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Cholera Vaccine Live Oral

Class: Vaccines
Brands: Vaxchora

Introduction

Live, attenuated bacterial vaccine containing Vibrio cholerae strain CVD 103-HgR derived from V. cholerae serogroup O1.1 2 3 Other cholera vaccines (e.g., oral inactivated vaccine containing whole-cell V. cholerae O1 with recombinant cholera toxin B subunit, oral inactivated vaccine containing whole-cell V. cholerae O1 and O139) may be available in other countries.2 4 6 7 8 11 115

Uses for Cholera Vaccine Live Oral

Prevention of Cholera Infection

Prevention of disease caused by V. cholerae serogroup O1 in adults 18 through 64 years of age traveling to cholera-affected areas.1

Cholera is an acute, intestinal infection caused by toxigenic V. cholerae and may be associated with sudden onset of profuse watery diarrhea and rapid progression to volume depletion, severe dehydration, hypovolemic shock, and death.3 5 7 8 11 115 Many individuals with V. cholerae infection are asymptomatic or have only mild to moderate disease;7 8 11 10–20% of infected individuals develop severe disease and potentially fatal dehydration.7 Transmitted principally by ingestion of water and/or food contaminated with feces from individuals with V. cholera infection and generally occurs in countries that lack clean drinking water or proper sanitation.5 7 8 11 115 Although more than 200 V. cholerae serogroups identified,11 only toxigenic strains of V. cholerae serogroups O1 and O139 have been associated with cholera epidemics; serogroup O1 is the leading cause of cholera worldwide.3 8 11 115

Cholera is uncommon in US, but endemic in approximately 50–60 countries, principally in less well-developed areas of the world that have poor sanitation and primitive water systems (e.g., areas of Africa, South and Southeast Asia, the Caribbean).3 5 7 9 11 115 In 2015, 172,454 cases (including 1304 fatalities) were reported in 42 different countries.8 9 However, many cases unreported and it has been estimated that up to 3–4 million cholera cases (up to 95,000–143,000 fatalities) may occur annually worldwide.3 8 9 11 Large cholera epidemic began in Haiti in 2010 following a devastating earthquake;9 115 CDC states cholera likely to persist at endemic levels in Haiti for the foreseeable future and sporadic cases may continue be associated with travel to and from Caribbean countries, including Haiti, the Dominican Republic, and Cuba.5 115

During 2001–2013, there were 123 confirmed cases of cholera in the US in individuals who had been traveling abroad.115 Risk of acquiring cholera is highest in those traveling to countries where cholera is endemic or epidemic, and is especially high in travelers who drink untreated water, eat raw or poorly cooked food (especially seafood), or do not follow proper hygiene recommendations while in cholera endemic or outbreak settings.115 Individuals at increased risk for poor clinical outcome if infected with toxigenic V. cholerae include those without rapid access to medical care and rehydration therapy; those with certain chronic medical conditions (e.g., immunosuppression, cardiovascular disease, renal disease); those with low gastric acidity related to antacid therapy, partial gastrectomy, or other causes; those with blood type O; and pregnant women.3 11

For US travelers, the US Public Health Service Advisory Committee on Immunization Practices (ACIP) recommends cholera vaccine live oral for adults 18 through 64 years of age who will be at increased risk of exposure to toxigenic V. cholerae O1 because they will be traveling to areas with active cholera transmission.3 4 These areas are defined as a province, state, or other administrative subdivision within a country with endemic or epidemic cholera caused by toxigenic V. cholerae O1.3 4 This includes areas that have had cholera activity within the past year and are prone to recurrence of cholera epidemics;3 does not include areas with only rare imported or sporadic cholera cases.3

ACIP states that routine use of cholera vaccine is not recommended for most travelers from the US since the majority do not visit areas with active cholera transmission and, therefore, are at low risk of exposure to toxigenic V. cholerae.3 4

Efficacy for prevention of cholera not established in individuals living in cholera-affected areas or in individuals who have preexisting immunity because of previous exposure to V. cholerae or previous vaccination with a cholera vaccine.1

Has not been shown to provide protection against disease caused by V. cholerae serogroup O139 or other non-O1 serogroups.1

All travelers to cholera-affected areas should follow safe food and water precautions and proper sanitation and personal hygiene measures, regardless of vaccination status.3 7 8 9 115 If severe diarrhea develops, traveler should seek prompt medical attention, particularly fluid replacement therapy.3

The most recent information regarding geographic areas where cholera is actively being transmitted and additional information on vaccination and other precautions for prevention of cholera are available from CDC at and .4 115

Cholera Vaccine Live Oral Dosage and Administration

Administration

Oral Administration

Administer orally as a single dose.1

Avoid eating or drinking for 60 minutes before and after ingestion of the vaccine.1

Provided by the manufacturer in single-dose carton that contains foil packet of lyophilized live, attenuated V. cholerae CVD 103-HgR (active component) and foil packet of dry powder buffer (buffer component).1 Reconstitute and mix these 2 components according to manufacturer's instructions to provide an oral suspension containing cholera vaccine live oral.1 (See Reconstitution under Dosage and Administration.)

