Palivizumab - Mechanism of Action, Indications, Dosage, and Adverse Drug Reactions

Overview:

Palivizumab is a synthetic antibody that protects against the respiratory syncytial virus (RSV), which can cause severe sickness in children. It is used to prevent lung illness in premature newborns as well as in those born with specific lung or cardiac abnormalities. It is most effective in children aged 24 months or younger at the onset of the RSV season. Palivizumab inhibits RSV cell replication in the body, thus offering passive protection against RSV infection. During the RSV season, healthcare providers inject it into a muscle once a month, protecting the child for around one month. It should not be administered to a child who has experienced a serious allergic response. Fever and redness are common side effects. Consult a healthcare provider for medical guidance on probable side effects and appropriate dosage. The Food and Drug Administration (FDA) of the United States authorized it in 1998.

Drug Group:

Palivizumab is a monoclonal antibody drug that prevents virus replication, belonging to the class of immunoglobulins. Immunoglobulins enhance the body's immune system, reducing infection risk in weakened individuals derived from healthy human blood with high levels of protective antibodies.

Indications:

Palivizumab is a monoclonal antibody that inhibits the F (fusion) protein of the respiratory syncytial virus (RSV) and is intended to prevent severe lower respiratory tract disease triggered by RSV in children at significant risk of RSV disease.

• In children with bronchopulmonary dysplasia (BPD) (a type of chronic lung illness affecting newborns, many of whom are premature and require oxygen therapy), newborns with a history of premature birth (less than or equal to 35 weeks gestational age), and children with hemodynamically severe congenital heart disease (CHD) (abnormalities in the heart's structure at birth, caused by incorrect utero formation of the heart or blood vessels), efficacy and safety were proven.

• Palivizumab's safety and efficacy in treating RSV infection have not been proven.

Contraindications:

Palivizumab is contraindicated in those with prior severe allergic reactions to Palivizumab.

Dosage Forms and Available Strengths:

Palivizumab is a single-dose liquid solution comprising 50 mg(milligrams) per 0.5 mL (milliliter) and 100 mg/mL, and 15mg/kg (milligrams per kilogram) of body weight is indicated for children with RSV infections, administered monthly intramuscularly. The first dose should be provided before the start of the RSV season, and the following doses should be administered monthly throughout. Palivizumab should be given to children who have undergone cardiopulmonary bypass (a surgical procedure where a machine temporarily replaces the heart and lungs, ensuring the body's blood and oxygen circulation) as soon as feasible following the procedure and then monthly after that. Palivizumab's efficacy at dosages less than 15 mg/kg or less frequently than monthly during the RSV season has not been shown.

For Patients

What Is Respiratory Syncytial Virus Infection?

Respiratory syncytial virus (RSV) is a common respiratory virus that causes mild, cold-like symptoms, with most people recovering in a week or two. The severity of RSV infection is determined by the infected person's age, health, and how the virus enters the body through the eyes, nose, or mouth. It spreads through infectious droplets, coughing or sneezing, or direct contact with an infected individual. Children under the age of two, premature infants, children with weakened immune systems, children in overcrowded childcare facilities, and individuals with asthma (a chronic lung disease affecting all ages, characterized by inflammation and muscle tightening around the airways, making breathing difficult.) or other lung and heart disorders, and people with weakened immune systems are particularly vulnerable. Severe cases, especially in kids with short Eustachian tubes, can result in pneumonia (a severe lung infection caused by bacteria, viruses, or fungi, resulting in the air sacs containing pus and other fluids.), bronchitis (a lung infection characterized by inflammation of bronchial tubes, leading to coughing and mucus production.), and middle ear infections. RSV prevention involves restricting contact with infants and cleaning hands while handling the newborn.

How Does Palivizumab Work?

Palivizumab is a monoclonal antibody that attaches to the surface of the RSV fusion protein A. This protein inhibits the virus from entering cells in the body, particularly those in the lungs, hence avoiding RSV infection. Palivizumab binds to and deactivates the fusion (F) glycoprotein on the surface of RSV, a membrane protein responsible for fusing the virus with its target cell. This mechanism aids the immune system in slowing or stopping the spread of the virus in the body. Palivizumab, used in injections, is greatly conserved among RSV subgroups.

What Are the Clinical Uses of Palivizumab?

