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Year : 2017  |  Volume : 15  |  Issue : 4  |  Page : 309-310

Medical news – from around the world


Date of Web Publication17-Nov-2017

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DOI: 10.4103/0973-4651.218652

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How to cite this article:
. Medical news – from around the world. Curr Med Issues 2017;15:309-10

How to cite this URL:
. Medical news – from around the world. Curr Med Issues [serial online] 2017 [cited 2020 Oct 26];15:309-10. Available from: https://www.cmijournal.org/text.asp?2017/15/4/309/218652



First gene therapy in clinical use?

The US FDA issued a historic decision recently making the first gene therapy available in the US, ushering in a new approach to the treatment of cancer and other serious and life-threatening diseases. The FDA approved tisagenlecleucel for certain paediatric and young adult patients with a form of acute lymphoblastic leukaemia (ALL).

Tisagenlecleucel, is a genetically modified autologous T-cell immunotherapy. Each dose of the drug is a customized treatment created using an individual patient's own T-cells. The patient's T-cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a specific protein (a chimeric antigen receptor or CAR) that directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface. Once the cells are modified, they are infused back into the patient to kill the cancer cells.

The safety and efficacy of tisagenlecleucel were demonstrated in one multicenter clinical trial of 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL. The overall re-mission rate within three months of treatment was 83%. The ethics of such genetic treatment however, continues to be a subject of debate.

Source: FDA News Release (online, 30 Aug, 2017)

The importance of physical appearance of meropenem



Betalactam antibiotics are unstable in aqueous media because of the high reactivity of the four-member betalactam ring which is very susceptible to hydrolysis. Monte Carlo Simulations (MCS) have determined prolonged infusion meropenem to be pharmacodynamically superior to standard infusion. However, meropenem has an extremely short stability after being mixed in solution. Studies examining stability have shown that meropenem prepared for infusion is stable for up to four hours at room temperature and up to 24 hours refrigerated (at concentrations up to 20 mg/L). Hence, the entire dose must be infused within 4 hours of mixing, if prolonged infusion is used.1

The drug is a white to pale yellow powder that yields a colourless to yellow solution depending on the concentration. The colour of the product mainly indicates chemical stability. According to Indian Pharmacopoeia, the product should be white to off white crystalline powder. The colour development of the reconstituted solution indicates formation of degradation products and it affects the stability of product after reconstitution. The reconstituted solutions are pale yellowish in colour and the colour of most generic meropenem brands after reconstitution is more yellowish when compared to innovator product.

One study2 compared the stability of different brands of meropenem injection and found that the intensity of the colour of reconstituted solutions is inversely proportional to its stability. The reconstituted solution with dark yellow colour had the least meropenem concentration. However all the brands were able to maintain the acceptable limit at the end of 6 hours.

Implication: Reconstituted solutions which are colourless to yellow are normal. Deep colours indicate reduced stability.

References

  1. Pai GK, Krishna V, Lewis S, Sree UM. Significance of reconstitution time and other physical parameters for evaluation of dry powder injecta-bles. Int J Pharm Pharm Sci. 2013 Sep 7;5(3):612–4.
  2. Delattre I, Bambeke FV, Tulkens PM. Comparative Instabilities and Release of Colored Products from Original and Generics of Meropenem When Prepared in Concentrated Solutions for Prolonged Infusion to Patients [Internet]. Poster presented at: ASM Microbe; 2017 Jun; New Orleans.


New oral drug for type 1 diabetes mellitus shows promise

The ideal treatment for type 1 diabetes mellitus (TIDM) should enable patients to maintain a glycated haemoglobin level lower than 7.0% without weight gain or an increased risk of hypoglycaemia and diabetic ketoacidosis. As of now, insulin is the only pharmacological treatment widely available for type 1 DM. The only therapy other than insulin for the treatment of T1DM is injectable pramlintide, which modestly reduces the glycated haemoglobin level and weight but is associated with an increased risk of severe hypoglycaemia. Pramlintide is available only in the US. However, with insulin, less than one third of adults with T1DM achieve a glycated haemoglobin level lower than 7.0%.