Oral suspension must be administered within 15 minutes after preparation.1 Swallow entire contents of the cup (100 mL) at one time.1

After the vaccine is administered, the cup (including any residue remaining in the cup), stirrer, and empty component packets are considered biohazardous materials;1 handle and dispose of according to standard procedures for medical waste.1 Use 70% isopropyl alcohol or 10% bleach to clean nondisposable equipment used to prepare the oral suspension and to inactivate any spilled vaccine.1

Reconstitution

Remove single-dose carton containing foil packet of lyophilized live, attenuated V. cholerae CVD 103-HgR (active component) and foil packet of dry powder buffer (buffer component) from freezer.1 Thawing unnecessary.1 Use within 15 minutes after removal from frozen storage;1 do not expose packets to temperatures >27°C.1 (See Storage under Stability.)

The buffer component must be reconstituted first.1 Open foil packet of buffer component with scissors and pour contents into a clean disposable cup containing 100 mL of cold or room temperature (5–22°C) purified bottled water;1 do not use tap water, nonpurified bottled water, or any other beverage or liquid.1 Effervescence will occur;1 stir with a disposable stirrer until powder buffer dissolves completely.1

After buffer component is dissolved, open foil packet containing lyophilized cholera vaccine (active component) with scissors and pour contents into the cup containing reconstituted buffer.1 Stir the mixture for at least 30 seconds to form a slightly cloudy suspension that may contain some white particles;1 lyophilized vaccine may not dissolve completely.1

If buffer component and active component are not reconstituted and mixed in proper sequence, discard the vaccine.1

Dosage

Adults

Prevention on Cholera Infection
Adults 18 through 64 Years of Age Traveling to Cholera-affected Areas
Oral

Administer a single dose of 100 mL of reconstituted oral suspension (see Reconstitution under Dosage and Administration).1 Give dose ≥10 days before potential exposure to cholera.1

Duration of immunity and protection against cholera after a single dose not fully determined (see Duration of Immunity under Cautions).1 3 Safety and efficacy of revaccination or booster doses not established;1 3 ACIP does not currently recommend use of booster doses.3

Special Populations

Hepatic Impairment

No specific dosage recommendations.1

Renal Impairment

No specific dosage recommendations.1

Geriatric Patients

Not indicated in geriatric adults ≥65 years of age.1

Cautions for Cholera Vaccine Live Oral

Contraindications

  • History of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine or to a previous dose of any cholera vaccine.1

Warnings/Precautions

Individuals with Altered Immunocompetence

Safety and efficacy not established in immunocompromised individuals.1 3 Immunologic response to the vaccine may be diminished in individuals with altered immunocompetence related to disease or immunosuppressive therapy.1 3

ACIP states that individuals with altered immunocompetence generally should not receive live vaccines since these individuals may be at increased risk for adverse reactions to such vaccines and may have diminished or suboptimal immune responses to vaccines.134

Transmission of Vaccine Strain of Vibrio cholera

Cholera vaccine live oral contains live, attenuated V. cholerae that may be shed in stool of vaccine recipients for ≥7 days and may be transmitted to close contacts (e.g., household contacts).1 3 6 Total duration of fecal shedding of the V. cholerae vaccine strain after vaccination is unknown.1

Fecal shedding of the vaccine strain has been detected as early as day 1 and has been highest on day 7 after vaccination.1 6 In one study, 11% of vaccinees shed the vaccine strain in their stools;1 6 no evidence that these individuals transmitted the vaccine strain to household contacts.6

Because of potential transmission of vaccine strain, vaccinees should take precautions (i.e., thorough and frequent handwashing, especially after bowel movements and before preparing and handling food) for ≥14 days after vaccination.1

Caution is advised when considering whether to administer cholera vaccine live oral to individuals with immunocompromised close contacts (e.g., individuals with malignancies or primary immunodeficiencies, individuals receiving immunosuppressive therapy).1

Limitations of Vaccine Efficacy

May not protect all vaccine recipients against cholera infection.1

Will not provide protection against V. cholerae serogroups not represented in the vaccine (e.g., V. cholerae serogroup O139, other non-O1 serogroups).1

Duration of Immunity

Duration of immunity and protection against cholera after vaccination with cholera vaccine live oral not fully determined.1 Data to date indicate duration of protection after a single dose is at least 3 months.1 2 3 In one study, approximately 90% of vaccinees still had vibriocidal antibody responses 6 months (180 days) after a single dose.2

Safety and efficacy of revaccination or booster doses not established.1 3

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune response in vaccinees.134

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.134 (See Storage under Stability.)

