ROTARIX

General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Inform the patient, parent, guardian, or responsible adult of the benefits and risks of the vaccine. Provide the Vaccine Information Statements from the manufacturer to the recipient or guardian before each immunization. These actions are required by the National Childhood Vaccine Injury Act of 1986.
-Record the manufacturer and lot number of the vaccine; date of administration; and the name, address, and title of the person who administered the vaccine in the recipient's permanent medical record. These actions are required by the National Childhood Vaccine Injury Act of 1986.

Route-Specific Administration

Oral Administration
-Do NOT administer parenterally.
-Do not mix with any other vaccines or solutions.
-The child may have food or drink, including breast milk, before or after vaccine administration.
Oral Liquid Formulations
RotaTeq
-Tear the protective pouch, and remove the dosing tube. Hold the tube vertically and tap the cap to remove any fluid from the dispensing tip. Turn the cap clockwise to puncture the dispensing tip. Turn the cap counterclockwise to remove the cap.
-Do not dilute or reconstitute the solution. Administer directly into the mouth by squirting the solution on the inside of the cheek. Give all the solution in the tube. A residual drop may remain in the tube tip.
-Do not give a replacement dose if an incomplete dose is received regardless of the reason. The infant should continue to receive any remaining doses in the recommended series.
-Storage: Administer as soon as possible after removing from refrigeration.

Rotarix
NOTE: Rotarix is supplied in 2 presentations, a vial and oral dosing applicator that requires reconstitution and an oral dosing applicator only that does not require reconstitution.

Reconstitution of Vial and Oral Dosing Applicator Presentation
-Remove vial cap and push transfer adaptor onto vial.
-Shake diluent in oral dosing applicator. The diluent should appear white and turbid. Connect the oral dosing applicator to the transfer adaptor.
-Push plunger to transfer the diluent into the vial. The vaccine solution should appear white and turbid. After reconstitution a single dose is 1 mL.
-Withdraw the vaccine into the oral dosing applicator.
-Twist to remove the oral dosing applicator.
-Storage: Store reconstituted vaccine refrigerated at 2 to 8 degrees C (36 to 46 degrees F) or at a controlled room temperature up to 25 degrees C (77 degrees F) for up to 24 hours after reconstitution. Do not freeze.

Preparation of Oral Dosing Applicator Only Presentation
-Remove protective tip cap from oral dosing applicator. The vaccine should be clear and colorless. A single dose is 1.5 mL.
-Storage: Store refrigerated at 2 to 8 degrees C (36 to 46 degrees F). Do not freeze. Keep in original package to protect from light.

Oral Administration
-Delay administration of Rotarix in infants with acute diarrhea or vomiting.
-Place the infant seated in a reclining position.
-Place the oral dosing applicator towards the inner cheek. Administer the entire contents into the infant's mouth.
-If the infant spits out or regurgitates most of the vaccine dose, consider a single replacement dose at the same vaccination visit.
-Dispose of the applicator and vaccine vial in a biohazard waste container.

Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as to the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Deaths that were reported across all RV5 (RotaTeq) clinical trials include 25 deaths in vaccine recipients compared to 27 deaths in placebo recipients. The most common cause of death was sudden infant death syndrome. In the Rotavirus Efficacy and Safety Trial (REST), no investigators blinded to treatment attributed deaths due to vaccination with RV5.

