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What's new in drug therapy
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What's new in drug therapy
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2017. | This topic last updated: Mar 16, 2017.

The following material represents a subset of new drugs, drug approvals, drug warnings, and drugs removed from the market from the past six months. This is not a complete list; it includes those topics considered by the authors and editors to be of particular interest or importance. For a complete list of new drug approvals, see

You can check drug interactions by going to the Lexi-Interact drug interactions program included with UpToDate. This program is available to online desktop and mobile web users and can be accessed from the Drug Interactions tab located in the top right corner of any screen and in the search results list after searching on a drug name. iOS and Android users may also purchase an installed app version of Lexi-Interact from the Clinical Drug Information online store.


Risk of hypoglycemia if repaglinide is given with clopidogrel (February 2017)

Clopidogrel, an antiplatelet drug whose glucuronide metabolite inhibits CYP2C8 hepatic metabolism, can increase levels of repaglinide, a CYP2C8 substrate, and cause hypoglycemia [1,2]. The prescribing information in the United States was recently revised to recommend against concomitant use and, if the combination cannot be avoided, to limit the total daily dose of repaglinide to 4 mg or less. Characterizing this interaction has contributed to a growing appreciation of CYP2C8 as a clinically relevant drug metabolizing enzyme leading to potential drug interactions with strong CYP2C8 inhibitors or inducers [2]. (See "Sulfonylureas and meglitinides in the treatment of diabetes mellitus", section on 'Precautions and side effects'.)

Dabigatran combined with certain statins associated with increased risk of major bleeding (February 2017)

An analysis of health records of nearly 46,000 Canadian patients showed that older adults (age ≥66) with atrial fibrillation taking dabigatran who also received simvastatin or lovastatin had approximately a 50 percent greater risk of hospitalization for major hemorrhage relative to those who used other statins [3]. Although the mechanism for this interaction is uncertain, until additional information becomes available, it may be prudent to choose a statin other than lovastatin or simvastatin for older patients receiving dabigatran, and for those with an elevated risk for serious bleeding. (See "Statins: Actions, side effects, and administration", section on 'Drug interactions'.)

Potential interaction between high-dose methotrexate and levetiracetam (November 2016)

Levetiracetam is sometimes used for prophylaxis and treatment of seizures in patients undergoing high-dose methotrexate (MTX) treatment for brain or other central nervous system (CNS) cancers, including lymphomas. Health Canada has issued a safety review describing a potential interaction between the two drugs, noting 13 reports received by the levetiracetam manufacturer and concluding that concurrent use can lead to significantly elevated levels of MTX and increased risk of toxicity [4]. The labeling is being revised to recommend careful MTX blood level monitoring. Additional details are available from Lexi-Interact, the drug interactions tool included within UpToDate. (See "Therapeutic use and toxicity of high-dose methotrexate", section on 'Coadministered drugs that may interfere with excretion'.)

Proton pump inhibitors may diminish capecitabine efficacy (October 2016)

Two recent studies suggest that proton pump inhibitors diminish the effectiveness of capecitabine in the treatment of colorectal and gastroesophageal cancer [5,6]. It is hypothesized that higher gastric pH levels may inhibit dissolution and absorption of capecitabine. Patients who are receiving a capecitabine-containing regimen for adjuvant treatment of colon cancer or other malignancies should, when possible, avoid taking concurrent proton pump inhibitors. (See "Adjuvant therapy for resected stage III (node-positive) colon cancer", section on 'Capecitabine'.)


Telotristat for refractory carcinoid syndrome diarrhea (March 2017)

Telotristat inhibits the production of serotonin by carcinoid tumors and reduces the frequency of carcinoid syndrome diarrhea. The randomized TELESTAR trial compared two doses of oral telotristat (250 mg and 500 mg, each taken three times daily) against placebo in 135 patients who had uncontrolled symptoms from carcinoid syndrome despite treatment with a somatostatin analog [7]. Treatment with telotristat at either dose was associated with a reduction in bowel movement frequency compared with placebo, and the drug was well tolerated. Based upon these results, telotristat has been approved in the United States, in combination with somatostatin analog therapy, for the treatment of adults with diarrhea related to carcinoid syndrome that is inadequately controlled by somatostatin analog therapy alone [8]. The recommended dose is 250 mg three times daily [9]. (See "Treatment of the carcinoid syndrome", section on 'Telotristat'.)

