conditions and opportunistic infections. In India adverse

drug reactions go unnoticed or are not reported.[3] Earlier antiretroviral drugs at their introduction stage are validated in white people but are now widely using in developing

countries.[4] So this study was aimed to determine the incidence of clinically significant adverse events after short term fixed dose regimen in terms of their causality, severity and

preventability.[5,6] Study also aimed to find out relationship between distribution of these ADRs with respect to age, sex, drug regimen, number of drugs and opportunistic infections.

MATERIALS AND METHODS Study settings

The study was designed to be a prospective observational study conducted in the Anti

Retroviral Therapy clinic, Department of Medicine, a tertiary care teaching hospital,

Kozhikode, Kerala, India over a period of 7 months from June 2013 to January 2014. Study

approved by the institutional ethics committee.

Data collection and study procedure

Total of 153 patients were enrolled in the study after signing the informed consent form. All

(3)

respective dosage, and route of administration with frequency, date of onset of reaction,

patient’s allergy status were noted. Data collected from patient’s case notes, treatment charts,

laboratory reports, consulting physicians and patient interview. Causality assessment between

the ADR and suspected drug therapy were assessed using the Naranjo probability scale. No

rechallenge was attempted in any patient. The severity of reaction was determined according

to modified Hartwig and Siegel scale and preventability by modified Schumock and Thornton

scale.

RESULTS

During the 7 months study period, 153 patients who were receiving antiretroviral therapy

were enrolled in the study. 85 were males and 68 were females. Tuberculosis was the most

common opportunistic infection with an incidence of 28% followed by candidiasis (16%) in

the study population. Out of 153 patients 62 patients experienced adverse drug reactions; of

them 46.8% were males and 53.2%were females. “Fig.1”

Prescribing Pattern of ART drugs in fixed combinations and Regimen wise distribution of ADR

Table 1

REGIMEN Total number of

patients on Regimen

Number of patients with ADR

Percentage of ADR Zidovudine, lamivudine, nevirapine

AZT+3TC+NVP 86 39 45.35

Zidovudine, lamivudine, efavirenz

AZT+3TC+EFV 49 19 38.77

Tenofavir,lamivudine,nevirapine

TDF+3TC+NVP 6 1 16.6

Tenofavir,lamivudine,efavirenz

TDF+3TC+EFV 6 1 16.6

Stavudine,lamivudine,nevirapine

D4T+3TC+NVP 6 2 33.3

(4)
[image:4.595.126.466.78.738.2]

Table 2

System wise distribution of ADRs

Increased risk of adverse drug reactions according to number of drugs used.

Type of ADR Frequency of ADR Percentage%

Nausea 20 19.04

Vomiting 10 9.5

Fatigue 2 1.9

Anemia 30 28.57

Lipodystrophy 2 1.9

Diarrhea 1 0.95

Jaundice 2 1.9

Skin rash 16 15.24

Decreased sleep 1 0.95

Neuropathy 4 3.8

Gastritis 3 2.85

Headache 1 0.95

Hair fall 2 1.9

Dyspepsia 4 3.8

(5)

Risk factors for adverse drug reactions to Anti retroviral drugs. table 3 Patient factors ADR occurrence in patients 1. Gender

Male female

29 33

2. Age 15-40 41-60 Above 60

37 23 2

3. CD4 count ˂ 200 cells/µL

˃200cells/µL

35 27

4. Number of drugs used 3-4

5-6 ˃6

11 23 28

5. Opportunistic infections Tuberculosis

candidiasis

16 8

Causality Assessment of ADRs

Causality assessment was done as per NARANJO’S ALGORITHM. Each questions in the

questionnaire is given a score (-1 to +2). Total score counted and ADR is scaled into the

[image:5.595.141.453.481.540.2]

following categories.

Table 4

Severity assessment of ADRs by Hartwig Severity assessment Scale

Table 5

Preventability Assessment by Schumock and Thornton Scale

Table 6

Causality Score No. of ADRs Percentage of ADRs

Possible 1-4 46 43.8

Probable 5-8 59 56.2

Definite 9 0 0

Severity Score No. of ADRs Percentage of ADRs

Mild Level 1 & 2 70 66.6

Moderate Level 3 & 4 33 31.4

Severe Level 5, 6 & 7 2 2

Preventability Number of ADRs Percentage of ADRs

Definitely Preventable 73 69.5

Probably Preventable 22 20.95

(6)

DISCUSSION

The study observed significant morbidity with HAART therapy. Out of the 153 patients 55.5

% were males, “Fig 1”. But female patients had more ADRs.[7]

Tuberculosis was the most

common opportunistic infection (28%). Among those 43 TB infected HIV patients 16

individuals developed ADRs. Fixed dose combination of zidovudine, lamivudine and

nevirapine was the most prescribed regimen (table 1). It is a combination of two nucleoside

reverse transcriptase inhibitors and one non nucleoside reverse transcriptase inhibitor. 45.35

