About
Vaccines
- ACWY Vax: Meningococcal polysaccharides serogroups A, C, W135 and Y.
- Ambirix: Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed).
- Arepanrix: AS03-Adjuvanted H1N1 Pandemic Influenza Vaccine.
- Boostrix: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, adsorbed.
- Cervarix: Human Papillomavirus vaccine (types 16, 18), recombinant, adjuvanted, adsorbed.
- Engerix-B: Hepatitis B Vaccine (Recombinant).
- Fendrix: Hepatitis B (rDNA) vaccine (adjuvanted, adsorbed).
- Fluarix: Influenza vaccine.
- FluLaval: Influenza vaccine.
- Havrix: Hepatitis A vaccine, inactivated.
- Hepatyrix: Hepatitis A (inactivated, adsorbed) and Typhoid Polysaccharide vaccine.
- Hiberix: Haemophilus B conjugate vaccine (tetanus toxoid conjugate).
- Infanrix: Diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed.
- Infanrix IPV: Diphtheria, tetanus, pertussis (acellular, component) and poliomyelitis (inactivated) vaccine (adsorbed).
- Infanrix IPV + HIB: Diphtheria, tetanus, pertussis (acellular, component) and poliomyelitis (inactivated) and Haemophilus influenzae serotype b conjugate vaccine (adsorbed).
- Kinrix: Diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine.
- Menitorix: Haemophilus influenza type b Polyribose ribitol phosphate and group C Meningococcal polysaccharide conjugate vaccine.
- Pandemrix: AS03-Adjuvanted H1N1 Pandemic Influenza Vaccine.
- Pediarix: Diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine combined.
- Poliomyelitis: Poliomyelitis monodose vaccine live (oral).
- Priorix: Measles, mumps and rubella vaccine (live attenuated virus).
- Rotarix: Human rotavirus vaccine, live attenuated.
- Twinrix: Combined hepatitis A (inactivated virus) and hepatitis B vaccine (genetically derived surface antigen).
- Typherix: Typhoid vaccine (purified polysaccharide antigen).
- Varilrix: Varicella in healthy adults and adolescents.
Vaccine Trials
GlaxoSmithKline Argentina Laboratories Company was fined 400,000 pesos by Judge Marcelo Aguinsky following a report issued by the National Administration of Medicine, Food and Technology (ANMAT in Spanish) for irregularities during lab vaccine trials conducted between 2007 and 2008 that allegedly killed 14 babies.
Likewise, two doctors -Héctor Abate, and Miguel Tregnaghi- were fined with 300,000 pesos each for irregularities during the studies.
The charges included experimenting with human beings as well falsifying parental authorizations so babies could participate in vaccine-trials conducted by the laboratory from 2007 to 2008.
Since 2007, 15,000 children under the age of one from Mendoza, San Juan and Santiago del Estero have been included in the research protocol, a statement of what the study is trying to achieve. Babies were recruited from poor families that attended to public hospitals.
A total of seven babies died in Santiago del Estero; five in Mendoza; and two in San Juan.
Pediatrician Ana Marchese, who reported the case through the Argentine Federation of Health Professionals (FESPROSA in Spanish), and was working at the Eva Perón children's public hospital in Santiago del Estero when the studies wee being conducted, said this morning in conversations with Continental AM radio that "GSK Argentina set an protocol at the hospital, and recruited several doctors working there."
"These doctors took advantage of many illiterate parents whom take their children for treatment by pressuring and forcing them into signing these 28-page consent forms and getting them involved in the trials."
"Laboratories can't experiment in Europe or the United States, so they come to do it in third-world countries."
Colombian and Panama were also chosen by GSK as staging grounds for trials of the vaccine against the pneumococcal bacteria.
- By Javier Cardenal Taján, Buenos Aires Herald (January, 2012) -
Likewise, two doctors -Héctor Abate, and Miguel Tregnaghi- were fined with 300,000 pesos each for irregularities during the studies.
The charges included experimenting with human beings as well falsifying parental authorizations so babies could participate in vaccine-trials conducted by the laboratory from 2007 to 2008.
Since 2007, 15,000 children under the age of one from Mendoza, San Juan and Santiago del Estero have been included in the research protocol, a statement of what the study is trying to achieve. Babies were recruited from poor families that attended to public hospitals.
A total of seven babies died in Santiago del Estero; five in Mendoza; and two in San Juan.
Pediatrician Ana Marchese, who reported the case through the Argentine Federation of Health Professionals (FESPROSA in Spanish), and was working at the Eva Perón children's public hospital in Santiago del Estero when the studies wee being conducted, said this morning in conversations with Continental AM radio that "GSK Argentina set an protocol at the hospital, and recruited several doctors working there."
"These doctors took advantage of many illiterate parents whom take their children for treatment by pressuring and forcing them into signing these 28-page consent forms and getting them involved in the trials."
"Laboratories can't experiment in Europe or the United States, so they come to do it in third-world countries."
Colombian and Panama were also chosen by GSK as staging grounds for trials of the vaccine against the pneumococcal bacteria.
- By Javier Cardenal Taján, Buenos Aires Herald (January, 2012) -
Influenza
Adverse Events
- Anaphylaxis.
- Allergic reactions include hives, angioedema, allergic asthma, and systemic anaphylaxis.
- Increased frequency of Guillain-Barré syndrome.
- Neurological disorders such as encephalopathy, optic neuritis/neuropathy, partial facial paralysis, and brachial plexus neuropathy.
- Microscopic polyangitis (vasculitis).
FluLaval
- Initial U.S. Approval: 2006.
- Each 0.5 mL dose contains 15 micrograms (mcg) of influenza virus hemagglutinin (HA) of each of the following 3 strains: A/Brisbane/59/2007, IVR-148 (H1N1), A/Uruguay/716/2007, NYMC X-175C (H3N2) (an A/Brisbane/10/2007-like virus), and B/Brisbane/60/2008.
