PENBRAYA

Jonny Nguyen2024 PharmD. CandidateUniversity of HoustonPreceptor: Dr. Rosemary OnuegbuPharmacy Care Service Manager Albertson/Randall/Tom Thumb (South Division)

PENBRAYA

Clinical Trials

PENBRAYA

Current Market

Diagnosis

Meningitis

Nguyen, N. (2022b, September 26). Neisseria meningitidis. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK549849/

NEISSERIA MENINGITIDIS

• Aerobic or facultative anaerobic, gram negative diplococcus
• Exclusively infects human
• 12 serotypes based on unique capsular polysaccharides with serotypes A, B, C, W, X, and Y, causing most meningococcal infections
• A and C = Africa
• B and C = Europe and the Americas
• Y = United States and Cancada
• W = Epidemic outbreak worldwide
• Signs and symptoms
• Meningococcal meningnitis
• Meningococcal septicemia (meningococcemia)

Centers for Disease Control and Prevention. (2022, February 7). Signs and symptoms of meningococcal disease. Centers for Disease Control and Prevention. https://www.cdc.gov/meningococcal/about/symptoms.html

• Nausea
• Vomiting
• Photophobia
• Altered mental state (confusion)

Additional symptoms:

Most common symptoms:

• FEVER

• HEADACHE
• STIFF NECK

Infection that cause swelling to the lining of the brain and spinal cord

Meningococcal meningitis

• Severe aches or pain in the muscles, joints, chest or abdomen (belly)
• Rapid breathing
• Diarrhea
• Later stages, a dark purple rash

Centers for Disease Control and Prevention. (2022, February 7). Signs and symptoms of meningococcal disease. Centers for Disease Control and Prevention. https://www.cdc.gov/meningococcal/about/symptoms.html

• Fevers and chills
• Fatigue (feeling tired)
• Vomiting
• Cold hands and feet

SYMPTOMS

Bloodstream infection, damaging the walls of the blood vessels, causing bleeding into the skin and organs

Meningococcal SEPTICEMIA

Centers for Disease Control and Prevention. (2022a, February 7). Meningococcal disease causes and how it spreads. Centers for Disease Control and Prevention. https://www.cdc.gov/meningococcal/about/causes-transmission.html

People do not usually catch the bacteria through casual contact or breathing air where someone who has the disease has been

Those at increased risk of illness include people in the same household, roommates, and anyone with direct contact with patient's oral secretion, such as kissing partner

Spread through respiratory and throat secretions (saliva or spit). For the bacteria to spread effectively. it requires close or lengthly contact

Those at Risk

Transmission

Epidemiology

About 1 in 10 people have N. meningitidis in the back of their nose and throat without being ill

TRANSMISSION

MicrobiologistsCollege studentsMilitary recruitsTravelers

PLACES AND SETTING

Centers for Disease Control and Prevention. (2023, May 1). Meningococcal disease risk factors. Centers for Disease Control and Prevention. https://www.cdc.gov/meningococcal/about/risk-factors.html

Complement inhibitors: Eculizumab (Soliris) Ravulizumab (Ultomiris)

Persistent complement component deficienciesFunctional and antomic aspleniaHIV infection

MEDICATIONS

MEDICAL CONDITION

AGE

Children younger than 1 yearTeens and younger adult (16-23 years old)Adults older than 65

RISK FACTORS

Mayo Foundation for Medical Education and Research. (2023, October 4). Meningitis. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/meningitis/diagnosis-treatment/drc-20350514#:~:text=A%20definitive%20diagnosis%20of%20meningitis,which%20bacterium%20caused%20the%20meningitis.

• Blood Culture
• Computed Tomography (CT) Scan

ADDITIONAL TESTING:

• CSF Glucose concentration <40mg/dL

• CSF to serum glucose ratio of ≤0.4

• Protein concentration >200 mg/dL

• White blood cell count above 1000/microL

FINDINGS

Initial approach to diagnosing suspected meningitis includes a lumbar puncture, collecting samples of blood or cerebrospinal fluid.