% of ADRs belongs to this regimen. Next prescribed regimen was zidovudine, lamivudine

and efavirenz.38.77% of ADRs occurred in this group. In both these regimen blood cell

complaints was the most reported ADR. Majority of cases anemia observed with in the first

four weeks of treatment. Another finding is improvement in hemoglobin level on

discontinuation of zidovudine. Majority of patients experienced vomiting within an hour

ingestion of zidovudine[8] (table 2). The organ system commonly affected by ADR was GIT,

“Fig. 2” which includes nausea, vomiting, diarrhea and gastritis in the first few weeks of

therapy and were self limiting. In this study we observed skin rashes in patients who were on

nevirapine containing regimen. Elevated liver enzymes were another problem with

nevirapine. Generally this was experienced by AZT+3TC+NVP regimen. In such situations

the regimen shifted to AZT+TC+EVZ. Majority of ADRs (45.16%) found in patients who

received more than 6 drugs comparing to patients who received 3 to 4 drugs which was

17.7%, “Fig.3”

HIV patients treated for opportunistic infections experience ADRs at higher rate than others.

The probability of occurrence of ADRs to antiretrovirals in patients with HIV and

tuberculosis was higher compared to HIV patients without any opportunistic infections. CD4

less than 200 cells/µL, female gender, tuberculosis and poly pharmacy were observed as risk

factors (table 3). In this study majority of ADRs, causality was “probable” (56.2%) and

“possible” `(43.8%) by using Naranjo’s algorithm. Causality assessment is the method by

which the extent of relationship between a drug suspected ADR is established. Majority of

ADRs were “preventable” (90.5%0 while 9.5% were “non preventable”.[9]

Most of the ADRs

were classified as “mild” (66.6%) where as 31.4% are moderate. Only 2 % were found to be

severe. In most of preventable ADRs, preventive measures for ADRs were advised to patients

like avoiding fatty foods and dairy products for prevention of nausea and vomiting in patients

receiving zidovudine. This study observed the most common cause of highly active

(7)

adverse effects like anaemia, eosinophilia, leucopenia, neutropenia, bicytopenia,

pancytopenia with zidovudine therapy.

CONCLUSIONS

ART exhibit greater level of efficacy with significant reduction in morbidity and mortality,

with satisfactory degree of toxicity. Combination treatment and presence of opportunistic

infections produces adverse events. So better understanding and close monitoring of adverse

drug reactions and its effective management is needed to support patients during their

treatment. There by we can improve the treatment outcome and quality of life of people

living with HIV/AIDS, with an added advantage of reduction in healthcare cost and drug

resistance

ACKNOWLEDGEMENTS: NIL

REFERENCES

1. World Health Organization,2013http://www.who.int/en

2. Patrice S, Juste MA, Ambroise A, Eliacin L et al. Early Vs standard anti retroviral

therapy for HIV infected adults in Haiti. NEJM, 2010; 363: 257-265.

3. Radhakrishnana R, sudha v. Highly active anti retroviral therapy induced adverse drug

reactions in Indian human immune deficiency virus positive patients. Pharmacy Practice,

2011; 9(1): 48-55.

4. Twisselmann B. Adverse effects of antiretroviral treatment for HIV infection. European

Surveilance, 2001; 5(44): 2049.

5. Naranjo C A, Busto U, Sellers E M. A method for estimating the probability of adverse

drug reactions. Clinical Pharmacology and Therapeutics, 1981; 30: 39-45

6. Hartwig SC, Siegel J, Scheneider PJ. Preventability and severity assessment in reporting

adverse drug reactions. American journal of Hospital Pharmacy, 1992; 49: 2229-2232

7. Harminder S, Navin D etal. A prospective, observational, cohort study to elicit adverse

effects of antiretroviral agents in a remote resource restricted tribal population of

Chhattisgargh. Indian Journal of Pharmacology, 2009; 41(5): 224-226.

8. Cooper CL, Breau C, Laroche A et al. Clinical outcomes of first antiretroviral regimen in

HIV/hepatitis virus C virus co-infection. HIV medicine, British HIV association, 2006:

7(1): 32-37.

9. Lau PM, Stewart K,Dooley MJ. Hospital admissions resulting from preventable adverse

Figure

Table 2
Table 4   Causality Possible Probable

References

Related documents

grade level expectations, teachers are educating students based upon their individual. characteristics versus what students in a particular grade level need

Figure 1 Effects of leaf essential oil (EO1 and EO2) and glibenclamide on serum glucose levels and liver glycogen levels in normal and alloxan-induced diabetic male wistar rats for

Apo A1: apolipoprotein A1; ApoB: apolipiprotein B; cIMT: carotid intima- media thickness; ESR: erythrocyte sedimentation rate; FMD: flow-mediated dilation; HDL:

A total of 2342 cataract patients older than 50 years old with cataract-induced visual impairment or who had undergone cataract surgery were recruited from rural and urban areas

According to the National Institute for Health and Care Excellence (NICE) guidelines [ 10 ], patients who suffer sus- pected thoracic or lumbosacral spine injury with

Aberrant expression and activation of matrix metalloproteinases have been detected in invasive pituitary adenomas as in malignancy and correlated to tumor invasion.. Therefore,

For the majority of adults only spontaneous elimination of urolithiasis were noted, 37.5% preserved until now a normal renal function and 62.5% of them reached ESRD at the median age