- Each dose may also contain residual amounts of egg proteins (≤1 mcg ovalbumin), formaldehyde (≤25 mcg), and sodium deoxycholate (≤50 mcg).
- Culture media: Chicken embryo.
- Excipients: Egg Albumin (Ovalbumin), Egg Protein, Formaldehyde or Formalin, Sodium Deoxycholate, Phosphate Buffers, Thimerosal (each 0.5 mL dose contains 25 mcg mercury).
- Randomized controlled clinical trials: United States + Canada = 1,049 adults.
- No controlled trials demonstrating a decrease in influenza disease after vaccination performed.
- Not evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.
- Safety and effectiveness not established in pregnant women, nursing mothers, and children.
- Appropriate medical treatment, including epinephrine, and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.
- Vaccination may not protect all susceptible individuals.
- As with any vaccine, broad use could reveal adverse events not observed in clinical trials.
- Postmarketing Experience: Lymphadenopathy; Conjunctivitis, eye pain, photophobia; Dysphagia, vomiting; Chest pain, injection site inflammation, rigors, asthenia, injection site rash, influenza-like symptoms, abnormal gait, injection site bruising, injection site sterile abscess; Allergic edema of the face, allergic edema of the mouth, anaphylaxis, allergic edema of the throat; Pharyngitis, rhinitis, laryngitis, cellulitis; Muscle weakness, back pain, arthritis; Dizziness, paresthesia, hypoesthesia, hypokinesia, tremor, somnolence, syncope, Guillain-Barré syndrome, convulsions/seizures, facial or cranial nerve paralysis, encephalopathy, limb paralysis; Insomnia; Dyspnea, dysphonia, bronchospasm, throat tightness; Urticaria, localized or generalized rash, pruritus, periorbital edema, sweating; Flushing, pallor.
Fluarix
- Initial U.S. Approval: 2005.
- Influenza virus subtypes A and type B contained in the vaccine, for use in persons 3 years of age and older.
- Culture media: Chicken embryo.
- Excipients: Egg Albumin (Ovalbumin), Egg Protein, Formaldehyde or Formalin, Gentamicin, Hydrocortisone, Octoxynol-10, á-Tocopheryl Hydrogen Succinate, Polysorbate 80, Sodium Deoxycholate, Sodium Phosphate, Thimerosal.
- 45 micrograms (mcg) hemagglutinin (HA) per 0.5-mL dose, in the recommended ratio of 15 mcg HA of each of the following 3 strains: A/Brisbane/59/2007, IVR-148 (H1N1), A/Uruguay/716/2007, NYMC X-175C (H3N2) (an A/Brisbane/10/2007-like virus), and B/Brisbane/60/2008.
- Each 0.5-mL dose also contains octoxynol-10 (TRITON X-100) ≤0.085 mg, α-tocopheryl hydrogen succinate ≤0.1 mg, and polysorbate 80 (Tween 80) ≤0.415 mg.
- Each dose may also contain residual amounts of hydrocortisone ≤0.0016 mcg, gentamicin sulfate ≤0.15 mcg, ovalbumin ≤1 mcg, formaldehyde ≤50 mcg, and sodium deoxycholate ≤50 mcg from the manufacturing process.
- Not evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.
- Not known whether is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when is administered to a nursing woman.
- No adequate and well-controlled studies in pregnant women.
- Do not administer to anyone with known systemic hypersensitivity reactions to egg proteins (a vaccine component) or a life-threatening reaction to previous administration of any influenza vaccine.
- Vaccination may not protect all susceptible individuals.
- There is the possibility that broad use could reveal adverse reactions not observed in clinical trials.
- Postmarketing Experience: Lymphadenopathy; Tachycardia; Vertigo; Conjunctivitis, eye irritation, eye pain, eye redness, eye swelling, eyelid swelling; Abdominal pain or discomfort, nausea, swelling of the mouth, throat, and/or tongue; Asthenia, chest pain, chills, feeling hot, injection site mass, injection site reaction, injection site warmth, body aches; Anaphylactic reaction including shock, anaphylactoid reaction, hypersensitivity, serum sickness; Injection site abscess, injection site cellulitis, pharyngitis, rhinitis, tonsillitis; Pain in extremity; Convulsion, dizziness, encephalomyelitis, facial palsy, facial paresis, Guillain-Barré syndrome, hypoesthesia, myelitis, neuritis, neuropathy, paresthesia; Asthma, bronchospasm, cough, dyspnea, respiratory distress, stridor; Angioedema, erythema, erythema multiforme, facial swelling, pruritus, rash, Stevens-Johnson syndrome, urticaria; Henoch-Schönlein purpura, vasculitis.
Arepanrix & Pandemrix
- Nano vaccine: Particle size of AS03 adjuvant is 150-155 nm, side effects even on the DNA level.
- Arepanrix: Authorized by Health Canada based on limited clinical testing in humans under the provision of an Interim Order issued on October 2009.
- Pandemrix: Approved for use by the European Commission in September 2009 upon recommendations of the European Medicines Agency for use when H1N1 influenza pandemic declared by the World Health Organization or European Union. Traces of toxic metals arsenic [As] = 2.421 ppm and tin [Sn] = 1.511 ppm found by Doctor in Sweden.
- 2-component vaccine consisting of an H1N1 immunizing antigen (as a suspension), and an AS03 adjuvant (as an oil-in-water emulsion).
- Antigen per 0.5mL dose: Split influenza virus, inactivated, containing antigen isolated from virus propagated in eggs equivalent to A/California/7/2009 (H1N1)v-like strain (X-179A) 3.75μg haemagglutinin.
- Preservative per 0.5mL dose: 5μg Thimerosal USP or 2.5 micrograms organic mercury (Hg).
- AS03 adjuvant per 0.5mL dose: 10.69 mg squalene, 11.86 mg DL-α-tocopherol, 4.86 mg polysorbate 80.
