Measles virus vaccine, live

No. 4589X/4309 ATTENUVAX (measles virus vaccine live) is supplied as follows: (1) a box of 10 single-dose vials of lyophilized vaccine (package A), NDC 0006-4589-00; and (2) a box of 10 vials of diluent (package B). To conserve refrigerator space, the diluent may be stored separately at room temperature.

Storage

During shipment, to ensure that there is no loss of potency, the vaccine must be maintained at a temperature of 10°C (50°F) or colder. Freezing during shipment will not affect potency.

Protect the vaccine from light at all times, since such exposure may inactivate the virus.

Before reconstitution, store the vial of lyophilized vaccine at 2-8°C (36-46°F) or colder. The diluent may be stored in the refrigerator with the lyophilized vaccine or separately at room temperature.

It is recommended that the vaccine be used as soon as possible after reconstitution. Store reconstituted vaccine in the vaccine vial in a dark place at 2-8°C (36-46°F) and discard if not used within 8 hours.

REFERENCES

14. Centers for Disease Control and Prevention. Recommended childhood immunization schedule — United States, January-June 1996, MMWR 44(51 & 52): 940-943, January 5, 1996.

15. Measles Prevention: Recommendations of the Immunization Practices Advisory Committee (ACIP), MMWR 38(S-9): 5-22, December 29, 1989.

16. Jong, E.C.: The Travel and Tropical Medicine Manual, W.B. Saunders Company, p. 12-16, 1987.

17. Committee on Immunization Council of Medical Societies, American College of Physicians, Phila. PA, Guide for Adult Immunization, First Edition, 1985.

18. King, G.E.; Markowitz, L.E.; Patriarca, P.A.; et al: Clinical Efficacy of Measles Vaccine During the 1990 Measles Epidemic, Pediatr. Infect. Dis. J. 10(12): 883-888, December 1991.

19. Krasinski, K.; Borkowski, W.: Measles and Measles Immunity in Children Infected With Human Immunodeficiency Virus, JAMA 261(17): 2512-2516, 1989.

35. Measles, Mumps, and Rubella — Vaccine Use and Strategies for Elimination of Measles, Rubella, and Congenital Rubella Syndrome and Control of Mumps: Recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR 47(RR-8): May 22, 1998.

Manuf. and Dist. by: Merck & Co. Inc., Whitehouse Station, New Jersey, NJ 08889, USA. Issued February 2006. FDA revision date: n/a

The following adverse reactions are listed in decreasing order of severity, without regard to causality, within each body system category and have been reported during clinical trials, with use of the marketed vaccine, or with use of polyvalent vaccine containing measles:

Body as a Whole

Panniculitis; atypical measles; fever; syncope; headache; dizziness; malaise; irritability.

Cardiovascular System

Vasculitis.

Digestive System

Diarrhea, vomiting, nausea.

Hemic and Lymphatic System

Thrombocytopenia (see WARNINGS, Thrombocytopenia); purpura; lymphadenopathy; leukocytosis.

Immune System

Anaphylaxis and anaphylactoid reactions have been reported as well as related phenomena such as angioneurotic edema (including peripheral or facial edema) and bronchial spasm in individuals with or without an allergic history.

Musculoskeletal

Arthralgia, myalgia.

Nervous System

Encephalitis; encephalopathy; measles inclusion body encephalitis (MIBE) (see CONTRAINDICATIONS); subacute sclerosing panencephalitis (SSPE); Guillain-Barré syndrome (GBS); febrile convulsions; afebrile convulsions or seizures; ataxia; ocular palsies.

Experience from more than 80 million doses of all live measles vaccines given in the U.S. through 1975 indicates that significant central nervous system reactions such as encephalitis and encephalopathy, occurring within 30 days after vaccination, have been temporally associated with measles vaccine very rarely.28 In no case has it been shown that reactions were actually caused by vaccine. The Centers for Disease Control and Prevention has pointed out that “a certain number of cases of encephalitis may be expected to occur in a large childhood population in a defined period of time even when no vaccines are administered”.29 However, the data suggest the possibility that some of these cases may have been caused by measles vaccines. The risk of such serious neurological disorders following live measles virus vaccine administration remains far less than that for encephalitis and encephalopathy with natural measles (one per two thousand reported cases).30

Post-marketing surveillance of the more than 200 million doses of M-M-R and M-M-R II that have been distributed worldwide over 25 years (1971-1996) indicates that serious adverse events such as encephalitis and encephalopathy continue to be rarely reported.10

There have been reports of subacute sclerosing panencephalitis (SSPE) in children who did not have a history of natural measles but did receive measles vaccine. Some of these cases may have resulted from unrecognized measles in the first year of life or possibly from the measles vaccination. Based on estimated nationwide measles vaccine distribution, the association of SSPE cases to measles vaccination is about one case per million vaccine doses distributed. This is far less than the association with natural measles, 6-22 cases of SSPE per million cases of measles. The results of a retrospective case-controlled study conducted by the Centers for Disease Control and Prevention suggest that the overall effect of measles vaccine has been to protect against SSPE by preventing measles with its inherent higher risk of SSPE.31

Respiratory System

Pneumonitis (see CONTRAINDICATIONS); cough; rhinitis.

