DRUGS & SUPPLEMENTS

Realdiron

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Realdiron uses


INDICATIONS AND USAGE

Hairy Cell Leukemia

INTRON® A is indicated for the treatment of patients 18 years of age or older with hairy cell leukemia.

Malignant Melanoma

Realdiron is indicated as adjuvant to surgical treatment in patients 18 years of age or older with malignant melanoma who are free of disease but at high risk for systemic recurrence, within 56 days of surgery.

Follicular Lymphoma

Realdiron is indicated for the initial treatment of clinically aggressive follicular Non-Hodgkin's Lymphoma in conjunction with anthracycline-containing combination chemotherapy in patients 18 years of age or older. Efficacy of Realdiron therapy in patients with low-grade, low-tumor burden follicular Non-Hodgkin's Lymphoma has not been demonstrated.

Condylomata Acuminata

Realdiron is indicated for intralesional treatment of selected patients 18 years of age or older with condylomata acuminata involving external surfaces of the genital and perianal areas (see DOSAGE AND ADMINISTRATION ).

The use of this product in adolescents has not been studied.

AIDS-Related Kaposi's Sarcoma

Realdiron is indicated for the treatment of selected patients 18 years of age or older with AIDS-Related Kaposi's Sarcoma. The likelihood of response to Realdiron therapy is greater in patients who are without systemic symptoms, who have limited lymphadenopathy and who have a relatively intact immune system as indicated by total CD4 count.

Chronic Hepatitis C

Realdiron is indicated for the treatment of chronic hepatitis C in patients 18 years of age or older with compensated liver disease who have a history of blood or blood-product exposure and/or are HCV antibody positive. Studies in these patients demonstrated that Realdiron therapy can produce clinically meaningful effects on this disease, manifested by normalization of serum alanine aminotransferase and reduction in liver necrosis and degeneration.

A liver biopsy should be performed to establish the diagnosis of chronic hepatitis. Patients should be tested for the presence of antibody to HCV. Patients with other causes of chronic hepatitis, including autoimmune hepatitis, should be excluded. Prior to initiation of Realdiron therapy, the physician should establish that the patient has compensated liver disease. The following patient entrance criteria for compensated liver disease were used in the clinical studies and should be considered before Realdiron treatment of patients with chronic hepatitis C:

  • No history of hepatic encephalopathy, variceal bleeding, ascites, or other clinical signs of decompensation
  • Bilirubin
Less than or equal to 2 mg/dL
  • Albumin
Stable and within normal limits
  • Prothrombin Time
Less than 3 seconds prolonged
  • WBC
Greater than or equal to 3000/mm3
  • Platelets
Greater than or equal to 70,000/mm3

Serum creatinine should be normal or near normal.

Prior to initiation of Realdiron therapy, CBC and platelet counts should be evaluated in order to establish baselines for monitoring potential toxicity. These tests should be repeated at Weeks 1 and 2 following initiation of Realdiron therapy, and monthly thereafter. Serum ALT should be evaluated at approximately 3-month intervals to assess response to treatment (see DOSAGE AND ADMINISTRATION ).

Patients with preexisting thyroid abnormalities may be treated if thyroid-stimulating hormone (TSH) levels can be maintained in the normal range by medication. TSH levels must be within normal limits upon initiation of Realdiron treatment and TSH testing should be repeated at 3 and 6 months (see PRECAUTIONS, Laboratory Tests ).

Realdiron in combination with REBETOL® is indicated for the treatment of chronic hepatitis C in patients 3 years of age and older with compensated liver disease previously untreated with alpha interferon therapy and in patients 18 years of age and older who have relapsed following alpha interferon therapy. See REBETOL prescribing information for additional information.

Chronic Hepatitis B

Realdiron is indicated for the treatment of chronic hepatitis B in patients 1 year of age or older with compensated liver disease. Patients who have been serum HBsAg positive for at least 6 months and have evidence of HBV replication (serum HBeAg positive) with elevated serum ALT are candidates for treatment. Studies in these patients demonstrated that Realdiron therapy can produce virologic remission of this disease (loss of serum HBeAg) and normalization of serum aminotransferases. Realdiron therapy resulted in the loss of serum HBsAg in some responding patients.

Prior to initiation of Realdiron therapy, it is recommended that a liver biopsy be performed to establish the presence of chronic hepatitis and the extent of liver damage. The physician should establish that the patient has compensated liver disease. The following patient entrance criteria for compensated liver disease were used in the clinical studies and should be considered before Realdiron treatment of patients with chronic hepatitis B:

  • No history of hepatic encephalopathy, variceal bleeding, ascites, or other signs of clinical decompensation
  • Bilirubin
Normal
  • Albumin
Stable and within normal limits
  • Prothrombin Time
Adults less than 3 seconds prolonged

Pediatrics less than or equal to 2 seconds prolonged

  • WBC
Greater than or equal to 4000/mm3
  • Platelets
Adults greater than or equal to 100,000/mm3

Pediatrics greater than or equal to 150,000/mm3


Patients with causes of chronic hepatitis other than chronic hepatitis B or chronic hepatitis C should not be treated with Realdiron. CBC and platelet counts should be evaluated prior to initiation of Realdiron therapy in order to establish baselines for monitoring potential toxicity. These tests should be repeated at treatment Weeks 1, 2, 4, 8, 12, and 16. Liver function tests, including serum ALT, albumin, and bilirubin, should be evaluated at treatment Weeks 1, 2, 4, 8, 12, and 16. HBeAg, HBsAg, and ALT should be evaluated at the end of therapy, as well as 3- and 6-months post-therapy, since patients may become virologic responders during the 6-month period following the end of treatment. In clinical studies in adults, 39% (15/38) of responding patients lost HBeAg 1 to 6 months following the end of Realdiron therapy. Of responding patients who lost HBsAg, 58% (7/12) did so 1 to 6 months post-treatment.

A transient increase in ALT greater than or equal to 2 times baseline value (flare) can occur during Realdiron therapy for chronic hepatitis B. In clinical trials in adults and pediatrics, this flare generally occurred 8 to 12 weeks after initiation of therapy and was more frequent in responders (adults 63%, 24/38; pediatrics 59%, 10/17) than in nonresponders (adults 27%, 13/48; pediatrics 35%, 19/55). However, in adults and pediatrics, elevations in bilirubin greater than or equal to 3 mg/dL (greater than or equal to 2 times ULN) occurred infrequently (adults 2%, 2/86; pediatrics 3%, 2/72) during therapy. When ALT flare occurs, in general, Realdiron therapy should be continued unless signs and symptoms of liver failure are observed. During ALT flare, clinical symptomatology and liver function tests including ALT, prothrombin time, alkaline phosphatase, albumin, and bilirubin, should be monitored at approximately 2-week intervals (see WARNINGS ).

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CONTRAINDICATIONS

INTRON® A is contraindicated in patients with:

  • Hypersensitivity to interferon alpha or any component of the product
  • Autoimmune hepatitis
  • Decompensated liver disease

Realdiron and REBETOL® combination therapy is additionally contraindicated in:

  • Patients with hypersensitivity to ribavirin or any other component of the product
  • Women who are pregnant
  • Men whose female partners are pregnant
  • Patients with hemoglobinopathies (e.g., thalassemia major, sickle cell anemia)
  • Patients with creatinine clearance less than 50 mL/min.

WARNINGS

General

Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some cases termination of INTRON® A therapy. Because of the fever and other "flu-like" symptoms associated with Realdiron administration, it should be used cautiously in patients with debilitating medical conditions, such as those with a history of pulmonary disease or diabetes mellitus prone to ketoacidosis. Caution should also be observed in patients with coagulation disorders (e.g., thrombophlebitis, pulmonary embolism) or severe myelosuppression.

Cardiovascular Disorders

Realdiron therapy should be used cautiously in patients with a history of cardiovascular disease. Those patients with a history of myocardial infarction and/or previous or current arrhythmic disorder who require Realdiron therapy should be closely monitored (see PRECAUTIONS, Laboratory Tests ). Cardiovascular adverse experiences, which include hypotension, arrhythmia, or tachycardia of 150 beats per minute or greater, and rarely, cardiomyopathy and myocardial infarction have been observed in some INTRON A-treated patients. Some patients with these adverse events had no history of cardiovascular disease. Transient cardiomyopathy was reported in approximately 2% of the AIDS-Related Kaposi's Sarcoma patients treated with Realdiron. Hypotension may occur during Realdiron administration, or up to 2 days post-therapy, and may require supportive therapy including fluid replacement to maintain intravascular volume.

Supraventricular arrhythmias occurred rarely and appeared to be correlated with preexisting conditions and prior therapy with cardiotoxic agents. These adverse experiences were controlled by modifying the dose or discontinuing treatment, but may require specific additional therapy.

Cerebrovascular Disorders

Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alpha-based therapies, including Realdiron. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made and a causal relationship between interferon alpha-based therapies and these events is difficult to establish.

Neuropsychiatric Disorders

DEPRESSION AND SUICIDAL BEHAVIOR INCLUDING SUICIDAL IDEATION, SUICIDAL ATTEMPTS, AND COMPLETED SUICIDES, HOMICIDAL IDEATION, AND AGGRESSIVE BEHAVIOR SOMETIMES DIRECTED TOWARDS OTHERS, HAVE BEEN REPORTED IN ASSOCIATION WITH TREATMENT WITH ALPHA INTERFERONS, INCLUDING Realdiron THERAPY. If patients develop psychiatric problems, including clinical depression, it is recommended that the patients be carefully monitored during treatment and in the 6-month follow-up period.

Realdiron should be used with caution in patients with a history of psychiatric disorders. Realdiron therapy should be discontinued for any patient developing severe psychiatric disorder during treatment. Obtundation and coma have also been observed in some patients, usually elderly, treated at higher doses. While these effects are usually rapidly reversible upon discontinuation of therapy, full resolution of symptoms has taken up to 3 weeks in a few severe episodes. If psychiatric symptoms persist or worsen, or suicidal or homicidal ideation or aggressive behavior towards others is identified, discontinue treatment with Realdiron and follow the patient closely, with psychiatric intervention as appropriate. Narcotics, hypnotics, or sedatives may be used concurrently with caution and patients should be closely monitored until the adverse effects have resolved. Suicidal ideation or attempts occurred more frequently among pediatric patients, primarily adolescents, compared to adult patients during treatment and off-therapy follow-up. Cases of encephalopathy have also been observed in some patients, usually elderly, treated with higher doses of Realdiron.

Treatment with interferons may be associated with exacerbated symptoms of psychiatric disorders in patients with co-occurring psychiatric and substance use disorders. If treatment with interferons is initiated in patients with prior history or existence of psychiatric condition or with a history of substance use disorders, treatment considerations should include the need for drug screening and periodic health evaluation, including psychiatric symptom monitoring. Early intervention for re-emergence or development of neuropsychiatric symptoms and substance use is recommended.

Bone Marrow Toxicity

Realdiron therapy suppresses bone marrow function and may result in severe cytopenias including aplastic anemia. It is advised that complete blood counts (CBC) be obtained pretreatment and monitored routinely during therapy (see PRECAUTIONS, Laboratory Tests ). Realdiron therapy should be discontinued in patients who develop severe decreases in neutrophil (less than 0.5 × 109/L) or platelet counts (less than 25 × 109/L) (see DOSAGE AND ADMINISTRATION, Guidelines for Dose Modification ).

Ophthalmologic Disorders

Decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots; optic neuritis, papilledema, and serous retinal detachment may be induced or aggravated by treatment with Realdiron or other alpha interferons. All patients should receive an eye examination at baseline. Patients with preexisting ophthalmologic disorders should receive periodic ophthalmologic exams during interferon alpha treatment. Any patient who develops ocular symptoms should receive a prompt and complete eye examination. Realdiron treatment should be discontinued in patients who develop new or worsening ophthalmologic disorders.