- Antigen suspension vial: Thimerosal, sodium chloride, disodium hydrogen phosphate, potassium dihydrogen phosphate, potassium chloride, water for injections. The drug substance contains trace residual amounts of egg proteins, formaldehyde, sodium deoxycholate and sucrose.
- Adjuvant emulsion vial: Sodium chloride, disodium hydrogen phosphate, potassium dihydrogen phosphate, potassium chloride, water for injections.
- Limited clinical experience in healthy adults aged 18-60 years and no clinical experience in the elderly, in children or in adolescents.
- Pregnancy and Lactation: No data.
- No studies on the effects on the ability to drive and use machines.
- Evaluation of pharmacokinetic properties not required for vaccines.
- Side Effects: Headache; Fatigue; Redness or swelling at the injection site; Shivering; Sweating; Aching muscles, joint pain; Reactions at the injection site such as bruising, itching and warmth; Fever; Swollen lympth nodes; Feeling sick, diarrhea; Dizziness; Generally feeling unwell; Unusual weakness; Vomiting, stomach pain, uncomfortable feeling in the stomach or belching after eating; Inability to sleep; Tingling or numbness of the hands or feet; Shortness of breath; Pain in the chest; Itching, rash; Pain in the back or neck, stiffness in the muscles, muscle spasms, pain in extremity such as leg or hand; Allergic reactions leading to a dangerous decrease of blood pressure, which, if untreated, may lead to shock; Fits; Severe stabbing or throbbing pain along one or more nerves; Low blood platelet count which can result in bleeding or bruising; Vasculitis (inflammation of the blood vessels which can cause skin rashes, joint pain and kidney problems); Narcolepsy; Neurological disorders such as encephalomyelitis (inflammation of the central nervous system), neuritis (inflammation of nerves), Guillain-Barré Syndrome.
Governments & H1N1 Influenza Vaccine
- 9 government contracts for a further 96 million doses.
- 22 government orders agreed to supply a further 149 million doses.
- Total number of doses ordered for pandemic vaccines: 440 million.
- Discussions with governments for further supplies.
- 60 million doses donation to the WHO for distribution to developing countries.
- 4th quarter of 2009: 130 million doses of pandemic adjuvanted vaccine shipped to governments. These shipments, together with pandemic vaccine products supplied to the US and other governments, amount to provisional, unaudited sales of £835 million.
- UK Government: 60 million doses.
- French Government: 50 million doses.
- Government of Belgium: 12.6 million doses (total population).
- Government of Japan: March 2010, amend existing contract to receive approximately 68% of the ordered vaccine.
- Government of Germany: January 2010, amend existing contract to receive approximately 70% of the ordered vaccine, equivalent to 34 million doses.
- Government of Finland: 5.3 million doses, expected to be used in conjunction with government's existing stockpile of GSK's adjuvant system. August 2010, National Institute for Health and Welfare suspends use of Pandemrix, linked in cases (over last 6 months) of narcolepsy among 79 children (300% increase) between the ages of 4 and 19, 76 also suffered from bouts of cataplexy, suffering hallucinations or paralysing physical collapses. 2011, Finnish and international researchers find conclusive link between Pandemrix and narcolepsy, Government and major insurance companies will pay for lifetime medical care for children diagnosed with narcolepsy after receiving the swine flu vaccine.
- US Government: A influenza antigen and proprietary adjuvant system AS03, 7.6 million doses of unadjuvanted pandemic vaccine, produced in multi-dose vials from bulk vaccine manufactured at facility in Quebec, 250 million doses of pandemic adjuvanted vaccine, and pandemic products worth $250 million. 2010, about 130.9 million (43% of US population) received a flu shot (8 million more than previous season), and about 49% of pregnant women (triple than previous season). 2011, 170 million doses to be made available, people can get their shots in doctors' offices, public health clinics, pharmacies and even retail stores, among other facilities.
2009
- The UK Government purchases 18 million treatment courses of antivirals and 10.6 million treatment courses of Relenza (zanamivir) for use in an influenza pandemic. The UK becomes the 2nd European country, alongside France, to hold a treatment stockpile sufficient to treat 50% of their population. Zanamivir constitutes approximately a 3rd of the UK's current antiviral stockpile. Since 2003, Relenza has been supplied to 26 governments for the purposes of pandemic stockpiling and on average the product constituted 13% of these stockpiles. Production levels for Relenza increased to produce between 50-60 million treatment packs of Relenza per year.
- New alliance with Shenzhen Neptunus Interlong Bio-Technique Co. Ltd. to develop and manufacture influenza vaccines in China.
- Worldwide agreements with Enigma Diagnostics Limited to develop and supply the first point-of-care diagnostic influenza tests to identify specific influenza virus strains using its real-time Polymerase Chain Reaction technology platform, the Enigma Mini Laboratory.
- Relenza Rotacaps, alternative Relenza treatment, granted temporary approval by Swedish regulators, as part of an application submitted under the European mutual recognition procedure for distribution during a pandemic. In discussions with regulatory authorities around the world to secure further approvals.
- Contracts in place to supply Relenza to over 60 governments.
- Allocated 10% of new Relenza production capacity for developing countries and intended donation of 2 million doses of Relenza to the WHO.
- Tiered-pricing policy for Relenza, again based on World Bank classification of countries.
- Donation to the WHO of 50 million doses of H5N1 pre-pandemic vaccine to the new candidate A (H1N1) adjuvanted influenza vaccine and supply to developing countries under a tiered-pricing policy based on World Bank classifications and GAVI Alliance eligibility.
- Worldwide collaboration and license agreement with Vivalis devoted to developing a new way of producing both seasonal and pandemic human influenza vaccines. Milestones included the designing of a manufacturing process capable of obtaining a high level of virus productivity compatible with industrial development and an important step in the characterization of the sanitary status of the EB66 cell line.
