Cervarix

Cervarix [Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant] Suspension for Intramuscular Injection is a vaccine is used to prevent cervical cancer caused by certain types of HPV (types 16 and 18) in girls and young women ages 10 through 25. Common side effects of Cervarix include injection site reactions (pain, swelling, or redness), headache, tired feeling, joint or muscle pain, nausea, vomiting, diarrhea, stomach pain, menstrual pain, runny or stuffy nose, sore throat, or cough. Temporary reactions to vaccines may also include fainting, dizziness, lightheadedness, vision changes, numbness or tingling, or seizure-like movements.

Immunization with Cervarix consists of 3 doses of 0.5-mL each, by intramuscular injection according to the following schedule: 0, 1, and 6 months. Cervarix may interact with steroids, chemotherapy or radiation, medicines to treat or prevent organ transplant rejection, or medications to treat psoriasis, rheumatoid arthritis, or other autoimmune disorders. Tell your doctor all medications and supplements you use and all vaccines you recently received. Cervarix is not expected to be harmful to a fetus. However, you should not receive HPV vaccine without telling your doctor if you are pregnant or plan to become pregnant before you have received all doses of this vaccine. It is unknown whether this vaccine passes into breast milk or if it could harm a nursing baby. Consult your doctor before breastfeeding.

Our Cervarix [Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant] Suspension for Intramuscular Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

You should not receive a booster vaccine if you have had a life-threatening allergic reaction after the first shot.

Developing cancer from HPV is much more dangerous to your health than receiving the vaccine to protect against it. However, like any medicine, this vaccine can cause side effects but the risk of serious side effects is extremely low.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

You may feel faint after receiving this vaccine. Some people have had seizure-like reactions after receiving this vaccine. Your doctor may want you to remain under observation during the first 15 minutes after the injection.

Other side effects may include:

• pain, swelling, or redness where the shot was given;
• headache, tired feeling;
• joint or muscle pain.
• nausea, vomiting, diarrhea, stomach pain;
• menstrual pain;
• runny or stuffy nose, sore throat, cough; or

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report vaccine side effects to the US Department of Health and Human Services at 1-800-822-7967.

Read the entire detailed patient monograph for Cervarix (Human Papillomavirus Bivalent Vaccine)

SIDE EFFECTS

The most common local adverse reactions ( ≥ 20% of subjects) were pain, redness, and swelling at the injection site.

The most common general adverse events ( ≥ 20% of subjects) were fatigue, headache, myalgia, gastrointestinal symptoms, and arthralgia.

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice. There is the possibility that broad use of CERVARIX could reveal adverse reactions not observed in clinical trials.

Studies in Females 9 Through 25 Years of Age

The safety of CERVARIX was evaluated by pooling data from controlled and uncontrolled clinical trials involving 23,952 females 9 through 25 years of age in the pre-licensure clinical development program. In these studies, 13,024 females (9 through 25 years of age) received at least one dose of CERVARIX and 10,928 females received at least one dose of a control [Hepatitis A Vaccine containing 360 EL.U. (10 through 14 years of age), Hepatitis A Vaccine containing 720 EL.U. (15 through 25 years of age), or Al(OH)3 (500 mcg, 15 through 25 years of age)].

Data on solicited local and general adverse events were collected by subjects or parents using standardized diary cards for 7 consecutive days following each vaccine dose (i.e., day of vaccination and the next 6 days). Unsolicited adverse events were recorded with diary cards for 30 days following each vaccination (day of vaccination and 29 subsequent days). Parents and/or subjects were also asked at each study visit about the occurrence of any adverse events and instructed to immediately report serious adverse events throughout the study period. These studies were conducted in North America, Latin America, Europe, Asia, and Australia. Overall, the majority of subjects were white (59.5%), followed by Asian (25.9%), Hispanic (8.5%), black (3.4%), and other racial/ethnic groups (2.7%).

