Gardasil: safety and side effects
In a commentary published in the Canadian Medical Association Journal ( CMAJ ), Abby Lippman, an epidemiologist at McGill University in Montreal, Canada, and colleagues wrote that there is no urgent need for wide-scale cervical cancer vaccinations because deaths from the disease have been declining.
A careful review of the literature reveals a sufficient number of unanswered questions to lead us to conclude that a universal immunization program is, at this time, premature and could possibly have unintended negative consequences for individuals and for society as a whole," said Lippman.
Gardasil protects against human papillomavirus ( HPV ) infection with the types 16 and 18, which cause about 70% of cervical, anal, and genital cancers, and it protects against types 6 and 11, which cause about 90% of genital warts.
Infection with papillomaviruses is common: more than six million new infections occur each year, and nearly three quarters of the US population aged between 15 and 49 have been infected with one of the papillomaviruses at some time.
Most papillomavirus infections do not cause cancer or, if they cause precancerous changes, are caught by cervical cancer screening.
Nevertheless, the US has about 10 000 new cases of cervical cancer a year, and about 3700 women die. Most deaths are in poor women who have seldom or never been screened.
According to Gardasil's label, a total of 102 subjects out of 21,464 total subjects ( 9- to 26-year-old girls and women and 9- to 15-year-old boys ) who received both Gardasil and placebo reported a serious adverse experience on day 1-15 following any vaccination visit during the clinical trials.
The most frequently reported serious adverse experiences for Gardasil compared to placebo and regardless of causality were: headache ( 0.03% Gardasil vs. 0.02% Placebo ), gastroenteritis ( 0.03% Gardasil vs. 0.01% Placebo ), appendicitis ( 0.02% Gardasil vs. 0.01% Placebo ), pelvic inflammatory disease ( 0.02% Gardasil vs. 0.01% Placebo ). One case of bronchospasm and 2 cases of asthma were reported as serious adverse experiences that occurred during day 1-15 of any vaccination visit.
According to EMEAs CHMP, the general safety profile of Gardasil is considered favourable. The safety database is large although for some separate age cohorts it might not sufficiently detect possibly precluded unexpected adverse reactions.
Specific studies of the vaccine in pregnant women were not conducted. However, during the clinical development program, 2,266 women ( vaccine: 1,115 vs. placebo: 1,151 ) reported at least one pregnancy. Overall, the numbers of pregnancies with an adverse outcome were comparable in subjects who received Gardasil and subjects who received placebo. For pregnancies with estimated onset within 30 days of vaccination, 5 cases of congenital anomaly were observed in the group that received Gardasil compared to 0 cases of congenital anomaly in the group that received placebo. Conversely, in pregnancies with onset more than 30 days following vaccination, 10 cases of congenital anomaly were observed in the group that received Gardasil compared with 16 cases of congenital anomaly in the group that received placebo. The types of anomalies observed were consistent with those generally observed in pregnancies in women aged 16 to 26 years.
The data on Gardasil administered during pregnancy did not indicate any safety signal. However, these data are insufficient to recommend use of Gardasil during pregnancy. Vaccination should, therefore, be postponed until after completion of pregnancy.
A total of 995 breastfeeding mothers were given Gardasil 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. Gardasil can be given to breastfeeding women.
Gardasil has not been studied in children below 9 years of age. Thus the use of vaccine should be avoided in that age group.
Judicial Watch released in May 2007 documents obtained from the FDA ( Food and Drug Administration ) under the provisions of the Freedom of Information Act, detailing 1,637 reports of adverse reactions to the vaccination for human papillomavirus, Gardasil.
As of May 11, 2007, the 1,637 adverse vaccination reactions reported via the Vaccine Adverse Event Reporting System ( VAERS ) included 371 serious reactions. Of the 42 women who received the vaccine while pregnant, 18 experienced side effects ranging from spontaneous abortion to fetal abnormalities.
Side effects published by Merck & Co warn the public about potential pain, fever, nausea, dizziness and itching after receiving the vaccine. Indeed, 77% of the adverse reactions reported were typical side effects to vaccinations. But other more serious side effects reported included paralysis, Bells Palsy, Guillain-Barre syndrome, and seizures.
VAERS is a post-marketing safety surveillance program, collecting information about adverse events ( possible side effects ) that occur after the administration of US licensed vaccines. The fact that an adverse event occurred following immunization is not conclusive evidence that the event was caused by a vaccine.
