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Find Lowest Prices on TRUMENBA® (meningococcal Group B Vaccine) Suspension for Intramuscular Injection DESCRIPTION Trumenba is a sterile suspension composed of two recombinant lipidated factor H binding protein (fHBP) variants from N. meningitidis serogroup B, one from fHBP subfamily A and one from subfamily B (A05 and B01, respectively).1 The proteins are individually produced in E. coli. Production strains are grown in defined fermentation growth media to a specific density. The recombinant proteins are extracted from the production strains and purified through a series of column chromatography steps. Polysorbate 80 (PS80) is added to the drug substances and is present in the final drug product. Each 0.5 mL dose contains 60 micrograms of each fHBP variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al³ as AlPO4 in 10 mM histidine buffered saline at pH 6.0. REFERENCES 1. Wang X, et al. Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the U.S. Vaccine 2011; 29:4739–4744.

Find Lowest Prices on BEXSERO (meningococcal group B caccine)  Suspension for Intramuscular Injection DESCRIPTION BEXSERO (Meningococcal Group B Vaccine) is a sterile, white, opalescent, suspension for intramuscular injection. Each 0.5-mL dose of BEXSERO is formulated to contain 50 micrograms each of recombinant proteins Neisserial adhesin A (NadA), Neisserial Heparin Binding Antigen (NHBA), and factor H binding protein (fHbp), 25 micrograms of Outer Membrane Vesicles (OMV), 1.5 mg aluminum hydroxide (0.519 mg of Al3+), 3.125 mg sodium chloride, 0.776 mg histidine, and 10 mg sucrose at pH 6.4 - 6.7. The NadA component is a fragment of the full-length protein derived from N. meningitidis strain 2996 (peptide 8 variant 2/3)5. The NHBA component is a recombinant fusion protein comprised of NHBA (peptide 2)5 and accessory protein 953 derived from N. meningitidis strains NZ98/254 and 2996, respectively. The fHbp component is a recombinant fusion protein comprised of fHbp (variant 1.1)5 and the accessory protein 936 derived from N. meningitidis strains MC58 and 2996, respectively. These 3 recombinant proteins are individually produced in Escherichia coli and purified through a series of column chromatography steps. The OMV antigenic component is produced by fermentation of N. meningitidis strain NZ98/254 (expressing outer membrane protein PorA serosubtype P1.4)6, followed by inactivation of the bacteria by deoxycholate, which also mediates vesicle formation. The antigens are adsorbed onto aluminum hydroxide. Each dose contains less than 0.01 micrograms kanamycin (by calculation). REFERENCES 5. Wang X, et al. Vaccine. 2011; 29:4739-4744. 6. Hosking J, et al. Clin Vaccine Immunol. 2007;14:1393-1399.

INDICATIONS Trumenba is indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B. Trumenba is approved for use in individuals 10 through 25 years of age. The effectiveness of the two-dose schedule of Trumenba against diverse N. meningitidis serogroup B strains has not been confirmed. DOSAGE AND ADMINISTRATION For intramuscular use only. Dose And Schedule Three-Dose Schedule Administer a dose (0.5 mL) at 0, 1–2, and 6 months. Two-Dose Schedule Administer a dose (0.5 mL) at 0 and 6 months. If the second dose is administered earlier than 6 months after the first dose, a third dose should be administered at least 4 months after the second dose. The choice of dosing schedule may depend on the risk of exposure and the patient's susceptibility to meningococcal serogroup B disease. Administration Shake syringe vigorously to ensure that a homogenous white suspension of Trumenba is obtained. Do not use the vaccine if it cannot be re-suspended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if particulate matter or discoloration is found. Inject each 0.5 mL dose intramuscularly, using a sterile needle attached to the supplied prefilled syringe. The preferred site for injection is the deltoid muscle of the upper arm. Do not mix Trumenba with any other vaccine in the same syringe. Use Of Trumenba With Other Meningococcal Group B Vaccines Sufficient data are not available on the safety and effectiveness of using Trumenba and other meningococcal group B vaccines interchangeably to complete the vaccination series. HOW SUPPLIED Dosage Forms And Strengths Trumenba is a suspension for intramuscular injection in 0.5 mL single-dose prefilled syringe. Trumenba is supplied in the following strengths and package configurations: Prefilled Syringe, 1 Dose (10 per package) – NDC 0005-0100-10. Prefilled Syringe, 1 Dose (5 per package) – NDC 0005-0100-05. After shipping, Trumenba may arrive at temperatures between 2°C to 25°C (36°F to 77°F). The tip cap and rubber plunger of the prefilled syringe are not made with natural rubber latex. Storage And Handling Upon receipt, store refrigerated at 2°C to 8°C (36°F to 46°F). Store syringes in the refrigerator horizontally (laying flat on the shelf) to minimize the re-dispersion time. Do not freeze. Discard if the vaccine has been frozen. Manufactured by: Pfizer Wyeth Pharmaceuticals Inc, A Subsidary of Pfizer Inc, Philadephia, PA 19101. Revised: Oct 2017.

