Gardasil 9 (Pf)

Drug overview for GARDASIL 9 (PF) (human papillomavirus vaccine, 9-valent/pf):

Generic name: human papillomavirus vaccine, 9-valent/PF
Drug class: Human Papillomavirus (HPV) Vaccines
Therapeutic class: Biologicals

Human papillomavirus (HPV) vaccine is an inactivated (recombinant) virus vaccine containing virus-like particles (VLPs) of the major capsid (L1) proteins of certain HPV types and is used to stimulate active immunity to the HPV serotypes represented in the vaccine. HPV vaccine is commercially available in the US as human papillomavirus 9-valent vaccine recombinant (9vHPV) containing VLPs of HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Other HPV vaccines (human papillomavirus quadrivalent vaccine (4vHPV), human papillomavirus bivalent vaccine (2vHPV)) are no longer available in the US.

No enhanced Uses information available for this drug.

DRUG IMAGES

GARDASIL 9 VIAL

The following indications for GARDASIL 9 (PF) (human papillomavirus vaccine, 9-valent/pf) have been approved by the FDA:

Indications:
Prevention of head and neck cancer due to human papillomavirus
Prevention of oropharyngeal cancer due to human papillomavirus
Vaccination to prevent anal cancer due to human papillomavirus
Vaccination to prevent cervical cancer due to human papillomavirus
Vaccination to prevent genital warts due to human papillomavirus
Vaccination to prevent vaginal cancer due to human papillomavirus
Vaccination to prevent vulvar cancer due to human papillomavirus

Professional Synonyms:
Active immunization against human papillomavirus anal cancer
Active immunization against human papillomavirus to prevent cervical cancer
Active immunization against human papillomavirus to prevent vulvar cancer
Active immunization to prevent cervical cancer due to human papillomavirus
Active immunization to prevent genital warts due to human papillomavirus
Active immunization to prevent human papillomavirus anal cancer
Active immunization to prevent human papillomavirus vaginal cancer
Active immunization to prevent human papillomavirus vulvar cancer
Human papillomavirus vaccination for vulvar cancer
Human papillomavirus vaccination to prevent genital warts
Vaccination for vaginal cancer due to human papillomavirus
Vaccination to prevent cervical cancer due to human papillomavirus infection
Vaccination to prevent human papillomavirus vulvar cancer
Verruca vulgaris virus vaccination to prevent vulvar cancer

The following dosing information is available for GARDASIL 9 (PF) (human papillomavirus vaccine, 9-valent/pf):

Dosing
Administration
Dosing Information
Generic

Efficacy of 9vHPV given in a 2-dose series in individuals 9 through 14 years of age is inferred from immunogenicity data. In a randomized, parallel-group study, immunogenicity of 9vHPV given in a 2-dose series (second dose given at 6 or 12 months after the first dose) to females and males 9 through 14 years of age was compared with immunogenicity of 9vHPV given in a 3-dose series (second and third doses given 2 and 6 months, respectively, after the first dose) in females 16 through 26 years of age. For all 9 HPV types contained in the vaccine, the immune response 1 month after the last dose in females and males 9 through 14 years of age who received 2 doses of the vaccine was noninferior to that in females 16 through 26 years of age who received 3 doses of the vaccine.

More than 98% of individuals enrolled in the study had an antibody response (seroconversion) to each of the 9 HPV types contained in the vaccine by 1 month after completion of the 2- or 3-dose vaccination series. In addition, geometric mean titers (GMTs) of antibodies to the 9 HPV vaccine types that were attained in individuals who received the 2-dose vaccination series were noninferior to GMTs attained in those who received the 3-dose vaccination series.

