Rotavirus Vaccine Live Oral

Class: Vaccines
VA Class: IM100
Brands: Rotarix, RotaTeq

Introduction

Live, attenuated virus vaccine.^{11 12 22} Rotavirus vaccine is commercially available in the US as a monovalent vaccine derived from a human rotavirus strain (Rotarix; RV1)^{11 12 22} and as a pentavalent vaccine containing 5 reassortant rotaviruses derived from human and bovine hosts (RotaTeq; RV5).^{1 2 3 9 11 12} Rotavirus vaccine is used to stimulate active immunity to the rotavirus serotypes represented in the vaccine.^{1 2 3 9 11 12 22} Various other rotavirus vaccines (e.g., other monovalent or multivalent human-animal reassortant vaccines) are being investigated or may be available in other countries.^{3 4 9}

Uses for Rotavirus Vaccine Live Oral

Prevention of Rotavirus Gastroenteritis

Rotarix (RV1): Prevention of gastroenteritis caused by rotavirus serotype G1 and non-G1 types (G3, G4, G9).^{11 12 22 23 24 25}

RotaTeq (RV5): Prevention of gastroenteritis caused by rotavirus serotypes G1, G2, G3, and G4.^{1 2 11 12 17 19}

Rotavirus is the leading cause of severe gastroenteritis in infants and young children.^{9 11 12 29} Worldwide, rotavirus gastroenteritis causes approximately 500,000 deaths each year in children <5 years of age; more than 80% of these deaths occur in developing countries.^{9 11} Prior to licensure of rotavirus vaccine, rotavirus gastroenteritis was estimated to cause up to 70,000 hospitalizations and up to 60–70 deaths each year in the US in children <5 years of age.^{11 12 29}

Slideshow: Foodborne Illness: The Guest Nobody Invited

The incidence of rotavirus disease decreased in the US after rotavirus vaccine (RotaTeq) was licensed in 2006.²⁹ Surveillance data collected by the National Respiratory and Enteric Virus Surveillance System (NREVSS) indicate that the 2007–2008 and 2008–2009 rotavirus seasons were shorter, had a later onset, and had substantially fewer reports of positive rotavirus test results compared with the 2000–2006 seasons.²⁹ These data suggest that rotavirus vaccination may provide clinical benefits to both vaccinated and unvaccinated individuals by reducing overall rotavirus transmission (i.e., herd immunity).²⁹ Continued surveillance is needed to further evaluate the effect of routine childhood vaccination against rotavirus disease in the US.²⁹

USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and American Academy of Family Physicians (AAFP) recommend that all infants be vaccinated against rotavirus gastroenteritis beginning at 6 weeks of age, unless contraindicated.^{11 12 17} (See Contraindications under Cautions.) These experts state give the first dose at 6 through 14 weeks of age (no later than 14 weeks 6 days of age) and complete the vaccination series by 8 months 0 days of age.^{11 12 17}

Data not available regarding the interchangeability of the commercially available rotavirus vaccines (Rotarix, RotaTeq).^{11 12} ACIP and AAP do not state a preference for either vaccine for primary immunization in infants.^{11 12} (See Dosage under Dosage and Administration.)

Data not available regarding efficacy and safety of rotavirus vaccine for postexposure prophylaxis after exposure to natural rotavirus.^{1 22}

Rotavirus Vaccine Live Oral Dosage and Administration

Administration

Oral Administration

Rotarix (RV1) and RotaTeq (RV5) are administered orally.^{1 22}

Do not administer by IM, IV, or sub-Q injection.^{1 22}

Do not mix with any other vaccine or solution.^{1 22}

Food or liquid intake (including breast milk) does not need to be restricted before or after administration of rotavirus vaccine.^{1 11 12 22}

May be given simultaneously with other age-appropriate vaccines during the same health-care visit.^{1 8 11 12 22} (See Interactions.)

Rotarix (RV1)

Reconstitute lyophilized vaccine using the diluent and transfer adapter provided by the manufacturer.²² Consult manufacturer’s information for complete reconstitution instructions.²² Reconstituted Rotarix is a white, turbid suspension.²²

Following reconstitution, administer orally directly from oral applicator provided by the manufacturer.²² Administer entire contents of the oral applicator into infant’s mouth on the inside of the cheek.²²

If an incomplete dose is given (e.g., infant spits or regurgitates during or after vaccine dose), the manufacturer states that a single replacement dose may be considered at the same vaccination visit.²² ACIP and AAP do not recommend a replacement dose if an incomplete dose is given since data not available on benefits or risks associated with readministration.^{11 12} Administer remaining dose of the 2-dose vaccination series at usually recommended interval (minimum interval 4 weeks between doses).^{11 12}