Skin

Stevens-Johnson syndrome; erythema multiforme; urticaria; rash.

Local reactions including burning/stinging at injection site; wheal and flare; redness (erythema); swelling; vesiculation at injection site.

Special Senses — Ear

Nerve deafness; otitis media.

Special Senses — Eye

Retinitis; optic neuritis; papillitis; retrobulbar neuritis; conjunctivitis.

Other

Death from various, and in some cases unknown, causes has been reported rarely following vaccination with measles, mumps, and rubella vaccines; however, a causal relationship has not been established. No deaths or permanent sequelae were reported in a published post-marketing surveillance study in Finland involving 1.5 million children and adults who were vaccinated with M-M-R II during 1982-1993.32

Under the National Childhood Vaccine Injury Act of 1986, health care providers and manufacturers are required to record and report certain suspected adverse events occurring within specific time periods after vaccination. However, the U.S. Department of Health and Human Services (DHHS) has established a Vaccine Adverse Event Reporting System (VAERS) which will accept all reports of suspected events.28 A VAERS report form as well as information regarding reporting requirements can be obtained by calling VAERS 1-800-822-7967.

ATTENUVAX * (Measles Virus Vaccine Live) is a live virus vaccine for vaccination against measles (rubeola).

ATTENUVAX is a sterile lyophilized preparation of a more attenuated line of measles virus derived from Enders' attenuated Edmonston strain and propagated in chick embryo cell culture.

The growth medium for measles is Medium 199 (a buffered salt solution containing vitamins and amino acids and supplemented with fetal bovine serum) containing SPGA (sucrose, phosphate, glutamate, and human albumin) as stabilizer and neomycin.

The cells, virus pools, fetal bovine serum, and human albumin are all screened for the absence of adventitious agents. Human albumin is processed using the Cohn cold ethanol fractionation procedure.

The reconstituted vaccine is for subcutaneous administration. Each 0.5 mL dose contains not less than 1,000 TCID 50 (tissue culture infectious doses) of measles virus. Each dose of the vaccine is calculated to contain sorbitol (14.5 mg), sodium phosphate, sucrose (1.9 mg), sodium chloride, hydrolyzed gelatin (14.5 mg), human albumin (0.3 mg), fetal bovine serum (<1 ppm), other buffer and media ingredients and approximately 25 mcg of neomycin. The product contains no preservative.

Before reconstitution, the lyophilized vaccine is a light yellow compact crystalline plug. ATTENUVAX, when reconstituted as directed, is clear yellow.

Hypersensitivity to any component of the vaccine, including gelatin.

Do not give ATTENUVAX to pregnant females; the possible effects of the vaccine on fetal development are unknown at this time. If vaccination of postpubertal females is undertaken, pregnancy should be avoided for 3 months following vaccination (see PRECAUTIONS , Pregnancy ).

Anaphylactic or anaphylactoid reactions to neomycin (each dose of reconstituted vaccine contains approximately 25 mcg of neomycin).

Febrile respiratory illness or other active febrile infection. However, the ACIP has recommended that all vaccines can be administered to persons with minor illnesses such as diarrhea, mild upper respiratory infection with or without low-grade fever, or other low-grade febrile illness.

Patients receiving immunosuppressive therapy. This contraindication does not apply to patients who are receiving corticosteroids as replacement therapy, e.g., for Addison's disease.

Individuals with blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems.

Primary and acquired immunodeficiency states, including patients who are immunosuppressed in association with AIDS or other clinical manifestations of infection with human immunodeficiency viruses; cellular immune deficiencies; and hypogammaglobulinemic and dysgammaglobulinemic states. Measles inclusion body encephalitis (MIBE), pneumonitis and death as a direct consequence of disseminated measles vaccine virus infection has been reported in immunocompromised individuals inadvertently vaccinated with measles-containing vaccine.

Individuals with a family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated.

General

Adequate treatment provisions including epinephrine injection (1:1000), should be available for immediate use should an anaphylactic or anaphylactoid reaction occur.