Efficacy of 9vHPV given in a 3-dose series in females 9 through 15 years of age is inferred from immunogenicity data. In one study, 600 females 9 through 15 years of age were randomized to receive 9vHPV or 4vHPV (no longer available in the US). Results from this study indicate that 99.7%

of females 9 through 15 years of age who received a 3-dose regimen of 9vHPV became seropositive for antibodies to HPV types 6, 11, 16, and 18 by 1 month after dose 3 and GMTs of these antibodies attained in this age group were noninferior to those attained in females 9 through 15 years of age who received 4vHPV. In another immunogenicity study, females 9 through 15 years of age who received a 3-dose regimen of 9vHPV became seropositive for antibodies to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 by 1 month after dose 3 and GMTs of these antibodies attained in this age group were noninferior to those attained in females 16-26 years of age for which positive efficacy data exist (i.e., immunogenicity bridging). Results from this study indicate that GMTs of these antibodies 1 month after the third vaccine dose range from approximately 708-6934 mMU/mL in those 9 through 15 years of age, and results of immunogenicity studies in females 16-26 years of age indicate that GMTs of these antibodies range from approximately 272-3523 mMU/mL in this older group.

Efficacy of 9vHPV given in a 3-dose series in males 9 through 15 years of age is inferred based on evidence that more than 99% of males 9 through 15 years of age became seropositive for antibodies to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 by 1 month after the third vaccine dose and GMTs of these antibodies attained in this age group are noninferior to those attained in females 16 through 26 years of age for which positive efficacy data exist (i.e., immunogenicity bridging). Immunogenicity studies in males 9 through 15 years of age indicate that GMTs of these antibodies 1 month after the third vaccine dose range from 912-8683 mMU/mL in this age group.

Safety and efficacy of 9vHPV for the prevention of disease caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 have been evaluated in a double-blind, randomized, active comparator-controlled study in 14,204 women 16 through 26 years of age at the time of enrollment (mean: 19.4-24.4 years of age) in the US and other countries. Study participants were randomized to receive a 3-dose series of either 9vHPV or 4vHPV (no longer available in the US). The second and third vaccine doses were given 2 and 6 months, respectively, after the first dose and the median duration of follow-up was 3.3

years. The prophylactic efficacy analysis was based on clinical endpoints including CIN (any grade including 2/3), AIS, VIN (any grade), VaIN (any grade), cervical carcinoma, vulvar cancer, or vaginal cancer related to HPV types 31, 33, 45, 52, and 58. The per-protocol efficacy (PPE) population consisted of those who completed the 3-dose vaccine series within 1 year of enrollment, did not have major study protocol deviations, and were naive (seronegative and cervicovaginal specimens PCR negative) to the relevant vaccine HPV types when tested prior to the first vaccine dose and at 1 month after the third dose.

Results from the efficacy analysis indicate that 9vHPV was effective in preventing HPV disease caused by HPV types 31, 33, 45, 52, and 58 in individuals who were seronegative and PCR negative to these HPV types at baseline. In the PPE population, the vaccine was 96.7% effective in preventing CIN 2/3, AIS, VIN 2/3, VaIN 2/3, cervical cancer, vulvar cancer, or vaginal cancer related to HPV types 31, 33, 45, 52, and 58 and 98.6%

effective in preventing CIN 1 related to HPV types 31, 33, 45, 52, and 58.

Efficacy of 9vHPV for the prevention of disease caused by HPV types 6, 11, 16, and 18, including genital warts, CIN (any grade including 2/3), AIS, VIN (any grade), and VaIN (any grade), is inferred from immunogenicity data. Efficacy of the vaccine is based on evidence that 99.7% of females 16 through 26 years of age who received 9vHPV become seropositive for antibodies to HPV types 6, 11, 16, and 18 by 1 month after dose 3 and the GMTs of these antibodies attained in this age group were noninferior to those attained in females 16 through 26 years of age who received 4vHPV and for which positive efficacy data exist (i.e., immunogenicity bridging).

Data indicate that 9vHPV was effective only against the HPV types represented in the vaccine and only when given prior to infection by these types. Women already infected with one or more vaccine-related HPV types prior to vaccination were protected from disease caused by the remaining vaccine HPV types to which they were naive (PCR negative and seronegative).

Efficacy of 9vHPV for the prevention of anal HPV infection, AIN, and anal cancer was not studied in women, but efficacy of the vaccine against anal disease caused by HPV types 6, 11, 16, and 18 is inferred from data in males.