Brodalumab for moderate to severe plaque psoriasis (February 2017)

Brodalumab, an anti-IL-17 receptor A monoclonal antibody, is a new addition to the armamentarium of highly effective biologic therapies for psoriasis. In February 2017, the US Food and Drug Administration approved brodalumab for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies [10]. Approval of brodalumab was based upon data from three randomized trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) that found brodalumab more effective than placebo [11,12]. However, suicidal ideation and behavior occurred in a small number of patients treated with brodalumab. As a result, the drug will only be available in the United States through a Risk Evaluation and Mitigation Strategy program designed to identify patients who develop new or worsening symptoms of depression or suicidality. (See "Treatment of psoriasis", section on 'Brodalumab'.)

Bezlotoxumab for secondary prevention of C. difficile infection (February 2017)

Bezlotoxumab is a monoclonal antibody against Clostridium difficile toxin B (which is essential for the virulence of the organism) that received US Food and Drug Administration approval in 2016 for secondary prevention of C. difficile infection in patients at high risk for recurrence. In two randomized trials including more than 2500 patients with C. difficile infection, the addition of bezlotoxumab to standard oral antibiotic therapy lowered the rate of recurrence (16 to 17 versus 26 to 28 percent with antibiotics alone) [13]. However, further evaluation to identify those who would be most likely to benefit is needed to define the optimal role of bezlotoxumab relative to other approaches to C. difficile infection treatment, including fecal microbiota transplant. (See "Clostridium difficile in adults: Treatment", section on 'Alternative therapies'.)

Nusinersen for spinal muscular atrophy (January 2017)

Nusinersen, an antisense oligonucleotide, is the first drug approved to treat spinal muscular atrophy (SMA) by the US Food and Drug Administration (FDA). In an interim analysis of the double-blind ENDEAR trial, which enrolled 82 infants with SMA, improvement in motor milestones was observed in 40 percent of patients treated with intrathecal nusinersen, versus none for those who received the sham procedure [14]. The FDA based its approval upon data from this trial and open-label studies in older patients with SMA [15,16]. We recommend nusinersen for most infants with SMA and select children ages 2 to 12 years with SMA. (See "Spinal muscular atrophy", section on 'Nusinersen'.)

Dosing interval for zoledronic acid in patients with bone metastases (January 2017)

For patients with bone metastases from a solid tumor, the approved dose and schedule of administration for zoledronic acid to reduce the frequency of skeletal-related events (SREs) is 4 mg every three to four weeks. Less frequent dosing is supported by data from CALGB (Alliance) trial 70604, which randomly assigned 1822 patients with bone metastases from breast or prostate cancer or multiple myeloma to the same dose of zoledronic acid every 4 or every 12 weeks for two years, starting with the first dose. There was no difference in the proportion of patients who developed at least one SRE (29.5 versus 28.6 percent) [17]. There are now sufficient data in breast and prostate cancer to support dosing of zoledronic acid every 12 rather than every 4 weeks, and we suggest this approach for most patients. We still prefer every-four-week dosing, at least initially, for patients who have extensive or highly symptomatic bone metastases. (See "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors", section on 'Dosing interval'.)

Rucaparib in BRCA mutation-associated advanced ovarian cancer (January 2017)

Poly-ADP ribose polymerase (PARP) inhibitors have activity against BRCA mutation-associated epithelial ovarian cancer. The PARP inhibitor rucaparib is now approved by the US Food and Drug Administration for BRCA mutation-associated advanced ovarian cancer that has been treated with two or more lines of chemotherapy, based on response rates of over 50 percent in such cancers [18,19]. We now offer rucaparib as an option in this setting. (See "Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal cancer: Platinum-resistant disease", section on 'Patients with a BRCA mutation'.)

Tenofovir alafenamide for the treatment of chronic hepatitis B virus infection (December 2016)

Tenofovir disoproxil fumarate is a first-line therapy for chronic hepatitis B virus (HBV) infection. A newer formulation of tenofovir, tenofovir alafenamide, was approved by the US Food and Drug Administration in November 2016 for the treatment of chronic HBV in patients with compensated liver disease [20]. In two large randomized noninferiority trials among patients with chronic HBV infection (both treatment-naive and experienced, and including patients positive or negative for HBV e antigen), tenofovir alafenamide resulted in similar rates of HBV suppression and fewer adverse effects on renal function and bone density at 48 weeks compared with tenofovir disoproxil fumarate [21,22]. Given these findings, tenofovir alafenamide is our preferred formulation for patients with chronic HBV who initiate therapy with tenofovir. We also favor switching those initially started on tenofovir disoproxil fumarate to tenofovir alafenamide. Given limited available safety data, we do not currently use tenofovir alafenamide in pregnant women. (See "Hepatitis B virus: Overview of management", section on 'Nucleos(t)ide analogues'.)

