Pharmaceutical Name

Trade (marketing or proprietary) name: RotaTeq, ROTARIX

Generic (nonproprietary or active ingredient) name: Rotavirus Vaccine, Live, Oral, Pentavalent Oral Solution

Indication and Usage

Reason the product has been approved for sale on the market.

RotaTeq is a vaccine indicated for the prevention of rotavirus gastroenteritis caused by types G1, G2, G3, G4, and G9. RotaTeq is approved for use in infants 6 weeks to 32 weeks of age.

ROTARIX is a vaccine indicated for the prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9). ROTARIX is approved for use in infants 6 weeks and up to 24 weeks of age.

Manufacturer Insert

Ingredients

Also known as “excipients” for vaccines.

RotaTeq is a live, oral pentavalent vaccine that contains 5 live reassortant rotaviruses. The rotavirus parent strains of the reassortants were isolated from human and bovine hosts. Each vaccine dose contains sucrose, sodium citrate, sodium phosphate monobasic monohydrate, sodium hydroxide, polysorbate 80, cell culture media, and trace amounts of fetal bovine serum. RotaTeq contains no preservatives.

ROTARIX (Rotavirus Vaccine, Live, Oral), for oral administration, is a live, attenuated rotavirus vaccine derived from the human 89-12 strain which belongs to G1P type. The lyophilized vaccine contains amino acids, dextran, Dulbecco’s Modified Eagle Medium (DMEM), sorbitol, and sucrose. DMEM contains the following ingredients: sodium chloride, potassium chloride, magnesium sulfate, ferric (III) nitrate, sodium phosphate, sodium pyruvate, D-glucose, concentrated vitamin solution, L-cystine, L-tyrosine, amino acids solution, Lglutamine, calcium chloride, sodium hydrogenocarbonate, and phenol red. The liquid diluent contains calcium carbonate, sterile water, and xanthan. The diluent includes an antacid component (calcium carbonate) to protect the vaccine during passage through the stomach and prevent its inactivation due to the acidic environment of the stomach.

In the manufacturing process, porcine-derived materials are used. Porcine circovirus type 1
(PCV-1) is present in ROTARIX. PCV-1 is not known to cause disease in humans.

Contraindications

Per the FDA, contraindications are conditions in a recipient that increases the risk for a serious adverse reaction. Product should not be administered when a patient has a listed contraindication.

RotaTeq

Hypersensitivity: A demonstrated history of hypersensitivity to any component of the vaccine. Infants who develop symptoms suggestive of hypersensitivity after receiving a dose of RotaTeq should not receive further doses of RotaTeq.

Severe Combined Immunodeficiency Disease: Infants with Severe Combined Immunodeficiency Disease (SCID) should not receive RotaTeq. Postmarketing reports of gastroenteritis, including severe diarrhea and prolonged shedding of vaccine virus, have been reported in infants who were administered RotaTeq and later identified as having SCID.

History of Intussusception: Infants with a history of intussusception should not receive RotaTeq.

ROTARIX

Hypersensitivity: A demonstrated history of hypersensitivity to any component of the vaccine. Infants who develop symptoms suggestive of hypersensitivity after receiving a dose ofROTARIX should not receive further doses of ROTARIX.

Gastrointestinal Tract Congenital Malformation: Infants with a history of uncorrected congenital malformation of the gastrointestinal tract (such as Meckel’s diverticulum) that would predispose the infant for intussusception should not receive ROTARIX.

History of Intussusception: Infants with a history of intussusception should not receive ROTARIX. In postmarketing experience, intussusception resulting in death following a second dose has been reported following a history of intussusception after the first dose.

Severe Combined Immunodeficiency Disease: Infants with Severe Combined Immunodeficiency Disease (SCID) should not receive ROTARIX. Postmarketing reports of gastroenteritis, including severe diarrhea and prolonged shedding of vaccine virus, have been reported in infants who were administered live, oral rotavirus vaccines and later identified as having SCID.

Warnings and Precautions

Per the FDA, warnings are clinically significant adverse reactions or risks. According to the CDC, a precaution is a condition in a recipient that might increase the risk for a serious adverse reaction, might cause diagnostic confusion, or might compromise the effectiveness of the product. In general, a product should be deferred when a precaution is present.

