Daclatasvir Dihydrochloride and Varicella Virus Vaccine Live

• Generic Name: daclatasvir
• Dosage Forms: n.a.
• Other Brand Names: Daklinza

Treatment of chronic HCV genotype 1 or genotype 3 infection in treatment-naive (previously untreated) or previously treated adults, including those with cirrhosis (compensated or decompensated), liver transplant recipients, and those with HIV coinfection.

Treatment of chronic HCV genotype 2 or genotype 4 infection; only limited data available.

Must be used in conjunction with other antivirals; do not use alone.

Usually used in a multiple-drug regimen that includes sofosbuvir (with or without ribavirin).

Efficacy of daclatasvir and sofosbuvir (with or without ribavirin) for treatment of HCV genotype 1a infection is reduced in cirrhotic patients with NS5A polymorphisms M28, Q30, L31, or Y93 at baseline. Consider screening for NS5A polymorphisms prior to initiation of treatment in cirrhotic patients with HCV genotype 1a infection. (See General under Dosage and Administration.)

Efficacy of daclatasvir and sofosbuvir (with or without ribavirin) is reduced in cirrhotic patients with HCV genotype 3 infection compared with those without cirrhosis.

Treatment of chronic HCV infection is complex and rapidly evolving; consult a specialist to obtain the most up-to-date information.

• Generic Name: varicella virus vaccine
• Dosage Forms: n.a.
• Other Brand Names: Varivax

Prevention of varicella (chickenpox) in adults, adolescents, and children ≥12 months of age.

Varicella is caused by primary infection with varicella zoster virus (VZV). In otherwise healthy children, varicella usually is an acute, self-limited disease characterized by fever, malaise, and a generalized vesicular rash consisting of 200–500 lesions. In neonates, adolescents, adults, and immunocompromised individuals, it may be a more serious illness associated with a greater number of lesions and an increased risk of complications (e.g., pneumonia, encephalitis, glomerulonephritis, bacterial superinfection including necrotizing fasciitis). In the past, there were an average of 4 million cases of varicella and 100–150 varicella-associated deaths each year in the US. Since 1995, when varicella vaccine became commercially available, there have been substantial decreases in the incidence of varicella and varicella-associated hospitalizations in the US in all age groups, especially in children 1–9 years of age. The number of hospitalizations and deaths from varicella decreased >90% in the US since 1996.

USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and American Academy of Family Physicians (AAFP) recommend that all susceptible children 12 months through 12 years of age be vaccinated against varicella, unless the vaccine is contraindicated. (See Contraindications under Cautions.)

ACIP, AAP, AAFP, American College of Obstetricians and Gynecologists (ACOG), and American College of Physicians (ACP) recommend that all susceptible adults and adolescents ≥13 years of age be vaccinated against varicella, unless contraindicated. (See Contraindications under Cautions.)

For internationally adopted children whose immune status is uncertain, vaccinations can be repeated or serologic tests performed to confirm immunity. Because varicella vaccine is not available in the majority of countries, especially developing countries, all internationally adopted children without reliable evidence of varicella immunity should be vaccinated according to the US recommended immunization schedule. (See Dosage and Administration.) Although serologic testing to verify immunization status in children >12 months of age is available, such testing prior to vaccination is not recommended in children <12 years of age coming from tropical countries, unless there is a history of the disease.

The fixed-combination vaccine containing measles, mumps, and rubella virus vaccine live (MMR) and varicella virus vaccine live (MMRV; ProQuad) may be used instead of the monovalent varicella vaccine in children 12 months through 12 years of age when a dose of MMR and a dose of varicella vaccine is indicated in this age group. ACIP, AAP, and AAFP state that use of a combination vaccine generally is preferred over separate injections of the equivalent component vaccines. However, although use of MMRV (ProQuad) reduces the number of required injections when both vaccines are indicated during a single health-care visit, there is some evidence that the relative risk for febrile seizures in infants 12 through 23 months of age may be higher with MMRV (ProQuad) than when a dose of Varivax and a dose of MMR are given concomitantly. (See Use of Fixed Combinations under Cautions.)

