Journal of Pharmaceutical Research

Remya Antony ¹, Sandhya Lakshmi ¹, Akhila Sivadas ², Wesley M. Jose ³, Neeraj Sidharthan ⁴, K. Pavithran ⁵

Affiliations
1 Amrita School of pharmacy, IN
2 Department of Oncology, Amrita Institute of Medical Sciences (AIMS), Kochi, IN
3 Department of Medical Oncology & Hematology, Amrita Institute of Medical Sciences (AIMS), Kochi, IN
4 Department of Hematology, Amrita Institute of Medical Sciences (AIMS), Kochi, IN
5 Department, Medical Oncology & Hematology, Amrita Institute of Medical Sciences (AIMS), Kochi, IN

Abstract

Tumour Lysis Syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Hyperuricaemia is one of the prominent features of TLS which if not adequately prevented or treated can lead to renal failure requiring dialysis.

Rasburicase is the most recent agent indicated for treating TLS which is a recombinant urate oxidase enzyme that will oxidize uric acid to allantoin, a metabolite with 5-10 fold greater solubility than uric acid and reduces serum uric acid (SUA) levels within four hours of administration.

The recommended dose according to US Food and Drug Administration is 0.15 to 0.2 mg/kg/d for 5 days.

This retrospective study was aimed to evaluate the clinical efficacy of fixed low dose Rasburicase (1.5mg) in hyperuricemic patients who was admitted under Medical Oncology, Department in Amrita Institute of Medical Sciences And Research Centre, Kochi.

55 patient received Rasburicase during the study period of approximately 3years (July 2012 - June2015). 52 patients (94.54%) showed reduction in serum uric acid level in day 1 and by day 3.All patients (100%) had significant reduction in SUA after administration.

In this study we found that Rasburicase significantly lowered the serum uric acid level. Single dose of 1.5mg of rasburicase was found to be effective in rapidly correcting the hyperuricemia in all these patients. This can lead to considerable cost saving in the treatment and prevention of TLS occurring in patients with both solid tumors and hematological malignancies.

The advantage of Rasburicase over Allopurinol is its rapid onset of action, efficacy in patients with renal dysfunction and is well tolerated with very few side effects.

Keywords

Tumour Lyses Syndrome, Serum Uric Acid, Rasburicase.

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K. Sukanya Mathew ¹, C. Parvathy Priya ¹, Akhila Sivadas ², K. Pavithran ³

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Department of Medical Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Department Medical Oncology, Amrita Institute of Medical Sciences, Kochi, IN

Abstract

Regorafenib is indicated for patients with metastatic colorectal cancer who have had previous treatment with multiple regimens. Here we report a 45 year old female who had carcinoma recto sigmoid and hemicolectomy with stage III disease.

She had adjuvant chemotherapy with 12 cycles of FOLFOX regimen [June 2011 - December 2011] and relapsed after 7 months. Then she was treated with Irinotecan 5FU/LV/Avastin for 6 cycles as a second line. She had a 6 months PFS from July 2012 - December 2012]. From January 2013 to October 2013, she was on follow up and the USG abdomen and PET scan showed relapse of the disease and so she was started on regorifinib 160 mg OD as the third line since November 2013.

After 2 weeks, she developed jaundice and hand foot syndrome and hence the dose was modified to 2 tablets/day. At this dose level she was tolerating it well and showed good clinical response. After 22 monthsrevaluation with CT scan, CEA showed progressive disease and hence chemotherapy was done again. She is in good performance status now with stage IV disease even after 50 Months from the diagnosis of stage IV cancer. Before the availability of these agents, the survival of these patients was less than 6 months. We emphasize that Regorifenib is an important role in the management of refractory metastatic colorectal cancer as a third line chemotherapy which has been approved by the US FDA.

Keywords

Regorafenib, Progression Free Survival (PFS).

