Infliximab - Uses, Dosage, Side Effects, and Drug Warnings

Overview:

Infliximab is a tumor necrosis factor (TNF)-alpha-inhibiting biological monoclonal-antibody medicine. In 1998, Food and Drug Administration (United States) approved Infliximab to treat Crohn's disease in adults and children six years and above, active rheumatoid arthritis, ulcerative colitis, psoriatic arthritis, ankylosing spondylitis, and chronic severe plaque psoriasis in adults.

Indications:

• Active Crohn’s disease (a disease where the body attacks the digestive tract lining, leading to diarrhea and pain) in adults and children above six years.

• Active ulcerative colitis (a condition affecting the lining of the large intestine in adults and above children six years) in adult patients with an unsatisfactory response to conventional therapy.

• Chronic severe plaque psoriasis (a skin disease in which scaly, red patches develop on certain body regions) in adult patients.

• Active rheumatoid arthritis (a disorder where the body attacks its joints, leading to pain, swelling, and loss of function).

• Active psoriatic arthritis (pain and swelling and scales on the skin).

• Ankylosing spondylitis (pain and damage to the joints of the spine and other areas).

Non-FDA Approved Indications:

• Bechet disease (a rare condition that causes inflammation of blood vessels throughout the body).

• Juvenile idiopathic arthritis.

• Relapsing polychondritis (a rare condition leading to cartilage inflammation in many areas of the body).

• Pyoderma gangrenosum (a rare condition that leads to the development of large, painful ulcers on the skin, most often on the legs).

• Pustular psoriasis (an immune-mediated rare systemic skin condition leading to the formation of yellowish pustules).

Studies have revealed that Infliximab is not proven effective in very young patients; however, not much data is available to support this.

Infliximab can be given with Methotrexate to avoid the host’s immunologic responses that can decrease the drug's effectiveness. Rheumatoid arthritis is the only indication approved by the Food and Drug Administration (FDA) where Methotrexate can be used simultaneously.

Warnings and Precautions:

• Allergies: The patient should inform the doctor about allergies to this drug, other medications, or any ingredients present in Infliximab. The doctor should also be informed about other allergies, like allergies to foods, preservatives, dyes, or animals.

• Pediatric: Major studies have shown that Infliximab injection can be used to treat Crohn's disease or ulcerative colitis in children six years and above. However, safety and efficacy have yet to be documented in children younger than six. No relevant studies have not been performed to establish a relationship between the age and effects of Infliximab injection in children with plaque psoriasis, ankylosing spondylitis, or psoriatic arthritis. Most studies have demonstrated that Infliximab injection is useless in children with juvenile rheumatoid arthritis.

• Geriatric: No specific study has documented any geriatric-specific problems that limit the use of Infliximab in the elderly population. However, geriatric patients are more prone to infections; hence the drug must be prescribed cautiously.

• Breastfeeding: No specific study has been performed on women to determine the risk to infants during the use of this medication during breastfeeding. Before prescribing this medication while breastfeeding, the potential risks and benefits must be calculated.

Drug Interactions:

Certain medications cannot be used together to avoid interactions; however, in some cases, sometimes these medications are prescribed by changing the dose and or taking the necessary precautions required.

It is not recommended to use Infliximab with the following:

Medications:

• Abatacept.

• Adalimumab.

• Alefacept.

• Anakinra.

• Anifrolumab.

• Baricitinib.

• Brodalumab.

• Certolizumab pegol.

• Cyclosporine.

• Etanercept.

• Fosphenytoin.

• Golimumab.

• Guselkumab.

• Ixekizumab.

• Natalizumab.

• Paclitaxel.

• Phenytoin.

• Quinidine.

• Rilonacept.

• Rituximab.

• Sarilumab.

• Sirolimus.

• Tacrolimus.

• Tocilizumab.

• Tofacitinib.

• Ustekinumab.

• Vedolizumab.