Special care should be taken to ensure that the injection does not enter a blood vessel.

Children and young adults who are known to be infected with human immunodeficiency viruses and are not immunosuppressed may be vaccinated. However, vaccinees who are infected with HIV should be monitored closely for vaccine-preventable diseases because immunization may be less effective than for uninfected persons (see CONTRAINDICATIONS ).

Vaccination should be deferred for 3 months or longer following blood or plasma transfusions, or administration of immune globulin (human).

There are no reports of transmission of live attenuated measles virus from vaccinees to susceptible contacts.

It has been reported that attenuated measles virus vaccine live may result in a temporary depression of tuberculin skin sensitivity. Therefore, if a tuberculin test is to be done, it should be administered either before or simultaneously with ATTENUVAX.

Children under treatment for tuberculosis have not experienced exacerbation of the disease when immunized with live measels virus vaccine; no studies have been reported to date of the effect of measles virus vaccines on untreated tuberculous children. However, individuals with active untreated tuberculosis should not be vaccinated.

As for any vaccine, vaccination with ATTENUVAX may not result in protection in 100% of vaccinees.

The health-care provider should determine the current health status and previous vaccination history of the vaccinee.

The health-care provider should question the patient, parent, or guardian about reactions to a previous dose of ATTENUVAX or other measles-containing vaccines.

Drug Interactions

See DOSAGE AND ADMINISTRATION , Use With Other Vaccines .

Information For Patients

The health-care provider should provide the vaccine information required to be given with each vaccination to the patient, parent or guardian.

The health-care provider should inform the patient, parent or guardian of the benefits and risks associated with vaccination. For risks associated with vaccination see WARNINGS , PRECAUTIONS , ADVERSE REACTIONS .

Patients, parents or guardians should be instructed to report any serious adverse reactions to their health-care provider who in turn should report such events to the U.S. Department of Health and Human Services through the Vaccine Adverse Event Reporting System (VAERS), 1-800-822-7967.

Pregnancy should be avoided for 3 months following vaccination, and patients should be informed of the reasons for this precaution (see CONTRAINDICATIONS and PRECAUTIONS , Pregnancy ).

Immunosuppressive Therapy

The immune status of patients about to undergo immunosuppressive therapy should be evaluated so that the physician can consider whether vaccination prior to the initiation of treatment is indicated (see CONTRAINDICATIONS and PRECAUTIONS ).

The ACIP has stated that "patients with leukemia in remission who have not received chemotherapy for at least 3 months may receive live-virus vaccines. Short-term (<2 weeks), low- to moderate-dose systemic corticosteroid therapy, topical steroid therapy (e.g., nasal, skin), long-term alternate-day treatment with low to moderate doses of short-acting systemic steroid, and intra-articular, bursal, or tendon injection of corticosteroids are not immunosuppressive in their usual doses and do not contraindicate the administration of measles vaccine."

Immune Globulin

Administration of immune globulins concurrently with ATTENUVAX may interfere with the expected immune response.

See also PRECAUTIONS , General .

Carcinogenesis, Mutagenesis, Impairment of Fertility

ATTENUVAX has not been evaluated for carcinogenic or mutagenic potential, or potential to impair fertility.

Pregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with ATTENUVAX. It is also not known whether ATTENUVAX can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Therefore, the vaccine should not be administered to pregnant females; furthermore, pregnancy should be avoided for 3 months following vaccination (see CONTRAINDICATIONS ).

In counseling women who are inadvertently vaccinated when pregnant or who become pregnant within 3 months of vaccination, the physician should be aware that reports have indicated that contracting natural measles during pregnancy enhances fetal risk. Increased rates of spontaneous abortion, stillbirth, congenital defects and prematurity have been observed subsequent to natural measles during pregnancy. There are no adequate studies of the attenuated (vaccine) strain of measles virus in pregnancy. However, it would be prudent to assume that the vaccine strain of virus is also capable of inducing adverse fetal effects.

Nursing Mothers

It is not known whether measles vaccine virus is secreted in human milk. Therefore, because many drugs are excreted in human milk, caution should be exercised when ATTENUVAX is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in infants below the age of 6 months have not been established (see also CLINICAL PHARMACOLOGY ).

Geriatric Use

Clinical studies of ATTENUVAX did not include sufficient numbers of seronegative subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects.

The following adverse reactions are listed in decreasing order of severity, without regard to causality, within each body system category and have been reported during clinical trials, with use of the marketed vaccine, or with use of polyvalent vaccine containing measles:

Body as a Whole

Panniculitis; atypical measles; fever; syncope; headache; dizziness; malaise; irritability.

Cardiovascular System

Vasculitis.

