Harmanjit Singh

Sofosbuvir: A novel treatment option for chronic hepatitis C infection

Hepatitis C currently infects more than 170 million people around the world, leading to significant morbidity and mortality. The current standard of care for HCV infection, including one of the two protease inhibitors, telaprevir or boceprevir, for 12-32 weeks, along with pegylated interferon alfa-2a (PEG-IFN-α) and ribavirin for up to 48 weeks, is unsatisfactory in many cases, either because of lack of efficacy or because of treatment-related adverse effects. There is an urgent need of new drugs with improved efficacy as well as a safety profile. Sofosbuvir, a recently approved nucleotide analog, is a highly potent inhibitor of the NS5B polymerase in the Hepatitis C virus (HCV), and has shown high efficacy in combination with several other drugs, with and without PEG-INF, against HCV. It offers many advantages due to its high potency, low side effects, oral administration, and high barrier to resistance. The efficacy and safety were demonstrated in many large and well-designed phase 2 and phase 3 clinical trials like NEUTRINO, PROTON, ELECTRON, ATOMIC, COSMOS, FUSION, FISSION, NUCLEAR, POSITRON, and the like. It is generally well-tolerated. Adverse events that occurred include: Headache, insomnia, fatigue, nausea, dizziness, pruritis, upper respiratory tract infections, rash, back pain, grade 1 anemia, and grade 4 lymphopenia; however, the exact safety profile can only be judged when this drug is actually used on a large scale.

Impact of antiepileptic drugs on bone health: Need for monitoring, treatment, and prevention strategies

Epilepsy is the most common neurological disorder affecting approximately 50 million people worldwide. In India, overall prevalence of epilepsy is reported to be 5.59/1000 population. Antiepileptic drugs (AEDs) constitute the main-stay of treatment with a large number of AEDs available in the market. High incidence of adverse effects is a major limitation with AEDs. One of the major concerns is significant metabolic effects on the bone. However, little attention has been paid to this issue because most of the bone effects remain subclinical for a long time and may take years to manifest clinically. The main effects include hypocalcemia, hypophosphatemia, reduced serum levels of Vitamin D, increase in parathormone (PTH) levels, and alterations in bone turnover markers. The CYP450 enzyme-inducing AEDs such as phenytoin, phenobarbital, carbamazepine, and primidone are the most common AEDs associated with bone disorders while the data regarding the effect of valproate and newer AEDs such as lamotrigine, gabapentin, vigabatrin, levetiracetam, and topiramate on bone metabolism and bone density are scanty and controversial. Deficiency of Vitamin D is commonly described as a cause for the bone loss in epileptic patients while others being decreased absorption of calcium, increased PTH levels, and inhibition of calcitonin secretion, etc. However, there are no formal practical guidelines for the management of bone disease among those taking AEDs. Evidence-based strategies regarding monitoring, prevention, and treatment of bone diseases in patients on AED therapy are needed.

Hypersensitivity reaction with deferasirox.

Thalassemias comprise a group of hereditary blood disorders. Thalassemia major presents with anemia within the first 2 years of life requiring frequent blood transfusions for sustaining life. Regular blood transfusions lead to iron overload-related complications. Prognosis of thalassemia has improved because of the availability of iron-chelating agents. Oral iron chelators are the mainstay of chelation therapy. Deferasirox is a new-generation oral iron chelator for once daily usage. We herein describe a patient of beta thalassemia major who developed an allergic manifestation in the form of erythematous pruritic skin rashes to the oral iron chelator deferasirox. This is a rare adverse reaction reported with deferasirox that led to a therapeutic dilemma in this particular case.

Sleep-walking a rarest side effect of zolpidem

A 46-years-old male, with past history of road traffic accident and with no current/past history of substance abuse and no family history of sleep-walking, took zolpidem 10 mg without any prescription and after few days, the patients son noticed the patient waking up in the middle of night and walking into their room with a staring expression and some incoherent speech. The patient had no memory of this event in the morning. This sleep-walking episode was attributed to zolpidem, as no medication change was made besides new start of zolpidem and the patient had no history of such episodes in the past. Zolpidem treatment was stopped, and since then, no further complaints of sleep-walking were reported.

Difference in occurrence of muscle-related adverse effects of statins among male and female geriatric patients: A cross-sectional observational study.