Efficacy of 9vHPV for the prevention of disease caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in males 16 through 26 years of age is inferred based on evidence from an open-label study that included males and females 16 through 26 years of age who received 9vHPV in a 3-dose series (second and third dose given 2 and 6 months, respectively, after first dose). Results from this study demonstrated that the immune response observed in males 16 through 26 years of age after the third vaccine dose was noninferior to that observed in females 16 through 26 years of age for which positive efficacy data exist (i.e., immunogenicity bridging). More than 99% of males and females 16 through 26 years of age became seropositive for antibodies to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

Efficacy and safety of 4vHPV in females 27 through 45 years of age are relevant to use of 9vHPV in females in this age group. Efficacy of 4vHPV for the prevention of HPV disease in females 27 through 45 years of age has been evaluated in a clinical trial that included a base study and a long-term study extension. A total of 3253 females in this age group were randomized 1:1 to receive 4vHPV or the preformed aluminum-containing adjuvant used in the vaccine (amorphous aluminum hydroxyphosphate sulfate (AAHS)) given in a 3-dose series.

Efficacy was based on a combined end point of persistent HPV type 6, 11, 16, or 18 infection, genital warts, vulvar and vaginal dysplastic lesions of any grade, CIN of any grade, AIS, and cervical cancer. The PPE population consisted of those who completed the 3-dose series of 4vHPV within 1 year of enrollment, did not have major deviations from the study protocol, and were naive (PCR negative and seronegative) to HPV types 6, 11, 16, and 18 prior to the first vaccine dose through month 7 (1 month after the third dose).

In the base study (median follow-up duration of 3.5 years after the third vaccine dose), efficacy of 4vHPV against the combined incidence of HPV 6-, 11-, 16-, and 18-related persistent infection, genital warts, VIN, VaIN, vulvar cancer, vaginal cancer, cervical dysplasia (any grade CIN), AIS, and cervical cancer was 87.7% in the PPE population. The efficacy estimate for the combined end point was driven principally by prevention of persistent infection.

Efficacy of 4vHPV against the combined incidence of HPV 6-, 11-, 16-, and 18-related genital warts or cervical dysplasia was 95% in the PPE population. Data from the base study did not demonstrate statistically significant efficacy of 4vHPV for the prevention of CIN 2/3, AIS, or cervical cancer related to HPV types 16 and 18; however, CIN 2/3 was observed in 1 individual in the 4vHPV group (tested positive by PCR for HPV 16 and HPV 51) compared with 5 cases in the placebo group.

In the long-term extension of this study (median follow-up duration of 8.9 years after the third vaccine dose), 600 study participants who had been randomized to receive 4vHPV in the base study were monitored for HPV 6-, 11-, 16-, and 18-related genital warts or cervical dysplasia. No cases of HPV 6-, 11-, 16-, or 18-related CIN (any grade) or genital warts were observed in the PPE population during the long-term extension phase.

Efficacy and safety of 4vHPV in males 27 through 45 years of age are relevant to use of 9vHPV in males in this age group. Efficacy of 4vHPV for the prevention of HPV disease in males 27 through 45 years of age is inferred from efficacy data from the clinical trial in females 27 through 45 years of age and is supported by immunogenicity data from a clinical trial that included 150 males 27 through 45 years of age who received a 3-dose regimen of 4vHPV (second and third doses given 2 and 6 months, respectively, after the first dose). In addition, results of a cross-study analysis of per-protocol immunogenicity populations that compared HPV 6, 11, 16, and 18 GMTs at month 7 in males 27 through 45 years of age (study A) to GMTs in males 16 through 26 years of age in whom efficacy of 4vHPV had been established (study B) indicated that GMT ratios (study A/study B) for antibodies to HPV 6, 11, 16, and 18 were 0.82,

0.79, 0.91, and 0.74,

respectively.

The dosage schedule (i.e., number of doses) for 9vHPV is based on age at the time the first dose is administered and the immunocompetence of the vaccinee. The manufacturer recommends a 2- or 3-dose series if HPV vaccination is initiated at 9 through 14 years of age and a 3-dose series if HPV vaccination is initiated at 15 through 45 years of age. The US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP), American Academy of Pediatrics (AAP), and other experts recommend a 2-dose series if initiated at 9 through 14 years of age and a 3-dose series if initiated at 15 through 45 years of age; these experts recommend that a 3-dose series of HPV vaccine be used in all immunocompromised individuals 9 years of age or older.