A selection of VAERS reports on Gardasil
1) Guillain-Barre syndrome, urticaria
Information has been received from a physician concerning a 13 year old female who on 22-Nov-2006 was vaccinated with HPV rL1 6 11 16 18 VLP vaccine. A few days later she had cold symptoms and was prescribed Azithromycin ( Zithromax ). A few days after that the patient developed hives and was prescribed Amoxicillin. A few days later the patient was hospitalized and diagnosed on 1-Dec-2006 with Guillian-Barre syndrome.
Information has been received from a nurse practitioner concerning a 19 year old female who on an unspecified date was vaccinated with a 0.5 ml dose of Gardasil. The patient was experiencing vomiting and diarrhea and had no fever prior to receiving the vaccination. Subsequently, the patient developed swelling of hands and feet and her face got puffy after receiving Gardasil. The patient was treated with an antihistamine.
Information has been received from a physician concerning a 17 year old female who on 11/21/06 was vaccinated with an initial dose of HPV vaccine IM in the deltoid. On 11/21/06, after the initial dose, the patient experienced a seizure. The patient was alert shortly after the event and was sent to the emergency department as a precaution. It is unknown if the patient was admitted to the hospital. The patient is recovering from seizure. The patient will not continue with subsequent doses of vaccine.
4) Facial palsy, hypoaesthesia, pain, paralysis
Influenza vaccine and human papillomavirus vaccine given to an 11 year old female, on November 10. Patient woke up with numbness on right side of face on November 11. Presented to Emergency Room on November 12 with Bells palsy of right side of face. Unable to move right side of face. Unable to close right eye. Previously healthy, no symptoms on day of vaccine administration.
5) Asthenia, Guillain-Barre syndrome, hypoaesthesia
Information has been received from a physician concerning a 16 year old female who on an unspecified date was vaccinated with the first dose of HPV vaccine. Subsequently the patient developed lower extremity weakness and was hospitalized for two days with Guillain-Barre syndrome. The patient received treatment with gamma globulin during her hospitalization. At the time of this report, the patient was back to school and was 99% recovered having only some area of numbness to her lower extremities.
6) Maculopapular rash
Information has been received from a physician concerning a female patient who on 11-Sep-2006 was vaccinated with her first dose of HPV rL1 6 11 16 18 VLP vaccine. The physician reported that within 24 hours of receiving the vaccine the patient developed a maculopapular rash all over the body.
7) Dyspnoea, pyrexia
Information has been received from a physician concerning an 18 year old female who on 14-Sep-2006 was vaccinated intramuscularly with a first 0.5 ml dose of HPV rLi 6 11 16 18 VLP vaccine. About an hour after receiving the vaccine, the patient developed shortness of breath and a fever. The patient was directed to the emergency room. It was noted that the patient's symptoms improved on therapy.
Information has been received from a 20 year old female patient who on 7-Aug-2006 was vaccinated intramuscularly with her first dose of HPV rLi 6 11 16 18 VLP vaccine. Concomitant therapy included Drospirenone (+) Ethinyl Estradiol. The patient stated that right after getting the shot she experienced pain in the upper arm on and off throughout the day. She also stated that the pain feels like she has a knife in her arm .
9) Chest discomfort, erythema, oedema peripheral
Information has been received from a nurse concerning her 17 year old with asthma who on 8/22/06 was vaccinated IM with HPV rL1 6 11 16 18 VLP vaccine ( 0.5 ml ). On 8/23/06 the patient developed a swollen thumb and her palms became red and hot. The patient later developed a tightness in her chest. The patient was immediately taken to a physician who immediately gave the patient a huge dose of Cetirizine hydrochloride and Acetaminophen.
10) Chest pain, dyspnoea, nausea, oedema peripheral, pain in extremity, swelling face, vomiting
Information has been received from a nurse practitioner concerning a 13 year old female who on 26-Mar-2007 was vaccinated with Gardasil. On 26-Mar-2007 the patient developed swelling of the arm, arm and chest pain, nausea, vomiting, facial swelling and difficulty breathing. The patient went to the emergency room and was treated with Phenergan. Subsequently, the patient recovered.
