Synagis

Palivizumab injection comes as a liquid to be injected into the muscles of the thigh by a doctor or nurse. The first dose of palivizumab injection is usually given before the beginning of RSV season, followed by a dose every 28 to 30 days throughout RSV season. RSV season usually starts in the fall and continues through spring (November through April ) in most parts of the United States but may be different where you live. Talk to your doctor about how many shots your child will need and when they will be given.

If your child has surgery for certain types of heart disease, your healthcare provider may need to give your child an additional dose of palivizumab injection soon after surgery, even if it has been less than 1 month from the last dose.

Your child may still get severe RSV disease after receiving palivizumab injection. Talk to your child's healthcare provider about the symptoms of RSV disease. If your child has an RSV infection, he should still continue to receive his scheduled palivizumab injections to help prevent serious disease from new RSV infections.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

• Synagis^®

Before using palivizumab, tell your child's doctor or pharmacist if your child is allergic to it; or to mouse proteins; or if your child has any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Tell the doctor your child's medical history, especially of: bleeding/blood clotting problems (e.g., thrombocytopenia, coagulation disorder), recent heart bypass surgery.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: "blood thinners" (e.g., warfarin, heparins).This medication may interfere with certain laboratory tests (including RSV diagnostic tests, virus culture tests), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

Get emergency medical help if your child has any of these signs of an allergic reaction: hives; difficult breathing; swelling of the face, lips, tongue, or throat.

Call your doctor at once if your child has a serious side effect such as:

• high fever, ear pain or drainage, tugging at the ear;
• warmth or swelling of the ear;
• crying or fussiness, especially while lying down;
• change in sleeping patterns;
• poor feeding or loss of appetite;
• easy bruising or bleeding; or
• trouble breathing.

Less serious side effects may include:

• low fever;
• cold symptoms such as stuffy nose, sneezing, cough;
• vomiting, diarrhea; or
• pain, redness, or swelling where the shot was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

• Respiratory Syncytial Virus

Synagis is a prescription medication used to help prevent a serious lung disease caused by Respiratory Syncytial Virus (RSV) in children younger than 24 months of age (at the start of dosing). Synagis belongs to a group of drugs called monoclonal antibodies which work by preventing the virus from replicating.

This medication comes in an injectable form to be given once a month for several months.

Common side effects include fever, rash, and redness or swelling at the injection site.

Tell your child’s healthcare provider about:

• any reactions you believe your child has ever had to Synagisis.
• any bleeding or bruising problems. Synagisis is given by injection. If your child has a problem with bleeding or bruises easily, an injection could cause a problem.
• any other medical problems.

Tell your child’s healthcare provider about all the medicines your child takes, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your child’s healthcare provider if your child takes a blood thinner medicine.

Antiviral; biosynthetic humanized form of a murine monoclonal antibody to the F surface glycoprotein of respiratory syncytial virus (RSV).1 2 3 4 5 6 7 8 50

Formal studies have not been conducted to evaluate potential interactions between palivizumab and other drugs.1

Specific Drugs

Drug	Interaction
Bronchodilators	Not specifically studied, but no apparent increase in adverse effects when used concomitantly1
Corticosteroids	Not specifically studied, but no apparent increase in adverse effects when used concomitantly1
Vaccines	No evidence that palivizumab interferes with the immune response to vaccines;1 8 no apparent increase in adverse effects when given concomitantly with routine childhood vaccines1

Palivizumab injection is used to prevent serious lung infection in children and babies caused by respiratory syncytial virus (RSV). It belongs to a group of medicines known as immunizing agents. This medicine works by giving your body antibodies to protect it against RSV infection.

RSV infection can cause serious problems that affect the lungs, such as pneumonia and bronchitis, and in severe cases can even cause death. These problems are more likely to occur in infants and children younger than 6 months of age with chronic lung disease and breathing problems. Babies who were born premature or babies who were born with heart disease may also have problems with RSV.

The onset of RSV activity usually occurs in November and continues through April, but it may begin earlier or continue later in certain communities. A good way to help prevent RSV infection is to receive palivizumab before the start of the RSV season.

This medicine is to be given only by or under the direct supervision of your doctor.

 Dosing Information

The recommended dose of Synagis is 15 mg per kg of body weight given monthly by intramuscular injection. The first dose of Synagis should be administered prior to commencement of the RSV season and the remaining doses should be administered monthly throughout the RSV season. Children who develop an RSV infection should continue to receive monthly doses throughout the RSV season. In the northern hemisphere, the RSV season typically commences in November and lasts through April, but it may begin earlier or persist later in certain communities.

Synagis serum levels are decreased after cardio-pulmonary bypass [see Clinical Pharmacology (12.3)]. Children undergoing cardio-pulmonary bypass should receive an additional dose of Synagis as soon as possible after the cardio-pulmonary bypass procedure (even if sooner than a month from the previous dose). Thereafter, doses should be administered monthly as scheduled.