RotaTeq

Managing Allergic Reactions: Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.

Immunocompromised Populations: No safety or efficacy data are available from clinical trials regarding the administration of RotaTeq to infants who are potentially immunocompromised including:

• Infants with blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system.
• Infants on immunosuppressive therapy (including high-dose systemic corticosteroids). RotaTeq may be administered to infants who are being treated with topical corticosteroids or inhaled steroids.
• Infants with primary and acquired immunodeficiency states, including HIV/AIDS or other clinical manifestations of infection with human immunodeficiency viruses; cellular immune deficiencies; and hypogammaglobulinemic and dysgammaglobulinemic states. There are insufficient data from the clinical trials to support administration of RotaTeq to infants with indeterminate HIV status who are born to mothers with HIV/AIDS.
• Infants who have received a blood transfusion or blood products, including immunoglobulins within 42 days.

Vaccine virus transmission from vaccine recipient to non-vaccinated contacts has been reported.

Intussusception: Following administration of a previously licensed live rhesus rotavirus reassortant vaccine, an increased risk of intussusception was observed. In a post-marketing observational study in the US cases of intussusception were observed in temporal
association within 21 days following the first dose of RotaTeq, with a clustering of cases in the first 7 days. In worldwide passive post-marketing surveillance, cases of intussusception have been reported in temporal association with RotaTeq.

Gastrointestinal Illness: No safety or efficacy data are available for administration of RotaTeq to infants with a history of gastrointestinal disorders including infants with active acute gastrointestinal illness, infants with chronic diarrhea and failure to thrive, and infants with a history of congenital abdominal disorders, and abdominal surgery. Caution is advised when considering administration of RotaTeq to these infants.

Shedding and Transmission Shedding of vaccine virus was evaluated among a subset of subjects in the Rotavirus Efficacy and Safety Trial (Study 006, also known as REST) 4 to 6 days after each dose and among all subjects who submitted a stool antigen rotavirus positive sample at any time. RotaTeq was shed in the stools of 32 of 360 [8.9%, 95% CI (6.2%, 12.3%)] vaccine recipients tested after dose 1; 0 of 249 [0.0%, 95% CI (0.0%, 1.5%)] vaccine recipients tested after dose 2; and in 1 of 385 [0.3%, 95% CI (<0.1%, 1.4%)] vaccine recipients after dose 3. In phase 3 studies, shedding was observed as early as 1 day and as late as 15 days after a dose. Transmission of vaccine virus was not evaluated in phase 3 studies. Transmission of vaccine virus strains from vaccinees to non-vaccinated contacts has been observed
post-marketing.

The potential risk of transmission of vaccine virus should be weighed against the risk of acquiring and transmitting natural rotavirus. Caution is advised when considering whether to administer RotaTeq to individuals with immunodeficient close contacts such as:

• Individuals with malignancies or who are otherwise immunocompromised;
• Individuals with primary immunodeficiency; or
• Individuals receiving immunosuppressive therapy.

Febrile Illness: Febrile illness may be reason for delaying use of RotaTeq except when, in the opinion of the physician, withholding the vaccine entails a greater risk. Low-grade fever (100.5°F [38.1°C]) itself and mild upper respiratory infection do not preclude vaccination with RotaTeq.

Incomplete Regimen: The clinical studies were not designed to assess the level of protection provided by only one or two doses of RotaTeq.

Limitations of Vaccine Effectiveness: RotaTeq may not protect all vaccine recipients against rotavirus.

Post-Exposure Prophylaxis: No clinical data are available for RotaTeq when administered after exposure to rotavirus.

Immunosuppressive therapies including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to vaccines.

ROTARIX

Latex: The tip caps of the prefilled oral applicators of diluent contain natural rubber latex which may cause allergic reactions.

Gastrointestinal Disorders: Administration of ROTARIX should be delayed in infants suffering from acute diarrhea or vomiting. Safety and effectiveness of ROTARIX in infants with chronic gastrointestinal disorders have not been evaluated.

