New Drug Update - Vaxchora®
Jack MaoUniversity of Pittsburgh School of Pharmacy
PharmD Candidate, Class of 2017
Vaxchora®
• Live oral cholera vaccine• Manufacturer: Paxvax, Inc.• Approved by FDA in June 2016
Dosing/Route of Administration
• Dose: Single dose (100 mL of reconstituted suspension)• Route of administration: oral
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
Therapeutic Information
• Indications• Vibrio cholerae serogroup O1 prophylaxis
• Unlabeled uses• No uses off-label
Contraindications/Precautions
• Contraindications• Severe hypersensitivity (anaphylaxis) to oral cholera vaccine
components or to a previous dose of any cholera vaccine
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
Adverse Effects
• Fatigue (31.3%)• Headache (28.9%)• Abdominal pain (18.7%)• Nausea/vomiting (18.3%)• Lack of appetite (16.5%)• Diarrhea (3.9%)• Fever (0.6%)
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.
Drug Interactions (cont.)
• Chloroquine (antimalarial prophylaxis)• Decreased immune response when administered concurrently
with Vaxchora®• Administer Vaxchora® at least 10 days before beginning
chloroquine
Renal/Hepatic Adjustment
• No renal/hepatic adjustment necessary
Monitoring Parameters
• Have not been established at this time (further post-marketing follow-up studies needed to determine)
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
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)
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
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
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%]
Primary literature – Study 2 addendum
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)
Results – Study 1+4
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
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.
Any questions?