August ID Update

Sanford Guide ID Update features current developments in infectious diseases, curated by the Sanford Guide Editorial Board. Links marked with an asterisk (*) provide details to Web Edition subscribers, while all other links are universal. If you received this message from a colleague, subscribe now.
 

August 2019

From CDC

  • Updated recommendations from the CDC Advisory Committee on Immunization Practices (ACIP) regarding prevention of Japanese encephalitis (JE) among US travelers and laboratory workers (MMWR Recomm Rep 2019;68(No. RR-2):1-33). The report summarizes the epidemiology of JE, describes the JE vaccine that is licensed and available in the US, and provides recommendations for its use. These recommendations update the 2010 release and are available on the CDC website.

Practice Pearls

  • Sofosbuvir/velpatasvir (Epclusa) is a pangenotypic, fixed-dose combination of sofosbuvir (NS5B RNA polymerase inhibitor) and velpatasvir (NS5A inhibitor) used for the treatment of chronic HCV. Velpatasvir is a lipophilic weak base with pH-dependent solubility (its solubility decreases as pH increases). Therefore, drugs like proton-pump inhibitors (PPI) impair velpatasvir absorption by raising gastric pH, and coadministration of sofosbuvir/velpatasvir with PPIs is generally not recommended. If it is medically necessary, the manufacturer recommends that sofosbuvir/velpatasvir be administered with food and taken four hours before omeprazole (20 mg). In a recent open-label, randomized, 3-arm crossover study, 11 healthy volunteers were administered a single dose of sofosbuvir/velpatasvir a) alone, b) with omeprazole (at steady-state concentrations), or c) with omeprazole combined with 250 mL of Coca-Cola. Pharmacokinetic sampling was performed on days 5-7 of each arm (see chart below). The data suggest that taking sofosbuvir/velpatasvir with Coca-Cola can overcome the interaction with proton-pump inhibitors, presumably by temporarily lowering gastric pH and thus enhancing velpatasvir solubility and absorption (Clin Pharmacol Ther 2019 Jul 17 [Epub ahead of print]).
    Study arm (seven days per arm, 7 days washout between arms) Velpatasvir AUC
    (geometric mean)
    Sofosbuvir/velpatasvir 400/100 mg on day 5 + 250 mL water 3742 mcg*hr/L
    Sofosbuvir/velpastavir 400/100 mg on day 5 + 250 mL water, omeprazole 40 mg qd (days 1-6) 2705 mcg*hr/L
    Sofosbuvir/velpastavir 400/100 mg on day 5 + 250 mL Coca-Cola, omeprazole 40 mg qd (days 1-6) 5981 mcg*hr/L

 

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of August 1, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since July 17]: Bacitracin ophthalmic ointment, Griseofulvin oral tablets, Letermovir tablets
    • [Shortage recently resolved]: Amphotericin B injection, Nelfinavir tablets, Valganciclovir oral powder for solution
    • [Continue to be in reduced supply]:
      • Aminoglycosides: Amikacin injection, Gentamicin ophthalmic ointment (unavailable), Tobramycin injection
      • Carbapenems: Meropenem injection
      • Cephalosporins: Cefazolin injection, Cefepime injection, Cefotaxime injection (unavailable), Cefoxitin injection, Ceftazidime injection, Ceftriaxone injection, Cefuroxime injection
      • Clindamycin injection
      • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Ciprofloxacin oral suspension, Gemifloxacin tablets
      • Glyco-, glycolipo-, lipopeptides: Daptomycin injection, Vancomycin injection
      • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable), Erythromycin lactobionate injection, Erythromycin 0.5% ophthalmic ointment
      • Nitrofurantoin oral suspension
      • Nitroimidazoles: Metronidazole injection
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline hyclate injection
      • Topical (miscellaneous) antibacterials: Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
      • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Nystatin oral suspension
      • Antiparasitic drugs: Pentamidine isethionate
      • Antiretroviral drugs: None
      • Antiviral drugs: Cidofovir injection (unavailable), Letermovir injection (unavailable)
      • Vaccines: Hepatitis A vaccine inactivated, Hepatitis B vaccine recombinant, Zoster vaccine recombinant (Shingrix), Yellow Fever vaccine (YF-VAX is unavailable, but Stamaril can be obtained through a limited number of clinics in the US. Click here).
  • Antimicrobial drugs newly discontinued: Quinidine gluconate IV (in December 2017). Product distribution will continue until expiration of current stock (March 2019).
    • Recent discontinuations: Terbinafine granules (in May 2017), MenHibrix (in February 2017), Elvitegravir (Vitekta, in December 2016), Peginterferon alfa-2b (in February 2016; 50 mcg vials still available in limited quantities), Boceprevir (in December 2015), Permethrin 1% topical lotion (in September 2015)
  • For detailed information including estimated resupply dates, see http://www.ashp.org/menu/DrugShortages