INDICATIONS BEXSERO is a vaccine indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B. BEXSERO is approved for use in individuals 10 through 25 years of age. Approval of BEXSERO is based on demonstration of immune response, as measured by serum bactericidal activity against three serogroup B strains representative of prevalent strains in the United States. The effectiveness of BEXSERO against diverse serogroup B strains has not been confirmed. DOSAGE AND ADMINISTRATION For intramuscular use only. Dose And Schedule Administer two doses (0.5-mL each) of BEXSERO at least 1 month apart. Administration Shake the syringe immediately before use to form a homogeneous suspension. Do not use the vaccine if it cannot be resuspended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if particulate matter or discoloration is found. Administer BEXSERO as a 0.5-mL intramuscular injection into the deltoid muscle of the upper arm. Use Of BEXSERO With Other Meningococcal Group B Vaccines Sufficient data are not available on the safety and effectiveness of using BEXSERO and other meningococcal group B vaccines interchangeably to complete the vaccination series. HOW SUPPLIED Dosage Forms And Strengths BEXSERO is a suspension for intramuscular injection in 0.5-mL single-dose pre-filled syringes. Storage And Handling BEXSERO is supplied as a 0.5-mL suspension in a glass pre-filled syringe. The tip caps of the pre-filled syringes contain natural rubber latex; the plungers are not made with natural rubber latex. Product presentations for BEXSERO are listed in Table 4 below: Table 4: Product Presentations for BEXSERO Presentation Carton NDC Number Components Pre-filled syringe Carton of 1 syringe 58160-976-06 0.5-mL single-dose pre-filled syringe NDC 58160-976-02 Carton of 10 syringes 58160-976-20 0.5-mL single-dose pre-filled syringe NDC 58160-976-02 Storage And Handling Do not freeze. Discard if the vaccine has been frozen. Store refrigerated, at 36°F to 46°F (2°C to 8°C). Protect from light. Do not use after the expiration date. Manufactured by : GSK Vaccines, Srl, Bellaria-Rosia 53018, Sovicille (SI), Italy, U.S. License No. 1617. Distributed by GlaxoSmithKline, Research Triangle Park, NC 27709. Revised: Oct 2017

PATIENT INFORMATION Prior to administration of this vaccine, the healthcare professional should inform the individual, parent, guardian, or other responsible adult of the following: The importance of completing the immunization series. Report any suspected adverse reactions to a healthcare professional. Provide the Vaccine Information Statements, which are available free of charge at the Centers for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines).

OVERDOSE No Information Provided CONTRAINDICATIONS Severe allergic reaction after a previous dose of Trumenba.

OVERDOSE No Information provided CONTRAINDICATIONS Hypersensitivity, including severe allergic reaction, to any component of the vaccine, or after a previous dose of BEXSERO [see DESCRIPTION].

