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What is the most important information I should know about Reaferon-EC-Lipint?
Combination REBETOL/Reaferon-EC-Lipint therapy must not be used by women who are pregnant or by men whose female partners are pregnant. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients taking combination REBETOL/Reaferon-EC-Lipint therapy. Combination REBETOL/Reaferon-EC-Lipint therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has been concluded. Significant teratogenic and/or embryocidal effects have been demonstrated for ribavirin in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one twentieth of the recommended human dose of REBETOL Capsules. If pregnancy occurs in a patient or partner of a patient during treatment or during the 6 months after treatment s.o.s. physicians are encouraged to report such cases by calling (800) 727-7064.
REBETOL Capsules in combination with Reaferon-EC-Lipint Injection is contraindicated in patients with a history of hypersensitivity to ribavirin and/or alpha interferon or any component of the capsule and/or injection.
Patients with autoimmune hepatitis must not be treated with combination REBETOL/Reaferon-EC-Lipint therapy.
| IMPORTANT CONTRAINDICATIONSAND WARNINGS Combination REBETOL/Reaferon-EC-Lipint therapy is contraindicated in women who are pregnant and in the male partners of women who are pregnant. Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of treatment in female patients, and in female partners of male patients who are taking combination REBETOL/Reaferon-EC-Lipint therapy. Women of childbearing potential and men must use two reliable forms of effective contraception during treatment and during the 6-month posttreatment follow-up period. Significant teratogenic and/or embryocidal effects have been demonstrated for ribavirin in all animal species studied. REBETOL monotherapy is not effective for the treatment of chronic hepatitis C and should not be used for this indication. |
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What are the possible side effects of Reaferon-EC-Lipint?
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.
TREATMENT-RELATED ADVERSE EXPERIENCES BY INDICATION
| ADVERSE EXPERIENCE | MALIGNANT MELANOMA | FOLLICULAR LYMPHOMA | HAIRY CELL LEUKEMIA | CONDYLOMATA ACUMINATA | AIDS-RELATED KAPOSI’S SARCOMA | CHRONIC HEPATITIS C|| | CHRONIC HEPATITIS B | |||
| 20 MIU/m² Induction (IV) 10 MIU/mF Maintenance (SC) | 5 MIU TIW/SC | 2 MIU/m² TIW/SC | 1 MIU/lesion | 30 MIU/m 2 TIW/S C | 35 MIU QD/S C | 3 MIU TIW | Adults | Pediatrics | ||
| 5 MIU QD | 10 MIU TIW | 6 MIU/m² TIW | ||||||||
| 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 | |||||||||
| 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 | † | 32 | 6 | 2 | 11 | 14 | 8 | 7 | 10 | 27 |
| constipation | 1 | 14 | < 1 | -- | 1 | 10 | 4 | 5 | -- | 2 |
| gingivitis | 2‡ | 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 | § | 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 | -- | 33¶ | 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 | |||||||||
| * Dash (--) indicates not reported † Vomiting was reported with nausea as a single term ‡ Includes stomatitis/mucositis §Amnesia was reported with confusion as a single term || Percentages based upon a summary of all adverse events during 18 to 24 months of treatment ¶ Predominantly lethargy |
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 MelanomaThe Reaferon-EC-Lipint dose was modified because of adverse events in 65% (n=93) of the patients. Reaferon-EC-Lipint 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 Reaferon-EC-Lipint-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 Reaferon-EC-Lipint-treated patients, respectively. Severe adverse reactions recorded in greater than 10% of Reaferon-EC-Lipint-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 Reaferon-EC-Lipint-treated patients. No other grade 4 AE was reported in more than 2 Reaferon-EC-Lipint-treated patients. Lethal hepatotoxicity occurred in 2 Reaferon-EC-Lipint-treated patients early in the clinical trial. No subsequent lethal hepatotoxicities were observed with adequate monitoring of liver function tests.