Endocrine Disorders

Infrequently, patients receiving Realdiron therapy developed thyroid abnormalities, either hypothyroid or hyperthyroid. The mechanism by which Realdiron may alter thyroid status is unknown. Patients with preexisting thyroid abnormalities whose thyroid function cannot be maintained in the normal range by medication should not be treated with Realdiron. Prior to initiation of Realdiron therapy, serum TSH should be evaluated. Patients developing symptoms consistent with possible thyroid dysfunction during the course of Realdiron therapy should have their thyroid function evaluated and appropriate treatment instituted. Therapy should be discontinued for patients developing thyroid abnormalities during treatment whose thyroid function cannot be normalized by medication. Discontinuation of Realdiron therapy has not always reversed thyroid dysfunction occurring during treatment. Diabetes mellitus has been observed in patients treated with alpha interferons. Patients with these conditions who cannot be effectively treated by medication should not begin Realdiron therapy. Patients who develop these conditions during treatment and cannot be controlled with medication should not continue Realdiron therapy.

Gastrointestinal Disorders

Hepatotoxicity, including fatality, has been observed in interferon alpha-treated patients, including those treated with Realdiron. Realdiron increases the risk of hepatic decompensation and death in patients with cirrhosis. Any patient developing liver function abnormalities during treatment should be monitored closely and if appropriate, treatment should be discontinued.

Pulmonary Disorders

Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis, some resulting in respiratory failure and/or patient deaths, may be induced or aggravated by Realdiron or other alpha interferons. Recurrence of respiratory failure has been observed with interferon rechallenge. The etiologic explanation for these pulmonary findings has yet to be established. Any patient developing fever, cough, dyspnea, or other respiratory symptoms should have a chest X-ray taken. If the chest X-ray shows pulmonary infiltrates or there is evidence of pulmonary function impairment, the patient should be closely monitored, and, if appropriate, interferon alpha treatment should be discontinued. While this has been reported more often in patients with chronic hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated with interferon alpha.

Autoimmune Disorders

Rare cases of autoimmune diseases including thrombocytopenia, vasculitis, Raynaud's phenomenon, rheumatoid arthritis, lupus erythematosus, and rhabdomyolysis have been observed in patients treated with alpha interferons, including patients treated with Realdiron. In very rare cases the event resulted in fatality. The mechanism by which these events developed and their relationship to interferon alpha therapy is not clear. Any patient developing an autoimmune disorder during treatment should be closely monitored and, if appropriate, treatment should be discontinued.

Human Albumin

The powder formulations of this product contain albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

AIDS-Related Kaposi's Sarcoma

Realdiron therapy should not be used for patients with rapidly progressive visceral disease (see CLINICAL PHARMACOLOGY ). Also of note, there may be synergistic adverse effects between Realdiron and zidovudine. Patients receiving concomitant zidovudine have had a higher incidence of neutropenia than that expected with zidovudine alone. Careful monitoring of the WBC count is indicated in all patients who are myelosuppressed and in all patients receiving other myelosuppressive medications. The effects of Realdiron when combined with other drugs used in the treatment of AIDS-related disease are unknown.

Chronic Hepatitis C and Chronic Hepatitis B

Patients with decompensated liver disease, autoimmune hepatitis or a history of autoimmune disease, and patients who are immunosuppressed transplant recipients should not be treated with Realdiron. There are reports of worsening liver disease, including jaundice, hepatic encephalopathy, hepatic failure, and death following Realdiron therapy in such patients. Therapy should be discontinued for any patient developing signs and symptoms of liver failure.

Chronic hepatitis B patients with evidence of decreasing hepatic synthetic functions, such as decreasing albumin levels or prolongation of prothrombin time, who nevertheless meet the entry criteria to start therapy, may be at increased risk of clinical decompensation if a flare of aminotransferases occurs during Realdiron treatment. In such patients, if increases in ALT occur during Realdiron therapy for chronic hepatitis B, they should be followed carefully, including close monitoring of clinical symptomatology and liver function tests including ALT, prothrombin time, alkaline phosphatase, albumin, and bilirubin. In considering these patients for Realdiron therapy, the potential risks must be evaluated against the potential benefits of treatment.

Peripheral Neuropathy

Peripheral neuropathy has been reported when alpha interferons were given in combination with telbivudine. In one clinical trial, an increased risk and severity of peripheral neuropathy was observed with the combination use of telbivudine and pegylated interferon alfa-2a as compared to telbivudine alone. The safety and efficacy of telbivudine in combination with interferons for the treatment of chronic hepatitis B has not been demonstrated.

Use with Ribavirin

REBETOL may cause birth defects and/or death of the unborn child. REBETOL therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Patients should use at least two forms of contraception and have monthly pregnancy tests (see CONTRAINDICATIONS and PRECAUTIONS, Information for Patients ).

Combination treatment with Realdiron and REBETOL was associated with hemolytic anemia. Hemoglobin less than 10 g/dL was observed in approximately 10% of adult and pediatric patients in clinical trials. Anemia occurred within 1 to 2 weeks of initiation of ribavirin therapy. Combination treatment with Realdiron and REBETOL should not be used in patients with creatinine clearance less than 50 mL/min. See REBETOL prescribing information for additional information.

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PRECAUTIONS

General

Acute serious hypersensitivity reactions have been observed rarely in INTRON® A-treated patients; if such an acute reaction develops, the drug should be discontinued immediately and appropriate medical therapy instituted. Transient rashes have occurred in some patients following injection, but have not necessitated treatment interruption.

While fever may be related to the flu-like syndrome reported commonly in patients treated with interferon, other causes of persistent fever should be ruled out.

There have been reports of interferon, including Realdiron, exacerbating preexisting psoriasis and sarcoidosis as well as development of new sarcoidosis. Therefore, Realdiron therapy should be used in these patients only if the potential benefit justifies the potential risk.

Variations in dosage, routes of administration, and adverse reactions exist among different brands of interferon. Therefore, do not use different brands of interferon in any single treatment regimen.

Triglycerides

Elevated triglyceride levels have been observed in patients treated with interferons, including Realdiron therapy. Elevated triglyceride levels should be managed as clinically appropriate. Hypertriglyceridemia may result in pancreatitis. Discontinuation of Realdiron therapy should be considered for patients with persistently elevated triglycerides (e.g., triglycerides greater than 1000 mg/dL) associated with symptoms of potential pancreatitis, such as abdominal pain, nausea, or vomiting.

Drug Interactions

Interactions between Realdiron and other drugs have not been fully evaluated. Caution should be exercised when administering Realdiron therapy in combination with other potentially myelosuppressive agents such as zidovudine. Concomitant use of alpha interferon and theophylline decreases theophylline clearance, resulting in a 100% increase in serum theophylline levels.

Information for Patients

Patients receiving Realdiron alone or in combination with REBETOL® should be informed of the risks and benefits associated with treatment and should be instructed on proper use of the product. To supplement your discussion with a patient, you may wish to provide patients with a copy of the MEDICATION GUIDE.

Patients should be informed of, and advised to seek medical attention for, symptoms indicative of serious adverse reactions associated with this product. Such adverse reactions may include depression, cardiovascular (chest pain), ophthalmologic toxicity (decrease in/or loss of vision), pancreatitis or colitis (severe abdominal pain), and cytopenias (high persistent fevers, bruising, dyspnea). Patients should be advised that some side effects such as fatigue and decreased concentration might interfere with the ability to perform certain tasks. Patients who are taking Realdiron in combination with REBETOL must be thoroughly informed of the risks to a fetus. Female patients and female partners of male patients must be told to use two forms of birth control during treatment and for six months after therapy is discontinued (see MEDICATION GUIDE ).

Patients should be advised to remain well hydrated during the initial stages of treatment and that use of an antipyretic may ameliorate some of the flu-like symptoms.

If a decision is made to allow a patient to self-administer Realdiron, they should be instructed, based on their treatment, if they should inject a dose of INTRON® A subcutaneously or intramuscularly. If it is too difficult for them to inject themselves, they should be instructed to ask someone who has been trained to give the injection to them. Patients should be instructed on the importance of site selection for self-administering the injection, as well as the importance on rotating the injection sites. A puncture resistant container for the disposal of needles and syringes should be supplied. Patients self-administering Realdiron should be instructed on the proper disposal of needles and syringes and cautioned against reuse.

Patients should be instructed that the Sterile Water for Injection vial supplied with Realdiron Powder for Injection contains an excess amount of diluent (5 mL) and only 1 mL should be withdrawn to reconstitute Realdiron Powder for Injection. The vial of Sterile Water for Injection is intended for single use only. Discard the unused portion of sterile water. Do not save or reuse.

Dental and Periodontal Disorders

Dental and periodontal disorders have been reported in patients receiving ribavirin and interferon combination therapy. In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the combination of REBETOL and Realdiron. Patients should brush their teeth thoroughly twice daily and have regular dental examinations. In addition, some patients may experience vomiting. If this reaction occurs, they should be advised to rinse out their mouth thoroughly afterwards.

Laboratory Tests

In addition to those tests normally required for monitoring patients, the following laboratory tests are recommended for all patients on Realdiron therapy, prior to beginning treatment and then periodically thereafter.

  • Standard hematologic tests - including hemoglobin, complete and differential white blood cell counts, and platelet count.
  • Blood chemistries - electrolytes, liver function tests, and TSH.
  • Monitor hepatic function with serum bilirubin, ALT, AST (aspartate aminotransferase), alkaline phosphatase, and LDH (lactate dehydrogenase) at 2, 8 and 12 weeks following initiation of Realdiron, then every 6 months while receiving Realdiron. Permanently discontinue Realdiron for evidence of severe (Grade 3) hepatic injury or hepatic decompensation (Child-Pugh score >6 [class B and C]).

Those patients who have preexisting cardiac abnormalities and/or are in advanced stages of cancer should have electrocardiograms taken prior to and during the course of treatment.

Mild-to-moderate leukopenia and elevated serum liver enzyme (SGOT) levels have been reported with intralesional administration of Realdiron (see ADVERSE REACTIONS ); therefore, the monitoring of these laboratory parameters should be considered.

Baseline chest X-rays are suggested and should be repeated if clinically indicated.

For malignant melanoma patients, differential WBC count and liver function tests should be monitored weekly during the induction phase of therapy and monthly during the maintenance phase of therapy.

For specific recommendations in chronic hepatitis C and chronic hepatitis B, see INDICATIONS AND USAGE .

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with Realdiron have not been performed to determine carcinogenicity.

Interferon may impair fertility. In studies of interferon administration in nonhuman primates, menstrual cycle abnormalities have been observed. Decreases in serum estradiol and progesterone concentrations have been reported in women treated with human leukocyte interferon.12 Therefore, fertile women should not receive Realdiron therapy unless they are using effective contraception during the therapy period. Realdiron therapy should be used with caution in fertile men.

Mutagenicity studies have demonstrated that Realdiron is not mutagenic.

Studies in mice (0.1, 1.0 million IU/day), rats (4, 20, 100 million IU/kg/day), and cynomolgus monkeys (1.1 million IU/kg/day; 0.25, 0.75, 2.5 million IU/kg/day) injected with Realdiron for up to 9 days, 3 months, and 1 month, respectively, have revealed no evidence of toxicity. However, in cynomolgus monkeys (4, 20, 100 million IU/kg/day) injected daily for 3 months with Realdiron, toxicity was observed at the mid and high doses and mortality was observed at the high dose.

However, due to the known species-specificity of interferon, the effects in animals are unlikely to be predictive of those in man.

Realdiron in combination with REBETOL should be used with caution in fertile men. See the REBETOL prescribing information for additional information.

Pregnancy Category C

Realdiron has been shown to have abortifacient effects in Macaca mulatta at 15 and 30 million IU/kg (estimated human equivalent of 5 and 10 million IU/kg, based on body surface area adjustment for a 60-kg adult). There are no adequate and well-controlled studies in pregnant women. Realdiron therapy should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pregnancy Category X applies to combination treatment with Realdiron and REBETOL (see CONTRAINDICATIONS ). See REBETOL prescribing information for additional information. Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. REBETOL therapy is contraindicated in women who are pregnant and in the male partners of women who are pregnant. See CONTRAINDICATIONS and the REBETOL prescribing information.

Ribavirin Pregnancy Registry

A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment and for 6 months following cessation of treatment. Physicians and patients are encouraged to report such cases by calling 1-800-593-2214.