SIDE EFFECTS In clinical studies, the most common solicited adverse reactions in adolescents and young adults were pain at the injection site (≥85%), fatigue (≥60%), headache (≥55%), and muscle pain (≥35%). Nausea was reported in up to 24% of adolescents in early phase studies. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in clinical practice. The safety of Trumenba was evaluated in 15,227 subjects 10 through 25 years of age in 11 clinical studies (8 randomized controlled and 3 supportive non-controlled studies) conducted in the U.S., Europe, Canada, Chile, and Australia. A total of 11,333 adolescents (10 through 18 years of age) and 3,894 adults (19 through 25 years of age) received at least one dose of Trumenba. A total of 5,501 subjects 10 through 25 years of age in the control groups received saline placebo and/or one of the following vaccine(s): Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant (HPV4) (Merck & Co., Inc.); Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap) (Sanofi Pasteur Ltd.); Meningococcal Polysaccharide (Serogroups A, C, Y and W-135) Diphtheria Toxoid Conjugate Vaccine (MCV4) (Sanofi Pasteur Inc.); a non-U.S. licensed reduced diphtheria toxoid, tetanus toxoid, acellular pertussis and inactivated polio virus vaccine (dTaP-IPV) (Sanofi Pasteur, Inc.); Hepatitis A Vaccine, Inactivated (HAV) (GlaxoSmithKline Biologicals). The safety evaluation in the clinical studies included an assessment of: (1) solicited local and systemic reactions, and use of antipyretic medication after each vaccination in an electronic diary maintained by the subject or the subject's parent/legal guardian and (2) spontaneous reports of adverse events (AEs), including serious adverse events (SAEs), throughout the study (day of vaccination through one month or 6 months after the last vaccination, depending on the study and safety parameter). In controlled studies, demographic characteristics were generally similar with regard to gender, race, and ethnicity among subjects who received Trumenba and those who received control. Overall, across the 11 studies, among the subjects who received Trumenba, 50.5% were male and 49.5% were female, and the majority were White (86.3%) and non-Hispanic/non-Latino (87.3%). Solicited Local And Systemic Adverse Reactions Study 1 was a Phase 3, randomized, active-controlled, observer-blinded, multicenter trial in the U.S., Canada, and Europe in which 2,693 subjects 10 to 18 years of age received at least 1 dose of Trumenba on a 0-, 2-, and 6- month schedule. A control group (n=897) received HAV at 0 and 6 months and saline at 2 months. 87.3% of subjects were White, 8.1% were Black or African-American, 0.4% were Asian, and 5.8% were Hispanic or Latino. Overall, 51.5% of subjects were male, 55.6% of participants were 10 to 14 years age, and 44.4% were 15 to 18 years of age. Study 2 was a Phase 3, randomized, placebo-controlled, observer-blinded, multicenter trial in the U.S., Canada, and Europe in which 2,471 subjects 18 to 25 years of age received at least 1 dose of Trumenba and 822 subjects received saline on a 0-, 2,- and 6- month schedule. 76.1% of subjects were White, 20.8% were Black or African-American, 1.6% were Asian, and 17.1% were Hispanic or Latino. Overall, 41.3% of subjects were male. Local adverse reactions at the Trumenba injection site and control (HAV/saline or saline) injection site were assessed in both studies. Tables 1 and 2 present the percentage and severity of reported local adverse reactions within 7 days following each dose of Trumenba or control (HAV/saline or saline) for Study 1 and Study 2, respectively. Local adverse reactions were reported more frequently following Trumenba compared to control (see Tables 1 and 2). Table 1: Percentages of Subjects 10 to 18 Years of Age (Study 1*) Reporting Local Adverse Reactions Within 7 Days After Each Vaccination Dose 1 Dose 2 Dose 3 Trumenba† HAV/Saline† Trumenba† HAV/Saline† Trumenba† HAV/Saline† Local Reaction N=2681 N=890 N=2545 N=843 N=2421 N=821 Pain‡ Any§ 86.7 47.0 77.7 15.2 76.0 34.0 Mild 41.1 36.5 39.4 12.3 34.1 23.8 Moderate 40.7 9.9 33.2 2.7 36.5 