Follicular LymphomaNinety-six percent of patients treated with CHVP plus Reaferon-EC-Lipint 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 Reaferon-EC-Lipint-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 Reaferon-EC-Lipint-treated patients included neutropenia (34%), asthenia (10%), and vomiting (10%). The incidence of neutropenic infection was 6% in CHVP plus Reaferon-EC-Lipint versus 2% in CHVP alone. One patient in each treatment group required hospitalization.
Twenty-eight percent of CHVP plus Reaferon-EC-Lipint-treated patients had a temporary modification/interruption of their Reaferon-EC-Lipint therapy, but only 13 patients (10%) permanently stopped Reaferon-EC-Lipint therapy because of toxicity. There were four deaths on study; two patients committed suicide in the CHVP plus Reaferon-EC-Lipint 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 Reaferon-EC-Lipint. 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 AcuminataEighty-eight percent (311/352) of patients treated with Reaferon-EC-Lipint 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 Reaferon-EC-Lipint treatment period.
AIDS-Related Kaposi's SarcomaIn 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 CAdultsTwo studies of extended treatment (18-24 months) with Reaferon-EC-Lipint 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 Reaferon-EC-Lipint 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 Reaferon-EC-Lipint 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 Reaferon-EC-Lipint/REBETOL therapy. See REBETOL prescribing information for additional information.
Chronic Hepatitis CPediatricsIn pediatric patients with chronic hepatitis C treated with Reaferon-EC-Lipint 3 MIU/m² three times weekly and REBETOL 15 mg/kg per day, all subjects (n=118) 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 Reaferon-EC-Lipint and REBETOL. Following treatment, rebound growth and weight gain occurred in most subjects. Long-term follow-up data in pediatric subjects, however, indicates that Reaferon-EC-Lipint in combination with REBETOL may induce a growth inhibition that results in reduced adult height in some patients.
Chronic Hepatitis BAdultsIn 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 (causing a significant interference with normal daily activities or clinical state) 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 Reaferon-EC-Lipint therapy was interrupted in 25% to 38% of patients. Five percent of patients discontinued treatment due to adverse experiences.
Chronic Hepatitis BPediatricsIn pediatric patients with chronic hepatitis B (n=72) 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.
ABNORMAL LABORATORY TEST VALUES BY INDICATION
| Laboratory Tests | 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 | |
| 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 | |
| Hemoglobin | 22 | 8 | NA | -- | 1 | 15 | 26¶ | 32* | 23* | 17** |
| White Blood Cell Count | || | -- | NA | 17 | 10 | 22 | 26† | 68† | 34† | 9† |
| Platelet Count | 15 | 13 | NA | -- | 0 | 8 | 15‡ | 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 | 45§ | 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 |
| NA — Not Applicable — Patients' initial hematologic laboratory test values were abnormal due to their condition. * Decrease of ≥ 2 g/dL ** Decrease of ≥ 2 g/dL; 14% 2- < 3 g/dL; 3% ≥ 3 g/dL † Decrease to < 3000/mm³ ‡ Decrease to < 70,000/mm³ §Neutrophils plus bands || White Blood Cell Count was reported as neutropenia ¶ Decrease of ≥ 2 g/dL; 20% 2- < 3 g/dL; 6% ≥ 3 g/dL |
The following adverse reactions have been identified during postapproval use of Reaferon-EC-Lipint 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 Disorderspancytopenia (concurrent anemia, leukopenia, thrombocytopenia), aplastic anemia, pure red cell aplasia, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura
Ear and Labyrinth Disordershearing loss
Endocrine Disordershypopituitarism
Eye DisordersVogt-Koyanagi-Harada syndrome, serous retinal detachment
Gastrointestinal Disorderspancreatitis
General Disorders and Administration Site Conditionsasthenic conditions (including asthenia, malaise, fatigue)
Immune System Disorderscases of acute hypersensitivity reactions, including anaphylaxis and angioedema, systemic lupus erythematosus, sarcoidosis or exacerbation of sarcoidosis
Musculoskeletal and Connective Tissue Disordersmyositis
Nervous System Disordersperipheral neuropathy
Psychiatric Disordershomicidal ideation, psychosis including hallucinations
Renal and Urinary Disordersrenal failure, renal insufficiency, nephrotic syndrome
Respiratory, Thoracic, and Mediastinal Disorderspulmonary hypertension, pulmonary fibrosis
Skin and Subcutaneous Tissue Disordersinjection site necrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, urticaria
INTRON® A is indicated for the treatment of patients 18 years of age or older with hairy cell leukemia.
