Actimmune

Name: Actimmune

Why is this medication prescribed?

Interferon gamma-1b injection is used to reduce the frequency and severity of serious infections in people with chronic granulomatous disease (an inherited immune system disease). It is also used to slow down worsening of their condition in people with severe, malignant osteopetrosis (an inherited bone disease). Interferon gamma-1b is in a class of medications called immunomodulators. It is not known exactly how interferon gamma-1b works to treat chronic granulomatous disease and osteopetrosis.

Brand names

  • Actimmune®

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include changes in you mental status, dizziness, loss of balance or coordination, or flu-like symptoms.

What should I avoid while using Actimmune (interferon gamma-1b)?

Drinking alcohol with this medicine can cause side effects.

This medicine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Interactions for Actimmune

No formal drug interaction studies to date.1

Specific Drugs

Drug

Interaction

Comments

Myelosuppressive agents

Possible additive myelosuppressive effects1

Use with caution1

Advice to Patients

  • Importance of advising patients not to administer the drug until their clinician has thoroughly trained them on proper administration methods (including aseptic technique) and proper disposal of used needles and syringes.1 27

  • Advise patients to notify their clinician if injection site reactions (e.g., persistent lumps, swelling, bruising, signs of infection or inflammation [pus, redness, pain]) occur.27

  • Risk of myelosuppression and adverse hepatic effects.1

  • Importance of taking interferon gamma-1b as prescribed.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Actimmune Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

More common
  • Chills
  • fever
Less common
  • Black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • confusion
  • cough or hoarseness
  • loss of balance control
  • lower back or side pain
  • mask-like face
  • painful or difficult urination
  • pinpoint red spots on the skin
  • shuffling walk
  • sore throat
  • stiffness of the arms or legs
  • trembling and shaking of the hands and fingers
  • trouble breathing
  • trouble speaking or swallowing
  • trouble thinking or concentrating
  • trouble walking
  • ulcers, sores, or white spots in the mouth
  • unusual bleeding or bruising
  • unusual tiredness or weakness
Incidence not known
  • Abdominal or stomach pain or tenderness
  • change in walking and balance
  • clay colored stools
  • clumsiness or unsteadiness
  • dark urine
  • decreased appetite
  • decreased frequency or amount of urine
  • general feeling of discomfort or illness
  • headache
  • increased thirst
  • itching or skin rash
  • joint or muscle pain
  • loss of appetite
  • lower back or side pain
  • muscle aches and pains
  • nausea and vomiting
  • numbness or tingling of the face, hands, or feet
  • painful or difficult urination
  • pale skin
  • redness and soreness of the eyes
  • runny nose
  • shivering skin
  • sweating
  • swelling of the face, fingers, or lower legs
  • trouble sleeping
  • weight gain
  • yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Diarrhea
  • redness or tenderness at the injection site
Less common
  • Back pain
  • dizziness
  • weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Signs of skin infection like oozing, heat, swelling, redness, or pain.
  • Feeling confused.
  • Change in balance.
  • Trouble walking.
  • Dizziness or passing out.
  • Seizures.
  • Hallucinations (seeing or hearing things that are not there).
  • Bruising, lump, or swelling at the injection site that does not go away.

Adverse Reactions

The following adverse reactions are described below and elsewhere in the warnings and precautions section of the labeling:

  • Cardiovascular Disorders [see Warnings and Precautions (5.1)]
  • Neurologic Disorders [see Warnings and Precautions (5.2)]
  • Bone Marrow Toxicity [see Warnings and Precautions (5.3)]
  • Hepatic Toxicity [see Warnings and Precautions (5.4)]
  • Hypersensitivity Reactions [see Warnings and Precautions (5.5)]
  • Renal Toxicity [see Warnings and Precautions (5.6)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following data on adverse reactions are based on the subcutaneous administration of Actimmune at a dose of 50 mcg/m2, three times weekly, in patients with CGD during a clinical trial in the United States and Europe.

The most common adverse reactions observed in patients with CGD are shown in the following table:

Table 2: Adverse Reactions Occurring in 2% or Greater of CGD Patients Receiving Actimmune in Clinical Trials
Adverse Reactions Percent of Patients
Actimmune
CGD (n=63)
Placebo
CGD (n=65)
Fever 52 28
Headache 33 9
Rash 17 6
Chills 14 0
Injection site erythema or tenderness 14 2
Fatigue 14 11
Diarrhea 14 12
Vomiting 13 5
Nausea 10 2
Myalgia 6 0
Arthralgia 2 0

Similar safety data were observed in 34 patients with SMO.

The clinical and laboratory toxicity associated with multiple dose studies of Actimmune is dose, route and schedule-dependent.