9.9 Severe 5.0 0.6 5.1 0.1 5.4 0.4 Redness¶ Any§ 16.2 1.3 12.5 0.6 13.9 1.1 Mild 5.6 1.2 5.2 0.6 4.9 1.0 Moderate 8.8 0.1 6.1 0.0 6.8 0.1 Severe 1.9 0.0 1.1 0.0 2.2 0.0 Swelling¶ Any§ 18.0 2.2 13.9 0.6 15.4 0.9 Mild 8.5 1.8 6.3 0.5 7.9 0.7 Moderate 8.8 0.4 7.3 0.1 6.8 0.1 Severe 0.7 0.0 0.2 0.0 0.7 0.0 *Study 1: National Clinical Trial (NCT) number NCT01830855. †Trumenba was administered at 0, 2, and 6 months. HAV was administered at 0 and 6 months and saline was administered at 2 months. ‡Mild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity). §"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination. ¶Mild (2.5–5.0 cm); moderate (>5.0–10.0 cm); severe (>10.0 cm). Table 2: Percentages of Subjects 18 to 25 Years of Age (Study 2*) Reporting Local Adverse Reactions Within 7 Days After Each Vaccination Dose 1 Dose 2 Dose 3 Trumenba† Saline† Trumenba† Saline† Trumenba† Saline† Local Reaction N=2425 N=798 N=2076 N=706 N=1823 N=624 Pain‡ Any§ 84.2 11.8 79.3 7.8 80.4 6.7 Mild 42.3 10.7 42.2 6.8 36.1 6.4 Moderate 37.1 1.1 32.7 1.0 38.9 0.3 Severe 4.8 0.0 4.4 0.0 5.3 0.0 Redness¶ Any§ 13.8 0.6 11.8 0.3 17.1 0.2 Mild 5.8 0.5 4.6 0.1 6.2 0.2 Moderate 7.1 0.0 6.3 0.0 8.6 0.0 Severe 0.9 0.1 0.9 0.1 2.3 0.0 Swelling¶ Any§ 15.5 0.6 14.0 0.4 16.6 0.3 Mild 8.5 0.3 7.7 0.3 8.8 0.0 Moderate 6.8 0.3 6.0 0.1 7.2 0.3 Severe 0.2 0.1 0.3 0.0 0.5 0.0 *Study 2: National Clinical Trial (NCT) number NCT01352845. †Trumenba was administered at 0, 2, and 6 months. Saline was administered at 0, 2, and 6 months. ‡Mild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity). §"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination. ¶Mild (2.5–5.0 cm); moderate (>5.0–10.0 cm); severe (>10.0 cm). In Study 1, mean duration of pain was 2.4 to 2.6 days (range 1–17 days), for redness 2.0 to 2.2 days (range 1– 12 days) and for swelling 2.0 to 2.1 days (range 1–21 days) in the combined Trumenba group. In Study 2, mean duration of pain was 2.6 to 2.8 days (range 1–67 days), for redness 2.2 to 2.5 days (range 1–13 days) and for swelling 2.1 to 2.6 days (range 1–70 days) in the Trumenba group. Tables 3 and 4 present the percentage and severity of reported solicited systemic adverse reactions within 7 days of each dose of Trumenba or control (HAV/saline or saline) for Study 1 and Study 2, respectively. Table 3: Percentages of Subjects 10 to 18 Years of Age (Study 1*) Reporting Systemic Adverse Reactions and Use of Antipyretic Medications Within 7 Days After Each Vaccination Dose 1 Dose 2 Dose 3 Trumenba† HAV/Saline† Trumenba† HAV/Saline† Trumenba† HAV/Saline† Systemic Reaction N=2681 N=890 N=2545 N=843 N=2421 N=821 Fever (≥38°C)‡ ≥38.0°C 6.4 1.9 2.0 1.5 2.7 2.3 3 8.0°C to <38.5°C 4.0 1.3 1.2 0.7 1.8 1.3 38.5°C to <39.0°C 1.9 0.3 0.7 0.7 0.6 0.4 39.0°C to ≤40.0°C 0.5 0.2 0.1 0.1 0.3 0.5 >40.0°C 0.0 0.0 0.0 0.0 0.0 0.0 Vomiting§ Any¶ 3.7 1.9 2.2 1.4 1.7 2.2 Mild 2.8 1.7 1.7 1.1 1.4 1.7 Moderate 0.9 0.2 0.4 0.4 0.3 0.5 Severe 0.0 0.0 0.0 0.0 0.0 0.0 Diarrhea# Any¶ 10.6 12.1 7.6 9.1 7.7 7.6 Mild 9.1 10.9 6.2 7.6 6.4 6.2 Moderate 1.3 1.1 1.3 1.2 1.0 1.1 Severe 0.3 0.1 0.1 0.4 0.3 0.2 Headacheþ Any¶ 51.8 37.2 37.8 28.1 35.4 24.8 Mild 28.7 24.0 20.2 15.7 18.9 13.5 Moderate 21.0 12.5 16.0 10.9 15.2 10.4 Severe 2.2 0.7 1.7 1.5 1.3 1.0 Fatigue Any¶ 54.0 40.3 38.3 26.3 35.9 24.4 Mild 27.8 23.5 20.6 13.2 18.4 13.5 Moderate 23.2 15.2 15.8 11.7 15.2 10.0 Severe 3.0 1.7 1.9 1.4 2.3 0.9 Chillsþ Any¶ 25.3 17.2 16.0 10.3 13.1 8.3 Mild 16.2 13.3 10.6 8.1 8.7 6.5 Moderate 8.0 3.5 4.8 1.8 3.8 1.7 Severe 1.2 0.4 0.6 0.5 0.5 0.1 Muscle pain (other than muscle pain at the injection site)þ Any¶ 24.4 19.2 17.8 10.3 17.6 11.1 Mild 13.2 13.5 8.7 5.2 9.5 6.6 Moderate 10.1 5.4 7.9 4.5 7.2 4.3 Severe 1.2 0.3 1.2 0.6 0.8 0.2 Joint painþ Any¶ 21.9 13.6 16.7 9.1 16.0 8.9 Mild 11.8 8.3 8.4 5.0 8.9 5.5 Moderate 8.7 4.6 7.5 3.4 5.9 3.0 Severe 1.4 0.7 0.8 0.7 1.2 0.4 Use of antipyretic medication 20.7 10.4 13.6 8.9 12.7 6.8 *Study 1: National Clinical Trial (NCT) number NCT01830855. †Trumenba was administered at 0, 2, and 6 months. HAV was administered at 0 and 6 months and saline was administered at 2 months. ‡Study 1: Fever (≥38°C): N=2679, 2540, and 2414 for Trumenba at Dose 1, Dose 2, and Dose 3, respectively; N=890, 840, and 819 for HAV/saline at Dose 1, Dose 2, and Dose 3, respectively. §Mild (1–2 times in 24 hours); moderate (>2 times in 24 hours); severe (requires intravenous hydration). ¶"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination. #Mild (2–3 loose stools in 24 hours); moderate (4–5 loose stools in 24 hours); severe (6 or more loose stools in 24 hours). þMild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity). Table 4: Percentages of Subjects 18 to 25 Years of Age (Study 2*) Reporting Systemic Adverse Reactions and Use of Antipyretic Medications Within 7 Days After Each Vaccination Dose 1 Dose 2 Dose 3 Trumenba† Saline† Trumenba† Saline† Trumenba† Saline† Systemic Reaction N=2425 N=798 N=2076 N=706 N=1823 N=624 Fever (≥38°C)‡ ≥38.0°C 2.4 0.6 1.2 1.0 2.0 0.6 3 8.0°C to <38.5°C 1.6 0.4 0.7 0.6 1.4 0.5 38.5°C to <39.0°C 0.7 0.0 0.4 0.3 0.4 0.2 39.0°C to ≤40.0°C 0.0 0.3 0.1 0.1 0.1 0.0 >40.0°C 0.0 0.0 0.0 0.0 0.1 0.0 Vomiting§ Any¶ 2.6 2.1 2.1 1.6 2.0 1.4 Mild 2.2 2.1 1.6 1.3 1.8 1.1 Moderate 0.4 0.0 0.5 0.3 0.2 0.3 Severe 0.0 0.0 0.0 0.0 0.0 0.0 Diarrhea# Any¶ 12.7 11.8 8.6 8.1 7.5 6.9 Mild 10.2 9.8 6.4 4.7 6.1 5.3 Moderate 2.4 1.9 1.7 2.8 1.2 1.3 Severe 0.2 0.1 0.5 0.6 0.2 0.3 Headacheþ Any¶ 43.9 36.2 33.1 24.9 32.5 21.6 Mild 24.3 22.1 18.4 13.6 17.6 12.5 Moderate 17.9 13.5 13.3 10.1 13.3 8.3 Severe 1.6 0.6 1.4 1.3 1.6 0.8 Fatigue Any¶ 50.9 39.8 39.2 27.3 39.3 24.5 Mild 25.4 23.2 20.6 13.9 18.9 13.1 Moderate 22.1 15.8 16.4 11.5 18.8 9.6 Severe 3.4 0.9 2.2 2.0 1.6 1.8 Chillsþ Any¶ 18.1 9.8 12.4 8.5 12.6 6.4 Mild 12.0 8.1 8.1 6.9 7.7 4.3 Moderate 4.9 1.6 3.5 1.6 4.2 2.1 Severe 1.1 0.0 0.8 0.0 0.8 0.0 Muscle pain (other than muscle pain at the injection site)þ Any¶ 25.9 14.5 15.6 8.5 16.9 7.5 Mild 13.0 9.6 7.6 5.8 8.9 4.5 Moderate 11.3 4.4 7.1 2.3 6.8 2.9 Severe 1.6 0.5 0.8 0.4 1.2 0.2 Joint painþ Any¶ 19.6 10.9 15.1 6.5 12.6 5.3 Mild 10.3 6.9 8.1 3.7 6.6 2.9 Moderate 7.9 3.5 6.2 2.5 5.4 2.4 Severe 1.4 0.5 0.9 0.3 0.6 0.0 Use of antipyretic medication 13.4 8.9 12.3 7.6 12.8 6.6 *Study 2: National Clinical Trial (NCT) number NCT01352845. †Trumenba was administered at 0, 2, and 6 months. Saline was administered at 0, 2, and 6 months. ‡Study 2: Fever (≥38°C): N=2415, 2067, and 1814 for Trumenba at Dose 1, Dose 2, and Dose 3, respectively; N=796, 705, and 621 for saline at Dose 1, Dose 2, and Dose 3, respectively. §Mild (1–2 times in 24 hours); moderate (>2 times in 24 hours); severe (requires intravenous hydration). ¶"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination. #Mild (2–3 loose stools in 24 hours); moderate (4–5 loose stools in 24 hours); severe (6 or more loose stools in 24 hours). þMild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity). The frequencies of adverse reactions were highest after the first dose regardless of the schedule. After subsequent doses, the frequencies of adverse reactions were similar regardless of dose number and schedule. Serious Adverse Events Overall in clinical studies in which 15,227 subjects 10 through 25 years of age received at least one dose of Trumenba, serious adverse events (SAEs) were reported by 269 (1.8%) subjects. Among the 8 controlled studies (Trumenba N=13,275, control N=5,501), SAEs were reported by 213 (1.6%) subjects and by 106 (1.9%) subjects who received at least one dose of Trumenba or control, respectively. Non-Serious Adverse Events Overall in clinical studies in which 15,227 subjects 10 through 25 years of age received Trumenba, non-serious AEs within 30 days after any dose were reported in 4,463 (29.3%) subjects. Among the 8 controlled studies (Trumenba N=13,275, control N=5,501), AEs that occurred within 30 days of vaccination were reported in 4,056 (30.6%) subjects who received Trumenba and 1,539 (28.0%) subjects in the control group, for individuals who received at least one dose. AEs that occurred at a frequency of at least 2% and were more frequently observed in subjects who received Trumenba than subjects in the control group were injection site pain, fever, and headache. Postmarketing Experience The following is considered an adverse reaction for Trumenba and was reported in the postmarketing experience. Because this reaction was derived from spontaneous reports, the frequency could not be determined. Immune System Disorders: Hypersensitivity reactions, including anaphylactic reactions. DRUG INTERACTIONS In clinical trials, Trumenba was administered concomitantly with HPV4 in adolescents 11 to <18 years of age and with MCV4 and Tdap in adolescents 10 to <13 years of age [see Clinical Studies and ADVERSE REACTIONS ].