RotaTeq (RV5)

Administer orally directly from the single-dose tubing supplied by the manufacturer.¹ Do not dilute.¹

Administer dose by gently squeezing entire contents of tubing into infant’s mouth toward the inner cheek.¹

If an incomplete dose is given (e.g., infant spits or regurgitates vaccine during or after vaccine dose), a replacement dose is not recommended since data not available on benefits or risks associated with readministration.^{1 11 12} Administer remaining doses of the 3-dose vaccination series at usually recommended intervals (minimum interval 4 weeks between doses).^{1 11 12}

Dosage

Dose and dosing schedule vary depending on the specific vaccine administered.^{1 22} Follow dosage recommendations for the specific preparation used.^{1 22}

The specific rotavirus vaccine (Rotarix or RotaTeq) used for the initial dose should be used to complete the vaccination series, whenever possible.^{11 12 22} If the specific rotavirus vaccine used for previous doses is unknown or unavailable, continue or complete the vaccination series with the currently available rotavirus vaccine; do not defer vaccination.^{11 12}

If RotaTeq or an unknown rotavirus vaccine was administered for any dose in the vaccination series, a total of 3 doses should be administered to complete the primary vaccination series.^{11 12}

ACIP, AAP, and AAFP state that the first dose of rotavirus vaccine should be given at 6 weeks through 14 weeks 6 days of age and should not be initiated in infants ≥15 weeks 0 days of age.^{11 12 17} If the first dose is inadvertently administered to an infant ≥15 weeks 0 days of age, complete the remainder of the vaccination series according to the recommended schedule.^{11 12} Timing of the first vaccine dose should not affect the safety and efficacy of subsequent doses.^{11 12} ACIP, AAP, and AAFP also state that the vaccination series should be completed by 8 months 0 days of age.^{11 12 17}

ACIP and AAP recommend a minimum interval of 4 weeks between doses of rotavirus vaccine.^{11 12}

In preterm infants who are medically stable, administer rotavirus vaccine at the usual chronologic age using usual dosage, provided the vaccine is administered to the age-eligible infant after or at the time of discharge from the neonatal intensive care unit (NICU) or hospital nursery.^{11 12} Theoretical risks of transmission of rotavirus vaccine virus to other hospitalized infants outweigh benefits of vaccination in age-eligible infants who will remain in the NICU or nursery after the dose.¹² (See Pediatric Use under Cautions.)

Because natural rotavirus infection frequently provides only partial immunity, ACIP and AAP recommend that the rotavirus vaccination series be initiated or completed in infants who had rotavirus gastroenteritis before receiving the complete series.^{11 12} (See Individuals with GI Disorders under Cautions.)

Pediatric Patients

Prevention of Rotavirus Gastroenteritis

Infants 6–24 Weeks of Age (Rotarix; RV1)

Primary immunization consists of a series of 2 doses.^{11 12 22} Each dose consists of the entire contents of the reconstituted single-dose vial.²²

Manufacturer recommends giving initial dose at 6 weeks of age and second dose at least 4 weeks after first dose.^{11 12 22} Manufacturer also recommends completing the 2-dose series by 6 months (24 weeks) of age.²²

ACIP, AAP, and AAFP recommend that infants receive Rotarix at 2 and 4 months of age with a minimum interval of 4 weeks between doses.^{11 12 17} ACIP, AAP, and AAFP also recommend completing the 2-dose series by 8 months 0 days of age.^{11 12 17}

Duration of immunity following the 2-dose vaccination series not fully determined.²² Need for revaccination or additional (booster) doses not determined.²² (See Duration of Immunity under Cautions.)

Infants 6–32 Weeks of Age (RotaTeq; RV5)

Primary immunization consists of a series of 3 doses.^{1 11 12} Each dose consists of the entire contents of the commercially available single-dose tubing.^{1 11}

Manufacturer recommends giving initial dose at 6 to 12 weeks of age and remaining 2 doses at 4- to 10-week intervals.^{1 11 12 17} Manufacturer recommends administering the third dose at ≤32 weeks of age.^{1 11 12 17}

ACIP, AAP, and AAFP recommend that RotaTeq be given at 2, 4, and 6 months of age with a minimum interval of 4 weeks between doses.^{11 12 17} ACIP and AAP also recommend completing the 3-dose series by 8 months 0 days of age.^{11 12}

Duration of immunity following the 3-dose vaccination series not fully determined.¹ Need for revaccination or additional (booster) doses not determined.¹ (See Duration of Immunity under Cautions.)