Background: Statins are the most widely used agents for the treatment of dyslipidaemias in geriatric patients. Muscle-related adverse effects (MRAE) are one of the most common toxicities of statins. Female gender has been mentioned as the risk factor for the development of MRAE of statins; however, there are inconclusive data regarding the difference in the occurrence of MRAE among male and female geriatric users. Objectives: The main objective was to find the difference in the occurrence of MRAE of statins among male and female geriatric statin users. Methods: In this cross-sectional, observational, comparative study, relevant patient information and MRAE associated with statin use were noted. Creatine phosphokinase (CPK) levels were obtained for all patients as this is considered as the marker for statin-induced muscle damage. The parameters were compared among male and female geriatric statin users. Results: 172 geriatric patients (86 male and 86 female statin users) were enrolled in the study. 38 (22%) geriatric statin users were found to have MRAE and significantly more number of female patients had MRAE as compared to male patients (25 vs. 13 P = 0.02). Significantly more number of female patients had elevated CPK as compared to male patients (20 vs. 8, P = 0.01). No significant difference was observed in CPK levels among male and female statin users. Conclusions: Statin-induced MRAE tend to occur with more frequency in geriatric female patients as compared to male geriatric patients; however, further research in the form of prospective studies is warranted.

Impact of regulatory spin of pioglitazone on prescription of antidiabetic drugs among physicians in India: A multicentre questionnaire-based observational study

Background & objectives: Pioglitazone was suspended for manufacture and sale by the Indian drug regulator in June 2013 due to its association with urinary bladder carcinoma, which was revoked within a short period (July 2013). The present questionnaire-based nationwide study was conducted to assess its impact on prescribing behaviour of physicians in India. Methods: Between December 2013 and March 2014, a validated questionnaire was administered to physicians practicing diabetes across 25 centres in India. Seven hundred and forty questionnaires fulfilling the minimum quality criteria were included in the final analysis. Results: Four hundred and sixteen (56.2%) physicians prescribed pioglitazone. Of these, 281 used it in less than the recommended dose of 15 mg/day. Most physicians (94.3%) were aware of recent regulatory events. However, only 333 (44.8%) changed their prescribing pattern. Seventeen of the 416 (4.1%) physicians who prescribed pioglitazone admitted having come across at least one type 2 diabetes mellitus patient (T2DM) who had urinary bladder carcinoma, and of these 13 said that it was in patients who took pioglitazone for a duration of more than two years. Only 7.8 per cent of physicians (n=58) categorically advocated banning pioglitazone, and the rest opined for its continuation or generating more evidence before decision could be taken regarding its use in T2DM. Interpretation & conclusions: Majority of the physicians though were aware of the regulatory changes with regard to pioglitazone, but their prescribing patterns were not changed for this drug. However, it was being used at lower than the recommended dose. There is a need for generating more evidence through improved pharmacovigilance activities and large-scale population-based prospective studies regarding the safety issues of pioglitazone, so as to make effectual risk-benefit analysis for its continual use in T2DM.

Difference in described indications of medicines among drug information sources in India: An issue urgently to be addressed

Background: Drug information can be obtained from various sources such as National Formularies, drug package inserts (PI), other sources such as Monthly Index of Medical Specialities (MIMS), Current Index of Medical Specialities, and the information available with the regulators. Any variation in the information available in different sources can promote irrational drug use. In this study, we assessed this variation in a sample of commonly used drugs. Materials and Methods: Fifty commonly used drugs were analyzed for any variation (both quantitative and qualitative) in information on indications as mentioned in commonly used drug information sources such as Central Drugs and Standards Control Organization (CDSCO) website, National Formulary of India (NFI), MIMS, and PI of medicines. Results: We observed a variation in average number of indications per drugs given in CDSCO (2.2 ± 0.25), NFI (3.51 ± 0.42), MIMS (2.98 ± 0.29), and PI (3.18 ± 3.52). The CDSCO and NFI did not contain information about indication for 10 and 17 drugs, respectively, while MIMS and PI contained information about all the selected drugs. A subset analysis was done for 24 such drugs which were mentioned in all the four sources and it was found that NFI had listed the maximum number of indications per drug (3.79 ± 0.53), followed by PI (3.08 ± 0.44), MIMS (3.04 ± 0.51), and CDSCO website (2.66 ± 0.37) and this difference was found to be statistically significant (P = 0.02). We also observed some gross qualitative variation regarding drug information given in different sources. Conclusion: Variation exists in the quantity and quality of information available on indications about drugs available in various sources. Necessary steps need to be taken to harmonize drug information available across various sources so as to provide reliable and uniform drug information thereby promoting rational drug use.