Comparative Efficacy and Safety of Clonazepam versus Nortrptilline on Menopausal Symptom among Forty Plus Women: A Prospective, Open-Label Randomized Study.

AIMS AND OBJECTIVES: The aim of this study is to compare the effect of clonazepam and nortryptiline on menopausal symptoms in above 40 years women. MATERIALS AND METHODS: A prospective, randomized, open-label comparative study was conducted in a tertiary care teaching hospital for 1 year. Patients were randomized into two groups. Both the groups had 60 patients, out of which Group A had 39 menopausal patients and Group B had 31 menopausal patients, respectively. Group 1 received tablet clonazepam 0.5 mg bed time orally daily. Group 2 received tablet nortryptiline 25 mg bed time orally daily. The primary efficacy end points were effect on menopausal symptoms evaluated by at 0, 4, and 8 weeks. RESULTS: Mean age since menopause was 45 ± 4.06 years, and the mean number of years since menopause was 9.18 ± 7.59 years clonazepam and nortryptiline recorded statistically comparable effect with numerical superiority of nortryptiline both at 4 and 8 weeks on mean Menopausal Symptom Score, thereby indicating that both the drugs may have directly/indirectly improved the mean menopausal symptoms equally. Improvement in the clonazepam group was numerically and statistically more than nortryptiline group at 4 and 8 weeks on mean Vasomotor Symptom Score with P < 0.01 in clonazepam group and P < 0.05 in nortryptiline group both at 4 and 8 weeks. Both the drugs showed comparable results on psychosocial symptom score both at 4 and 8 weeks with numerical superiority in nortryptiline group. Clonazepam group showed more improvement on mean physical score than nortryptiline group numerically and statistically. Both the drugs showed comparable results on mean sexual symptom score at 4 weeks, but nortryptiline proved to be statistically better at 8 weeks P < 0.01 versus P < 0.05 in clonazepam group. CONCLUSION: Clonazepam and nortryptiline recorded statistically comparable effect at 4 and 8 weeks on mean menopausal symptom. Both the drugs were equally safe and did not recorded any serious Adverse Drug Reaction (ADRs).

Comparative Efficacy and Safety of Clonazepam versus Nortriptyline in Restless Leg Syndrome among Forty Plus Women: A Prospective, Open-Label Randomized Study.

AIMS AND OBJECTIVES: The aim of this study is to compare the effect of clonazepam and nortriptyline on rate, frequency, and severity of restless leg syndrome (RLS) in above 40 years women suffering from RLS. MATERIALS AND METHODS: A prospective, randomized, open-label comparative study was conducted at a tertiary care teaching hospital for 1 year. Restless legs syndrome (RLS) diagnosis was based on four essential clinical criteria established by the International RLS Study Group in 2003. Patients were randomized into two groups. Group 1 received tablet clonazepam 0.5 mg bedtime orally daily. Group 2 received tablet nortriptyline 25 mg bedtime orally daily. The primary efficacy endpoints by the International Restless leg Syndrome Scale (IRLS) were evaluated at 0, 4, and 8 weeks. Adverse drug events and safety assessment for vital signs such as blood pressure, pulse, heart rate, waist circumference, and body mass index were compared between two groups. RESULTS: Effect on mean IRLSS was statistically more in clonazepam group in comparison to nortriptyline group with comparable results at 8 weeks (P < 0.001), but at 4 weeks, nortriptyline showed less improvement (P < 0.01) versus P < 0.001 in nortriptyline group. Thus, nortriptyline reported relatively more improvement on IRLSS numerically in comparison to clonazepam. Nortriptyline proved to be statistically better in improving the frequency of RLS with comparison to clonazepam, whereas the results were comparable with regard to rate and the severity of RLS. Both the groups were relatively safe and did not produce any change in biochemical parameters and were free from any serious or severe adverse events and overall, both the treatments were well tolerated. CONCLUSION: Both the drugs provided clinically and statistical significant effect on RLS when compared with their respective baselines. However, nortriptyline proved to be statistically better in improving the frequency of RLS in comparison to clonazepam, whereas the results were comparable with regard to rate and the severity of RLS on intergroup comparison. Both the drugs were well tolerated.

A Prospective, Randomized, Open-Label Study Comparing the Efficacy and Safety of Clonazepam versus Nortriptyline on Quality of Life in 40+ Years old Women Presenting with Restless Leg Syndrome.