Special Populations

Hepatic Impairment

No specific dosage recommendations.^{1 22}

Renal Impairment

No specific dosage recommendations.^{1 22}

Geriatric Patients

Not indicated in adults, including geriatric adults.^{1 22}

Cautions for Rotavirus Vaccine Live Oral

Contraindications

• Rotarix (RV1)

• Known hypersensitivity to Rotarix or any vaccine component (e.g., latex).²² (See Latex Sensitivity under Cautions.)

• Do not give additional doses to infants who experienced symptoms suggestive of hypersensitivity following any previous dose.^{11 12 22}

• History of uncorrected congenital malformation of the GI tract (e.g., Meckel’s diverticulum) that would predispose infant to intussusception.²²

• Severe combined immunodeficiency disease (SCID).²² (See Individuals with Altered Immunocompetence under Cautions.)

• RotaTeq (RV5)

• Known hypersensitivity to RotaTeq or any vaccine component.^{1 11 12}

• Do not give additional doses to infants who experienced symptoms suggestive of hypersensitivity following any previous dose.^{1 11 12}

• SCID.^{1 34} (See Individuals with Altered Immunocompetence under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Review infant immunization history to determine whether there is a history of hypersensitivity or other reactions to any vaccine components.^{1 22}

Latex Sensitivity

Rotarix: Packaging components (tip cap and rubber plunger of oral applicator) contain dry natural latex.^{11 12 22}

Some individuals may be hypersensitive to natural latex proteins.⁸ Take appropriate precautions if Rotarix is administered to individuals with a history of latex sensitivity.⁸

ACIP states that vaccines supplied in vials or syringes containing dry natural rubber or natural rubber latex may be administered to individuals with latex allergies other than anaphylactic allergies (e.g., history of contact allergy to latex gloves), but should not be used in those with a history of severe (anaphylactic) allergy to latex, unless the benefits of vaccination outweigh the risk of a potential allergic reaction.^{8 11}

Consider use of RotaTeq (latex-free) as an alternative to Rotarix^. in infants with severe allergy to latex.¹¹ Some experts prefer that infants with spina bifida or bladder exstrophy, who are at high risk for acquiring latex allergy, receive RotaTeq (latex-free) as an alternative to Rotarix to minimize latex exposure.^{11 12} Administer Rotarix if it is the only rotavirus vaccine available since the benefit of rotavirus vaccination is considered to be greater than the risk for latex sensitization.^{11 12}

Individuals with Altered Immunocompetence

Safety and efficacy not established in immunocompromised or potentially immunocompromised infants.^{1 11 12 22 30} Examples include infants with blood dyscrasias, leukemia, lymphoma, or other malignant neoplasms affecting bone marrow or the lymphatic system; those receiving immunosuppressive therapy (see Interactions); those with primary and acquired immunodeficiency states such as HIV/AIDS or other clinical manifestations of HIV infection, cellular immune deficiencies, or hypogammaglobulinemic and dysgammaglobulinemic states; and those of indeterminate HIV status born to HIV-infected mothers (HIV-exposed).^{1 11 12 22 30}

There have been postmarketing reports of vaccine-acquired rotavirus gastroenteritis, with severe diarrhea and prolonged vaccine virus shedding, in infants who received Rotarix or RotaTeq and were subsequently diagnosed with SCID.^{1 22 33 34} Some of these infants continued to shed vaccine virus for 5–12 months.³³ Do not use Rotarix or RotaTeq in infants with SCID.^{1 22 33 34}

Consider the potential risks and benefits of administering rotavirus vaccine to infants with known or suspected altered immunocompetence.^{11 12 30} Consultation with an immunologist or infectious diseases specialist is advised.^{11 12 30}

ACIP, AAP, CDC, National Institutes of Health (NIH), HIV Medicine Association of IDSA, and Pediatric Infectious Diseases Society state that use of rotavirus vaccine in HIV-infected or HIV-exposed infants is supported since HIV diagnosis in infants born to HIV-infected mothers may not be established before the recommended age for the first dose of the vaccine, only 1.5–3% of HIV-exposed infants in the US will eventually be determined to be HIV infected, and the rotavirus strains used in the vaccines are considerably attenuated.^{11 12 30}

Individuals with GI Disorders

Rotarix: Manufacturer states the vaccine is contraindicated in infants with a history of uncorrected congenital malformation of the GI tract (e.g., Meckel’s diverticulum) that would predispose to intussusception.²² Manufacturer states safety and efficacy not evaluated in infants with chronic GI disorders;²² delay administration of the vaccine in infants with acute diarrhea or vomiting.²²