Fever is a common event reported after rotavirus vaccine administration; however, in clinical trials, the incidences reported were generally similar between the rotavirus vaccine and placebo groups. Safety information collected from parents or guardians of 6138 recipients of RV5 (RotaTeq) included reports of fever in 42.6% within 42 days of any dose compared to 42.8% of patients who received placebo (n = 5573). Additionally, detailed safety information of adverse effects occurring within the first week of administration was collected from a cohort of patients in phase 3 studies receiving RV5 or placebo. Fever (>= 100.5 degrees F or 38.1 degrees C) was noted in 17.1-20% of active treatment groups vs. 16-19% of placebo groups. In addition, serious fever was reported in 0.1% of patients receiving both the vaccine and placebo. Among premature infants (25-36 weeks gestational age), fever occurred after a RV5 dose 18.1%, 25%, and 14.8% of infants within 1 week after doses 1, 2, and 3 in the series, respectively. Fever also occurred in 25% of patients after the first dose of RV1 (Rotarix) and 28% of patients after the second dose compared to 33% and 34% of patients receiving placebo. Among 36,150 infants who received RV5 in phase 3 clinical trials, 5 cases of Kawasaki disease, a condition is characterized by high fever and inflammation of the blood vessels, were noted. In contrast, 1 case was reported among 35,536 infants who received placebo. Three additional reports of Kawasaki disease have been noted through routine monitoring of the Vaccine Adverse Event Reporting System (VAERS). In a prospective post-marketing observational safety study using a medical claims database, the risk of Kawasaki disease resulting in ED visits or hospitalization during 30 days after any dose of RV5 was evaluated (n = 85,150). One case of Kawasaki disease was confirmed 23 days post-dose 3; among concurrent controls that received only DTaP, 1 case was also confirmed. In placebo-controlled trials of RV1, Kawasaki disease was reported in 18 RV1 recipients and in 9 placebo recipients for a relative risk of 1.71 (95% CI, 0.71-4.38). The time of onset of Kawasaki disease after RV1 administration ranged from 3 days to 19 months. A known cause and effect relationship between rotavirus vaccine administration or any vaccine and the occurrence of Kawasaki disease does not exist. In a cohort of patients from the REST trial, parents or guardians recorded adverse events daily during the first week after each of the 3 doses of RV5 or placebo; the size of each treatment or placebo group ranged from 4382-5616 infants. Irritability frequency (7.1% after dose 1, 6% after dose 2, and 4.3% after dose 3) was similar to placebo treated patients. Among premature infants (25-36 weeks gestational age), irritability occurred in 3.9%, 2.9%, and 8.1% of infants within 1 week after doses 1, 2, and 3 in the series, respectively. In regard to RV1, similar percentages of patients who received either RV1 or placebo experienced irritability (42-52% vs. 42-52%). Healthcare providers are encouraged to report any cases of Kawasaki disease or other severe adverse events to the VAERS.

The safety of rotavirus vaccine (RV5 or RotaTeq) has been studied in over 70,000 infants who received the vaccine or placebo in three phase 3 clinical trials. In a safety cohort, parents or guardians recorded adverse events during the first week after each of the 3 required doses; the size of each treatment or placebo group ranged from 4382-5616 infants. Vomiting was reported in 3.6-6.7% of the active groups vs. 3.2-5.4% of placebo patients, with higher frequencies occurring with the first dose of the vaccine series. Diarrhea frequency ranged from 6.1-10.4% in the active groups vs. 5.4-9.1% of placebo patients, again with higher frequencies during the first dose. Adverse event frequencies occurring within 42 days of any vaccine dose (n = 6138) compared to placebo (n = 5573) were also monitored; statistically higher incidences were seen for diarrhea (24.1% vaccine vs. 21.3% placebo) and vomiting (15.2% vs. 13.6%). Hematochezia occurred within 42 days of any dose in 0.6% of infants who received of RV5 (n = 6130) or placebo (n = 5560). Among 2070 preterm infants (25-36 weeks gestational age), adverse events reported within the first week of RV5 administration included vomiting (5.8% after dose 1, 2.9% after dose 2, and 4.4% after dose 3) and diarrhea (6.5% after dose 1, 7.3% after dose 2, and 3.7% after dose 3). In regard to RV1 (Rotarix), similar percentages of patients who received either RV1 or placebo had anorexia (21-25% RV1 vs. 21-25% placebo), vomiting (8-13% vs. 8-11%), flatulence (2.2% vs. 1.3%), or diarrhea (3-4% vs. 3%). Serious adverse events including diarrhea (0.02% RV1 vs. 0.07% placebo) and dehydration (0.02 vs. 0.06) occurred during a 31-day period following vaccination in 8 clinical trials. Gastroenteritis, regarded as a serious adverse event, occurred in 0.2% of RV5 recipients compared to 0.3% with placebo. Gastroenteritis with viral shedding in infants with severe combined immunodeficiency disease (SCID) has been observed during post-marketing surveillance. Counsel patients to report any signs or symptoms of a systemic reaction to a health care provider.

