new drugs and medical issues 2014 2 (2)

NEW DRUGSAND MEDICAL ISSUES

2014

SAMIR EL ANSARY

Zerbaxa (ceftolozane and tazobactam) Injection

Company: Cubist Pharmaceuticals, Inc.Date of Approval: December 19, 2014

Treatment for: Intraabdominal Infection, Urinary Tract Infection

Zerbaxa (ceftolozane and tazobactam) is a cephalosporin and beta-lactamase inhibitor

combination for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary

tract infections (cUTI).

Rapivab (peramivir) InjectionCompany: BioCryst Pharmaceuticals, Inc.

Date of Approval: December 19, 2014

Treatment for: Influenza

Rapivab (peramivir) is an influenza virus neuraminidase inhibitor indicated for the

treatment of acute uncomplicated influenza in adults.

FDA Approves Rapivab (peramivir) to Treat Influenza Infection - December 22, 2014

http://www.drugs.com/newdrugs/fda-approves-rapivab-peramivir-influenza-infection-4134.html

Saxenda (liraglutide) InjectionCompany: Novo Nordisk Inc.


Treatment for: Obesity

Saxenda (liraglutide) is a once-daily glucagon-like peptide-1 (GLP-1) analogue for the

treatment of obesity.FDA Approves Saxenda (liraglutide [rDNA origin] injection) for

Obesity - December 23, 2014

http://www.drugs.com/newdrugs/fda-approves-saxenda-liraglutide-rdna-origin-obesity-4136.html

Namzaric (donepezil and memantine) Company: Actavis plc and Adamas Pharmaceuticals Inc.


Treatment for: Alzheimer's Disease

Namzaric (memantine hydrochloride extended-release and donepezil hydrochloride) is an NMDA receptor

antagonist and acetylcholinesterase inhibitor fixed-dose combination for the treatment of moderate to severe

Alzheimer’s disease.

Viekira Pak (ombitasvir/paritaprevir/ritonavir with

dasabuvir) TabletsCompany: AbbVie Inc.


Treatment for: Chronic Hepatitis C

Viekira Pak (ombitasvir/paritaprevir/ritonavir with dasabuvir) is an NS5A inhibitor, NS3/4A protease

inhibitor and CYP3A inhibitor combination co-packaged with a non-nucleoside NS5B palm polymerase inhibitor for the treatment of patients with genotype 1 chronic

hepatitis C virus (HCV) infection.

(tobramycin) Inhalation Solution

Company: PulmoFlow, Inc.Date of Approval: December 2, 2014

Treatment for: Cystic FibrosisKitabis Pak (tobramycin) is an aminoglycoside inhalation solution co-packaged with a

PARI LC PLUS® Reusable Nebulizer for the management of cystic fibrosis

Xigduo XR(dapagliflozin and metforminhydrochloride) Extended-Release Tablets

Company: AstraZenecaDate of Approval: October 30, 2014

Treatment for: Diabetes Type 2

Xigduo XR (dapagliflozin and metformin hydrochloride) is a once-daily sodium-glucose cotransporter 2 (SGLT2) inhibitor and biguanide combination for the treatment

of type 2 diabetes.

Sotylize(sotalol hydrochloride) Oral Solution

Company: Arbor PharmaceuticalsDate of Approval: October 22, 2014

Treatment for: Ventricular Arrhythmia, Atrial Fibrillation, Atrial Flutter

Sotylize (sotalol hydrochloride) is an antiarrhythmicindicated for the treatment of ventricular arrhythmias

and the maintenance of normal sinus rhythm in patients with history of highly symptomatic atrial

fibrillation/flutter

http://www.drugs.com/mtm/sotalol.html

Long-acting beta agonist olodaterol for use in COPD

(August 2014)

Olodaterol, a once-daily, long-acting beta agonist (LABA), is approved for the treatment of COPD in the United States, Canada, Russia, Denmark, and several other

countries; it is not approved for use in asthma.

In two trials that included a total of 1838 subjects with moderate-to-severe COPD, 24 weeks of olodaterol

resulted in significant improvement in airflow limitation and quality of life, compared with placebo .