- Agreement with Kaketsuken to co-develop influenza vaccines, including pandemic influenza vaccines, produced using EB66 cell-culture technology in Japan.
- GSK expects to increase annual production capacity of Relenza to 190 million treatment courses by the end of 2009.
- European Commission grants marketing authorisation of pandemic (H1N1) adjuvanted vaccine Pandemrix for pandemic H1N1 2009 influenza.
- Agreement with the World Health Organization to donate 50 million doses of adjuvanted pandemic H1N1 influenza vaccine to WHO for distribution to developing countries most in need.
- FDA approves supplemental biologics license application for unadjuvanted influenza A (H1N1) pandemic vaccine.
- Health Canada approves adjuvant-free H1N1 vaccine for pregnant women and healthy individuals aged 10 to 64.
- 172,000 doses of Arepanrix, distributed to almost half of the country, recalled after 6 Canadians experienced severe allergic reaction called anaphylaxis, which causes breathing problems, low blood pressure and swelling of the tongue, lips and eyes. Confirmed 24 cases including one person who died after getting vaccinated.
- World Health Organization awards prequalification for global use of Arepanrix, adjuvanted H1N1 pandemic vaccine manufactured in Canada.
2008
- European licence for Pandemrix, a "mock-up" pandemic vaccine, and first company to obtain a European licence for a pre-pandemic vaccine, Prepandrix, designed to raise immune protection against several strains of the H5N1 virus.
- Exclusive Cooperation Agreement with Shenzhen Neptunus Interlong Bio-Technique Co. Ltd. as a preliminary step in forming a Joint Venture company to co-develop seasonal influenza vaccines and pre-pandemic/pandemic influenza vaccines, firstly targeting against strains of the virus specific to China, Hong Kong and Macau.
2007
- Contract from the U.S. Department of Health and Human Services for the development of pre-pandemic and pandemic flu vaccines.
- Donation of 50 million doses of H5N1 adjuvanted pre-pandemic influenza vaccine to the World Health Organization in support of stockpile initiative.
- Second task order for 22.5 million doses of 15µg H5N1 bulk vaccine antigen from the U.S. Department of Health and Human Services.
- Agreement with the UK Government to provide pandemic influenza vaccine in the event of a flu pandemic.
- Agreement with Vivalis to develop and commercialise new human influenza vaccines based on Vivalis' proprietary EBx cell line technology. Under this worldwide collaboration and license agreement, Vivalis participates in the vaccine process development, and GlaxoSmithKline Biologicals is entitled to use Vivalis' avian embryonic stem cell derived EBx cell lines and related technologies to produce seasonal and pandemic human flu vaccines.
- New generation H5N1 split antigen pre-pandemic influenza vaccine accepted for review by the Committee for Medicinal Products for Human Use in Europe.
2006
- GSK produces over 10 million packs of anti-flu treatment Relenza in one year.
- International clinical human trial programme to test two pandemic vaccines against the H5N1 strain of the avian influenza virus in humans.
- $274 million contract from the U.S. Department of Health and Human Services to speed the development of new cell culture-based seasonal and pandemic influenza vaccines and to scale-up cell culture manufacturing capability at Marietta facility.
- Daronrix, first generation alum-adjuvanted inactivated whole virus candidate flu vaccine for use once a pandemic has officially been declared by the WHO/E.U., receives positive opinion from Europe's Committee for Medicinal Products for Human Use. This is a first step in the preparation against a possible H5N1 pandemic.
- Task order for 5 million doses of H5N1 clade 2 bulk antigen at 15µg HA/dose from the U.S. Department of Health and Human Services.
- Shipping of 25 million doses of Fluarix and FluLaval to U.S.
- Supply contract with the Swiss Federal Office of Public Health for 8 million doses of H5N1 antigen influenza vaccine and its proprietary adjuvant for pre-pandemic use.
- Licensing agreement with Simcere Pharmaceutical Group of Nanjing, China, granting Simcere the right to manufacture and sell the anti-viral influenza treatment zanamivir in China, Indonesia, Thailand, Vietnam and all Least Developed Countries.
- Approval in the European Union of anti-viral Relenza (zanamivir for inhalation) in the prevention (prophylaxis) of influenza A and B in adults and children 5 years of age and above.
- Agreement with the U.S. Government to provide the anti-viral Relenza (zanamivir for inhalation) as they prepare for a potential influenza pandemic.
2005
- Acquisitions: ID Biomedical Corporation, major influenza vaccine manufacturer; Vaccine manufacturing site in Marietta, Pennsylvania, for cell-culture-based flu vaccines and secondary operations; Corixa Corporation, for developing innovative adjuvants designed to stimulate immunity.
- FDA approves Fluarix, an influenza virus vaccine.
- CEO JP Garnier meets U.S. President Bush to discuss pandemic flu planning.
Rotavirus
Rotarix
- FDA approval: 2008.
- Liquid suspension of the live attenuated human rotavirus RIX4414 strain.
- Doses: 1-mL administered orally, 1st dose at 6 weeks of age, 2nd dose after an interval of at least 4 weeks and prior to 24 weeks of age.
- Each 1-mL dose contains a suspension of at least 106.0 median Cell Culture Infective Dose of live, attenuated human G1P rotavirus after reconstitution.
- Live, attenuated rotavirus vaccine derived from the human 89-12 strain which belongs to G1P type. The rotavirus strain is propagated on Vero cells. After reconstitution, the final formulation (1 mL) contains at least 106 median Cell Culture Infective Dose of live, attenuated rotavirus.
- The lyophilized vaccine contains amino acids, dextran, Dulbecco's Modified Eagle Medium, sorbitol, and sucrose.
