Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Recombinant Vaccine

Registered South African indications:

• Prevention of cervical, vulvar, vaginal and anal cancer, pre-cancerous or dysplastic lesions, genital warts and infections caused by the human papillomavirus (HPV) in females
• Prevention of external genital lesions and infection and certain diseases caused by HPV types included in the vaccine (males)

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Individuals who develop symptoms indicative of hypersensitivity after receiving a dose of quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine should not receive further doses of quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Active human papillomavirus (HPV) infections
• Active HPV-related cancers
• Congenital or acquired immunodeficiency
• Thrombocytopaenia
• Coagulation disorders

Forms avail. in SA and covered in this monograph: inj

South African registered indications and dosages

Prevention of cervical, vulvar, vaginal and anal cancer, pre-cancerous or dysplastic lesions, genital warts and infections caused by the human papillomavirus (HPV) in females (≤45 years)
- Cervical, vulvar, vaginal and anal cancer caused by HPV types 16 and 18
- Genital warts (condyloma acuminata) caused by HPV 6 and 11
- Provides protection against HPV 31-, 33-, 52- and 58-related CIN grades (up to 26 years)
And infections and the following pre-cancerous or dysplastic lesions caused by HPV types 6, 11, 16 and 18:
- Cervical intraepithelial neoplasia (CIN) grade 2 and 3 and Cervical adenocarcinoma in situ (AIS)
- Cervical intraepithelial neoplasia (CIN) grade 1
- Vulvar intraepithelial neoplasia (VIN) grade 2 and grade 3
- Vaginal intraepithelial neoplasia (VaIN) grade 2 and grade 3
- VIN grade 1 and VaIN grade 1
- Anal intraepithelial neoplasia (AIN) grades 1, 2 and 3
Prevention of external genital lesions and infection and the following diseases caused by HPV types included in the vaccine in males (≤26 years)
- Anal cancer caused by HPV types 16 and 18
- Genital warts (condyloma acuminata) caused by HPV types 6 and 11
And the following pre-cancerous or dysplastic lesions caused by HPV types 6, 11, 16 and 18:
- Anal intraepithelial neoplasia (AIN) grades 1, 2 and 3

• IM: First dose: 0.5ml, at elected date; Second dose: 0.5ml, 2 months after first dose; Third dose: 0.5ml, 6 months after first dose

Quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine should be administered as soon as possible after being removed from refrigeration

Individuals are encouraged to adhere to the 0, 2, and 6 months vaccination schedule. However in clinical studies, efficacy has been demonstrated in individuals who have received all 3 doses within a 1-year period. The second dose should be administered at least 1 month after the first dose, and the third dose should be administered at least 3 months after the second dose. All three doses should be given within a 1-year period

The use of quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine should be in accordance with official recommendations. It is recommended that individuals who receive a first dose of quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine complete the vaccination course with quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine. The need for a booster dose has not been established

See Additional Prescribing Points for method of admin.

Paed. forms avail. in SA and covered in this monograph: inj

South African registered indications and dosages

Prevention of cervical, vulvar, vaginal and anal cancer, pre-cancerous or dysplastic lesions, genital warts and infections caused by the human papillomavirus (HPV) in females
- Cervical, vulvar, vaginal and anal cancer caused by HPV types 16 and 18
- Genital warts (condyloma acuminata) caused by HPV 6 and 11
- Provides protection against HPV 31-, 33-, 52- and 58-related CIN grades
And infections and the following pre-cancerous or dysplastic lesions caused by HPV types 6, 11, 16 and 18:
- Cervical intraepithelial neoplasia (CIN) grade 2 and 3 and Cervical adenocarcinoma in situ (AIS)
- Cervical intraepithelial neoplasia (CIN) grade 1
- Vulvar intraepithelial neoplasia (VIN) grade 2 and grade 3
- Vaginal intraepithelial neoplasia (VaIN) grade 2 and grade 3
- VIN grade 1 and VaIN grade 1
- Anal intraepithelial neoplasia (AIN) grades 1, 2 and 3
Prevention of external genital lesions and infection and the following diseases caused by HPV types included in the vaccine in males
- Anal cancer caused by HPV types 16 and 18
- Genital warts (condyloma acuminata) caused by HPV types 6 and 11
And the following pre-cancerous or dysplastic lesions caused by HPV types 6, 11, 16 and 18:
- Anal intraepithelial neoplasia (AIN) grades 1, 2 and 3

• Younger than 9 years: Not established for use
• Between 9-13 years: IM: See adult dosage OR 2 dose schedule: First dose: 0.5ml, at elected date; Second dose: 0.5ml, 6 months or 12 months after the 1st dose (i.e 0, 6 months schedule or 0, 12 months schedule)
• 14 years and older: See adult dosage

Quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine should be administered as soon as possible after being removed from refrigeration

Individuals are encouraged to adhere to the 0, 2, and 6 months vaccination schedule. However in clinical studies, efficacy has been demonstrated in individuals who have received all 3 doses within a 1-year period. The second dose should be administered at least 1 month after the first dose, and the third dose should be administered at least 3 months after the second dose. All three doses should be given within a 1-year period

The use of quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine should be in accordance with official recommendations. It is recommended that individuals who receive a first dose of quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine complete the vaccination course with quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine. The need for a booster dose has not been established

See Additional Prescribing Points for method of admin.

