4- Thursday Pharmacotherapy News – 23th September

1 – INR Response to Low-Dose Vitamin K in Warfarin Patients

• Literature suggests that 2 mg of vitamin K intravenously (IV) provides a similar effect as 10 mg to reverse warfarin. Doses <5 mg haven’t been studied in depth.
• The objective was to determine the international normalized ratio (INR) reduction effect of ultra low-dose (ULD) IV vitamin K.
• This retrospective, observational cohort study compared IV vitamin K doses of 0.25-0.5 mg (ULD) versus 1-2 mg (standard low dose [SLD]). The primary outcome assessed ΔINR at 36 hours; secondary outcomes assessed ΔINR at 12 hours and 30-day venous thromboembolism (VTE) and mortality rates.
• ULD IV vitamin K reversed INR similarly to doses of 1-2 mg without rebound.
• A ULD strategy may be considered in patients requiring more cautious reversal.

Source: SAGE Journal

2 – High- Versus Low-Molecular-Weight Hyaluronic Acid for the Treatment of Rotator Cuff Tendinopathy: A Triple-Blind Randomized Comparative Trial

• Shoulder pain most commonly originates from the tendon structures of the rotator cuff.
• This study compared the clinical effects of high- versus low-molecular-weight (LMW) hyaluronic acid for the management of rotator cuff tendinopathy.
• Both medications are effective for the treatment of tendinopathy.
• The benefits last at least for 3 months, and pain alleviation lasts partially for 6 months.
• The shoulder injection of LMW hyaluronate is more tolerable to the patient.
• Therefore, we recommend LMW hyaluronate as the first choice for the management of rotator cuff tendinopathy.

Source: SAGE Journal

3 – Low Serum Albumin Level Is a Risk Factor for Delayed Methotrexate Elimination in High-Dose Methotrexate Treatment

• In high-dose methotrexate (HD-MTX) therapy, delayed elimination of MTX from plasma leads to severe adverse effects.
• However, the risk factors for the delayed elimination of plasma MTX are still unclear.
• The purpose of this study was to investigate the factors related to the delayed MTX elimination in HD-MTX monotherapy.
• This study showed that low ALB is a risk factor for delayed MTX elimination in HD-MTX monotherapy.
• Pharmacokinetic analysis is needed to establish the dose of HD-MTX in patients with a low ALB level.

Source: SAGE Journal

4- Effects of liraglutide on visceral and ectopic fat in adults with overweight and obesity at high cardiovascular risk: a randomised, double-blind, placebo-controlled, clinical trial

• Visceral and ectopic fat are key drivers of adverse cardiometabolic outcomes in obesity.
• This study aimed to evaluate the effects of injectable liraglutide 3·0 mg daily on body fat distribution in adults with overweight or obesity without type 2 diabetes at high cardiovascular disease risk.
• In adults with overweight or obesity at high cardiovascular disease risk, once-daily liraglutide 3·0 mg plus lifestyle intervention significantly lowered visceral adipose tissue over 40 weeks of treatment.
• Visceral fat reduction may be one mechanism to explain the benefits seen on cardiovascular outcomes in previous trials with liraglutide among patients with type 2 diabetes.

Source: The Lancet

5 – Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial

• COVID-19 can lead to multiorgan failure.
• Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney.
• This study aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness.
• In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated.

Source: The Lancet

6 – Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial

• Semaglutide is an effective treatment for type 2 diabetes; however, 20–30% of patients given semaglutide 1·0 mg do not reach glycaemic treatment goals.
• This study aimed to investigate the efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with or without a sulfonylurea.
• Semaglutide 2·0 mg was superior to 1·0 mg in reducing HbA1c, with additional bodyweight loss and a similar safety profile.
• This higher dose provides a treatment intensification option for patients with type 2 diabetes treated with semaglutide in need of additional glycaemic control.

Source: The Lancet

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