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Park-wylliescalera A, Tseng A, Rourke S. High rate of discontinuation of highly active .... Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley J et al.

Mohd.Azharuddin et al. / IJPPDR / 4(1), 2014, 8-11.

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NEVIRAPINE INDUCED SKIN RASHES AMONG HIV PAEDIATRIC PATIENTS- 3 CASE STUDY REPORTS Mohd.Azharuddin*, Ushasree Puneem1, Subash Vijaya Kumar1, G.Ashwini2 */1Department of Pharmacy Practice, VCOP, MGM Hospital, Warangal, Andhra Pradesh, India. 2 ART Centre, MGM Hospital, Warangal, Andhra Pradesh, India.

ABSTRACT Nevirapine – NRTI’s licensed for first line drug regimen in HIV infections. It is relatively non-toxic in nature and potentially antiviral effects of other NRTI’s like Lamivudine although Nevirapine is a well-tolerated, certain (dermatological) cutaneous side effect like skin rash. We report a case series of skin rashes in 3 HIV infected paediatric patients, probably due to Nevirapine. Adverse cutaneous drug reactions are distressing to both the patient and physician. Mortality can occurs in severe reactions, but even without this quality of life may be significantly diminished due to hospitalization, prolongation of hospital stay and increased morbidity, Furthermore, the development of a skin eruption is frequently cite and as a reason for discontinuation of treatment without completing therapeutic course. Keywords: Nevirapine, Skin rashes, Gender, Age. INTRODUCTION Highly active antiretroviral therapy (HAART) has been shown significantly to reduce progression to AIDS-defining illnesses, AIDS-related hospitalization and mortality in both clinical trials and a number of large observational studies [1-3]. However, discontinuation of HAART therapy may lead to suboptimal therapy and ultimately to treatment failure [4]. This underlines the importance of optimizing initial HAART as success of salvage therapies after failure of initial HAART is limited. Recent data indicate that the overall discontinuation or modification rates of HAART regimen among patients range from 8 to 59% (median 33%) [5]. Nevirapine (NVP) is the preferred NRTI in firstline antiretroviral regimens in pregnancy because of substantial clinical experience with pregnant women and it’s proven efficacy in reducing Mother-to-child transmission [6,7]. The most frequent adverse event of NVP are hepatotoxicity and cutaneous report an increased risk of severe hepatotoxicity and cutaneous rash in women with CD4 count >250 cells/mm3 [8-12], based on these findings, WHO recommends avoiding NVP in women, including pregnant women, with CD4 counts between 250

and 350 cells/mm3, or if no other options exist as it is often the case in resource-limited settings, using it with caution and close monitoring during the first 12 weeks of therapy. Although some cases have been reported in pregnant women, it is still not known whether pregnancy increases the risk of the occurrence of hepatotoxicity or rash [12-14]. In resource-limited settings, where NVP is widely used in women and during pregnancy whatever the level of CD4, there is little data on the occurrence of hepatotoxicity and/or rash according to CD4, and all except one study did not find this association[15-19]. CASE 1 An 8 years old male patient present a prescription for SLN (150mg+150mg+200mg) BD, known case of HIV since august 2008, mode of transmission was vertical transmission. He has chief complaints of fever and rashes since 3 days, where as his ART started on October 2013 (SLN ), contained for 15 days, 2 weeks after initiation of ART he presented with complaints of high grade fever and skin rash which was erythmatous papular purities involved in upper and lower four limbs figure 1.

Corresponding Author:- Mohd. Azharuddin Email : [email protected]

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On examination his vital parameters are normal except a few subcentimetric cervical lymph nodes. His systematic examination revealed hepatomegaly, rest of the systemic examination is normal. Laboratory investigation revealed is anaemic ( Hb%=7.5 gram% ) and on further biochemical investigation reveals that WBC count 11000mm3 , platelet 3.5 lakh cells, He had abnormal Liver function tests with ALT 105 U/L, AST 45 U/L all other renal function tests are normal. Whereas, Ultra sound revealed hepatomegaly. He was managed by stopping nevirapine at presentation putting his on alternative ART regimen (ZLE) (300mg+150mg+600mg). He was started on oral prednisolone 100 mg OD, paracetamol 250mg for every 4th hourly, chlorphenaramine maleate 1mg for 2 days fever subsidized after stopping nevirapine, moreover, rashes decreased after 10 days, He was became normal and symptomatically relieved after two weeks. CASE 2 A 3 year old female paediatric patient walking outpatient clinic of ART centre of government hospital, Warangal, She was known case of HIV since from March 2007 on ZLN regimen, her mode of transmission by unsafe injection. She has come with her chief complaints of rashes, cough, and fever since 5 days after initiation of ART regimen figure 2. She was referred to the department of dermatology unit 9 (KMC) Warangal, she had no surgical history, no family history of HIV on examination and all