• Warfarin.

• Zoster vaccine.

Vaccines:

• Adenovirus vaccine type 4.

• Adenovirus vaccine type 7.

• Bacillus of Calmette and Guerin (BCG) vaccine.

• Dengue tetravalent vaccine.

• Influenza virus vaccine.

• Measles virus vaccine.

• Mumps Virus Vaccine.

• Poliovirus vaccine.

• Rotavirus vaccine.

• Rubella virus vaccine.

• Smallpox vaccine.

• Typhoid vaccine.

• Varicella virus vaccine.

• Yellow fever vaccine.

Other Interactions:

Certain drugs must not be used with food since interactions might occur. Using alcohol or tobacco with certain medicines can also lead to interactions. The healthcare professional must be informed about medicine with food, alcohol, or tobacco.

For Patients:

Why Is Infliximab Prescribed?

Infliximab is used for the treatment of certain autoimmune disorders (disorders where the immune system destroys the healthy parts of the body), including

• Rheumatoid arthritis (a disorder where the body attacks its joints, leading to pain, swelling, and loss of function).

• Crohn's disease (a disease where the body attacks the digestive tract lining, leading to diarrhea and pain) in adults and children above six years.

• Ulcerative colitis (a condition affecting the lining of the large intestine in adults and above children six years) in adult patients with an unsatisfactory response to conventional therapy.

• Ankylosing spondylitis (pain and damage to the joints of the spine and other areas).

• Plaque psoriasis (a skin disease in which scaly, red patches form on some areas of the body).

• Psoriatic arthritis (pain, swelling, and scales on the skin).

Infliximab injection products belong to a class of drugs called tumor necrosis factor-alpha (TNF-alpha) that work by inhibiting the action of TNF-alpha (responsible for inflammation). Infliximab injection products help control the symptoms but will not cure the condition.

How Should Infliximab Be Used?

Infliximab injection products are available in a powder mixed with sterile water and administered into a vein by a nurse or doctor. It is administered in a doctor's clinic, usually at the beginning of treatment every two to eight weeks. Taking the entire dose of an Infliximab injection takes around two hours. If Crohn's disease does not improve after 14 weeks, the doctor might discontinue the product.

Infliximab injection products can lead to severe adverse reactions, including allergic reactions at the time of infusion and the following two hours. A doctor or nurse has to monitor the patient while administering this drug. The patient might be given other medications to prevent reactions to an Infliximab injection product. The doctor or nurse must be informed immediately in case the following symptoms are experienced:

• Hives.

• Rash.

• Itching.

• Vision loss.

• Fever.

• Chills.

• Swelling of the face, eyes, throat, mouth, tongue, lips, hands, ankles, feet, or lower legs.

• Difficulty breathing or swallowing.

• Flushing.

• Dizziness.

• Fainting.

• Seizures.

• Chest pain.

Other Uses of Infliximab:

Infliximab injection products can also sometimes be used to treat Behcet's syndrome (a condition characterized by ulcers in the mouth and on the genitals with inflammation of different body parts).

What Special Precautions Should Be Taken?

1. Allergies: The patient should inform the doctor about allergies to this drug, any other medications made from murine proteins, or any ingredients present in Infliximab. The doctor should also be informed about other allergies, like allergies to foods, preservatives, dyes, or animals. The patient should be aware of the delayed allergic reaction that can occur 3 to 12 days after administering the Infliximab injection product.

2. Drug History: The doctor should be provided with a list of prescribed or non-prescribed drugs that the patient is taking, including vitamins and natural or herbal supplements. Patients should inform the doctor if they take anticoagulants (blood thinners) such as Warfarin, Cyclosporine, and Theophylline.

3. Medical History: The patient must inform the doctor about the following conditions:

• Heart failure (a condition when the heart cannot pump enough blood to various parts of the body). The doctor usually does not advise Infliximab injection products.