Digestive System

Diarrhea.

Hemic and Lymphatic System

Thrombocytopenia (see WARNINGS , Thrombocytopenia ); purpura; lymphadenopathy; leukocytosis.

Immune System

Anaphylaxis and anaphylactoid reactions have been reported as well as related phenomena such as angioneurotic edema (including peripheral or facial edema) and bronchial spasm in individuals with or without an allergic history.

Nervous System

Encephalitis; encephalopathy; measles inclusion body encephalitis (MIBE) (see CONTRAINDICATIONS ); subacute sclerosing panencephalitis (SSPE); Guillain-Barré Syndrome (GBS); febrile convulsions; afebrile convulsions or seizures; ataxia; ocular palsies.

Experience from more than 80 million doses of all live measles vaccines given in the U.S. through 1975 indicates that significant central nervous system reactions such as encephalitis and encephalopathy, occurring within 30 days after vaccination, have been temporally associated with measles vaccine very rarely. In no case has it been shown that reactions were actually caused by vaccine. The Centers for Disease Control and Prevention has pointed out that "a certain number of cases of encephalitis may be expected to occur in a large childhood population in a defined period of time even when no vaccines are administered". However, the data suggest the possibility that some of these cases may have been caused by measles vaccines. The risk of such serious neurological disorders following live measles virus vaccine administration remains far less than that for encephalitis and encephalopathy with natural measles (one per two thousand reported cases).

Post-marketing surveillance of the more than 200 million doses of M-M-R and M-M-R II that have been distributed worldwide over 25 years (1971-1996) indicates that serious adverse events such as encephalitis and encephalopathy continue to be rarely reported.

There have been reports of subacute sclerosing panencephalitis (SSPE) in children who did not have a history of natural measles but did receive measles vaccine. Some of these cases may have resulted from unrecognized measles in the first year of life or possibly from the measles vaccination. Based on estimated nationwide measles vaccine distribution, the association of SSPE cases to measles vaccination is about one case per million vaccine doses distributed. This is far less than the association with natural measles, 6-22 cases of SSPE per million cases of measles. The results of a retrospective case-controlled study conducted by the Centers for Disease Control and Prevention suggest that the overall effect of measles vaccine has been to protect against SSPE by preventing measles with its inherent higher risk of SSPE.

Respiratory System

Pneumonitis (see CONTRAINDICATIONS ); cough; rhinitis.

Skin

Stevens-Johnson Syndrome; erythema multiforme; urticaria; rash.

Local reactions including burning/stinging at injection site; wheal and flare; redness (erythema); swelling; vesiculation at injection site.

Special Senses--Ear

Nerve deafness; otitis media.

Special Senses--Eye

Retinitis; optic neuritis; papillitis; retrobulbar neuritis; conjunctivitis.

Other

Death from various, and in some cases unknown, causes has been reported rarely following vaccination with measles, mumps, and rubella vaccines; however, a causal relationship has not been established. No deaths or permanent sequelae were reported in a published post-marketing surveillance study in Finland involving 1.5 million children and adults who were vaccinated with M-M-R II during 1982-1993.

Under the National Childhood Vaccine Injury Act of 1986, health-care providers and manufacturers are required to record and report certain suspected adverse events occurring within specific time periods after vaccination. However, the U.S. Department of Health and Human Services (DHHS) has established a Vaccine Adverse Event Reporting System (VAERS) which will accept all reports of suspected events. A VAERS report form as well as information regarding reporting requirements can be obtained by calling VAERS 1-800-822-7967.

No. 4709--ATTENUVAX is supplied as a single-dose vial of lyophilized vaccine, NDC 0006-4709-00, and a vial of diluent.

No. 4589X/4309--ATTENUVAX is supplied as follows: (1) a box of 10 single-dose vials of lyophilized vaccine (package A), NDC 0006-4589-00; and (2) a box of 10 vials of diluent (package B). To conserve refrigerator space, the diluent may be stored separately at room temperature.

Storage

During shipment, to ensure that there is no loss of potency, the vaccine must be maintained at a temperature of 10°C (50°F) or colder. Freezing during shipment will not affect potency.

Protect the vaccine from light at all times, since such exposure may inactivate the virus.

Before reconstitution, store the vial of lyophilized vaccine at 2-8°C (36-46°F) or colder. The diluent may be stored in the refrigerator with the lyophilized vaccine or separately at room temperature.

It is recommended that the vaccine be used as soon as possible after reconstitution. Store reconstituted vaccine in the vaccine vial in a dark place at 2-8°C (36-46°F) and discard if not used within 8 hours.

                         9243205  Issued September 2002

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