Adalimumab

Dosage for adalimumab varies significantly depending on the condition being treated. It is critical to follow the specific schedule provided by your specialist.

• Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis: The standard dose is 40 mg administered every other week. Some patients with RA who are not receiving methotrexate may benefit from increasing the frequency to 40 mg every week or 80 mg every other week.
• Crohn’s Disease and Ulcerative Colitis: Treatment typically begins with an 'induction phase' to quickly lower inflammation. The initial dose is 160 mg on Day 1 (given as four 40 mg injections in one day or two 40 mg injections per day over two consecutive days), followed by 80 mg two weeks later (Day 15). Two weeks after that (Day 29), the maintenance dose of 40 mg every other week begins.
• Plaque Psoriasis and Uveitis: The initial dose is 80 mg, followed by 40 mg every other week starting one week after the initial dose.
• Hidradenitis Suppurativa: The initial dose is 160 mg (Day 1), followed by 80 mg on Day 15. Beginning on Day 29, the maintenance dose is 40 mg every week or 80 mg every other week.

Adalimumab is approved for several pediatric conditions, with dosing usually based on body weight to ensure safety and efficacy.

• Polyarticular Juvenile Idiopathic Arthritis: For children 2 years of age and older, the dose is typically 10 mg every other week for those weighing 10 kg to <15 kg, 20 mg every other week for 15 kg to <30 kg, and 40 mg every other week for those weighing 30 kg or more.
• Pediatric Crohn’s Disease: For children 6 years and older, the induction and maintenance doses are stratified by weight (e.g., <40 kg vs. ≥40 kg). For those ≥40 kg, the induction is 160 mg on Day 1 and 80 mg on Day 15, with maintenance of 40 mg every other week.
• Pediatric Ulcerative Colitis: Similar weight-based induction and maintenance schedules apply for children 5 years of age and older.

Renal Impairment

Adalimumab has not been formally studied in patients with renal (kidney) impairment. However, since monoclonal antibodies are not cleared by the kidneys, dosage adjustments are generally not required. Your doctor will monitor your kidney function as part of routine care.

Hepatic Impairment

There are no specific studies of adalimumab in patients with hepatic (liver) impairment. Because it is cleared via proteolysis rather than liver metabolism, dose adjustments are not typically recommended, but caution is advised in patients with severe liver disease.

Elderly Patients

Clinical trials did not identify significant differences in safety or efficacy between patients over 65 and younger adults. However, because the risk of infection is generally higher in the elderly, healthcare providers will exercise extra caution when prescribing adalimumab to this population.

Adalimumab is administered by subcutaneous injection into the thigh or abdomen.

1. 1Preparation: Remove the pen or syringe from the refrigerator 15 to 30 minutes before injecting to allow it to reach room temperature. This reduces injection site pain.
2. 2Site Selection: Choose a different site each time you give yourself an injection (at least one inch away from the previous site). Do not inject into areas where the skin is tender, bruised, red, or hard.
3. 3Cleaning: Clean the injection site with an alcohol swab and let it air dry.
4. 4Injection: Follow the specific instructions for your pen or syringe device. Most pens require you to press the device firmly against the skin and push a button.
5. 5Storage: Adalimumab must be refrigerated at 36°F to 46°F (2°C to 8°C). Do not freeze. If traveling, it can be stored at room temperature (up to 77°F/25°C) for a single period of up to 14 days, protected from light.

If you miss a dose of adalimumab, inject the missed dose as soon as you remember. Then, take your next dose at your next regularly scheduled time. Do not inject two doses at once to make up for a missed one. If you are unsure when to take your next dose, contact your healthcare provider.

In clinical trials, doses up to 10 mg/kg (several times the standard dose) have been administered without evidence of dose-limiting toxicity. However, if an overdose occurs, you should be monitored for any signs or symptoms of adverse reactions. Seek emergency medical attention or contact a Poison Control Center immediately if an accidental large overdose occurs.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or frequency without medical guidance.

Adalimumab affects the immune system, and while most patients tolerate it well, some side effects are frequent. The most common adverse reaction reported in clinical trials (occurring in up to 20% of patients) is injection site reactions. These may include redness, itching, pain, swelling, or bruising where the shot was given. Most of these reactions are mild and resolve within a few days.