Long-acting beta agonist

Olodaterolfor use in COPD

(August 2014)

Similar results were seen in a separate pair of trials that included a total of 1266 subjects and lasted 48 weeks . In

all reports, adverse events with olodaterol were comparable to those of placebo

Bronchoscopic lung volume reduction with

Nitinol coilsin severe emphysema

(October 2014)Bronchoscopic placement of nitinol coils is an

experimental method to treat emphysema. When the coils are deployed in areas of emphysema, they resume

their coiled shape, collecting and collapsing the surrounding lung tissue and thereby reducing

hyperinflation.



In a multicenter, observational study, 60 patients with severe heterogeneous emphysema underwent

bronchoscopic placement of nitinol coils (55 bilateral, 5 unilateral) with a median of 10 coils per lobe .

Serious adverse events included seven COPD exacerbations, four pneumothoraces, and one

episode of hemoptysis.



The remaining patients experienced modest but sustained improvements in quality of life and lung

function at six and 12 months. Randomized trials with a longer duration of follow-up are needed to confirm

these findings.

StatinTherapy does not reduce COPD

exacerbations (June 2014)

In observational studies of chronic obstructive pulmonary disease (COPD), statins have been associated with a reduced rate and severity of exacerbations, rate

of hospitalizations, and mortality.

StatinTherapy does not reduce COPD exacerbations

(June 2014)

However, these beneficial effects were not supported in a trial that randomly assigned 885 participants with

COPD, but without other indications or contraindications for statin therapy, to simvastatin or placebo for up to 36

months . Simvastatin did not reduce the rate of exacerbations or

the time to first exacerbation

Prophylactic antibioticsDo not benefit patients with acute liver

failure (October 2014)

The role of prophylactic antibiotics in the treatment of patients with acute liver failure is controversial.

In a retrospective study of 1551 patients with acute liver failure, antimicrobial prophylaxis did not reduce the incidence of bloodstream infection or mortality .

Antibiotic decontamination of the digestive tract in the ICU and

antimicrobial resistance (October 2014)

The use of prophylactic antibiotics to decontaminate the oropharyngeal and/or digestive tracts of critically ill patients and reduce the risk of infection confers a

modest mortality benefit but is not widely used, in part, because of concern that it can promote antimicrobial

resistance.



A large multicenter cluster-randomized trial in intensive care units in the Netherlands compared resistance rates

with selective oropharyngeal decontamination (SOD; antibiotics applied to the oropharynx only) and selective digestive decontamination (SDD; antibiotics applied to the oropharynx and through a nasogastric tube plus a

different intravenous antibiotic).



Rates of rectal colonization with highly resistant bacteria were overall lower with SDD than SOD, but colonization

with aminoglycoside-resistant gram-negative bacilli increased more over time with SDD than SOD.



Given the very low baseline rate of antimicrobial resistance in the Netherlands and the absence of a

control group that received no prophylactic antibiotics, these findings do not sufficiently allay concerns about

long-term antimicrobial resistance with antibiotic use for decontamination of the gastrointestinal tract.

Restrictive transfusion threshold safe in septic shock(October 2014)

Blood transfusion using a lower (restrictive) hemoglobin threshold has been adopted in a variety of settings, including hemodynamically stable patients in

the intensive care unit.

However, debate has remained regarding the safety of this approach in patients with septic shock.


A new randomized trial has shown that a restrictive hemoglobin threshold of 7 g/dL can be used in this

setting. The Transfusion Requirements in Septic Shock (TRISS) trial randomly assigned 998 patients with

septic shock to a restrictive or a liberal transfusion strategy (hemoglobin threshold of 7 or 9 g/dL) .


All outcomes were similar between the two groups at 90 days, including mortality, cardiac ischemia, and

transfusion reactions. We and other experts agree that for most patients with

septic shock, red blood cell transfusion should be reserved for those with a hemoglobin of ≤7 g/dL.

Enteral versus parenteral nutrition in critically ill patients

(October 2014)

In critically ill patients, the benefits of enteral nutrition compared with parenteral nutrition are unclear, with

small randomized trials suggesting marginal benefit to enteral nutrition in surgical patients.

One large multicenter randomized trial compared enteral nutrition with parenteral nutrition in 2400

critically ill patients, most of whom had medical rather than surgical illnesses .

Enteral versus parenteral nutrition in critically ill patients

(October 2014)

There was no difference in mortality or rates of infections between the groups. These findings support the continued use of enteral nutrition in both medical

and surgical patients who are critically ill, when feasible.