• Phototherapy treatment (a psoriasis treatment that exposes the skin to ultraviolet light).

• Disorders of the nervous system, like Guillain-Barre syndrome (tingling and paralysis due to nerve damage suddenly), multiple sclerosis (loss of coordination, numbness, and weakness due to nerve damage), or optic neuritis (inflammation of the optic nerve that links the eye to the brain).

• Chronic obstructive pulmonary disease (a group of disorders that affect the lungs and airways).

• Cancer of any type.

• Bleeding disorders.

• Heart disease.

4. Pregnancy and Breastfeeding: No specific study has been performed on women to determine the risk to infants while using this medication during breastfeeding. Before prescribing this medication while breastfeeding, the potential risks and benefits must be calculated. The baby may need to take certain vaccinations later than usual.

5. Vaccination: The doctor must be informed about the recently received vaccine. The patient must talk to their doctor before taking vaccinations. Adults and children must receive all vaccines before starting Infliximab treatment.

What Special Dietary Instructions Must Be Followed?

The patient can continue the normal diet unless advised by the doctor otherwise.

Side Effects of Infliximab:

Infliximab injection can cause certain side effects. The patient must inform the doctor in case of any of the following symptoms:

• Nausea.

• Heartburn.

• Headache.

• Runny nose.

• Vaginal itching, pain, burning, or other signs of yeast infection.

• White patches in the mouth.

• Flushing.

Sometimes the side effects can be severe. The following side effects are uncommon; however, the doctor must be informed immediately if these side effects occur:

• Irregular heartbeat.

• Chest pain.

• Any type of rash.

• Pain in the arms, back, neck, or jaw.

• Stomach pain.

• Loss of balance or coordination.

• Pale skin.

• Sudden, severe headache.

• Swelling of the feet, ankles, stomach, or lower legs.

• Sudden weight gain.

• Shortness of breath.

• Blurred vision or vision changes.

• Sudden weakness of an arm or leg (usually on one side of the body) or the face.

• Muscle or joint pain.

• Numbness or tingling in any part of the body.

• Sudden confusion, trouble speaking, or trouble understanding.

• Sudden trouble walking.

• Seizures.

• Dizziness or faintness.

• Unusual bruising or bleeding.

• Yellowing of the skin or eyes.

• Dark-colored urine.

• Loss of appetite.

• Pain in the upper right part of the stomach.

• Blood in stool.

• Red, scaly patches or pus-filled bumps on the skin.

Infliximab injection can increase the chances of developing lymphoma and other cancers. Before starting the treatment, the patient must ask the doctor about the potential side effects.

Storage and Disposal:

This medication is stored at the doctor’s clinic.

What Should Be Done in Case of an Overdose?

In case of an overdose, the poison control helpline must be contacted immediately.

Other Information:

Maintaining a written list of all the prescribed and non-prescribed (over-the-counter) drugs that are taking the patient, including other supplements like vitamins or minerals are taking. The patient should carry this list for every visit to a doctor or a hospital. It is extremely important in case of emergencies. The doctor may suggest certain laboratory tests before administering Cariprazine to check the body's response to this medication.

Warning:

Infliximab injection products decrease the ability to fight infection and increase the risk of acquiring a severe infection that might spread throughout the body. In case of such infections, the patient has to be hospitalized as they can be fatal sometimes. The patients must inform the doctor if they are taking any medications that decrease the immunity like Abatacept, Anakinra, Methotrexate, steroids such as Methylprednisolone, Dexamethasone, Prednisolone or Prednisone, or Tocilizumab.

The doctor monitors the signs of infection while administrating the Infliximab injection. The patient must consult the doctor if any of the following symptoms are experienced:

• Weakness.

• Sweating.

• Difficulty breathing.

• Diarrhea.

• Stomach pain.

• Sore throat.

• Cough.

• Coughing up bloody mucus.

• Extreme tiredness.

• Flu-like symptoms.

• Fever.