Do not administer vaccine that has been mishandled or has not been stored at the recommended temperature.134

If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether the vaccine is usable.134

Specific Populations

Pregnancy

Data not available to date regarding use in pregnant women.3

Because cholera vaccine live oral not absorbed systemically following oral administration, vaccination during pregnancy not expected to result in fetal exposure.1 3

Consider that cholera infection is associated with adverse pregnancy outcomes, including fetal death.1 Also consider that the V. cholerae vaccine strain may be shed in stools of vaccinated mothers for ≥7 days after vaccination and potentially could be transmitted to the infant during vaginal delivery.1 3

Pregnancy registry at 800-533-5899.1

Lactation

Data not available to date regarding use in nursing women.3

Because cholera vaccine live oral not absorbed systemically following oral administration, exposure to the vaccine not expected in breast-fed infants.1 3

Pediatric Use

Safety and efficacy not established in children and adolescents <18 years of age.1

Geriatric Use

Safety and efficacy not established in adults ≥65 years of age.1

Common Adverse Effects

Tiredness,1 2 headache,1 2 abdominal pain,1 2 nausea,1 2 vomiting,1 2 lack of appetite,1 2 diarrhea.1 2

Interactions for Cholera Vaccine Live Oral

Vaccines

Data not available regarding concurrent administration with other vaccines,1 3 10 including other vaccines used in travelers (e.g., typhoid vaccine, yellow fever vaccine).3 10

Specific Drugs

Drug

Interaction

Comments

Antibacterial agents

Antibacterials active against V. cholerae vaccine strain may prevent degree of replication needed to induce immune response;1 specific data not available10

Duration of possible interference probably depends on antimicrobial activity and half-life of the antibacterial agent3

Manufacturer states do not give cholera vaccine live oral until ≥14 days after completion of oral or parenteral antibacterial therapy1

If travel to cholera endemic or epidemic area cannot be postponed, ACIP states it may be acceptable to give cholera vaccine live oral <14 days after discontinuance of antibacterial therapy3

Chloroquine

Data from a similar vaccine suggest potential for diminished or suboptimal antibody response to cholera vaccine live oral1 10

Give cholera vaccine live oral ≥10 days before initiating chloroquine antimalarial prophylaxis1

Immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticosteroids, cytotoxic drugs, radiation)

Potential for decreased or suboptimal antibody response to cholera vaccine live oral1 134

Optimum interval between discontinuance of immunosuppressive therapy and subsequent administration of a live vaccine not determined134

Typhoid vaccine live oral Ty21a

Possibility that buffer component of cholera vaccine live oral may interfere with typhoid vaccine live oral Ty21a enteric-coated tablets;3 specific data not available3

When both vaccines indicated, some experts recommend giving first dose of typhoid vaccine live oral Ty21a ≥8 hours after cholera vaccine live oral3

Stability

Storage

Oral

For Oral Suspension

Single-dose carton containing foil packet of lyophilized live, attenuated V. cholerae CVD 103-HgR (active component) and foil packet of dry powder buffer (buffer component): Store in a freezer at −25 to −15°C;1 protect from light and moisture.1

After removal from frozen storage, complete reconstitution and mixing (see Reconstitution under Dosage and Administration) within 15 minutes;1 do not expose to temperatures >27°C.1

Actions

  • Cholera vaccine live oral contains live, attenuated V. cholerae strain CVD 103-HgR and is used to stimulate active immunity to V. cholerae serogroup O1.1 2

  • Vaccine strain is constructed from V. cholerae O1 classical Inaba strain 569B by deleting the catalytic domain sequence of cholera toxin A subunit gene (ctxA), which prevents the vaccine strain from synthesizing active cholera toxin.1 The nontoxic, immunogenic cholera toxin B subunit gene (ctxB) is retained in the vaccine strain.1 6 10

  • Following oral administration, the live, attenuated V. cholerae CVD 103-HgR vaccine strain replicates in the GI tract and induces a local mucosal immune response in the small intestine.1 10

  • Exact immunologic mechanism of action unknown;1 10 may be related to intestinal secretory IgA that may act directly against lipopolysaccharide and cholera toxin.10 Because intestinal secretory IgA cannot be easily measured in clinical trials, serum vibriocidal antibodies have been used to indicate an immune response to cholera vaccine live oral;10 not known whether presence of elevated serum vibriocidal antibodies is associated with local gut immunity.10

  • Following a single dose of cholera vaccine live oral in adults 18 through 45 years of age, seroconversion (defined as at least fourfold increase in serum vibriocidal antibody titers from baseline to day 10 after vaccination) occurred in approximately 90–94% of vaccinees within 10 days after the dose.1 2 Seroconversion rate in adults 46 through 64 years of age appears to be similar to that in adults 18 through 45 years of age.1

  • Duration of immunity and protection against cholera after vaccination with cholera vaccine live oral not fully determined.1 3 Data to date indicate duration of protection after a single dose is at least 3 months.1 2 (See Duration of Immunity under Cautions.)