Immune modulatory enteral feeds in critically ill patients

(August 2014)

Small retrospective studies have suggested that high-protein enteral formulas with immune modulating

nutrients (IMHP), such as glutamine, selenium, and omega-3 fatty acids, may improve survival and reduce

the rate of infections in critically ill patients.

The effect of IMHP was examined in a multicenter, randomized, double-blind trial of 301 mechanically

ventilated adult patients (MetaPlus) .


(August 2014)

There was no difference reported in the rate of infections, duration of mechanical ventilation, or length

of ICU or hospital stay.

Use of IMHP was associated with a higher six-month mortality rate (54 versus 35 percent) in one predefined subpopulation of medical patients, which was not seen

in the surgical or trauma patients.


(August 2014)

These findings are consistent with previous large randomized trials of high-protein formulas

supplemented with glutamine or omega-3 fatty acids alone, which also found lack of benefit and possible

harmful effects.

Palliative care of patients in the intensive care unit(July 2014)

The traditional goals of intensive care unit (ICU) care are to reduce the morbidity and mortality associated

with critical illness, maintain organ function, and restore health.

When the acute illness or accompanying organ dysfunction is refractory to treatment, these goals of

care can no longer be met.


When aggressive care is likely to result in outcomes that are not congruent with patient values and

preferences, ICU clinicians must ensure that patients die with dignity.


A paradigm to assist in the delivery of palliative care to patients dying in the ICU has been developed that is

termed the “ABCDs (attitudes, behaviors, compassion, and dialogue) of dignity-conserving care” .

Practical preparatory procedures to ensure patient comfort and dignity before withdrawal of life support

are also available

Intraoperative PEEP (June 2014)

The optimal level of intraoperative positive end-expiratory pressure (PEEP) for mechanically ventilated

patients undergoing surgery is unknown.

In the PROVHILO trial, 900 patients undergoing abdominal surgery and at moderate risk of pulmonary

complications were randomly assigned to receive either high levels (12 cm H2O) or low levels (≤2 cm

H2O) of PEEP, administered at a constant tidal volume of 8 mL/kg .


The rate of postoperative complications, length of ICU stay, and mortality were no different between the

groups. However, patients on high levels of PEEP were more likely to become hypotensive (46 versus 36 percent)

and require vasopressor support (62 versus 52 percent).


High levels of PEEP intraoperatively do not appear to be of benefit and may be harmful in patients

undergoing abdominal surgery, although the level of PEEP used in this study (12 cm H2O) was unusually

high, which may have mitigated any potential benefit.

Further studies are needed before an optimal level of PEEP can be recommended in this population.

NEW ANTIBIOTICS 2014

• SAMIR EL ANSARY

Critical Care Antibiotics

INTERSTITIAL LUNG DISEASEAutologous hematopoietic stem cell

therapy in systemic sclerosis (July 2014)

In the Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial, a total of 156

patients with early diffuse cutaneous systemic sclerosis (dcSSc) were randomly assigned to receive either hematopoietic stem cell transplant (HSCT) or 12

monthly pulses of intravenous cyclophosphamide .



The primary end point was event-free survival, defined as the time until death due to any cause or the development of persistent major organ failure.

The study found that HSCT resulted in worse early, but better long-term, event-free and overall survival.



HSCT was associated with significant improvements in lung function, skin softness, functional ability, and

quality of life, but also with more viral infections and reduced renal function.



Patients who have severe skin disease with or without moderate (but not severe) internal organ involvement, and who continue to have progressive disease despite

an initial trial of immunosuppression, should be referred for further evaluation to specialized centers

with expertise performing HSCT for scleroderma.



(See "Immunomodulatory and antifibrotic approaches to the treatment of systemic sclerosis (scleroderma)",

section on 'Autologous stem cell transplantation'.)

http://www.uptodate.com/contents/immunomodulatory-and-antifibrotic-approaches-to-the-treatment-of-systemic-sclerosis-scleroderma?source=see_link&anchor=H8

LUNG CANCERCombination chemotherapy for patients with a late

relapse of small cell lung cancer (June 2014)

Treatment of patients with relapsed small cell lung cancer is a difficult problem that is usually managed

with single agent chemotherapy.

In a randomized phase III trial in patients with a sensitive relapse (ie, more than 90 days after

completion of their initial combination chemotherapy), treatment with a platinum-based combination regimen

significantly increased overall and progression-free survival .