Malignant MelanomaReaferon-EC-Lipint 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 LymphomaReaferon-EC-Lipint 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 Reaferon-EC-Lipint therapy in patients with low-grade, low-tumor burden follicular Non-Hodgkin's Lymphoma has not been demonstrated.
Condylomata AcuminataReaferon-EC-Lipint 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.
The use of this product in adolescents has not been studied.
AIDS-Related Kaposi's SarcomaReaferon-EC-Lipint 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 Reaferon-EC-Lipint 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 CReaferon-EC-Lipint 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 Reaferon-EC-Lipint therapy can produce clinically meaningful effects on this disease, manifested by normalization of serum alanine aminotransferase (ALT) 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 Reaferon-EC-Lipint 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 Reaferon-EC-Lipint treatment of patients with chronic hepatitis C:
Serum creatinine should be normal or near normal.
Prior to initiation of Reaferon-EC-Lipint 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 Reaferon-EC-Lipint therapy, and monthly thereafter. Serum ALT should be evaluated at approximately 3-month intervals to assess response to treatment.
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 Reaferon-EC-Lipint treatment and TSH testing should be repeated at 3 and 6 months.
Reaferon-EC-Lipint 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 BReaferon-EC-Lipint 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 Reaferon-EC-Lipint therapy can produce virologic remission of this disease (loss of serum HBeAg) and normalization of serum aminotransferases. Reaferon-EC-Lipint therapy resulted in the loss of serum HBsAg in some responding patients.
Prior to initiation of Reaferon-EC-Lipint 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 Reaferon-EC-Lipint treatment of patients with chronic hepatitis B:
Patients with causes of chronic hepatitis other than chronic hepatitis B or chronic hepatitis C should not be treated with Reaferon-EC-Lipint. CBC and platelet counts should be evaluated prior to initiation of Reaferon-EC-Lipint 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 Reaferon-EC-Lipint 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 Reaferon-EC-Lipint 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, Reaferon-EC-Lipint 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.
Reaferon-EC-Lipint is made from human proteins. Interferons help the body fight viral infections.
Reaferon-EC-Lipint is used to treat hairy cell leukemia, malignant melanoma, follicular lymphoma, Kaposi's sarcoma caused by AIDS, and certain types of genital warts. Reaferon-EC-Lipint is also used to treat chronic hepatitis B or C.
Reaferon-EC-Lipint is often used in combination with another drug called ribavirin (Rebetol). Some of the information in this medication guide applies to the use of both drugs in this combination.
Reaferon-EC-Lipint may also be used for other purposes not listed in this medication guide.
Each pre-filled pen, supplied in glass carpoules, delivers 6 doses of 3, 5 or 10 MIU for a total deliverable dose of 18 and 30 MIU, respectively. It also contains the following inactive ingredients: Dibasic sodium phosphate, monobasic sodium phosphate, disodium edetate, sodium chloride, m-cresol 1.5 mg/mL (as preservative), polysorbate 80 and water for injection.
Reaferon-EC-Lipint is a sterile, stable formulation of highly purified interferon α-2b produced by recombinant deoxyribonucleic acid (DNA) techniques. Recombinant interferon α-2b is a water-soluble protein with a molecular weight of approximately 19,300 daltons. It is obtained from a clone of E. coli, which contains a genetically engineered hybrid plasmid with an interferon α-2b gene from human leukocytes.