Solicited Adverse Events: The reported frequencies of solicited local injection site reactions (pain, redness, and swelling) and general adverse events (fatigue, fever, gastrointestinal symptoms, headache, arthralgia, myalgia, and urticaria) within 7 days after vaccination in females 9 through 25 years of age are presented in Table 1. An analysis of solicited local injection site reactions by dose is presented in Table 2. Local reactions were reported more frequently with CERVARIX when compared with the control groups; in ≥ 76% of recipients of CERVARIX, these local reactions were mild to moderate in intensity. Compared with dose 1, pain was reported less frequently after doses 2 and 3 of CERVARIX, in contrast to redness and swelling where there was a small increased incidence. There was no increase in the frequency of general adverse events with successive doses.

Table 1: Rates of Solicited Local Adverse Reactions and General Adverse Events in Females 9 Through 25 Years of Age Within 7 Days of Vaccination (Total Vaccinated Cohort^a)

	CERVARIX (9-25 years) %	HAV 720b (15-25 years) %	HAV 360c (10-14 years) %	Al(OH)3 Controld (15-25 years) %
Local Adverse Reaction	N = 6,669	N = 3,079	N = 1,027	N = 549
Pain	91.9	78.0	64.2	87.2
Redness	48.4	27.6	25.2	24.4
Swelling	44.3	19.8	17.3	21.3
General Adverse Event	N = 6,670	N = 3,079	N = 1,027	N = 549
Fatigue	54.6	53.7	42.3	53.6
Headache	53.4	51.3	45.2	61.4
GIe	27.9	27.3	24.6	32.8
Fever ( ≥ 99.5°F)	12.9	10.9	16.0	13.5
Rash	9.5	8.4	6.7	10.0
	N = 6,119	N = 3,079	N = 1,027	-
Myalgiaf	48.8	44.9	33.1	-
Arthralgiaf	20.7	17.9	19.9	-
Urticariaf	7.2	7.9	5.4	-
a Total vaccinated cohort included subjects with at least one documented dose (N). b HAV 720 = Hepatitis A Vaccine control group [720 EL.U. of antigen and 500 mcg Al(OH)3]. c HAV 360 = Hepatitis A Vaccine control group [360 EL.U. of antigen and 250 mcg of Al(OH)3]. d Al(OH)3 Control = control containing 500 mcg Al(OH)3. e GI = Gastrointestinal symptoms, including nausea, vomiting, diarrhea, and/or abdominal pain. f Adverse events solicited in a subset of subjects.

Table 2: Rates of Solicited Local Adverse Reactions in Females 9 Through 25 Years of Age by Dose Within 7 Days of Vaccination (Total Vaccinated Cohort^a)

	CERVARIX (9-25 years) %			HAV 720b (15-25 years) %			HAV 360c (10-14 years) %			Al(OH)3 Controld (15-25 years) %
	Post-Dose			Post-Dose			Post-Dose			Post-Dose
	1	2	3	1	2	3	1	2	3	1	2	3
N	6,653	6,428	6,168	3,070	2,919	2,758	1,027	1,021	1,011	546	521	500
Pain	87.0	76.4	78.5	65.6	54.4	56.1	48.5	38.5	36.9	79.1	66.8	72.4
Pain, Grade 3e	7.5	5.6	7.7	2.0	1.4	2.0	0.8	0.2	1.6	9.0	6.0	8.6
Redness	28.4	30.1	35.7	16.6	15.2	16.1	15.6	13.3	12.1	11.5	11.5	15.6
Redness, > 50 mm	0.2	0.5	1.0	0.1	0.1	0.0	0.1	0.2	0.1	0.2	0.0	0.0
Swelling	22.8	25.5	32.7	10.5	9.4	10.5	9.4	8.6	7.6	10.3	10.4	12.0
Swelling, > 50 mm	1.1	1.0	1.3	0.2	0.2	0.2	0.4	0.3	0.0	0.0	0.0	0.0
a Total vaccinated cohort included subjects with at least one documented dose (N). b HAV 720 = Hepatitis A Vaccine control group [720 EL.U. of antigen and 500 mcg Al(OH)3]. c HAV 360 = Hepatitis A Vaccine control group [360 EL.U. of antigen and 250 mcg of Al(OH)3]. d Al(OH)3 Control = control containing 500 mcg Al(OH)3. e Defined as spontaneously painful or pain that prevented normal daily activities.