LUNG CANCERCombination chemotherapy for patients with a late

relapse of small cell lung cancer (June 2014)

However, severe hematologic toxicity was increased. For patients with a sensitive relapse, treatment with the

original platinum-based combination or a novel platinum-based combination can be considered. (See "Treatment of refractory and relapsed small cell lung

cancer", section on 'Combination chemotherapy'.)

http://www.uptodate.com/contents/treatment-of-refractory-and-relapsed-small-cell-lung-cancer?source=see_link&anchor=H4086093

Novel anticoagulant strategies with potentially lower bleeding risk

(December 2014)

Anticoagulants reduce the risk of thromboembolism, but this benefit is balanced by an increased risk of

bleeding.

Two new strategies for anticoagulation are in development that may carry a lower risk of bleeding

compared with currently available agents.


(December 2014)

The first uses an antisense oligonucleotide to reduce production of coagulation factor XI (FXI-ASO).

In patients undergoing knee replacement, treatment with FXI-ASO was associated with a 3 percent risk of

venous thromboembolism, compared with approximately 30 percent with low molecular weight

heparin, without increasing bleeding .


(December 2014)

However, the duration of anticoagulation was long, injection site reactions were common, and no antidote

is available.


(December 2014)

The second strategy targets polyphosphate, a pro-thrombotic substance released from activated platelets

or microbes . In preclinical models, polyphosphate inhibitors have shown reduced arterial thrombosis without increased

bleeding. Additional studies are awaited to determine the role of

these new strategies in clinical practice.

Mortality benefit for thrombolysis in patients with acute pulmonary embolus

(June 2014)

Thrombolytic therapy is of uncertain benefit in patients with pulmonary embolus (PE).

A meta-analysis of 16 trials reported that, compared to anticoagulation alone, thrombolytic therapy was

associated with a lower all-cause mortality (2.2 versus 3.9 percent) and a reduced rate of recurrent thromboembolism (1.2 versus 3.0 percent).


(June 2014)

However, it increased the risk of major hemorrhage (9.2 versus 3.4 percent) including intracranial

hemorrhage (1.5 versus 0.2 percent).

No mortality benefit was reported in older patients (>65 years), a population in whom the risk of

hemorrhage was greatest.


(June 2014)

The data were not robust for any one specific patient population, nor was the optimal agent, dose, or method of delivery identified. Thus, the routine

administration of thrombolytic therapy for patients with PE remains questionable and the decision to administer it should continue to be made on an

individual patient basis.

CPAP therapy for older adults with obstructive sleep apnea

(October 2014)

Continuous positive airway pressure (CPAP) is the mainstay of therapy for most adults with obstructive

sleep apnea (OSA), but previous clinical trials have enrolled primarily younger adults.


(October 2014)

In a multicenter trial that included 278 adults ≥65 years of age with newly diagnosed OSA, patients

randomized to receive CPAP therapy plus best supportive care had improvement in daytime

sleepiness compared with those assigned to best supportive care alone .


(October 2014)

The benefits of CPAP were present at both three- and 12-month time points and were greater in those with

higher CPAP usage and higher baseline sleepiness scores. Secondary endpoints, including quality of life,

mobility, cognitive function, and cardiovascular events, were similar between groups

Orexin receptor antagonist suvorexant for treatment of insomnia

(August 2014)

The first dual orexin receptor antagonist, suvorexant(Belsomra), has been approved by the US Food and

Drug Administration for the treatment of insomnia but is not yet available for clinical use.

Orexin is a hypothalamic neuropeptide that plays a key role in regulating wakefulness and the sleep-wake

cycle.


(August 2014)

In clinical trials for up to one year, suvorexant was associated with improved subjective total sleep time

and time to sleep onset compared with placebo .

The most common adverse effect is somnolence, and next-day driving impairment has been seen in both

men and women at the maximum approved dose (20 mg).


(August 2014)

The role for this novel medication, which is expected to be a C-IV controlled substance, remains to be

determined, as suvorexant has not yet been compared with other pharmacologic or behavioral therapies for

insomnia

Lower risk of fatal bleeding with target specific oral anticoagulants versus warfarin

(November 2014)

All anticoagulants carry a risk of bleeding, and the lack of an antidote for direct factor Xa inhibitors

(rivaroxaban, apixaban, edoxaban) and the direct thrombin inhibitor dabigatran increases concerns

about this risk.