The risk of intussusception (a GI obstruction in which one segment of the bowel becomes enfolded within another segment) with the use of currently available rotavirus vaccines has not been clearly determined, but both RV1 (Rotarix) and RV5 (RotaTeq) are contraindicated for use by patients with a history of intussusception. An increased risk of intussusception was reported with the previously licensed rotavirus vaccine: live-rhesus rotavirus-based vaccine (RRV-TV or RotaShield), which was withdrawn from the U.S. market in October 1999. In pre-marketing clinical trials, no increased risk of intussusception for RV1 or for RV5 was noted when compared to placebo. In a large phase 3 clinical trial with RV5, intussusception occurred in 13 vaccine recipients (n = 34,837) and in 15 placebo recipients (n = 34,788) within 1 year after the first dose. Intussusception was confirmed in 6 vaccine recipients and in 5 placebo recipients within a 42 day window after any dose; however, no cases were confirmed in any vaccine recipient within 42 days after the first dose, which was the period of highest risk for RRV-TV. The relative risk of intussusception among vaccine recipients, as compared to placebo recipients, was 1.6 (95% CI, 0.4-6.4) during the 42-day period after any dose, a result that met prespecified criteria for an acceptable safety profile. In trials of RV1, the risk of intussusception was evaluated in infants that received RV1 (n = 31,673) or placebo (n = 31,552). Six cases of intussusception within 31 days after any dose occurred with RV1 compared to 7 cases with placebo; in the 100 days following dose 1, 9 cases were reported with RV1 compared to 16 with placebo. Cases of intussusception have been reported in temporal association with RV1 and with RV5 during the post-marketing period; some cases have resulted in death. In a post-marketing surveillance study, cases of intussusception were noted in temporal association within 21 days after the first dose of RV5, with a clustering of cases in the first 7 days. These results showed approximately 1-1.5 excess cases of intussusception per 100,000 vaccinated US infants within 21 days after the first dose of RV5. In a prospective self-controlled cases series of 2 years duration in Mexico with observation of over 1 million infants, clustering of intussusception 1 week after dose 1 was observed in infants that received RV1; the relative incidence was 6.49 (95% CI 4.17-10.09, p < 0.001). The relative incidence of intussusception post-dose 2 was 1.29 (95% CI 0.8-2.11, p = 0.29), and within 31 days of vaccination was 1.75 (95% CI 1.24-2.48, p = 0.001). The attributable risk of intussusception within 1 week of dose 1 was approximated at 3-4 additional cases of intussusception per 100,000 vaccinated infants. This study did not take into account all medical conditions that may predispose the infant to intussusception. In the first year of life, the background rate for intussusception hospitalizations in the US is approximately 34 per 100,000 infants. The risk of intussusception within 21 days after the first dose must be balanced with the well-documented benefits of rotavirus vaccine. An increased risk of intussusception was not detected in US infants who received RV5 in a prospective cohort study. During the study, 786,725 doses (309,844 first doses) were administered. Following dose 1, intussusception occurred in 7 infants, compared to 5.7 expected cases in infants who received other vaccines without concomitant RV5; for 30 days following all RV5 doses, 21 cases of intussusception occurred compared to 20.9 expected cases. In a large post-marketing database US safety study (n = 85,150) of RV5, an increased risk of intussusception was not detected; intussusception occurred in 6 patients within 30 days of receiving any RV5 dose compared with 5 cases in a concurrent DTaP control group (relative risk 0.8, 95% CI, 0.22-3.52). Administration of the first and last doses at different age ranges within the recommended age window has not demonstrated any impact on intussusception frequency.

Seizures reported as serious adverse events occurred in < 0.1% (n > 70,000) of rotavirus vaccine or placebo recipients in phase 3 clinical trials; the differences were not statistically significant. Febrile seizures occurred in 5 patients in each group.

Adverse events reported with post-marketing use of rotavirus vaccine included anaphylactoid reactions and angioedema. Urticaria and idiopathic thrombocytopenic purpura have also been observed. Due to the uncontrolled nature of post-marketing reports, neither the frequency nor a definitive causal relationship to the vaccine can be established. Appropriate medical treatment should be immediately available in the event of a serious allergic reaction to the vaccine.