- Dulbecco's Modified Eagle Medium contains sodium chloride, potassium chloride, magnesium sulfate, ferric (III) nitrate, sodium phosphate, sodium pyruvate, D-glucose, concentrated vitamin solution, L-cystine, L-tyrosine, amino acids solution, L-glutamine, calcium chloride, sodium hydrogenocarbonate, and phenol red.
- The liquid diluent contains calcium carbonate, sterile water, xanthan, and an antacid component (calcium carbonate).
- Contaminated with DNA from porcine circovirus 1, a virus from pigs, in both the cell bank and the seed from which the vaccine is derived, suggesting presence from the early stages of vaccine development.
- Vaccinations: More than 1 million children in the United States and 30 million worldwide.
- 8 clinical studies: 68 deaths following administration of Rotarix (1/540) and 50 deaths following placebo administration (1/689). The most commonly reported cause of death following vaccination was pneumonia, observed in 19 recipients of Rotarix and 10 placebo recipients.
- Postmarketing Experience: Intussusception (including death), hematochezia,
gastroenteritis with vaccine viral shedding in infants with Severe Combined Immunodeficiency
Disease; Idiopathic thrombocytopenic purpura; Kawasaki disease; Maladministration.
- Animal reproduction studies not conducted.
- Not known whether can cause fetal harm when administered to a pregnant woman or can
affect reproduction capacity.
- Safety and effectiveness in infants younger than 6 weeks or older than 24 weeks of age not evaluated.
- Not evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.
Varicella
Varilrix
- Lyophilised preparation of the live attenuated Oka strain of varicella-zoster virus, obtained by propagation of the virus in MRC5 human diploid cell culture.
- Each 0.5ml dose of the reconstituted vaccine contains not less than 10 plaque-forming units of the varicella-zoster virus, amino acids, human albumin, lactose, neomycin sulphate, polyalcohols, mannitol, sorbitol.
- Manufacture includes exposure to bovine derived materials.
- As for any vaccine, may not result in protection from subsequent infection with varicella virus in 100% of subjects.
- Duration of protection: Unknown.
- Safety and efficacy not established in persons who are known to be infected with HIV, with or without evidence of immunosuppression.
- Contraindicated in pregnant women as the possible effects on foetal development are unknown.
- Pregnancy should be avoided for 3 months after vaccination.
- Effect on breast fed infants of the administration to their mothers not evaluated in clinical studies.
- May be administered at the same time as a measles-containing vaccine.
- Salicylates should be avoided for 6 weeks after varicella vaccination as Reye's syndrome has
been reported following the use of salicylates during natural varicella infection.
- Post-marketing Data: Encephalitis viral, herpes zoster and varicella; Hypersensitivity, anaphylactic reactions; Convulsions, cerebellar ataxia.
- Events reported in children: Pain at the injection site, redness, swelling, swelling (>2cm), redness (>2cm), injection site reaction, contact dermatitis; Fever, rash, injury, viral infection; Varicella-like rash, fever >39°C, fatigue, pain, infection, bacterial infection, fungal infection; Malaise; Pruritis, eczema, purpura, sweat gland disorder, dry skin, urticaria; Diarrhoea, abdominal pain, vomiting, toothache, nausea, dyspepsia; Arthralgia, myalgia; Headache, nervousness, somnolence, irritability; URTI, coughing, pharyngitis, rhinitis, asthma, sinusitis, respiratory disorder; Conjunctivitis, otitis media, earache.
- Events reported in adults: Pain at the injection site, injection site reaction, redness, injection site inflammation, injection site mass; Fever, fatigue, chest pain, injury, malaise, infection viral, Varicella-like rash; Dermatitis, pruritis, rash, urticaria; Diarrhoea, abdominal pain, vomiting, nausea, gastroenteritis; Headache, dizziness, migraine, somnolence, irritability; URTI, pharyngitis, asthma, bronchitis, coughing, sinusitis, rhinitis, sputum increased; Lymphadenopathy, lymphadenopathy cervical; Arthralgia, back pain, myalgia; Conjunctivitis.
Diphtheria and Tetanus
Pediarix
- Diphtheria and tetanus toxoids, inactivated pertussis toxin, formaldehyde-treated filamentous hemagglutinin and pertactin (69 kiloDalton outer membrane protein), hepatitis B surface antigen, plus poliovirus Type 1 (Mahoney), Type 2 (MEF-1), and Type 3 (Saukett).
- Diphtheria toxoid, tetanus toxoid, and pertussis antigens = Infanrix.
- Hepatitis B surface antigen = Engerix-B.
- Diphtheria and Tetanus Toxoids Adsorbed Combined Bulk (For Further Manufacturing Use) manufactured by Novartis Vaccines and Diagnostics GmbH & Co., Marburg, Germany.
- Culture media: Bovine protein, Lathan medium derived from bovine casein, Linggoud-Fenton medium derived from bovine extract, Monkey kidney tissue culture (Vero), synthetic or semisynthetic.
- Excipients: Aluminum Hydroxide, Aluminum Phosphate, Bovine Protein, Lactalbumin, Hydrolysate, Formaldehyde or Formalin, Glutaraldhyde, Monkey Kidney Tissue, Neomycin, 2-Phenoxyethanol, Polymyxin B, Polysorbate 80, Yeast Protein.
- Indicated for active immunization against diphtheria, tetanus, pertussis (whooping cough), all known subtypes of hepatitis B virus, and poliomyelitis caused by poliovirus Types 1, 2, and 3 as a 3-dose primary series in infants born of HBsAg-negative mothers, beginning as early as 6 weeks of age.
- Should not be administered to any infant before the age of 6 weeks, or to individuals 7 years of age or older.
- Infants born of HBsAg-positive mothers should receive Hepatitis B Immune Globulin (Human) and monovalent Hepatitis B Vaccine (Recombinant) within 12 hours of birth and should complete the hepatitis B vaccination series according to a particular schedule.
- Infants born of mothers of unknown HBsAg status should receive monovalent Hepatitis B Vaccine (Recombinant) within 12 hours of birth and should complete the hepatitis B vaccination series according to a particular schedule.