ACIP states that evidence of varicella immunity includes documentation of age-appropriate vaccination against varicella, laboratory evidence of immunity or laboratory confirmation of prior varicella, birth in the US before 1980 (except pregnant women, immunocompromised individuals, health-care personnel), diagnosis or verification of history of varicella by health-care provider, or diagnosis or verification of history of herpes zoster (shingles, zoster) by health-care provider. Individuals without such evidence should be considered susceptible to varicella.

Health-care personnel should ensure that they are immune to varicella, especially those who have close contact with individuals at high risk for serious complications from varicella. ACIP and the Hospital Infection Control Practices Advisory Committee of the US Public Health Service (HICPAC) recommend vaccination against varicella in all susceptible health-care personnel. This protects the worker following varicella exposure in the workplace and also may help reduce nosocomial transmission of VZV.

Travelers should be vaccinated against varicella. Varicella occurs worldwide. Although vaccination against varicella is not a requirement for entry into any country (including the US), CDC states that individuals traveling or living abroad should ensure that they are immune.

Certain immunocompromised individuals at risk of severe complications from varicella may benefit from vaccination against the disease. However, varicella vaccine generally is contraindicated in adults, adolescents, and children who are immunocompromised. (See Individuals with Altered Immunocompetence under Cautions.)

ACIP, AAP, CDC, National Institutes of Health (NIH), HIV Medicine Association of the Infectious Diseases Society of America (IDSA), Pediatric Infectious Diseases Society, and others recommend that vaccination against varicella be considered for certain HIV-infected individuals, especially those who are asymptomatic or only mildly symptomatic. These experts state that, after weighing risks and benefits, use of monovalent varicella vaccine should be considered in HIV-infected children 1–8 years of age with age-specific CD4+ T-cell percentages ≥15% and may be considered in HIV-infected adults, adolescents, and children >8 years of age with CD4+ T-cell counts ≥200/mm3. Other HIV-infected adults, adolescents, or children who are more severely immunocompromised should not receive varicella vaccine. (See Individuals with Altered Immunocompetence under Cautions.)

Although monovalent varicella vaccine was previously used under an investigational protocol in certain children and adolescents with acute lymphocytic (lymphoblastic) leukemia (ALL) in remission, this protocol has been terminated. The ACIP and AAP state that varicella vaccine should not be used routinely in susceptible children with leukemia and use of the vaccine in leukemic children in remission who do not have evidence of immunity to varicella should only be undertaken with expert guidance and only if antiviral therapy is available in case complications occur. (See Individuals with Altered Immunocompetence under Cautions.)

Postexposure vaccination in susceptible adults, adolescents, or children with recent exposure to varicella, unless contraindicated.

Prevention and control of varicella outbreaks (e.g., in child-care facilities, schools, institutions). Varicella outbreaks can persist for up to 4–6 months.

May prevent varicella or modify severity of the disease if given within 3 days, and possibly up to 5 days, after exposure.

If the exposure does not cause infection, postexposure vaccination should provide protection against subsequent exposure. If the exposure results in infection, vaccination during the presymptomatic or prodromal stage of varicella does not appear to increase risk for vaccine-associated adverse effects or cause more severe natural disease.

During varicella outbreaks, ACIP recommends a second dose of varicella vaccine for those who previously received only a single dose, provided the age-appropriate time interval has elapsed since the first dose (i.e., 3 months for children 12 months through 12 years of age, at least 4 weeks for adults and adolescents ≥13 years of age).

In hospital settings, consider postexposure vaccination for unvaccinated health-care personnel who have no evidence of immunity at the time of varicella exposure. Preexposure vaccination is the preferred method for preventing varicella in health-care settings.

When varicella vaccine cannot be used (e.g., pregnant women, neonates, immunocompromised individuals) and postexposure prophylaxis is considered necessary, passive immunization with varicella zoster immune globulin (VZIG) is recommended to prevent or reduce severity of varicella. The only VZIG preparation currently available for use in the US (VariZIG; Cangene) must be obtained through an investigational new drug (IND) expanded access protocol from the distributor (FFF Enterprises at 800-843-7477). If VZIG is not available for postexposure prophylaxis, immune globulin IV (IGIV) can be used.