11) Worsening asthma, dyspnoea
Information has been received from a healthcare professional concerning a 23 year old woman with asthma ( diagnosed at the age of 5 year old ) and outdoor allergies who on 19-Apr-2007 was vaccinated IM in left arm deltoid with a first dose of Gardasil. Concomitant therapy included Montelukast ( Singulair ), Loratadine (+) Pseudoephedrine ( Claritin D ) and Albuterol ( Ventolin ). On 20-Apr-2007, patient woke up with short of breath. Her rescue inhaler did not help so she used her nebulizer. On 21-Apr-2007 she used her nebulizer again. On 22-Apr-2007, she did 6 nebulizer treatment within one-two hours before being admitted at the hospital. In the hospital she had additional nebulizer treatment ( 10+ ) times and steroid injections. Patient stated that this was her worst asthma attack since being diagnosed. Patient recovered.
Information has been received from a nurse practitioner concerning a 21 year old female who had a biopsy on 8-May-2007 ( reason not reported ) and was also vaccinated with Gardasil at 8:00 pm. Concomitant therapy included Ethinyl Estradiol (+) Norethindrone acetate ( Loestrin ). On 9-May-2007 the patient became paralyzed from the neck down and was taken to the emergency room by ambulance.
13 ) Gingival bleeding
Information has been received from a physician's assistant concerning a female who on 18-Jan-2007 was vaccinated with Gardasil. There was no concomitant medication. After vaccination on 18-Jan-2007 and 22-Mar-2007, the patient experienced bleeding gums. The duration and extent of the bleeding gums was unknown. It was unknown if the bleeding got worse with the second vaccination. The patient's father is an oral surgeon and felt that the bleeding of the gums was related to the Gardasil vaccination. The patient's bleeding gums persisted.
14) Chest pain, dyspnoea, limb discomfort, muscle spasms
Information has been received from an office receptionist concerning a 20 year old woman with family history of heart disease, allergic reaction to antibiotics, who on 2-Feb-2007 was vaccinated IM with a first dose of Gardasil. Concomitant therapy included Ortho Tri-Cyclen Lo ( Norgestimate / Ethinyl Estradiol ). On 2-Feb-2007 the patient developed arm soreness but otherwise felt fine. In April 2007 patient was vaccinated IM with the second dose of Gardasil. Within one to one and half hours after the second injection patient developed muscle spasm in chest area which radiated from left chest to center. She described pain as sharp intermittent and took her breath away. On 18-APR-2007 she took Advil ( Ibuprofen ) for something else ( not specified ) and it helped pain a little but was not relieved. The physician instructed patient to go the emergency room ( ER ). Patient was planning to go to the ER on 19-Apr-2007. At the time of this report the patient had not recovered.
15 ) Urticaria
Information has been received from a physician, concerning a 16 year old female patient, who on 12-Feb-2007 was vaccinated with the first dose of Gardasil, and reported no symptoms or concerns. On 9-Apr-2007, the patient was vaccinated with the second dose, 0.5ml, IM, of Gardasil. Concomitant therapy included Augmentin (( Amoxicillin / Clavulanate potassium ). On 12-Apr-2007, three days after the second vaccination was administered, the patient experienced urticaria all over her body, especially on her extremities and face. Treatment included Benadryl ( Diphenhydramine ). At the time of this report, the physician confirmed the patient was recovering from the urticaria.
16 ) Injection site pain, pain in extremity
Information has been received from a health professional concerning a female who on 14-Mar-2007 was vaccinated with the first dose of Gardasil, IM in the right deltoid. Concomitant therapy included Mircette ( Ethinyl Estradiol and Desogestrel ) and vitamins. Subsequently, immediately following the vaccination the patient experienced pain in the injection site arm. The patient recovered from the pain in "a day or two" but it returned on approximately 18-Mar-2007. This pain was described as a shooting pain in the injection site arm " down to the elbow " that occurred when the arm was moved. There was no pain on touch. It was reported that the pain was worst at the end of the day and immediately upon arising. The patient was treated with Advil ( Ibuprofen ) which was reported to have helped the pain. The patient was examined at her physician's office on 26-Mar-2007 and was prescribed Tylenol ( Acetaminophen ) with Codeine. Subsequently, the patient called into the office on 9-Apr-2007 and reported that the pain in the arm was still present and had worsened.
17 ) Diplegia, Guillain-Barre syndrome, pain
Information has been received from a pediatric physician concerning a 14 year old female who was vaccinated with a dose of Gardasil. Subsequently the patient developed Guillain-Barre syndrome which he thought was " pain and paralysis in the legs ". The patient's outcome was unknown.
18) Foetal disorder, club foot, umbilical cord abnormality
Information has been received through the Merck Pregnancy Registry from a nurse concerning an 18 year old female who on 27-Oct-2006 was vaccinated with Gardasil, when she was 17 1/7 weeks pregnant. Subsequently, the infant was born with a left club foot and two vessel umbilical cord.