RotaTeq: Manufacturer states use caution in infants with a history of GI disorders (e.g., active acute GI illness, chronic diarrhea and failure to thrive, history of congenital abdominal disorders, abdominal surgery, intussusception); safety and efficacy data not available in these infants.^{1 11} Manufacturer states the vaccine may be used in infants with controlled gastroesophageal reflux disease (GERD).¹

Although safety and efficacy of rotavirus vaccine not evaluated in infants with preexisting chronic GI disorders, ACIP and AAP state that the benefits of the vaccine outweigh theoretical risks in those with preexisting GI tract conditions (e.g., congenital malabsorption syndrome, Hirschsprung disease, short-gut syndrome) if they are not receiving immunosuppressive therapy.^{11 12}

Data not available regarding use of rotavirus vaccine in infants with concurrent acute gastroenteritis; immunogenicity and efficacy may be compromised in these infants.^{11 12} ACIP and AAP state that the vaccine can be administered to infants with mild acute gastroenteritis (particularly if a delay in vaccination may result in the child becoming ineligible to receive the vaccine based on age at first dose), but recommend that the vaccine not be administered to infants with acute, moderate-to-severe gastroenteritis until improvement of the condition is noted.^{11 12}

Hematochezia reported rarely within 42 days after a dose of RotaTeq; incidence was similar to that observed in those receiving placebo during clinical trials.^{1 11 12} Data from postmarketing surveillance include reports of hematochezia following use of Rotarix or RotaTeq.^{1 22} Causal relationship between administration of rotavirus vaccine and occurrence of hematochezia not established.¹

Intussusception

A previously available rotavirus vaccine live oral (RotaShield; Wyeth) was voluntarily withdrawn from US market in 1999 following postmarketing reports of intussusception in infants receiving the vaccine.^{1 2 6 7 9 11 12 13 14 27} Data indicated the period of highest risk of intussusception associated with RotaShield was the first 42 days following the initial vaccine dose.^{1 2 6}

Although some cases of intussusception have been reported in temporal association with Rotarix or RotaTeq, data to date from clinical trials do not indicate an increased risk of intussusception with these currently available rotavirus vaccines compared with placebo.^{1 2 11 12 19 22 24}

Because of possible underreporting, limitations and assumptions in the analysis of data from the Vaccine Adverse Event Reporting System (VAERS), and the limited number of infants vaccinated with rotavirus vaccine to date, the possibility of a small increased risk of intussusception cannot be excluded.^{13 26 27} Closely monitor infants receiving rotavirus vaccine for intussusception, particularly during the first week following vaccination.^{10 36} Report any cases of intussusception or other serious events possibly associated with the vaccine to VAERS at 800-822-7967 or .^{13 14 36} For more information, see the FDA website at .¹⁴

Infants with a history of intussusception may be at higher risk for another episode, but data not available regarding administration of rotavirus vaccine to infants with a history of intussusception.^{11 12} Consider potential risks and benefits of vaccination in infants with a previous episode.^{11 12}

Rotarix (RV1)

Data to date from clinical trials of Rotarix do not indicate an increased risk of intussusception compared with placebo.^{11 12 22 24} In one randomized study conducted in Latin America and Finland, 63,225 infants received a 2-dose regimen of Rotarix or placebo and were monitored for intussusception for 31 days after each dose and for a median duration of 100 days after the first dose.^{22 24} There were 6 cases of confirmed intussusception in vaccine recipients and 7 cases in placebo recipients within 31 days following administration of either dose.^{22 24} After the 31-day observation period, there were 3 additional cases of intussusception in those who received vaccine and 9 cases in those who received placebo.^{22 24} There were no confirmed cases of intussusception in vaccine recipients within the first 14 days after the initial vaccine dose.²² In a subset of infants followed up to 1 year after the first vaccine dose, there were 4 cases of intussusception in vaccine recipients compared with 14 cases in placebo recipients.²² All infants who developed intussusception recovered without sequelae.^{22 24}

Interim data from a hospital-based, postmarketing active surveillance study in a birth cohort of infants in Mexico suggest an increased risk of intussusception in the 31-day period following administration of the first dose of Rotarix.^{22 36} Most cases of intussusception in this study occurred during the first 7 days following vaccination;^{22 36} worldwide passive postmarketing surveillance data also suggest that most cases of intussusception occur during the 7-day period following the first dose of Rotarix.²² When the relative risk of intussusception observed in the interim analysis of this Mexican study (i.e., 1.8) is applied to estimates of background rates of hospitalizations due to intussusception in infants <1 year of age in the US (i.e., 34 cases per 100,000 infants), the estimated increase is approximately 0–4 additional cases per 100,000 vaccinated infants within the 31 days following the first vaccine dose.^{22 36 37} FDA will review the final study report of the Mexican postmarketing surveillance study and is continuing to evaluate the association between Rotarix and intussusception using other ongoing studies.³⁶