Nursing Mothers

It is not known whether this drug is excreted in human milk. However, studies in mice have shown that mouse interferons are excreted into the milk. Because of the potential for serious adverse reactions from the drug in nursing infants, a decision should be made whether to discontinue nursing or to discontinue Realdiron therapy, taking into account the importance of the drug to the mother.

Pediatric Use

General

Safety and effectiveness in pediatric patients have not been established for indications other than chronic hepatitis B and chronic hepatitis C.

Chronic Hepatitis B

Safety and effectiveness in pediatric patients ranging in age from 1 to 17 years have been established based upon one controlled clinical trial.

Chronic Hepatitis C

Safety and effectiveness in pediatric patients ranging in age from 3 to 16 years have been established based upon clinical studies in 118 patients. See REBETOL prescribing information for additional information. Suicidal ideation or attempts occurred more frequently among pediatric patients compared to adult patients (2.4% versus 1%) during treatment and off-therapy follow-up (see WARNINGS, Neuropsychiatric Disorders ). During a 48-week course of therapy there was a decrease in the rate of linear growth (mean percentile assignment decrease of 7%) and a decrease in the rate of weight gain (mean percentile assignment decrease of 9%). A general reversal of these trends was noted during the 24-week post-treatment period.

Long-term data in a limited number of patients suggests that combination therapy may induce a growth inhibition that results in reduced final adult height in some patients (see ADVERSE REACTIONS, Chronic Hepatitis C Pediatrics ).

Geriatric Use

In all clinical studies of Realdiron, including studies as monotherapy and in combination with REBETOL (ribavirin USP) Capsules, only a small percentage of the subjects were aged 65 and over. These numbers were too few to determine if they respond differently from younger subjects except for the clinical trials of Realdiron in combination with REBETOL, where elderly subjects had a higher frequency of anemia (67%) than did younger patients (28%).

In a database consisting of clinical study and postmarketing reports for various indications, cardiovascular adverse events and confusion were reported more frequently in elderly patients receiving Realdiron therapy compared to younger patients.

In general, Realdiron therapy should be administered to elderly patients cautiously, reflecting the greater frequency of decreased hepatic, renal, bone marrow, and/or cardiac function and concomitant disease or other drug therapy. Realdiron is known to be substantially excreted by the kidney, and the risk of adverse reactions to Realdiron may be greater in patients with impaired renal function. Because elderly patients often have decreased renal function, patients should be carefully monitored during treatment, and dose adjustments made based on symptoms and/or laboratory abnormalities (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION ).

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ADVERSE REACTIONS

General

The adverse experiences listed below were reported to be possibly or probably related to INTRON® A therapy during clinical trials. Most of these adverse reactions were mild to moderate in severity and were manageable. Some were transient and most diminished with continued therapy.

The most frequently reported adverse reactions were "flu-like" symptoms, particularly fever, headache, chills, myalgia, and fatigue. More severe toxicities are observed generally at higher doses and may be difficult for patients to tolerate.

Dosing Regimens

Percentage of PatientsDash (--) indicates not reported

MALIGNANT MELANOMA FOLLICULAR LYMPHOMA HAIRY CELL LEUKEMIA CONDYLOMATA ACUMINATA AIDS-RELATED KAPOSI'S SARCOMA CHRONIC HEPATITIS CPercentages based upon a summary of all adverse events during 18 to 24 months of treatment CHRONIC HEPATITIS B
Adults Pediatrics
20 MIU/m2

Induction (IV)

10 MIU/m2

Maintenance

(SC)

5 MIU

TIW/SC

2 MIU/m2

TIW/SC

1 MIU/lesion 30 MIU/m2

TIW/SC

35 MIU

QD/SC

3 MIU

TIW

5 MIU

QD

10 MIU

TIW

6 MIU/m2

TIW

ADVERSE EXPERIENCE N=143 N=135 N=145 N=352 N=74 N=29 N=183 N=101 N=78 N=116
Application-Site Disorders 20
  injection site

  inflammation

-- 1 -- -- -- -- 5 3 -- --
  other (≤5%) burning, injection site bleeding, injection site pain, injection site reaction (5% in chronic hepatitis B pediatrics), itching
Blood Disorders (<5%) anemia, anemia hypochromic, granulocytopenia, hemolytic anemia, leukopenia, lymphocytosis, neutropenia (9% in chronic hepatitis C, 14% in chronic hepatitis B pediatrics), thrombocytopenia (10% in chronic hepatitis C) (bleeding 8% in malignant melanoma), thrombocytopenia purpura
Body as a Whole
  facial edema -- 1 -- <1 -- 10 <1 3 1 <1
  weight decrease 3 13 <1 <1 5 3 10 2 5 3
  other (≤5%) allergic reaction, cachexia, dehydration, earache, hernia, edema, hypercalcemia, hyperglycemia, hypothermia, inflammation nonspecific, lymphadenitis, lymphadenopathy, mastitis, periorbital edema, poor peripheral circulation, peripheral edema (6% in follicular lymphoma), phlebitis superficial, scrotal/penile edema, thirst, weakness, weight increase
Cardiovascular System Disorders (<5%) angina, arrhythmia, atrial fibrillation, bradycardia, cardiac failure, cardiomegaly, cardiomyopathy, coronary artery disorder, extrasystoles, heart valve disorder, hematoma, hypertension (9% in chronic hepatitis C), hypotension, palpitations, phlebitis, postural hypotension, pulmonary embolism, Raynaud's disease, tachycardia, thrombosis, varicose vein
Endocrine System Disorders (<5%) aggravation of diabetes mellitus, goiter, gynecomastia, hyperglycemia, hyperthyroidism, hypertriglyceridemia, hypothyroidism, virilism
Flu-like Symptoms
  fever 81 56 68 56 47 55 34 66 86 94
  headache 62 21 39 47 36 21 43 61 44 57
  chills 54 -- 46 45 -- -- -- -- -- --
  myalgia 75 16 39 44 34 28 43 59 40 27
  fatigue 96 8 61 18 84 48 23 75 69 71
  increased sweating 6 13 8 2 4 21 4 1 1 3
  asthenia -- 63 7 -- 11 -- 40 5 15 5
  rigors 2 7 -- -- 30 14 16 38 42 30
  arthralgia 6 8 8 9 -- 3 16 19 8 15
  dizziness 23 -- 12 9 7 24 9 13 10 8
  influenza-like symptoms 10 18 37 -- 45 79 26 5 -- <1
  back pain -- 15 19 6 1 3 -- -- -- --
  dry mouth 1 2 19 -- 22 28 5 6 5 --
  chest pain 2 8 <1 <1 1 28 4 4 -- --
  malaise 6 -- -- 14 5 -- 13 9 6 3
  pain (unspecified) 15 9 18 3 3 3 -- -- -- --
  other (<5%) chest pain substernal, hyperthermia, rhinitis, rhinorrhea
Gastrointestinal System Disorders
  diarrhea 35 19 18 2 18 45 13 19 8 12
  anorexia 69 21 19 1 38 41 14 43 53 43
  nausea 66 24 21 17 28 21 19 50 33 18
  taste alteration 24 2 13 <1 5 7 2 10 -- --
  abdominal pain 2 20 <5 1 5 21 16 5 4 23
  loose stools -- 1 -- <1 -- 10 2 2 -- 2
  vomiting Vomiting was reported with nausea as a single term 32 6 2 11 14 8 7 10 27
  constipation 1 14 <1 -- 1 10 4 5 -- 2
  gingivitis 2Includes stomatitis/mucositis 7 -- -- -- 14 -- 1 -- --
  dyspepsia -- 2 -- 2 4 -- 7 3 8 3
  other (<5%) abdominal ascites, abdominal distension, colitis, dysphagia, eructation, esophagitis, flatulence, gallstones, gastric ulcer, gastritis, gastroenteritis, gastrointestinal disorder (7% in follicular lymphoma), gastrointestinal hemorrhage, gastrointestinal mucosal discoloration, gingival bleeding, gum hyperplasia, halitosis, hemorrhoids, increased appetite, increased saliva, intestinal disorder, melena, mouth ulceration, mucositis, oral hemorrhage, oral leukoplakia, rectal bleeding after stool, rectal hemorrhage, stomatitis, stomatitis ulcerative, taste loss, tongue disorder, tooth disorder
Liver and Biliary System Disorders (<5%) abnormal hepatic function tests, biliary pain, bilirubinemia, hepatitis, increased lactate dehydrogenase, increased transaminases (SGOT/SGPT) (elevated SGOT 63% in malignant melanoma and 24% in follicular lymphoma), jaundice, right upper quadrant pain (15% in chronic hepatitis C), and very rarely, hepatic encephalopathy, hepatic failure, and death
Musculoskeletal System Disorders
  musculoskeletal pain -- 18 -- -- -- -- 21 9 1 10
  other (<5%) arteritis, arthritis, arthritis aggravated, arthrosis, bone disorder, bone pain, carpal tunnel syndrome, hyporeflexia, leg cramps, muscle atrophy, muscle weakness, polyarteritis nodosa, tendinitis, rheumatoid arthritis, spondylitis
Nervous System and Psychiatric Disorders
  depression 40 9 6 3 9 28 19 17 6 4
  paresthesia 13 13 6 1 3 21 5 6 3 <1
  impaired concentration -- 1 -- <1 3 14 3 8 5 3
  amnesia Amnesia was reported with confusion as a single term 1 <5 -- -- 14 -- -- -- --
  confusion 8 2 <5 4 12 10 1 -- -- 2
  hypoesthesia -- 1 <5 1 -- 10 -- -- -- --
  irritability 1 1 -- -- -- -- 13 16 12 22
  somnolence 1 2 <5 3 3 -- 33Predominantly lethargy 14 9 5
  anxiety 1 9 5 <1 1 3 5 2 -- 3
  insomnia 5 4 -- <1 3 3 12 11 6 8
  nervousness 1 1 -- 1 -- 3 2 3 -- 3
  decreased libido 1 1 <5 -- -- -- 1 5 1 --
  other (<5%) abnormal coordination, abnormal dreaming, abnormal gait, abnormal thinking, aggravated depression, aggressive reaction, agitation (7% in chronic hepatitis B pediatrics), alcohol intolerance, apathy, aphasia, ataxia, Bell's palsy, CNS dysfunction, coma, convulsions, delirium, dysphonia, emotional lability, extrapyramidal disorder, feeling of ebriety, flushing, hearing disorder, hearing impairment, hot flashes, hyperesthesia, hyperkinesia, hypertonia, hypokinesia, impaired consciousness, labyrinthine disorder, loss of consciousness, manic depression, manic reaction, migraine, neuralgia, neuritis, neuropathy, neurosis, paresis, paroniria, parosmia, personality disorder, polyneuropathy, psychosis, speech disorder, stroke, suicidal ideation, suicide attempt, syncope, tinnitus, tremor, twitching, vertigo (8% in follicular lymphoma)
Reproduction System Disorders (<5%) amenorrhea (12% in follicular lymphoma), dysmenorrhea, impotence, leukorrhea, menorrhagia, menstrual irregularity, pelvic pain, penis disorder, sexual dysfunction, uterine bleeding, vaginal dryness
Resistance Mechanism Disorders
  moniliasis -- 1 -- <1 -- 17 -- -- -- --
  herpes simplex 1 2 -- 1 -- 3 1 5 -- --
  other (<5%) abscess, conjunctivitis, fungal infection, hemophilus, herpes zoster, infection, infection bacterial, infection nonspecific (7% in follicular lymphoma), infection parasitic, otitis media, sepsis, stye, trichomonas, upper respiratory tract infection, viral infection (7% in chronic hepatitis C)
Respiratory System Disorders
  dyspnea 15 14 <1 -- 1 34 3 5 -- --
  coughing 6 13 <1 -- -- 31 1 4 -- 5
  pharyngitis 2 8 <5 1 1 31 3 7 1 7
  sinusitis 1 4 -- -- -- 21 2 -- -- --
  nonproductive coughing 2 7 -- -- -- 14 0 1 -- --
  nasal congestion 1 7 -- 1 -- 10 <1 4 -- --
  other (≤5%) asthma, bronchitis (10% in follicular lymphoma), bronchospasm, cyanosis, epistaxis (7% in chronic hepatitis B pediatrics), hemoptysis, hypoventilation, laryngitis, lung fibrosis, pleural effusion, orthopnea, pleural pain, pneumonia, pneumonitis, pneumothorax, rales, respiratory disorder, respiratory insufficiency, sneezing, tonsillitis, tracheitis, wheezing
Skin and Appendages Disorders
  dermatitis 1 -- 8 -- -- -- 2 1 -- --
  alopecia 29 23 8 -- 12 31 28 26 38 17
  pruritus -- 10 11 1 7 -- 9 6 4 3
  rash 19 13 25 -- 9 10 5 8 1 5
  dry skin 1 3 9 -- 9 10 4 3 -- <1
  other (<5%) abnormal hair texture, acne, cellulitis, cyanosis of the hand, cold and clammy skin, dermatitis lichenoides, eczema, epidermal necrolysis, erythema, erythema nodosum, folliculitis, furunculosis, increased hair growth, lacrimal gland disorder, lacrimation, lipoma, maculopapular rash, melanosis, nail disorders, nonherpetic cold sores, pallor, peripheral ischemia, photosensitivity, pruritus genital, psoriasis, psoriasis aggravated, purpura (5% in chronic hepatitis C), rash erythematous, sebaceous cyst, skin depigmentation, skin discoloration, skin nodule, urticaria, vitiligo
Urinary System Disorders (<5%) albumin/protein in urine, cystitis, dysuria, hematuria, incontinence, increased BUN, micturition disorder, micturition frequency, nocturia, polyuria (10% in follicular lymphoma), renal insufficiency, urinary tract infection (5% in chronic hepatitis C)
Vision Disorders (<5%) abnormal vision, blurred vision, diplopia, dry eyes, eye pain, nystagmus, photophobia

Hairy Cell Leukemia

The adverse reactions most frequently reported during clinical trials in 145 patients with hairy cell leukemia were the "flu-like" symptoms of fever (68%), fatigue (61%), and chills (46%).

