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![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%]](https://image.slidesharecdn.com/e59cb351-f66c-47c5-8c16-85902fd6af5b-161217155217/85/New-Drug-Update-Vaxchora-17-320.jpg)
![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.](https://image.slidesharecdn.com/e59cb351-f66c-47c5-8c16-85902fd6af5b-161217155217/85/New-Drug-Update-Vaxchora-22-320.jpg)
![Cholera Disease hya 2[1] [Read-Only].pptx](https://cdn.slidesharecdn.com/ss_thumbnails/choleradiseasehya21read-only-230528122422-1de77771-thumbnail.jpg?width=640&height=640&fit=bounds)
New Drug Update - Vaxchora
- 1. New Drug Update- Vaxchora® Jack Mao University of Pittsburgh School of Pharmacy PharmD Candidate, Class of 2017
- 2. Vaxchora® • Live oralcholera vaccine • Manufacturer: Paxvax, Inc. • Approved by FDA in June 2016
- 3. Dosing/Route of Administration •Dose: Single dose (100 mL of reconstituted suspension) • Route of administration: oral
- 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
- 5. Therapeutic Information • Indications •Vibrio cholerae serogroup O1 prophylaxis • Unlabeled uses • No uses off-label
- 6. Contraindications/Precautions • Contraindications • Severehypersensitivity (anaphylaxis) to oral cholera vaccine components or to a previous dose of any cholera vaccine
- 7. Contraindications/Precautions (cont.) • Precautions • Immunologicresponse 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
- 8. 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%)
- 9. Drug Interactions • Chemotherapeuticagents (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
- 11. Renal/Hepatic Adjustment • Norenal/hepatic adjustment necessary
- 12. Monitoring Parameters • Havenot been established at this time (further post-marketing follow-up studies needed to determine)
- 13. Patient Education • Preventscholera • 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%]
- 18. Primary literature –Study 2 addendum
- 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)
- 20.
- 21. Cost • List RetailPrice $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.
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