DIAGNOSIS

Centers for Disease Control and Prevention. (2021, July 15). Bacterial meningitis. Centers for Disease Control and Prevention. https://www.cdc.gov/meningitis/bacterial.html

Therapy duration can range from 7 to 21 days based on causative organisms

THE EMPIRIC PLAN

Streptococcus Pneumoniae

Group B Streptococcus

Neisseria Meningitidis

Haemophilus Influenza

3RD GEN CEPHALOSPORIN:- Ceftriaxone DOSE: 2g every 12 hours- CeftriAXone DOSE: 2g every 12 hours DOSE: 4TH GEN CEPHAlosporin- Cefepime DOSE: 2G every 8 hours

THE PATHOGEN

Hasbun, R. (n.d.). Initial therapy and prognosis of community-acquired bacterial meningitis in adults. UpToDate. https://www.uptodate.com/contents/initial-therapy-and-prognosis-of-community-acquired-bacterial-meningitis-in-adults

• Listeria coverage (gram-positive bacilli)

AMPICILLIN

• 3rd generation cephalosporin
• Equivalent to ceftriaxone
• Safe for neonates

• 4th-generation cephalosporin
• Increased activity against pseudomonas

• Gram-positive coverage (MRSA)
• Also used for resistant pneumococcus

• 3rd generation Cephalosporin
• Gram-negative coverage
• Effective against
• Streptococcus pneumoniae
• Neisseria meningitidis
• Potent CNS penetration

VANCOMYCIN

CEFTRIAXONE

CEFOTAXIME

CEFEPIME

Shikha S Vasudeva, M. (2023, November 1). Meningitis treatment & management. Approach Considerations, Treatment of Subacute Meningitis, Treatment of Bacterial Meningitis. https://emedicine.medscape.com/article/232915-treatment#d8

Adults older than 50 and immunocompromised

Adult -18- 49

More than 1 month

Neonates - Up to 1 month

*: Ceftazidime or Cefepime

TREATMENT

1. Ceftriaxone IV and
2. Vancomycin IV and
3. Ampicillin IV

1. Ceftriaxone IV and
2. Vancomycin IV

1. Ampicillin IV and
2. Ceftriaxone IV

1. Ampicillin IV and
2. Cefotaxime IV (or equivalent*) or Gentamicin IV and
3. Acyclovir IV

Hasbun, R. (n.d.). Initial therapy and prognosis of community-acquired bacterial meningitis in adults. UpToDate. https://www.uptodate.com/contents/initial-therapy-and-prognosis-of-community-acquired-bacterial-meningitis-in-adults

REDUCTION OF INTRACRANIALPRESSURE

Pressure exceeding 20mmHg are abnormal and should be treated. If left untreated, complication can worsen into cerebral herniation

To further reduce the risk of seizures from occurring, management of fluid and electrolytes balance

FLUID MANAGEMENT

SUPPORTIVE CARE

Meningococcal B

Meningococcal ACWY

Centers for Disease Control and Prevention. (2023b, December 6). Adult immunization schedule notes. Centers for Disease Control and Prevention. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult-schedule-notes.html#note-mening

minimum age: 2 years

minimum age: 2 months

• Routine vaccination
• 2 dose series at age 11-12 years; 16 years
• Special situations
• Anatomical or functional asplenia (including sickle cell disease), HIV infection, persistent complement component deficient, complement inhibitor (eculizumab, ravulizumab)
• First-year college students who live in residential housing (if not previously vaccinated at age 16 years or older or military recruit
• Travel in countries with hyper endemic or epidemic meningoccal disease, or microbiologists routinely exposed to Neisseria meningitidis

MenQuadfi

MenVeo

MenACWY

Centers for Disease Control and Prevention. (2023b, December 6). Adult immunization schedule notes. Centers for Disease Control and Prevention. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult-schedule-notes.html#note-mening

Delay MenB until after pregnancy unless at risk and vaccination benefit outweighs potential risk

