Gardasil 9

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Gardasil 9

Classes

Papillomavirus Vaccines

Administration

 
NOTE: According to U.S. federal laws, the health care provider must record in the patient's permanent record the manufacturer, lot number, administration date, and the name and address of the person administering the vaccine.
Inform the patient, parent, guardian, or responsible adult of the benefits and risks of the vaccine. Provide the Vaccine Information Statements from the manufacturer to the recipient or guardian before each immunization. The action is required by the National Childhood Vaccine Injury Act of 1986.
If a human papillomavirus (HPV) vaccine has been previously given, question the patient, parent, or guardian about any symptoms or signs of an adverse reaction.
Complete a Vaccine Adverse Event Reporting System (VAERS) report form if adverse events have been identified. The reporting of events is required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is 1—800—822—7967. Also, report an adverse event to the manufacturer. Depending on the adverse reaction, a subsequent dose may be contraindicated 
Health care professionals administering vaccines should take appropriate precautions to prevent allergic reactions in vaccine recipients. The health care professional should have immediate availability of epinephrine (1:1000) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Following vigorous shaking, the vaccine is a cloudy white suspension. If discoloration or visible particulate matter are present, discard the vaccine dose.
Do not mix with any other vaccine or product in the same syringe.

Intramuscular Administration

Use the vaccine as supplied; no dilution or reconstitution is necessary.
Both the prefilled syringe and single-dose vial require vigorous shaking prior to administration to ensure a homogenous white suspension; DO NOT administer if the vaccine cannot be re-suspended.
Single-dose vial: Using a sterile needle and syringe, withdraw the 0.5 mL dose and administer immediately.
Prefilled syringe: Attach a sterile needle by twisting in a clockwise direction. Administer entire dose contained within the syringe.
Prior to administration, clean skin over the injection site with a suitable cleansing agent.
The preferred injection site is the deltoid muscle of the upper arm or the higher anterolateral area of the thigh. Do NOT inject into the gluteal area or other areas where there may be a major nerve trunk.
Aspirate before injecting the dose to avoid injecting the vaccine into a blood vessel. If blood appears in the syringe, remove the needle and discard the vaccine. Use a new dose to try again.
Carefully observe patients for approximately 15 minutes after administration of the vaccine; syncope may occur.
Storage of unopened vials/syringes: Store refrigerated at 2—8 degrees C (36 to 46 degrees F); do not freeze. Administer as soon as possible after being removed from refrigeration. Total time (cumulative multiple excursions) outside of refrigeration [temperatures 8—25 degrees C (46 to 77 degrees F)] must not exceed 72 hours. Cumulative multiple excursions between 0—2 degrees C (32 to 36 degrees F) are also permitted if total time does not exceed 72 hours.

Adverse Reactions
Severe

myelitis / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
Guillain-Barre syndrome / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
muscle paralysis / Delayed / Incidence not known
seizures / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

Moderate

edema / Delayed / 0-49.0
erythema / Early / 0-42.3
hematoma / Early / 0.9-4.8
bleeding / Early / 1.0-1.0
acute disseminated encephalomyelitis / Delayed / Incidence not known
lymphadenopathy / Delayed / Incidence not known

Mild

injection site reaction / Rapid / 0-90.3
headache / Early / 7.3-19.6
fever / Early / 1.0-10.4
pruritus / Rapid / 1.0-7.7
nausea / Early / 1.0-4.4
fatigue / Early / 1.4-3.4
dizziness / Early / 0.7-3.0
abdominal pain / Early / 0.7-1.7
diarrhea / Early / 0.3-1.2
influenza / Delayed / 1.2-1.2
myalgia / Early / 0.7-1.0
malaise / Early / Incidence not known
syncope / Early / Incidence not known
urticaria / Rapid / Incidence not known
arthralgia / Delayed / Incidence not known
purpura / Delayed / Incidence not known
vomiting / Early / Incidence not known
chills / Rapid / Incidence not known
asthenia / Delayed / Incidence not known

Common Brand Names

Gardasil 9

Dea Class

Rx

Description

Recombinant vaccine
Used for immunization against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58
Only for prophylaxis; not for HPV treatment

Dosage And Indications
For human papillomavirus (HPV) infection prophylaxis. Intramuscular dosage Adults 18 to 45 years