Palivizumab is a drug used in high-risk pediatric patients to prevent serious lower respiratory tract infections caused by respiratory syncytial virus (RSV). In these high-risk patients, it may minimize the severity of RSV infection and hospitalizations. Premature newborns, infants with a history of bronchopulmonary dysplasia (a type of chronic lung illness affecting newborns, many of whom are premature and require oxygen therapy), and infants with hemodynamically significant congenital heart disease are all suitable for the medication. However, It is not intended for adults or immunocompromised children and does not treat active RSV infection.

How Is Palivizumab Administered?

Follow the appropriate aseptic technique for the administration of Palivizumab as follows:

• Palivizumab is an antiviral medicine injected intramuscularly (IM), preferably in the anterolateral part of the thigh, by a doctor or nurse.

• During expected periods of RSV risk in the community, providing 15 mg/kg of body weight is recommended once a month. The first dose should be delivered prior to the onset of the RSV season, with further doses administered monthly throughout the season.

• In the northern hemisphere, the RSV season typically begins in November and lasts until April, but it may begin earlier or continue longer in certain regions. Children who contract RSV should continue to receive monthly dosages throughout the season.

• It is critical to discuss with the doctor the amount of injections the kid will require and when the shots will be administered. If the child has undergone surgery for certain heart conditions, an additional dose may be required shortly after. To avoid serious sickness from new infections, it is critical to address the symptoms of RSV disease with a healthcare professional.

What Are the Side Effects of Palivizumab?

Palivizumab may have certain unintended consequences in addition to its beneficial advantages. Although not all of these adverse effects are possible, if any of these effects occur, they may necessitate medical treatment.

If any of the following side effects develop while taking Palivizumab, contact the doctor or nurse right away:

More common side effects are

• The color of the fingernails, lips, skin, palms, or nail beds is bluish.

• Blurred vision.

• Confusion.

• Cough.

• Breathing difficulties.

• Swallowing difficulties.

• Dizziness, faintness, or lightheadedness upon abruptly rising from a sleeping or seated posture.

• Rapid heartbeat.

• Fever.

• Welts or hives.

• Breathing that is uneven, rapid, slow, or shallow.

• Itching.

• Hive-like swelling of the face, eyes, lips, tongue, throat, hands, legs, feet, or genital organs.

• Strength or energy loss.

• Discomfort or weakening of the muscles.

• Redness of the skin

• A rash on the skin.

• Sweating.

• Chest constriction.

• Unresponsiveness.

• Unexpected exhaustion or weakness.

• Wheezing.

The occurrence is unknown.

• The stools are black and tarry.

• Gums are bleeding.

• Blood in the pee or feces.

• The skin has little red patches.

• Bruising or bleeding is rare.

Palivizumab could trigger side effects that do not necessitate medical attention and may resolve on its own throughout treatment. Consult the doctor if any of these symptoms persist or become bothersome.

What Are the Things to Inform the Doctor Before Taking Palivizumab?

Here are some essential things to inform the doctor before starting Palivizumab treatment:

• Inform the pediatrician and pharmacist if the child is allergic to Palivizumab, any other drugs, or any ingredients in the Palivizumab injection. Request a list of the components from the pharmacist.

• Inform the pharmacist and doctor about any additional prescription and over-the-counter (OTC) drugs, vitamins, nutritional supplements, and herbal products the child intends to take. Make sure to mention anticoagulants (sometimes known as blood thinners). The doctor may need to adjust the child's medication dosages or closely watch for negative effects.

• Inform the doctor if the child has a low platelet count or has ever had a bleeding disorder.

• If the child is undergoing dental surgery, inform the doctor or dentist that the child receives a Palivizumab injection.

Dietary Considerations: None

Missed Dose:

Contact the doctor immediately if the child fails to appear for a Palivizumab injection appointment.

Overdose:

In an overdose, seek emergency medical attention or call the Poison helpline. If the victim collapses, experiences a seizure (a spike in uncontrolled electrical activity between brain cells can induce transitory changes in muscle tone, movements, behaviors, sensations, or awareness states.), struggles with breathing, or cannot be awakened, immediately contact emergency services.

Storage:

Palivizumab should be kept in its original container between 2 and 8 degrees Celsius (36 and 46 degrees Fahrenheit), not frozen, and not used after its expiration date.

For Doctors

Pharmacodynamics

Palivizumab has anti-respiratory syncytial virus (RSV) neutralizing and fusion-inhibitory activities. This is to prevent RSV proliferation and dissemination. Palivizumab is given to pediatric patients to prevent the occurrence of a lower respiratory tract illness.