If interruptions occur resulting in an interval between doses longer than recommended, there is no need to start the vaccination series over.

An accelerated schedule for the HPV vaccination series (i.e., using intervals between doses shorter than recommended) should not be used.

Human papillomavirus 9-valent vaccine recombinant (9vHPV) is administered by IM injection. The vaccine should not be administered IV, subcutaneously, or intradermally. Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination; such reactions may be accompanied by transient neurologic signs (e.g., tonic-clonic limb movements).

Syncope occurs most frequently in adolescents and young adults. Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope. Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination.

If syncope occurs, the patient should be observed until symptoms resolve. 9vHPV may be given simultaneously with other age-appropriate vaccines. (See Drug Interactions: Vaccines.) When multiple vaccines are administered during a single health-care visit, each parenteral vaccine should be given using separate syringes and different injection sites. Injection sites should be separated by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.

No dosing information available.

No generic dosing information available.

The following drug interaction information is available for GARDASIL 9 (PF) (human papillomavirus vaccine, 9-valent/pf):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 1 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Non-Live or Non-Replicating Vaccines/Teplizumab SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Teplizumab may cause lymphopenia and alter the immune system's response to vaccines.(1) CLINICAL EFFECTS: Administration of a non-live vaccine within the 2 weeks prior to, during, or for 6 weeks following teplizumab therapy may result in decreased effectiveness of the vaccine.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Ideally, administer vaccines prior to initiating teplizumab therapy. The manufacturer of teplizumab states that non-live vaccines (e.g., inactivated or mRNA vaccines) are not recommended within the 2 weeks prior to, during, or for 6 weeks after stopping teplizumab therapy.(1) The immune response to non-live vaccines should be monitored in patients who receive teplizumab within these time frames. The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) states that non-live vaccines should be used with caution in patients who are severely immunosuppressed. Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(2) For COVID-19 vaccines, the CDC advises planning for vaccination at least 2 weeks before starting or resuming immunosuppressive therapy. Patients should be offered and given a COVID-19 vaccine even if the use and timing of immunosuppressive agents cannot be adjusted. The CDC states that an age-appropriate mRNA COVID-19 vaccine is preferred over the Janssen COVID-19 vaccine for the primary and booster doses for immunocompromised patients. All immunocompromised patients over 5 years of age should receive at least 1 booster dose if eligible. See the CDC's Interim Clinical Considerations for Use of COVID-19 Vaccines for age- and product-specific recommendations.(3) DISCUSSION: Vaccinations may be less effective if administered within 2 weeks before, during, and for 6 weeks following teplizumab therapy.(1)	TZIELD

Drug Interaction

Drug Names

Non-Live or Non-Replicating Vaccines/Teplizumab

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Teplizumab may cause lymphopenia and alter the immune system's response to vaccines.(1)

CLINICAL EFFECTS: Administration of a non-live vaccine within the 2 weeks prior to, during, or for 6 weeks following teplizumab therapy may result in decreased effectiveness of the vaccine.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Ideally, administer vaccines prior to initiating teplizumab therapy. The manufacturer of teplizumab states that non-live vaccines (e.g., inactivated or mRNA vaccines) are not recommended within the 2 weeks prior to, during, or for 6 weeks after stopping teplizumab therapy.(1) The immune response to non-live vaccines should be monitored in patients who receive teplizumab within these time frames.

The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) states that non-live vaccines should be used with caution in patients who are severely immunosuppressed. Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(2) For COVID-19 vaccines, the CDC advises planning for vaccination at least 2 weeks before starting or resuming immunosuppressive therapy.