INTRODUCTION: Restless legs syndrome (RLS) is a neurological disorder characterized by an urge to move the legs usually accompanied by unpleasant leg sensations. RLS also impacts health related quality of life (QOL) in patients suffering from it. Further, it affects women more than men. Although a voluminous literature of studies is available evaluating the role of benzodiazepines (clonazepam and antidepressant (nortriptyline) in the treatment of RLS, but to the best of our knowledge, no comparative study is available comparing both of these drugs for efficacy and safety for the treatment of RLS QoL among 40 + years old women. MATERIALS AND METHODS: A prospective, randomized, open label comparative study was conducted in Postgraduate Department of Pharmacology in collaboration with the Department of General Medicine, Government Medical College, Jammu, a tertiary care teaching hospital for 1 year. CONCLUSION: Clonazepam proved to be significantly better in improving RLSQoL score. Difference between respective baselines of both groups was statistically insignificant.

Zidovudine-induced nail hyper-pigmentation in 45-year-old women prescribed for HIV/tuberculosis co-infection.

Zidovudine is an important component of first-line antiretroviral treatment regimens used to manage HIV and tuberculosis (TB) co-infection. Nail pigmentation is documented both in adult as well as pediatric HIV patients, but to the best of our knowledge, it has not been reported in 45-year-old women of HIV/TB co-infection. Such an adverse drugs reactions (ADR), although is harmless and reversible, psychological aspects of such ADR may be immense to the extent that it can negatively affect the compliance and result in therapeutic failure. Thus, it is worth reporting.

Bleomycin Containing Chemotherapeutic Regimen Induced Acquired Partial Lipodystrophy.

Bleomycin toxicity predominantly affects the skin and lungs. Cutaneous toxicity classically known to present with bleomycin are flagellate erythema and drug rash. We hereby report an isolated case of (bleomyicn)-induced acquired partial (lipodytrophy) having potential cosmetic implications in a young women prescribed postoperatively following a case of germ cell carcinoma of ovary (endodermal sinus tumor).

Adverse Drug Reaction Profile in Patients on Anti-tubercular Treatment Alone and in Combination with Highly Active Antiretroviral Therapy.

BACKGROUND AND OBJECTIVES: Adverse drug reactions are very common among patients on anti-tubercular treatment alone or in combination with highly active antiretroviral therapy but comparatively studied very less. Hence, the current study was done to evalaute the adverse drug reaction (ADR) profile in patients receiving anti-tubercular treatment (ATT) and ATT with highly active antiretroviral therapy (HAART). MATERIALS AND METHODS: A one year prospective, cross-sectional observational study was undertaken using suspected adverse drug data collection form available under Pharmacovigilance Programme of India. RESULTS: Seventy four patients receiving ATT & 32 patients on both ATT & HAART presented with 74 and 45 adverse drug events (ADE) respectively. Males were more affected than females in both the groups. DOTS category- 1 regimen was mostly responsible for ADE in both the groups. Epigastric pain was the most common ADE in TB patients, while anaemia was the most common presentation in TB with HIV group. On comparison, ADE rate of TB with HIV co-morbid patients was more (55.8%) than TB patients (0.36%) (p < 0.001). Urban population presented more with ADR in TB/HIV group unlike rural population in TB group (p<0.0001). Whereas, illiterate were more involved in TB group unlike literate in TB/HIV group (p<0.05). Type A reactions were more common in TB group (p < 0.001). Addition of drugs for the management of ADR events was more in TB/HIV group (p < 0.001) as compared to TB group. Rest all the parameters were comparable. CONCLUSION: The study underscores that concomitant HAART and ATT, result in more ADRs in comparison to ATT alone demanding collaboration & integration of National AIDS Control programme and PvPI to enhance drug safety in this field.

Upper gastrointestinal bleed in a post menopausal woman due to combination of high first dose aspirin and clopidogrel prescribed for acute coronary syndrome.

Combination of aspirin, clopidogrel and enoxaparin remains the standard treatment for acute coronary syndrome (ACS) but is known to increase the incidence of upper gastrointestinal bleed (UGIB). We hereby report an unusual case of gastrointestinal bleed (GIB) as it resulted inspite of proton pump inhibitor (PPI) prophylaxis within the second day of treatment in a post-menopausal woman (PMW) with high first dose of aspirin clopidogrel dual combination in a patient of ACS.

Drug-induced diseases (DIDs): An experience of a tertiary care teaching hospital from India.

