PreHevbrio: A New 3-Antigen Hepatitis B Vaccine for Adults.

OBJECTIVE: The main objective of this article is to review the immunogenicity and safety of the 3-antigen recombinant hepatitis B vaccine (3A-HepB) in adults. DATA SOURCES: A literature search was performed using PubMed and Google Scholar (2000 to June 2022) with the search terms hepatitis B vaccine and 3-antigen. Other resources included the Centers for Disease Control and Prevention, conference abstracts of liver meetings, the prescribing information, and the manufacturer's website. STUDY SELECTION AND DATA EXTRACTION: All English-language articles of studies assessing the immunogenicity and safety of 3A-HepB in humans were included. DATA SYNTHESIS: The 3A-HepB is licensed to prevent infection caused by all known subtypes of the hepatitis B virus in adults. It contains 3 hepatitis B surface antigens. The 3A-HepB has been shown to be noninferior to a single-antigen hepatitis B vaccine (1A-HepB). It is administered intramuscularly as a 3-dose series at 0, 1, and 6 months. The most commonly reported local reactions were injection site pain and tenderness, and the most commonly reported systemic reactions were headache, fatigue, and myalgia. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The introduction of 3A-HepB represents another step toward reducing the rates of new hepatitis B infections. However, clinical trials are needed to assess the immunogenicity of 3A-HepB in individuals at high-risk of nonresponse or low response to 1A-HepB, such as those with renal or hepatic impairment and those with altered immunocompetence. CONCLUSIONS: The 3A-HepB represents another vaccine to prevent hepatitis B in adults. It is safe and immunogenic but is associated with more adverse reactions than 1A-HepB.

Ibrexafungerp: A new triterpenoid antifungal.

PURPOSE: The pharmacology, microbiology, pharmacokinetics, pharmacodynamics, efficacy, safety, and role of ibrexafungerp in the treatment of fungal infections are reviewed. SUMMARY: Ibrexafungerp is the first triterpenoid antifungal. Similarly to echinocandins, it inhibits the synthesis of 1,3-ß-d-glucan. However, it binds to a different site on the enzyme than echinocandins, resulting in limited cross-resistance. Ibrexafungerp exerts concentration-dependent fungicidal activity against Candida species and retains in vitro activity against most fluconazole-resistant strains. It is also active against Aspergillus species. Ibrexafungerp has been shown to be safe and effective in the treatment of vulvovaginal candidiasis caused by Candida albicans in phase 2 and phase 3 clinical trials. It is approved for vulvovaginal candidiasis in adult and postmenarchal pediatric females and is given as two 150-mg tablets orally, administered 12 hours apart. Ibrexafungerp is contraindicated in pregnancy. The most commonly reported adverse reactions were diarrhea, nausea, abdominal pain, dizziness, and vomiting. Ibrexafungerp should be avoided with strong or moderate CYP3A inducers, and the dose should be reduced with strong CYP3A inhibitors. Ibrexafungerp may be useful for patients who are not able to receive fluconazole or prefer oral therapy for the treatment of vulvovaginal candidiasis. However, it is more expensive than the 150-mg tablet of generic fluconazole, which is the current standard of care for vulvovaginal candidiasis. Clinical trials are ongoing for recurrent and complicated vulvovaginal candidiasis as well as invasive candidiasis and pulmonary aspergillosis. CONCLUSION: Ibrexafungerp is an alternative to fluconazole for the treatment of vulvovaginal candidiasis in nonpregnant females. It has the potential to be useful for recurrent and complicated vulvovaginal candidiasis as well as certain invasive fungal infections.

Lefamulin: The First Systemic Pleuromutilin Antibiotic.

OBJECTIVE: To review the pharmacology, microbiology, efficacy, and safety of lefamulin. DATA SOURCES: A literature search was performed using PubMed and Google Scholar (2010 to end-April 2020) with the search terms BC-3781 and lefamulin. Other resources included abstracts presented at recent conferences, prescribing information, and the manufacturer's and Food and Drug Administration websites. STUDY SELECTION AND DATA EXTRACTION: All relevant English-language articles of studies assessing the efficacy and safety of lefamulin were included. DATA SYNTHESIS: Lefamulin is a pleuromutilin antibiotic with activity against Staphylococcus aureus, Streptococcus pneumoniae, and atypical bacteria. Lefamulin, given at the dose of 150 mg intravenously or 600 mg orally on an empty stomach every 12 hours for 5 to 7 days, was proven noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia (CABP). Common adverse reactions include injection site reactions, hepatic enzyme elevation, gastrointestinal upset, hypokalemia, insomnia, and headache. Lefamulin is associated with QT prolongation, and concomitant use with CYP3A substrates that prolong the QT interval is contraindicated. Lefamulin may cause fetal harm. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Lefamulin is a novel antibiotic with a unique mechanism of action. It represents an alternative option to ß-lactams and macrolides in the treatment of adults with CABP and an alternative option to amoxicillin and doxycycline in the outpatient setting given the rise in resistance to macrolides and safety concerns with fluoroquinolones. Nausea, vomiting, and diarrhea may limit the tolerability of the oral formulation. CONCLUSIONS: Lefamulin is the first systemic pleuromutilin antibiotic that has proven safe and effective for adults with CABP.