Chemical Taxonomy

Palivizumab is a humanized monoclonal antibody targeting the F protein of respiratory syncytial virus (RSV) created utilizing recombinant DNA (deoxyribonucleic acid) technology. Palivizumab is made up of human and mouse antibody sequences, with the human heavy chain formed from IgG1 constant domains and the variable framework portions of VH genes Cor and Cess, and the human light chain derived from Ck constant domains and VL gene K104 with Jk-4. Palivizumab is made up of two heavy chains and two light chains and is derived from a stable murine myeloma cell line (NS0).

Mechanism of Action

Palivizumab binds to the RSV fusion glycoprotein. This stops it from attaching to and being taken up by host cell receptors.

Pharmacokinetics

Palivizumab has a pharmacokinetic profile similar to that of a human IgG1 antibody in terms of volume of distribution and half-life. Palivizumab is most likely eliminated through opsonization by the reticuloendothelial system. Palivizumab's half-life is stated to be 18 days on average. However, according to other sources, the half-life can range from 17 to 26.8 days. It should be noted that the values are based on adult volunteer studies, and only trough serum concentrations were recorded in the critical pediatric clinical efficacy study. Individual patient features, like with any medicine, might alter pharmacokinetics. For information suited to individual patient needs, always consult a healthcare provider.

Warnings and Precautions:

The warnings and precautions associated are as follows:

• Hypersensitivity Reactions: Following initial or re-exposure to Palivizumab, incidents of anaphylaxis and anaphylactic shock, even fatal cases, have been described. Other acute hypersensitivity events, some of which were severe, have been documented following initial or re-exposure to Palivizumab. Some of the signs and symptoms include Urticaria, pruritus, angioedema, dyspnea, respiratory failure, cyanosis, hypotonia, hypotension, and unresponsiveness. There is no established connection between these reactions and the production of antibodies to Palivizumab. Palivizumab should be stopped immediately if a serious hypersensitivity reaction occurs. If anaphylaxis or another severe hypersensitivity reaction occurs, administer necessary drugs such as Epinephrine and provide supportive care as needed. If a mild hypersensitivity reaction occurs, expert opinion should be utilized when reintroducing Palivizumab.

• Coagulation Disorders: Palivizumab is only for intramuscular use. Like any intramuscular injection, Palivizumab should be administered carefully to children with thrombocytopenia or another clotting condition.

• RSV Diagnostic Test Interference: Palivizumab may disrupt immunological RSV diagnostic tests, including antigen detection and viral culture assays, due to its suppression of virus reproduction in cell culture. It does not affect reverse transcriptase polymerase chain reaction assays, potentially leading to false-negative results. Therefore, diagnostic test results should be combined with clinical findings for medical decision-making.

• Treatment of RSV Disease: Palivizumab's safety and efficacy for treating RSV disease have not been demonstrated.

• Proper Administration: A preservative is not present in the single-dose vial of Palivizumab. Palivizumab should be administered once the dose is removed from the vial. It is not necessary to re-enter the vial. Any unused portion should be discarded.

Drug Interactions:

With no official drug-drug interaction investigations, a clinical study found no significant increase in adverse events among children getting regular childhood immunizations, influenza vaccines, bronchodilators, or corticosteroids (such as prednisone, hydrocortisone, betamethasone).

Clinical Studies:

Palivizumab, a prophylactic against RSV infection in children at high risk of hospitalization, was tested in two randomized studies for safety and efficacy. One study included 1502 children under the age of 24 months with BPD or newborns born prematurely, while the other included 1287 children with hemodynamically severe congenital heart disease. Participants were given 15 mg per kilogram of Palivizumab or an equivalent volume of placebo intramuscularly once a month for five months. In both trials, there was a statistically significant reduction in RSV hospitalization. However, clinical investigations did not show that children hospitalized with RSV infection who got Palivizumab for RSV prophylaxis were less severe than those who received a placebo. Palivizumab appears to be a better choice for children at high risk of hospitalizations, according to the findings.

Use in Specific Populations

• Pregnancy Category C: Palivizumab is not recommended for adult use. When delivered to a pregnant woman, it is unknown whether Palivizumab can cause fetal damage or alter reproductive potential.

• Pediatric Use: Palivizumab's safety and efficacy for children over 24 months at the beginning of dosing have yet to be established.