Topical crisaborole for atopic dermatitis (December 2016)

A topical preparation containing 2% crisaborole, an investigational boron-based, small-molecule, phosphodiesterase-4 inhibitor, was approved by the US Food and Drug Administration in December 2016 for the treatment of mild to moderate atopic dermatitis in patients two years of age and older [23]. In four-week clinical trials, topical crisaborole was more effective than placebo in reducing pruritus, skin inflammation, excoriation, and lichenification. However, trials comparing topical crisaborole with other topical treatments for atopic dermatitis are lacking. (See "Treatment of atopic dermatitis (eczema)", section on 'Crisaborole'.)

Iloprost therapy for severe frostbite (December 2016)

For years, no effective therapy was available to prevent tissue necrosis and subsequent amputation in patients with severe frostbite, but an increasing body of evidence suggests that treatment with iloprost, a prostacyclin analog (IV formulation not available in the United States) can prevent such injury in appropriately selected patients. According to one open-label randomized trial [24], a growing number of case reports [25], and revised management recommendations from wilderness medicine experts [26], treatment with iloprost is effective and safe. We suggest treatment with iloprost (where available), with or without tPA, for patients with severe frostbite (Grade 2-4) if given within 48 hours of the initial insult. (See "Frostbite", section on 'Prostacyclin therapy for severe injury presenting within 48 hours'.)

Vaginal prasterone for dyspareunia in postmenopausal women (November 2016)

In November 2016, the US Food and Drug Administration approved the use of prasterone (also known as dehydroepiandrosterone [DHEA]) for treatment of dyspareunia in women with vulvovaginal atrophy (VVA) due to menopause [27]. In an earlier randomized trial of women with VVA and moderate to severe dyspareunia, 12 weeks of daily intravaginal DHEA resulted in improved scores for pain during sexual activity and other key domains of female sexual function (desire, arousal, lubrication, orgasm, satisfaction) compared with placebo [28]. However, patients may find daily dosing more cumbersome than twice-weekly dosing with vaginal estrogen preparations. (See "Treatment of genitourinary syndrome of menopause (vulvovaginal atrophy)", section on 'Dehydroepiandrosterone (prasterone)'.)

Ustekinumab for anti-TNF refractory Crohn disease (November 2016)

Ustekinumab is approved for use in adult patients with moderate to severely active Crohn disease who have failed conventional therapy, but efficacy in inducing clinical remission in patients with disease refractory to anti-tumor necrosis factor (anti-TNF) therapy had not been previously established. In two randomized induction trials, approximately 1300 patients with Crohn disease and nonresponse or intolerable side effects to anti-TNF therapy were assigned to eight weeks of intravenous ustekinumab or placebo [29]. Those who responded to ustekinumab were assigned to 44 weeks of subcutaneous maintenance with ustekinumab or placebo. Patients assigned to ustekinumab had significantly higher clinical response rates at week six and rates of remission at week 44 as compared with placebo, demonstrating a role for ustekinumab in patients who have failed anti-TNF therapy. (See "Overview of the medical management of severe or refractory Crohn disease in adults", section on 'Ustekinumab'.)

Adalimumab for noninfectious uveitis (November 2016)

Patients with noninfectious uveitis can benefit from effective and safe glucocorticoid-sparing therapy. Two well-designed, randomized trials showed that adalimumab was effective in the treatment of noninfectious intermediate, posterior, and pan-uveitis [30,31]. In these trials, adalimumab improved the time-to-treatment failure in patients with uveitis who followed a tapering schedule for oral glucocorticoids. Both the European Medicines Agency and the US Food and Drug Administration recommended approval of adalimumab for adults with these forms of uveitis. (See "Uveitis: Treatment", section on 'Anti-tumor necrosis factor-alpha'.)

Olaratumab in combination for advanced soft-tissue sarcoma (November 2016)

Olaratumab is a monoclonal antibody that binds to the platelet-derived growth factor receptor alpha (PDGFRA) and blocks binding of PDGF ligands. In a randomized phase II study comparing doxorubicin with or without olaratumab in previously untreated patients with locally advanced or metastatic soft tissue sarcoma (STS) from a variety of histologic subtypes, initial combination therapy was associated with improved median overall survival (27 versus 15 months) [32]. Grade 3 or 4 neutropenia, mucositis, nausea, vomiting, and diarrhea were all more common with combined therapy. Based upon these results, and consistent with the recent approval of olaratumab in the United States for this indication [33], we suggest doxorubicin plus olaratumab rather than doxorubicin alone for first-line treatment of patients who cannot be cured with radiation or surgery and who have a type of STS for which anthracyclines represent appropriate chemotherapy. (See "Systemic treatment of metastatic soft tissue sarcoma", section on 'Doxorubicin plus olaratumab'.)