Other common side effects include:

• Upper Respiratory Infections: Such as the common cold, sinus infections, or sore throat. Because adalimumab lowers the immune response, you may catch colds more easily.
• Headache: Often mild to moderate and may occur shortly after the injection.
• Rash: A generalized skin rash may occur as the body adjusts to the medication.
• Nausea: Some patients report mild stomach upset following administration.

These side effects occur in a smaller percentage of patients but are still well-documented:

• Hypertension (High Blood Pressure): New or worsening high blood pressure has been noted.
• Back Pain: Musculoskeletal discomfort can occur, particularly in patients being treated for arthritis.
• Urinary Tract Infections (UTIs): Increased susceptibility to bladder infections.
• Flu-like Symptoms: Fever, chills, and body aches that typically subside within 24–48 hours of the dose.

Rare but significant side effects include:

• Lupus-like Syndrome: Symptoms include joint pain, a rash on the cheeks or arms that worsens in the sun, and extreme fatigue. This usually resolves after stopping the drug.
• Demyelinating Diseases: Rare cases of disorders like Multiple Sclerosis (MS) or Guillain-Barré syndrome have been reported. Symptoms include numbness, tingling, vision changes, or muscle weakness.
• Cytopenias: A significant drop in white blood cells (leukopenia), red blood cells (anemia), or platelets (thrombocytopenia).

> Warning: Stop taking Adalimumab and call your doctor immediately or seek emergency care if you experience any of the following:

1. 1Signs of Serious Infection: Fever, sweats, chills, muscle aches, cough, shortness of breath, blood in phlegm, weight loss, warm/red/painful skin or sores on your body, diarrhea or stomach pain, burning when you urinate.
2. 2Allergic Reactions (Anaphylaxis): Hives, swelling of the face, tongue, or throat, and difficulty breathing.
3. 3Hepatitis B Reactivation: For carriers of the virus, symptoms include muscle aches, feeling very tired, dark urine, yellow skin or eyes (jaundice), little or no appetite, vomiting, and clay-colored bowel movements.
4. 4Heart Failure: New or worsening symptoms such as shortness of breath, swelling of your ankles or feet, and sudden weight gain.
5. 5Liver Problems: Feeling very tired, skin or eyes looking yellow, poor appetite or vomiting, pain on the right side of your stomach (abdomen).

With prolonged use of adalimumab, the primary concern is the risk of malignancies (cancers). Because TNF-alpha helps the body identify and destroy cancer cells, blocking it may increase the risk of lymphoma and other cancers. There have been cases of non-melanoma skin cancer; therefore, regular skin examinations are recommended for patients on long-term therapy. Additionally, long-term immunosuppression can lead to 'opportunistic infections'—infections caused by organisms that usually do not cause disease in healthy people, such as certain fungi (histoplasmosis, coccidioidomycosis).

The FDA has issued a Black Box Warning for adalimumab, the highest level of alert, regarding two major risks:

1. 1Serious Infections: Patients treated with adalimumab are at increased risk for developing serious infections that may lead to hospitalization or death. These include active tuberculosis (TB), bacterial sepsis, and invasive fungal infections. Patients should be tested for latent TB before starting adalimumab and monitored during treatment.
2. 2Malignancy: Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers. A rare type of cancer called Hepatosplenic T-cell lymphoma (HSTCL) has occurred, primarily in young men with Crohn's disease or ulcerative colitis who were also taking other immunosuppressants like azathioprine.

Report any unusual symptoms, no matter how minor they seem, to your healthcare provider immediately.

Adalimumab is a powerful immunomodulator, and its use requires careful medical supervision. Before starting treatment, you must inform your doctor if you have any history of recurring infections, have lived in areas where certain fungal infections (like histoplasmosis) are common, or have a history of tuberculosis. You should not start adalimumab if you have an active, clinically significant infection.

SERIOUS INFECTIONS: Patients treated with adalimumab are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Adalimumab should be discontinued if a patient develops a serious infection or sepsis. Reported infections include:

• Active tuberculosis, including reactivation of latent TB.
• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, and aspergillosis.
• Bacterial, viral, and other infections due to opportunistic pathogens.