The safety of RV5 (RotaTeq) has been studied in over 70,000 infants who received rotavirus vaccine or placebo in phase 3 clinical trials. Roughly 2.5% of infants in each group had a serious adverse event reported within the 42-day period of a dose. Reported serious respiratory adverse events for RV5 (RotaTeq) compared to placebo included bronchiolitis (0.6% RV5 vs. 0.7% placebo) and pneumonia (0.2 vs. 0.2%). In 2070 preterm infants (25-36 weeks gestational age) who received RV5 or placebo, bronchiolitis occurred in 1.4% and 2% of vaccine and placebo recipients, respectively. During the entire course of 8 clinical studies, 68 (0.19%) deaths after RV1 (Rotarix) administration to 36,755 patients and 50 (0.15%) deaths after placebo administration to 34,454 patients occurred. The most commonly reported cause of death after vaccination was pneumonia, which was observed in 19 (0.05%) RV1 recipients and in 10 (0.03%) placebo recipients. In a detailed safety cohort study in a subset of patients from the REST trial (n = 11,711) adverse events with frequencies that were statistically higher with RV5 compared to placebo included bronchospasm (1.1% RV5 vs. 0.7% placebo), naso-pharyngitis (6.9% vs. 5.8%), and otitis media (14.5% vs. 13%). During clinical trials with RV1, similar percentages of patients who received either RV1 or placebo had cough (28-31% vs. 30-33%) or rhinorrhea (28-31% vs 30-33%). Counsel patients to report any signs or symptoms of a systemic reaction to a health care provider.

Urinary tract infections or cystitis was a serious adverse event reported in 0.1% of rotavirus vaccine (RV5 or RotaTeq) recipients (n = 36,165) within 42 days after a dose. Urinary tract infections also occurred in 0.1% of placebo patients (n = 35,560). Counsel patients to report any signs or symptoms of a systemic reaction to a health care provider.

Prior to administration, inform the parent, guardian, or responsible adult of the benefits and risks of the vaccine, and provide the Vaccine Information Statement, accessible at the Centers for Disease Control and Prevention (CDC) website. These actions are required by the National Childhood Vaccine Injury Act of 1986. If a dose of rotavirus vaccine has been previously given, question the parent or guardian about previous adverse reactions that may preclude further administration. Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Rotavirus vaccine may be administered to eligible infants before, concurrent with, or after administration of any blood product.

Rotavirus vaccines including RV1 (Rotarix) and RV5 (RotaTeq) are contraindicated for use by patients with a demonstrated history of hypersensitivity to any vaccine component. Do not administer further doses to infants who develop symptoms suggestive of hypersensitivity. Determine prior vaccine history and current health status before administration of rotavirus vaccine. Patients with latex hypersensitivity may be inappropriate candidates for Rotarix. The tip caps of the prefilled oral applicators contain natural latex rubber. The vial stoppers are latex-free. Ensure appropriate medical treatment is immediately available in the event of a serious allergic reaction to the vaccine.

The rotavirus vaccine should never be administered by parenteral administration; it is for oral use only.

Febrile illness may be reason for delaying use of rotavirus vaccine except when, in the opinion of the physician, withholding the vaccine entails a greater risk. The Advisory Committee on Immunization Practices (ACIP) recommends that infants with moderate-to-severe illness should be vaccinated as soon as they have recovered from the acute phase of the illness. Do not delay vaccination if a mild respiratory infection or other mild acute illness with or without fever is present. ACIP recommends to delay vaccination with acute moderate or severe gastroenteritis until the condition improves; do not administer the vaccine during acute vomiting or diarrhea. Infants with mild acute gastroenteritis can be vaccinated, especially if a delay in vaccination might make the child ineligible to receive vaccine. As no efficacy or safety data are available in infants with on-going acute gastrointestinal illness including chronic diarrhea or vomiting, cautious administration advised. Infants who have had rotavirus gastroenteritis before receiving the full course of rotavirus vaccine should still initiate or complete the dosing schedule because the initial infection frequently provides only partial immunity.

