Prodigrip

Prodigrip uses

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Description
• Clinical pharmacology
• Non-clinical toxicology
• Clinical studies
• References
• How supplied/storage and handling
• Patient counseling information
• Prodigrip reviews

1 INDICATIONS AND USAGE

Fluzone^® High-Dose is a vaccine indicated for active immunization for the prevention of Prodigrip disease caused by Prodigrip A subtype viruses and type B virus contained in the vaccine.

Prodigrip is approved for use in persons 65 years of age and older.

Prodigrip is a vaccine indicated for active immunization for the prevention of Prodigrip disease caused by Prodigrip A subtype viruses and type B virus contained in the vaccine. (1)

Prodigrip is approved for use in persons 65 years of age and older. (1)

2 DOSAGE AND ADMINISTRATION

• For intramuscular use only

• For intramuscular use only

A single 0.5 mL dose for intramuscular injection in adults 65 years of age and older.

2.1 Dose and Schedule

Prodigrip should be administered as a single 0.5 mL injection by the intramuscular route in adults 65 years of age and older.

2.2 Administration

Inspect Prodigrip visually for particulate matter and/or discoloration prior to administration. If either of these conditions exist, the vaccine should not be administered.

Before administering a dose of vaccine, shake the prefilled syringe.

The preferred site for intramuscular injection is the deltoid muscle. The vaccine should not be injected into the gluteal area or areas where there may be a major nerve trunk.

Do not administer this product intravenously or subcutaneously.

Prodigrip should not be combined through reconstitution or mixed with any other vaccine.

3 DOSAGE FORMS AND STRENGTHS

Prodigrip is a suspension for injection.

Prodigrip is supplied in prefilled syringes (gray syringe plunger rod), 0.5 mL, for adults 65 years of age and older.

Suspension for injection in prefilled syringe (gray plunger rod), 0.5 mL. (3)

4 CONTRAINDICATIONS

A severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine [see Description (11) ], including egg protein, or to a previous dose of any Prodigrip vaccine is a contraindication to administration of Prodigrip.

Severe allergic reaction to any component of the vaccine, including egg protein, or after previous dose of any Prodigrip vaccine. (4)

5 WARNINGS AND PRECAUTIONS

• If Guillain-Barré syndrome has occurred within 6 weeks following previous Prodigrip vaccination, the decision to give Prodigrip should be based on careful consideration of the potential benefits and risks. (5.1)

5.1 Guillain-Barré Syndrome

If Guillain-Barré syndrome (GBS) has occurred within 6 weeks following previous Prodigrip vaccination, the decision to give Prodigrip should be based on careful consideration of the potential benefits and risks. The 1976 swine Prodigrip vaccine was associated with an elevated risk of GBS. Evidence for a causal relation of GBS with other Prodigrip vaccines is inconclusive; if an excess risk exists, it is probably slightly more than 1 additional case per 1 million persons vaccinated.

5.2 Preventing and Managing Allergic Reactions

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

5.3 Altered Immunocompetence

If Prodigrip is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the expected immune response may not be obtained.

5.4 Limitations of Vaccine Effectiveness

Vaccination with Prodigrip may not protect all recipients.

6 ADVERSE REACTIONS

• In adults ≥65 years of age, the most common injection-site reaction was pain ; the most common solicited systemic adverse events were myalgia, malaise, and headache (>10%). (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Sanofi Pasteur Inc., Discovery Drive, Swiftwater, PA 18370 at 1-800-822-2463 (1-800-VACCINE) or VAERS at 1-800-822-7967 or www.vaers.hhs.gov.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trial(s) of a vaccine cannot be directly compared to rates in the clinical trial(s) of another vaccine and may not reflect the rates observed in practice.

Two clinical studies have evaluated the safety of Prodigrip.

