Pharmacology
Mechanism of Action
Dengue tetravalent vaccine is a live vaccine that offers active immunization against dengue serotypes 1, 2, 3 and 4 in individuals previously infected with dengue fever.
Efficacy: In patients 9 to 16 years of age seropositive for dengue at baseline, the dengue tetravalent vaccine demonstrated 77% to 81% efficacy to any dengue virus serotypes after the third dose.
Pharmacokinetics/Pharmacodynamics
Duration of Action
Efficacy of 77% to 81% was demonstrated over a period of 12 months.
Use: Labeled Indications
Dengue disease, prevention: Prevention of dengue disease caused by dengue virus serotypes 1, 2, 3 and 4 in patients 9 to 16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas.
Limitations of use: Not approved for use in individuals not previously infected by any dengue virus serotype or for whom this information is unknown. Those not previously infected are at increased risk for severe dengue disease when vaccinated and subsequently infected with dengue virus. Previous dengue infection can be assessed through a medical record of a previous laboratory-confirmed dengue infection or through serological testing prior to vaccination. The safety and effectiveness of dengue tetravalent vaccine (live) have not been established in individuals living in dengue nonendemic areas who travel to dengue endemic areas.
Contraindications
Severe hypersensitivity to dengue tetravalent vaccine (live) or any component of the formulation; severe immunodeficiency or immunosuppression due to disease or therapy
Dosage and Administration
Dosing: Pediatric
Dengue disease (fever) prevention (immunization): Note: Should only be used in individuals with previous dengue disease (laboratory-confirmed) and living in endemic areas. Administration to individuals without previous infection increases the risk of severe dengue disease.
Children ≥9 years and Adolescents ≤16 years: SubQ: 0.5 mL/dose for 3 doses administered at 0, 6, and 12 months.
Storage
Store lyophilized vaccine antigen and diluent refrigerated at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. After reconstitution, use immediately or store refrigerated for up to 30 minutes; discard if not used within 30 minutes of reconstitution.
Drug Interactions
Axicabtagene Ciloleucel: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of infection may be increased. Axicabtagene Ciloleucel may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live virus vaccines for at least 6 weeks prior to initiation of lymphodepleting therapy, during axicabtagene ciloleucel infusion, and after treatment until full immune recovery is achieved. Consider therapy modification
AzaTHIOprine: May enhance the adverse/toxic effect of Vaccines (Live). AzaTHIOprine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose azathioprine (3 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of azathioprine should be avoided. Consider therapy modification
Belimumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Consider therapy modification
Daclizumab: May enhance the adverse/toxic effect of Vaccines (Live). Daclizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination
Dimethyl Fumarate: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, Dimethyl Fumarate may increase the risk of vaccinal infection. Dimethyl Fumarate may diminish the therapeutic effect of Vaccines (Live). Management: Canadian labeling for dimethyl fumarate states that live attenuated vaccine administration is not recommended during treatment. U.S. labeling does not mention this. Consider therapy modification
Dupilumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination
Fingolimod: May enhance the adverse/toxic effect of Vaccines (Live). Vaccinal infections may develop. Fingolimod may diminish the therapeutic effect of Vaccines (Live). Avoid combination
Guselkumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination
Immune Globulins: May diminish the therapeutic effect of Vaccines (Live). Management: Consult full interaction monograph for dose interval recommendations. This interaction does not apply to oral Ty21a typhoid vaccine or others listed as exceptions. Consider therapy modification
Immunosuppressants: May enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: AzaTHIOprine; Beclomethasone (Oral Inhalation); Betamethasone (Systemic); Budesonide (Systemic); Corticotropin; Cortisone; Cytarabine (Liposomal); Deflazacort; DexAMETHasone (Systemic); Fludrocortisone; Fluticasone (Oral Inhalation); Hydrocortisone (Systemic); Leflunomide; Mercaptopurine; Methotrexate; MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE; Triamcinolone (Systemic). Avoid combination
Leflunomide: May enhance the adverse/toxic effect of Vaccines (Live). Leflunomide may diminish the therapeutic effect of Vaccines (Live). Management: The ACIP guidelines state that live-attenuated vaccines should generally be avoided for at least 3 months after cessation of immunosuppressant therapy. However, the ACR does not recommend avoiding live vaccines in patients being treated with leflunomide. Consider therapy modification
Mercaptopurine: May enhance the adverse/toxic effect of Vaccines (Live). Mercaptopurine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose 6-mercaptopurine (1.5 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of mercaptopurine should be avoided. Consider therapy modification