RotaTeq (RV5)

Data accumulated to date regarding RotaTeq do not indicate an increased risk of intussusception compared with placebo.^{1 2 11 12 19} In one randomized study, >60,000 infants received a 3-dose regimen of RotaTeq or placebo and were monitored for intussusception at 7, 14, and 42 days after each dose and every 6 weeks for 1 year after the initial dose.^{1 2} A total of 13 vaccine recipients and 15 placebo recipients developed confirmed cases of intussusception within 1 year following the first dose.¹ There were 6 or 5 confirmed cases of intussusception that occurred within 42 days following any dose of vaccine or placebo, respectively; there were no confirmed cases of intussusception reported within the first 42 days following the initial vaccine dose.^{1 2} All infants who developed intussusception recovered without sequelae, except one child who died from postoperative sepsis.^{1 2}

Postmarketing surveillance has identified some cases of intussusception (including a death) in temporal association with RotaTeq.^{1 13 14 26 27} A total of 160 confirmed cases of intussusception (but no related fatalities) were reported to VAERS during the first 19 months of postmarketing surveillance (February 1, 2006 to September 25, 2007).²⁷ Of these 160 cases, 47 occurred within 21 days following vaccination, including 27 that occurred within the first 7 days.²⁷ Twenty-two of these infants required surgery; intussusception in the other 25 infants resolved through use of enema reduction.²⁷ Updated surveillance data from VAERS indicate that a total of 267 confirmed cases of intussusception were reported between February 1, 2006 and March 31, 2008.²⁶ Of these 267 cases, 91 occurred within 21 days following vaccination, including 48 that occurred within the first 7 days.²⁶ One fatality was reported in an infant 18 days following administration of the second dose of RotaTeq .²⁶ Among the VAERS reports of intussusception, more cases have been reported within 7 days than within 14 or 21 days following the first dose of RotaTeq.^{11 26}

Based on the assumption that 75% of intussusception cases were reported to VAERS and that 75% of rotavirus vaccine doses distributed were administered, the reported number of intussusception cases in RotaTeq recipients during the first 2 years of postmarketing surveillance did not exceed the number of expected cases during 1–7 or 1–21 days following vaccination.²⁷ After 2 years of postmarketing surveillance, VAERS data did not show an increased risk of intussusception within 21 days following any dose of RotaTeq.²⁶

FDA states that currently available evidence does not suggest an increased risk of intussusception in infants following vaccination with RotaTeq; however, studies are ongoing and additional information is being evaluated.³⁶ Preliminary analysis of data from the Vaccine Safety Datalink (VSD) project does not show a significant increased risk of intussusception with RotaTeq.³⁶ However, the VSD study is not large enough to date to rule out the increased level of risk for intussusception suggested by the preliminary data from the postmarketing study of Rotarix in Mexico.³⁶ (See Rotarix [RV1] under Cautions: Intussusception.)

Because postmarketing reports to date do not suggest an association between RotaTeq and intussusception,^{13 26 27 36} CDC recommends routine vaccination of infants at 2, 4, and 6 months of age.¹³

Transmission of Vaccine Virus

Rotarix contains live, attenuated rotavirus¹ and RotaTeq contains live reassortant rotaviruses.²²

Viral shedding occurs in vaccine recipients.^{1 11 12 22} Up to 26% of those receiving Rotarix shed vaccine virus in their stools after the first dose; peak shedding occurs at approximately day 7 after the first dose.²² Up to 9% of infants receiving RotaTeq shed vaccine virus in their stools after the first dose (as early as day 1 and as late as day 15 following the dose); viral shedding occurs rarely after subsequent doses of RotaTeq.¹

Although not specifically studied, rotavirus vaccine virus could potentially be transmitted between vaccinees and susceptible contacts.^{1 11 12 22} There have been postmarketing reports of vaccine virus transmission to unvaccinated contacts of infants who received RotaTeq.¹

Caution advised when considering whether to administer rotavirus vaccine to infants with close contacts who are immunocompromised (e.g., individuals who have malignancies, primary immunodeficiencies, or are receiving immunosuppressive therapy).¹ Manufacturers state weigh risk of possible vaccine virus transmission against risk of infant developing natural rotavirus infection that could be transmitted to susceptible contacts.^{1 22}

ACIP and AAP state that infants living in households with individuals who are immunocompromised may be vaccinated with rotavirus vaccine.^{8 11 12} Protection of immunocompromised household contacts afforded by rotavirus vaccination of infants in the household and prevention of wild-type rotavirus disease outweighs the small risk of transmitting vaccine virus to the susceptible individual and any subsequent theoretical risk of vaccine virus-associated disease.^{11 12}