Malignant Melanoma

The Realdiron dose was modified because of adverse events in 65% of the patients. Realdiron therapy was discontinued because of adverse events in 8% of the patients during induction and 18% of the patients during maintenance. The most frequently reported adverse reaction was fatigue, which was observed in 96% of patients. Other adverse reactions that were recorded in greater than 20% of INTRON A-treated patients included neutropenia (92%), fever (81%), myalgia (75%), anorexia (69%), vomiting/nausea (66%), increased SGOT (63%), headache (62%), chills (54%), depression (40%), diarrhea (35%), alopecia (29%), altered taste sensation (24%), dizziness/vertigo (23%), and anemia (22%).

Adverse reactions classified as severe or life threatening (ECOG Toxicity Criteria grade 3 or 4) were recorded in 66% and 14% of INTRON A-treated patients, respectively. Severe adverse reactions recorded in greater than 10% of INTRON A-treated patients included neutropenia/leukopenia (26%), fatigue (23%), fever (18%), myalgia (17%), headache (17%), chills (16%), and increased SGOT (14%). Grade 4 fatigue was recorded in 4% and grade 4 depression was recorded in 2% of INTRON A-treated patients. No other grade 4 AE was reported in more than 2 INTRON A-treated patients. Lethal hepatotoxicity occurred in 2 INTRON A-treated patients early in the clinical trial. No subsequent lethal hepatotoxicities were observed with adequate monitoring of liver function tests (see PRECAUTIONS, Laboratory Tests ).

Follicular Lymphoma

Ninety-six percent of patients treated with CHVP plus Realdiron therapy and 91% of patients treated with CHVP alone reported an adverse event of any severity. Asthenia, fever, neutropenia, increased hepatic enzymes, alopecia, headache, anorexia, "flu-like" symptoms, myalgia, dyspnea, thrombocytopenia, paresthesia, and polyuria occurred more frequently in the CHVP plus INTRON A-treated patients than in patients treated with CHVP alone. Adverse reactions classified as severe or life threatening (World Health Organization grade 3 or 4) recorded in greater than 5% of CHVP plus INTRON A-treated patients included neutropenia (34%), asthenia (10%), and vomiting (10%). The incidence of neutropenic infection was 6% in CHVP plus Realdiron versus 2% in CHVP alone. One patient in each treatment group required hospitalization.

Twenty-eight percent of CHVP plus INTRON A-treated patients had a temporary modification/interruption of their Realdiron therapy, but only 13 patients (10%) permanently stopped Realdiron therapy because of toxicity. There were four deaths on study; two patients committed suicide in the CHVP plus Realdiron arm and two patients in the CHVP arm had unwitnessed sudden death. Three patients with hepatitis B (one of whom also had alcoholic cirrhosis) developed hepatotoxicity leading to discontinuation of Realdiron. Other reasons for discontinuation included intolerable asthenia (5/135), severe flu symptoms (2/135), and one patient each with exacerbation of ankylosing spondylitis, psychosis, and decreased ejection fraction.

Condylomata Acuminata

Eighty-eight percent of patients treated with Realdiron for condylomata acuminata who were evaluable for safety reported an adverse reaction during treatment. The incidence of the adverse reactions reported increased when the number of treated lesions increased from one to five. All 40 patients who had five warts treated reported some type of adverse reaction during treatment.

Adverse reactions and abnormal laboratory test values reported by patients who were re-treated were qualitatively and quantitatively similar to those reported during the initial Realdiron treatment period.

AIDS-Related Kaposi's Sarcoma

In patients with AIDS-Related Kaposi's Sarcoma, some type of adverse reaction occurred in 100% of the 74 patients treated with 30 million IU/m2 three times a week and in 97% of the 29 patients treated with 35 million IU per day.

Of these adverse reactions, those classified as severe (World Health Organization grade 3 or 4) were reported in 27% to 55% of patients. Severe adverse reactions in the 30 million IU/m2 TIW study included: fatigue (20%), influenza-like symptoms (15%), anorexia (12%), dry mouth (4%), headache (4%), confusion (3%), fever (3%), myalgia (3%), and nausea and vomiting (1% each). Severe adverse reactions for patients who received the 35 million IU QD included: fever (24%), fatigue (17%), influenza-like symptoms (14%), dyspnea (14%), headache (10%), pharyngitis (7%), and ataxia, confusion, dysphagia, GI hemorrhage, abnormal hepatic function, increased SGOT, myalgia, cardiomyopathy, face edema, depression, emotional lability, suicide attempt, chest pain, and coughing (1 patient each). Overall, the incidence of severe toxicity was higher among patients who received the 35 million IU per day dose.

Chronic Hepatitis C

Adults

Two studies of extended treatment with Realdiron show that approximately 95% of all patients treated experience some type of adverse event and that patients treated for extended duration continue to experience adverse events throughout treatment. Most adverse events reported are mild to moderate in severity. However, 29/152 (19%) of patients treated for 18 to 24 months experienced a serious adverse event compared to 11/163 (7%) of those treated for 6 months. Adverse events which occur or persist during extended treatment are similar in type and severity to those occurring during short-course therapy.

Of the patients achieving a complete response after 6 months of therapy, 12/79 (15%) subsequently discontinued Realdiron treatment during extended therapy because of adverse events, and 23/79 (29%) experienced severe adverse events (WHO grade 3 or 4) during extended therapy.

In patients using combination treatment with Realdiron and REBETOL, the primary toxicity observed was hemolytic anemia. Reductions in hemoglobin levels occurred within the first 1 to 2 weeks of therapy. Cardiac and pulmonary events associated with anemia occurred in approximately 10% of patients treated with INTRON A/REBETOL therapy. See REBETOL prescribing information for additional information.

Chronic Hepatitis C

Pediatrics

In pediatric patients with chronic hepatitis C treated with Realdiron 3 MIU/m2 three times weekly and REBETOL 15 mg/kg per day, all subjects had at least one adverse event during 24-48 weeks of treatment, of which 80% were considered to be mild or moderate in severity. Six percent discontinued therapy due to adverse reactions and dose modifications were required in 30% of subjects, most commonly for anemia and neutropenia. Adverse events occurring in more than 50% of subjects included headache, fever, fatigue and anorexia. Adverse events occurring in 20-50% of subjects included influenza-like symptoms, abdominal pain, vomiting, nausea, myalgia, pharyngitis, diarrhea, viral infection, rigors, weight decrease, musculoskeletal pain, alopecia and dizziness. The most common laboratory test abnormalities were neutropenia (34%) and anemia (27%). Depression was reported in 13% (n=15) of children. Three of these subjects had suicidal ideation, and one attempted suicide. Weight loss and slowed growth are common in pediatric patients during combination therapy with Realdiron and REBETOL. Following treatment, rebound growth and weight gain occurred in most subjects. Long-term follow-up data in pediatric subjects, however, indicates that Realdiron in combination with REBETOL may induce a growth inhibition that results in reduced adult height in some patients (see PRECAUTIONS, Pediatric Use).

Chronic Hepatitis B

Adults

In patients with chronic hepatitis B, some type of adverse reaction occurred in 98% of the 101 patients treated at 5 million IU QD and 90% of the 78 patients treated at 10 million IU TIW. Most of these adverse reactions were mild to moderate in severity, were manageable, and were reversible following the end of therapy.

Adverse reactions classified as severe were reported in 21% to 44% of patients. The severe adverse reactions reported most frequently were the "flu-like" symptoms of fever (28%), fatigue (15%), headache (5%), myalgia (4%), rigors (4%), and other severe "flu-like" symptoms, which occurred in 1% to 3% of patients. Other severe adverse reactions occurring in more than one patient were alopecia (8%), anorexia (6%), depression (3%), nausea (3%), and vomiting (2%).

To manage side effects, the dose was reduced, or Realdiron therapy was interrupted in 25% to 38% of patients. Five percent of patients discontinued treatment due to adverse experiences.

Chronic Hepatitis B

Pediatrics

In pediatric patients with chronic hepatitis B during 16-24 weeks of treatment, the most frequently reported adverse events were those commonly associated with interferon treatment: flu-like symptoms (100%), gastrointestinal system disorders (46%), and nausea and vomiting (40%). Neutropenia (13%) and thrombocytopenia (3%) were also reported. None of the adverse events was life threatening and most were moderate to severe and resolved upon dose reduction or drug discontinuation.

Dosing Regimens

Percentage (%) of Patients

MALIGNANT MELANOMA FOLLICULAR LYMPHOMA HAIRY CELL LEUKEMIA CONDYLOMATA ACUMINATA AIDS-RELATED KAPOSI'S SARCOMA CHRONIC HEPATITIS C CHRONIC HEPATITIS B
Adults Pediatrics
20 MIU/m2

Induction (IV)

10 MIU/m2

Maintenance

(SC)

5 MIU

TIW/SC

2 MIU/m2

TIW/SC

1 MIU/lesion 30 MIU/m2

TIW/SC

35 MIU

QD/SC

3 MIU

TIW

5 MIU

QD

10 MIU

TIW

6 MIU/m2

TIW

Laboratory Tests N=143 N=135 N=145 N=352 N=69-73 N=26-28 N=140-171 N=96-101 N=75-103 N=113-115
NA - Not Applicable - Patients' initial hematologic laboratory test values were abnormal due to their condition.
Hemoglobin 22 8 NA -- 1 15 26Decrease of ≥2 g/dL; 20% 2-<3 g/dL; 6% ≥3 g/dL 32Decrease of ≥2 g/dL 23 17Decrease of ≥2 g/dL; 14% 2-<3 g/dL; 3% ≥3 g/dL
White Blood Cell Count White Blood Cell Count was reported as neutropenia -- NA 17 10 22 26Decrease to <3000/mm3 68 34 9
Platelet Count 15 13 NA -- 0 8 15Decrease to <70,000/mm3 12 5 1
Serum Creatinine 3 2 0 -- -- -- 6 3 0 3
Alkaline Phosphatase 13 -- 4 -- -- -- -- 8 4 0
Lactate Dehydrogenase 1 -- 0 -- -- -- -- -- -- --
Serum Urea Nitrogen 12 4 0 -- -- -- -- 2 0 2
SGOT 63 24 4 12 11 41 -- -- -- --
SGPT 2 -- 13 -- 10 15 -- -- -- --
Granulocyte Count
  • Total
92 36 NA -- 31 39 45Neutrophils plus bands 75 61 70
  • 1000-<1500/mm3
66 -- -- -- -- -- 32 30 32 43
  • 750-<1000/mm3
-- 21 -- -- -- -- 10 24 18 18
  • 500-<750/mm3
25 -- -- -- -- -- 1 17 9 7
  • <500/mm3
1 13 -- -- -- -- 2 4 2 2

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Realdiron alone or in combination with REBETOL. 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.

