Humira

The most common side effects are:

• headache,
• rash,
• nausea and
• stomach upset.

Adalimumab may cause swelling, redness, pain and itching at the site of injection. Adalimumab suppresses the immune system and is therefore associated with minor infections of the urinary tract, respiratory tract, and sinuses. Like other drugs that block TNF, use of adalimumab also has been associated with serious infections such as tuberculosis, sepsis (bacteria in the blood) and fungal infections. Individuals with active infections should not be treated with adalimumab. Adalimumab also may worsen the symptoms of diseases of the nervous system. In studies some patients who used adalimumab or other TNF blocking drugs developed cancer. Since patients with rheumatoid arthritis have a higher rate of cancers than the general population, the connection between cancer and use of adalimumab is unclear.

Other side effects of adalimumab include:

• hypersensitivity reactions (including anaphylaxis) and
• reduced levels in the blood of platelets and red cells (aplastic anemia).

Adalimumab may increase the risk of reactivating hepatitis B virus in chronic carriers of the virus.

• AbbVie Inc.

Tell your doctor if you are pregnant or planning to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Humira falls into category B. Humira can cross the placenta during the third trimester of pregnancy. No harm was observed in studies performed in pregnant animals. Because animal studies cannot always predict how these medications may affect humans, Humira should be used during pregnancy only if clearly needed.

Biologic response modifier and disease-modifying antirheumatic drug (DMARD); a recombinant DNA-derived human immunoglobulin G1 (IgG1) monoclonal antibody specific for human tumor necrosis factor (TNF; TNF-α).1

• It is used to treat rheumatoid arthritis.
• It is used to treat psoriatic arthritis.
• It is used to treat Crohn's disease.
• It is used to treat ankylosing spondylitis.
• It is used to treat plaque psoriasis.
• It is used to treat ulcerative colitis.
• It is used to treat juvenile arthritis.
• It is used to treat a skin problem called hidradenitis suppurativa.
• It is used to treat uveitis.
• It may be given to you for other reasons. Talk with the doctor.

Use Humira as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into the fatty part of the skin.
• If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot.
• Wash your hands before and after use.
• Follow how to use as you have been told by the doctor or read the package insert.
• Do not shake the solution.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not give if the solution is not clear and colorless.
• Do not give into red or irritated skin.
• Move the site where you give the shot with each shot.
• If it makes the shot feel better, this medicine can be taken out of the refrigerator 15 to 30 minutes before using. Allow to sit at room temperature without removing the cap or cover. Do not heat Humira.
• Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.
• Throw syringe away after use. Do not use the same syringe more than one time.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• If you are not sure what to do if you miss a dose, call your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Stuffy nose.
• Runny nose.
• Belly pain.
• Upset stomach.
• Back pain.
• Irritation where the shot is given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Rheumatoid Arthritis

Humira is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. Humira can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs).

Juvenile Idiopathic Arthritis

Humira is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. Humira can be used alone or in combination with methotrexate.

Psoriatic Arthritis

Humira is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. Humira can be used alone or in combination with non-biologic DMARDs.

Ankylosing Spondylitis

Humira is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.

Adult Crohn’s Disease

Humira is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. Humira is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

Pediatric Crohn’s Disease

Humira is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active Crohn’s disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate.

Ulcerative Colitis

Humira is indicated for inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine or 6-mercaptopurine (6-MP). The effectiveness of Humira has not been established in patients who have lost response to or were intolerant to TNF blockers [see Clinical Studies (14.7)].

Plaque Psoriasis

Humira is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. Humira should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician [see Boxed Warning and Warnings and Precautions (5)].

Hidradenitis Suppurativa

Humira is indicated for the treatment of moderate to severe hidradenitis suppurativa.

Uveitis

Humira is indicated for the treatment of non-infectious intermediate, posterior and panuveitis in adult patients.

Mechanism of Action

Adalimumab binds specifically to TNF-alpha and blocks its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface TNF expressing cells in vitro in the presence of complement. Adalimumab does not bind or inactivate lymphotoxin (TNF-beta). 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. Increased levels of TNF are also found in psoriasis plaques. In Ps, treatment with Humira may reduce the epidermal thickness and infiltration of inflammatory cells. The relationship between these pharmacodynamic activities and the mechanism(s) by which Humira exerts its clinical effects is unknown.

Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 with an IC50 of 1-2 X 10-10M).

