Twinrix

Twinrix is a vaccine used for the prevention of disease caused by hepatitis A virus and infection by all known subtypes of hepatitis B virus.

Twinrix is approved for use in persons 18 years of age or older.

Serious side effects have been reported with Twinrix including the following:

• Allergic reactions. Tell your healthcare provider about any signs or symptoms of  allergic reactions, which include the following:
  • chest pain
  • swelling of the face, eyes, lips, tongue, arms, or legs
  • difficulty breathing or swallowing
  • rash
• Latex. The tip caps of the prefilled syringes may contain natural rubber latex which may cause allergic reactions in latex-sensitive individuals.
• Fainting. Fainting can occur in association with administration of Twinrix.
• Limitations of vaccine effectiveness. Vaccination with Twinrix may not protect all individuals.
• Altered immunocompetence. If Twinrix is administered to immunocompromised persons, including persons receiving immunosuppressive therapy, the expected immune response may not be obtained.
• Moderate or severe illness. To avoid confusion when diagnosing between illness and possible vaccine adverse effects, vaccination with Twinrix should be postponed in persons with moderate or severe illness associated with fever unless they are at immediate risk of hepatitis A or hepatitis B infection.
• Multiple sclerosis. Results from 2 clinical studies indicate that there is no association between hepatitis B vaccination and the development of multiple sclerosis, and that vaccination with hepatitis B vaccine does not appear to increase the short-term risk of relapse in multiple sclerosis.

Do not get Twinrix if you had a severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis A-containing or hepatitis B-containing vaccine, or to any component of Twinrix, including yeast and neomycin.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Twinrix falls into category C. No studies have been conducted in animals, and no well-controlled studies have been done in pregnant women. Twinrix should only be given to a pregnant woman if clearly needed. 

In deciding to use a vaccine, the risks of taking the vaccine must be weighed against the good it will do. This is a decision you and your doctor will make. For this vaccine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of hepatitis A and hepatitis B combination vaccine in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies on the relationship of age to the effects of hepatitis A and hepatitis B combination vaccine have not been performed in the geriatric population. However, no geriatric-specific problems have been documented to date.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this vaccine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to neomycin or
• Allergy to yeast—Should not be used in patients with these conditions.

• Moderate or severe illness with fever—Your dose may need to be given at a later time.

• Weak immune system from a disease or medicine—The vaccine may not work as well in patients with this condition.

• If you have an allergy to Twinrix (hepatitis A and hepatitis B recombinant vaccine) or any part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have an infection or an illness with a fever.

This is not a list of all drugs or health problems that interact with Twinrix.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Twinrix® [Hepatitis A & Hepatitis B (Recombinant) Vaccine] is a sterile bivalent vaccine containing the antigenic components used in producing HAVRIX® (Hepatitis A Vaccine) and ENGERIX-B® [Hepatitis B Vaccine (Recombinant)]. Twinrix is a sterile suspension of inactivated hepatitis A virus (strain HM175) propagated in MRC-5 cells, and combined with purified surface antigen of the hepatitis B virus. The purified hepatitis B surface antigen (HBsAg) is 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.

A 1.0-mL dose of vaccine contains 720 ELISA Units of inactivated hepatitis A virus and 20 mcg of recombinant HBsAg protein. One 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. The manufacturing procedures used to manufacture Twinrix result in a product that contains no more than 5% yeast protein.

Twinrix is formulated without preservatives.

Twinrix is available in vials and 2 types of prefilled syringes. One type of prefilled syringe has a tip cap which may contain natural rubber latex. The other type has a tip cap and a rubber plunger which contain dry natural latex rubber. The vial stopper does not contain latex. (See HOW SUPPLIED.)

Twinrix is supplied as a sterile suspension for intramuscular administration. The vaccine is ready for use without reconstitution; it must be well shaken before administration to obtain a homogeneous, turbid, white suspension.