Sotagliflozin is a new oral inhibitor of sodium-glucose transporters 1 and 2 (SGLT1 and SGLT2). SGLT1 inhibition reduces glucose absorption in the proximal intestine, which significantly blunts and delays postprandial hyperglycaemia. SGLT2 inhibition decreases renal glucose reabsorption. In phase 2 studies, the administration of sotagliflozin improved glycaemic control and lowered body weight among patients with type 1 or 2 diabetes. However, there is no oral medication available for use in combination with insulin to lower glucose level in patients with T1DM.

According to the authors of a study published in the New England Journal of Medicine (NEJM, 13 Sep, 2017), Sotagliflozin has the potential to become the first oral medication to be approved for the treatment of type 1 diabetes mellitus (T1DM), and the first new innovative treatment for the condition since insulin was discovered more than a century ago.

The double-blind, randomized control trial conducted in 19 countries, comprised 1,402 trial participants with T1DM who were assigned to either 400mg sotagliflozin or placebo, to be taken daily alongside their insulin therapy. At week 24, the results showed that a significantly larger proportion of patients taking the active drug achieved the primary end point of a glycated haemoglobin level lower than 7% and no episodes of severe hypoglycaemia or diabetic ketoacidosis (28.6% vs 15.2%). The use of sotagliflozin was also associated with significant decreases in fasting plasma glucose level, insulin dose, weight and systolic blood pressure.

The double-blind, randomized control trial conducted in 19 countries, comprised 1,402 trial participants with T1DM who were assigned to either 400mg sotagliflozin or placebo, to be taken daily alongside their insulin therapy. At week 24, the results showed that a significantly larger proportion of patients taking the active drug achieved the primary end point of a glycated haemoglobin level lower than 7% and no episodes of severe hypoglycaemia or diabetic ketoacidosis (28.6% vs 15.2%). The use of sotagliflozin was also associated with significant decreases in fasting plasma glucose level, insulin dose, weight and systolic blood pressure.

References

Garg S, Henry R, Banks P et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes. N Engl J Med 2017.

New drugs in India: Brivaracetam, Treosulfan, Ribociclib & Dienogest

The Central Drugs Standard Control Organization (CDSCO) has last month approved three drugs (brivaracetam, treosulfan, ribociclib & dienogest) to be manufactured and marketed in the country.

Brivaracetam is an analogue of levetiracetam used as an adjunct in the treatment of partial seizures with or without secondary generalization in patients aged 16 years and older. The daily oral dose of brivaracetam is given in two divided doses. The initial dose is 50 or 100mg daily which may be adjusted thereafter to a dose of 50 to 200mg daily, according to response. As with other antiepileptics, the drug should not be stopped abruptly to prevent withdrawal symptoms. The safety profile is similar to that of levetiracetam.

Treosulfan injection (5 g/vial) has been approved for the conditioning treatment prior to haematopoietic stem-cell transplantation. Treosulfan is an antineoplastic agent related to busulfan, which is reported to act by alkylation after conversion in vivo to epoxide compounds.

Ribociclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6. These kinases are involved in cell proliferation, and their inhibition results in prevention of cancer cell growth. Ribociclib is given with an aromatase inhibitor as initial therapy in postmenopausal women for advanced or metastatic breast cancer that is oestrogen-receptor positive and human epidermal growth factor receptor 2 (HER2)-negative. The recommended dose is 600mg once daily by mouth for 21 days followed by 7 treatment-free days.

Dienogest is a nonethinylated progestogen structurally related to nortestosterone. It is reported to have anti-androgenic properties. The drug is used in the management of endometriosis in an oral dose of 2mg daily; it is given in a continuous regimen regard-less of menstrual bleeding.




 

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