ARE NOT INTERCHANGABLE

MenB

minimum age: 10 years

Trumenba

minimum age: 10 years

Bexsero

• Shared Clinical Decision-Making
• 2 dose series at age 16-23 (preferred 16-18)
• Special situations
• Anatomical or functional asplenia (including sickle cell disease), HIV infection, persistent complement component deficient, complement inhibitor (eculizumab, ravulizumab)
• Prolonged increased risk for exposure (microbiologists routinely working with Neisseria meningitidis)

ARE NOT INTERCHANGABLE

• Routine vaccination
• 2 doise series at age 11-12 years; 16 years
• Special situations
• Anatomical or functional asplenia (including sickle cell disease), HIV infection, persistent complement component deficient, complement inhibitor (eculizumab, ravulizumab)
• First-year college students who live in residential housing (if not previousbly vaccinated at age 16 years or older or military recruit
• Travel in countries with hyperendemic or epidemic meningoccal disease, or microbiologists routinely exposed to Neisseria meningitidis

MenQuadfi

MenVeo

MenACWY

• Shared Clinical Decision-Making
• 2 dose sereis at age 16-23 (preferred 16-18)
• Special situations
• Anatomical or functional asplenia (including sickle cell disease), HIV infection, persistent complement component deficient, complement inhibitor (eculizumab, ravulizumab)
• Prolonged increased risk for exposure (microbiologists routinely working with Neisseria meningitidis)

Bexsero

Trumenba

MenB

Center for Biologics Evaluation and Research. (n.d.). Penbraya. U.S. Food and Drug Administration. https://www.fda.gov/vaccines-blood-biologics/vaccines/penbraya

• Guillain-Barre Syndrome

• Tetanus Immunization

• Limitation of vaccine effectiveness

• Acute alert reaction
• Syncope
• Altered Immunocompotence

WARNING AND PRECAUTIONS

• Pain at injfection site
• Fatigue
• Hedache
• Muscle pain
• Injection site redness
• Injection site swelling
• Joint pain
• Chills

ADVERSE REACTIONS

• Administer 2 doses (approximately 0.5ml each), 6 months
• PEMBRAYA is a suspension for injection

DOSAGE AND ADMINISTRATION

• PENBRAYA is indicated for active

immunization to prevent invasive diseasecaused by Neisseria meningitidis serogroups A, B, C, W, and Y.

• PENBRAYA is approved for

use in individuals 10 through 25 years of age.

INDICATION & USE

PENBRAYA

Dosing recommendations: Penbraya (meningococcal A,B,C,W,Y vaccine) safety info. HCP site. (n.d.). https://penbraya.pfizerpro.com/dosing-recommendations

Center for Biologics Evaluation and Research. (n.d.). Penbraya. U.S. Food and Drug Administration. https://www.fda.gov/vaccines-blood-biologics/vaccines/penbraya

• Complemented-mediated antibody-dependeny killing of N. meningitidis.
• Vaccination induces production of bactericidal antibodies specific to the capsule polysaccharides of N. meningitidis serogroups A, C, W and Y and to fHbp subfamily A and B variants of N. meningitidis group B

MECHANISMS OF ACTION

Center for Biologics Evaluation and Research. (n.d.). Penbraya. U.S. Food and Drug Administration. https://www.fda.gov/vaccines-blood-biologics/vaccines/penbraya

Safety and effectiveness not established in <10 years of age. Fever has been reported in 90% of infant (<1 year) with reduce dose of Trumenba*

There are no data available to assess the effects on breastfed infant or on milk production/excretion

There are no clinical studies of PENBRAYA in pregnant individual.There is a pregnancy exposure registry currently

GERIATRIC

PEDIATRIC

LACTATION

PREGNANCY

Safety and effectiveness have not been established in individuals older than 65

*PENBRAYA contains the same MenB component and quantity as Trumenba

SPECIFIC POPULATION

Center for Biologics Evaluation and Research. (n.d.). Penbraya. U.S. Food and Drug Administration. https://www.fda.gov/vaccines-blood-biologics/vaccines/penbraya

WHATS IN THE BOX?