SIDE EFFECTS The most common solicited adverse reactions observed in clinical trials were pain at the injection site (≥83%), myalgia (≥48%), erythema (≥45%), fatigue (≥35%), headache (≥33%), induration (≥28%), nausea (≥18%), and arthralgia (≥13%). Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice. In four clinical trials, 3,058 individuals aged 10 through 25 years received at least one dose of BEXSERO, 1,436 participants received only BEXSERO, 2,089 received only placebo or a control vaccine, and 1,622 participants received a mixed regimen (placebo or control vaccine and BEXSERO). In a randomized controlled study1 conducted in U.S. and Poland, 120 participants aged 10 through 25 years received at least one dose of BEXSERO, including 112 participants who received 2 doses of BEXSERO 2 months apart; 97 participants received saline placebo followed by MENVEO [Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine]. Across groups, median age was 13 years, males comprised 49%, and 60% were white; 34% were Hispanic, 4% were black, <1% were Asian, and 2% were other. In a second randomized controlled study2 conducted in Chile, all subjects (N = 1,622) aged 11 through 17 years received at least one dose of BEXSERO. This study included a subset of 810 subjects who received 2 doses of BEXSERO 1 or 2 months apart. A control group of 128 subjects received at least 1 dose of placebo containing aluminum hydroxide. A subgroup of 128 subjects received 2 doses of BEXSERO 6 months apart. In this study, median age was 14 years, males comprised 44%, and 99% were Hispanic. In a third randomized controlled study3 conducted in the United Kingdom (U.K.), 974 university students aged 18 through 24 years received at least 1 dose of BEXSERO, including 932 subjects who received 2 doses of BEXSERO 1 month apart. Comparator groups received 1 dose of MENVEO followed by 1 dose of placebo containing aluminum hydroxide (n = 956) or 2 doses of IXIARO (Japanese Encephalitis Vaccine, Inactivated, Adsorbed) (n = 947). Across groups, median age was 20 years, males comprised 46%, and 88% were white, 5% were Asian, 2% were black, <1% were Hispanic, and 4% were other. In an uncontrolled study4 conducted in Canada and Australia, 342 participants aged 11 through 17 years received at least 1 dose of BEXSERO, including 338 participants who received 2 doses of BEXSERO 1 month apart. The median age was 13 years, males comprised 55%, and 80% were white, 10% were Asian, 4% were Native American/Alaskan, and 4% were other. Local and systemic reactogenicity data were solicited from all participants in the studies conducted in Chile, U.S./Poland, Canada/Australia, and in a subset of participants in the U.K. study. Reports of unsolicited adverse events occurring within the first 7 days after each vaccination were collected in all studies. In the U.S./Poland study, reports of unsolicited adverse events were collected up to one month after the second vaccination. Reports of all serious adverse events, medically attended adverse events, and adverse events leading to premature withdrawal were collected throughout the study period for the studies conducted in Chile (12 months), U.K. (12 months), U.S./Poland (8 months), and Canada/Australia (2 months). Solicited Adverse Reactions The reported rates of local and systemic reactions among participants aged 10 through 25 years following each dose of BEXSERO administered 2 months apart or control in the U.S./Polish study1 are presented in Table 1. Table 1: Percentage of U.S. and Polish Participants Aged 10 through 25 Years Reporting Solicited