Patients should be offered and given a COVID-19 vaccine even if the use and timing of immunosuppressive agents cannot be adjusted. The CDC states that an age-appropriate mRNA COVID-19 vaccine is preferred over the Janssen COVID-19 vaccine for the primary and booster doses for immunocompromised patients. All immunocompromised patients over 5 years of age should receive at least 1 booster dose if eligible. See the CDC's Interim Clinical Considerations for Use of COVID-19 Vaccines for age- and product-specific recommendations.(3)

DISCUSSION: Vaccinations may be less effective if administered within 2 weeks before, during, and for 6 weeks following teplizumab therapy.(1)

TZIELD

There are 8 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Non-Live or Non-Replicating Vaccines/Fingolimod SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Fingolimod is an immunosuppressant and may alter the immune system's response to vaccines.(1) CLINICAL EFFECTS: Administration of a vaccine during and for 2 months following fingolimod therapy may result in decreased effectiveness of the vaccine.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Ideally, administer vaccines prior to initiating fingolimod therapy. The immune response to non-live vaccines should be monitored in patients receiving fingolimod or who have received fingolimod in the previous two months. Vaccinations given during and for 2 months after stopping fingolimod therapy may need to be repeated.(1,2) The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) states that non-live vaccines should be used with caution in patients who are severely immunosuppressed. Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(3) DISCUSSION: Vaccinations may be less effective during and for 2 months following fingolimod therapy(1) however they are considered safe to administer.(2)	FINGOLIMOD, GILENYA, TASCENSO ODT
Non-Live or Non-Replicating Vaccines/Siponimod SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Siponimod is an immunosuppressant and may alter the immune system's response to vaccines.(2) CLINICAL EFFECTS: Administration of a vaccine during and for up to 1 month after discontinuation of siponimod therapy may result in decreased effectiveness of the vaccine. Siponimod treatment should be paused 1 week prior and for 4 weeks after vaccination.(2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Ideally, administer vaccines prior to initiating siponimod therapy. The immune response to non-live vaccines should be monitored in patients receiving siponimod or who have received siponimod in the previous week. Vaccinations given during and for up to 1 month after discontinuation of siponimod therapy may need to be repeated.(2) The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) states that non-live vaccines should be used with caution in patients who are severely immunosuppressed. Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(3) DISCUSSION: Vaccinations may be less effective if administered during and for up to 1 month after siponimod treatment(2) however they are considered safe to administer.(1)	MAYZENT
Non-Live or Non-Replicating Vaccines/Satralizumab SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Satralizumab is an immunosuppressant and may alter the immune system's response to vaccines.(1) CLINICAL EFFECTS: Administration of a vaccine during satralizumab therapy may result in decreased effectiveness of the vaccine. If possible, non-live vaccines should be administered at least two weeks prior to initiation of satralizumab.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Ideally, administer vaccines two weeks prior to initiating satralizumab therapy. The immune response to non-live vaccines should be monitored in patients receiving satralizumab. Vaccinations given during satralizumab therapy may need to be repeated.(1) Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(2) DISCUSSION: Vaccinations may be less effective if administered during satralizumab treatment.(1)	ENSPRYNG