The pattern of solicited local adverse reactions and general adverse events following administration of CERVARIX was similar between the age cohorts (9 through 14 years and 15 through 25 years).

Unsolicited Adverse Events: The frequency of unsolicited adverse events that occurred within 30 days of vaccination ( ≥ 1% for CERVARIX and greater than any of the control groups) in females 9 through 25 years of age are presented in Table 3.

Table 3: Rates of Unsolicited Adverse Events in Females 9 Through 25 Years of Age Within 30 Days of Vaccination ( ≥ 1% For CERVARIX and Greater Than HAV 720, HAV 360, or Al(OH)₃ Control) (Total Vaccinated Cohort^a)

	CERVARIX % N = 6,893	HAV 720b % N = 3,186	HAV 360c % N = 1,032	Al(OH)3 Controld % N = 581
Headache	5.2	7.6	3.3	9.3
Nasopharyngitis	3.7	3.4	5.9	3.3
Influenza	3.1	5.6	1.3	1.9
Pharyngolaryngeal pain	2.9	2.7	2.2	2.2
Dizziness	2.2	2.6	1.5	3.1
Upper respiratory infection	2.0	1.3	6.7	1.5
Chlamydia infection	1.9	4.4	0.0	0.0
Dysmenorrhea	1.9	2.3	1.9	4.0
Pharyngitis	1.4	1.8	2.2	0.5
Injection site bruising	1.4	1.8	0.7	1.5
Vaginal infection	1.3	2.2	0.1	0.9
Injection site pruritus	1.3	0.5	0.6	0.2
Back pain	1.1	1.3	0.7	3.1
Urinary tract infection	1.0	1.4	0.3	1.2
a Total vaccinated cohort included subjects with at least one dose administered (N). b HAV 720 = Hepatitis A Vaccine control group [720 EL.U. of antigen and 500 mcg Al(OH)3]. c HAV 360 = Hepatitis A Vaccine control group [360 EL.U. of antigen and 250 mcg of Al(OH)3]. d Al(OH)3 Control = control containing 500 mcg Al(OH)3.

New Onset Autoimmune Diseases (NOADs): The pooled safety database, which included controlled and uncontrolled trials which enrolled females 9 through 25 years of age, was searched for new medical conditions indicative of potential new onset autoimmune diseases. Overall, the incidence of potential NOADs, as well as NOADs, in the group receiving CERVARIX was 0.8% (96/12,772) and comparable to the pooled control group (0.8%, 87/10,730) during the 4.3 years of follow-up (Table 4).

In the largest randomized, controlled trial (Study 2) which enrolled females 15 through 25 years of age and which included active surveillance for potential NOADs, the incidence of potential NOADs and NOADs was 0.8% among subjects who received CERVARIX (78/9,319) and 0.8% among subjects who received Hepatitis A Vaccine [720 EL.U. of antigen and 500 mcg Al(OH)3] control (77/9,325).

Table 4: Incidence of New Medical Conditions Indicative of Potential New Onset Autoimmune Disease and New Onset Autoimmune Disease Throughout the Follow-up Period Regardless of Causality in Females 9 Through 25 Years of Age (Total Vaccinated Cohort^a)