Pregnancy

• Caution;
• Specific studies of the vaccine in pregnant women were not conducted. During the clinical development program, 3,819 women (vaccine = 1,894 vs. placebo = 1,925) reported at least one pregnancy. There were no significant differences in types of anomalies or proportion of pregnancies with an adverse outcome in human papillomavirus vaccine and placebo treated individuals. These data on pregnant women (more than 1000 exposed outcomes) indicate no malformative nor feto/ neonatal toxicity
• The data on human papillomavirus vaccine administered during pregnancy did not indicate any safety signal. However, these data are insufficient to recommend use of human papillomavirus vaccine during pregnancy. Vaccination should be postponed until completion of pregnancy

Breastfeeding

• Compatible
• In breastfeeding mothers given human papillomavirus vaccine or placebo during the vaccination period of the clinical trials the rates of adverse reactions in the mother and the breastfed infant were comparable between the vaccination and the placebo groups. In addition, vaccine immunogenicity was comparable among breastfeeding mothers and women who did not breastfeed during the vaccine administration
• Therefore human papillomavirus vaccine can be used during breastfeeding

Renal Impairment

• Caution; no information available

Hepatic Impairment

• Caution; no information available

Elderly

• Caution; no information available

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Acute disseminated encephalomyelitis
• Dizziness
• Guillain-Barré syndrome
• Syncope 

Gastrointestinal Disorders

• Nausea and vomiting

Musculoskeletal Disorders

• Pain in extremity
• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Injection site cellulitis
• Hypersensitivity reactions
• Pyrexia
• Chills

Immune, Blood and Lymphatic System Disorders

• Idiopathic thrombocytopenic purpura
• Lymphadenopathy

• Immunoglobulin products
• Blood-derived products

None routine

Method of Administration

• The quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine should be administered intramuscularly in the deltoid region of the upper arm or in the higher anterolateral area of the thigh
• The vaccine must not be injected intravascularly. Neither subcutaneous nor intradermal administration has been studied. These methods of administration are not recommended
• The pre-filled syringe is for single use only and should not be used for more than one individual. For single-use vials, a separate sterile syringe and needle must be used for each individual
• The vaccine should be used as supplied; no dilution or reconstitution is necessary. The full recommended dose of the vaccine should be used.
• Shake well before use. Thorough agitation immediately before administration is necessary to maintain suspension of the vaccine
• After thorough agitation, the quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine is a white, cloudy liquid. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Discard the product if particulates are present or if it appears discoloured

Single dose vial use

• Withdraw the 0.5ml dose of vaccine from the single-dose vial using a sterile needle and syringe free of preservatives, antiseptics, and detergents
• Once the single-dose vial has been penetrated, the withdrawn vaccine should be used promptly, and the vial must be discarded

Pre-filled syringe use

• Inject the entire contents of the pre-filled syringe
• For pre-filled single-dose syringes pre-assembled with a needle guard (safety) device, use the enclosed needle for administration. If a different needle is chosen, ensure it fits securely on the syringe and is no longer than 2.5cm (1 inch) to ensure proper functioning of the needle guard device. Two detachable labels are provided, which can be removed after the needle is guarded
• To avoid premature activation of the safety device, do not touch the trigger fingers during any of the following steps:
  • Remove syringe tip cap and needle cap
  • Attach Luer needle by pressing both anti-rotation tabs to secure the syringe and attach Luer needle by twisting in a clockwise direction until secured
  • Remove needle sheath
  • Administer the injection per standard protocol as stated in the dosage sections
  • Depress the plunger while grasping the finger flange until the entire dose has been given. The needle guard device will not activate to cover and protect the needle unless the entire dose has been administered
  • While keeping the plunger depressed, remove the needle from the vaccine recipient
  • Slowly release the plunger, allowing the syringe to move up until the entire needle is guarded
  • For documentation of vaccination, remove detachable labels by pulling slowly on them
  • Dispose of in an approved sharps container

Human papillomavirus vaccine is an adjuvanted non-infectious recombinant quadrivalent vaccine prepared from the highly purified virus-like particles (VLPs) of the major capsid L1 protein of HPV types 6, 11, 16 and 18. The VLPs contain no viral DNA, they cannot infect cells, reproduce or cause disease. Human papilloma virus only infects humans, but animal studies with analogous papillomaviruses suggest that the efficacy of LI VLP vaccines is mediated by the development of a humoral immune response.

Human Papiloma virus: Type 6/ Type 16/ Type 18/ Type 11

Injection (per 0.5ml) 20µg/40µg/20µg/40µg

• Gardasil (MSD) originator