Non-Live or Non-Replicating Vaccines/Ublituximab SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ublituximab is an immunosuppressant and may alter the immune system's response to vaccines.(1) CLINICAL EFFECTS: Administration of a non-live vaccine within 2 weeks before or during ublituximab therapy may result in decreased effectiveness of the vaccine. If possible, non-live vaccines should be administered at least two weeks prior to initiating ublituximab therapy.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Ideally, administer non-live vaccines at least two weeks prior to initiating ublituximab therapy. The immune response to non-live vaccines should be monitored in patients receiving ublituximab. Vaccinations given during ublituximab therapy may need to be repeated.(1) Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(2) DISCUSSION: Vaccinations may be less effective if administered within 2 weeks before or during ublituximab treatment.(1)	BRIUMVI
Systemic Corticosteroids; Corticotropin/Non-Live or Non-Replicating Vaccines SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Corticosteroids and corticotropin suppress the immune system and may alter the immune system's response to vaccines.(1) CLINICAL EFFECTS: Vaccines administered during or within 2 weeks prior to therapy with corticosteroids or corticotropin may result in decreased effectiveness of the vaccine.(1) PREDISPOSING FACTORS: Patients receiving immunosuppressive doses of corticosteroids or corticotropin for equal to or greater than 14 consecutive days.(1) PATIENT MANAGEMENT: The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) states that non-live vaccines should be used with caution in patients who are severely immunosuppressed, including those who are receiving or have received high-dose, systemic steroids for greater than or equal to 14 consecutive days. When initiating immunosuppressives doses of corticosteroids, wait 2 weeks after a non-live vaccines is administered. However, if patients require therapy for chronic inflammatory conditions, do not delay therapy due to past vaccines.(1) The immune response to non-live vaccines should be monitored in patients receiving corticosteroids. Vaccinations given during corticosteroid therapy may need to be repeated.(1) Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(1) DISCUSSION: Vaccinations given during and within 2 weeks prior to corticosteroid therapy may be less effective. However they are considered safe to administer.(1) Many clinicians consider a dose equivalent to either 2 mg/kg of body weight or a total of 20 mg/day of prednisone as sufficiently immunosuppressive to raise safety concerns about live-virus vaccines.(1) Immunization procedures may be undertaken in patients receiving corticosteroids when the therapy is short term (less than 2 weeks); low to moderate dose; long-term, alternate-day treatment with short-acting preparations; maintenance physiologic doses (replacement therapy); or administered topically (skin or eyes), by aerosol, or by intra-articular, bursal, or tendon injection.(1)	ACTHAR, ACTHAR SELFJECT, ADRENOCORTICOTROPHIC HORMONE, ALDOSTERONE, ALKINDI SPRINKLE, ANUCORT-HC, ANUSOL-HC, BECLOMETHASONE DIPROPIONATE, BETA 1, BETALOAN SUIK, BETAMETHASONE ACETATE MICRO, BETAMETHASONE ACETATE-SOD PHOS, BETAMETHASONE DIPROPIONATE, BETAMETHASONE SOD PHOS-ACETATE, BETAMETHASONE SOD PHOS-WATER, BETAMETHASONE SODIUM PHOSPHATE, BETAMETHASONE VALERATE, BSP 0820, BUDESONIDE, BUDESONIDE DR, BUDESONIDE EC, BUDESONIDE ER, BUDESONIDE MICRONIZED, BUPIVACAINE-DEXAMETH-EPINEPHRN, CELESTONE, CLOBETASOL PROPIONATE MICRO, CORTEF, CORTENEMA, CORTICOTROPHIN, CORTIFOAM, CORTISONE ACETATE, CORTROPHIN, DEFLAZACORT, DEPO-MEDROL, DESONIDE MICRONIZED, DESOXIMETASONE, DESOXYCORTICOSTERONE ACETATE, DEXABLISS, DEXAMETHASONE, DEXAMETHASONE ACETATE, DEXAMETHASONE ACETATE MICRO, DEXAMETHASONE INTENSOL, DEXAMETHASONE ISONICOTINATE, DEXAMETHASONE MICRONIZED, DEXAMETHASONE SOD PHOS-WATER, DEXAMETHASONE SODIUM PHOSPHATE, DEXAMETHASONE-0.9% NACL, DMT SUIK, DOUBLEDEX, EMFLAZA, EOHILIA, FLUDROCORTISONE ACETATE, FLUNISOLIDE, FLUOCINOLONE ACETONIDE, FLUOCINOLONE ACETONIDE MICRO, FLUOCINONIDE MICRONIZED, FLUTICASONE PROPIONATE, FLUTICASONE PROPIONATE MICRO, HEMADY, HEMMOREX-HC, HEXATRIONE, HYDROCORTISONE, HYDROCORTISONE ACETATE, HYDROCORTISONE SOD SUCCINATE, KENALOG-10, KENALOG-40, KENALOG-80, LIDOCIDEX-I, MAS CARE-PAK, MEDROL, MEDROLOAN II SUIK, MEDROLOAN SUIK, METHYLPREDNISOLONE, METHYLPREDNISOLONE AC MICRO, METHYLPREDNISOLONE ACETATE, METHYLPREDNISOLONE SODIUM SUCC, MILLIPRED, MILLIPRED DP, MOMETASONE FUROATE, ORAPRED ODT, ORTIKOS, PEDIAPRED, PREDNISOLONE, PREDNISOLONE ACETATE MICRONIZE, PREDNISOLONE MICRONIZED, PREDNISOLONE SODIUM PHOS ODT, PREDNISOLONE SODIUM PHOSPHATE, PREDNISONE, PREDNISONE INTENSOL, PREDNISONE MICRONIZED, PRO-C-DURE 5, PRO-C-DURE 6, PROCTOCORT, RAYOS, SOLU-CORTEF, SOLU-MEDROL, TAPERDEX, TARPEYO, TRIAMCINOLONE, TRIAMCINOLONE ACETONIDE, TRIAMCINOLONE DIACETATE, TRIAMCINOLONE DIACETATE MICRO, TRILOAN II SUIK, TRILOAN SUIK, UCERIS, VERIPRED 20, ZCORT