Intravenous carbamazepine approved for use in adults (November 2016)

An intravenous (IV) preparation of carbamazepine has been approved by the US Food and Drug Administration for use as short-term replacement therapy in adult patients on stable doses of oral carbamazepine who are transiently unable to ingest oral preparations [34]. The recommended IV conversion dose is 70 percent of the total daily oral dose, divided into four equal doses and given every six hours. (See "Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects", section on 'Carbamazepine'.)

Eteplirsen for Duchenne muscular dystrophy (September 2016)

Small studies of eteplirsen, an exon 51 skipping drug, suggest that it can increase dystrophin production in skeletal muscle without drug-related adverse effects in patients with Duchenne muscular dystrophy (DMD) with an amenable dystrophin gene mutation. Based upon this finding, the US Food and Drug Administration granted accelerated approval of eteplirsen in September 2016 for the treatment patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping [35]. The mutation is present in approximately 13 percent of patients with DMD. (See "Treatment of Duchenne and Becker muscular dystrophy", section on 'Eteplirsen'.)

Nivolumab dose regimen (September 2016)

Nivolumab is an IgG4 monoclonal antagonist antibody to PD-1 that is US Food and Drug Administration (FDA)-approved for the treatment of several types of malignancies. The FDA has modified the approved dose regimen for advanced renal cell carcinoma, melanoma, and non-small cell lung cancer to 240 mg intravenously every two weeks until disease progression or intolerable toxicity [36]. This new dose replaces the previous regimen of 3 mg/kg and is based on population pharmacokinetic analyses demonstrating comparable efficacy and safety in patients with these cancers. For patients with Hodgkin lymphoma, or for those with melanoma being treated concurrently with ipilimumab, the recommended dose of nivolumab remains unchanged (3 mg/kg and 1 mg/kg, respectively). (See "Immunotherapy of non-small cell lung cancer with immune checkpoint inhibition", section on 'Nivolumab' and "Immunotherapy of renal cell carcinoma" and "Immunotherapy of advanced melanoma with immune checkpoint inhibition".)


Antipsychotic drugs and risk of falls and fracture (March 2017)

In a large, population-based sample of Finnish people with Alzheimer disease, new users of antipsychotic medication had an increased risk of hip fractures from the first days of use [37]. Subsequent to multiple similar reports in patients with varied disorders, the US Food and Drug Administration (FDA) issued a warning that antipsychotic drugs may cause falls and fractures as a result of somnolence, postural hypotension, and/or motor and sensory instability, and recommended that a fall risk assessment be completed when initiating antipsychotic treatment and recurrently for patients continuing on long-term antipsychotics. (See "Second-generation antipsychotic medications: Pharmacology, administration, and side effects", section on 'Falls'.)

Differences in anaphylaxis treatment by age (February 2017)

Epinephrine given by intramuscular (IM) injection is the treatment of choice for anaphylaxis, but clinicians are sometimes reluctant to administer it, particularly to older adults. In a retrospective study of nearly 500 children and adults with anaphylaxis presenting to the emergency department, patients >50 years of age were less likely to receive epinephrine (36 versus 61 percent) compared with younger patients [38]. In addition, among patients who were given epinephrine, older adults were more likely to receive excessive doses when epinephrine was administered intravenously (IV). IM epinephrine was well-tolerated by patients of all ages, while IV administration was associated with a higher rate of cardiovascular complications. These findings support our recommendations to administer epinephrine by IM injection whenever possible and reserve IV administration for refractory cases. (See "Anaphylaxis: Emergency treatment", section on 'Situations requiring caution'.)

High-risk drug prescribing in adults with dementia (February 2017)

Older adults with dementia are at heightened risk for adverse drug effects from anticholinergic drugs, benzodiazepines, and opioids, among many others. Despite these risks, polypharmacy remains common in this population. In a study that included over 75,000 adults with dementia, 44 percent of patients were prescribed at least one potentially unsafe medication (mostly drugs with high anticholinergic activity), and rates were consistently higher in patients receiving care from multiple providers [39]. These results highlight the need for careful monitoring of drug therapy in patients with dementia and the importance of communication among providers before starting new therapies. (See "Safety and societal issues related to dementia", section on 'Polypharmacy'.)