Methotrexate: May enhance the adverse/toxic effect of Vaccines (Live). Methotrexate may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose methotrexate (0.4 mg/kg/week or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses of methotrexate should be avoided. Consider therapy modification
Ocrelizumab: May enhance the adverse/toxic effect of Vaccines (Live). Ocrelizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination
Rabies Immune Globulin (Human): May diminish the therapeutic effect of Vaccines (Live). Management: Avoid administering the measles vaccine within 4 months after administration of rabies immune globulin. Avoid administering other live vaccines within 3 months after administration of rabies immune globulin. Consider therapy modification
Risankizumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination
Tildrakizumab: May enhance the adverse/toxic effect of Vaccines (Live). The risk for contracting an infection from the vaccine may be increased. Tildrakizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination
Tisagenlecleucel: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of infection may be increased. Tisagenlecleucel may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live virus vaccines for two weeks prior to initiation of lymphodepleting therapy, during tisagenlecleucel infusion, and after treatment until full immune recovery is achieved. Consider therapy modification
Tuberculin Tests: Vaccines (Live) may diminish the diagnostic effect of Tuberculin Tests. Management: If a parenteral live vaccine has been recently administered, a scheduled PPD skin test should not be administered for at least 4-6 weeks following the administration of the vaccine. Consider therapy modification
Vaccines (Live): May diminish the therapeutic effect of other Vaccines (Live). Management: Two or more injectable or nasally administered live vaccines not administered on the same day should be separated by at least 28 days (ie, 4 weeks). If not, the vaccine administered second should be repeated at least 4 week later. Exceptions: Adenovirus (Types 4, 7) Vaccine; Cholera Vaccine; Rotavirus Vaccine. Monitor therapy
Venetoclax: May enhance the adverse/toxic effect of Vaccines (Live). Venetoclax may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live, attenuated vaccines before, during, or after (prior to B-cell recovery) venetoclax treatment. Avoid combination
Adverse Reactions
>10%:
Central nervous system: Headache (30%), malaise (19% to 21%)
Local: Pain at injection site (23% to 32%)
Neuromuscular & skeletal: Myalgia (20% to 29%), asthenia (18% to 25%)
1% to 10%: Local: Swelling at injection site (2% to 4%)
<1%, postmarketing, and/or case reports: Abdominal pain, anaphylaxis, dyspnea, erythema of skin, hematoma at injection site, hypersensitivity reaction, injection site pruritus, local anesthesia (injection site), status asthmaticus, urticaria, vertigo, vomiting
Warnings/Precautions
Concerns related to adverse effects:
- Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (ACIP [Kroger 2017]).
- Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Kroger 2017]).
Concurrent drug therapy issues:
- Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist (ACIP [Kroger 2017]).
Special populations:
- Adults: Not intended for use in patients >16 years of age.
- Altered immunocompetence: Use is contraindicated in severely immunocompromised patients (eg, patients receiving chemo-/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]); may have a reduced response to vaccination or may have an adverse event secondary to replication.
- Persons not previously infected with dengue virus: Do not administer to persons not previously infected with dengue virus; administration to these persons is associated with an increased risk of severe dengue disease when the vaccinated individual is subsequently infected with any dengue virus serotype. Prior to vaccination, evaluate individuals for prior dengue infection (ie, documentation of previous laboratory-confirmed infection or perform serotesting).
Other warnings/precautions:
- Appropriate use: Only for use in patients with laboratory-confirmed previous dengue infection and living in endemic areas.
- Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Kroger 2017]).
Monitoring Parameters
Observe for anaphylaxis and syncope for 15 minutes following administration (ACIP [Kroger 2017]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.
Pregnancy
Pregnancy Considerations
Information related to the use of dengue tetravalent vaccine (live) in pregnancy is limited (Skipetrova 2018). It is not known if the live virus from this vaccine can be transmitted from mother to fetus; however, vertical transmission of dengue virus has been reported in infected females with viremia at delivery
Maternal infection with dengue virus may increase the risk of adverse pregnancy outcomes.
Data collection to monitor pregnancy and infant outcomes following maternal immunization with dengue tetravalent vaccine (live) is ongoing. Healthcare providers are encouraged to enroll females vaccinated during pregnancy in the Pregnancy Registry (800-822-2463); females may also enroll themselves.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience muscle pain; headache; loss of strength and weakness; or injection site pain, redness, or edema. Have patient report immediately to prescriber dizziness or passing out (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