Pharmacodynamics

After treatment with Humira, a decrease in levels of acute phase reactants of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and serum cytokines (IL-6) was observed compared to baseline in patients with rheumatoid arthritis. A decrease in CRP levels was also observed in patients with Crohn’s disease, ulcerative colitis and hidradenitis suppurativa. Serum levels of matrix metalloproteinases (MMP-1 and MMP-3) that produce tissue remodeling responsible for cartilage destruction were also decreased after Humira administration.

Pharmacokinetics

The maximum serum concentration (Cmax) and the time to reach the maximum concentration (Tmax) were 4.7 ± 1.6 µg/mL and 131 ± 56 hours respectively, following a single 40 mg subcutaneous administration of Humira to healthy adult subjects. The average absolute bioavailability of adalimumab estimated from three studies following a single 40 mg subcutaneous dose was 64%. The pharmacokinetics of adalimumab were linear over the dose range of 0.5 to 10.0 mg/kg following a single intravenous dose.

The single dose pharmacokinetics of adalimumab in RA patients were determined in several studies with intravenous doses ranging from 0.25 to 10 mg/kg. The distribution volume (Vss) ranged from 4.7 to 6.0 L. The systemic clearance of adalimumab is approximately 12 mL/hr. The mean terminal half-life was approximately 2 weeks, ranging from 10 to 20 days across studies. Adalimumab concentrations in the synovial fluid from five rheumatoid arthritis patients ranged from 31 to 96% of those in serum.

In RA patients receiving 40 mg Humira every other week, adalimumab mean steady-state trough concentrations of approximately 5 µg/mL and 8 to 9 µg/mL, were observed without and with methotrexate (MTX), respectively. MTX reduced adalimumab apparent clearance after single and multiple dosing by 29% and 44% respectively, in patients with RA. Mean serum adalimumab trough levels at steady state increased approximately proportionally with dose following 20, 40, and 80 mg every other week and every week subcutaneous dosing. In long-term studies with dosing more than two years, there was no evidence of changes in clearance over time.

Adalimumab mean steady-state trough concentrations were slightly higher in psoriatic arthritis patients treated with 40 mg Humira every other week (6 to 10 µg/mL and 8.5 to 12 µg/mL, without and with MTX, respectively) compared to the concentrations in RA patients treated with the same dose.

The pharmacokinetics of adalimumab in patients with AS were similar to those in patients with RA.

In patients with CD, the loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira on Week 2 achieves mean serum adalimumab trough levels of approximately 12 µg/mL at Week 2 and Week 4. Mean steady-state trough levels of approximately 7 µg/mL were observed at Week 24 and Week 56 in CD patients after receiving a maintenance dose of 40 mg Humira every other week.

In patients with UC, the loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira on Week 2 achieves mean serum adalimumab trough levels of approximately 12 µg/mL at Week 2 and Week 4. Mean steady-state trough level of approximately 8 µg/mL was observed at Week 52 in UC patients after receiving a dose of 40 mg Humira every other week, and approximately 15 µg/mL at Week 52 in UC patients who increased to a dose of 40 mg Humira every week.

In patients with Ps, the mean steady-state trough concentration was approximately 5 to 6 µg/mL during Humira 40 mg every other week monotherapy treatment.

In subjects with HS, a dose of 160 mg Humira on Week 0 followed by 80 mg on Week 2 achieved serum adalimumab trough concentrations of approximately 7 to 8 µg/mL at Week 2 and Week 4. The mean steady-state trough concentrations at Week 12 through Week 36 were approximately 7 to 11 µg/mL during Humira 40 mg every week treatment.

In patients with UV, the mean steady concentration was approximately 8 to 10 µg/mL during Humira 40 mg every other week treatment.

Population pharmacokinetic analyses in patients with RA revealed that there was a trend toward higher apparent clearance of adalimumab in the presence of anti-adalimumab antibodies, and lower clearance with increasing age in patients aged 40 to >75 years.

Minor increases in apparent clearance were also predicted in RA patients receiving doses lower than the recommended dose and in RA patients with high rheumatoid factor or CRP concentrations. These increases are not likely to be clinically important.

No gender-related pharmacokinetic differences were observed after correction for a patient’s body weight. Healthy volunteers and patients with rheumatoid arthritis displayed similar adalimumab pharmacokinetics.

No pharmacokinetic data are available in patients with hepatic or renal impairment.