Non-Live or Non-Replicating Vaccines/Etrasimod SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Etrasimod is an immunosuppressant and may alter the immune system's response to vaccines.(1) CLINICAL EFFECTS: Administration of a vaccine during and for up to 5 weeks after discontinuation of etrasimod therapy may result in decreased effectiveness of the vaccine. Etrasimod treatment should be paused 5 weeks prior and for 4 weeks after vaccination.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Ideally, administer vaccines prior to initiating etrasimod therapy. The immune response to non-live vaccines should be monitored in patients receiving etrasimod or who have received etrasimod in the previous 5 weeks. Vaccinations given during and for up to 5 weeks after discontinuation of etrasimod therapy may need to be repeated.(1) The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) states that non-live vaccines should be used with caution in patients who are severely immunosuppressed. Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(2) DISCUSSION: Vaccinations may be less effective if administered during and for up to 5 weeks after etrasimod treatment.(1) However they are considered safe to administer.	VELSIPITY
Non-Live or Non-Replicating Vaccines/Ozanimod SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ozanimod is an immunosuppressant and may alter the immune system's response to vaccines.(1) CLINICAL EFFECTS: Administration of a vaccine during and for up to 3 months after discontinuation of ozanimod therapy may result in decreased effectiveness of the vaccine. Ozanimod treatment should be paused 3 months prior and for 1 month after vaccination.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Ideally, administer vaccines prior to initiating ozanimod therapy. The immune response to non-live vaccines should be monitored in patients receiving ozanimod or who have received ozanimod in the previous 3 months. Vaccinations given during and for up to 3 months after discontinuation of ozanimod therapy may need to be repeated.(1) The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) states that non-live vaccines should be used with caution in patients who are severely immunosuppressed. Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(2) DISCUSSION: Vaccinations may be less effective if administered during and for up to 3 months after ozanimod treatment.(1) However they are considered safe to administer.	ZEPOSIA
Non-Live or Non-Replicating Vaccines/Ponesimod SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ponesimod is an immunosuppressant and may alter the immune system's response to vaccines.(1) CLINICAL EFFECTS: Administration of a vaccine during and for up to 2 weeks after discontinuation of ponesimod therapy may result in decreased effectiveness of the vaccine. Ponesimod treatment should be paused 1-2 weeks prior and for 4 weeks after vaccination.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Ideally, administer vaccines prior to initiating ponesimod therapy. The immune response to non-live vaccines should be monitored in patients receiving ponesimod or who have received ponesimod in the previous 2 weeks. Vaccinations given during and for up to 2 weeks after discontinuation of ponesimod therapy may need to be repeated.(1) The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) states that non-live vaccines should be used with caution in patients who are severely immunosuppressed. Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(2) DISCUSSION: Vaccinations may be less effective if administered during and for up to 2 weeks after ponesimod treatment.(1) However they are considered safe to administer.	PONVORY