0.5 mL IM for 3 doses. Administer the second dose 1 to 2 months after the first and the third dose 6 months (minimum 5 months) after the first. Repeat doses if administered too soon.[53026] [58618] For routine vaccination, ACIP recommends administering the first dose at age 11 or 12 years, or any time between 13 and 26 years if not previously vaccinated.[53026] The CDC recommends vaccination for adults through 26 years of age who have not already been vaccinated or who have not completed the 3-dose series. If any recipient reaches age 27 years before the 3-dose series is complete, the second and/or third doses may be administered after 26 years of age to complete the series. For adults 27 to 45 years of age, ACIP recommends shared clinical decision making regarding the decision to vaccinate patients who are not adequately vaccinated.[64986]

Adolescents 15 to 17 years of age

0.5 mL IM for 3 doses. Administer the second dose 1 to 2 months after the first and the third dose 6 months (minimum 5 months) after the first. Repeat doses if administered too soon.[53026] [58618] For routine vaccination, ACIP recommends administering the first dose at age 11 or 12 years, or any time between 13 and 26 years if not previously vaccinated.[53026]

Children and Adolescents 9 to 14 years of age

0.5 mL IM for 2 or 3 doses. For the 2 dose regimen, give the second dose 6 to 12 months (minimum 5 months) after the first. For the 3 dose regimen, give the second dose 1 to 2 months after the first and the third dose 6 months (minimum 5 months) after the first. Repeat doses if administered too soon.[53026] [58618] ACIP recommends routine vaccination with 2 doses if series is initiated before age 15. Administer at age 9 for children with any history of sexual abuse or assault; vaccination may be administered starting at age 9, even in the absence of a high risk condition. For routine vaccination, administer the first dose at age 11 or 12, or any time between age 13 and 26 if not previously vaccinated.[53026] Patients who are HIV positive or immunosuppressed for other reasons should receive 3 doses.[61840]

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Drug Interactions

Deucravacitinib: (Moderate) Patients receiving immunosuppressant medications may have a diminished vaccine response. When feasible, administer indicated vaccines at least two weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Elivaldogene Autotemcel: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to non-live vaccines. When feasible, administer indicated vaccines at least six weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Ocrelizumab: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
Ofatumumab: (Major) Administer all needed non-live vaccines according to immunization guidelines at least 2 weeks before initiation of ofatumumab. Ofatumumab may interfere with the effectiveness of inactivated vaccines due to its actions, which cause B-cell depletion.
Satralizumab: (Major) Administer all non-live vaccines according to immunization guidelines at least 2 weeks before initiation of satralizumab.
Siponimod: (Moderate) Administer all non-live vaccines at least 2 weeks before siponimod initiation, whenever possible. Vaccines may be less effective if given during siponimod treatment. Patients should be considered unimmunized if vaccinated within a 14-day period before starting immunosuppresive therapy or during immunosuppressive therapy, and should they be revaccinated at least 3 months after therapy is discontinued if immune competence is restored.
Ublituximab: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to non-live vaccines. When feasible, administer indicated vaccines at least two weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.

How Supplied

Gardasil 9 Intramuscular Inj Susp

Maximum Dosage
Adults

46 years and older: Safety and efficacy not established.
18 to 45 years: 0.5 mL IM.

Geriatric

Safety and efficacy not established.

Adolescents

13 to 17 years: 0.5 mL IM.

Children

9 years and older: 0.5 mL IM.
8 years and younger: Safety and efficacy not established.

Infants

Safety and efficacy not established.

Neonates

Safety and efficacy not established.

Mechanism Of Action

The human papillomavirus (HPV) only infects humans. An infection from this virus can cause squamous cell cervical cancer and cervical adenocarcinoma and their precursor lesions, which are cervical intraepithelial neoplasia (CIN) 1, 2, and 3 and adenocarcinoma in situ (AIS), respectively. HPV also causes anal cancer, vulvar cancer, vaginal cancer, and genital warts (condyloma acuminata), which are growths of the cervicovaginal, vulvar, and the external genitalia that rarely progress to cancer. The HPV 6, 11, 16, and 18 types cause 35% to 50% of all CIN 1, VIN 1, and VaIN 1 cases and 90% of genital wart cases. Further, the HPV 16 and 18 types cause approximately 70% of cervical cancer, AIS, CIN 3, VIN 2/3, and VaIN 2/3 cases and 50% of CIN 2 cases.[54770]
 
The exact mechanism by which the HPV 9-valent vaccine protects against type-specific HPV infection and sequela is unknown. Receipt of the HPV 9-valent vaccine is thought to result in a humoral immune response directed against HPV-L1 capsid proteins. The vaccine contains recombinant L1 protein, which is the major antigenic protein of the capsid of HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. These L1 proteins are produced in brewers yeast (i.e., Saccharomyces cerevisiae), purified, and adsorbed on an aluminum-containing adjuvant (amorphous aluminum hydroxyphosphate sulfate or AAHS).[58618]
 