To minimize potential vaccine virus transmission from the vaccinee, advise all household contacts to use hygienic measures (e.g., good hand washing) following contact with feces from a vaccinated infant (e.g., diaper changing) for at least 1 week after each vaccine dose.^{11 12}

If hospitalization of an infant recently vaccinated with rotavirus vaccine occurs for any reason, use standard precautions to prevent the spread of vaccine virus in the hospital setting.^{11 12} Because of the possible risk of transmission of rotavirus vaccine virus to other hospitalized infants, if a preterm infant previously vaccinated with rotavirus vaccine requires readmission to the NICU or hospital nursery within 2 weeks following a dose of the vaccine, initiate contact precautions for the preterm infant and maintain these precautions for 2–3 weeks following the dose.¹² (See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.)

Kawasaki Disease

Kawasaki disease reported during phase 3 clinical trials of RotaTeq in 5 out of 36,150 infants who received the vaccine and in 1 out of 35,536 infants who received placebo.^{1 15} Additional 3 cases in vaccinated infants reported to VAERS and 1 unconfirmed case reported through the VSD Project.¹⁵

Kawasaki disease also has been reported in 18 infants who received Rotarix during clinical trials.²²

Causal relationship between rotavirus vaccine or any vaccine and the occurrence of Kawasaki disease not established.¹⁵ To date, the number of reported cases of Kawasaki disease occurring in association with use of RotaTeq does not exceed the number of expected cases occurring randomly in this population.¹⁵ Postmarketing surveillance data to date do not indicate that RotaTeq is associated with an increased risk of Kawasaki disease.¹¹

Report any case of Kawasaki disease occurring following administration of rotavirus vaccine (or any other vaccine) to VAERS at 800-822-7967 or .¹⁵ For more information, see FDA website at .¹⁵

Concomitant Illness

A decision to administer or delay administration of rotavirus vaccine in an infant with current or recent febrile illness depends on the severity of symptoms and etiology of the illness.¹ Manufacturer of RotaTeq states presence of low-grade fever (<38.1°C) or mild upper respiratory infection does not preclude vaccination.¹

ACIP and AAP state that rotavirus vaccine may be administered to infants with transient, mild illnesses (with or without low-grade fever),^{8 11 12} but defer vaccination of individuals with moderate or severe acute illness until after recovery from the acute phase of illness.^{8 11 12}

Limitations of Vaccine Effectiveness

May not protect all vaccine recipients against rotavirus infection.¹

Data not available to determine the level of protection provided against rotavirus infection in infants who have not received the complete vaccination series (i.e., have received only a single dose of Rotarix or only 1 or 2 doses of RotaTeq).^{1 22}

Duration of Immunity

Duration of protection against rotavirus gastroenteritis following the 2-dose vaccination series of Rotarix or 3-dose vaccination series of RotaTeq not fully determined.^{1 22} Efficacy beyond the second rotavirus season after vaccination has not been evaluated to date.^{1 22}

Risk of Adventitious Agents

Porcine-derived materials are used in the manufacture of Rotarix and Rotateq; DNA from porcine circoviruses is present in the vaccines.^{1 22 31 32}

In March 2010, after becoming aware that DNA from porcine circovirus type 1 (PCV1) was present in Rotarix, FDA advised that use of the vaccine be temporarily suspended as a safety precaution pending further investigation.^{31 32} In May 2010, FDA provided additional information that DNA fragments from PCV1 and porcine circovirus type 2 (PCV2) were detected in RotaTeq.^{31 32} After careful evaluation, FDA decided that it was appropriate to resume use of Rotarix and continue use of RotaTeqfor prevention of rotavirus infection in infants.^{31 32}

FDA states that there is no evidence to date that PCV1 or PCV2 can cause clinical infection or disease in humans or that either virus poses a safety risk in humans.^{31 32} Because available evidence supports the safety of Rotarix and RotaTeq in infants, FDA states that clinical benefits of vaccination against rotavirus infection outweigh any theoretical risks from the presence of PCV1 or PCV2 in rotavirus vaccines.^{31 32} FDA and the manufacturers will continue to investigate the presence of porcine virus in Rotarix and RotaTeq and evaluate safety data from ongoing studies.^{31 32}

Improper Storage and Handling

Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.⁸

Do not administer rotavirus vaccine that has been mishandled or has not been stored at the recommended temperature.⁸ (See Storage under Stability.)