(November 2014)

Reassuringly, a meta-analysis of 12 randomized trials in patients with atrial fibrillation or venous

thromboembolism that compared bleeding risk with these agents versus vitamin K antagonists found lower rates of fatal bleeding, major bleeding, and intracranial bleeding with the direct factor Xa and direct thrombin

inhibitors


(November 2014)

Individual patient factors continue to play a role in anticoagulant choice and the development of reversal

agents for the factor Xa and thrombin inhibitors is underway.

Investigational agent for reversal of multiple anticoagulants

(November 2014)

Reversal agents for the target specific oral anticoagulants are lacking.

In a study of 80 healthy volunteers given a therapeutic dose of the direct factor Xa inhibitor edoxaban, a

reversal agent under development (PER977) normalized the whole blood clotting time within 10

minutes; in contrast, normalization of the clotting time took 12 to 15 hours in individuals given edoxaban

followed by placebo .

Investigational agent for reversal of multiple anticoagulants

(November 2014)

Agents for the target specific oral anticoagulants are lacking.

In addition to binding direct factor Xa inhibitors, PER977 also binds the direct thrombin inhibitor dabigatran, as well as unfractionated and low

molecular weight heparins.

Infection prevention measures for cystic fibrosis

(October 2014)Evidence is accumulating that a variety of

respiratory pathogens can be transmitted among individuals with cystic fibrosis (CF) within the

health care system.

In particular, highly transmissible strains of Pseudomonas aeruginosa have been reported.


(October 2014)Compared with sporadic strains of P. aeruginosa,

infection with highly transmissible strains is associated with increased need for health care

and antibiotics. To minimize risk of transmission, the CF

Foundation has published updated guidelines for infection prevention and control to be applied to all individuals with CF, regardless of respiratory

tract culture results .


(October 2014)

The guidelines include the following measures:●Clinicians should use contact precautions

(gown and surgical masks) at all times when caring for patients with CF.

●Patients with CF should wear surgical masks in the health care setting.


(October 2014)

The guidelines include the following measures:●Patients with CF should not congregate within

or outside of the health care setting, should remain at least six feet away from other patients with CF, and be cared for in single-patient rooms

when they require admission

Ivacaftor for cystic fibrosis (August 2014)

Ivacaftor is a drug that restores function of the mutant ion channel in patients with cystic fibrosis

(CF) due to a G551D mutation.

In initial randomized trials, beneficial effects of ivacaftor significantly exceeded those of any other CF

treatments. Now, a multicenter longitudinal study demonstrates

improvements in pulmonary function and weight gain, reduced hospitalization, and decreased

Pseudomonas aeruginosa colonization— all within six months of initiation .

Ivacaftor for cystic fibrosis(August 2014)

Ivacaftor is a drug that restores function of the mutant ion channel in patients with cystic fibrosis

(CF) due to a G551D mutation.

These findings further establish the importance of ivacaftor in the treatment

of CF due to G551D or other “gating” mutations.

Cardiovascular outcomes and azithromycinuse for pneumonia

(June 2014)

Large observational studies have shown conflicting results with regards to a possible increase in

cardiovascular mortality associated with azithromycinuse.

A more recent large cohort study evaluated the association between azithromycin use and all-cause

mortality and cardiovascular events in more than 60,000 United States veterans ≥65 years of age who were

hospitalized with pneumonia .


(June 2014)

Ninety-day mortality was significantly lower in those who were treated with an azithromycin-containing

regimen versus those who received other guideline-concordant antibiotics.

Compared with patients who did not receive azithromycin, those who received azithromycin were

slightly more likely to have a myocardial infarction, but not arrhythmias, heart failure, or any cardiac event.


(June 2014)

An analysis of these data suggested that seven deaths were averted for each non-fatal myocardial infarction

associated with azithromycin use, reflecting a net benefit of azithromycin for patients ≥65 years of age with pneumonia. (See "Azithromycin, clarithromycin,

and telithromycin", section on 'QT interval prolongation and cardiovascular events'.)

http://www.uptodate.com/contents/azithromycin-clarithromycin-and-telithromycin?source=see_link&anchor=H22

GOOD LUCK

SAMIR EL ANSARY

ICU PROFESSOR

AIN SHAMS

CAIRO

[email protected]

new drugs and medical issues 2014 2 (2)

Health & Medicine

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