Study 1 (NCT00391053, see http://clinicaltrials.gov) was a multi-center, double-blind pre-licensure trial conducted in the US. In this study, adults 65 years of age and older were randomized to receive either Prodigrip or Fluzone (2006-2007 formulation). The study compared the safety and immunogenicity of Prodigrip to those of Fluzone. The safety analysis set included 2573 Prodigrip recipients and 1260 Fluzone recipients.

Table 1 summarizes solicited injection-site reactions and systemic adverse events reported within 7 days post-vaccination via diary cards. Onset was usually within the first 3 days after vaccination and a majority of the reactions resolved within 3 days. Solicited injection-site reactions and systemic adverse events were more frequent after vaccination with Prodigrip compared to Fluzone.

Within 6 months post-vaccination, 156 (6.1%) Prodigrip recipients and 93 (7.4%) Fluzone recipients experienced a serious adverse event (SAE). No deaths were reported within 28 days post-vaccination. A total of 23 deaths were reported during Days 29 – 180 post-vaccination: 16 (0.6%) among Prodigrip recipients and 7 (0.6%) among Fluzone recipients. The majority of these participants had a medical history of cardiac, hepatic, neoplastic, renal, and/or respiratory diseases. These data do not provide evidence for a causal relationship between deaths and vaccination with Prodigrip.

Study 2 (NCT01427309, see http://clinicaltrials.gov) was a multi-center, double-blind post-licensure efficacy trial conducted in the US and Canada over two Prodigrip seasons. In this study, adults 65 years of age and older were randomized to receive either Prodigrip or Fluzone (2011-2012 and 2012-2013 formulations). The study compared the efficacy and safety of Prodigrip to those of Fluzone. The safety analysis set included 15,992 Prodigrip recipients and 15,991 Fluzone recipients.

Within the study surveillance period (approximately 6 to 8 months post-vaccination), 1323 (8.3%) Prodigrip recipients and 1442 (9.0%) Fluzone recipients experienced an SAE. Within 30 days post-vaccination, 204 (1.3%) Prodigrip recipients and 200 (1.3%) Fluzone recipients experienced an SAE. The majority of these participants had one or more chronic comorbid illnesses. A total of 167 deaths were reported within 6 to 8 months post-vaccination: 83 (0.5%) among Prodigrip recipients and 84 (0.5%) among Fluzone recipients. A total of 6 deaths were reported within 30 days post-vaccination: 6 (0.04%) among Prodigrip recipients and 0 (0 %) among Fluzone recipients. These data do not provide evidence for a causal relationship between deaths and vaccination with Prodigrip.

6.2 Post-Marketing Experience

The following events have been spontaneously reported during the post-approval use of Fluzone or Prodigrip. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. Adverse events were included based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to Fluzone or Prodigrip.

Events Reported During Post-Approval Use of Fluzone.

• Blood and Lymphatic System Disorders: Thrombocytopenia, lymphadenopathy
• Immune System Disorders: Anaphylaxis, other allergic/hypersensitivity reactions (including urticaria, angioedema)
• Eye Disorders: Ocular hyperemia
• Nervous System Disorders: Guillain-Barré syndrome (GBS), convulsions, febrile convulsions, myelitis (including encephalomyelitis and transverse myelitis), facial palsy (Bell's palsy), optic neuritis/neuropathy, brachial neuritis, syncope (shortly after vaccination), dizziness, paresthesia
• Vascular Disorders: Vasculitis, vasodilatation/flushing
• Respiratory, Thoracic and Mediastinal Disorders: Dyspnea, pharyngitis, rhinitis, cough, wheezing, throat tightness
• Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome
• General Disorders and Administration Site Conditions: Pruritus, asthenia/fatigue, pain in extremities, chest pain
• Gastrointestinal Disorders: Vomiting

Other Events Reported During Post-Approval Use of Prodigrip.

• Gastrointestinal Disorders: Nausea, diarrhea
• General Disorders and Administration Site Conditions: Chills

7 DRUG INTERACTIONS

Data evaluating the concomitant administration of Prodigrip with other vaccines are not available.