BACKGROUND & OBJECTIVES: Drug-induced diseases (DIDs) are well known but least studied. Data on DIDs from India are not available. Hence, this retrospective cross-sectional study was undertaken using suspected adverse drug reaction (ADR) data collected form Pharmacovigilance Programme of India (PvPI) to evaluate profile of DIDs over two years, in a tertiary care teaching hospital from north India. METHODS: The suspected ADRs in the form of DID were evaluated for drug and disease related variables and were classified in terms of causality. RESULTS: DID rate was 38.80 per cent. Mean duration of developing DIDs was 26.05 ± 9.6 days; 25.16 per cent had more than one co-morbid condition. Geriatric population (53.99%) accounted for maximum DIDs followed by adult (37.79%) and paediatric (8.21%). Maximum events were probable (93.98%) followed by possible (6.04%). All DIDs required intervention. Gastritis (7.43%), diarrhoea (5.92%), anaemia (4.79%), hypotension (2.77%), hepatic dysfunction (2.69%), hypertension (1.51%), myalgia (1.05%), and renal dysfunction (1.01%) were some of the DIDs. Anti tubercular treatment (ATT), anti retroviral treatment (ART), ceftriaxone injection, steroids, non-steroidal anti-inflammatory drugs, antimicrobials and anticancer drugs were found as commonly offending drugs. INTERPRETATION & CONCLUSIONS: Our findings show that DIDs are a significant health problem in our country, which need more attention.

Comparative evaluation of efficacy and safety of combination of metformin-vidagliptin versus metfromin-glimepiride in most frequently used doses in patients of type 2 diabetes mellitus with inadequately controlled metformin monotherapy-A randomised open label study.

AIM AND OBJECTIVE: The aim was to evaluate and compare the efficacy and safety of combinations of metformin-vidagliptin (MF-VG) and metfromin-glimepiride (MF-GP) in type 2 diabetes mellitus (T2DM) patients. MATERIALS AND METHODS: A comparative randomized open-label trial was conducted on patients with uncomplicated T2DM, on treatment with MF for 4 months out of which on maximum tolerated dose of MF (1000-2500 mg/day) for 4 weeks, glycosylated Haemoglobin [HbA1c]) ≥6.5%, fasting blood glucose (FBG) ≥126 mg/dl and post prandial glucose (PPG) ≥200 mg/dl were included in the study. Patients were randomized to receive MF (500 mg BD) + VG (50 mg BD) or MF (500 mg BD) + GP (2 mg BD). RESULTS: Both the groups caused significant decline in blood glucose levels both FBG as well as PPG levels (P < 0.01). HbA1c was also reduced significantly in both groups at 12 weeks (P < 0.01). Total serum cholesterol, triglycerides, low-density lipoprotein and very low-density lipoprotein decreased significantly, whereas high-density lipoprotein levels increased significantly from baseline levels in both the groups (P < 0.01). Intergroup comparison failed to demonstrate any statistical difference on all of above parameters. Both weight and body mass index did not alter statistically from baseline in either of the groups as well as demonstrated no difference statistically on comparison (P > 0.05). At the end of the study, both liver functions tests and renal functions tests remained unaltered statistically and within normal clinical range in both the groups (P > 0.05). However, hypoglycemia and other adverse events were numerically more in MF + GP group. CONCLUSION: Both the regimens on comparison revealed similar efficacy and safety thereby failing to prove superiority over each other.

Cycloserine induced psychosis with hepatic dysfunction.

With the increase in the cases of multidrug resistance tuberculosis, second line anti-tubercular drugs like the cycloserine are being prescribed frequently. Isoniazid and ethambutol are reported to cause psychosis like state; however, few reports of cycloserine induced psychosis are available. To the best of our knowledge, this is the first case of cycloserine induced psychosis with hepatic dysfunction.

Under-reporting of adverse drug reactions: a challenge for pharmacovigilance in India.

AIM: The aim was to evaluate the extent and factors responsible for underreporting (UR) of adverse drug reactions (ADRs) in India. MATERIALS AND METHODS: A retrospective observational, cross-sectional prospective questionnaire-based analysis was undertaken to evaluate the extent and factors for UR of ADRs in pharmacovigilance. RESULTS: At the time, this report was prepared, 90 ADR Monitoring Centers (AMC) were operational in India. Indian AMC functional rate was 56.45%. The average number of Individual Case Safety Reports reported by our center via VigiFlow per month was 48.038. In a period of the 3 years the total number of ADRs reported was 3024. The average number of reports per month was 80.08. Active surveillance versus spontaneous reporting contributed 66.13% versus 33.86% of the total ADRs (P < 0.0001). Outpatient Department (OPD) contribution was 76.05% and indoor contribution was 23.94% of total reports (P < 0.0001). Department of Medicine (33%), followed by oncology (19.27%) and chest disease (13.49%) contributed maximally. The contribution of Pharmacology ADR monitoring OPD was 16.20%. Eye, ear, nose and throat and surgery, private Medical Colleges, hospitals in periphery, sub-district and district contributed no ADRs. ADR detection rates by clinical presentation, biochemical investigation and diagnostic tools were 84.33%, 14.57%, and 1.09% respectively (P < 0.0001). Reporting by postgraduate, registrars, consultants and nurses were 72.65%, 6.58%, 16.56% and 4.19% respectively (P < 0.0001). PG students in Pharmacology contributed an average number of 5.61 ADR reports/month. The lack of knowledge and awareness about Pharmacovigilance Programme of India (PvPI), lethargy, indifference, insecurity, complacency, workload, lack of training were the common factors responsible for UR. Major academic activity, exams, thesis and synopsis submission time influenced reporting of ADRs by postgraduate students. CONCLUSION: UR is a matter of concern PvPI. Multiple interventions are needed to improve ADR reporting.