Metformin use in patients with diabetes and renal impairment, heart failure, or chronic liver disease (January 2017)

In a systematic review of 17 observational studies comparing diabetes regimens with and without metformin, metformin use was associated with lower all-cause mortality among patients with heart failure, renal impairment, or chronic liver disease with hepatic impairment [40]. In addition, metformin use in patients with renal impairment or heart failure was associated with fewer heart failure readmissions. This study supports a recent US Food and Drug Administration (FDA) labeling revision for metformin, which will increase use in patients with renal impairment. Metformin remains contraindicated in patients with estimated glomerular filtration rate (eGFR) <30 mL/min, concurrent active or progressive liver disease, or unstable or acute heart failure with risk of hypoperfusion and hypoxemia. Recommendations regarding metformin use in patients with an eGFR between 30 and 45 mL/min vary and UpToDate authors individualize decisions about metformin use in such patients. (See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'.)

Relative cardiovascular safety of celecoxib, naproxen, and ibuprofen (December 2016)

The cardiovascular (CV) safety of celecoxib, the COX-2 selective nonsteroidal anti-inflammatory drug (NSAID), compared with other NSAIDs, is a matter of debate. In a randomized trial (PRECISION) involving over 24,000 patients with arthritis and either known CV disease or CV risk factors, the CV safety of celecoxib was noninferior to both naproxen and ibuprofen, two nonselective NSAIDs [41]. Depending upon the analysis, about 2 to 5 percent of subjects experienced a CV event during follow-up, which was slightly lower than the expected event rate. Despite some limitations, this trial suggests that celecoxib in moderate doses can be administered, when indicated, without concern about increased CV risk compared with the nonselective nonsteroidal agents naproxen and ibuprofen. (See "COX-2 selective inhibitors: Adverse cardiovascular effects", section on 'Celecoxib' and "Nonselective NSAIDs: Adverse cardiovascular effects", section on 'Risk of myocardial infarction, stroke, and death'.)

FDA issues warning about anesthesia for pregnant patients and children under three years of age (December 2016)

The US Food and Drug Administration has warned about potential negative effects on the developing brain from administration of anesthetics and sedatives to pregnant women and children under age three, especially for repeated exposures or procedures lasting more than three hours [42]. However, the degree of risk remains unclear. A single, brief exposure to anesthesia probably does not cause neurotoxicity in healthy young children. Further study is required to determine the effects of prolonged or repeated anesthetics, variability among anesthetic agents and combinations of drugs, and patient factors that may confer vulnerability to anesthetic neurotoxicity. At present, there is no compelling evidence that any specific anesthetic agent should be avoided during pregnancy or in young children, or that necessary surgery should be delayed because of concerns about neurotoxicity. (See "Management of the pregnant patient undergoing nonobstetric surgery", section on 'Fetal brain development'.)

FDA warning removed from varenicline for smoking cessation (December 2016)

In 2009, the US Food and Drug Administration (FDA) required varenicline packaging to include a boxed warning about potential neuropsychiatric side effects, but this warning has been removed in 2016 [43], based on results of a randomized trial that found no difference in adverse neuropsychiatric events comparing varenicline with nicotine patch or placebo in patients with or without a coexisting psychiatric disorder [44]. As with any medication, we advise that patients should be told to contact their clinician if they or their family notice any unusual behavior or mood symptoms as well as any new or worsening symptoms of cardiovascular disease. (See "Pharmacotherapy for smoking cessation in adults", section on 'Safety'.)

Ibrutinib and Pneumocystis pneumonia (December 2016)

The Bruton tyrosine kinase inhibitor ibrutinib has not clearly been associated with an increased risk of opportunistic infections, but cases have been reported. In a series of 96 patients receiving ibrutinib as the sole agent for chronic lymphocytic leukemia (CLL), five were reported to have Pneumocystis pneumonia [45]. All of the infections were grade ≤2 and resolved with oral trimethoprim-sulfamethoxazole. A limitation is that the diagnoses were made by polymerase chain reaction (PCR) of bronchoalveolar lavage fluid, which could represent a false positive in the setting of colonization with Pneumocystis. Nevertheless, clinicians should have a high index of suspicion for Pneumocystis pneumonia in patients receiving ibrutinib, and the diagnosis should be sought in those with compatible signs and symptoms. (See "Risk of infections in patients with chronic lymphocytic leukemia", section on 'Ibrutinib' and "Prevention of infections in patients with chronic lymphocytic leukemia", section on 'Ibrutinib and idelalisib'.)

