Infliximab – Side effects and Dosage

Background

Infliximab is a tumor necrosis factor (TNF-alpha or TNF-α) blocker and a chimeric monoclonal IgG1 antibody composed of human constant (75%) and murine variable (25%) regions. Infliximab is produced by a recombinant cell line cultured by continuous perfusion. Tumor necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine involved in chronic inflammatory diseases. Its hyperactivity and enhanced signalling pathways can be observed in inflammatory diseases where it activates further pro-inflammatory cascades. By binding to both the soluble subunit and the membrane-bound precursor of TNF-α, infliximab disrupts the interaction of TNF-α with its receptors and may also cause lysis of cells that produce TNF-α.

Infliximab was first approved by the FDA in 1998 under the market name Remicade as an intravenous injection. It is indicated for the treatment of various inflammatory disorders such as adult or pediatric Chron’s disease, adult or pediatric ulcerative colitis, rheumatoid arthritis in combination with methotrexate, ankylosing spondyliti, psoriatic arthritis, and plaque psoriasis. In clinical trials, multiple infusions of infliximab displayed in a reduction of signs and symptoms of inflammatory diseases and induction of remission in patients who have had an inadequate response to alternative first-line therapies for that disorder.

There are currently two biosilimars of infliximab available in the US market that demonstrate a high degree of similarity to the reference product, Remicade. They are approved for all eligible indications of the reference product. Inflectra, a first biosimilar drug product, was approved in 2016. In December 2017, Ixifi, a second biosimilar that was developed by Pfizer, was granted approval by the FDA.

Properties and Characteristics of Infliximab

Drug class	Tumor necrosis factor
Brand Names	Avsola, Flixabi, Inflectra, Remicade, Renflexis
Synonyms	Infliximab, Infliximab (genetical recombination), Infliximab-abda, Infliximab-axxq, Infliximab-dyyb, Infliximab-qbtx
Molecular Formula	C₆₄₂₈H₉₉₁₂N₁₆₉₄O₁₉₈₇S₄₆
Molecular Weight	149,100 daltons
Structural formula of main components
Pure active ingredient	infliximab
Appearance	White powder
Melting point	61°C (FAB fragment), 71°C (whole mAb)
Solubility	>10 mg/mL
Excretion	Excreted by the kidney
Storage	Store unopened Infliximab vials in a refrigerator at 2°C to 8°C (36°F to 46°F).
Available Forms	Injection, Powder
Prescription	Doctor prescription is required before consumption

Why is Infliximab prescribed?

Infliximab injection products are used to relieve the symptoms of certain autoimmune disorders (conditions in which the immune system attacks healthy parts of the body and causes pain, swelling, and damage) including:

Rheumatoid arthritis (a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) that is also being treated with methotrexate (Rheumatrex, Trexall),
Crohn’s disease (a condition in which the body attacks the lining of the digestive tract, causing pain, diarrhea, weight loss, and fever) in adults and children 6 years of age or older that has not improved when treated with other medications,
Ulcerative colitis (condition that causes swelling and sores in the lining of the large intestine) in adults and children 6 years of age or older that has not improved when treated with other medications,
Ankylosing spondylitis (a condition in which the body attacks the joints of the spine and other areas causing pain and joint damage),
Plaque psoriasis (a skin disease in which red, scaly patches form on some areas of the body) in adults when other treatments are less appropriate,
Psoriatic arthritis (a condition that causes joint pain and swelling and scales on the skin).

Side-effects and risks of Infliximab

Like all drugs, infliximab can sometimes cause side effects. Some common side effects include:

A blocked or runny nose
Headaches
Dizziness
Flushing
A rash
Stomach pain
Indigestion
Feeling sick.

A faster or irregular heartbeat is also quite common – you should speak to your doctor if this happens to you.

Because infliximab affects the immune system, it can make you more likely to pick up infections. In rare cases, your body might not produce enough of the blood cells that help to fight infections or stop bleeding.