8 USE IN SPECIFIC POPULATIONS

Safety and effectiveness of Prodigrip has not been established in pregnant women.

8.1 Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with Prodigrip. It is also not known whether Prodigrip can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Prodigrip should be given to a pregnant woman only if clearly needed.

8.4 Pediatric Use

Safety and effectiveness of Prodigrip in persons <65 years of age have not been established.

8.5 Geriatric Use

Safety, immunogenicity, and efficacy of Prodigrip have been evaluated in adults 65 years of age and older. [See Adverse Reactions (6.1) and Clinical Studies (14) ]

11 DESCRIPTION

Prodigrip (Influenza Vaccine) for intramuscular injection is an inactivated Prodigrip vaccine, prepared from Prodigrip viruses propagated in embryonated chicken eggs. The virus-containing allantoic fluid is harvested and inactivated with formaldehyde. Prodigrip virus is concentrated and purified in a linear sucrose density gradient solution using a continuous flow centrifuge. The virus is then chemically disrupted using a non-ionic surfactant, octylphenol ethoxylate (Triton^® X-100), producing a "split virus". The split virus is further purified and then suspended in sodium phosphate-buffered isotonic sodium chloride solution. The Prodigrip process uses an additional concentration factor after the ultrafiltration step in order to obtain a higher hemagglutinin (HA) antigen concentration.

Prodigrip suspension for injection is clear and slightly opalescent in color.

Neither antibiotics nor preservative are used in the manufacture of Prodigrip.

The Prodigrip prefilled syringe presentation is not made with natural rubber latex.

Prodigrip is standardized according to United States Public Health Service requirements and is formulated to contain HA of each of the following three Prodigrip strains recommended for the 2017-2018 Prodigrip season: A/Michigan/45/2015 X-275 (H1N1), A/Hong Kong/4801/2014 X-263-B(H3N2), and B/Brisbane/60/2008(B Victoria Lineage). The amounts of HA and other ingredients per dose of vaccine are listed in Table 2.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Prodigrip illness and its complications follow infection with Prodigrip viruses. Global surveillance of Prodigrip identifies yearly antigenic variants. For example, since 1977, antigenic variants of Prodigrip A (H1N1 and H3N2) viruses and Prodigrip B viruses have been in global circulation. Specific levels of hemagglutination inhibition (HI) antibody titer post-vaccination with inactivated Prodigrip virus vaccines have not been correlated with protection from Prodigrip virus infection. In some human studies, antibody titers ≥1:40 have been associated with protection from Prodigrip illness in up to 50% of participants.

Antibodies against one Prodigrip virus type or subtype confer limited or no protection against another. Furthermore, antibodies to one antigenic variant of Prodigrip virus might not protect against a new antigenic variant of the same type or subtype. Frequent development of antigenic variants through antigenic drift is the virologic basis for seasonal epidemics and the reason for the usual change of one or more new strains in each year's Prodigrip vaccine. Therefore, Prodigrip vaccines are standardized to contain the hemagglutinins of Prodigrip virus strains representing the Prodigrip viruses likely to be circulating in the US during the Prodigrip season.

Annual vaccination with the current vaccine is recommended because immunity during the year after vaccination declines and because circulating strains of Prodigrip virus change from year to year.

13 NON-CLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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

14 CLINICAL STUDIES

14.1 Immunogenicity of Prodigrip in Adults 65 Years of Age and Older

Study 1 was a multi-center, double-blind pre-licensure trial conducted in the US in which adults 65 years of age and older were randomized to receive either Prodigrip or Fluzone (2006-2007 formulation). The study compared the safety and immunogenicity of Prodigrip to those of Fluzone. For immunogenicity analyses, 2576 participants were randomized to Prodigrip and 1275 participants were randomized to Fluzone. Females accounted for 51.3% of participants in the Prodigrip group and 54.7% of participants in the Fluzone group. In both groups, the mean age was 72.9 years (ranged from 65 through 97 years in the Prodigrip group and 65 through 94 years in the Fluzone group); 35% of participants in the Prodigrip group and 36% of participants in the Fluzone group were 75 years of age or older. Most participants in the Prodigrip and Fluzone groups, respectively, were White (91.7% and 92.9%), followed by Hispanic (4.8% and 3.7%), and Black (2.7% and 2.7%).