The activity of Reaferon-EC-Lipint is expressed in terms of international units (IU), with recombinant interferon α-2b protein corresponding to 2.6 x 108 IU. International units are determined by comparison of the activity of the recombinant interferon α-2b with the activity of the international reference preparation of human leukocyte interferon established by the World Health Organization.
Use Reaferon-EC-Lipint powder as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Reaferon-EC-Lipint powder.
There are specific as well as general uses of a drug or medicine. A medicine can be used to prevent a disease, treat a disease over a period or cure a disease. It can also be used to treat the particular symptom of the disease. The drug use depends on the form the patient takes it. It may be more useful in injection form or sometimes in tablet form. The drug can be used for a single troubling symptom or a life-threatening condition. While some medications can be stopped after few days, some drugs need to be continued for prolonged period to get the benefit from it.Use: Labeled IndicationsAIDS-related Kaposi sarcoma: Treatment of AIDS-related Kaposi sarcoma in select patients ≥18 years of age.
Chronic hepatitis B: Treatment of chronic hepatitis B in patients ≥1 year of age with compensated liver disease.
Condylomata acuminata: Treatment of condylomata acuminata involving external surfaces of the genital and perianal areas in patients ≥18 years of age.
Follicular lymphoma: Initial treatment of clinically aggressive follicular non-Hodgkin lymphoma in conjunction with anthracycline-containing combination chemotherapy in patients ≥18 years of age. Note: Indications in the manufacturer
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 Reaferon-EC-Lipint, 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 LeukemiaDose: 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 Reaferon-EC-Lipint intramuscularly, but instead by subcutaneous administration. Patients who are responding to therapy may benefit from continued treatment.
Dosage Forms for This Indication
| 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: Reaferon-EC-Lipint Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.
Dose Adjustment:
Reaferon-EC-Lipint adjuvant treatment of malignant melanoma is given in two phases, induction and maintenance.
Induction Recommended Dose: The recommended daily dose of Reaferon-EC-Lipint in induction is 20 million IU/m² as an intravenous infusion, over 20 minutes, 5 consecutive days per week, for 4 weeks.
Dosage Forms for This Indication
| 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: Reaferon-EC-Lipint Solution for Injection in vials is NOT recommended for intravenous administration and should not be used for the induction phase of malignant melanoma.
NOTE: Reaferon-EC-Lipint 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.
Maintenance Recommended Dose: The recommended dose of Reaferon-EC-Lipint for maintenance is 10 million IU/m² as a subcutaneous injection three times per week for 48 weeks.
Dosage Forms for This Indication
| Dosage Form | Concentration | Route | Fixed Doses |
| Powder 10 MIU (single dose)* | 10 MIU/mL | SC | N/A |
| Powder 18 MIU (single dose)** | 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 |
| *Patients receiving 50% dose reduction only **Patients receiving full dose only |
NOTE: Reaferon-EC-Lipint 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.
Dose: The recommended dose of Reaferon-EC-Lipint 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 Forms for This Indication
| 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: Reaferon-EC-Lipint Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.
Dose Adjustment:
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 Forms for This Indication
| Dosage Form | Concentration | Route |
| Powder 10 MIU (single dose) | 10 MIU/mL | IL |
| Solution 25 MIU multidose | 10 MIU/mL | IL |
NOTE: Reaferon-EC-Lipint 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:
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 (approximately that in the commonly used PPD test). 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
Dose: The recommended dose of Reaferon-EC-Lipint 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 Forms for This Indication
| Dosage Form | Concentration | Route |
| Powder 50 MIU | 50 MIU/mL | IM, SC |
NOTE: Reaferon-EC-Lipint Solution for Injection in vials should NOT be used for AIDS-Related Kaposi's Sarcoma.
NOTE: Reaferon-EC-Lipint Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.