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Malini Muraleedharan Nair ¹, Hisham Ahamed ², Akhila Sivadas ³

Affiliations
1 Amrita School of Pharmacy, AIMS , Kochi, IN
2 Cardiology Department, AIMS, Kochi, IN
3 Department of Oncology, AIMS, Kochi, IN

Abstract

Anti-arrhythmic drugs like amiodarone have the potential to prolong QT intervals which can result in Torsades de pointe arrhythmia.

Eventhough it has few pro-arrhythmic effects, it has a rare chance (<2%) of causing QT prolongation which is associated with TdP (torsado de pointes). If TdP is rapid or prolonged, it can lead to ventricular fibirillation and sudden cardiac arrest.

We report on a case of a 50 year old male who is admitted with Atrial Flutter (2:1 AV block). He was started on oral Amiodarone (400mg/day) and was planned for elective DC version. His serial ECG was monitored and he converted to sinus rhythm (HR-56/min) on the third day. Subsequent ECGs showed progressive prolongation of the QTc interval (calculated with Bazet's formula). Amiodarone dose was reduced (100mg/day) and further monitoring revealed gradual normalisation of the QTc interval.

Review of the patients medication did not reveal the presence of any other drug capable of prolonging QTc. It has been well recognized that a prolonged QT interval (congenital or acquired) on the surface ECG is associated with an increased risk of TdP and sudden death.

By far, the most common cause of acquired long QT syndrome is drug induced with anti-arrhythmic drugs being the most commonly implicated. Co- administration of multiple drugs especially with other QT prolonging drugs and hepatic cytochrome P450 CYP3A4 iso-enzyme inhibitors must be avoided. Health care providers must be careful about the adverse effect (TdP) which is a potentially fatal condition.

Keywords

Amiodarone, Atrial Flutter, TdP, Bazet's Formula.

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Delcey Reachel Varghese ¹, Mary Sruthi Johny ², Akhila Sivadas ³, K. Pavithran ⁴

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Pharmacovigilance of India, AIMS, IN
3 Oncology Department, AIMS, IN
4 Department Medical Oncology & Hematology, AIMS, IN

Abstract

Adverse drugs reactions (ADRs) are noxious, unintended, and undesirable effects that occur as a result of drug treatment at doses normally used in man for diagnosis, prophylaxis, and treatment.

Due to the limitations of clinical trials, it is not possible to have a complete knowledge regarding all ADRs at the time of drug approval, necessitating drug safety follow-ups after releasing to the market. Pharmacovigilance has been defined as a science regarding the detection, assessment, understanding and prevention of ADRs, with its ultimate goal being improving pharmacotherapy. The most important finding of this study is the significant improvement in ADR reporting after education and establishment of Pharmacovigilance Centers.

In this study we collected and analyzed the adverse drug reactions reported by clinical pharmacist from oncology department to pharmacovigilance, 101 adverse drug reaction cases were reported from oncology to pharmacovigilance for a period of 11 months (September 2014-july 2015).

It was found that out of 101 cases, 51 males (50.49%) and 50 females (49, 50%) ADR cases were reported. Among which most reported were from between the age group 60-70 yrs (24 cases with 23.76%) with case of ALL (24 cases with 23.76%) which was treated with L-Asparginase.From the whole study done, itching (24 cases with 23.76%) was the most occurant Adverse Drug Reaction.

As a clinical pharmacist, it is our duty to encourage and educate other healthcare professionals for reporting adverse drug reactions.

We hereby conclude that clinical pharmacy service has an excellent role in designing and conducting the pharmacovigilance system in the hospitals by establishing specified centers with clearly defined objectives and tasks.

Keywords

PV (Pharmacovigilance), ADRs (Adverse Drug Reactions).

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Aloysius James ¹, Akhila Sivadas ², K. Pavithran ³

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Department of Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Department Medical Oncology & Hematology, AIMS, Kochi, IN

Abstract

INTRODUCTION: Abiraterone acetate is a selective inhibitor of androgen biosynthesis that potently and irreversibly blocks CYP17, a crucial enzyme in testosterone and oestrogen synthesis, resulting in virtually undetectable serum and intratumoral androgens.