Blood and Lymphatic System Disorders

pancytopenia (concurrent anemia, leukopenia, thrombocytopenia), aplastic anemia, pure red cell aplasia, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura

Cardiac Disorders

pericarditis

Ear and Labyrinth Disorders

hearing loss

Endocrine Disorders

hypopituitarism

Eye Disorders

Vogt-Koyanagi-Harada syndrome, serous retinal detachment

Gastrointestinal Disorders

pancreatitis

General Disorders and Administration Site Conditions

asthenic conditions (including asthenia, malaise, fatigue)

Immune System Disorders

cases of acute hypersensitivity reactions, including anaphylaxis and angioedema, systemic lupus erythematosus, sarcoidosis or exacerbation of sarcoidosis

Infections and Infestations

hepatitis B virus reactivation in HCV/HBV co-infected patients

Musculoskeletal and Connective Tissue Disorders

myositis

Nervous System Disorders

peripheral neuropathy

Psychiatric Disorders

homicidal ideation, psychosis including hallucinations

Renal and Urinary Disorders

renal failure, renal insufficiency, nephrotic syndrome

Respiratory, Thoracic, and Mediastinal Disorders

pulmonary hypertension, pulmonary fibrosis

Skin and Subcutaneous Tissue Disorders

injection site necrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, urticaria

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OVERDOSAGE

There is limited experience with overdosage. Postmarketing surveillance includes reports of patients receiving a single dose as great as 10 times the recommended dose. In general, the primary effects of an overdose are consistent with the effects seen with therapeutic doses of Realdiron. Hepatic enzyme abnormalities, renal failure, hemorrhage, and myocardial infarction have been reported with single administration overdoses and/or with longer durations of treatment than prescribed. Toxic effects after ingestion of Realdiron are not expected because interferons are poorly absorbed orally. Consultation with a poison center is recommended.

Treatment

There is no specific antidote for Realdiron. Hemodialysis and peritoneal dialysis are not considered effective for treatment of overdose.

DOSAGE AND ADMINISTRATION

General

IMPORTANT: INTRON® A is supplied as 1) Powder for Injection/Reconstitution; 2) Solution for Injection in Vials. Not all dosage forms and strengths are appropriate for some indications. It is important that you carefully read the instructions below for the indication you are treating to ensure you are using an appropriate dosage form and strength.

To enhance the tolerability of Realdiron, injections should be administered in the evening when possible.

To reduce the incidence of certain adverse reactions, acetaminophen may be administered at the time of injection.

The solution should be allowed to come to room temperature before using.

Hairy Cell Leukemia


Dose

The recommended dose for the treatment of hairy cell leukemia is 2 million IU/m2 administered intramuscularly or subcutaneously 3 times a week for up to 6 months. Patients with platelet counts of less than 50,000/mm3 should not be administered Realdiron intramuscularly, but instead by subcutaneous administration. Patients who are responding to therapy may benefit from continued treatment.

Dosage Form Concentration Route Fixed Doses
Powder 10 MIU (single dose) 10 MIU/mL IM, SC N/A
Solution 18 MIU multidose 6 MIU/mL IM, SC N/A
Solution 25 MIU multidose 10 MIU/mL IM, SC N/A

NOTE: Realdiron Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment

  • If severe adverse reactions develop, the dosage should be modified or therapy should be temporarily withheld until the adverse reactions abate and then resume at 50% (1 MIU/m2 TIW).
  • If severe adverse reactions persist or recur following dosage adjustment, Realdiron should be permanently discontinued.
  • Realdiron should be discontinued for progressive disease or failure to respond after six months of treatment.

Malignant Melanoma

(see DOSAGE AND ADMINISTRATION, General )

Realdiron adjuvant treatment of malignant melanoma is given in two phases, induction and maintenance.

Induction Recommended Dose

The recommended daily dose of Realdiron in induction is 20 million IU/m2 as an intravenous infusion, over 20 minutes, 5 consecutive days per week, for 4 weeks.

Dosage Form Concentration Route
Powder 10 MIU 10 MIU/mL IV
Powder 18 MIU 18 MIU/mL IV
Powder 50 MIU 50 MIU/mL IV

NOTE: Realdiron Solution for Injection in vials is NOT recommended for intravenous administration and should not be used for the induction phase of malignant melanoma.

NOTE: Realdiron Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment

NOTE: Regular laboratory testing should be performed to monitor laboratory abnormalities for the purpose of dose modifications (see PRECAUTIONS, Laboratory Tests ).

  • Realdiron should be withheld for severe adverse reactions, including granulocyte counts greater than 250/mm3 but less than 500/mm3 or SGPT/SGOT greater than 5-10× upper limit of normal, until adverse reactions abate. Realdiron treatment should be restarted at 50% of the previous dose.
  • Realdiron should be permanently discontinued for:
    • Toxicity that does not abate after withholding Realdiron
    • Severe adverse reactions which recur in patients receiving reduced doses of Realdiron
    • Granulocyte count less than 250/mm3 or SGPT/SGOT of greater than 10× upper limit of normal

Maintenance Recommended Dose

The recommended dose of Realdiron for maintenance is 10 million IU/m2 as a subcutaneous injection three times per week for 48 weeks.

Dosage Form Concentration Route Fixed Doses
Powder 10 MIU (single dose)Patients receiving 50% dose reduction only 10 MIU/mL SC N/A
Powder 18 MIU (single dose)Patients receiving full dose only 18 MIU/mL SC N/A
Solution 18 MIU multidose 6 MIU/mL SC N/A
Solution 25 MIU multidose 10 MIU/mL SC N/A

NOTE: Realdiron Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment

NOTE: Regular laboratory testing should be performed to monitor laboratory abnormalities for the purpose of dose modifications (see PRECAUTIONS, Laboratory Tests ).

  • Realdiron should be withheld for severe adverse reactions, including granulocyte counts greater than 250/mm3 but less than 500/mm3 or SGPT/SGOT greater than 5-10× upper limit of normal, until adverse reactions abate. Realdiron treatment should be restarted at 50% of the previous dose.
  • Realdiron should be permanently discontinued for:
    • Toxicity that does not abate after withholding Realdiron
    • Severe adverse reactions which recur in patients receiving reduced doses of Realdiron
    • Granulocyte count less than 250/mm3 or SGPT/SGOT of greater than 10× upper limit of normal

Follicular Lymphoma


Dose

The recommended dose of Realdiron for the treatment of follicular lymphoma is 5 million IU subcutaneously three times per week for up to 18 months in conjunction with anthracycline-containing chemotherapy regimen and following completion of the chemotherapy regimen.

Dosage Form Concentration Route Fixed Doses
Powder 10 MIU (single dose) 10 MIU/mL SC N/A
Solution 18 MIU multidose 6 MIU/mL SC N/A
Solution 25 MIU multidose 10 MIU/mL SC N/A

NOTE: Realdiron Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment

  • Doses of myelosuppressive drugs were reduced by 25% from a full-dose CHOP regimen, and cycle length increased by 33% when alpha interferon was added to the regimen.
  • Delay chemotherapy cycle if neutrophil count was less than 1500/mm3 or platelet count was less than 75,000/mm3.
  • Realdiron should be permanently discontinued if SGOT exceeds greater than 5× the upper limit of normal or serum creatinine greater than 2.0 mg/dL (see WARNINGS ).
  • Administration of Realdiron therapy should be withheld for a neutrophil count less than 1000/mm3, or a platelet count less than 50,000/mm3.
  • Realdiron dose should be reduced by 50% (2.5 MIU TIW) for a neutrophil count greater than 1000/mm3, but less than 1500/mm3. The Realdiron dose may be re-escalated to the starting dose (5 million IU TIW) after resolution of hematologic toxicity (ANC greater than 1500/mm3).

Condylomata Acuminata

(see DOSAGE AND ADMINISTRATION, General )

Dose

The recommended dose is 1.0 million IU per lesion in a maximum of 5 lesions in a single course. The lesions should be injected three times weekly on alternate days for 3 weeks. An additional course may be administered at 12 to 16 weeks.

Dosage Form Concentration Route
Powder 10 MIU 10 MIU/mL IL
Solution 25 MIU multidose 10 MIU/mL IL

NOTE: Realdiron Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

NOTE: Do not use the following formulations for this

Indication:

  • the 18 million or 50 million IU Powder for Injection
  • the 18 million IU multidose Realdiron Solution for Injection

Dose Adjustment

None

Technique for Injection

The injection should be administered intralesionally using a Tuberculin or similar syringe and a 25- to 30-gauge needle. The needle should be directed at the center of the base of the wart and at an angle almost parallel to the plane of the skin. This will deliver the interferon to the dermal core of the lesion, infiltrating the lesion and causing a small wheal. Care should be taken not to go beneath the lesion too deeply; subcutaneous injection should be avoided, since this area is below the base of the lesion. Do not inject too superficially since this will result in possible leakage, infiltrating only the keratinized layer and not the dermal core.

AIDS-Related Kaposi's Sarcoma

(see DOSAGE AND ADMINISTRATION, General )

Dose

The recommended dose of Realdiron for Kaposi's Sarcoma is 30 million IU/m2/dose administered subcutaneously or intramuscularly three times a week until disease progression or maximal response has been achieved after 16 weeks of treatment. Dose reduction is frequently required.

Dosage Form Concentration Route
Powder 50 MIU 50 MIU/mL IM, SC

NOTE: Realdiron Solution for Injection in vials should NOT be used for AIDS-Related Kaposi's Sarcoma.

NOTE: Realdiron Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment

  • Realdiron dose should be reduced by 50% or withheld for severe adverse reactions.
  • Realdiron may be resumed at a reduced dose if severe adverse reactions abate with interruption of dosing.
  • Realdiron should be permanently discontinued if severe adverse reactions persist or if they recur in patients receiving a reduced dose.

Chronic Hepatitis C

Dose

The recommended dose of Realdiron for the treatment of chronic hepatitis C is 3 million IU three times a week (TIW) administered subcutaneously or intramuscularly. In patients tolerating therapy with normalization of ALT at 16 weeks of treatment, Realdiron therapy should be extended to 18 to 24 months (72 to 96 weeks) at 3 million IU TIW to improve the sustained response rate (see CLINICAL PHARMACOLOGY, Chronic Hepatitis C ). Patients who do not normalize their ALTs or have persistently high levels of HCV RNA after 16 weeks of therapy rarely achieve a sustained response with extension of treatment. Consideration should be given to discontinuing these patients from therapy.

When Realdiron is administered in combination with REBETOL®, patients with impaired renal function and/or those over the age of 50 should be carefully monitored with respect to the development of anemia. See REBETOL prescribing information for dosing when used in combination with REBETOL for adults and pediatric patients.

Dosage Form Concentration Route Fixed Doses
Solution 18 MIU multidose 6 MIU/mL IM, SC N/A

Dose Adjustment

If severe adverse reactions develop during Realdiron treatment, the dose should be modified or therapy should be temporarily discontinued until the adverse reactions abate. If intolerance persists after dose adjustment, Realdiron therapy should be discontinued.

Chronic Hepatitis B Adults

(see DOSAGE AND ADMINISTRATION, General )

Dose

The recommended dose of Realdiron for the treatment of chronic hepatitis B is 30 to 35 million IU per week, administered subcutaneously or intramuscularly, either as 5 million IU daily or as 10 million IU three times a week (TIW) for 16 weeks.

Dosage Form Concentration Route Fixed Doses
Powder 10 MIU (single dose) 10 MIU/mL IM, SC N/A
Solution 25 MIU multidose 10 MIU/mL IM, SC N/A

NOTE: Realdiron Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Adults – HCV/HBV co-infection

The safety and efficacy of Realdiron alone or in combination with boceprevir or ribavirin for the treatment of chronic hepatitis C genotype 1 infection in patients co-infected with hepatitis B virus (HBV) and HCV have not been studied.

Chronic Hepatitis B Pediatrics

Dose

The recommended dose of Realdiron for the treatment of chronic hepatitis B is 3 million IU/m2 three times a week (TIW) for the first week of therapy followed by dose escalation to 6 million IU/m2 TIW (maximum of 10 million IU TIW) administered subcutaneously for a total duration of 16 to 24 weeks.

Dosage Form Concentration Route Fixed Doses
Powder 10 MIU (single dose) 10 MIU/mL SC N/A
Solution 25 MIU multidose 10 MIU/mL SC N/A

NOTE: Realdiron Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.

Dose Adjustment

If severe adverse reactions or laboratory abnormalities develop during Realdiron therapy, the dose should be modified (50% reduction) or discontinued if appropriate, until the adverse reactions abate. If intolerance persists after dose adjustment, Realdiron therapy should be discontinued.

For patients with decreases in white blood cell, granulocyte or platelet counts, the following guidelines for dose modification should be followed:

Realdiron Dose White Blood Cell Count Granulocyte Count Platelet Count
Reduce 50% <1.5 × 109/L <0.75 × 109/L <50 × 109/L
Permanently Discontinue <1.0 × 109/L <0.5 × 109/L <25 × 109/L

Realdiron therapy was resumed at up to 100% of the initial dose when white blood cell, granulocyte, and/or platelet counts returned to normal or baseline values.

PREPARATION AND ADMINISTRATION

Reconstitution of INTRON® A Powder for Injection

Reconstitute Realdiron Powder for Injection with 1 mL of Sterile Water for Injection, USP. The Sterile Water for Injection supplied contains 5 mL and is intended for single use. Discard the unused portion. The reconstituted solution is clear and colorless to light yellow. The Realdiron powder reconstituted with Sterile Water for Injection USP is a single-use vial and does not contain a preservative. DO NOT RE-ENTER VIAL AFTER WITHDRAWING THE DOSE. DISCARD UNUSED PORTION. Once the dose from the single-dose vial has been withdrawn, the sterility of any remaining product can no longer be guaranteed. Pooling of unused portions of some medications has been linked to bacterial contamination and morbidity.

-   Intramuscular, Subcutaneous, or Intralesional Administration

Inject 1 mL Diluent (Sterile Water for Injection USP) for Realdiron into the Realdiron vial. Swirl gently to hasten complete dissolution of the powder. The appropriate Realdiron dose should then be withdrawn and injected intramuscularly, subcutaneously, or intralesionally (see MEDICATION GUIDE and Instructions for Use for detailed instructions).

Please refer to the MEDICATION GUIDE and Instructions for Use for detailed, step-by-step instructions on how to inject the Realdiron dose. After preparation and administration of the Realdiron injection, it is essential to follow the procedure for proper disposal of syringes and needles (see MEDICATION GUIDE and Instructions for Use for detailed instructions).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

-   Intravenous Infusion

The infusion solution should be prepared immediately prior to use. Based on the desired dose, the appropriate vial strength of Realdiron should be reconstituted with the diluent provided. Inject 1 mL Diluent (Sterile Water for Injection USP) for Realdiron into the Realdiron vial. Swirl gently to hasten complete dissolution of the powder. The appropriate Realdiron dose should then be withdrawn and injected into a 100-mL bag of 0.9% Sodium Chloride Injection USP. The final concentration of Realdiron should not be less than 10 million IU/100 mL.

Realdiron Solution for Injection in Vials

Realdiron Solution for Injection is supplied in two multidose vials. The solutions for injection do not require reconstitution prior to administration; the solution is clear and colorless.

The appropriate dose should be withdrawn from the vial and injected intramuscularly, subcutaneously, or intralesionally.

Realdiron Solution for Injection is not recommended for intravenous administration.

Please refer to the MEDICATION GUIDE and Instructions for Use for detailed, step-by-step instructions on how to inject the Realdiron dose. After preparation and administration of Realdiron, it is essential to follow the procedure for proper disposal of syringes and needles.

HOW SUPPLIED

INTRON® A Powder for Injection

Realdiron Powder for Injection, 10 million IU per vial and Diluent for Realdiron 5 mL per vial; boxes containing 1 Realdiron vial and 1 vial of Realdiron Diluent (NDC 0085-4350-01).

Realdiron Powder for Injection, 18 million IU per vial and Diluent for Realdiron (Sterile Water for Injection USP) 5 mL per vial; boxes containing 1 vial of Realdiron and 1 vial of Realdiron Diluent (NDC 0085-4351-01).

Realdiron Powder for Injection, 50 million IU per vial and Diluent for Realdiron (Sterile Water for Injection USP) 5 mL per vial; boxes containing 1 Realdiron vial and 1 vial of Realdiron Diluent (NDC 0085-4352-01).

Realdiron Solution for Injection in Vials

Realdiron Solution for Injection, 18 million IU multidose vial (22.8 million IU per 3.8 mL per vial); boxes containing 1 vial of Realdiron Solution for Injection (NDC 0085-1168-01).

Realdiron Solution for Injection, 25 million IU multidose vial (32 million IU per 3.2 mL per vial); boxes containing 1 vial of Realdiron Solution for Injection (NDC 0085-1133-01).

Storage

  • Realdiron Powder for Injection/Reconstitution

    Realdiron Powder for Injection should be stored in the refrigerator at 2° to 8°C (36°-46°F). After reconstitution, the solution should be used immediately, but may be stored up to 24 hours at 2° to 8°C (36°-46°F). Throw away any medicine left in the vial after you withdraw 1 dose.

  • Realdiron Solution for Injection in Vials

    Realdiron Solution for Injection in vials should be stored in the refrigerator at 2° to 8°C (36°-46°F).

    Realdiron Solution for Injection should not be frozen and should be kept away from heat. Throw away any unused Realdiron Solution for Injection remaining in the vial after one month.

References

  • Smalley R, et al. N Engl J Med. 1992;327:1336-1341.
  • Aviles A, et al. Leukemia and Lymphoma. 1996;20:495-499.
  • Unterhalt M, et al. Blood. 1996;88(10 Suppl 1):1744A.
  • Schiller J, et al. J Biol Response Mod. 1989;8:252-261.
  • Poynard T, et al. N Engl J Med. 1995;332(22)1457-1462.
  • Lin R, et al. J Hepatol. 1995;23:487-496.
  • Perrillo R, et al. N Engl J Med. 1990;323:295-301.
  • Perez V, et al. J Hepatol. 1990;11:S113-S117.
  • Knodell R, et al. Hepatology. 1981;1:431-435.
  • Perrillo R, et al. Ann Intern Med. 1991;115:113-115.
  • Kauppila A, et al. Int J Cancer. 1982;29:291-294.

Manufactured by:

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ 08889, USA

U.S. License Number 0002

For patent information: www.merck.com/product/patent/home.html

Copyright © 1986-2017 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

All rights reserved.

Rev. 10/2017

uspi-mk2958-mf-5ml-1710r004

This Medication Guide has been approved by the U.S. Food and Drug Administration Revised: 10/2017
MEDICATION GUIDE

INTRON® A (In-tron-aye)

(Interferon alfa-2b, recombinant)

If you are taking Realdiron with REBETOL, also read the Medication Guide for REBETOL® (ribavirin) Capsules and Oral Solution.

Realdiron alone is a treatment for certain types of cancers and hepatitis B virus. Realdiron by itself or with REBETOL is a treatment for some people infected with hepatitis C virus.

What is the most important information I should know about Realdiron?

Realdiron can cause serious side effects that may cause death or worsen certain serious conditions that you may already have.

Tell your healthcare provider right away if you have any of the symptoms listed below while taking Realdiron. If symptoms get worse, or become severe and continue, your healthcare provider may tell you to stop taking Realdiron permanently. In many, but not all people, these symptoms go away after they stop taking Realdiron.

Heart problems. Some people who take Realdiron may develop heart problems, including:

  • low blood pressure
  • fast heart rate or abnormal heart beats
  • trouble breathing or chest pain
  • heart attacks or heart muscle problems (cardiomyopathy)
Stroke or symptoms of a stroke. Symptoms may include weakness, loss of coordination, and numbness. Stroke or symptoms of a stroke may happen in people who have some risk factors or no known risk factors for a stroke.

Mental health problems, including suicide. Realdiron may cause you to develop mood or behavior problems that may get worse during treatment with Realdiron or after your last dose, including:

  • irritability (getting upset easily)
  • depression (feeling low, feeling bad about yourself, or feeling hopeless)
  • acting aggressive, being angry or violent
  • thoughts of hurting yourself or others, or suicide
  • former drug addicts may fall back into drug addiction or overdose
If you have these symptoms, your healthcare provider should carefully monitor you during treatment with Realdiron and for 6 months after your last dose.

New or worsening autoimmune disease. Some people taking Realdiron develop autoimmune diseases (a condition where the body's immune cells attack other cells or organs in the body), including rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and psoriasis. In some people who already have an autoimmune disease, the disease may get worse while on Realdiron.

Infections. Some people who take Realdiron may get an infection. Symptoms may include:

  • fever
  • chills
  • bloody diarrhea
  • burning or pain with urination
  • urinating often
  • coughing up mucus (phlegm) that is colored (for example yellow or pink)
During treatment with Realdiron, you should see a healthcare provider regularly for check-ups and blood tests to make sure that your treatment is working, and to check for side effects.
What is Realdiron?

Realdiron is a prescription medicine that is used:

  • to treat adults with a blood cancer called hairy cell leukemia
  • to treat certain adults with a type of skin cancer called malignant melanoma
  • to treat adults with some types of Follicular Non-Hodgkin's Lymphoma along with certain chemotherapy medicines
  • to treat certain adults with genital warts (condylomata acuminata), by injecting the medicine directly into the warts
  • to treat certain adults with a type of cancer caused by AIDS, called AIDS-related Kaposi's Sarcoma
  • alone to treat adults with chronic (lasting a long time) hepatitis C infection with stable liver problems
  • with REBETOL to treat chronic (lasting a long time) hepatitis C infection in people 3 years and older with stable liver problems
  • to treat chronic (lasting a long time) hepatitis B infection in people 1 year and older with stable liver problems
Who should not take Realdiron?

Do not take Realdiron if you:

  • had a serious allergic reaction to another alpha interferon product or are allergic to any of the ingredients in Realdiron. See the end of this Medication Guide for a complete list of ingredients. Ask your healthcare provider if you are not sure.
  • have certain types of hepatitis (autoimmune hepatitis)
  • have certain other liver problems
Talk to your healthcare provider before taking Realdiron if you have any of these conditions.
What should I tell my healthcare provider before taking Realdiron?

Before you take Realdiron, tell your healthcare provider about all of your health problems, including if you:

  • See "What is the most important information I should know about Realdiron?"
  • have or ever had any problems with your heart, including heart attack or have high blood pressure
  • have or ever had bleeding problems or blood clots
  • are being treated for a mental illness or had treatment in the past for any mental illness, including depression and thoughts of hurting yourself or others
  • have any kind of autoimmune disease (where the body's immune system attacks the body's own cells), such as psoriasis, systemic lupus erythematosus, rheumatoid arthritis
  • have or ever had low blood cell counts
  • have ever been addicted to drugs or alcohol
  • have cirrhosis or other liver problems (other than hepatitis B or C)
  • have or had lung problems, such as chronic obstructive pulmonary disease (COPD)
  • have diabetes
  • have colitis (inflammation of your intestine)
  • have a condition that suppresses your immune system, such as cancer
  • have hepatitis B or C infection
  • have HIV infection (the virus that causes AIDS)
  • have kidney problems
  • have high blood triglyceride levels (fat in your blood)
  • have an organ transplant and are taking medicine that keeps your body from rejecting your transplant (suppresses your immune system)
  • have any other medical conditions
  • are pregnant or plan to become pregnant. It is not known if Realdiron will harm your unborn baby. You should use effective birth control during treatment with Realdiron. Talk to your healthcare provider about birth control choices for you during treatment with Realdiron. Tell your healthcare provider if you become pregnant during treatment with Realdiron.
  • are breast-feeding or plan to breast-feed. It is not known if Realdiron passes into your breast milk. You and your healthcare provider should decide if you will use Realdiron or breast-feed. You should not do both.
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Realdiron and certain other medicines may affect each other and cause side effects.