Altered Immunocompetence: Safety and effectiveness of ROTARIX in infants with known primary or secondary immunodeficiencies, including infants with human immunodeficiency virus (HIV), infants on immunosuppressive therapy, or infants with malignant neoplasms affecting the bone marrow or lymphatic system have not been established.

Shedding and Transmission: Rotavirus shedding in stool occurs after vaccination with peak excretion occurring around Day 7 after Dose 1. One clinical trial demonstrated that vaccinees transmit vaccine virus to healthy seronegative contacts. The potential for transmission of vaccine virus following vaccination should be weighed against
the possibility of acquiring and transmitting natural rotavirus. Caution is advised when
considering whether to administer ROTARIX to individuals with immunodeficient close
contacts, such as individuals with malignancies, primary immunodeficiency or receiving
immunosuppressive therapy.

Intussusception: Following administration of a previously licensed oral live rhesus rotavirus-based vaccine, an increased risk of intussusception was observed.1 The risk of intussusception with ROTARIX was evaluated in a pre-licensure randomized, placebo-controlled safety study (including 63,225 infants) conducted in Latin America and Finland. No increased risk of intussusception was observed in this clinical trial following administration of ROTARIX when compared with placebo.

In a postmarketing, observational study conducted in Mexico, cases of intussusception were
observed in temporal association within 31 days following the first dose of ROTARIX, with a
clustering of cases in the first 7 days.

Other postmarketing observational studies conducted in Brazil and Australia also suggest an increased risk of intussusception within the first 7 days following the second dose of ROTARIX.

In worldwide passive postmarketing surveillance, cases of intussusception have been reported in temporal association with ROTARIX.

Post-exposure Prophylaxis: Safety and effectiveness of ROTARIX when administered after exposure to rotavirus have not been evaluated.

Manufacturer-Listed Adverse Reactions

Per the CDC, adverse reactions are an undesirable medical condition that has been demonstrated to be caused by a vaccine. Evidence for the causal relation is usually obtained through randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine strain from the pathogenic site, or recurrence of the condition with repeated vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.

RotaTeq can cause: Anaphylactic reaction, Intussusception (including death), Hematochezia, Gastroenteritis (Stomach Flu), Vaccine viral shedding, Urticaria (Hives), Angioedema, Kawasaki disease, and transmission of vaccine virus strains from vaccine recipient to non-vaccinated contacts.

ROTARIX can cause: Intussusception, Death (listed twice), Hematochezia, Gastroenteritis (Stomach Flu), Viral Shedding, Idiopathic thrombocytopenic purpura, Kawasaki disease, Maladministration.

Limitations of Effectiveness

RotaTeq may not protect all vaccine recipients against rotavirus.

Specific Populations

Pregnancy

RotaTeq is not approved for individuals 32 weeks of age and older. No human or animal data are available to assess vaccine-associated risks in pregnancy.

Breastfeeding

No human or animal data are available to assess the impact of RotaTeq on milk production, its presence in breast milk, or its effect on the breastfed infant.

Fertility

RotaTeq has not been evaluated for its carcinogenic or mutagenic potential or its potential to impair fertility.

ROTARIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

Pediatric

Safety and effectiveness of RotaTeq have not been established in infants less than 6 weeks of age or greater than 32 weeks of age. Data are available from clinical studies to support the use of RotaTeq in pre-term infants according to their age in weeks since birth. Data are available from clinical studies to support the use of RotaTeq in infants with controlled gastroesophageal reflux disease.

Safety and effectiveness of ROTARIX in infants younger than 6 weeks or older than 24 weeks of age have not been evaluated. The effectiveness of ROTARIX in pre-term infants has not been established.

Mechanism of Action

This is the specific biochemical interaction through which a drug or vaccine substance produces its pharmacological effect. This section also includes the minimum protective level designated for a certain disease.

RotaTeq

The exact immunologic mechanism by which RotaTeq protects against rotavirus gastroenteritis is unknown. RotaTeq is a live viral vaccine that replicates in the small intestine and induces immunity.

ROTARIX

The exact immunologic mechanism by which ROTARIX protects against rotavirus gastroenteritis is unknown. ROTARIX contains a live, attenuated human rotavirus that replicates in the small intestine and induces immunity.

Analytical Deep Dive

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