The rotavirus vaccines RV1 (Rotarix) and RV5 (RotaTeq) are contraindicated for use by infants with a history of intussusception. In 2 randomized, double-blind, placebo-controlled trials of RV1 or RV5, the risk of intussusception after immunization was no greater in infants that received the vaccines compared to those who received placebo. However, intussusception has been temporally associated with rotavirus vaccine during post-marketing experience; some cases have resulted in death. In a post-marketing surveillance study, cases of intussusception were noted in temporal association within 21 days after the first dose of RV5, with a clustering of cases in the first 7 days. These results showed approximately 1-1.5 excess cases of intussusception per 100,000 vaccinated US infants within 21 days after the first dose of RV5. In a previous prospective, post-marketing, observational cohort study, a statistically significantly higher risk of intussusception was not noted for those who received RV5 compared with those in the DTaP control group. RV1 is also contraindicated for use by patients with GI disease who have a history of uncorrected congenital malformation of the gastrointestinal tract such as Meckel's diverticulum that would predispose the infant for intussusception. Infants with preexisting, chronic GI conditions who are not undergoing immunosuppressive therapy should benefit from rotavirus vaccination; the Advisory Committee on Immunization Practices (ACIP) considers benefits to outweigh the theoretical risks. However, the safety and efficacy of rotavirus vaccine have not been established for infants with preexisting conditions such as congenital malabsorption syndrome; Hirschsprung's disease; short-gut syndrome; persistent vomiting of unknown cause; chronic diarrhea; failure to thrive; a history of congenital abdominal disorders; or abdominal surgery. The use of rotavirus vaccine in infants with controlled gastroesophageal reflux disease (GERD) is supported by data from clinical trials.

The rotavirus vaccines RV1 (Rotarix) and RV5 (RotaTeq) are contraindicated for use by patients with a history of severe combined immunodeficiency (SCID). Reports of gastroenteritis, including severe diarrhea and prolonged shedding of vaccine virus, have been reported post-marketing in infants who were administered RV5 and later identified as having SCID. Caution is advised when considering whether to administer the rotavirus vaccine to individuals with immunodeficient close contacts; transmission of vaccine virus strains from vaccinees to non-vaccinated contacts has been observed. In RV5 studies, rotavirus shedding in the stool was observed as early as 1 day and as late as 15 days after a dose, with up to 8.9% of 360 infants experiencing shedding post-dose. In RV1 studies, peak shedding occurred around day 7 after dose 1, and 18.8% (95% CI 10.9-29) of twin infants who did not receive RV1 tested positive for the virus in their stool after their twin received rotavirus vaccine. The Advisory Committee on Immunization Practices (ACIP) generally favors vaccination of the infant in order to protect the vaccinee and contacts against rotavirus gastroenteritis. ACIP recommends that persons with most forms of immunosuppression should not receive rotavirus vaccine themselves until immune function improves because of a risk of severe or prolonged gastroenteritis. In addition to an increased risk of gastroenteritis, immunosuppression may reduce the immune response to rotavirus vaccine. Potentially immunocompromised patients include those with blood dyscrasias or any neoplastic disease that causes bone marrow suppression or affects the lymphatic system such as leukemia or lymphoma; those receiving chemotherapy or radiation therapy; those on immunosuppressive therapy such as high-dose systemic corticosteroids; cellular immune deficiencies; hypogammaglobulinemic and dysgammaglobulinemic states (e.g., hypogammaglobulinemia, agammaglobulinemia); and those with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). In support of vaccinating HIV-exposed or infected infants, the ACIP suggests healthcare providers consider that the vaccine undergoes considerable attenuation and that the diagnosis of HIV might not be established before the first scheduled dose of rotavirus vaccine. Corticosteroid therapy usually is not a contraindication to administering live-virus vaccines when administration is short-term (< 2 weeks); a low-to-moderate dose (< 2 mg/kg of body weight or 20 mg/day of prednisone or equivalent for persons who weigh > 10 kg when administered for < 2 weeks); long-term, alternate-day treatment with short-acting preparations; maintenance physiologic doses (replacement therapy); or when administered topically (skin, eyes), inhaled, or by local injection. Healthcare providers should wait at least 1 month after discontinuation of high dose corticosteroid therapy given for more than 2 weeks before administering rotavirus vaccine. Blood products, including antibody containing products, are not considered contraindications for the rotavirus vaccine. Rotavirus vaccine may be administered to eligible infants before, concurrent with, or after administration of any blood product. Patients with leukemia, lymphoma, or other neoplastic disease whose disease is in remission and whose chemotherapy or radiation therapy has been terminated for at least 3 months can receive live-virus vaccines.

Safety and efficacy of the rotavirus vaccine have not been established in neonates and infants < 6 weeks of age.