The primary endpoints of the study were HI GMTs and seroconversion rates 28 days after vaccination. Pre-specified statistical superiority criteria required that the lower limit (LL) of the 2-sided 95% CI of the GMT ratio (Fluzone High-Dose/Fluzone) be greater than 1.50 for at least two of the strains, and if one strain failed, non-inferiority of that strain must be demonstrated (LL>0.67), and that the lower limit of the 2-sided 95% CI of the seroconversion rate difference (Fluzone High-Dose minus Fluzone) be greater than 10% for at least two of the strains, and if one strain failed, non-inferiority of that strain must be demonstrated (LL>-10%). As shown in Table 3, statistically superior HI GMTs and seroconversion rates after vaccination with Prodigrip compared to Fluzone were demonstrated for Prodigrip A subtypes, A (H1N1) and A (H3N2), but not for Prodigrip type B. For strain B, non-inferiority of Prodigrip compared to Fluzone was demonstrated for both the HI GMTs and seroconversion rates.

14.2 Efficacy of Prodigrip in Adults 65 Years of Age and Older

Study 2 (NCT01427309) was a multi-center, double-blind post-licensure efficacy trial conducted in the US and Canada in which adults 65 years of age and older were randomized (1:1) to receive either Prodigrip or Fluzone. The study was conducted over two Prodigrip seasons (2011-2012 and 2012-2013); 53% of participants enrolled in the first year of the study were re-enrolled and re-randomized in the second year. The per-protocol analysis set for efficacy assessments included 15,892 Prodigrip recipients and 15,911 Fluzone recipients. The majority (67%) of participants in the per-protocol analysis set for efficacy had one or more high-risk chronic comorbid conditions.

In the per-protocol analysis set, females accounted for 57.2% of participants in the Prodigrip group and 56.1% of participants in the Fluzone group. In both groups, the median age was 72.2 years (range 65 through 100 years). Overall, most participants in the study were White (95%); approximately 4% of study participants were Black, and approximately 6% reported Hispanic ethnicity.

The primary endpoint of the study was the occurrence of laboratory-confirmed Prodigrip (as determined by culture or polymerase chain reaction) caused by any Prodigrip viral type/subtype in association with influenza-like illness (ILI), defined as the occurrence of at least one of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing; concurrent with at least one of the following systemic signs or symptoms: temperature >99.0°F, chills, tiredness, headaches or myalgia. Participants were monitored for the occurrence of a respiratory illness by both active and passive surveillance, starting 2 weeks post-vaccination for approximately 7 months. After an episode of respiratory illness, nasopharyngeal swab samples were collected for analysis; attack rates and vaccine efficacy were calculated.

A secondary endpoint of the study was the occurrence of culture-confirmed Prodigrip caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations in association with a modified CDC-defined ILI, defined as the occurrence of a temperature > 99.0°F (> 37.2°C) with cough or sore throat. The efficacy of Prodigrip relative to Fluzone for this endpoint was 51.1% (95% CI: 16.8; 72.0).

15 REFERENCES

• Lasky T, Terracciano GJ, Magder L, et al. The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 Prodigrip vaccines. N Engl J Med 1998;339:1797-802.
• Baxter, R, et al. Lack of Association of Guillain-Barré Syndrome with Vaccinations. Clin Infect Dis 2013;57(2):197-204.
• Hannoun C, Megas F, Piercy J. Immunogenicity and protective efficacy of Prodigrip vaccination. Virus Res 2004;103:133-138.
• Hobson D, Curry RL, Beare AS, Ward-Gardner A. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with Prodigrip A2 and B viruses. J Hyg Camb 1972;70:767-777.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Single-dose, prefilled syringe, without needle, 0.5 mL (not made with natural rubber latex). Supplied as package of 10 (NDC 49281-401-65).