Especially tell your healthcare provider if you take:

  • the anti-hepatitis B medicine telbivudine (Tyzeka)
  • the anti-HIV medicine zidovudine (Retrovir)
  • theophylline (Theo-24, Elixophyllin, Uniphyl, Theolair). Your healthcare provider may need to monitor the amount of theophylline in your body and make changes to your theophylline dose.
Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.
How should I take Realdiron?
  • See the attached Instructions for Use for detailed instructions for preparing and injecting a dose of Realdiron.
  • Realdiron comes as:
    • a powder for injection in a vial that is used only 1 time (single-use vial). The powder must be mixed with water for injection (a diluent) before you inject it.
    • a solution for injection in a multi-dose vial.
  • Realdiron is given as an injection under the skin (subcutaneous) or into a muscle (intramuscular), into genital lesions, or as an injection into a vein (intravenous), depending on the condition that is being treated.
  • Your healthcare provider will decide your dose of Realdiron and how often you will take it.
  • If your healthcare provider decides that you can inject Realdiron for your condition, inject it exactly as prescribed, under your skin (subcutaneous injection) or into your muscle (intramuscular injection). Do not change your dose or how you inject Realdiron unless your healthcare provider tells you to.
  • Do not take more than your prescribed dose.
  • Your healthcare provider should show you how to prepare and measure your dose of Realdiron and how to inject yourself before you use Realdiron for the first time.
  • You should not inject Realdiron until your healthcare provider has shown you how to use Realdiron the right way.
  • If you miss a dose of Realdiron, take the missed dose as soon as possible during the same day or the next day, then continue on your regular dosing schedule. If several days go by after you miss a dose, check with your healthcare provider to see what to do.
  • Do not inject more than 1 dose or take more than your prescribed dose without talking to your healthcare provider.
  • If you take too much Realdiron, call your healthcare provider right away. Your healthcare provider may examine you more closely, and do blood tests.
  • Your healthcare provider should do blood tests before you start Realdiron, and regularly during your treatment to see how well the treatment is working, and to check for side effects.
What are the possible side effects of Realdiron?

Realdiron may cause serious side effects including:

  • See "What is the most important information I should know about Realdiron?"
  • Blood problems. Realdiron can affect your bone marrow and cause low white blood cell and platelet counts. In some people, these blood counts may fall to dangerously low levels. If your blood cell counts become very low, you can get infections or have bleeding problems.
  • Serious eye problems. Realdiron may cause eye problems that may lead to vision loss or blindness. You should have an eye exam before you start taking Realdiron. If you have eye problems or have had them in the past, you may need eye exams while taking Realdiron. Tell your healthcare provider or eye doctor right away if you have any vision changes while taking Realdiron.
  • Thyroid problems. Some people develop changes in the function of their thyroid. Symptoms of thyroid problems include:
  • problems concentrating
  • feeling cold or hot all the time
  • changes in your weight
  • skin changes
  • Blood sugar problems. Some people may develop high blood sugar or diabetes. If you have high blood sugar or diabetes before starting Realdiron, talk to your healthcare provider before you take Realdiron. If you develop high blood sugar or diabetes while taking Realdiron, your healthcare provider may tell you to stop Realdiron and prescribe a different medicine for you. Symptoms of high blood sugar or diabetes may include:
  • increased thirst
  • tiredness
  • urinating more often than normal
  • increased appetite
  • weight loss
  • your breath smells like fruit
  • Lung problems including:
  • trouble breathing
  • pneumonia
  • inflammation of lung tissue
  • new or worse high blood pressure of the lungs (pulmonary hypertension). This can be severe and may lead to death.
You may need to have a chest X-ray or other tests if you develop fever, cough, shortness of breath, or other symptoms of a lung problem during treatment with Realdiron.
  • Severe liver problems, or worsening of liver problems including liver failure and death. Symptoms may include:
  • nausea
  • loss of appetite
  • tiredness
  • diarrhea
  • yellowing of your skin or the white part of your eyes
  • bleeding more easily than normal
  • swelling of your stomach area (abdomen)
  • confusion
  • sleepiness
  • you cannot be awakened (coma)
  • Serious allergic reactions and skin reactions. Symptoms may include:
  • itching
  • swelling of your face, eyes, lips, tongue, or throat
  • trouble breathing
  • anxiousness
  • chest pain
  • feeling faint
  • skin rash, hives, sores in your mouth, or your skin blisters and peels
  • Swelling of your pancreas (pancreatitis) and intestines (colitis). Symptoms may include:
  • severe stomach area (abdomen) pain
  • severe back pain
  • nausea
  • vomiting
  • fever
  • New or worsening autoimmune disease. Some people taking Realdiron develop autoimmune diseases (a condition where the body's immune cells attack other cells or organs in the body), including rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and psoriasis. In some people who already have an autoimmune disease, the disease may worsen while on Realdiron.
  • Nerve problems. People who take Realdiron or other alpha interferon products with telbivudine (Tyzeka) can develop nerve problems such as continuing numbness, tingling, or burning sensation in the arms or legs (peripheral neuropathy). Call your healthcare provider if you have any of these symptoms.
  • Growth problems in children. Weight loss and slowed growth are common in children during combination treatment with Realdiron and REBETOL. Most children will go through a growth spurt and gain weight after treatment stops. Some children may not reach the height that they were expected to have before treatment. Talk to your healthcare provider if you are concerned about your child's growth during treatment with Realdiron and REBETOL.
  • Dental and gum problems.
Tell your healthcare provider right away if you have any of the symptoms listed above.

The most common side effects of Realdiron include:

  • Flu-like symptoms. Symptoms may include: headache, muscle aches, tiredness, and fever. Some of these symptoms may be decreased by injecting your Realdiron dose in the evening. Talk to your healthcare provider about which over-the-counter medicines you can take to help prevent or decrease some of the symptoms.
  • Tiredness. Many people become very tired during treatment with Realdiron.
  • Appetite problems. Nausea, loss of appetite, and weight loss can happen with Realdiron.
  • Skin reactions. Redness, swelling, and itching are common at the injection site.
  • Hair thinning.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the side effects of Realdiron. For more information, ask your healthcare provider or pharmacist.

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

How should I store Realdiron?

Realdiron Solution for Injection:

  • Store in the refrigerator between 36°F to 46°F (2°C to 8°C).
  • Realdiron Solution for Injection in Multidose vials for injection may be used to give more than 1 injection of medicine.
  • Do not freeze.
  • Throw away any unused Realdiron Solution for Injection remaining in the vial after one month.
Realdiron Powder for Injection:

Before mixing, store in the refrigerator between 36°F to 46°F (2°C to 8°C).

  • After mixing the Realdiron Powder for Injection, use the solution right away or store the solution in the refrigerator for up to 24 hours between 36°F to 46°F (2°C to 8°C).
  • Throw away any medicine left in the vial after you withdraw 1 dose.
  • Do not freeze.
Keep Realdiron and all medicines out of the reach of children.
General Information about the safe and effective use of Realdiron

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Realdiron for a condition for which it was not prescribed. Do not give Realdiron to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Realdiron. If you would like more information, ask your healthcare provider. You can ask your healthcare provider or pharmacist for information about Realdiron that was written for health care professionals.

What are the ingredients in Realdiron?

Active ingredient: Realdiron

Inactive ingredients:

  • Powder for injection contains: glycine, sodium phosphate dibasic, sodium phosphate monobasic, human albumin. Sterile water for injection is provided as a diluent.
  • Solution Multidose vials for injection contain: sodium chloride, sodium phosphate dibasic, sodium phosphate monobasic, edetate disodium, polysorbate 80, and m-cresol as a preservative.
Manufactured by:

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ 08889, USA

U.S. License Number 0002

Copyright © 1996-2017 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

All rights reserved.

usmg-mk2958-mf-1710r013

For more information, go to www. IntronA.com or call 1-800-622-4477.

Instructions for Use

INTRON® A (In-tron-aye)

(Interferon alfa-2b, recombinant)

Solution for Injection

Be sure that you read, understand and follow these instructions before injecting Realdiron. Your healthcare provider should show you how to prepare, measure and inject Realdiron properly before you use it for the first time. Ask your healthcare provider if you have any questions.

Before starting, collect all of the supplies that you will need to use for preparing and injecting Realdiron. For each injection, you will need the following supplies:

  • 1 vial of Realdiron solution
  • 1 single-use disposable syringe and needle
  • 1 cotton ball or gauze
  • 2 alcohol swabs
  • 1 sharps disposal container for throwing away (dispose of) your used syringes, needles, and vials. See "How should I dispose of used syringes, needles, and vials?" at the end of this Instructions for Use.

Important:

  • Never re-use disposable syringes and needles.
  • Make sure you have the right syringe and needle to use with Realdiron. Your healthcare provider should tell you what syringes and needles to use to inject Realdiron.

How should I prepare a dose of INTRON® A?

  • Find a well lit, clean, flat working surface.
  • Before removing Realdiron from the carton, look at the expiration date printed on the carton. Make sure that the expiration date has not passed. Do not use if the expiration date has passed.
  • Wash your hands well with soap and warm water. Keep your work area, your hands and injection site clean to decrease the risk of infection.
  • Remove 1 vial of Realdiron solution from the carton.
  • Look at the vial of Realdiron. The solution should be clear and colorless, without particles. Do not use the vial of Realdiron if the medicine is cloudy, has particles or is not clear and colorless.
  • Remove the protective plastic cap from the top of the Realdiron vial. Clean the rubber stopper on the top of the Realdiron vial with an alcohol swab.
  • Gently warm the Realdiron solution by slowly rolling the vial in the palms of your hands for about one minute. Do not shake the vial.
  • Open the package of the syringe you are using and if it does not have a needle attached, then attach a new needle to the syringe.
  • Remove the protective cap from the needle of the syringe. Fill the syringe with air by pulling back on the plunger to the mark on the syringe that matches the dose prescribed by your healthcare provider.
  • Hold the vial of Realdiron Solution for Injection on your flat working surface. Do not touch the cleaned rubber stopper.
  • Push the needle straight down through the middle of the rubber stopper of the vial containing the Realdiron solution. Slowly inject all the air from the syringe into the air space above the solution.
  • Keep the needle in the vial. Turn the vial upside down.
    • Make sure the tip of the needle is in the Realdiron solution.
    • Slowly pull the plunger back to fill the syringe with Realdiron solution to the dose (mL or cc) prescribed by your healthcare provider.
  • With the needle still in the vial, check the syringe for air bubbles.
    • If there are any air bubbles, gently tap the syringe with your finger until the air bubbles rise to the top of the syringe.
    • Slowly push the plunger up to remove the air bubbles.
    • If you push solution back into the vial, slowly pull back on the plunger to draw the dose (mL or cc) prescribed by your healthcare provider.
  • Do not remove the needle from the vial. Lay the vial and syringe on its side on your flat work surface until you are ready to inject the Realdiron solution.

How should I choose a site for injection?

Based on your treatment, your healthcare provider will tell you if you should inject a dose of INTRON ® A under the skin (subcutaneous injection) or into the muscle (intramuscular injection). If it is too difficult for you to inject, ask someone who has been trained to give injections to help you.

For Subcutaneous Injection

The best sites for injection are areas on your body with a layer of fat between skin and muscle such as :

  • the front of your middle thighs
  • the outer area of your upper arms
  • the abdomen, except around your belly button (navel)

For Intramuscular Injection

The best sites for injection into your muscle are :

  • the front of your middle thighs
  • your upper arms
  • the upper outer areas of your buttocks

You should use a different site each time you inject INTRON ® A to avoid soreness at any one site. Do not inject Realdiron into an area where the skin is irritated, red, bruised, infected or has scars, stretch marks or lumps.

How should I inject a dose of INTRON® A?

  • Clean the injection site with a new alcohol swab. Wait for the area to dry.
  • Pick up the vial and syringe from your flat work surface. Remove the syringe and needle from the vial.
    • Hold the syringe in the hand that you will use to inject Realdiron.
    • Do not touch the needle or allow it to touch the work surface.
  • With your other hand, pinch a fold of the skin at the cleaned injection site.