vitals are normal, she had No history of cervical nodes, and systemic examination are normal, her laboratory investigations reveals that haemoglobin 11 gram%, TLC 10200 cells/cmm, serum creatinine 0.7 mg/dL, serum bilirubin was 0.9 mg/dl. The child condition was managed by stopping Nevirapine and alters the ART regimen to improve the patient compliance although the patient condition was improved with antihistamic drugs, anti pyretic drug, replacing drug ZLN with ZLE and supportive medications used to improve the patient outcome. CASE 3 A 7 years old male patient walking outpatient clinic of ART centre of government hospital, Warangal, he was known case of HIV since from august 2007 on ZLN therapy, His mode of transmission by vertical transmission. He come with chief complaints of rashes, head ache, fever and cough since 6 days after initiation of ARV regimen. Figure 3. He was advised to the paracetamol 500mg every 4th hourly, anti-histamic drug 1mg OD for 2 days, on examination his vital parameters were normal and his laboratory investigations were haemoglobin 9.2 gram%, TLC was 1820 and serum creatinine was 0.8 mg%, all other findings are normal and then patient medication was replaced by SLN with SLE his symptoms was symptomatically relieved and patient condition was came normal after a couple of weeks.

Figure 1. Erythmatous papular purities involved in upper and lower four limbs

Figure 2. Left hand rashes over the HIV patients

Figure 3. Rashes over the Right hand of HIV patients

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DISCUSSION HIV infected paediatric patients are at risk of developing mucocutaneous drug reaction nearly 80% patients experience ADR’S at some time during the treatment from immune deregulation/altered drug metabolism [20, 21]. DRESS syndrome is a life-threatening adverse reaction to a drug. Earlier there was no consistent name for this syndrome and it was named after the culprit drug as phenytoin syndrome, allopurinol hypersensitivity syndrome. Nevirapine is a non-nucleoside HIV-reverse transcriptase that is used in combination with other antiretroviral agents, Rash is the most frequent adverse event associated with nevirapine therapy. Nevirapineinduced DRESS was first with nevirapine therapy. This report highlight the importance of consider nevirapineinduced of cutaneous side effect of nevirapine which can range from drug rash, stopping Nevirapine and administration of steroids remains the mainstay of management of this condition. The common adverse effect NRTI’s are rashes and hepatitis Ganger et al [22]. Were the first to suggest altered forward a higher frequency of rash women taking Nevirapine than among men, three studies provide further support of this sex difference [23]. The exact reason for sex differences in AR’S to antiretroviral drugs cannot be explored. Although several studies in human pharmacology has described differences in patients in drug response toxicities between male and female. Sex difference are difficult to ascribe to simple distinct mechanism difference in drug levels/in drug

response depends on sociocultural, psycho perceptual and behavioral factors, body size and composition , genetic, molecular, biochemical factors and hormonal/reproductive influence [24] difference in weight and BMI between male and female may be playing important role. Some drugs lack metabolic pathways in which significant difference between male and female. Subjects have been demonstrated sex difference in fast composition and the impact on drug distribution may also play a role. As may the genomic constitution difference that exist between men and women and they maybe in which this difference affect the levels of various enzymes involved in drug metabolism [25]. Adverse cutaneous drug reactions are distressing to both the patient and physician. Mortality can occurs in severe reactions, but even without this quality of life may be significantly diminished due to hospitalization, prolongation of hospital stay and increased morbidity [26], Furthermore, the development of a skin eruption is frequently cite and as a reason for discontinuation of treatment without completing therapeutic course [27], Drug reaction are common for litigation too. Not warning a patient about potential adverse events prescribing the common medic legal pitfalls and therefore should not be taken lightly. CONCLUSION Since Nevirapine has been an effective, safe and widely used ART drugs, clinician must be aware of such severe ADR’S to Nevirapine, which may required treatment discontinuation, So that after the treatment plan in such paediatric patients.

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