The most common adverse reactions include constitutional symptoms such as fever, headache, chills, myalgia or fatigue which may decrease in severity as treatment continues.

Less Common Adverse Reactions

The following adverse reactions are assessed as potentially related to Actimmune (interferon gamma-1b) therapy:

Blood and Lymphatic System neutropenia (reversible), febrile neutropenia, leukopenia, and thrombocytopenia.

Cardiovascular angina pectoris, arrhythmia, atrial fibrillation, atrioventricular block, cardiac failure (including congestive cardiac failure), tachyarrhythmia, heart block, (acute) myocardial infarction, myocardial ischemia, syncope, and tachycardia.

Gastrointestinal abdominal pain, dyspepsia, gastrointestinal bleeding, granulomatous colitis, hepatic insufficiency, and pancreatitis, including pancreatitis with fatal outcome.

General Disorders and Administration Site Conditions asthenia, chest pain/discomfort, influenza-like illness/flu-like symptoms, injection site hemorrhage, injection site pain, malaise, rigors, and weakness.

Hepatobiliary Disorders hepatic insufficiency and hepatomegaly.

Immunological hypersensitivity, increased autoantibodies, lupus-like syndrome (including systemic lupus erythematosus-flares and drug-induced lupus erythematosus), and Stevens-Johnson syndrome.

Infections and Infestations upper respiratory tract infection.

Investigations blood alkaline phosphatase increased, liver function tests abnormal/elevation of hepatic enzymes, increased triglycerides, and weight decreased.

Metabolic hyponatremia, hypokalemia, hyperglycemia, and hypertriglyceridemia.

Musculoskeletal back pain, clubbing, and muscle spasms.

Nervous System dizziness (excluding vertigo), gait disturbance, headache, Parkinsonian symptoms, convulsion/seizure (including grand mal convulsions), and transient ischemic attacks.

Psychiatric confusion, depression, disorientation, hallucinations, mental status changes, and mental status decreased.

Pulmonary tachypnea, bronchospasm, pulmonary edema, and interstitial pneumonitis.

Renal acute renal failure (which may be reversible) and proteinuria.

Skin and Subcutaneous Tissue Disorders atopic dermatitis, (exacerbation of) dermatomyositis, transient cutaneous rash, and urticaria.

Vascular Disorder deep venous thrombosis, hypotension, pulmonary embolism.

Abnormal Laboratory Test Values: Elevations of ALT and AST have been observed [see Warnings and Precautions (5.4)].

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Actimmune. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Children with CGD less than 3 years of age:

Data on the safety and activity of Actimmune in 37 patients under the age of 3 years was pooled from four uncontrolled postmarketing studies. The rate of serious infections per patient-year in this uncontrolled group was similar to the rate observed in the Actimmune treatment groups in controlled trials. Developmental parameters (height, weight and endocrine maturation) for this uncontrolled group conformed to national normative scales before and during Actimmune therapy.

In 6 of the 10 patients receiving Actimmune therapy before age one year 2-fold to 25-fold elevations from baseline of AST and/or ALT were observed. These elevations occurred as early as 7 days after starting treatment. Treatment with Actimmune was interrupted in all 6 of these patients and was restarted at a reduced dosage in 4. Liver transaminase values returned to baseline in all patients and transaminase elevation recurred in one patient upon Actimmune rechallenge. An 11-fold alkaline phosphatase elevation and hypokalemia in one patient and neutropenia (ANC = 525 cells/mm3) in another patient resolved with interruption of Actimmune treatment and did not recur with rechallenge.

In the postmarketing safety database clinically significant adverse reactions observed during Actimmune therapy in children under the age of three years (n=14) included: two cases of hepatomegaly, and one case each of Stevens-Johnson syndrome, granulomatous colitis, urticaria, and atopic dermatitis.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. In clinical trials, 8 out of 33 Actimmune-treated patients developed non-neutralizing antibodies to interferon gamma-1b. No neutralizing antibodies to Actimmune have been detected in patients. In a Phase 1 study, none of the 38 Actimmune-treated healthy volunteers developed non-neutralizing antibodies to interferon gamma-1b.

The detection of antibody formation, including neutralizing antibody, in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Actimmune with the incidence of antibodies to other products may be misleading.

Overdose

Central nervous system adverse reactions including decreased mental status, gait disturbance and dizziness have been observed, particularly in patients receiving doses greater than 100 mcg/m²/day by intravenous or intramuscular administration. These abnormalities were reversible within a few days upon dose reduction or discontinuation of therapy. Reversible neutropenia, elevation of hepatic enzymes and of triglycerides, and thrombocytopenia have also been observed.

Interferon gamma-1b Breastfeeding Warnings

There are no data on the excretion of interferon gamma-1b into human milk. The manufacturer recommends that due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

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