Cervarix - Drug Monograph

Introduction

Cervarix is a bivalent human papillomavirus (HPV) vaccine indicated for the prevention of cervical cancer, precancerous cervical lesions, and precancerous anal lesions caused by specific HPV types. It is a non-infectious recombinant vaccine prepared from virus-like particles (VLPs) of the L1 capsid protein of HPV types 16 and 18.

Mechanism of Action

Cervarix induces humoral immune responses through the production of neutralizing antibodies against HPV types 16 and 18. The vaccine contains VLPs that mimic the natural virus but lack viral DNA, making them non-infectious. These VLPs are assembled using recombinant DNA technology and are combined with the AS04 adjuvant system containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and aluminum hydroxide, which enhances the immune response and promotes longer-lasting antibody titers.

Indications

• Prevention of cervical cancer caused by HPV types 16 and 18
• Prevention of cervical intraepithelial neoplasia (CIN) grades 1, 2, and 3
• Prevention of adenocarcinoma in situ (AIS)
• Prevention of anal intraepithelial neoplasia (AIN) grades 1, 2, and 3

Approved for use in females aged 9 through 45 years.

Dosage and Administration

• Standard dosage: 0.5 mL intramuscular injection
• Administration schedule: 3-dose series at 0, 1, and 6 months
• Route: Intramuscular injection, preferably in the deltoid muscle
• Special populations: No dosage adjustment required for renal or hepatic impairment
• Preparation: Shake well before use; administer immediately after preparation

Pharmacokinetics

• Absorption: Not applicable as vaccine induces immune response rather than systemic absorption
• Distribution: Localized immune response at injection site with systemic antibody production
• Metabolism: Degraded by proteinases at injection site
• Elimination: Not characterized as vaccine components are processed through normal protein degradation pathways
• Antibody response: Peak antibody titers observed approximately 7 months after first dose

Contraindications

• History of severe allergic reaction to any component of Cervarix
• Hypersensitivity to previous dose of Cervarix
• Anaphylactic reaction to latex (pre-filled syringe tip cap contains latex)

Warnings and Precautions

• Syncope may occur following vaccination; observe patients for 15 minutes post-administration
• Not for treatment of active HPV infection or cervical cancer
• Does not protect against all HPV types or against existing HPV infections
• Immunocompromised patients may have reduced immune response
• Pregnancy: Category B - use only if clearly needed
• Not recommended for use in males

Drug Interactions

• Immunosuppressive therapies may diminish immune response
• Can be administered concurrently with other vaccines using separate injection sites
• No specific drug interaction studies conducted
• No interactions expected with hormonal contraceptives

Adverse Effects

• Injection site reactions (pain, redness, swelling)
• Fatigue
• Headache
• Myalgia
• Gastrointestinal symptoms

• Fever
• Arthralgia
• Urticaria
• Rash

• Anaphylaxis
• Syncope
• Lymphadenopathy

Monitoring Parameters

• Documentation of vaccination dates and completion of series
• Local injection site reactions
• Systemic symptoms post-vaccination
• Antibody titers not routinely monitored in clinical practice
• Routine cervical cancer screening should continue as recommended

Patient Education

• Complete all three doses for optimal protection
• Common side effects include arm soreness, headache, and fatigue
• Vaccine does not treat existing HPV infections
• Continue regular cervical cancer screening as recommended
• Report any severe reactions to healthcare provider
• Vaccine does not protect against all HPV types or other sexually transmitted infections
• Inform healthcare provider of any allergies, especially to latex

References

1. FDA prescribing information for Cervarix. Silver Spring, MD: Food and Drug Administration; 2021. 2. Paavonen J, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types: final analysis of a double-blind, randomised study in young women. Lancet. 2009;374(9686):301-314. 3. World Health Organization. Human papillomavirus vaccines: WHO position paper. Wkly Epidemiol Rec. 2017;92(19):241-268. 4. Centers for Disease Control and Prevention. HPV vaccine recommendations. MMWR Recomm Rep. 2019;68(32):698-702. 5. Schiller JT, et al. An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Vaccine. 2008;26 Suppl 10:K53-K61.