Protect the vaccine from light at all times;^{1 8 20 22} exposure to light may inactivate the vaccine virus.²⁰

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.⁸ If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether the vaccine is usable.^{8 20}

Specific Populations

Pregnancy

Category C.^{1 22}

Not indicated for use in adults, including pregnant women.^{1 22}

ACIP and AAP state that infants living in households with pregnant women may receive rotavirus vaccine.^{11 12} Risk of acquiring rotavirus infection from potential exposure to vaccine virus considered very low since most women of childbearing age would be expected to have preexisting immunity to rotavirus.^{11 12}

No evidence to date that rotavirus infection during pregnancy poses any fetal risk.¹¹ Vaccination of infants against rotavirus would avoid potential exposure of pregnant women to natural rotavirus from unvaccinated infants with rotavirus gastroenteritis.^{11 12}

Lactation

Not indicated for use in adults, including nursing women.^{1 22}

ACIP and AAP state that breast-feeding infants may receive the rotavirus vaccine since efficacy in breast-feeding infants appears to be similar to that in infants not breast-feeding.^{11 12}

Pediatric Use

Rotarix: Manufacturer states that safety and efficacy not established in infants <6 weeks or >24 weeks of age.²² Efficacy in preterm infants not established;²² safety data to date in preterm infants indicate serious adverse events in 5.2% of vaccine recipients compared with 5% of placebo recipients.²² No deaths or cases of intussusception reported in this patient population to date.²²

RotaTeq: Manufacturer states that safety and efficacy not established in infants <6 weeks or >32 weeks of age.¹ Data support use of RotaTeq in preterm infants (i.e., gestational age 25–36 weeks) according to age in weeks since birth.¹

Pending additional data, ACIP and AAP state that the benefits of routine vaccination with rotavirus vaccine outweigh theoretical risks in medically stable preterm infants.^{11 12} These experts state that clinically stable preterm infants who meet age requirements (at least 6 weeks and not greater than 14 weeks 6 days of age) may receive the first dose of rotavirus vaccine after or at the time of discharge from the NICU or hospital nursery.^{11 12} However, the possible risk of transmission of rotavirus vaccine virus to other hospitalized infants outweigh benefits of vaccination in age-eligible infants who will remain in the NICU or nursery after the dose.¹² If a preterm infant who previously received rotavirus vaccine requires readmission to the NICU or hospital nursery within 2 weeks following a dose of the vaccine, initiate contact precautions for the preterm infant and maintain such precautions for 2–3 weeks following the vaccine dose.¹²

Geriatric Use

Not indicated in adults, including geriatric adults.^{1 22}

Common Adverse Effects

Fever,^{1 22} diarrhea,¹ vomiting,^{1 22} loss of appetite,²² fussiness/irritability,^{1 22} otitis media,¹ cough/runny nose,²² nasopharyngitis,¹ bronchospasm.¹

Interactions for Rotavirus Vaccine Live Oral

Other Vaccines

Simultaneous administration with other age-appropriate vaccines or toxoids (e.g., haemophilus b conjugate [Hib], poliovirus vaccine inactivated [IPV], hepatitis B [HepB], inactivated influenza virus vaccines, measles, mumps, and rubella virus vaccine live [MMR], pneumococcal conjugate vaccine, diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed [DTaP]) during the same health-care visit is not expected to affect immunologic responses or adverse reactions to any of the vaccines.^{1 8 11 12 22 28}

Specific Drugs

Stability

Storage

Oral

For Suspension

Rotarix (RV1): 2–8°C.²² Store diluent at 20–25°C.²² Do not freeze; if freezing occurs, discard vaccine.²² Protect from light.²²

After reconstitution, store for up to 24 hours at 2–8°C or at room temperature (up to 25°C).²² Discard reconstituted vaccine if not used within 24 hours.²² Do not freeze reconstituted vaccine; discard if frozen.²²

Does not contain thimerosal or any other preservatives.²²

Solution

RotaTeq (RV5): 2–8°C for up to 24 months.^{1 20} Protect from light.^{1 20}

Does not contain thimerosal or any other preservatives.¹

Actions

• Rotarix (RV1) is a lyophilized vaccine containing live, attenuated rotavirus derived from a human strain (89–12) belonging to serotype G1P[8] type.²²

• RotaTeq (RV5) is an oral solution containing live reassortant rotaviruses that represent the G serotypes responsible for most cases of rotavirus gastroenteritis worldwide (G1, G2, G3, G4) and the most common P serotype associated with these strains (P1A; genotype P[8]).^{1 3 5 9}

• Porcine-derived materials are used during the manufacture of Rotarix and RotaTeq;^{1 22} DNA from porcine circoviruses has been detected in the vaccines.^{1 22 31 32} (See Risk of Adventitious Agents under Cautions.)

