4. Pharmacology
• Therapeutic class: vaccine
• Mechanism of action
• Live attenuated vaccine
• Vaccine strain in Vaxchora® creates an incomplete, nontoxic
version of the cholera toxin
• Vaxchora® live attenuated cholera bacteria replicate in the
gastrointestinal tract, which stimulates immune response
(creation of antigen-specific antibodies against strain), providing
immunity against cholera bacteria
• Reason for introduction
• Approved for active immunization against disease caused by
Vibrio cholerae serogroup O1 (no protection against O139 or
other non-O1 groups)
• Approved for use in adults 18 through 64 years of age traveling to
cholera-affected areas
7. Contraindications/Precautions
(cont.)
• Precautions
• Immunologic response may be diminished in
immunocompromised patients
• Caution use in patients with immunocompromised close
contacts; transmission of vaccine strain to non-vaccinated close
contacts may occur through stool shedding from the recipient for
at least 7 days
9. Drug Interactions
• Chemotherapeutic agents (i.e. cisplatin, axitinib, afatinib, etc.) for
irradiation, antimetabolites, alkylating agents, cytotoxic drugs,
corticosteroids (i.e. prednisone, prednisolone, dexamethasone;
when used in greater than physiologic doses)
• Increased risk of infection by live vaccine due to decreased immune
response
• Those whose disease is in remission, have restored
immunocompetence, and have discontinued chemotherapy for at
least 3 months are eligible to receive
• Systemic antibiotics (i.e. azithromycin, cefazolin, cefixime, cefoxitin,
etc.)
• Prevent sufficient degree of multiplication of vaccine strain bacteria
to occur in order to induce protective immune response
• Do not administer Vaxchora® to patients who have received oral or
parenteral antibiotics within 14 days prior to vaccination.
10. Drug Interactions (cont.)
• Chloroquine (antimalarial prophylaxis)
• Decreased immune response when administered concurrently
with Vaxchora®
• Administer Vaxchora® at least 10 days before beginning
chloroquine
12. Monitoring Parameters
• Have not been established at this time (further post-marketing
follow-up studies needed to determine)
13. Patient Education
• Prevents cholera
• Side effects may include tiredness, headache, lack of appetite,
abdominal pain, nausea/vomiting/diarrhea
• Prevent transmission of vaccine strain to close contacts by
thoroughly washing hands after using the bathroom and
before preparing or handling food for at least 14 days after
dose
• Take drug at least 60 minutes before or 60 minutes after food
& drinks.
• Call your doctor right away should you experience any of
these symptoms (allergic reaction to drug):
• Itching or hives, swelling in face or hands, swelling or tingling in
mouth or throat, chest tightness, trouble breathing
14. Patient Education (cont.)
• If you are pregnant while taking this vaccine, register for the
pregnancy registry by calling 1-800-533-5899
• Exercise caution regarding food and water consumed in cholera-
affected areas in accordance with recommendations from the
Centers for Disease Control & Prevention for the prevention of
cholera in travelers
(https://www.cdc.gov/cholera/prevention.html)
15. Primary literature – Study 2
• Two studies cited in FDA approval/package insert to support
use
• One was efficacy study (Study 2)
• Randomized, double-blind study saline placebo-controlled V.
cholerae challenge study
• 197 subjects ages 18-45 with no prior history of cholera infection
or travel to cholera-endemic area in previous 5 years randomized
in 1:1 ratio to receive Vaxchora® or placebo (95 Vaxchora®
recipients, 102 placebo recipients after randomization)
• Subjects admitted to inpatient unit, had nothing by mouth from
midnight before ingestion of challenge strain (except water and
120 mL sodium bicarbonate buffer 1 minute prior to strain
ingestion), and had nothing by mouth 90 minutes after ingestion
of challenge strain
16. Primary literature – Study 2
(cont.)
• Challenge consisted of 1 x 105 CFU live wild type V-cholerae El Tor
Inaba N16961 in 30 mL NaHCO3 buffer
• Challenges split into 2 cohorts of either 10-day or 3 month
challenges; primary objective: demonstrate efficacy of single
Vaxchora® dose in prevention of moderate to severe diarrhea
following challenge at 10 days and 3-months post vaccination
• Severe diarrhea criteria
• Defined as cumulative diarrhea purge ≥ 3 L within 10 days after
challenge
• Diarrheal stool
• Defined as ≥ 2 unformed stools (takes shape of container) in 48-
hr period ≥ 200 g or single unformed stool ≥ 300 g
• Vaxchora® recipients challenged at 10 days and 3 months
compared with pooled group of placebo saline recipients
challenged at 10 days and 3 months
17. Primary literature – Study 2
(cont.)
• Of 95 Vaxchora® recipients, 68 were challenged; 35 were
challenged at 10 days, 33 at 3 months post-vaccination
• Of 102 placebo recipients, 66 were challenged; 33 at 10 days,
33 at 3 months post vaccination
• Vaccine efficacy against occurrence of moderate to severe
diarrhea
• At 10 days: 90.3 % [95% CI 62.7%, 100.0%]
• At 3 months: 79.5% [95% CI 49.9%, 100.0%]
19. Primary literature 2 – Study
1+4
• Study 1
• Conducted in U.S. and Australia – a randomized double-blind,
saline placebo-controlled safety + immunogenicity study
• 3146 subjects ages 18-45 not previously exposed to cholera
randomized 8:1 to receive 1 dose of Vaxchora® or placebo
• Study 4
• Conducted in U.S. – a randomized, double-blind, saline placebo-
controlled and immunogenicity study
• 398 subjects ages 46-64 with no prior history of cholera infection
or travel to cholera-endemic area in previous 5 years randomized
3:1 to receive 1 dose of Vaxchora or placebo
• Primary endpoint was seroconversion rate at 10 days post-
vaccination measured using a vibriocidal antibody assay
(Inaba)
21. Cost
• List Retail Price $225 per dose
• Wholesale Acquisition Cost (if part of the Big Three:
AmeriSource Bergen, Cardinal, McKesson): $191.25 per dose
• If buying 3+ doses in one order, shipping cost of $25 is waived
22. Sources
• Cholera vaccine, live. Micromedex Solutions. Truven Health
Analytics, Inc. Ann Arbor, MI. Available at:
http://www.micromedex.com. Accessed December 14, 2016.
• Vaxchora® [package insert]. Redwood City, CA: Paxvax Inc;
2016.