Center for Biologics Evaluation and Research. (n.d.). Penbraya. U.S. Food and Drug Administration. https://www.fda.gov/vaccines-blood-biologics/vaccines/penbraya

10

DETAILED INSTRUCTIONS

Reconstitution of Lyophilized MenACWY Component with MenB Component to form PENBRAYA• Inject the entire contents of the syringe containing the MenB Component into the vial.• Do not remove the empty syringe.• While holding the plunger rod down, gently swirl the vial in a circularmotion until the powder is completely dissolved (less than 1 minute).

Connection of syringe to vial adapter• Hold the syringe’s Luer lock adapter and connect it to the vial adapter by turning clockwise.• Stop turning when you feel resistance, overtightening the syringe may result in leaking during use.• Once the syringe is securely attached to the vial adapter, there will be a small space between the top of the vial adapter and the Luer lock adapter of the syringe.

Removal of syringe cap• For all syringe assembly steps, hold the syringe only by the Luer lock adapter located at the tip of the syringe. This will prevent the Luer lock adapter from detaching during use.• Remove the syringe cap by slowly turning the cap counter-clockwise while holding the Luer lock adapter.

Resuspension of the MenB Component• Shake the syringe vigorously to obtain a white homogenous suspension. Do not use if the contents cannot be resuspended.

Attachment of vial adapter• Hold the base of the vial on a flat surface.• Keep the vial adapter in the packaging and orient it vertically over the center of the vial so that the adapter spike aligns with the center of thevial’s rubber stopper.• Connect the vial adapter to the vial with a straight downward push. The vial adapter will lock into place.• Do not push vial adapter in at an angle as this may result in leaking during use.• Remove the vial adapter packaging.

Preparation of vial and vial adapter• Remove plastic flip-off cap from vial.• Cleanse the rubber stopper.• Without removing the vial adapter from its packaging, peel off the top cover.

Center for Biologics Evaluation and Research. (n.d.). Penbraya. U.S. Food and Drug Administration. https://www.fda.gov/vaccines-blood-biologics/vaccines/penbraya

After reconstitution, administer PENBRAYA immediately or store between 2°C and 30°C (36°F and 86°F) anduse within 4 hours. Discard reconstituted vaccine if not used within 4 hours.

FOR INTRAMUSCULAR USE ONLY

ADMINISTRATION

10

Visual inspection• PENBRAYA is a homogeneous white suspension. If the vaccine is not a homogenous suspension, shake to resuspend prior to administration.• Parenteral drug products should be inspected visually for particulate matterand discoloration prior to administration, whenever solution and container permit. Discard if either condition is present.

Attachment of needle• Attach a sterile needle suitable for intramuscular injection to the syringe containing PENBRAYA.

Disconnection of syringe• Hold the Luer lock adapter of the syringe and disconnect the syringe from the vial adapter by turning counter-clockwise.

Withdrawal of PENBRAYA• Invert the vial completely with the vial adapter and syringe still attached.• Slowly withdraw the entire contents into the syringe to ensure an approximately 0.5 mL dose of PENBRAYA for administration.• Do not pull the plunger rod out.

• Participants who received MenABCWY had comparable (noninferior) antibody responses against N meningitidis to participants who received Menveo.
• Participants who received MenABCWY had comparable (noninferior) antibody responses against N meningitidis toparticipants who received Trumenba.

Pfizer. (2023, April 18). MenABCWY Noninferiority Study in Healthy Participants ≥10 to &lt;26 Years of Age. Clinicaltrials.gov. https://clinicaltrials.gov/study/NCT04440163

MenABCWY Noninferiority Study in Healthy Participants ≥10 to <26 Years of Age

Pfizer. (2023, April 18). MenABCWY Noninferiority Study in Healthy Participants ≥10 to &lt;26 Years of Age. Clinicaltrials.gov. https://clinicaltrials.gov/study/NCT04440163

MenABCWY Noninferiority Study in Healthy Participants ≥10 to <26 Years of Age

Immunogenicity and safety of a pentavalent meningococcal ... - the lancet. (n.d.). https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00191-3/fulltext