AIM: To study the clinical outcome of Abiraerone Acetate in castration resistant prostate cancer patients, by measuring their PSA (Prostate specific antigen) value.

To find out the effect of Abiraterone acetate on lab parameters(Serum Creatinine. Potassium, CBC) by administering this drug.

METHODS: This is a retrospective analysis to evaluate the efficacy and safety of abiraterone acetate in castration resistant prostate cancer patients. 14 men with CRPC who experienced treatment failure with one or more lines of treatment (hormonal manipulation or chemotherapy) were given abiraterone acetate (1,000 mg daily) with prednisone (5 mg twice daily).

RESULTS AND DISCUSSION: 42% patients shows good response in reduction in PSA value and 16% had progression and 42% had stable disease. Haemoglobin, Potassium and Serum Creatinine levels were not affected by Abiraterone. One patient had severe GI intolerance and the drug had to be stopped. In this study the final analysis shows that abiraterone acetate significantly lowered the PSA value and prolonged progression free survival in patients with metastatic castration-resistant prostate cancer who have progressed after first line or second line treatment. The median duration of drug exposure and overall average median survival of CRPC who received AA was found to be 11.1 months [range 3-18]. Abiraterone plus prednisone therapy can be given orally in an outpatient setting, providing an additional benefit for both patients and clinicians.

Keywords

Abiraterone Acetate (AA), Prostate-Specific Antigen (PSA), Castration-Resistant Prostate Cancers (CRPCS).

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Chanshi Chandran ¹, Karthika Ashok ¹, Raghuveer Prabhu ², Akhila Sivadas ³

Affiliations
1 Amrita school of pharmacy, Kochi, IN
2 Department of Medical Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Department of Oncology, Amrita Institute of Medical Sciences, Kochi, IN

Abstract

Hydroxyurea is an anti cancer chemotherapeutic drug .For high risk patients of essential thromocytosis (ET) , interferon and hydroxyurea are available agents in India to reduce their platelet count.

Interferon is not an attractive agent due to its parentral mode of delivery and systemic side effects. Here, we aim to evaluate the efficacy of hydroxyurea in these subset of patients to normalize their platelet counts.

This Retrospective study was conducted in the department of medical oncology and hematology at Amrita institute of medical science. We collected the data by reviewing the electronic medical records of the patients with ET in which 23 patients were seen to be at high risk for thrombotic events,Out of these 23 high risk patients 17 were females and 6 were males and belonged to the mean age of 55.17 years.

We found that 37.5 % showed complete response, 41.67 % showed partial response and 16.67 % showed no response. From this study we could observe that only 80% of patients benefited from hydroxyurea therapy and there is unmet need for an oral cytoreductive agent with good safety profile in ET.

Keywords

Hydroxyurea, Essential Thrombocytosis( ET), Cytoreductive Agent.

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Bini Vincent ¹, Akhila Sivadas ², Ameer Shahjahan ¹, K. Pavithran ³

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Department of Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Medical Oncology & Hematology, Amrita Institute of Medical Sciences, Kochi, IN

Abstract

Oxaliplatin is a third-generation platinum analogue that is mainly used in the treatment of advanced colorectal cancer. The reported incidence of hypersensitivity reactions to oxaliplatin, especially after multiple cycles of therapy, is less than 1%.

Anaphylactic shock refers to anaphylaxis vasodilation , resulting in low blood pressure, severe bronchoconstriction.

Here we report a patient with adenocarcinoma of the colon who developed an anaphylactic shock following oxaliplatin administration during the sixth cycle of combination chemotherapy with FOLFOX-4 regimen (Oxaliplatin, 5-fluorouracil and leucovorin), despite the usual premedication with dexamethasone.