The HPV 9-valent vaccine series elicited detectable antibody concentrations against those HPV types contained within the vaccine; however, the minimum anti-HPV titer needed to confer protective efficacy has not been determined. To evaluate efficacy against HPV types 31, 33, 45, 52, and 58, the vaccine was administered to 7,099 girls and women age 16 to 26 years. In this study primary efficacy was determined based on a composite clinical endpoint of cervical, vulvar, vaginal cancers and neoplasia. An analysis of the data starting 7 months post-dose found the vaccine to be effective in preventing HPV type 31-, 33-, 45-, 52-, and 58-related persistent infections and diseases, as observed through a reduction in the incidence of Pap test abnormalities, cervical and external genital biopsy, and definitive therapy. For HPV 6, 11, 16, and 18, immunogenicity was determined by comparing the vaccine induced geometric mean titers (GMTs) with those induced by the HPV quadrivalent vaccine (Gardasil quadrivalent). At 7 months post-dose, Gardasil 9 was found to be non-inferior to Gardasil quadrivalent, with 99.7% of girls and women (age 9 to 26 years) becoming seropositive for each of the 4 HPV types. Results from these two studies were subsequently used to infer vaccine efficacy in boys and girls age 9 to 15 years. This was accomplished through a non-inferiority comparison of the GMTs in boys and girls age 9 to 15 years with those observed in females age 16 to 26 years.[58618]
 
One study evaluated the immune response to Gardasil 9 in 921 girls and women (ages 12 to 26 years) who had recently received (within a 1 year period) 3 Gardasil quadrivalent injections. Data from this study found the anti-HPV 31, 33, 45, 52, and 58 GMTs induced by Gardasil 9 to be 25% to 63% of those that were observed in Gardasil 9 recipients who had not previously received Gardasil quadrivalent. The clinical relevance if these results are unknown. Efficacy of Gardasil 9 in preventing infections/diseases from HPV types 31, 33, 45, 52, and 58 in individuals previously vaccinated with Gardasil quadrivalent has not been evaluated.[58618]
 
The duration of immunity after vaccination with the Gardasil 9 series has not been established. Peak anti-HPV GMTs are observed at month 7; however, despite the decline after month 7, a similar proportion of vaccine recipients remain seropositive to each vaccine HPV type at month 24.[58618]

Pharmacokinetics

The human papillomavirus 9-valent vaccine is administered intramuscularly. Vaccination does not ensure immunity. Distrubution, metabolism, and excretion of the vaccine have not been defined.
 
Pooled data from clinical trials found >= 99.5% of vaccine recipients became seropositive for each of the 9 human papillomavirus (HPV) types contained within the vaccine by month 7. Peak anti-HPV geometric mean titers (GMTs) are observed at month 7; however despite the decline after month 7, a similar proportion of vaccine recipients remain seropositive to each vaccine HPV type at month 24. The duration of immunity has not been established.

Pregnancy And Lactation
Pregnancy

No adequate and well controlled studies have been conducted in pregnant women. It is unknown whether this vaccine can cause fetal harm or affect reproductive capacity. If a woman is found to be pregnant after initiating the vaccination series, delay the remainder of the 2- or 3-dose regimen until after completion of the pregnancy. In clinical trials, women were tested for pregnancy before each dose; if pregnancy was detected, completion of the regimen was deferred until pregnancy resolution. During a five year pregnancy registry there were 1,640 pregnancies with known outcomes. Rates of miscarriage (6.8%; 111/1,640) and major birth defects (2.4%; 37/1,527) were consistent with pregnancy outcomes observed in the general population. Two post-marketing studies included 1,740 pregnancies and found no suggestion of increased risk in the rate of assessed outcomes with vaccine administration during pregnancy. The manufacturer recommends administration during pregnancy only if clearly needed. Vaccinees and health care providers are encouraged to report any vaccine exposure during pregnancy by calling 1-800-986-8999.

Data are limited regarding use of the human papillomavirus 9-valent vaccine during breast-feeding and its excretion in human milk is unknown. The manufacturer recommends caution when administering to nursing women; however, according the Advisory Committee on Immunization Practices (ACIP), vaccines administered to a lactating woman do not affect the safety of breast-feeding. In addition, breast-feeding does not adversely affect immunization and is not a contraindication for any inactivated recombinant vaccine. In fact, limited data suggest breast-feeding may enhance the immune response to certain antigens. Also, no serious adverse events in a breast-fed infant have been associated with the use of an inactivated recombinant vaccine. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.