Tell your doctor or rheumatology nurse straight away if you develop any signs of infection. These include a sore throat or fever, or any other new symptoms that concern you.

If any of these symptoms are severe, your infliximab may need to be stopped. Your doctor may also recommend that you temporarily stop infliximab if you are taking antibiotics.

You should also see your doctor if you develop chickenpox or shingles, or if you come into contact with someone who has chickenpox or shingles. These infections can be severe if you’re on infliximab. You may need antiviral treatment, and your infliximab may be stopped until you’re better.

Some people may have a negative reaction to the infusion. This is more likely during or soon after the first few infusions.

Some drugs, like infliximab, may make you more sensitive to the sun and could put you at a higher risk of skin cancer. To be on the safe side, make sure to wear sunscreen and regularly check your skin for any new spots or changes to your freckles or moles.

Very rarely, infliximab may cause a condition called drug-induced lupus. Symptoms include a rash, fever and increased joint pain. If you have any of these symptoms, you should tell your rheumatology team. It’ll usually clear up when you stop taking infliximab. Before starting infliximab, you may have a blood test to see if you have had lupus before. If you have had the condition, you will have the lupus antibody in your blood.

Regular check-ups and tests while you’re on infliximab will help to pick up any problems. This should happen at least every six months, though in some cases your doctor may suggest more frequent checks.

Mechanism of action

Infliximab is a IgG1κ monoclonal antibody that binds to soluble and transmembrane forms of TNF-α with high affinity to disrupt the pro-inflammatory cascade signalling. Binding of the antibody to TNF-α prevents TNF-α from interacting with its receptors. Infliximab does not neutralize TNF-β (lymphotoxin-α), a related cytokine that utilizes the same receptors as TNF-α Label. Blocked actions of TNF-α further leads to downregulation of local and systemic pro-inflammatory cytokines (i.e. IL-1, IL-6), reduction of lymphocyte and leukocyte migration to sites of inflammation, induction of apoptosis of TNF-producing cells (i.e. activated monocytes and T lymphocytes), increased levels of nuclear factor-κB inhibitor, and reduction of reduction of endothelial adhesion molecules and acute phase proteins. Its inhibitory actions on TNF-α were demonstrated in human fibroblasts, endothelial cells, neutrophils, B and Tlymphocytes and epithelial cells Label. Infliximab also atteunates the production of tissue degrading enzymes synthesized by synoviocytes and/or chondrocytes. According to a transgenic mice study that developed polyarthritis due to consitutive levels of human TNF-α, infliximab decreased synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal.

Drug Interactions with Infliximab

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. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Abatacept
Bacillus of Calmette and Guerin Vaccine, Live
Certolizumab Pegol
Dengue Tetravalent Vaccine, Live
Fosphenytoin
Golimumab
Influenza Virus Vaccine, Live
Measles Virus Vaccine, Live
Natalizumab
Paclitaxel
Quinidine
Rilonacept
Sarilumab
Tacrolimus
Ustekinumab
Varicella Virus Vaccine, Live
Warfarin
Yellow Fever Vaccine
Zoster Vaccine, Live

Other Interactions

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.

Dosage and Administration

Dosage In Adult Crohn’s Disease

The recommended dosage of Infliximab is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adults with moderately to severely active CD or fistulizing CD. For adult patients who respond and then lose their response, consideration may be given to treatment with 10 mg/kg every 8 weeks. Patients who do not respond by Week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue Infliximab in these patients.

Dosage In Pediatric Crohn’s Disease

The recommended dosage of Infliximab for pediatric patients 6 years and older with moderately to severely active CD is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks.

Dosage In Adult Ulcerative Colitis

Dosage In Pediatric Ulcerative Colitis

The recommended dosage of Infliximab for pediatric patients 6 years and older with moderately to severely active UC is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks.