Hypersensitivity to any component of the vaccine, including yeast and neomycin, is a contraindication (see DESCRIPTION). This vaccine is contraindicated in patients with previous hypersensitivity to Twinrix or monovalent hepatitis A or hepatitis B vaccines.

General:

Prior to immunization with Twinrix, the patient's current health status and medical history should be reviewed. The physician should review the patient's immunization history for possible vaccine sensitivity, previous vaccination-related adverse reactions and occurrence of any adverse–event-related symptoms and/or signs, in order to determine the existence of any contraindication to immunization with Twinrix and to allow an assessment of benefits and risks. Appropriate medical treatment and supervision should be readily available for immediate use in case of a rare anaphylactic reaction following the administration of the vaccine. Epinephrine injection (1:1,000) and other appropriate agents used for the control of immediate allergic reactions must be immediately available. As with other vaccines, although a moderate or severe acute illness is sufficient reason to postpone vaccination, minor illnesses such as mild upper respiratory infections with or without low-grade fever are not contraindications.20

Twinrix should be given with caution in persons with bleeding disorders such as hemophilia or thrombocytopenia and in persons on anticoagulant therapy, with steps taken to avoid the risk of hematoma following the injection.20

A separate, sterile syringe and needle or a sterile disposable unit should be used for each patient to prevent the transmission of other infectious agents from person to person. Needles should be disposed of properly and should not be recapped.

As with any vaccine, if administered to immunosuppressed persons, including individuals receiving immunosuppressive therapy, the expected immune response may not be obtained.

Multiple Sclerosis: Results from 2 clinical studies indicate that there is no association between hepatitis B vaccination and the development of multiple sclerosis,21 and that vaccination with hepatitis B vaccine does not appear to increase the short-term risk of relapse in multiple sclerosis.22

Information for Vaccine Recipients:

Vaccine recipients should be informed by their healthcare provider of the potential benefits and risks of immunization with Twinrix. When educating vaccine recipients regarding potential side effects, clinicians should emphasize that components of Twinrix cannot cause hepatitis A or hepatitis B infection.

Vaccine recipients should be instructed to report any severe or unusual adverse reactions to their healthcare provider.

The vaccine recipients should be given the Vaccine Information Statements, which are required by the National Childhood Vaccine Injury Act of 1986 to be given prior to immunization. These materials are available free of charge at the CDC website (www.cdc.gov/vaccines). The Vaccine Adverse Events Reporting System (VAERS) toll-free number is 1-800-822-7967. Reporting forms may also be obtained at the VAERS website at www.vaers.hhs.gov.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Twinrix has not been evaluated for its carcinogenic potential, mutagenic potential, or potential for impairment of fertility.

Pregnancy:

Pregnancy Category C. Animal reproduction studies have not been conducted with Twinrix. It is also not known whether Twinrix can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Twinrix should be given to a pregnant woman only if clearly indicated (see INDICATIONS AND USAGE).

Pregnancy Registry:

GlaxoSmithKline maintains a surveillance registry to collect data on pregnancy outcomes and newborn health status outcomes following vaccination with Twinrix during pregnancy. Women who receive Twinrix during pregnancy should be encouraged to contact GlaxoSmithKline directly or their healthcare provider should contact GlaxoSmithKline by calling 1-888-452-9622.

Nursing Mothers:

It is not known whether Twinrix is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Twinrix is administered to a nursing woman.

Pediatric Use:

Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

Geriatric Use:

Clinical studies of Twinrix did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