Immunogenicity and safety of a pentavalent meningococcal ABCWY vaccine in adolescents and young adults

A trial to describe the safety and immunogenicity of Menabcwy when administered on 2 schedules - full text view. ClinicalTrials.gov. (n.d.). https://classic.clinicaltrials.gov/ct2/show/NCT04440176

Immunogenicity and safety of a pentavalent meningococcal ABCWY vaccine in adolescents and young adults

A trial to describe the safety and immunogenicity of Menabcwy when administered on 2 schedules - full text view. ClinicalTrials.gov. (n.d.). https://classic.clinicaltrials.gov/ct2/show/NCT04440176

Immunogenicity and safety of a pentavalent meningococcal ABCWY vaccine in adolescents and young adults

Estimated completed time: March 17, 2024

CURRENTLY ACTIVE

A trial to describe the safety and immunogenicity of Menabcwy when administered on 2 schedules - full text view. ClinicalTrials.gov. (n.d.). https://classic.clinicaltrials.gov/ct2/show/NCT04440176

A Trial to Describe the Safety and Immunogenicity of MenABCWY When Administered on 2 Schedules

7. Shikha S Vasudeva, M. (2023, November 1). Meningitis treatment & management. Approach Considerations, Treatment of Subacute Meningitis, Treatment of Bacterial Meningitis. https://emedicine.medscape.com/article/232915-treatment#d8 8. Hasbun, R. (n.d.). Initial therapy and prognosis of community-acquired bacterial meningitis in adults. UpToDate. https://www.uptodate.com/contents/initial-therapy-and-prognosis-of-community-acquired-bacterial-meningitis-in-adults 9. Centers for Disease Control and Prevention. (2023b, December 6). Adult immunization schedule notes. Centers for Disease Control and Prevention. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult-schedule-notes.html#note-mening 10. Dosing recommendations: Penbraya (meningococcal A,B,C,W,Y vaccine) safety info. HCP site. (n.d.). https://penbraya.pfizerpro.com/dosing-recommendations 11. Center for Biologics Evaluation and Research. (n.d.). Penbraya. U.S. Food and Drug Administration. https://www.fda.gov/vaccines-blood-biologics/vaccines/penbraya 12. Pfizer. (2023, April 18). MenABCWY Noninferiority Study in Healthy Participants ≥10 to &lt;26 Years of Age. Clinicaltrials.gov. https://clinicaltrials.gov/study/NCT04440163 13. Immunogenicity and safety of a pentavalent meningococcal ... - the lancet. (n.d.). https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00191-3/fulltext 14. A trial to describe the safety and immunogenicity of Menabcwy when administered on 2 schedules - full text view. ClinicalTrials.gov. (n.d.). https://classic.clinicaltrials.gov/ct2/show/NCT04440176

1. Nguyen, N. (2022b, September 26). Neisseria meningitidis. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK549849
2. Centers for Disease Control and Prevention. (2022, February 7). Signs and symptoms of meningococcal disease. Centers for Disease Control and Prevention. https://www.cdc.gov/meningococcal/about/symptoms.html
3. Centers for Disease Control and Prevention. (2022a, February 7). Meningococcal disease causes and how it spreads. Centers for Disease Control and Prevention. https://www.cdc.gov/meningococcal/about/causes-transmission.html
4. Centers for Disease Control and Prevention. (2023, May 1). Meningococcal disease risk factors. Centers for Disease Control and Prevention. https://www.cdc.gov/meningococcal/about/risk-factors.html
5. Mayo Foundation for Medical Education and Research. (2023, October 4). Meningitis. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/meningitis/diagnosis-treatment/drc-20350514#:~:text=A%20definitive%20diagnosis%20of%20meningitis,which%20bacterium%20caused%20the%20meningitis.
6. Centers for Disease Control and Prevention. (2021, July 15). Bacterial meningitis. Centers for Disease Control and Prevention. https://www.cdc.gov/meningitis/bacterial.html

REFERNCE