16.2 Storage and Handling

Store Prodigrip refrigerated at 2° to 8°C (35° to 46°F). DO NOT FREEZE. Discard if vaccine has been frozen.

Do not use after the expiration date shown on the label.

17 PATIENT COUNSELING INFORMATION

• Inform the patient or caregiver that Prodigrip contains killed viruses and cannot cause Prodigrip.
• Among persons aged 65 years and older, Prodigrip stimulates the immune system to produce antibodies that help protect against Prodigrip.
• Among persons aged 65 years and older, Prodigrip offers better protection against Prodigrip as compared to Fluzone.
• Annual Prodigrip vaccination is recommended.
• Instruct vaccine recipients and caregivers to report adverse reactions to their healthcare provider and/or to Vaccine Adverse Event Reporting System (VAERS).

Fluzone is a registered trademark of Sanofi Pasteur Inc.

Manufactured by:

Sanofi Pasteur Inc.

Swiftwater PA 18370 USA

7032

Patient Information Sheet

Fluzone^® High-Dose

Prodigrip Vaccine

Please read this information sheet before getting Prodigrip vaccine. This summary is not intended to take the place of talking with your healthcare provider. If you have questions or would like more information, please talk with your healthcare provider.

What is Prodigrip vaccine?

Prodigrip is a vaccine that helps protect against Prodigrip illness (flu).

Prodigrip vaccine is for people 65 years of age and older.

Vaccination with Prodigrip vaccine may not protect all people who receive the vaccine.

Who should not get Prodigrip vaccine?

You should not get Prodigrip vaccine if you:

• ever had a severe allergic reaction to eggs or egg products.
• ever had a severe allergic reaction after getting any flu vaccine.
• are younger than 65 years of age.

Tell your healthcare provider if you have or have had:

• Guillain-Barré syndrome (severe muscle weakness) after getting a flu vaccine.
• problems with your immune system as the immune response may be diminished.

How is Prodigrip vaccine given?

Prodigrip vaccine is a shot given into the muscle of the arm.

What are the possible side effects of Prodigrip vaccine?

The most common side effects of Prodigrip vaccine are:

• pain, redness, and swelling where you got the shot
• muscle ache
• tiredness
• headache

These are not all of the possible side effects of Prodigrip vaccine. You can ask your healthcare provider for a list of other side effects that is available to healthcare professionals.

Call your healthcare provider for advice about any side effects that concern you. You may report side effects to the Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967 or http://vaers.hhs.gov.

Why should I get Prodigrip vaccine instead of Fluzone vaccine?

An efficacy study in adults 65 years of age and older has demonstrated that Prodigrip vaccine offers better protection against Prodigrip than Fluzone vaccine.

What are the ingredients in Prodigrip vaccine?

Prodigrip vaccine contains 3 killed flu virus strains.

Inactive ingredients include formaldehyde and octylphenol ethoxylate.

Manufactured by: Sanofi Pasteur Inc.

Swiftwater, PA 18370 USA

Prodigrip pharmaceutical active ingredients containing related brand and generic drugs:

• Influenza Vaccine

Prodigrip available forms, composition, doses:

• N/A

Prodigrip destination | category:

• Human:
• Vaccines, antisera and immunologicals

Prodigrip Anatomical Therapeutic Chemical codes:

• J07BB - Influenza vaccines

Prodigrip pharmaceutical companies:

• Sanofi-Aventis

References

1. Dailymed."FLUBLOK (INFLUENZA VACCINE) INJECTION, SOLUTION [PROTEIN SCIENCES CORPORATION]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Depending on the reaction of the Prodigrip after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Prodigrip not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology