Measles Virus Vaccine

Measles Virus Vaccine, Live Attenuated (Dried)

Connaught

Vaccine

Action And Clinical Pharmacology: Measles Virus Vaccine, Live, Attenuated (Dried) is prepared in avian leucosis-free chick embryo fibroblast cultures from the Edmondston Strain of attenuated measles virus, obtained from Dr. J.F. Enders and given an additional 69 passages in chick embryo cell cultures. The diluent for reconstitution for the 1 dose vial is Water for Injection (WFI). The diluent for reconstitution for the 10 dose vial is Phosphate Buffered Saline with 40 to 70 ppm Tween 80.

The clinical trial of Measles Virus Vaccine, Live, Attenuated (Dried) involved 5 lots of vaccine and was administered to 378 individuals between 11 to 17 months of age. Serologic response 4 weeks following vaccination equal to or greater than 1:8 by hemagglutination-inhibition test (method I) was demonstrated in 99% of the 374 vaccinees for whom serum samples were available and in 97% by virus neutralization test (method II).

The serum sero-conversion rate for individual vaccine lots ranged from 98 to 100% by test method I and from 92 to 100% by test method II. The overall geometric mean-titre was 36.0 by test method I, with the titre ranging from 31.2 to 39.8 for the individual lots. The overall geometric mean-titre was 21.8 by test method II, with the titre ranging from 16.9 to 27.0 for individual vaccine lots.

Similar results were obtained in a previous clinical trial of 1 142 vaccinees of whom 98% demonstrated post-vaccine serologic response equal to or greater than 1:8 by hemagglutination-inhibition test.

Indications And Clinical Uses: For the active immunization of children against measles (rubeola). It does not protect against German measles (rubella).

This vaccine is recommended routinely for all children at, or as soon as practicable after, their first birthday. If a goal of measles elimination is adopted, a second dose of measles vaccine is required. It is given at 4 to 6 years of age. The minimum interval between the 2 doses should be at least 1 month.

Measles vaccine is also recommended for children and adolescents who have never had documented measles or who have received live attenuated vaccine before the age of 12 months and for persons of any age known to be seronegative. Routine primary immunization of adults born prior to 1957 is not usually necessary because they are very likely to have acquired immunity by natural infection.

Children, who, in accordance with previous recommendations, received vaccine prior to 1 year of age, or who were given a dose of further attenuated vaccine accompanied by immune globulin, human, may not be fully protected. It is recommended that such children be revaccinated with live measles vaccine.

Despite the risk of local reaction (see Adverse Effects), persons who have previously been given inactivated vaccine alone or followed by live vaccine within 3 months should be revaccinated with live vaccine to avoid the severe atypical form of natural measles that may occur.

Contra-Indications: Immunization with Measles Virus Vaccine, Live, Attenuated (Dried) should be deferred in the presence of any acute illness, including febrile illness. Minor illness, such as the common cold, are very prevalent in children and are not contraindications to immunization; however, febrile illness is a reason to defer immunization.

Allergic reaction to any component of Measles Virus Vaccine, Live, Attenuated (Dried) is a contraindication to vaccination.

Elective immunization should be deferred during an outbreak of poliomyelitis.

Measles Virus Vaccine, Live, Attenuated (Dried) should not be administered to any individual whose immune mechanism is impaired as the result of disease, injury, or therapy including the following: (a) individuals with blood dyscrasias, lymphomas, or other generalized malignancies, (b) individuals undergoing treatment with immunosuppressive agents of any kind or with primary immunodeficiency, e.g. agammaglobulinemia, dysgammaglobulinemia, hypogammaglobulinemia.

Pregnancy: Measles Virus Vaccine, Live, Attenuated (Dried) should not be administered to pregnant women, since the possible effect of attenuated measles virus on the fetus is not known.

If a measles-susceptible woman is exposed to measles during pregnancy, one should consider the possibility of providing temporary passive immunity through the administration of immune globulin, human.

Human Immunodeficiency Virus (HIV) Infected Persons: Measles Virus Vaccine, Live, Attenuated, (Dried) is recommended for asymptomatic and symptomatic HIV-infected children since no increased incidence or severity of adverse events has been observed following vaccination of such children, and severe disease and fatalities have been associated with natural infection. Because the immune response may be impaired, such children should receive IG following recognized exposures to measles, HIV-infected infants who are receiving IGIV prophylaxis are unlikely to respond to Measles Virus Vaccine and, therefore, vaccine need not be administered.

Manufacturers' Warnings In Clinical States: If Measles Virus Vaccine, Live, Attenuated (Dried) is used in persons with malignancies, receiving immunosuppressive therapy, or who are otherwise immunocompromised, the expected immune response may not be obtained.

As with any vaccine, vaccination with Measles Virus Vaccine, Live Attenuated (Dried) may not protect 100% of susceptible individuals.

Precautions: Live measles vaccine is grown in chick fibroblast cultures and not in eggs. Egg albumin and yolk components are absent from these cultures. Hypersensitivity reactions very rarely follow the administration of live measles vaccine. Most of these reactions are considered minor and consist of wheal and flare or urticaria at the injection site. With over 190 million doses of measles vaccine distributed in the USA, there have been less than 10 reported cases of immediate severe allergic reactions in children who had histories of anaphylactoid reactions to egg ingestion. Extreme caution should be exercised if the vaccine is administered to persons with a history of anaphylactoid reactions subsequent to egg ingestion. Egg allergies which are not anaphylactoid in nature and allergies to chicken and feathers do not appear to constitute an increased risk of reaction to the vaccine. The attending physician must weigh the benefits of immunization against the potential risks of hypersensitivity reactions.

General: The possibility of allergic reactions in individuals sensitive to components of the vaccine should be evaluated. Epinephrine HCl solution (1:1 000) should be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs.

Prior to an injection of any vaccine, all known precautions should be taken to prevent adverse reactions. This includes a review of the patient's history with respect to possible hypersensitivity to the vaccine or similar vaccine.

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

A separate, sterile syringe and needle or a sterile disposable unit should be used for each individual patient to prevent transmission of hepatitis or other infectious agents from one person to another. Do not recap needles after vaccine administration.

Administer the vaccine s.c., do not administer i.v.

Children: The vaccine should be given with caution to children with a history of febrile convulsions.

Drug Interactions: Administration of the vaccine should be deferred at least 3 months after administration of human immune globulin, plasma or whole blood. If repeated or large amounts of these substances have been given, a longer interval should be allowed.

Administration of attenuated live-virus measles vaccine may temporarily depress tuberculin skin sensitivity. Therefore, if a tuberculin test is to be done, it should be scheduled before administering measles vaccine or on the day of vaccination with reading 48 to 72 hours later. Otherwise, it should be postponed for 4 to 6 weeks. This avoids the possibility of a false-negative response. Although tuberculosis may be exacerbated by natural measles infection, there is no evidence that measles vaccine has such effect.

One live vaccine may interfere with the effectiveness of another, and to minimize this possibility, 2 or more live vaccines should preferably be administered at different sites with separate syringes either on the same day or be separated by an interval of at least 1 month. Simultaneous administration of Measles Virus Vaccine, Live, Attenuated (Dried) and inactivated vaccines may be performed provided the vaccines are administered separately and at different sites with separate syringes with observance of the precautions that apply to the individual vaccines.

Adverse Reactions: Local erythema and/or swelling around the site of injection are not uncommon and regional lymphadenopathy may occur rarely.

Fever or mild rash, or both, may occur 5 to 12 days after administration of Measles Virus Vaccine, Live, Attenuated (Dried). Based on clinical trials, the febrile response would be expected to be mild, £37.7°C in 48-57%, moderate 37.8-39.4°C in 39-47% and high >39.4°C in 4-5% of recipients. With high temperatures the possibility of development of convulsions is present.

Rash may occur in 12 to 16% of vaccinees and is usually minimal.

Reactions which may be temporally associated with administration of measles vaccine such as encephalitis and encephalopathy have been reported to occur approximately once per million doses. Following natural measles infections, the incidence of such neurological disorders is approximately one per thousand reported cases.

There have been reports of subacute sclerosing panencephalitis (SSPE) in individuals who have no history of measles but who have received measles vaccine. However, studies have shown that the incidence of SSPE in measles vaccine recipients (about one case per million doses of vaccine distributed) is significantly less than the 5 to 10 SSPE cases per million cases of natural measles. It would appear that measles vaccine significantly reduces the chance of developing SSPE by protecting against measles.

Local reactions characterized by marked swelling, redness and vesiculation at the injection site of attenuated live virus measles vaccines have occurred in children who have previously received killed measles vaccine.

On rare occasions, more severe reactions have been reported. These included prolonged high fevers and extensive local reactions which required hospitalization.

Health care providers should report any adverse occurrences temporally related to the administration of the product in accordance with local requirements and report to the Medical Director at Connaught Laboratories Limited, 1755 Steeles Avenue West, Toronto, Ontario, Canada, M2R 3T4.

Dosage And Administration: One dose of 0.5 mL of Measles Virus Vaccine, Live, Attenuated (Dried) s.c., at 12 months of age, or as soon as possible thereafter. If a goal of measles elimination is adopted, a second dose of 0.5 mL Measles Virus Vaccine is required. It is given at 4 to 6 years of age. The minimum interval between the 2 doses should be at least 1 month.

Parenteral biological products should be inspected visually prior to and following vaccine reconstitution for extraneous particulate matter and/or discoloration prior to administration. If these conditions exist, vaccine should not be administered.

The vaccine should be administered by s.c. injection which may conveniently be made near the insertion of the deltoid muscle. The vaccine must not be injected i.v. The site of the injection should be prepared with a suitable antiseptic.

Caution: A new sterile plastic disposable syringe should be used for each injection of the vaccine because certain preservatives, antiseptics and detergents will inactivate the live measles virus in the vaccine (see Precautions).

Withdrawing the Sterile Diluent from a Sealed Glass Ampul: Tap the ampul to ensure that the diluent is in the lower portion rather than the neck of the ampul. Wipe the neck of the ampul with a suitable antiseptic. Using a sterile piece of cotton or a sterile towel, break off the top of the ampul at the scored line (no file is required). Then with a sterile syringe and needle withdraw the required volume (see Reconstitution) of sterile diluent from the ampul, holding the syringe in such a way that the point is kept immersed throughout the withdrawal.

Withdrawing the Sterile Diluent from a Rubber-Stoppered Vial: Do not remove the rubber stopper from the vial.

Apply a sterile piece of cotton moistened with a suitable antiseptic to the surface of the rubber stopper of the vial of sterile diluent and allow to dry. Then with a sterile syringe pierce the centre of the rubber stopper, invert the vial, slowly inject into it the air contained in the syringe, and, keeping the point of the needle immersed, withdraw into the syringe 0.6 mL of sterile diluent. Then holding the syringe-plunger steady, withdraw the needle from the vial.

Reconstitution of Freeze-Dried Vaccine: Do not remove the rubber stopper from the vial.

Apply a sterile piece of cotton with a suitable antiseptic to the surface of the rubber stopper of the vial of vaccine. Holding the plunger of the syringe containing the diluent, pierce the centre of the rubber stopper in the vial and inject the required volume of sterile diluent into the freeze-dried vaccine. Do not try to force all of the diluent into the vial at once as this will create pressure. It is necessary to gradually allow air to escape into the syringe by intermittently aspirating air from the vial while injecting the diluent into the vial. Do not remove the needle from the stopper until the required volume of diluent has been injected. The required volume for reconstitution is 0.6 mL for the single dose vial and 6 mL for the 10 dose vial. Shake the vial gently until a fine, even suspension results. Avoid foaming since this will prevent withdrawal of the proper dose. Withdraw the required dose (0.5 mL) of the reconstituted vaccine into the syringe.

Carefully insert the needle into the subcutaneous tissue. In order to avoid i.v. injection, pull back on the plunger of the syringe to make certain that no blood is withdrawn before injecting the vaccine.

The vaccine should be used immediately after reconstitution and any reconstituted vaccine not used within 8 hours must be discarded.

Availability And Storage: 1 single dose vial of vaccine with 1 vial or ampul of 0.6 mL sterile diluent for the reconstitution of a single dose and in a 10 dose vial of vaccine with 1 ampul of 6 mL sterile diluent for the reconstitution of 10 doses.

The vaccine is freeze-dried in single and multidose vials. Each dose contains not less than 1 000 TCID50 of measles virus.

The freeze-dried vaccine and sterile diluent should be stored and transported between 2 and 8°C. Do not freeze. Reconstituted vaccine must be protected from light and maintained at 2 to 8°C.