	CERVARIX N = 12,772 n (%)c	Pooled Control Groupb N = 10,730 n (%)c
Total Number of Subjects With at Least One Medical Condition	96 (0.8)	87 (0.8)
Arthritisd	9 (0.1)	4 (0.0)
Celiac disease	2 (0.0)	5 (0.0)
Dermatomyositis	0 (0.0)	1 (0.0)
Diabetes mellitus insulin-dependent (Type 1 or unspecified)	5 (0.0)	5 (0.0)
Erythema nodosum	3 (0.0)	0 (0.0)
Hyperthyroidisme	15 (0.1)	15 (0.1)
f Hypothyroidismf	30 (0.2)	28 (0.3)
Inflammatory bowel diseaseg	8 (0.1)	4 (0.0)
Multiple sclerosis	4 (0.0)	1 (0.0)
Myelitis transverse	1 (0.0)	0 (0.0)
Optic neuritis/Optic neuritis retrobulbar	3 (0.0)	1 (0.0)
Psoriasish	8 (0.1)	11 (0.1)
Raynaud’s phenomenon	0 (0.0)	1 (0.0)
Rheumatoid arthritis	4 (0.0)	3 (0.0)
Systemic lupus erythematosusi	2 (0.0)	3 (0.0)
Thrombocytopeniaj	1 (0.0)	1 (0.0)
Vasculitisk	1 (0.0)	3 (0.0)
Vitiligo	2 (0.0)	2 (0.0)
a Total vaccinated cohort included subjects with at least one documented dose (N). b Pooled Control Group = Hepatitis A Vaccine control group [720 EL.U. of antigen and 500 mcg Al(OH)3], Hepatitis A Vaccine control group [360 EL.U. of antigen and 250 mcg of Al(OH)3], and a control containing 500 mcg Al(OH)3. c n (%): number and percentage of subjects with medical condition. d Term includes reactive arthritis and arthritis. e Term includes Basedow's disease, goiter, and hyperthyroidism. f Term includes thyroiditis, autoimmune thyroiditis, and hypothyroidism. g Term includes colitis ulcerative, Crohn's disease, proctitis ulcerative, and inflammatory bowel disease. h Term includes psoriatic arthropathy, nail psoriasis, guttate psoriasis, and psoriasis. i Term includes systemic lupus erythematosus and cutaneous lupus erythematosus. j Term includes idiopathic thrombocytopenic purpura and thrombocytopenia. k Term includes leukocytoclastic vasculitis and vasculitis.

Serious Adverse Events

In the pooled safety database, inclusive of controlled and uncontrolled studies, which enrolled females 9 through 72 years of age, 5.3% (864/16,381) of subjects who received CERVARIX and 5.9% (814/13,811) of subjects who received control reported at least one serious adverse event, without regard to causality, during the entire follow-up period (up to 7.4 years).

Among females 9 through 25 years of age enrolled in these clinical studies, 6.3% of subjects who received CERVARIX and 7.2% of subjects who received the control reported at least one serious adverse event during the entire follow-up period (up to 7.4 years).

Deaths

In completed and ongoing studies which enrolled 57,323 females 9 through 72 years of age, 37 deaths were reported during the 7.4 years of follow-up: 20 in subjects who received CERVARIX (0.06%, 20/33,623) and 17 in subjects who received control (0.07%, 17/23,700). Causes of death among subjects were consistent with those reported in adolescent and adult female populations. The most common causes of death were motor vehicle accident (5 subjects who received CERVARIX; 5 subjects who received control) and suicide (2 subjects who received CERVARIX; 5 subjects who received control), followed by neoplasm (3 subjects who received CERVARIX; 2 subjects who received control), autoimmune disease (3 subjects who received CERVARIX; 1 subject who received control), infectious disease (3 subjects who received CERVARIX; 1 subject who received control), homicide (2 subjects who received CERVARIX; 1 subject who received control), cardiovascular disorders (2 subjects who received CERVARIX), and death of unknown cause (2 subjects who received control). Among females 10 through 25 years of age, 31 deaths were reported (0.05%, 16/29,467 of subjects who received CERVARIX and 0.07%, 15/20,192 of subjects who received control).

Postmarketing Experience

In addition to reports in clinical trials, worldwide voluntary reports of adverse events received for CERVARIX since market introduction (2007) are listed below. This list includes serious events or events which have suspected causal association to CERVARIX. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccination.

Blood and Lymphatic System Disorders: Lymphadenopathy.

Immune System Disorders: Allergic reactions (including anaphylactic and anaphylactoid reactions), angioedema, erythema multiforme.

Nervous System Disorders: Syncope or vasovagal responses to injection (sometimes accompanied by tonic-clonic movements).

Read the entire FDA prescribing information for Cervarix (Human Papillomavirus Bivalent Vaccine)

Read the Cervarix User Reviews »

© Cervarix Patient Information is supplied by Cerner Multum, Inc. and Cervarix Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.