To evaluate efficacy and safety of Caralluma fimbriata in overweight and obese patients: A randomized, single blinded, placebo control trial.

AIM: The aim of the following study is to evaluate the efficacy and safety of Caralluma fimbriata extract (CFE) in overweight and obese individuals in a prospective, randomized, placebo controlled trial. MATERIALS AND METHODS: Commercially available CFE was assessed in overweight and obese individuals. A total of 89 patients were randomized into a treatment group (n = 47) and placebo group (n = 42) to receive either CFE in the form capsules/oral 500 mg b.d. for 12 weeks or matching placebo in similar way. Patients were evaluated clinically and biochemically at 4, 8 and 12 weeks for anthropometric measurements, appetite, biochemical investigations and other safety parameters. RESULTS: At the end of study period both CFE and placebo for 12 weeks caused only numerical reduction in weight, body mass index, waist circumference, hip circumference and waist hip ratio in overweight and obese individuals. However, these parameters failed to attain significant statistical levels (P ≥ 0.05). CFE and placebo both failed to elucidate any modification of the appetite. There were no significant changes in the biochemical and clinical parameters in both the test and placebo group. However, CFE was well-tolerated and adverse events noted were mild and transient in nature. CONCLUSION: A commercially available extract of CFE in an oral dose of 1 g/day claimed to have anti-obesity effect failed to yield any positive results on anthropometry and appetite in overweight and obese individuals beyond placebo. There were also no significant differences in the clinical and biochemical parameters. However, CFE was well tolerated. Thereby, underscoring the need to carry more research before CFE is recommended as an anti-obesity drug.

First Indian study evaluating role of biochemical investigations and diagnostic tools in detection of adverse drug reactions.

AIM OF STUDY: To evaluate the role of biochemical investigations (BI) and diagnostic tools (DT) in ADR detection. MATERIALS AND METHODS: An observational prospective cross-sectional study was done using suspected ADR data collection form. RESULTS: A total of 2381 ADR related events were recorded in two years. Total number/percentage of biochemical abnormalities (BA) related ADR detection rate was 14.57% and of DT was 1.091% in contrast to 84.33% recorded with clinical presentation. Maximum cases were inward patients (87.13%), 67.02% were recorded by active surveillance. ADR detection rate at one point & detection on follow up was 56.31% Vs 46.38%. ADR detection rate of ECG, endoscopy, X-ray were 0.57%, 0.22%, 0.22% and of CT scan, MRI, DEXA scan, USG and biopsy was 0.04% each. Maximum ADRs were severe/serious, latent and Type-A in nature. Anemia (4.6%), followed by liver dysfunction (2.8%), renal dysfunction, electrolyte imbalance, hyperglycemia (1.1% each), abnormal coagulation profile (1%), decrease platelet count (0.8%), hypoglycemia (0.7%) were the most common BAs. Anti retroviral drugs (ART), tirofiban and methotrexate accounted for anemia, ART and anti tubercular drugs for liver & renal dysfunction, insulin for hypoglycemia, tirofiban, paclitaxel, capecipabine and ifosfamide for thrombocytopenia, hematuria by enoxaparin & dyslipidemia with ART were common ADRs. CONCLUSION: BI and DT can play very important role in ADR detection.

Comparative efficacy and safety of triple therapy (ramipril, telmisartan, hydrochlorothiazide) vs dual anti hypertensive therapy (ramipril or telmisartan, hydrochlorothiazide) in stage 2 hypertensive patients.