  • Cholera vaccine live oral not absorbed systemically following oral administration.1 Approximately 11% of adults who receive a single dose of cholera vaccine live oral shed the vaccine strain of V. cholerae in their stools for ≥7 days after the dose.1 6 (See Transmission of Vaccine Strain of Vibrio cholerae under Cautions.)

Advice to Patients

  • Advise patients of the risks and benefits of vaccination with cholera vaccine.1

  • Advise patients that routine vaccination against cholera not recommended in the US,3 but may be used to prevent cholera in certain individuals traveling to cholera-affected areas.1 3

  • Advise patients that cholera vaccine may not provide complete protection in all vaccinees and will not protect against disease due to cholera strains not represented in the vaccine.1 Advise vaccinees of the importance of taking precautions against exposure to cholera by avoiding contact with or ingestion of potentially contaminated food or water.1

  • Advise patients that the vaccine strain of V. cholerae may be shed in stool for ≥7 days after vaccination and potentially can be transmitted to close contacts (e.g., household contacts).1 To minimize the risk of transmission of vaccine strain, advise patients to take precautions (e.g., thorough and frequent handwashing, especially after bowel movements and before handling or preparing food) for ≥14 days after vaccination.1 (See Transmission of Vaccine Strain of Vibrio cholerae under Cautions.)

  • Inform vaccine recipients about the most common adverse reactions reported within 7 days after vaccination with cholera vaccine live oral (e.g., tiredness, headache, abdominal pain, nausea/vomiting, lack of appetite, diarrhea) and importance of contacting a clinician if any adverse reactions occur.1 Clinicians or individuals can report any adverse reactions that occur following vaccination to VAERS at 800-822-7967 or or to the manufacturer at 800-533-5899.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinician if they are or plan to become pregnant or are breast-feeding.1 Report any exposure to cholera vaccine live oral that occurs during pregnancy to the pregnancy registry at 800-533-5899.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Cholera Vaccine Live Oral

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Kit, for oral use

Powder for oral suspension, 4 x 108 to 2 x 109 CFU of live attenuated Vibrio cholerae CVD 103-HgR per packet (active component)

Powder for oral suspension, sodium bicarbonate 2.16–2.41 g, sodium carbonate 0.24–0.49 g, ascorbic acid 1.5–1.8 g, and lactose 0.18–0.22 g per packet (buffer component)

Vaxchora

PaxVax

AHFS DI Essentials. © Copyright 2017, Selected Revisions July 24, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. PaxVax. Vaxchora (cholera vaccine live oral) prescribing information. Redwood City, CA; 2016 Jun.

2. Chen WH, Cohen MB, Kirkpatrick BD et al. Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor. Clin Infect Dis. 2016; 62:1329-35. [PubMed 27001804]

3. Wong KK, Burdette E, Mahon BE et al. Recommendations of the Advisory Committee on Immunization Practices for Use of Cholera Vaccine. MMWR Morb Mortal Wkly Rep. 2017; 66:482-485. [PubMed 28493859]

4. Centers for Disease Control and Prevention. Cholera: vaccines. From the CDC website. Accessed 2017 May 1.

5. . An oral cholera vaccine for travelers (Vaxchora). Med Lett Drugs Ther. 2016; 58:113-4. [PubMed 27552209]

6. Chen WH, Greenberg RN, Pasetti MF et al. Safety and immunogenicity of single-dose live oral cholera vaccine strain CVD 103-HgR, prepared from new master and working cell banks. Clin Vaccine Immunol. 2014; 21:66-73. [PubMed 24173028]

7. World Health Organization Global Taskforce on Cholera Control. Prevention and control of cholera outbreaks: WHO policy and recommendations. 2016. From WHO web site.

8. World Health Organization. Cholera. From WHO website. Accessed 2017 Feb 6.

9. . Cholera, 2015. Wkly Epidemiol Rec. 2016; 91:433-40. [PubMed 27665620]

10. US Food and Drug Administration. Center for Biologics Evaluation and Research. BLA number 125597/0: Clinical Review: From FDA website. Accessed 2016 Dec.

11. Clemens JD, Nair GB, Ahmed T et al. Cholera. Lancet. 2017; [PubMed 28302312]

115. Centers for Disease Control and Prevention. CDC health information for international travel, 2016. Atlanta, GA: US Department of Health and Human Services. Updates may be available at CDC website.

134. National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011; 60:1-64. [PubMed 21293327]

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