All the initial 10 cycles of chemotherapy with FOLFOX-4 was very well tolerated. He had a grade 1 neuropathy after his 9^th cycle and grade 2 in 10^th cycle. During his 11th cycle of chemotherapy, immediately after starting oxaliplatin, he developed severe hypotension, tachycardia, painful burning sensation all over the body and diffuse pruritis and was diagnosed to have anaphylactic shock. He responded to adrenalin, intravenous steroids and IV fluids and the reaction got resolved completely. After stabilization chemotherapy was continued by skipping oxaliplatin.

A Taiwan study in 2006 by Lee et al reported that 4 cases out of 303 patients who developed serious adverse reactions following oxaliplatin with an incidence of 1.32%.

Previous studies showed that anaphylaxis occurs after 7-9 cycles. Our patient developed during the 11^th cycle. Physicians should be vigilant on every patient on oxaliplatin especially after the first 6 cycles.

Since data are insufficient to proveprolongation of infusion time as well as the prophylactic use of steroid and antihistamines is effective, the rechallenge with oxaliplatin should be done only in selected patients.

Keywords

Oxaliplatin, Anaphylaxis.

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S. Sandhya Lekshmi ¹, Remya Antony ¹, Akhila Sivadas ², K. Pavithran ³

Affiliations
1 Amrita School of Pharmacy, Amrita Institute of Medical Sciences and Research Centre, Kochi, IN
2 Department of Oncology, Amrita Institute of Medical Sciences and Research Centre, Kochi, IN
3 Department Medical Oncology & Hematology, Amrita Institute of Medical Sciences and Research Centre, Kochi, IN

Abstract

Primary cutaneous large B-cell lymphoma, leg type (PCLBCL-LT), is a rare and aggressive neoplasm. Patients with PCLBCL, LT present with red to bluish nodules or tumors on one or both lower legs. Only about 10% to 15% of these patients are noted to develop lesions outside of the lower extremities. Compared with other subtypes of PCBCLs (PCMZL and PCFCL), these tumors are more aggressive with worse outcomes, as they frequently disseminate to lymph nodes and visceral organs.

Here we report a 56 year old male with multiple smooth swellings of varying size over the right shin with edema, which started as erythematous patches. He was treated with topical steroids and oral antibiotics. But lesion progressed so he was underwent skin biopsy. The biopsy reported as Primary cutaneous large B-cell lymphoma, leg type.

Initial PET-CT scan showed Non Hodgins lymphoma. He was staged to have stage IV. He was treated with Rituximab, cyclophosphomide, doxorubicin, vincristine, and prednisone (R-CHOP). After 4 cycles he attained complete response clinically and by PET-CT scan. After 6 cycles of R-CHOP, he was given local radiotherapy also. Post treatment he is on regular follow up and is doing well.

Keywords

PCLBCL-LT (Primary Cutaneous Large B-Cell Lymphoma, Leg Type), Non Hodgkins Lymphoma, R-CHOP.

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Dhanya Susan ¹, Mary Sruthi Johny ², Akhila Sivadas ³, Thrasiama Thomas ⁴

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Pharmacovigilance Programme of India, Amrita Institute of Medical Sciences, Kochi, IN
3 Department of Oncology, Amrita Institute of Medical Sciences, Kochi, IN
4 Amrita Institute of Medical Sciences, Kochi, IN

Abstract

Steven Johnson Syndrome (SJS) is an acute systemic disorder presenting as severe mucosal erosions with erythematous , cutaneous macules or atypical targets.

Here we discussed a case of 39 year old women who developed drug induced steven Johnson syndrome (SJS). she was on Amoxicillin - Clavulanic acid(penicillin antibiotic) and Paracetamol for the management of fever and cough. Later she developed peeling of skin over lips , painful reddish lesions over 75% of her skin surface including back of trunk, front of chest, hands, legs, palms and soles. Her eyes, mouth and genital organs were also affected.

Blood investigations revealed LFT was elevated herpes simplex virus IgM was borderline and IgG HSV was elevated( 5.5). her blood cultures were negative.

Patients symptoms started to develop on 2^nd day of treatment with amoxicillin/clavulanic acid( Augmentin) 625mg OD. adverse reaction was managed with IV steroids,oral cyclosporine and other conservative measures. After 2 weeks her lesions subsided and steroids were tapered. During her discharge, she was haemodynamically stable, LFT was improved and her lesions were exfoliating.