AIM: To evaluate the comparative efficacy and safety of ramipril 5mg plus hydrochlorothiazide 12.5mg (R + HCTZ), telmisartan 40mg plus hydrochlorothiazide12.5mg (T + HCTZ) and ramipril 2.5mg plus telmisartan 20mg plus hydrochlorothiazide12.5mg (R + T + HCTZ) in patients with stage 2 hypertension. MATERIALS AND METHODS: A prospective, open label, randomized comparative study was conducted to study the comparative efficacy and safety of R+HCTZ (group 1), T+HCTZ (group 2)and R+T+TCTZ (group3) in 88 patients with stage 2 hypertension without co-morbid conditions. Echocardiography was done to assess left ventricular function. Patients were followed up to 24 weeks and any ADR occurring in this period was recorded. RESULTS: All the three treatment groups showed significant fall in both systolic and diastolic blood pressure compared to the baseline scores (p<0.0001). Intergroup comparison did not reveal any significant difference. Total number of adverse drug events reported were 15. Group III had higher percentage ADRs. Dry cough (8) was most common ADR. The echocardiography parameters did not change from baseline values with all three treatment regimens. CONCLUSION: All three medications were of equal efficacy in patients with stage 2 hypertension without co morbid conditions, failing to prove superiority over each other.

Prevalence of vitamin d deficiency among Indian menopausal women and its correlation with diabetes: A first Indian cross sectional data.

AIM AND OBJECTIVE: To evaluate prevalence of Vitamin D deficiency and establish any correlation between diabetes and vitamin D deficiency among postmenopausal women. MATERIALS AND METHODS: The 25-hydroxy vitamin D [25 (OH) D] concentrations were measured by competitive in-vitro quantitative immunoassay. The subjects were classified as vitamin D-deficient, insufficient or sufficient on the basis of 25 (OH) D concentrations of < 20 ng/mL, 20-30 ng/mL or > 30 ng/mL respectively. The apparently normal postmenopausal women (PMW) were subjected to fasting blood sugar levels to analyse any correlation between vitamin D deficiency and diabetes. RESULTS: Vitamin D deficiency was observed in 53.35% of the population, 19.48% had insufficiency and 26.83% had adequate Vitamin D levels. In 12.14% of the study population fasting blood glucose was > 110 mg/dl and rest of the subjects were between the normal range which is 70-110mg/dl. Correlation between raised blood sugar levels and Vitamin D deficiency among PMW was non-significant (P = 0.324). CONCLUSION: High prevalence of vitamin D deficiency exists among apparently healthy Indian PMW. However, the current study failed to show any statistical correlation between vitamin D deficiency and existence of diabetes, which may be due to small sample size.

Gastrointestinal bleed induced by a fixed dose combination of rabeprazole and diclofenac sodium.

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause gastrointestinal (GI) bleed. Co-administration of proton pump inhibitors (PPIs) has been widely suggested as one of the strategies to prevent these GI complications among NSAIDs users. Herein, we present a case of severe GI bleeding in a patient taking fixed dose combination (FDC) of rabeprazole (20 mg) and diclofenac sodium (100 SR).

Comparative evaluation of aliskiren, ramipril, and losartan on psychomotor performance in healthy volunteers: A preliminary report.

AIM: To compare the effects of aliskiren, ramipril, and losartan on the psychomotor performance in healthy volunteers. MATERIALS AND METHODS: In this preliminary, single-dose, open-label, cross-over study conducted in 12 healthy volunteers, psychomotor assessment was carried out by four tests: Simple reaction time (SRT), multiple choice reaction time test (MCRT), critical flicker fusion frequency threshold test (CFFT), and tracking performance test (TPT). Each volunteer received a single dose of each of the three test drugs with a washout period of 10 days between different test sessions and then evaluated for post-drug scores at 2-h intervals up to 12 h and then at 24 h. The changes from the baseline scores by the test drug were statistically analyzed. RESULTS: All the three antihypertensive drugs caused significant improvement in a similar fashion on SRT, MCRT calculated as error index, CFFT, and TPT. Aliskiren caused numerically more improvement than the other two test drugs, suggesting better cognitive profile. However, inter-drug comparisons were nonsignificant. CONCLUSION: The results of the study highlight improvement of the cognitive functions equally by ramipril, losartan, and aliskiren. The results of the study could be of immense clinical utility in ambulatory hypertensive patients especially engaged in sensory-motor coordination tasks like driving and operating on mechanical tools.

Angioedema due to fixed dose combination of telmisartan plus ramipril.

The risk for angioedema has been suggested lower with angiotensin receptor blockers (ARBs) than with angiotensin-converting enzyme inhibitors (ACEIs) or aliskiren. Many isolated reports do exist, reporting angioedema with ARBs such as olmesartan, valsartan, losartan and telmisartan. To the best of our knowledge this is the first case report of telmisartan plus ramipril fixed dose combination leading to angioedema from India questioning the rationality of ARBs plus ACEIs combination in the treatment of hypertension.