• Warm, red, or painful skin.

Sometimes tuberculosis (a severe lung infection) or hepatitis B (a virus affecting the liver) can be present without any disease symptoms. In such cases, Infliximab injection can increase the risk of the infection and development of symptoms or severity of the disease. The doctor usually starts the medications for these infections before administration of Infliximab infection. The doctor usually performs skin tests to detect inactive tuberculosis and blood test for hepatitis B infection. The doctor must be informed if the patient has tuberculosis or hepatitis B.

Some children and teenagers who take Infliximab injections or similar medications might develop severe or life-threatening cancers, including lymphoma. In certain cases, teenage and young adult males who received Infliximab or similar medications reported hepatosplenic T-cell lymphoma (HSTCL), a severe form of cancer that can be deadly within a short duration. Most individuals who developed HSTCL had undergone treatment for Crohn's disease or ulcerative colitis with an Infliximab injection along with another medication like Azathioprine or 6-Mercaptopurine. Inform the doctor if the child has ever had any type of cancer.

The doctor must be informed if the patient develops the following symptoms:

• Unexplained weight loss.

• Swollen glands in the neck.

• Easy bruising or bleeding.

• Underarms or groin.

For Doctors:

Indications:

• Active Crohn’s disease in adults and children six years and above.

• Active ulcerative colitis in adults and children (six years or older) in adult patients with an unsatisfactory response to conventional therapy.

• Chronic severe plaque psoriasis in adult patients.

• Active rheumatoid arthritis.

• Active psoriatic arthritis.

• Ankylosing spondylitis.

Non-FDA Approved Indications:

• Bechet disease (a rare condition that causes inflammation of blood vessels throughout the body).

• Juvenile idiopathic arthritis.

• Relapsing polychondritis (a rare condition leading to cartilage inflammation in many areas of the body).

• Pyoderma gangrenosum (a rare condition that leads to the development of large, painful ulcers on the skin, most often on the legs).

• Pustular psoriasis (an immune-mediated rare systemic skin condition leading to the formation of yellowish pustules).

Pharmacology:

Mechanism of Action

Infliximab is a type of biological therapy that stimulates the body's immune system and helps treat a disease. Infliximab is a purified, monoclonal antibody protein chimeric IgG (immunoglobulin G) derived from recombinant DNA. Infliximab contains murine and human components constraining tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a signaling protein involved in acute phase reactions and systemic inflammation. It is produced by

• Macrophages.

• CD4+ lymphocytes.

• Natural killer cells.

• Neutrophils.

• Mast cells.

• Eosinophils.

• Neurons.

This TNF-alpha inhibition stops the inflammatory reaction's cascade, improving disease conditions.

Half-life in Adults: 7 to 12 days.

TNF-alpha is responsible for increasing adhesion molecule release, inducing proinflammatory cytokines, and enhancing the migration of leukocytes via increased endothelial permeability from blood vessels into the surrounding tissues.

Infliximab causes these physiological responses as it shows a high affinity for TNF-alpha.

Administration

1. Active Crohn’s Disease: In adults and children (six years and above) who did not respond well to conventional therapy, the induction dose is 5 milligrams per kilogram, administered intravenously at 0, 2, and 6 weeks, followed by a maintenance dose every eight weeks. In patients not responding accurately to this treatment, a 10 milligrams per kilogram dose is considered.

2. Active Ulcerative Colitis: In adult patients who did not respond well to conventional therapy, the usual initial dose is 5 milligrams per kilogram intravenously at 0, 2, and 6 months, followed by 5 milligrams per kilogram every eight weeks as a maintenance dose.

3. Active Rheumatoid Arthritis: Induction therapy at 3 milligrams per kilogram is given at 0, 2, and 6 weeks, followed by a maintenance dose every eight weeks.

4. Active Ankylosing Spondylitis: Initial dose of 5 milligrams per kilogram intravenous is given at 0, 2, and 6 weeks, followed by a maintenance dose every six weeks.