- The primary immunization series is 3 doses of 0.5 mL, given intramuscularly, at 6 to 8 week intervals (preferably 8 weeks). The customary age for the first dose is 2 months of age, but it may be given starting at 6 weeks of age.
- As with any vaccine, may not protect 100% of individuals receiving the vaccine.
- Not evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.
- Not indicated for women of child-bearing age.
- Animal reproduction studies not conducted.
- Not known whether can cause fetal harm when administered to a pregnant woman or if can affect reproductive capacity.
- Not indicated for use in adult populations.
- Safety and effectiveness in infants younger than 6 weeks of age not evaluated.
- In 14 clinical trials, 5 deaths were reported among 8,088 (1/1617) recipients. Included 2 cases of Sudden Infant Death Syndrome, 1 case of convulsive disorder, 1 case of congenital immunodeficiency with sepsis, and 1 case of neuroblastoma.
- Postmarketing Reports: Cyanosis; Diarrhea, vomiting; Fatigue, injection site cellulitis, injection site induration, injection site itching, injection site nodule/lump, injection site pain, injection site reaction, injection site redness, injection site swelling, injection site vesicles, injection site warmth, irritability, limb pain, limb swelling, pyrexia, Sudden Infant Death Syndrome; Anaphylactic reaction, anaphylactoid reaction, hypersensitivity; Upper respiratory tract infection; Abnormal liver function tests; Anorexia; Bulging fontanelle, convulsions, depressed level of consciousness, encephalitis, febrile convulsion, hypotonia, hypotonic-hyporesponsive episode, lethargy, somnolence; Crying, insomnia, nervousness, restlessness, screaming, unusual crying; Apnea, cough, dyspnea; Angioedema, erythema, rash, urticaria; Pallor, petechiae.
Kinrix
- Initial U.S. Approval: 2008.
- Each 0.5-mL dose is formulated to contain 25 Lf of diphtheria toxoid, 10 Lf of tetanus toxoid, 25 mcg of inactivated pertussin toxin , 25 mcg of filamentous hemagglutinin, 8 mcg of pertactin (69 kiloDalton outer membrane protein), 40 D-antigen Units of Type 1 poliovirus (Mahoney), 8 DU of Type 2 poliovirus (MEF-1), and 32 DU of Type 3 poliovirus (Saukett).
- Each 0.5-mL dose contains 4.5 mg of NaCl and aluminum adjuvant (not more than 0.6 mg aluminum by assay). Each dose also contains ≤100 mcg of residual formaldehyde and ≤100 mcg of polysorbate 80 (Tween 80). Neomycin sulfate and polymyxin B are used in the poliovirus vaccine manufacturing process and may be present in the final vaccine at ≤0.05 ng neomycin and ≤0.01 ng polymyxin B per dose.
- Diphtheria toxin: Produced by growing Corynebacterium diphtheriae in Fenton medium containing a bovine extract.
- Tetanus toxin: Produced by growing Clostridium tetani in a modified Latham medium derived from bovine casein.
- Acellular pertussis antigens (PT, FHA, and pertactin): Isolated from Bordetella pertussis culture grown in modified Stainer-Scholte liquid medium.
- PT and FHA: Isolated from the fermentation broth; pertactin is extracted from the cells by heat treatment and flocculation. The antigens are purified in successive chromatographic and precipitation steps. PT is detoxified using glutaraldehyde and formaldehyde. FHA and pertactin are treated with formaldehyde.
- Diphtheria and tetanus toxoids and pertussis antigens (inactivated PT, FHA, and pertactin): Individually adsorbed onto aluminum hydroxide.
- Each of the 3 strains of poliovirus is individually grown in VERO cells, a continuous line of monkey kidney cells, cultivated on microcarriers. Calf serum and lactalbumin hydrolysate are used during VERO cell culture and/or virus culture.
- Indicated for active immunization against diphtheria, tetanus, pertussis, and poliomyelitis as the 5th dose in the diphtheria, tetanus, and acellular pertussis (DTaP) vaccine series and the 4th dose in the inactivated poliovirus vaccine (IPV) series in children 4 through 6 years of age whose previous DTaP vaccine doses have been with Infanrix and/or Pediarix for the 1st 3 doses and Infanrix for the 4th dose.
- Animal reproduction studies: Not conducted.
- Not known whether can cause fetal harm when administered to a pregnant woman or can affect
reproduction capacity.
- Not evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.
- Safety and effectiveness in children younger than 4 years of age and children 7 to 16 years of age not evaluated. Not approved for use in persons in these age groups.
Infanrix
- Culture media: Cohen-Wheeler or Stainer-Scholte media, Lathan medium derived from bovine casein, Linggoud-Fenton medium derived from bovine extract, synthetic or semisynthetic.
- Excipients: Aluminum Hydroxide, Bovine Extract, Formaldehyde or Formalin, Glutaraldhyde, 2-Phenoxyethanol, Polysorbate 80.
Meningitis
Menitorix (2011)
- Therapeutic Goods Administration (Australia) approval: August 2010.
- White powder of Hib-MenC vaccine in a glass vial, together with half a millilitre (0.5 ml) of clear colourless sodium chloride solvent in a pre-filled syringe for a 1 dose vaccine. This powder is dissolved in the solvent provided, just before injection (into the muscle).
- After reconstitution, one dose (0.5 ml) contains: Haemophilus influenzae type b Polyribose ribitol phosphate (5 μg); Conjugated to tetanus toxoid as carrier protein (12.5 μg); Group C Meningococcal polysaccharide (5 μg); Conjugated to tetanus toxoid as carrier protein (5 μg).
- The powder for reconstitution also contains the excipients, trometamol and sucrose.
- Does not protect against meningitis caused by other bacteria or viruses, including other types and groups of Haemophilus or Neisseria bacteria.