1. Dienstag JL, Routenberg JA, Purcell RH, et al. Foodhandler-associated outbreak of hepatitis Type A: an immune electron microscopic study. Ann Intern Med. 1975;83:647-650. 2. Mackowiak PA, Caraway CT, Portnoy BL. Oyster-associated hepatitis: lessons from the Louisiana experience. Am J Epidemiol. 1976;103(2):181-191. 3. Woodson RD, Clinton JJ. Hepatitis prophylaxis abroad. Effectiveness of immune serum globulin in protecting Peace Corps volunteers. JAMA. 1969;209(7):1053-1058. 4. Krugman S, Giles JP. Viral hepatitis. New light on an old disease. JAMA. 1970;212(6):1019-1029. 5. Hadler SC, Erben JJ, Francis DP, et al. Risk factors for hepatitis A in day-care centers. J Infect Dis. 1982;145(2):255-261. 6. Hadler SC. Global impact of hepatitis A virus infection changing patterns. In: Hollinger FB, Lemon SM, Margolis H, eds. Viral Hepatitis and Liver Disease. Baltimore, MD: Williams & Wilkins; 1991:14-20. 7. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. Atkinson W, Hamborsky J, McIntyre L, Wolfe S, eds. 10th ed. Washington DC: Public Health Foundation; 2007:197-234. 8. Lemon SM. Type A viral hepatitis: new developments in an old disease. N Engl J Med. 1985;313(17):1059-1067. 9. Sjogren MH, Tanno H, Fay O, et al. Hepatitis A virus in stool during clinical relapse. Ann Intern Med. 1987;106:221-226. 10. Chiriaco P, Guadalupi C, Armigliato M, et al. Polyphasic course of hepatitis type A in children. J Infect Dis. 1986;153(2):378-379. 11. Data on file (TWR101), GlaxoSmithKline. 12. Koff RS. Hepatitis B and hepatitis D. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious Diseases. Philadelphia, PA: WB Saunders Company; 1992:709-716. 13. Frisch-Niggemeyer W, Ambrosch F, Hofmann H. The assessment of immunity against hepatitis B after vaccination. J Bio Stand. 1986;14(3):255-258. 14. Beasley RP, Hwang LY, Stevens CE, et al. Efficacy of hepatitis B immune globulin for prevention of perinatal transmission of the hepatitis B virus carrier state: final report of a randomized double-blind, placebo-controlled trial. Hepatology. 1983;3(2):135-141. 15. Centers for Disease Control and Prevention. Proposed vaccine information materials for hepatitis B, haemophilus influenza type B (Hib), varicella (chickenpox), and measles, mumps, rubella (MMR) vaccines. Federal Register. September 3, 1998;63(171):47026-47031. 16. Chang MH, Chen CJ, Lai MS. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. N Engl J Med. 1997;336(26):1855-1859. 17. Lee MS, Kim DH, Kim H, et al. Hepatitis B vaccination and reduced risk of primary liver cancer among male adults: A cohort study in Korea. Int J Epidemiol. 1998;27:316-319. 18. Centers for Disease Control and Prevention. 1998 Guidelines for treatment of sexually transmitted diseases. MMWR. 1999;47(RR-1):99-104. 19. Centers for Disease Control and Prevention. Hepatitis surveillance report No. 57. Atlanta, GA: DHHS; 2000:12. 20. Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2006;55(RR-15):1-48. 21. Ascherio A, Zhang SM, Hernán MA, et al. Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med. 2001;344(5):327-332. 22. Confavreux C, Suissa S, Saddier P, et al. Vaccination and the risk of relapse in multiple sclerosis. N Engl J Med. 2001;344(5):319-326. 23. Centers for Disease Control and Prevention. Vaccine adverse event reporting system United States. MMWR. 1990;39(41):730-733.

Twinrix, HAVRIX, ENGERIX-B, and TIP-LOK are registered trademarks of GlaxoSmithKline. ENZYMUN-TEST is a registered trademark of Boehringer Mannheim Immunodiagnostics. AUSAB is a registered trademark of Abbott Laboratories.

Manufactured by GlaxoSmithKline Biologicals

Rixensart, Belgium, US License No. 1617

Distributed by GlaxoSmithKline Research Triangle Park, NC 27709

©2011, GlaxoSmithKline. All rights reserved.

January 2011

TWR:16PI

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad dizziness or passing out.
• A burning, numbness, or tingling feeling that is not normal.
• Trouble controlling body movements.
• Change in eyesight.