Dosage In Rheumatoid Arthritis

The recommended dosage of Infliximab is 3 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 3 mg/kg every 8 weeks thereafter for the treatment of moderately to severely active RA. Infliximab should be given in combination with methotrexate. For patients who have an incomplete response, consideration may be given to adjusting the dosage up to 10 mg/kg every 8 weeks or treating as often as every 4 weeks bearing in mind that risk of serious infections is increased at higher doses per infusion or more frequent dosing.

Dosage In Ankylosing Spondylitis

The recommended dosage of Infliximab is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 6 weeks thereafter for the treatment of active AS.

Dosage In Psoriatic Arthritis

Dosage In Plaque Psoriasis

The recommended dosage of Infliximab in adult patients is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of chronic severe (i.e., extensive and/or disabling) Ps.

Overdose and Contraindications of Infliximab

Single doses up to 20 mg/kg have been administered without any direct toxic effect. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately.

Contraindications

The use of Infliximab at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure.

Infliximab is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab or any of the inactive ingredients of Infliximab or any murine proteins.

Infliximab warnings

This drug comes with several warnings.

Allergy warning

Infliximab can cause a severe allergic reaction. This reaction can happen while you’re getting treatment or up to two hours after. Symptoms may include:

Hives (red, raised, itchy patches of skin)
Trouble breathing
Chest pain
High or low blood pressure. Signs of low blood pressure include:
- Dizziness
- Feeling faint
- Trouble breathing
- Fever and chills

Sometimes infliximab can cause a delayed allergic reaction. Reactions may occur 3 to 12 days after receiving your injection. Tell your doctor right away if you have any of these signs of delayed allergic reaction:

Fever
Rash
Headache
Sore throat
Muscle or joint pain
Swelling of your face and hands
Trouble swallowing

Warnings for people with certain health conditions

For people with infections: Tell your doctor if you have any kind of infection, even if it’s small, such as an open cut or a sore that looks infected. Your body may have a harder time fighting off the infection while you’re taking infliximab.

For people with tuberculosis (TB): Infliximab affects your immune system and may make it easier for you to get TB. Your doctor may test you for TB before starting the drug.

For people with hepatitis B: If you carry the hepatitis B virus, it can become active while you use infliximab. If the virus becomes active again, you’ll need to stop taking the drug and treat the infection. Your doctor may do blood tests before you start treatment, during treatment, and for several months following treatment with infliximab.

For people with blood problems: Infliximab may affect your blood cells. Tell your doctor about any problems you have with your blood before you start taking infliximab.

For people with nervous system problems: Infliximab may make symptoms of some nervous system problems worse. Use it with caution if you have multiple sclerosis or Guillain-Barre syndrome.

For people with heart failure: This medication may make heart failure worse. Call your doctor right away if you get symptoms of worsening heart failure. Symptoms may include shortness of breath, swelling of your ankles or feet, and sudden weight gain. You’ll need to stop taking infliximab if your heart failure gets worse.

Warnings for other groups

For pregnant women: Infliximab is a pregnancy category B drug. That means two things:

Studies of the drug in pregnant animals have not shown risk to the fetus.
There aren’t enough studies done in pregnant women to show if the drug poses a risk to the fetus.

Tell your doctor if you’re pregnant or plan to become pregnant. Infliximab should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Call your doctor if you become pregnant while taking this drug.

For women who are breastfeeding: It is unknown if this drug passes into breast milk. If infliximab is passed to your child through your breast milk, it could cause serious side effects.

You and your doctor may need to decide whether you’ll take infliximab or breastfeed.

For seniors: You may be at higher risk for a serious infection while taking infliximab if you’re over the age of 65 years.

For children: Infliximab hasn’t been shown to be safe and effective for Crohn’s disease or ulcerative colitis in people younger than 6 years.

The safety and effectiveness of infliximab for other conditions haven’t been established in people younger than 18 years.

PillsLog.com | Instantly Drugs information Instantly find your pills from our A to Z list Medicines and Prescription Drug information for consumers and medical health professionals.