- As with all vaccines, it may not protect all people who are vaccinated.
- Adverse Effects Clinical Trial Data: Irritability, crying; Drowsiness; Loss of appetite, diarrhoea, vomiting; Dermatitis atopic, rash; Injection site reaction including pain, redness, swelling, fever (rectal 38°C), injection site reaction including induration and nodule, fever (rectal >39.5°C).
- Post Marketing Data: Lymphadenopathy; Febrile seizures, hypotonia, headache, dizziness; Apnoea in very premature infants (≤28 weeks of gestation); Allergic reactions (including urticaria and anaphylactoid reactions).
- Side effects: Pain, redness or swelling at the site of the injection; Fever (more than or equal to 38°C), high fever (more than 39.5°C); Drowsiness; Loss of appetite; Irritability; Injection site reaction, such as a hard lump; Crying; Diarrhoea; Vomiting; Skin allergies; Generally feeling unwell; Rash; Convulsions (fits) caused by a fever.
- Other possible side effects: Severe skin reactions, collapse or shock-like state (hypotonic-hyporesponsiveness episode), faints, seizures in patients with pre-existing seizure disorders, hypoaesthesia, paraesthesia, relapse of nephrotic syndrome, arthralgia, petechiae and/or purpura.
- Sudden life-threatening allergic reaction, symptoms include sudden signs of allergy such as: rash, itching or hives on the skin; swelling of the face, lips, tongue or other parts of the body; shortness of breath, wheezing or trouble breathing.
- Not a complete list of all possible side-effects, others may occur in some people and there may be some side-effects not yet known.
- Since the Hib capsular polysaccharide antigen is excreted in the urine, a false positive urine test for Hib infection can be observed within 1-2 weeks following vaccination.
- As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.
- It should under no circumstances be administered intravascularly or intradermally.
- Not intended for adult use.
- No data on infants born before 36 weeks gestation.
- No data on the use in immunodeficient subjects.
- No data on subcutaneous administration.
- No data on the potential of impair fertility.
- The carcinogenic potential has not been established.
- Not evaluated for genotoxicity.
- Primary vaccination in infants from 6 weeks up to 12 months of age: 3 doses, each of 0.5 ml, should be given with an interval of at least 1 month between doses.
- Overdosage: Insufficient data are available. Contact the Poisons Information Centre for advice on overdose management.
Hepatitis
Hepatyrix
- Hepatitis A (inactivated) and Typhoid Polysaccharide vaccine (adsorbed).
- 25 micrograms of the Vi polysaccharide antigen, part of the typhi (Ty2 strain) bacterium that causes typhoid fever.
- 1440 ELISA units of hepatitis A viral protein.
- Excipients: Sodium chloride, Water for injections.
Ambirix (2007)
- First authorisation: August 2002.
- Latest renewal: September 2007.
- Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed).
- 2 injections within 12 months, used in infants, children and adolescents from 1 year.
- Cannot completely prevent infections with hepatitis A or B viruses, even after received both doses.
- Former formulation: Thiomersal and preservative containing vaccine.
- Active substances: Hepatitis A virus (inactivated), 720 ELISA Units, produced on human diploid (MRC-5) cells and adsorbed on aluminium hydroxide, hydrated 0.05 milligrams Al3+; Hepatitis B surface antigen, 20 micrograms, produced in yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology and adsorbed on aluminium phosphate 0.4 milligrams Al3+.
- Excipients: Sodium chloride and water for injections.
- Evaluation of pharmacokinetic properties is not required for vaccines.
- Side effects during clinical trials: Pain or discomfort at the injection site or redness; Tiredness; Irritability; Headache; Loss of appetite; Swelling at the injection site; Fever (more than 38°C); Drowsiness; Stomach and digestive complaints waste; Itchy or blistering, swelling of the eyes and face,
difficulty in breathing or swallowing, a sudden drop in blood pressure and loss of consciousness; Flu-like symptoms, including chills, and muscle and joint pains; Fits, dizziness, pins and needles, multiple sclerosis, disease of the nerves of the eye, loss of sensation in, or of the ability to move some parts of the body, severe headache with stiff neck, disruption of the normal brain functions; Faints; Inflammation of some blood vessels; Feeling or being sick, loss of appetite, diarrhoea and stomach pains; Abnormal laboratory liver test results; Swelling of the glands; Bleeding or bruising more easily than normal due to a drop in a type of blood cell called platelets.
- Postmarketing Experience: Abnormal liver function tests; Thrombocytopenia, thrombocytopenic purpura, lymphadenopathy; Syncope, dizziness, paresthesia, convulsions; Nausea, vomiting, diarrhoea, abdominal pain; Rash, pruritis, urticaria; Decreased appetite; Hypotension; Flu-like symptoms, fatigue; Allergic reactions including anaphylactic and anaphylactoid reactions and serum sickness like disease; Multiple sclerosis, myelitis, facial palsy, polyneuritis such as Guillain-Barré syndrome (with ascending paralysis), encephalitis, encephalopathy; Optic neuritis; Erythema exsudativum multiforme; Meningitis; Vasculitis.
Engerix-B
- Purified surface antigen of the virus obtained by culturing genetically engineered Saccharomyces cerevisiae cells, which carry the surface antigen gene of the hepatitis B virus.
- Culture media: Yeast or yeast extract.
- Excipients: Aluminum Hydroxide, Phosphate Buffers, Thimerosal, Yeast Protein.
- Pediatric/Adolescent: Each 0.5-mL dose contains 10 mcg of hepatitis B surface antigen adsorbed on 0.25 mg aluminum as aluminum hydroxide, sodium chloride (9 mg/mL) and phosphate buffers (disodium phosphate dihydrate, 0.98 mg/mL; sodium dihydrogen phosphate dihydrate, 0.71 mg/mL).