The efficacy of Synagis at doses less than 15 mg per kg, or of dosing less frequently than monthly throughout the RSV season, has not been established.

Administration Instructions

• DO NOT DILUTE THE PRODUCT.
• DO NOT SHAKE OR VIGOROUSLY AGITATE THE VIAL.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use any vials exhibiting particulate matter or discoloration.
• Using aseptic techniques, attach a sterile needle to a sterile syringe. Remove the flip top from the Synagis vial and wipe the rubber stopper with a disinfectant (e.g., 70% isopropyl alcohol). Insert the needle into the vial and withdraw into the syringe an appropriate volume of solution. Administer immediately after drawing the dose into the syringe.
• Synagis should be administered in a dose of 15 mg per kg intramuscularly using aseptic technique, preferably in the anterolateral aspect of the thigh. The gluteal muscle should not be used routinely as an injection site because of the risk of damage to the sciatic nerve. The dose (volume of injection in mL) per month = patient weight (kg) x 15 mg per kg ÷ 100 mg per mL of Synagis. Injection volumes over 1 mL should be given as a divided dose.
• Synagis is supplied as a single-dose vial and does not contain preservatives. Do not re-enter the vial after withdrawal of drug; discard unused portion. Only administer one dose per vial.
• Use sterile disposable syringes and needles. To prevent the transmission of hepatitis viruses or other infectious agents from one person to another, DO NOT reuse syringes and needles.

Synagis is contraindicated in children who have had a previous significant hypersensitivity reaction to Synagis [see Warnings and Precautions (5.1)].

The most serious adverse reactions occurring with Synagis are anaphylaxis and other acute hypersensitivity reactions [see Warnings and Precautions (5.1)].

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to Synagis (n=1639) compared with placebo (n=1143) in children 3 days to 24.1 months of age at high risk of RSV-related hospitalization in two clinical trials. Trial 1 was conducted during a single RSV season and studied a total of 1502 children less than or equal to 24 months of age with BPD or infants with premature birth (less than or equal to 35 weeks gestation) who were less than or equal to 6 months of age at study entry. Trial 2 was conducted over four consecutive seasons among a total of 1287 children less than or equal to 24 months of age with hemodynamically significant congenital heart disease.

In Trials 1 and 2 combined, fever and rash were each reported more frequently among Synagis than placebo recipients, 27% versus 25%, and 12% versus 10%, respectively. Adverse reactions observed in the 153-patient crossover study comparing the liquid and lyophilized formulations were comparable for the two formulations, and were similar to those observed with Synagis in Trials 1 and 2.

Immunogenicity

In Trial 1, the incidence of anti-palivizumab antibody following the fourth injection was 1.1% in the placebo group and 0.7% in the Synagis group. In children receiving Synagis for a second season, one of the fifty-six children had transient, low titer reactivity. This reactivity was not associated with adverse events or alteration in serum concentrations. Immunogenicity was not assessed in Trial 2.

A trial of high-risk preterm children less than or equal to 24 months of age was conducted to evaluate the immunogenicity of the lyophilized formulation of Synagis (used in Trials 1 and 2 above) and the liquid formulation of Synagis. Three hundred seventy-nine children contributed to the 4 to 6 months post-final dose analysis. The rate of anti-palivizumab antibodies at this time point was low in both formulation groups (anti-palivizumab antibodies were not detected in any subject in the liquid formulation group and were detected in one subject in the lyophilized group (0.5%), with an overall rate of 0.3% for both treatment groups combined).

These data reflect the percentage of children whose test results were considered positive for antibodies to palivizumab in an enzyme-linked immunosorbent assay (ELISA) and are highly dependent on the sensitivity and specificity of the assay.

The ELISA has substantial limitations in detecting anti-palivizumab antibodies in the presence of palivizumab. Immunogenicity samples tested with the ELISA assay likely contained palivizumab at levels that may interfere with the detection of anti-palivizumab antibodies.

An electrochemical luminescence (ECL) based immunogenicity assay, with a higher tolerance for palivizumab presence compared to the ELISA, was used to evaluate the presence of anti-palivizumab antibodies in subject samples from two additional clinical trials. The rates of anti-palivizumab antibody positive results in these trials were 1.1% and 1.5%.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Synagis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System Disorders: severe thrombocytopenia (platelet count less than 50,000 per microliter)

General Disorders and Administration Site Conditions: injection site reactions

Limited information from post-marketing reports suggests that, within a single RSV season, adverse events after a sixth or greater dose of Synagis are similar in character and frequency to those after the initial five doses.

Synagis should not be given to a child who has had a severe allergic reaction to palivizumab.

To make sure Synagis is safe for your child, tell your doctor if the child has ever had:

• a bleeding or blood clotting disorder; or

• low levels of platelets in the blood.