In Study JIA-I for patients with polyarticular JIA who were 4 to 17 years of age, the mean steady-state trough serum adalimumab concentrations for patients weighing <30 kg receiving 20 mg Humira subcutaneously every other week as monotherapy or with concomitant MTX were 6.8 µg/mL and 10.9 µg/mL, respectively. The mean steady-state trough serum adalimumab concentrations for patients weighing ≥30 kg receiving 40 mg Humira subcutaneously every other week as monotherapy or with concomitant MTX were 6.6 µg/mL and 8.1 µg/mL, respectively. In Study JIA-II for patients with polyarticular JIA who were 2 to <4 years of age or 4 years of age and older weighing <15 kg, the mean steady-state trough serum adalimumab concentrations for patients receiving Humira subcutaneously every other week as monotherapy or with concomitant MTX were 6.0 µg/mL and 7.9 µg/mL, respectively.

In pediatric subjects with CD weighing ≥ 40 kg, the mean ±SD serum adalimumab concentrations were 15.7±6.5 mcg/mL at Week 4 following subcutaneous doses of 160 mg at Week 0 and 80 mg at Week 2 and the mean ±SD steady-state trough serum adalimumab concentrations were 10.5±6.0 mcg/mL at Week 52 following subcutaneous doses of 40 mg every other week. In pediatric subjects with CD weighing < 40 kg, the mean ±SD serum adalimumab concentrations were 10.6±6.1 mcg/mL at Week 4 following subcutaneous doses of 80 mg at Week 0 and 40 mg at Week 2 and the mean ±SD steady-state trough serum adalimumab concentrations were 6.9±3.6 mcg/mL at Week 52 following subcutaneous doses of 20 mg every other week.

Some people using Humira have developed a rare fast-growing type of lymphoma (cancer). This condition affects the liver, spleen, and bone marrow, and it can be fatal. Humira can also lower blood cells that help your body fight infections and help your blood to clot. Serious and sometimes fatal infections may occur during treatment with Humira.

Call your doctor at once if you have symptoms such as fever, night sweats, weight loss, feeling full after eating only a small amount, pain in your upper stomach, easy bruising or bleeding, dark urine, or jaundice (yellowing of the skin or eyes).

Humira can lower blood cells that help your body fight infections and help your blood to clot. Your blood may need to be tested often. Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding injury. Serious and sometimes fatal infections may occur during treatment with Humira. Tell your doctor at once if you develop signs of infection.

You should not use Humira if you are allergic to adalimumab, or if you have an active infection.

Some people using Humira have developed a rare fast-growing type of lymphoma (cancer). This condition affects the liver, spleen, and bone marrow, and it can be fatal. This has occurred mainly in teenagers and young adults using Humira or similar medicines to treat Crohn's disease or ulcerative colitis. However, people with autoimmune disorders may have a higher risk of lymphoma.

To make sure Humira is safe for you, tell your doctor if you have ever had:

• chronic infections;

• cancer;

• hepatitis B;

• congestive heart failure;

• any numbness or tingling, or a nerve-muscle disorder such as multiple sclerosis or Guillain-Barre syndrome;

• an allergy to latex rubber; or

• if you have recently received or are scheduled to receive any vaccine.

Make sure you are current on all vaccines before you start treatment with Humira.

Tell your doctor if you have ever had tuberculosis, if anyone in your household has tuberculosis, or if you have recently traveled to an area where tuberculosis is common.

Some infections are more likely to occur in certain areas of the world. Tell your doctor where you live and where you have recently traveled or plan to travel to during treatment.

It is not known whether Humira will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

If you have a baby after receiving adalimumab during pregnancy, tell the baby's doctor before your baby is given any vaccines.

It is not known whether adalimumab passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Humira should not be given to a child younger than 2 years old (or 6 years old if treating Crohn's disease). Children using Humira should be current on all childhood immunizations before starting treatment.

Using this medicine may increase your risk of certain types of cancer, such as lymphoma (cancer of the lymph nodes), or melanoma (a tumor that usually affects the skin). You may also develop an autoimmune disorder such as a lupus-like syndrome. Talk with your doctor about your specific risk.

Common side effects of Humira include: upper respiratory tract infection, headache, injection site reaction, skin rash, antibody development, sinusitis, and pain at injection site. Other side effects include: urinary tract infection, abdominal pain, and flu-like symptoms. See below for a comprehensive list of adverse effects.