Local and Systemic Adverse Reactions within 7 Days after BEXSERO or Control, by Dose Solicited Reactiona Dose 1 Dose 2b BEXSERO n = 110-114 Placebo (Saline) n = 94-96 BEXSERO n = 107-109 MENVEO n = 90-92 Local Adverse Reactions Pain Any Mild Moderate Severe 90 27 83 43 27 20 18 26 44 5 37 9 20 2 29 8 Erythema Any 1-25 mm >25-50 mm >50-100 mm >100 mm 50 13 45 26 41 11 36 13 6 1 5 6 3 0 5 4 0 0 0 2 Induration Any 1-25 mm >25-50 mm >50-100 mm >100 mm 32 10 28 23 24 9 22 16 7 0 4 0 1 1 2 4 0 0 0 2 Systemic Adverse Reactions Fatigue Any 37 22 35 20 Mild 19 17 18 11 Moderate 14 5 10 7 Severe 4 0 6 2 Nausea Any 19 4 18 4 Mild 12 3 10 3 Moderate 4 1 5 1 Severe 4 0 4 0 Myalgia Any 49 26 48 25 Mild 21 20 16 14 Moderate 16 5 19 7 Severe 12 1 13 4 Arthralgia Any 13 4 16 4 Mild 9 3 8 2 Moderate 3 1 6 2 Severe 2 0 2 0 Headache Any 33 20 34 23 Mild 19 15 21 8 Moderate 9 4 6 12 Severe 4 1 6 3 Fever ≥38°C 1 1 5 0 38.0-38.9°C 1 1 4 0 39.0-39.9°C 0 0 1 0 ≥40°C 0 0 0 0 Clinicaltrials.gov Identifier NCT01272180. a Erythema and induration: Any (≥1 mm). Pain and systemic reactions: mild (transient with no limitation in normal daily activity); moderate (some limitation in normal daily activity); severe (unable to perform normal daily activity). b Administered 2 months after Dose 1. Solicited adverse reaction rates were similar among participants aged 11 through 24 years who received BEXSERO in the other 3 clinical studies,2,3,4 except for severe myalgia which was reported by 3% to 7% of subjects. Severe pain was reported by 8% of university students in the U.K.3 Non-serious Adverse Events In the 3 controlled studies1,2,3 (BEXSERO n = 2,221, control n = 2,204), non-serious unsolicited adverse events that occurred within 7 days of any dose were reported by 439 (20%) participants receiving BEXSERO and 197 (9%) control recipients. Unsolicited adverse events that were reported among at least 2% of participants and were more frequently reported in participants receiving BEXSERO than in control recipients were injection site pain, headache, and injection site induration unresolved within 7 days, and nasopharyngitis. Serious Adverse Events Overall, in clinical studies, among 3,058 participants aged 10 through 25 years who received at least 1 dose of BEXSERO, 66 (2.1%) participants reported serious adverse events at any time during the study. In the 3 controlled studies1,2,3 (BEXSERO n = 2,716, Control n = 2,078), serious adverse events within 30 days after any dose were reported in 23 (0.8%) participants receiving BEXSERO and 10 (0.5%) control recipients. Additional Pre-licensure Safety Experience In response to outbreaks of serogroup B meningococcal disease at 2 universities in the U.S., BEXSERO was administered as a 2-dose series at least 1 month apart. Information on serious adverse events was collected for a period of 30 days after each dose from 15,351 individuals aged 16 through 65 years who received at least 1 dose. Overall 50 individuals (0.3%) reported serious adverse events, including one event considered related to vaccination, a case of anaphylaxis within 30 minutes following vaccination. Postmarketing Experience Adverse event reports received for BEXSERO marketed outside the U.S. are listed below. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency, or to establish a causal relationship to vaccination. This list includes serious events or events which have suspected causal association to BEXSERO. General Disorders And Administration Site Conditions Injection site reactions (including extensive swelling of the vaccinated limb, blisters at or around the injection site, and injection site nodule which may persist for more than 1 month). Immune System Disorders Allergic reactions (including anaphylactic reactions), rash, eye swelling. Nervous System Disorders Syncope, vasovagal responses to injection. DRUG INTERACTIONS Sufficient data are not available to establish the safety and immunogenicity of concomitant administration of BEXSERO with recommended adolescent vaccines. REFERENCES 1. NCT01272180 (V102_03). 2. NCT00661713 (V72P10). 3. NCT01214850 (V72_29). 4. NCT01423084 (V72_41).