Type 1 diabetes mellitus and anti-PD-1 immunotherapy (December 2016)

Checkpoint inhibitor immunotherapy with an anti-programmed cell death 1 (PD-1) receptor antibody, often in conjunction with ipilimumab, has resulted in the acute onset of type 1 diabetes mellitus in rare cases. This may be manifested by severe hyperglycemia or diabetic ketoacidosis [46]. These patients have remained insulin-dependent for diabetic control following management of their acute episode. Blood glucose is typically monitored weekly during the first 12 weeks of therapy with the combination of nivolumab plus ipilimumab. (See "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Type 1 diabetes mellitus'.)

Combination antiretroviral treatment in pregnancy (November 2016)

Combination antiretroviral treatment (ART) has become the worldwide standard of care for HIV-infected pregnant women, both for their own health and for prevention of HIV transmission to their infants. In a large randomized trial of HIV-infected pregnant women in Africa and India, antepartum ART (with one of two different protease inhibitor-based regimens) resulted in lower transmission rates compared with zidovudine plus single-dose nevirapine (0.5 versus 1.8 percent) [47]. Rates of preterm birth at <37 weeks were higher with the ART regimens than with zidovudine, but more significant prematurity (<34 weeks) and neonatal deaths were not increased. Clinicians should discuss with patients the potential risk for adverse pregnancy outcome with certain ART regimens. (See "Safety and dosing of antiretroviral medications in pregnancy", section on 'Preterm birth'.)

Cardiotoxicity of checkpoint inhibitor immunotherapy (November 2016)

Checkpoint inhibitor immunotherapy for melanoma and other cancers may result in severe or fatal cardiotoxicity, even in the absence of a history of significant cardiac risk factors [48]. High-dose steroids are indicated to treat myositis and other cardiac complications, but symptoms may progress in some cases despite steroids. The early institution of more aggressive immunosuppressive therapy and monitoring should be considered for patients without an immediate response to high-dose steroids. (See "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Cardiotoxicity'.)

HBV reactivation during HCV antiviral therapy (October 2016)

Reactivation of hepatitis B virus (HBV) infection, including cases with fatal fulminant hepatitis, has been reported in several patients receiving direct-acting antiviral therapy for hepatitis C virus (HCV) infection [49]. Patients should be tested for HBV coinfection prior to initiation of HCV therapy, with HBV treatment initiated for those who meet criteria (table 1). HBV surface antigen (HBsAg) positive patients who do not initially meet HBV treatment criteria should be monitored with HBV DNA testing during HCV treatment. In patients with a positive HBV core antibody (HBcAb) but negative HBsAg, we check liver enzymes during HCV treatment and perform reflex HBsAg and HBV DNA testing for unexplained elevations. (See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection", section on 'HBV coinfection' and "Overview of the management of chronic hepatitis C virus infection", section on 'Other monitoring'.)

Updated MASCC/ESMO guidelines for nausea and emesis related to cancer treatment (October 2016)

Updated guidelines for prevention and management of cancer therapy-associated nausea and vomiting are available from the Multinational Association of Supportive Care in Cancer and the European Society of Medical Oncology (table 2), the consensus panel also provides guidance on the use of prophylactic antiemetics in patients undergoing radiation therapy. (See "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults", section on 'Recommendations for specific groups'.)

Thrombotic microangiopathy from interferon (October 2016)

Drug-induced thrombotic microangiopathy (DITMA) has been described with a number of chemotherapeutic, immunosuppressive, and other drugs. Unlike thrombotic thrombocytopenic purpura (TTP), DITMA is not associated with severely reduced ADAMTS13 activity, and the principal treatment is drug discontinuation rather than plasma exchange. A new report has provided strong evidence for interferon as a cause of TMA [51]. Patients receiving interferon who develop signs of a TMA should have the drug discontinued promptly before organ failure develops. (See "Drug-induced thrombotic microangiopathy", section on 'Immunosuppressive agents'.)