Description: Rotavirus vaccine is a live virus vaccine administered orally for immunization against rotavirus gastroenteritis, the most common cause of severe gastroenteritis in infants and children. Rotavirus gastroenteritis produces significant morbidity that can lead to fatalities. Different formulations of the vaccine exist: a pentavalent human-bovine rotavirus vaccine (RV5 or RotaTeq) and a monovalent human rotavirus vaccine (RV1 or Rotarix). RV5 protects against rotavirus gastroenteritis caused by the serotypes G1, G2, G3, G4, and G9, while RV1 protects against rotavirus gastroenteritis caused by the serotypes G1, G3, G4, and G9. Efficacy studies have demonstrated protection rates against severe rotavirus disease of 92% to 98% and 85% to 96% for RV5 and RV1, respectively. Sustained protection against rotavirus disease has also been observed up until at least 4 years for RV5 and until at least 2 years of age for RV1. Vaccine efficacy for preventing rotavirus-associated hospitalizations and emergency department visits has been noted to be approximately 84% to 96% and 70% to 96% for patients immunized with RV5 and RV1, respectively. The first rotavirus vaccine (RRV-TV or Rotashield) was associated with intussusception and subsequently withdrawn from the US market; concern that RV1 or RV5 may increase the risk for intussusception motivated investigation during clinical trials. In 2 randomized, double-blind, placebo-controlled trials of RV1 or RV5, the risk of intussusception after immunization was no greater in infants that received the vaccines compared to those who received placebo. However, intussusception has been temporally associated with rotavirus vaccine during postmarketing experience, particularly within the first 7 days after vaccination. RV5 (RotaTeq) and RV1 (Rotarix) are FDA-approved for use in infants as young as 6 weeks.

General dosing information:
-The Advisory Committee on Immunization Practices (ACIP) does not express a preference for the use of RV1 (Rotarix) or RV5 (RotaTeq) for rotavirus prophylaxis. RV5 protects against rotavirus gastroenteritis caused by the serotypes G1, G2, G3, G4, and G9, while RV1 protects against rotavirus gastroenteritis caused by the serotypes G1, G3, G4, and G9.
-No data are available on the degree of protection against rotavirus disease provided if the full series is not received.
-Infants who have had rotavirus gastroenteritis before receiving the full course of rotavirus vaccinations should still initiate or complete the 3-dose schedule because the initial infection frequently provides only partial immunity. No data are available on post-exposure prophylaxis with rotavirus vaccine.
-It is recommended that the same brand of rotavirus vaccine be given for the entire immunization series since no safety and efficacy data regarding interchangeability are available. Do not defer completion of the immunization series if a previous product given is not available or unknown; continue to complete the series with available product. If previous vaccine product is unknown or if any known dose in the previous series was RV5 (RotaTeq), a total of 3 doses should be administered.
-If a first dose of the vaccine is inadvertently given at 15 weeks of age and older, the series may be completed before age 8 months, 0 days according to ACIP and manufacturer immunization recommendations.
-Use caution in infants born to female patients who received IgG antibodies (e.g., infliximab) during pregnancy, as IgG antibodies have been detected in the serum of infants up to 6 months of age. The risk of infection with live vaccine use may be greater in this patient population.