WARNINGS Included as part of the "PRECAUTIONS" Section PRECAUTIONS Management Of Allergic Reactions Epinephrine and other appropriate agents used to manage immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur following administration of Trumenba. Altered Immunocompetence Individuals with altered immunocompetence may have reduced immune responses to Trumenba. Limitation Of Vaccine Effectiveness As with any vaccine, vaccination with Trumenba may not protect all vaccine recipients against N. meningitidis serogroup B infections. Nonclinical Toxicology Trumenba has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility in males. Vaccination of female rabbits with Trumenba had no effect on fertility [see Pregnancy]. Use In Specific Populations Pregnancy Risk Summary All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. There are no adequate and well-controlled studies of Trumenba in pregnant women. Available human data on Trumenba administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy. Two developmental toxicity studies were performed in female rabbits administered Trumenba prior to mating and during gestation. The dose was 0.5 mL at each occasion (a single human dose is 0.5 mL). These studies revealed no evidence of harm to the fetus or offspring (until weaning) due to Trumenba [see Animal Data]. Animal Data Two developmental toxicity studies were performed in female rabbits. Animals were administered Trumenba by intramuscular injection 17 days and 4 days prior to mating and on gestation Days 10 and 24. The dose was 0.5 mL at each occasion (a single human dose is 0.5 mL). No adverse effects on pre-weaning development up to post-natal day 21 were observed. There were no fetal malformations or variations observed due to the vaccine. Lactation Risk Summary Available data are not sufficient to assess the effects of Trumenba on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Trumenba and any potential adverse effects on the breastfed child from Trumenba or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine. Pediatric Use Safety and effectiveness have not been established in children <10 years of age. In a clinical study, 90% of infants <12 months of age who were vaccinated with a reduced dosage formulation had fever. Geriatric Use Safety and effectiveness of Trumenba in adults older than 65 years of age have not been established.

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Preventing And Managing Allergic Reactions Appropriate observation and medical treatment should always be readily available in case of an anaphylactic event following the administration of the vaccine. Syncope Syncope (fainting) can occur in association with administration of BEXSERO. Ensure procedures are in place to avoid injury from falling associated with syncope. Latex The tip caps of the pre-filled syringes contain natural rubber latex which may cause allergic reactions in latex-sensitive individuals. Limitation Of Vaccine Effectiveness BEXSERO may not protect all vaccine recipients. BEXSERO may not provide protection against all meningococcal serogroup B strains [see CLINICAL PHARMACOLOGY]. Altered Immunocompetence Individuals with altered immunocompetence may have reduced immune responses to BEXSERO. Nonclinical Toxicology BEXSERO has not been evaluated for carcinogenic or mutagenic potential or impairment of male fertility. Use In Specific Populations Pregnancy Pregnancy Category B. Reproduction studies have been performed in rabbits at doses up to 15 times the human dose on a body-weight basis and have revealed no evidence of impaired fertility in females or harm to the fetus due to BEXSERO. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, BEXSERO should be used during pregnancy only if clearly needed. Pregnancy Registry For BEXSERO GlaxoSmithKline maintains a surveillance registry to collect data on pregnancy outcomes and newborn health status outcomes following exposure to BEXSERO during pregnancy. Women who receive BEXSERO during pregnancy should be encouraged to contact GlaxoSmithKline directly or their healthcare provider should contact GlaxoSmithKline by calling 1-877-413-4759. Nursing Mothers It is not known whether BEXSERO is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BEXSERO is administered to a nursing woman. Pediatric Use Safety and effectiveness of BEXSERO have not been established in children younger than 10 years. Geriatric Use Safety and effectiveness of BEXSERO have not been established in adults older than 65 years.