Omadacycline: A New Tetracycline Antibiotic.

OBJECTIVE: To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosage, and administration of omadacycline, a new tetracycline antibiotic. DATA SOURCES: A literature search through PubMed, Google Scholar, and clinicaltrials.gov was conducted (2008 to October 2018) using the search terms omadacycline and PTK-0796. Abstracts presented at recent conferences, prescribing information and information from the FDA and the manufacturer's website were reviewed. STUDY SELECTION AND DATA EXTRACTION: Preclinical data and published phase 1, 2, and 3 studies were evaluated. DATA SYNTHESIS: Omadacycline displays in vitro activity against a wide range of bacteria. Clinical trials have shown that omadacycline is noninferior to linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia (CABP). A loading dose of 200 mg intravenously (IV) once or 100 mg IV twice or 450 mg orally once is recommended followed by a maintenance dose of 100 mg IV or 300 mg orally once daily. No dosage adjustment is needed in patients with renal or hepatic impairment. Omadacycline is well tolerated, with nausea being a common adverse effect, but is associated with food and drug interactions. Relevance to Patient Care and Clinical Practice: Omadacycline is active against staphylococci, including methicillin-resistant strains, and streptococci, including tetracycline-resistant strains, as well as atypical bacteria. Omadacycline provides clinicians with an additional parenteral and oral option for the treatment of adults with ABSSSI and CABP. CONCLUSION: Omadacycline is an alternative treatment option for ABSSSI and CABP.

Shingrix: The New Adjuvanted Recombinant Herpes Zoster Vaccine.

OBJECTIVES: To review the immunogenicity, efficacy, and safety of the herpes zoster subunit vaccine (HZ/su) for use in adult patients for the prevention of shingles. DATA SOURCES: A literature search through PubMed was conducted (June 2008 to October 2017) using the terms shingles vaccine and varicella zoster virus. References from retrieved articles and the prescribing information were also reviewed for any additional material. STUDY SELECTION/DATA EXTRACTION: The literature search was limited to human studies published in English. Randomized controlled, multicenter trials were reviewed and included to evaluate the safety and efficacy of HZ/su. Literature on the epidemiology and pathology of herpes zoster virus infections and recommendations from the Advisory Committee on Immunization Practices (ACIP) were also reviewed. DATA SYNTHESIS: HZ/su is a new adjuvanted recombinant vaccine approved by the Food and Drug Administration for the prevention of herpes zoster in adults 50 years of age and older. HZ/su significantly reduced the risk of developing herpes zoster by more than 90% as compared with placebo and displayed a comparable adverse effect profile. The most common local adverse events were injection site pain, redness, and swelling, and the most common systemic adverse events were myalgia, fatigue, and headache. The ACIP recommends the routine use of HZ/su as the preferred vaccine for the prevention of herpes zoster in immunocompetent adults 50 years of age and older. CONCLUSIONS: Based on published immunogenicity, efficacy, and safety data, as well as the recent recommendations by the ACIP, HZ/su should be included on both hospital and community pharmacy formularies and recommended to all immunocompetent patients older than 50 years to prevent herpes zoster.

Sofosbuvir/Velpatasvir: The First Pangenotypic Direct-Acting Antiviral Combination for Hepatitis C.