19) Facial pain, facial palsy, facial paresis, pain in extremity, syncope
Information has been received from a health professional concerning a 26 year old female with no medical history or allergies, who in June 2007, was vaccinated with a dose of Gardasil. There was no concomitant medication. In June 2007, the patient experienced severe pain in her arm, fainted, facial weakness, Bells palsy, and facial pain after being vaccinated with Gardasil. The patient did go to the Emergency Room, however, was not admitted to the hospital. At the time of this report, the patient had not recovered. Severe pain in arm, fainted, facial weakness, Bells palsy, and facial pain were considered to be disabling.
20) Lymphadenopathy, surgery
Information has been received from a physician concerning his daughter ( age not reported ) with no pertinent medical history or drug reactions/allergies who on an unspecified date was vaccinated with a first and second dose of Gardasil. Concomitant therapy included Cetirizine ( Zyrtec ). Within 2 weeks of the first vaccination, the patient experienced enlarged lymph nodes at different locations on the same side as the Gardasil injection. Outpatient surgery was performed to remove the lymph node (s) after the 1st dose of Gardasil. Within 2 weeks of receiving the second dose of the vaccine, the patient developed enlarged lymph nodes on the side of the neck. At the time of reporting the patient had not recovered and additional surgery was planned. The physician felt that the event was serious because outpatient surgery was performed.
21) Abdominal pain, diarrhoea, fatigue, nausea, pain
Information has been received from a healthcare worker concerning a 26 year old female with allergic reaction to Cipro ( Ciprofloxacin ) who on 19-Mar-2007 was vaccinated with Gardasil, Concomitant therapy included Estrostep ( Norethindrone and Ethinyl Estradiol ) and acne medication. On 19-Mar-2007 the patient experienced abdominal cramping, diarrhea, nausea, body aching and fatigue for 24 hours after receiving her first dose of the vaccine. The next day, 20-Mar-2007, the patient fully recovered from abdominal cramping, diarrhea, nausea, body aching and fatigue.
22) Guillain-Barre syndrome, hypoaesthesia, muscular weakness
Information has been received from a physician concerning a 16 year old female who on 16-Apr-2007 was vaccinated with a dose of Gardasil. Since 1 day post-injection, the patient had progressive bilateral leg numbness and motor weakness. The physician inquired about the possibility of Guillian-Barre syndrome. At the time of this report, the outcome was unknown. Upon internal review, progressive bilateral leg numbness and motor weakness were considered to be other important medical events.
23 ) Muscular weakness, paraesthesia
Information has been received from a physician concerning an 18 year old female patient who on 29-Jan-2007 was vaccinated in her left arm with her first dose of Gardasil. Concomitant therapy included meningococcal vaccine ( unspecified ). On 29-Jan-2007 after receiving the injection the patient experienced weakness and tingling in her left arm which spread over the entire length of her arm and also to her jaw. She experienced so much discomfort in her jaw that she had difficulty chewing. An examination of the patient ruled out Guillain-Barre syndrome. The above reaction eventually resolved in two weeks and on approximately 12-Feb-2007, the patient recovered. The physician considered the events to be disabling.
24) Abdominal pain, vomiting, appendicitis
Less than 3 hours following the vaccination a 20 year old female developed severe abdominal cramps and vomited. Subsequently had persistent abdominal pain that was localized to the right lower quadrant. A CT ( computed tomography ) of the abdomen was performed the evening of 11/29/06 which revealed appendicitis. A surgical consultation was requested and days of hospitalization are unknown yet at this time.
25) Arthralgia, dermographism, oedema peripheral, urticaria
Information has been received from a physician concerning her 20 year old daughter who on 11-Jan-2007 was vaccinated IM with a 0.5 ml dose of Gardasil vaccine. Fifteen minutes after the vaccination, welts appeared on the patient's neck and spread all over the body. Dermatographia resulted all over the patient's body, her hands and feet were swollen, and she experienced arthritic pain in her joints. It was reported that the patient was not able to walk because of the pain. The patient was treated with Cetirizine, Dexamethasone and Hydroxyzine. At the time of this report, the patient was not recovered. Welts, dermatographia, peripheral swelling, arthritic-like joint pain and the patient's inability to walk were considered to be disabling events.
Source: 1) VAERS, 2007; 2) EMEA, 2007; Judicial Watch, 2007; CMAJ, 2007
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