Health care providers must be careful regarding the adverse effects of the drugs especially the one is the Stevens-Johnson syndrome (SJS) which is a potentially fatal condition with mortality rate below 5 percent.

This reaction is of shorter duration and with rechallenge. The most commonly and widely prescribed drug regimens should also be used judiciously and continuously monitored to prevent such a fatal adverse drug reactions.

Keywords

Steven Johnson Syndrome (SJS).

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Karthika Ashok Kumar ¹, Akhila Sivadas ², A. S. Ananya Dutt ¹, Chanshi Chandran ¹, M. V. Thampi ³, K. Pavithran ⁴

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Department of Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Department of Pathology, Amrita Institute of Medical Sciences, Kochi, IN
4 Department Medical Oncology & Hematology, Amrita Institute of Medical Sciences, Kochi, IN

Abstract

The discovery of 1p and 19q chromosomal arms deletion in glial tumors influences both more objective diagnosis and more accurate prediction of chemotherapy response.

As a result an attempt has been made to detect deletion using fluorescence in-situ hybridization (FISH) and analyzed its prognostic value in a cohort of glial tumor patients from Amrita Institute of Medical Sciences and Research Center Kochi.

FISH was performed on 66 FFPE tissue sections by using Vyis LSI 1p36/LSI 1q25 and LSI 19p13/LSI 19q13dual coloured FISH probe sets. Signals were scored from at least 150-250 non-overlapping, intact nuclei. 163 cases were analyzed. Both 1p and 19q deletions was observed only in 28/163 (17.17%), - 1p/+ 19q deletion 80/163 (49.07%) and+1p/-19q deletion 55/163(33.74%) .

In this work presented the FISH was successfully applied to identify deletion 1p/19q. Its incidence depends on the type of diagnosed gliomas. In contrast to reported data, the present study reveals 49.07% deletion - 1p/ + 19q.

Deletions also have prognostic significance in the test group what constitutes the basis for inclusion of determining deletion 1 p/19q into diagnostic and treatment algorithm.

Keywords

FISH, Deletion 1p/19q, Glioma.

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Jisha S. Das ¹, Akhila Sivadas ², Ameer Shajahan ¹, K. Pavithran ³

Affiliations
1 Amrita School of Pharmacy, Kochi, IN
2 Department of Oncology, Amrita Institute of Medical Sciences, Kochi, IN
3 Department Medical Oncology & Hematology, Amrita Institute of Medical Sciences, Kochi, IN

Abstract

Cardiotoxicity associated with 5-fluorouracil (FU) is an uncommon, but potentially lethal, complication. Cardiac toxicity of 5FU include acute coronary syndrome (ACS), cardiomyopathy, vasospastic angina, coronary thrombosis and dissection, malignant arrhythmias, and sudden cardiac death.

With shorter bolus regimens, the incidence of cardiotoxicity typically lies between 1.6% to 3% of cases and with more prolonged regimens, these percentages increase to 7.6% to 18%.

We intend to share four cases which showed cardiac toxicity on chemotherapy with 5FU.

All our patients were getting continuous infusion regimens. 2 patients had arrhythmias one SVT and one bradycardia), one had reversible cardiomyopathy and one had acute coronary vasospam.

2 patients were suffering from carcinoma esophagus and one from carcinoma nasopharynx and another from cholangiocarcinoma. All were not having any cardiac risk factors. In all our cases the event was completely reversible. Except in the patient who had cardiomyopathy, chemotherapy was continued without any further issues.

Here we Concluded With increased usage of 5-FU for the treatment of gastrointestinal malignancies, cardiotoxicities may be expected to be encountered more frequently in the future. A pre-chemotherapy history, physical examination and a basic cardiac evaluation and monitoring in high risk cases might be able to prevent such events.

Keywords

5-FU, Cardiotoxicity.

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