For rotavirus infection prophylaxis:
Oral dosage (RotaTeq):
Infants 6 to 32 weeks: 2 mL PO for 3 doses with an interval at least 4 weeks between doses, ideally given at 2, 4, and 6 months. The first dose may be given as young as 6 weeks. The maximum age recommended by ACIP for administration of the first dose in the series is 14 weeks, 6 days; the FDA-approved product labeling recommends administration by 12 weeks. The maximum age for the final dose is 8 months, 0 days. Do not initiate the series if the infant is 15 weeks and older. If an incomplete dose is administered for any reason, a replacement dose is not recommended. Clinically stable premature infants may be vaccinated according to chronological age using the same schedule as long as the vaccine is administered at the time of discharge or after discharge from the neonatal intensive care unit or nursery.
Oral dosage (Rotarix vial and oral dosing applicator presentation):
NOTE: Rotarix is supplied in 2 presentations, a vial and oral dosing applicator that requires reconstitution and an oral dosing applicator only that does not require reconstitution. Dosage is dependent on the presentation used.
Infants 6 to 24 weeks: 1 mL PO for 2 doses with an interval at least 4 weeks between doses, ideally given at 2 and 4 months. The first dose in the series may be given as young as 6 weeks; the maximum age for administration is 14 weeks, 6 days. The maximum age recommended by ACIP for final dose administration is 8 months, 0 days; however, the FDA-approved product labeling recommends completion by 24 weeks. Do not initiate the series if the infant is 15 weeks and older. If an incomplete dose is administered for any reason, a replacement dose is not recommended by ACIP, although the product labeling states that a single replacement dose may be considered. Clinically stable premature infants may be vaccinated according to chronological age using the same schedule as long as the vaccine is administered at the time of discharge or after discharge from the neonatal intensive care unit or nursery.
Infants 25 to 32 weeks*: 1 mL PO for last dose in series with an interval of at least 4 weeks between doses; do not initiate series in patients older than 14 weeks, 6 days. The maximum age recommended by ACIP for final dose administration is 8 months, 0 days; however, the product labeling recommends completion by 24 weeks. If an incomplete dose is administered for any reason, a replacement dose is not recommended by ACIP, although the product labeling states that a single replacement dose may be considered.
Oral dosage (Rotarix oral dosing applicator only presentation):
NOTE: Rotarix is supplied in 2 presentations, a vial and oral dosing applicator that requires reconstitution and an oral dosing applicator only that does not require reconstitution. Dosage is dependent on the presentation used.
Infants 6 to 24 weeks: 1.5 mL PO for 2 doses with an interval at least 4 weeks between doses, ideally given at 2 and 4 months. The first dose in the series may be given as young as 6 weeks; the maximum age for administration is 14 weeks, 6 days. The maximum age recommended by ACIP for final dose administration is 8 months, 0 days; however, the FDA-approved product labeling recommends completion by 24 weeks. Do not initiate the series if the infant is 15 weeks and older. If an incomplete dose is administered for any reason, a replacement dose is not recommended by ACIP, although the product labeling states that a single replacement dose may be considered. Clinically stable premature infants may be vaccinated according to chronological age using the same schedule as long as the vaccine is administered at the time of discharge or after discharge from the neonatal intensive care unit or nursery.
Infants 25 to 32 weeks*: 1.5 mL PO for last dose in series with an interval of at least 4 weeks between doses; do not initiate series in patients older than 14 weeks, 6 days. The maximum age recommended by ACIP for final dose administration is 8 months, 0 days; however, the product labeling recommends completion by 24 weeks. If an incomplete dose is administered for any reason, a replacement dose is not recommended by ACIP, although the product labeling states that a single replacement dose may be considered.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established.
-Infants
Younger than 6 weeks: Safety and efficacy have not been established.
6 to 32 weeks: 2 mL/dose PO of RV5 (RotaTeq); 1.5 mL/dose PO of RV1 (Rotarix oral dosing applicator only); 1 mL/dose PO of RV1 (Rotarix vial and oral dosing applicator).
Older than 32 weeks: Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Adolescents
Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. However, consult current immunization schedules for recommended vaccines for use in young dialysis patients; the ACIP states that all routine vaccinations are likely effective in patients with chronic renal disease.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: The exact immunologic mechanism by which rotavirus vaccine protects against rotavirus gastroenteritis is unknown. The live viral vaccine replicates in the small intestine and induces immunity. A relationship between antibody responses to rotavirus vaccine and protection against rotavirus gastroenteritis has not been established.

Pharmacokinetics: The rotavirus vaccine is administered orally. The pharmacokinetics of the vaccine are not well defined.


-Special Populations
Pediatrics
Infants >= 6 weeks
After 2 doses of RV1 (Rotarix), 86.5% of 787 infants seroconverted as compared with 6.7% of 420 placebo recipients. Similar findings were noted in another study (76.8% of 393 of RV1 recipients vs. 9.7% of 341 placebo recipients); seroconversion was defined as the appearance of anti-rotavirus serum IgA antibodies (concentration >= 20 units/ml) after vaccination of infants previously negative for rotavirus. A relationship between antibody responses and protection from clinical rotavirus disease is not established.

During phase 3 studies, an increase in the concentration of anti-rotavirus serum IgA antibodies was used as a marker of seroconversion from RV5 (RotaTeq). After a 3-dose regimen, 93-100% of 439 RV5 recipients achieved a 3-fold or more rise in serum anti-rotavirus IgA compared with 12-20% of 397 placebo recipients. A relationship between antibody responses and protection from clinical rotavirus disease is not established.