• Following vaccination, the live, attenuated virus (Rotarix) or reassortant rotaviruses (RotaTeq) replicate in the small intestine and induce active immunity to rotavirus serotypes represented in the vaccine.^{1 2 3 9 22}

• Rotavirus is the leading cause of severe acute gastroenteritis in infants and young children worldwide^{9 11 12 29} and >95% of these infections occur within the first 5 years of life.^{1 9 11} Most severe cases occur among infants and young children >6 months and <24 months of age.¹

• Exact immunologic mechanism by which Rotarix or RotaTeq protects against rotavirus gastroenteritis not known.^{1 2 9 22}

• Correlation between antibody response to rotavirus vaccine and protection against rotavirus gastroenteritis not established to date.^{5 22}

• Data suggest that serum neutralizing antibodies, fecal anti-rotavirus IgA, and serum anti-rotavirus IgA may correlate with protection against rotavirus gastroenteritis.⁵

• Studies using Rotarix indicate that 76.8–86.5% of vaccine recipients seroconvert after 2 doses.²² Seroconversion in these studies was defined as appearance of anti-rotavirus IgA antibody in infants previously negative for rotavirus.²²

• Studies using RotaTeq indicate a threefold or greater increase in serum anti-rotavirus IgA concentrations in 93–100% of infants who received a 3-dose vaccination series compared with 12–20% of infants who received placebo.^{1 2 11 19}

• Up to 26% of infants who receive Rotarix shed vaccine virus in their stools after the first dose; peak shedding occurs at approximately day 7 after the dose.²²

• Up to 9% of infants who receive RotaTeq shed vaccine virus in their stools after the first dose (as early as day 1 and as late as day 15 following the dose); viral shedding occurs rarely after subsequent doses.¹

Advice to Patients

• Prior to administration of each vaccine dose, provide copy of manufacturer’s patient information to the patient’s parent or guardian.^{1 16 22 35} Also provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient’s parent or legal representative (VISs are available at ).^{1 21 22}

• Advise patient’s parent or guardian of the risks and benefits of vaccination.^{1 22}

• Advise patient’s parent or guardian that porcine circoviruses (or fragments of the viruses) have been found in rotavirus vaccines, and that there is no evidence to date that these viruses cause infection or disease in humans or pose a safety risk. (See Risk of Adventitious Agents under Cautions.)^{1 16 21 22 35}

• Advise patient’s parent or guardian that the vaccine may provide protection against diarrhea and vomiting caused by rotavirus, but not due to other causes.^{16 21}

• Advise patient’s parent or guardian that rotavirus vaccine may not provide complete protection in all vaccinees.^{1 16 22} In addition, the vaccine will not protect against disease due to rotavirus strains not represented in the vaccine.^{1 22}

• Advise patient’s parent or guardian of the possible risk of vaccine virus transmission to rotavirus-susceptible individuals, including close or household contacts with a weakened immune system or pregnant women who have not had rotavirus infection.^{1 16 22 35}

• Importance of informing clinicians if a child has any illness with fever, diarrhea, or vomiting; has failure to gain weight or is not growing as expected; has a blood disorder, any type of cancer, a weakened immune system (e.g., HIV infection, SCID), or a history of GI problems (e.g., blockage, abdominal surgery); or receives treatment that may weaken the immune system (e.g., high-dose corticosteroids).^{1 16 22 35}

• For infants receiving Rotarix (2-dose vaccination series) or RotaTeq (3-dose vaccination series), advise the patient’s parent or guardian of the importance of completing the vaccination series by the time the infant is 8 months 0 days of age, unless contraindicated.^{11 12 17}

• Importance of informing clinicians if any adverse reactions (including allergic reactions) occur.^{1 14 16 22 35} Clinicians or individuals can report any adverse reactions that occur following vaccination to VAERS at 800-822-7967 or .^{1 14 16 21 22}

• Advise patient’s parent or guardian that the vaccine should not be administered to children who had an allergic reaction following a prior vaccine dose or in those allergic to any vaccine component.^{1 16 22 35}

• Importance of informing clinicians immediately if a child develops vomiting, diarrhea, severe stomach pain, blood in stools, change in bowel movements, or high fever since these may be signs of intussusception (a serious and potentially life-threatening condition that occurs when the intestine gets blocked or twisted).^{14 16 22 35} Contact clinicians if child has any of these symptoms following vaccination, especially if symptoms occur within 7 days following first dose of vaccine, but even if they occur several weeks following last vaccine dose.^{14 16 35 36}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.^{1 22}

• Importance of informing patients of other important precautionary information.^{1 22} (See Cautions.)

Preparations

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