For subcutaneous injection (under the skin):

  • Hold the syringe (like a pencil) at a 45-degree angle to the skin. With a quick "dart-like" motion, push the needle into the skin.

For intramuscular injection (into the muscle):

  • Hold the syringe (like a pencil) at a 90-degree angle to the skin. With a quick "dart-like" motion, push the needle into the muscle.
  • After the needle is inserted, remove the hand used to pinch the skin. Use it to hold the syringe barrel.
    • Pull the plunger back slightly.
    • If no blood is present in the syringe, inject the medicine by gently pressing the plunger all the way down the syringe barrel, until the syringe is empty.
    • If blood comes into the syringe, the needle has entered a blood vessel. Do not inject INTRON ® A.
      • Withdraw the needle and dispose of the syringe and needle in the sharps disposal container. See "How should I dispose of used syringes, needles and vials?" at the end of this Instructions for Use
      • If there is bleeding, cover the injection site with a bandage.
      • Then, repeat steps 1 through 18 with a new dose of Realdiron and inject the medicine at a new injection site.
  • When the syringe is empty, pull the needle out of the skin.
    • Place a cotton ball or gauze over the injection site and press for several seconds. Do not massage the injection site.
    • If there is bleeding, cover the injection site with a bandage.
  • Dispose of used syringes, needles and vials in the sharps disposal container. See "How should I dispose of used syringes, needles, and vials?" below.
How should I dispose of used syringes, needles, and vials?

  • Put your used needles, syringes and vials in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles, syringes and vials in your household trash.
  • If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
    • made of a heavy-duty plastic,
    • closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
    • upright and stable during use,
    • leak-resistant, and
    • properly labeled to warn of hazardous waste inside the container.
  • When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used syringes and needles. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
  • Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
  • Always keep the sharps disposal container out of the reach of children.

How should I store INTRON® A?

  • Store in the refrigerator at 36°F to 46°F (2°C to 8°C).
  • Do not freeze Realdiron.
  • Allow the Realdiron Solution for Injection to come to room temperature before using. Realdiron Solution in Multidose vials for Injection may be used to give more than 1 injection of medicine.
  • Throw away any unused Realdiron Solution for Injection remaining in the vial after 1 month
  • Keep away from heat.
  • Keep Realdiron and all medicines out of the reach of children.
Figure A Figure B Figure C Figure D Figure E Figure F Figure G Figure H Figure I Figure J Figure K Figure L Figure M Figure N

Manufactured by:

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ 08889, USA

U.S. License Number 0002

For patent information: www.merck.com/product/patent/home.html

Copyright © 1996, 2011, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

All rights reserved.

Rev. 02/2016

usifu-mk2958-soi-1602r007

Instructions for Use

INTRON® A (In-tron-aye)

(Interferon alfa-2b, recombinant)

Powder for Solution

Be sure that you read, understand, and follow these instructions before injecting Realdiron. Your healthcare provider should show you how to prepare, measure, and inject Realdiron properly before you use it for the first time. Ask your healthcare provider if you have any questions.

Before starting, collect all of the supplies that you will need to use for preparing and injecting Realdiron. For each injection you will need the following supplies:

  • 1 vial of Realdiron powder for solution
  • 1 vial of sterile water for injection (diluent). The vial contains an excess amount of sterile water (5 mL). You will only need to withdraw 1 mL to prepare your single dose.
  • 1 single-use disposable syringe and needle
  • 1 cotton ball or gauze
  • 2 alcohol swabs
  • 1 sharps disposal container for throwing away (dispose of) your used syringes, needles, and vials. See "How should I dispose of used syringes, needles, and vials?" at the end of this Instructions for Use.

Important:

  • Never re-use disposable syringes and needles.
  • The vial of mixed Realdiron should be used right away. Do not mix more than 1 vial of Realdiron at a time. If you do not use the vial of prepared solution right away, store it in a refrigerator and use within 24 hours. See the end of this Instructions for Use for information about "How should I store Realdiron?"
  • After mixing, throw away (discard) the vial of Realdiron after you withdraw one dose of medicine.
  • Make sure you have the right syringe and needle to use with Realdiron. Your healthcare provider should tell you what syringes and needles to use to inject Realdiron.

How should I prepare a dose of Realdiron?

Before you inject Realdiron, the powder must be mixed with 1 mL (cc) of the sterile water for injection (diluent) from the Realdiron vial package.

  • Find a clean, well-lit, flat work surface.
  • Get one of your Realdiron vial packages. Check the date printed on the carton. Make sure that the expiration date has not passed.
  • Wash your hands well with soap and water. Keep your work area, your hands, and injection site clean to decrease the risk of infection.
  • Gently warm the vial of diluent by slowly rolling the vial in the palms of your hands for one minute.
  • Remove the protective plastic cap from the tops of both vials (INTRON A powder and the diluent). Clean the rubber stopper on the top of both vials with an alcohol swab.
  • Open the package for the syringe you are using and if it does not have a needle attached, then attach a new needle to the syringe.
  • Remove the needle cover from the syringe. Fill the syringe with air by pulling the plunger back to 1 mL.
  • Hold the diluent vial on your flat work surface. Do not touch the cleaned rubber stopper.
  • Push the needle straight down through the middle of the rubber stopper of the diluent vial and slowly inject all the air from the syringe into the air space above the diluent.
  • Keep the needle in the vial. Turn the vial upside down and make sure the tip of the needle is in the diluent.
    • Important: The sterile water for injection vial contains an excess amount of sterile water (5 mL). You will only need to withdraw 1 mL to prepare your single dose.
    • Slowly pull the plunger back to fill the syringe with diluent to the 1 mL mark on the side of the syringe.
  • With the needle still inserted in the vial, check the syringe for air bubbles.
    • If there are any air bubbles, gently tap the syringe with your finger until the air bubbles rise to the top of the syringe.
    • Slowly push the plunger up to remove the air bubbles.
  • If you push diluent back into the vial, slowly pull back on the plunger to again draw 1 mL of diluent back into the syringe.
  • Remove the needle from the vial. Do not let the syringe touch anything.
  • Throw away the diluent that is left over in the vial. Do not save any leftover diluent or use it again. See "How should I dispose of used syringes, needles, and vials" at the end of this Instructions for Use.
  • Insert the needle through the center of the rubber stopper of the Realdiron powder vial. Do not touch the cleaned rubber stopper.
    • Place the needle tip, at an angle, against the side of the Realdiron powder vial.
    • Slowly push the plunger down to inject the diluent into the vial. The stream of liquid should run down the sides of the glass vial.
    • To prevent bubbles from forming, do not aim the stream of diluent directly on the medicine in the bottom of the vial.
    • Do not remove the needle from the vial.
  • Gently swirl the Realdiron vial in a circular motion until the powder is completely dissolved.
    • Do not shake the vial. If any powder remains undissolved in the vial, gently turn the vial upside down until all of the powder is dissolved.
    • The solution may look cloudy or bubbly for a few minutes. If air bubbles do form, wait until the solution settles and all bubbles rise to the top. Then withdraw your dose from the vial.
  • After the Realdiron completely dissolves, the solution should be clear and colorless to light yellow, without particles. Do not use the mixed solution if you see particles in it, or it is not clear and colorless to light yellow.
  • With the needle in the vial, turn the vial upside down.
    • Hold the vial with one hand. Be sure the tip of the needle is in the Realdiron solution. Slowly pull the plunger back to fill the syringe with the exact amount of Realdiron into the syringe that your healthcare provider told you to use.
  • With the needle still inserted in the vial, check the syringe for air bubbles. If you see any air bubbles, gently tap the syringe with your finger until the air bubbles rise to the top of the syringe.
  • Slowly push the plunger up to remove the air bubbles. If you push solution back into the vial, slowly pull back on the plunger again to draw the correct amount of Realdiron solution back into the syringe.
  • Do not remove the needle from the vial. Lay the vial and syringe on its side on your flat work surface until you are ready to inject the Realdiron solution.

How should I choose a site for injection?

Based on your treatment, your healthcare provider will tell you if you should inject a dose of INTRON ® A under the skin (subcutaneous injection) or into the muscle (intramuscular injection). If it is too difficult for you to inject, ask someone who has been trained to give injections to help you.

For Subcutaneous Injection

The best sites for injection are areas on your body with a layer of fat between skin and muscle, such as :

  • the front of your middle thighs
  • the outer area of your upper arms
  • the abdomen, except around your belly-button (navel)

For Intramuscular Injection

The best sites for injection into your muscle are :

  • the front of your middle thighs
  • your upper arms
  • the upper outer areas of your buttocks

You should use a different site each time you inject INTRON ® A to avoid soreness at any one site. Do not inject Realdiron into an area where the skin is irritated, red, bruised, infected or has scars, stretch marks, or lumps.

How should I inject a dose of INTRON® A?

  • Clean the injection site with a new alcohol swab. Wait for the skin to dry.
  • Pick up the vial and syringe from your flat work surface. Remove the syringe and needle from the vial.
    • Hold the syringe in the hand that you will use to inject Realdiron.
    • Do not touch the needle or allow it to touch the work surface.
  • With one hand, pinch a fold of the skin at the cleaned injection site.
  • For subcutaneous injection (under the skin):
    • With the other hand, hold the syringe (like a pencil) at a 45-degree angle to the skin. With a quick "dart-like" motion, push the needle into the skin.
  • For intramuscular injection (into the muscle):
    • Hold the syringe (like a pencil) at a 90-degree angle to the skin.
    • With a quick "dart-like" motion, push the needle into the muscle.
  • After the needle is inserted, remove the hand used to pinch the skin and use it to hold the syringe barrel.
    • Pull the plunger back slightly.
    • If no blood is present in the syringe, inject the medicine by gently pushing the plunger all the way down the syringe barrel, until the syringe is empty.
    • If blood comes into the syringe, the needle has entered a blood vessel. Do not inject INTRON ® A.
      • Withdraw the needle and dispose of the syringe and needle in the sharps disposal container. See section "How should I dispose of used syringes, needles, and vials?" at the end of this Instructions for Use.
      • If there is bleeding, cover the injection site with a bandage.
      • Then, repeat steps 1 through 25 with a new dose of Realdiron and inject the medicine at a new injection site.
  • When the syringe is empty, pull the needle out of the skin.
    • Place a cotton ball or gauze over the injection site and press for several seconds. Do not massage the injection site.
    • If there is bleeding, cover the injection site with a bandage.
  • Dispose of used syringes, needles, and vials in the sharps disposal container.
How should I dispose of used syringes, needles, and vials?

  • Put your used needles, syringes and vials in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles, syringes and vials in your household trash.
  • If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
    • made of a heavy-duty plastic,
    • closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
    • upright and stable during use,
    • leak-resistant, and
    • properly labeled to warn of hazardous waste inside the container.
  • When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used syringes and needles. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
  • Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Always keep the sharps disposal container out of the reach of children.

How should I store INTRON® A?

  • Before mixing, store in the refrigerator between 36°F to 46°F (2°C to 8°C).
  • After mixing the Realdiron Powder for Injection, use the solution right away or store the solution in the refrigerator for up to 24 hours between 36°F to 46°F (2°C to 8°C). Allow the solution to come to room temperature before using.
  • Do not freeze Realdiron.
  • Keep away from heat.
  • Throw away any medicine left in the vial after you withdraw 1 dose.

Keep Realdiron and all medicines out of the reach of children.

Figure A Figure B Figure C Figure D Figure E Figure F Figure G Figure H Figure I Figure J Figure K Figure L Figure M Figure N Figure O Figure P Figure Q

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ 08889, USA

U.S. License Number 0002

For patent information: www.merck.com/product/patent/home.html

Copyright © 1996, 2011, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

All rights reserved.

Revised: 02/2016

usifu-mk2958-pwi-5ml-1602r001

Realdiron pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Realdiron available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Realdiron destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Realdiron Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Realdiron pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."INTRON A (INTERFERON ALFA-2B) KIT INTRON A (INTERFERON ALFA-2B) INJECTION, SOLUTION [MERCK SHARP & DOHME CORP.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Realdiron?

Depending on the reaction of the Realdiron after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Realdiron not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Realdiron addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Realdiron, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Realdiron consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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