Moderate List
No disease contraindications

The following adverse reaction information is available for GARDASIL 9 (PF) (human papillomavirus vaccine, 9-valent/pf):

Overview
Severe
Less Severe

Adverse reaction overview.

In females 9 through 26 years of age, the most common adverse reactions to 9vHPV are injection site reactions, including pain (89-90%), swelling (40-48%), erythema (34%), pruritus (4-6%), and hematoma (1-4%), and systemic reactions, including headache (11-15%), fever (5-7%), nausea (3-4%), dizziness (1-3%), fatigue (2%), and oropharyngeal pain (1-3%). In males 9 through 26 years of age, the most common adverse reactions to 9vHPV are injection site reactions, including pain (63-72%), swelling (20-27%), erythema (21-25%), and hematoma (1%), and systemic reactions, including headache (7-9%), fever (2-9%), nausea (1%), dizziness (1%), and fatigue (1%).

There are 16 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Anaphylaxis Appendicitis Asthma Bronchospastic pulmonary disease Cellulitis Deep venous thrombosis Gastroenteritis Guillain-barre syndrome Idiopathic thrombocytopenic purpura Inflammatory disease of female pelvic organs Myelitis Pancreatitis Pulmonary thromboembolism Seizure disorder Syncope Thromboembolic disorder

There are 31 less severe adverse reactions.

More Frequent	Less Frequent
Headache disorder Injection site erythema Injection site inflammation Injection site sequelae Pain	Bruising Dizziness Fatigue Fever Hematoma Induration of skin Nausea Pain in oropharynx Pruritus of skin Skin swelling Upper abdominal pain

Rare/Very Rare
Arthralgia Arthritis Autoimmune hemolytic anemia Chills Cough Diarrhea General weakness Insomnia Lymphadenopathy Malaise Myalgia Nasal congestion Toothache Urticaria Vomiting

The following precautions are available for GARDASIL 9 (PF) (human papillomavirus vaccine, 9-valent/pf):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of 9vHPV have not been established in females or males younger than 9 years of age.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

There are no adequate and well-controlled studies using 9vHPV in pregnant women. The manufacturer states that human data to date have not demonstrated any vaccine-associated risk of major birth defects and miscarriages when 9vHPV is administered during pregnancy. ACIP, AAP, American College of Obstetricians and Gynecologists (ACOG), and other experts state that HPV vaccine is not recommended for use in pregnant women.

Although pregnancy testing is not needed before initiation of the HPV vaccination series, health-care providers should question sexually active individuals about the possibility of pregnancy. HPV vaccination should be deferred until pregnancy is completed. If a woman is found to be pregnant after the HPV vaccine series is initiated, ACIP, AAP, ACOG, and other experts state that no intervention is needed, but any remaining doses of the series should be deferred until after completion of the pregnancy.

To monitor pregnancy outcomes in women who receive 9vHPV during pregnancy, the manufacturer has established a pregnancy registry. Any exposure to 9vHPV that occurs around the time of conception or during pregnancy can be reported to the pregnancy registry at 800-986-8999.

Data are insufficient to assess the effects of 9vHPV on the breast-fed infant or on milk production/excretion. The manufacturer of 9vHPV states that the benefits of breast-feeding and the importance of the vaccine to the woman should be considered along with the potential adverse effects on the breast-fed child from the vaccine or from the underlying maternal condition (i.e., susceptibility to HPV infection). ACIP states that inactivated vaccines do not pose any unusual risks for the mother or her breast-fed infant. These and other experts state that HPV vaccine may be administered to women who are breast-feeding.

Safety and efficacy of 9vHPV have not been established in females or males 65 years of age or older.

The following icd codes are available for GARDASIL 9 (PF) (human papillomavirus vaccine, 9-valent/pf)'s list of indications:

Prevention of head and neck cancer due to HPV
Z23	Encounter for immunization
Prevention of oropharyngeal cancer due to HPV
Z23	Encounter for immunization
Vaccination to prevent anal cancer due to HPV
Z23	Encounter for immunization
Vaccination to prevent cervical cancer due to HPV
Z23	Encounter for immunization
Vaccination to prevent genital warts due to HPV
Z23	Encounter for immunization
Vaccination to prevent vaginal cancer due to HPV
Z23	Encounter for immunization
Vaccination to prevent vulvar cancer due to HPV
Z23	Encounter for immunization