OBJECTIVES: To review the pharmacology, efficacy, and safety of sofosbuvir/velpatasvir in the treatment of patients with hepatitis C virus (HCV) infection. DATA SOURCES: A literature search through PubMed was conducted (June 2008 to August 2016) using the terms GS-5816, velpatasvir, and sofosbuvir. References from retrieved articles and the prescribing information were reviewed for any additional material. STUDY SELECTION/DATA EXTRACTION: The literature search was limited to human studies published in English. Phase I, II, and III studies of sofosbuvir/velpatasvir for HCV were identified. DATA SYNTHESIS: Sofosbuvir/velpatasvir is indicated for adult patients with chronic HCV genotype 1 through 6. It is given without ribavirin in patients with or without compensated cirrhosis and with ribavirin in patients who have decompensated cirrhosis. The ASTRAL-1 study demonstrated that sofosbuvir 400 mg plus velpatasvir 100 mg for 12 weeks was effective at achieving high sustained virological response (SVR12) rates in patients with HCV genotype 1, 2, 4, 5, or 6. The ASTRAL-2 and ASTRAL-3 studies demonstrated that the same regimen was effective at achieving high SVR12 rates in patients with HCV genotype 2 or 3. The ASTRAL-4 study demonstrated that the same regimen plus ribavirin was effective at achieving high SVR12 rate in patients with decompensated cirrhosis. The most common adverse reactions (≥10% of patients) associated with sofosbuvir/velpatasvir were headache and fatigue. CONCLUSIONS: Sofosbuvir/velpatasvir is safe and effective to treat HCV genotypes 1, 2, 3, 4, 5, and 6 in patients with or without compensated cirrhosis. The addition of ribavirin is recommended in patients with decompensated cirrhosis.

Tedizolid: A New Oxazolidinone Antibiotic for Skin and Soft Tissue Infections.

OBJECTIVE: To review the chemistry, pharmacology, microbiology, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, drug interactions, dosing, and administration of tedizolid phosphate (TDZ). DATA SOURCES: A search of PubMed using the terms "tedizolid," "torezolid," "TR-701," "TR-700," "DA-7157," and "DA-7218" was performed. The manufacturer's Web site was also reviewed to further identify relevant information. STUDY SELECTION: All English-language articles from 2006 to November 2014 appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not uncovered in the searches. DATA SYNTHESIS: TDZ is the second oxazolidinone antibiotic with a spectrum of activity targeted against gram-positive organisms including methicillin-resistant Staphylococcus aureus . It is administered via intravenous infusion or orally without regard to food. The primary route of elimination is fecal excretion. Advanced age, hepatic dysfunction, or renal impairment does not alter its disposition. Phase III clinical trials have demonstrated that TDZ 200 mg daily for 6 days is noninferior to linezolid 600 mg twice daily for 10 days in the treatment of adults with skin and soft tissue infections caused or suspected to be caused by gram-positive organisms. TDZ has a side effect profile similar to that of linezolid and a lower potential for drug interactions. CONCLUSION: TDZ has been shown to be safe and effective for the treatment of adults with skin and soft tissue infections. Further research is needed to refine its role, particularly for the treatment of patients requiring a longer duration of therapy and in those receiving concomitant serotonergic agents.

Ceftolozane/Tazobactam: A New Cephalosporin and ß-Lactamase Inhibitor Combination.

OBJECTIVE: To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosage, and administration of ceftolozane/tazobactam, a new antipseudomonal cephalosporin combined with a well-established ß-lactamase inhibitor. DATA SOURCES: A literature search through clinicaltrials.gov and PubMed was conducted (January 2007-May 2015) using the search terms ceftolozane, ceftolozane/tazobactam, FR264205, CXA-101/tazobactam, and CXA-201. References from retrieved articles and abstracts presented at recent meetings were reviewed to identify additional material. The prescribing information was also reviewed. STUDY SELECTION AND DATA EXTRACTION: Preclinical data as well as phase 1, 2, and 3 studies published in English were evaluated. DATA SYNTHESIS: Ceftolozane/tazobactam displays enhanced potency against Pseudomonas aeruginosa in vitro. Clinical trials have shown that ceftolozane/tazobactam is noninferior to levofloxacin for the treatment of complicated urinary tract infections (76.9% vs 68.4%, 95% CI = 2.3-14.6) and when used in combination with metronidazole is noninferior to meropenem for the treatment of complicated intra-abdominal infections (83% vs 87.3%, 95% CI = -8.91 to 0.54). An alternate antibiotic should be considered in patients who have a severe ß-lactam allergy or an estimated creatinine clearance between 30 and 50 mL/min. Ceftolozane/tazobactam is well tolerated, with few drug interactions and no effects on the cytochrome P450 system. CONCLUSIONS: In an era of increasing resistance to antimicrobials, ceftolozane/tazobactam provides clinicians with an additional treatment option for infections caused by multidrug-resistant Gram-negative organisms, including extended-spectrum ß-lactamase-producing bacteria and Pseudomonas aeruginosa.

Fidaxomicin: a novel macrolide antibiotic for Clostridium difficile infection.