MALIGNANCY: Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL) have occurred in patients treated with TNF blockers. HSTCL is an aggressive and often fatal cancer.

• Allergic Reactions: Serious allergic reactions, including anaphylaxis, have been reported. If you experience difficulty breathing, chest tightness, or severe rash, seek emergency help immediately.
• Hepatotoxicity: Severe hepatic reactions, including acute liver failure, have been reported in patients receiving TNF blockers. If you develop jaundice (yellowing of the skin/eyes) or severe abdominal pain, contact your doctor.
• Neurological Events: TNF blockers have been associated with rare cases of new-onset or exacerbation of central nervous system demyelinating diseases, including multiple sclerosis and optic neuritis. Use with caution in patients with pre-existing or recent-onset demyelinating disorders.
• Hematologic Events: Rare reports of pancytopenia (reduction in all blood cell types) and aplastic anemia have occurred. Seek medical advice if you develop a persistent fever, bruising, or bleeding.
• Heart Failure: Cases of worsening congestive heart failure (CHF) and new-onset CHF have been reported. Adalimumab should be used with caution in patients with heart failure.

Your healthcare provider will require several tests before and during treatment:

• TB Screening: A skin test or blood test (IGRA) for tuberculosis is mandatory before the first dose.
• Hepatitis B Screening: Testing for HBV infection is required, as the drug can cause reactivation of the virus.
• Complete Blood Count (CBC): To monitor for changes in white blood cells, red blood cells, and platelets.
• Liver Function Tests (LFTs): To monitor for potential drug-induced liver injury.
• Skin Exams: Regular check-ups to look for non-melanoma skin cancers.

Adalimumab typically does not affect the ability to drive or operate machinery. However, if you experience side effects like dizziness or vision changes, you should avoid these activities until the symptoms resolve.

There is no direct contraindication between alcohol and adalimumab. However, both alcohol and some medications often taken with adalimumab (like methotrexate) can stress the liver. It is best to discuss your alcohol consumption with your doctor to ensure it is safe in the context of your overall treatment plan.

Do not stop taking adalimumab without consulting your doctor. Stopping the medication can cause your underlying condition (like Crohn's or RA) to flare up significantly. Unlike some medications, adalimumab does not typically cause a 'withdrawal syndrome,' but the return of disease symptoms can be severe. If you need to stop the drug for surgery or because of an infection, your doctor will provide a specific plan for when to restart.

> Important: Discuss all your medical conditions with your healthcare provider before starting Adalimumab.

• Live Vaccines: You should not receive live vaccines (e.g., MMR, Varicella, Yellow Fever, Intranasal Flu vaccine) while taking adalimumab. Because adalimumab suppresses the immune system, the vaccine virus could replicate and cause a serious infection. It is recommended that all pediatric patients be brought up to date with all immunizations before starting adalimumab.

• Abatacept (Orencia): Concurrent administration of adalimumab and abatacept is associated with an increased risk of serious infections without providing additional clinical benefit. This combination is generally avoided.
• Anakinra (Kineret): Similar to abatacept, combining adalimumab with this interleukin-1 receptor antagonist increases the risk of serious infections and neutropenia (low white blood cell count) without added therapeutic advantage.
• Other Biologics: Using adalimumab with other biologic DMARDs (like rituximab, tocilizumab, or infliximab) is not recommended due to the significantly increased risk of profound immunosuppression.

• Methotrexate (MTX): While frequently used together for superior results in RA, methotrexate reduces the clearance of adalimumab by about 29% to 44%. This actually increases the levels of adalimumab in the blood, which is often therapeutically beneficial, but it may also increase the risk of side effects. No specific dose adjustment is usually required, but monitoring is essential.
• Corticosteroids and NSAIDs: Many patients take prednisone or ibuprofen alongside adalimumab. While there is no direct chemical interaction, the combined use can increase the overall risk of certain side effects, such as gastrointestinal issues or increased infection risk.
• Cytochrome P450 Substrates: The formation of CYP450 enzymes can be suppressed by high levels of cytokines (like TNF-alpha) during chronic inflammation. When adalimumab clears the inflammation, CYP450 activity may return to normal. This could lead to decreased blood levels of drugs metabolized by these enzymes (like warfarin or cyclosporine). Your doctor may need to monitor the levels of these drugs when you start or stop adalimumab.