Pharmacotherapy for antipsychotic-induced akathisia in schizophrenia (October 2016)

Benzodiazepines, beta blockers, and the anticholinergic drug benztropine are believed to be comparably effective in the treatment of akathisia in schizophrenia patients, based upon limited data from small clinical trials. Until recently, we favored benzodiazepines for first line treatment of akathisia. Earlier in 2016, however, a large retrospective analysis of claims and mortality data reported an increased mortality risk associated with benzodiazepine use in patients with schizophrenia [52]. Subsequently, a dose-related relationship between cumulative benzodiazepine use and increased mortality was found in a national registry study of over 20,000 Swedish adults with schizophrenia [53]. Although the study designs do not allow causality to be determined, based upon these findings, we now suggest that a beta blocker, such as propranolol, be used as first-line treatment for akathisia. Benzodiazepines remain an option, particularly in patients who do not respond to a beta blocker or benztropine. (See "Pharmacotherapy for schizophrenia: Side effect management", section on 'Akathisia'.)

Pulmonary toxicity of anti-PD-1 and anti-PD-L1 antibodies (September 2016)

Pulmonary toxicity is an uncommon but potentially fatal complication of treatment with checkpoint inhibitor immunotherapy targeting programmed cell death-1 (PD-1) or its ligand (PD-L1). The incidence of pneumonitis was 5 percent in a series of 915 patients treated with one of these agents [54]. All patients had immunotherapy withheld until toxicity resolved, and this was sufficient to reverse toxicity in most patients with grade 1 pneumonitis (table 3). For those with more severe toxicity, corticosteroids were indicated. Five out of 43 patients worsened and died despite therapy, mostly attributed to infectious complications or tumor progression. (See "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Pneumonitis'.)

Medication modification following fracture in older adults (September 2016)

Adverse drug effects are a particularly important issue for geriatric patients and may be unrecognized as a cause of illness or injury. A study reviewed data from a sample of 168,000 Medicare patients seen for treatment of hip, shoulder, or wrist fractures [55]. In the four months prior to presentation, three-quarters of the patients had been taking a nonopioid drug associated with increased fracture risk (eg sedatives, atypical antipsychotics, tricyclic antidepressants, or antihypertensives). In the four months after the fracture, such drugs were discontinued for 7 percent but were newly prescribed for another 7 percent. Review of drug therapy, with assessment of the need for ongoing therapy and discontinuation of nonessential medications, is indicated when patients present with an injury or illness that might relate to an adverse effect of a medication. (See "Drug prescribing for older adults", section on 'Review current drug therapy'.)

Safety of inhaled glucocorticoid-LABA combination therapy in asthma (September 2016)

In early studies, a small increase in asthma-related deaths associated with salmeterol led the US Food and Drug Administration to place a boxed warning on the use of long-acting beta agonists (LABAs) in asthma. While concerning, the number of events was small, and it could not be determined if the potential risk of salmeterol could be mitigated by combining LABAs with inhaled glucocorticoids. Three large randomized trials including 30,000 children and adults found no increase in asthma-related adverse events or deaths among patients who used combination inhalers with salmeterol or formoterol plus an inhaled glucocorticoid versus glucocorticoid monotherapy [56-58]. These studies support the safety of these fixed-dose combination inhalers in patients with moderate-to-severe asthma. (See "Beta agonists in asthma: Controversy regarding chronic use", section on 'Potential risk mitigation'.)


High-dose influenza vaccine in older adults (March 2017)

For influenza vaccination of adults ≥65 years of age, we recommend the high-dose inactivated influenza vaccine, which has previously been shown to be more immunogenic and modestly more effective at preventing influenza infection than the standard-dose vaccine. In a study of United States Medicare beneficiaries ≥65 years of age, the high-dose vaccine was more effective than the standard-dose vaccine for preventing postinfluenza death during the 2012-2013 influenza season, a season when circulation of H3N2 influenza A (a strain associated with severe disease) was common [59]. In contrast, it was not more effective for preventing postinfluenza death during the following season, when H1N1 influenza A (a strain associated with mild disease) predominated. This difference was likely due to the difficulty in demonstrating benefit during a mild influenza season, when death is a rare outcome. The high-dose vaccine was associated with a reduced risk of hospitalization during both seasons. (See "Seasonal influenza vaccination in adults", section on 'High-dose vaccine'.)

Recommended immunization schedule—United States, 2017 (March 2017)

The Advisory Committee on Immunization Practices has released the 2017 recommended immunization schedule for children and adolescents in the United States [60,61]. New recommendations include the following:

All infants should now receive monovalent hepatitis B vaccine within 24 hours of birth; earlier recommendations allowed some infants born to hepatitis B surface antigen-negative mothers to receive the vaccine after discharge. (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Mother's HBsAg status unknown, birth weight ≥2 kg'.)