OBJECTIVE: To review the chemistry, pharmacology, microbiology, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, drug interactions, dosing, and administration of fidaxomicin (FDX). DATA SOURCES: A search of PubMed using the terms "fidaxomicin," "OPT-80," "PAR-101," "OP-1118," "difimicin," "tiacumicin," and "lipiarmycin" was performed. All English-language articles from 1983 to November 2013 were reviewed for relevance. Bibliographies of all articles were reviewed as well as the manufacturer's Web site to further identify relevant information. STUDY SELECTION: All English-language articles from 1983 to November 2013 appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not identified in the searches. DATA SYNTHESIS: FDX is the first macrolide antibiotic with a narrow spectrum of activity targeted against Clostridium difficile. It is administered orally without regard to food. The primary route of elimination is fecal excretion. Advanced age, hepatic dysfunction, or renal impairment do not alter its disposition. Phase III clinical trials have demonstrated that FDX 200 mg twice daily for 10 days is noninferior to vancomycin 125 mg four times daily for 10 days in the treatment of adults with C. difficile infection and is associated with lower recurrence rates. FDX has a favorable side effect profile and a low potential for drug interactions. CONCLUSION: FDX has been shown to be safe and effective in the treatment of adults with C. difficile infection. Further research and pharmacoeconomic studies are needed to clarify and refine its role in the treatment of patients at high risk for recurrence.

Prevnar 13, the new 13-valent pneumococcal conjugate vaccine.

OBJECTIVE: To review the immunogenicity, efficacy, and safety of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in pediatric patients. DATA SOURCES: A MEDLINE search (2000-September 2011) was conducted using the key words Streptococcus pneumoniae and pneumococcal conjugate vaccine for clinical trials, limited to studies conducted in humans and published in English. STUDY SELECTION AND DATA EXTRACTION: Randomized, controlled, multicenter trials were reviewed and included to evaluate the safety and efficacy of PCV13. Literature on the epidemiology and pathology of pneumococcal infections and recommendations from the Advisory Committee on Immunization Practices (ACIP) were also reviewed. DATA SYNTHESIS: PCV13 is approved for routine vaccination of all infants as a 4-dose series at age 2, 4, 6, and 12-15 months for children who previously received 1 or more doses of the 7-valent pneumococcal conjugate vaccine (PCV7), and for children with underlying medical conditions that increase their risk for pneumococcal disease or its complications. PCV13 has comparable immunogenicity to the serotypes common with PCV7 and also provides protection against 6 additional pneumococcal serotypes. PCV13 has also been shown to have a comparable adverse reaction profile to PCV7. CONCLUSIONS: Based on published immunogenicity and safety data, as well as the recent recommendations by the ACIP for routine use in infants and indications for high-risk pediatric patients, PCV13 is a revised formulation of pneumococcal vaccine that should be included on pharmacy formularies.

Echinocandins: the newest class of antifungals.

OBJECTIVE: To review the mechanism of action, antifungal spectrum of activity, pharmacodynamics, pharmacokinetics, clinical efficacy, and safety of the echinocandins. DATA SOURCES: A MEDLINE search (1982-May 2009) was conducted for articles published in the English language using the key words caspofungin, micafungin, anidulafungin, and echinocandins. STUDY SELECTION AND DATA EXTRACTION: Medicinal chemistry, in vitro, and animal studies, as well as human trials were reviewed for information on the pharmacodynamics, pharmacokinetics, efficacy, and safety of each echinocandin. Clinical trials were reviewed and included to compare and contrast the available echinocandins. DATA SYNTHESIS: Three echinocandin antifungal agents are currently approved for use in the US: caspofungin, micafungin, and anidulafungin. The echinocandins have a unique mechanism of action, inhibiting beta-(1,3)-D-glucan synthase, an enzyme that is necessary for the synthesis of an essential component of the cell wall of several fungi. The echinocandins display fungistatic activity against Aspergillus spp. and fungicidal activity against most Candida spp., including strains that are fluconazole-resistant. The echinocandins have been shown to be efficacious for the treatment of esophageal candidiasis, candidemia, and invasive candidiasis. In addition, caspofungin has demonstrated efficacy as empiric treatment of febrile neutropenia and salvage therapy for the treatment of invasive aspergillosis, and it is the only echinocandin approved for use in pediatric patients. Micafungin is the only echinocandin approved for use as prophylaxis against Candida infections in patients undergoing hematopoietic stem cell transplantation. Overall, resistance to echinocandins is still rare, and all agents are well tolerated, with similar adverse effect profiles and few drug-drug interactions. CONCLUSIONS: Echinocandins, the newest addition to the arsenal of antifungals, offer potential advantages over other classes of agents. Clinicians should assess their distinguishing characteristics, including route of metabolism, drug interaction profile, and approved indications for use, when determining which agent to include on a formulary.