There are no known significant interactions between adalimumab and specific foods. Unlike some medications, it is not affected by grapefruit juice or dairy products. Since the drug is injected, its absorption is not influenced by the contents of your stomach.

• Echinacea: Often used to 'boost' the immune system, Echinacea may theoretically oppose the immunosuppressive effects of adalimumab. Its use is generally discouraged in patients on biologic therapy.
• St. John’s Wort: While primarily known for interacting with liver enzymes, its effect on the immune system is not fully understood in the context of biologics. Consult your doctor before using.
• Immunosuppressive Herbs: Herbs like astragalus or licorice root may have complex effects on the immune system and should be used with caution.

Adalimumab does not typically interfere with standard laboratory chemical tests. However, it can significantly lower markers of inflammation such as C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR). While this is a sign the drug is working, it may mask the signs of a new, unrelated infection or inflammatory process.

For each major interaction, the clinical consequence is usually an increased risk of infection or a change in the drug's effectiveness. The management strategy always involves close clinical monitoring by a specialist and regular blood work to ensure the safety of the combination.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter drugs.

There are very few absolute contraindications for adalimumab, but they are critical:

1. 1Hypersensitivity: Adalimumab must NEVER be used in patients with a known hypersensitivity to adalimumab or any of its components (such as mannitol, polysorbate 80, or sodium phosphate). An allergic reaction can range from a mild rash to life-threatening anaphylaxis. The mechanism involves the immune system identifying the drug itself as a foreign invader and launching an immediate, severe inflammatory response.
2. 2Active, Severe Infection: Adalimumab should not be initiated in patients with active, clinically important infections, including localized infections or sepsis. Because the drug blocks TNF-alpha, which is essential for the body’s 'first responder' defense against bacteria and viruses, taking it during an active infection could allow the pathogen to spread rapidly and become fatal.

These conditions require a careful risk-benefit analysis by your specialist:

• Latent Tuberculosis (TB): If a patient tests positive for latent TB, they must begin treatment for TB before starting adalimumab. Starting adalimumab in someone with untreated latent TB carries a very high risk of the TB 'awakening' and becoming a systemic, life-threatening disease.
• Congestive Heart Failure (CHF): TNF blockers have been linked to the worsening of heart failure. Patients with NYHA Class III or IV heart failure should generally avoid adalimumab unless no other options exist.
• Demyelinating Disorders: Patients with a history of Multiple Sclerosis or Guillain-Barré syndrome are at risk for disease flares when taking TNF blockers.
• Hepatitis B Carriers: There is a high risk of viral reactivation, which can lead to liver failure. If used, these patients must be monitored with frequent liver tests and viral load counts.
• History of Malignancy: Because the drug suppresses the immune system's ability to 'surveil' for cancer cells, a history of lymphoma or skin cancer requires a detailed discussion about the potential for recurrence.

Patients who have had a severe allergic reaction to other TNF blockers (like infliximab or etanercept) may be at an increased risk of a reaction to adalimumab, although they are chemically different molecules. Additionally, the needle cover of some pre-filled syringes may contain natural rubber (latex), which can cause reactions in latex-sensitive individuals. Always check the specific product packaging for latex warnings.

> Important: Your healthcare provider will evaluate your complete medical history, including any past infections or cancers, before prescribing Adalimumab.

Adalimumab is not considered a known teratogen (a substance that causes birth defects). However, it is an IgG1 antibody, and these are known to cross the placenta, especially during the third trimester.

• Risks: Data from pregnancy registries do not show an increased rate of major birth defects compared to the general population. However, because the drug crosses the placenta, the infant may have higher levels of the drug in their blood at birth.
• Clinical Considerations: If adalimumab is used during pregnancy, the infant's immune system may be temporarily suppressed. This is particularly important for the administration of live vaccines (like the BCG vaccine) to the infant; it is generally recommended to wait at least 5 to 6 months after birth before giving live vaccines to babies exposed to adalimumab in utero.