5. Active Psoriatic Arthritis: Initial dose of 5 milligrams per kilogram intravenous is given at 0, 2, and six weeks, followed by a maintenance dose of eight weeks.

6. Chronic Severe Plaque Psoriasis: In adult patients an initial dose of 5 milligrams per kilogram intravenous is given at 0, 2, and 6 weeks, followed by a maintenance dose every eight weeks.

Certain studies have documented that Infliximab can cause type I and III hypersensitivity reactions.

Strategies used to prevent Infliximab-induced infusion reactions include

• Administration of antihistamine and Acetaminophen 90 minutes before infusion.

• A test dose of Infliximab should be given first.

• Patients who have shown an allergic reaction to Infliximab in the past should receive Prednisone, antihistamine, and Acetaminophen before receiving this drug.

Dosage Adjustments:

• No dosage adjustments have been advised in patients with renal or hepatic impairment.

• Dosage adjustment is not usually required in patients with mild heart failure, but adequate monitoring is essential.

• In patients with severe heart failure, dosage adjustment is required to keep the dose less than or equal to 5 milligrams per kilogram.

Adverse Effects:

Infliximab is a generally safe medication. However, with the increase in dose or age of the patients. Certain adverse effects include

• Infections, especially in patients on additional immunosuppressive therapy.

• Infusion-related reactions.

• Headache.

• Nausea.

• Abdominal pain.

• Alanine transaminase elevation.

• Dyspepsia.

• Diarrhea.

• Constipation.

• Hepatotoxicity.

• Heart failure.

• Hypertension.

• Anemia, leukopenia, neutropenia, thrombocytopenia.

• Demyelination disease.

• Paradoxical reaction.

• Tuberculosis reactivation.

• Malignancy.

• Reactivation of hepatitis B.

• Transient vision loss.

• Psoriasis.

• Lupus-like syndrome.

• Vitiligo or other autoimmune disorders.

Infliximab can cross the placenta and is found in the serum of infants whose mothers received Infliximab during pregnancy for up to six months. Agranulocytosis and reactions to living vaccines in these infants have been reported. Therefore, it is recommended to delay the administration of live vaccines for six months or more.

Patients might develop antibodies against Infliximab, which lowers the drug's efficacy and causes infusion reactions. This risk can be reduced by co-administration of other immunosuppressors like Methotrexate.

Contraindications:

Careful administration of Infliximab can be done in certain conditions, but it is contraindicated in the following conditions:

• Heart failure.

• Previous hypersensitivity reaction to Infliximab.

• Current severe infection (sepsis, tuberculosis).

• Active infection.

Infliximab must be used with caution in the following conditions:

• Preexisting demyelinating disease.

• Mild to moderate heart failure.

• History of seizures.

• Uncontrolled diabetes mellitus.

• Patients over 65 years.

• Moderate to severe chronic obstructive pulmonary disease (COPD).

Infliximab can cause a cross-reaction with some drugs (Abatacept, Adalimumab, Etanercept). Infliximab is contraindicated in patients requiring live vaccines like the cholera vaccine, live virus MMR (measles, mumps, and rubella) vaccine, and smallpox vaccine.

Generally, vaccination should occur more than four weeks before or over three months following immunosuppressive therapy with Infliximab.

Toxicity:

Infliximab is usually administered in a medical setup by a healthcare professional. Toxicity is rarely reported. Therefore, there is no specific treatment required for Infliximab toxicity. Supportive treatment is usually considered best in such cases.

Involvement of the Healthcare Team:

Infliximab is frequently prescribed by primary caregivers, nursing practitioners, and other healthcare professionals to evaluate tuberculosis, hepatitis B, and cardiac status before administering the drug. Close patient monitoring is essential as Infliximab has mild to moderate adverse effects. A proper interprofessional team approach is required to ensure the best outcomes and prevent adverse effects.