When administered during pregnancy, the tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine should be given as early as possible between 27 and 36 weeks of gestation. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)

For individuals receiving the meningococcal serogroup B vaccine MenBFHbp (Trumenba), two doses are recommended for healthy adolescents and young adults who are not at increased risk for meningococcal disease. Three doses are recommended for individuals ≥10 years of age at increased risk for meningococcal disease and for use during serogroup B meningococcal disease outbreaks (table 4). Previously, three doses were recommended for all recipients. The dosing frequency and interval for the other serogroup B vaccine, MenB-4C (Bexsero), have not changed. (See "Meningococcal vaccines", section on 'Serogroup B meningococcus vaccines'.)

Meningococcal conjugate vaccination for HIV-infected patients (November 2016)

Growing evidence has suggested that HIV-infected individuals have a disproportionate incidence of invasive meningococcal disease, with an estimated risk 5 to 13 times that of the general population. Because of this, the Centers for Disease Control and Prevention in the United States now recommends meningococcal conjugate vaccination (with MenACWY-CRM [Menveo] or MenACWY-D [Menactra]) for all HIV-infected individuals older than two months [62]. This includes a primary vaccine series for those who have not previously received it and interval booster doses every several years; the precise schedule depends on the age of the patient (table 4). Individuals may also have separate indications for serogroup B meningococcal vaccination. Evidence of vaccine efficacy in HIV-infected patients is limited to immunologic outcomes. (See "Immunizations in HIV-infected patients", section on 'Meningococcal vaccine' and "Meningococcal vaccines".)

HPV vaccine dosing for individuals younger than 15 years (November 2016)

For individuals younger than 15 years receiving human papillomavirus (HPV) vaccination, two vaccine doses administered at least six months apart are now recommended by the Centers for Disease Control and Prevention in the United States [63]. This new vaccine schedule is similar to schedules used in other countries and is supported by data demonstrating that two vaccine doses in young females have similar immunogenicity to three doses. However, the efficacy of fewer than three doses for prevention of cervical neoplastic disease has not been directly established. Three doses are still recommended for individuals older than 15 years because they have lower immunologic responses to HPV vaccination. (See "Recommendations for the use of human papillomavirus vaccines", section on 'Immunization schedule'.)

Complement-mediated HUS, eculizumab, meningococcal group B vaccine, and risk for hemolytic anemia (September 2016)

The introduction of eculizumab (a monoclonal antibody that blocks activation of the terminal complement cascade) has significantly improved the outcome of patients with complement-mediated hemolytic uremic syndrome (HUS), a rare, potentially life-threatening disease. Eculizumab therapy increases the risk of meningococcal infection, and vaccination against Neisseria meningitidis (with a quadrivalent vaccine and, for patients older than 10 years, a serogroup B vaccine) has been recommended in treated patients. However, a review from Health Canada reported an increased risk of hemolytic anemia following receipt of the multicomponent meningococcal serogroup B vaccine (Bexsero, MenB-4C) among patients who were already being treated with eculizumab [64]. To minimize the risk of hemolysis, serogroup B meningococcal vaccination should be performed prior to the initiation of eculizumab therapy, if possible. In cases where prior vaccination is not possible, the manufacturer of eculizumab recommends that serogroup B meningococcal vaccination should be administered when patients are stable and their disease is well controlled and it is assumed that the blood level of eculizumab is high. (See "Complement-mediated hemolytic uremic syndrome", section on 'Adverse effects'.)

Investigational inactivated vaccine to prevent zoster and postherpetic neuralgia (September 2016)

The live attenuated zoster vaccine reduces the risk of herpes zoster with a reported vaccine efficacy of 60 to 70 percent in adults 50 years and older but appears to have decreased efficacy in adults 70 years and older. In an initial trial of the experimental recombinant inactivated zoster vaccine (HZ/su), administered in two doses, overall vaccine efficacy was 97 percent in adults 50 years and older. In a subsequent randomized, placebo-controlled trial of 13,900 patients aged 70 and older, vaccine efficacy for preventing herpes zoster and postherpetic neuralgia was each approximately 90 percent after a mean 3.7-year follow-up [65]. No serious adverse events were reported in either trial; however, reactions such as pain at the injection site and myalgias were more common among those who received the vaccine. If approved, this inactivated vaccine may be particularly useful for such older individuals and immunocompromised individuals who cannot receive live vaccines, but it requires two doses for initial protection. (See "Vaccination for the prevention of shingles (herpes zoster)", section on 'Investigational vaccines'.)

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