Adalimumab is excreted in human breast milk in very small amounts. Because it is a large protein molecule, most of the drug that is ingested by the infant via breast milk is likely broken down in the baby’s digestive tract before it can be absorbed into their bloodstream. Most experts and clinical guidelines suggest that breastfeeding while taking adalimumab is likely safe and that the benefits of breastfeeding outweigh the potential risks.

Adalimumab is approved for several pediatric conditions, including polyarticular JIA (ages 2+), pediatric Crohn's (ages 6+), pediatric Ulcerative Colitis (ages 5+), and pediatric Uveitis (ages 2+).

• Growth: There is no evidence that adalimumab negatively impacts growth; in fact, by controlling systemic inflammation (especially in Crohn's), it may help children reach their normal growth potential.
• Safety: The safety profile in children is generally similar to adults, though the risk of certain rare malignancies (like HSTCL) is a specific concern for this population.

In clinical trials, approximately 10% of patients with RA were 65 years of age or older. While no overall differences in effectiveness were observed, the frequency of serious infection in patients over 65 was higher than in younger patients. Because older adults naturally have a higher baseline risk of infections and malignancies, healthcare providers will monitor this population very closely.

No formal studies have been conducted in patients with renal impairment. However, since adalimumab is a large protein cleared by the reticuloendothelial system and not the kidneys, renal failure is not expected to significantly change the drug's levels. No dose adjustment is typically recommended for patients with reduced GFR or those on dialysis.

Adalimumab has not been studied in patients with hepatic impairment. While the drug is not metabolized by the liver, severe liver disease can affect the body's overall protein handling. Caution is advised, and your doctor will monitor liver enzymes (ALT/AST) regularly.

> Important: Special populations require individualized medical assessment and frequent follow-up to ensure safety.

Adalimumab is a human recombinant IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). It is produced by recombinant DNA technology in a mammalian cell expression system. Adalimumab binds with high affinity and specificity to the soluble and transmembrane forms of TNF-alpha, but not to TNF-beta (lymphotoxin). TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF are found in the synovial fluid of patients with RA, JIA, PsA, and AS and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases. In plaque psoriasis, TNF levels are elevated in the skin lesions. In Crohn's and UC, TNF mediates the mucosal inflammation that leads to ulceration and GI symptoms.

After treatment with adalimumab, there is a rapid decrease in levels of acute phase reactants of inflammation (C-reactive protein and erythrocyte sedimentation rate) and serum cytokines (IL-6). In patients with rheumatoid arthritis, adalimumab reduces the levels of enzymes (matrix metalloproteinases) that cause tissue remodeling responsible for cartilage destruction. The onset of action varies; some patients with RA or psoriasis see improvement in 1–2 weeks, while for others, it may take up to 12 weeks to see the full therapeutic effect.

| Parameter | Value |

|---|---|

| Bioavailability | ~64% (Subcutaneous) |

| Protein Binding | Not applicable (it is a protein itself) |

| Half-life | 10 to 20 days (Average ~14 days) |

| Tmax | 131 ± 56 hours |

| Metabolism | Proteolysis (Reticuloendothelial system) |

| Excretion | Not renally excreted; cleared via cellular uptake |

• Molecular Formula: C6428H9912N1694O1987S46
• Molecular Weight: Approximately 148 kilodaltons (kDa)
• Structure: Adalimumab consists of 1330 amino acids and is a glycoprotein. It is composed of two IgG1 heavy chains and two kappa light chains.
• Solubility: It is supplied as a sterile, preservative-free solution for subcutaneous administration. The solution is clear and colorless.

Adalimumab is a Tumor Necrosis Factor (TNF) Blocker and a Biologic Disease-Modifying Antirheumatic Drug (bDMARD). It is part of a class that includes other medications such as Infliximab (Remicade), Etanercept (Enbrel), Certolizumab pegol (Cimzia), and Golimumab (Simponi). Among these, adalimumab is unique as the first fully human-sequence antibody, whereas infliximab is chimeric (part mouse, part human).