- Adult: Each 1-mL adult dose contains 20 mcg of hepatitis B surface antigen adsorbed on 0.5 mg aluminum as aluminum hydroxide, sodium chloride (9 mg/mL) and phosphate buffers (disodium phosphate dihydrate, 0.98 mg/mL; sodium dihydrogen phosphate dihydrate, 0.71 mg/mL).
- Dosing Schedules: 1st dose; 2nd dose, 1 month later; 3rd dose, 6 months after 1st dose.
- Not evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.
- Animal reproduction studies not conducted.
- Not known whether can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
- Not known whether is excreted in human milk.
- Adverse Reactions: Dizziness, headache; Fever (>37.5°C), injection site erythema, injection site induration, injection site swelling; Upper respiratory tract illnesses; Lymphadenopathy; Anorexia; Agitation, insomnia; Somnolence, tingling; Flushing, hypotension; Abdominal pain/cramps, constipation, diarrhea, nausea, vomiting; Erythema, petechiae, pruritus, rash, sweating, urticaria; Arthralgia, back pain, myalgia, pain/stiffness in arm, shoulder, or neck; Chills, influenza-like symptoms, injection site ecchymosis, injection site pain, injection site pruritus, irritability, malaise, weakness.
- Postmarketing Reports: Herpes zoster, meningitis; Thrombocytopenia; Allergic reaction, anaphylactoid reaction, anaphylaxis. Arthralgia/arthritis (usually transient), fever, and dermatologic reactions such as urticaria, erythema multiforme, ecchymoses, and erythema nodosum; Encephalitis, encephalopathy, migraine, multiple sclerosis, neuritis, neuropathy including hypoesthesia, paresthesia, Guillain-Barré syndrome and Bell's palsy, optic neuritis, paralysis, paresis, seizures, syncope, transverse myelitis; Conjunctivitis, keratitis, visual disturbances; Earache, tinnitus, vertigo; Palpitations, tachycardia; Vasculitis; Apnea, bronchospasm including asthma-like symptoms; Dyspepsia; Alopecia, angioedema, eczema, erythema multiforme including Stevens-Johnson syndrome, erythema nodosum, lichen planus, purpura; Arthritis, muscular weakness; Injection site reaction; Abnormal liver function tests.
Havrix
- Culture media: Human diploid tissue culture, MRC-5.
- Excipients: Aluminum Hydroxide, Amino Acids, Formaldehyde or Formalin, MRC-5, Cellular Protein, Neomycin Sulfate, 2-Phenoxyethanol, Phosphate Buffers, Polysorbate.
Twinrix
- Sterile suspension of inactivated hepatitis A virus (strain HM175) propagated in MRC-5 cells, and combined with purified surface antigen (HBsAg) of the hepatitis B virus obtained by culturing genetically engineered Saccharomyces cerevisiae cells, which carry the surface antigen gene of the hepatitis B virus, in synthetic media containing inorganic salts, amino acids, dextrose, and vitamins. Bulk preparations of each antigen are adsorbed separately onto aluminum salts and then pooled during formulation.
- Contains the antigenic components used in producing Havrix and Engerix-B, for persons 18 years of age or older.
- Culture media: Human diploid tissue culture (MRC-5), yeast or yeast extract.
- Excipients: Aluminum Hydroxide, Aluminum Phosphate, Amino Acids, Dextrose, Formaldehyde or Formalin, Inorganic Salts, MRC-5 Cellular Protein, Neomycin Sulfate, 2-Phenoxyethanol, Phosphate Buffers, Polysorbate 20, Thimerosal.
- 1.0-mL dose of vaccine contains 720 ELISA Units of inactivated hepatitis A virus and 15-20 mcg of recombinant HBsAg protein.
- 1 dose of vaccine also contains 0.45 mg of aluminum in the form of aluminum phosphate and aluminum hydroxide as adjuvants, amino acids, sodium chloride, phosphate buffer, polysorbate 20, Water for Injection, traces of formalin (not more than 0.1 mg), and residual MRC-5 cellular proteins (not more than 2.5 mcg).
- Neomycin sulfate, an aminoglycoside antibiotic, is included in the cell growth media; only trace amounts (not more than 20 ng) remain following purification.
- Primary immunization for adults consists of 3 doses, given on a 0, 1, and 6-month schedule. Alternatively, a 4-dose schedule, given on days 0, 7 and 21 to 30 followed by a booster dose at month 12 may be used.
- As with any vaccine, vaccination may not protect 100% of recipients.
- Not evaluated for carcinogenic potential, mutagenic potential, or potential for impairment of fertility.
- Healthcare providers are encouraged to register pregnant women in the GlaxoSmithKline vaccination pregnancy registry.
- Not known whether is excreted in human milk.
- Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
- As with any vaccine, broad use could reveal adverse events not observed in clinical trials.
- Postmarketing Reports: Herpes zoster, meningitis; Thrombocytopenia, thrombocytopenic purpura; Allergic reaction, anaphylactoid reaction, anaphylaxis, serum sickness–like syndrome days to weeks after vaccination including arthralgia/arthritis (usually transient), fever, urticaria, erythema multiforme, ecchymoses, and erythema nodosum; Bell's palsy, convulsions, encephalitis, encephalopathy, Guillain-Barré syndrome, hypoesthesia, myelitis, multiple sclerosis, neuritis, neuropathy, optic neuritis, paralysis, paresis, transverse myelitis; Conjunctivitis, visual disturbances; Earache, tinnitus; Palpitations, tachycardia; Vasculitis; Bronchospasm including asthma-like symptoms, dyspnea; Dyspepsia; Hepatitis, jaundice; Alopecia, angioedema, eczema, erythema multiforme, erythema nodosum, hyperhydrosis, lichen planus; Arthritis, muscular weakness; Chills, injection site reaction, malaise; Abnormal liver function tests.
The House Reform Committee (1999)
Judy Converse
Betty Fluck
Betty Fluck