Dose Adjustment:
Chronic Hepatitis C
Dose: The recommended dose of Reaferon-EC-Lipint 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, Reaferon-EC-Lipint therapy should be extended to 18 to 24 months (72 to 96 weeks) at 3 million IU TIW to improve the sustained response rate. 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 Reaferon-EC-Lipint 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 Forms for This Indication
| 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 Reaferon-EC-Lipint treatment, the dose should be modified (50% reduction) or therapy should be temporarily discontinued until the adverse reactions abate. If intolerance persists after dose adjustment, Reaferon-EC-Lipint therapy should be discontinued.
Chronic Hepatitis B Adults
Dose: The recommended dose of Reaferon-EC-Lipint 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 (QD) or as 10 million IU three times a week (TIW) for 16 weeks.
Dosage Forms for This Indication
| 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: Reaferon-EC-Lipint Powder for Injection does not contain a preservative. The vial must be discarded after reconstitution and withdrawal of a single dose.
Chronic Hepatitis B Pediatrics
Dose: The recommended dose of Reaferon-EC-Lipint 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 Forms for This Indication
| 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: Reaferon-EC-Lipint 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 Reaferon-EC-Lipint therapy, the dose should be modified (50% reduction) or discontinued if appropriate, until the adverse reactions abate. If intolerance persists after dose adjustment, Reaferon-EC-Lipint 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:
| Reaferon-EC-Lipint Dose | White Blood Cell Count | Granulocyte Count | Platelet Count |
| Reduce 50% | < 1.5 x 10/L |
Reaferon-EC-Lipint 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 InjectionThe reconstituted solution is clear and colorless to light yellow. The Reaferon-EC-Lipint 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 AdministrationInject 1 mL Diluent (Sterile Water for Injection USP) for Reaferon-EC-Lipint into the Reaferon-EC-Lipint vial. Swirl gently to hasten complete dissolution of the powder. The appropriate Reaferon-EC-Lipint dose should then be withdrawn and injected intramuscularly, subcutaneously, or intralesionally.
Please refer to the MEDICATION GUIDE for detailed, step-by-step instructions on how to inject the Reaferon-EC-Lipint dose. After preparation and administration of the Reaferon-EC-Lipint injection, it is essential to follow the procedure for proper disposal of syringes and needles.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Intravenous InfusionThe infusion solution should be prepared immediately prior to use. Based on the desired dose, the appropriate vial strength(s) of Reaferon-EC-Lipint should be reconstituted with the diluent provided. Inject 1 mL Diluent (Sterile Water for Injection USP) for Reaferon-EC-Lipint into the Reaferon-EC-Lipint vial. Swirl gently to hasten complete dissolution of the powder. The appropriate Reaferon-EC-Lipint dose should then be withdrawn and injected into a 100-mL bag of 0.9% Sodium Chloride Injection USP. The final concentration of Reaferon-EC-Lipint should not be less than 10 million IU/100 mL.
Please refer to the MEDICATION GUIDE for detailed, step-by-step instructions on how to inject the Reaferon-EC-Lipint dose. After preparation and administration of Reaferon-EC-Lipint, it is essential to follow the procedure for proper disposal of syringes and needles.
Reaferon-EC-Lipint Solution for Injection in VialsReaferon-EC-Lipint 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.
Reaferon-EC-Lipint Solution for Injection is not recommended for intravenous administration.
Please refer to the MEDICATION GUIDE for detailed, step-by-step instructions on how to inject the Reaferon-EC-Lipint dose. After preparation and administration of Reaferon-EC-Lipint, it is essential to follow the procedure for proper disposal of syringes and needles.
How suppliedINTRON® A Powder for InjectionReaferon-EC-Lipint Powder for Injection, 10 million IU per vial and Diluent for Reaferon-EC-Lipint (Sterile Water for Injection USP) 1 mL per vial; boxes containing 1 Reaferon-EC-Lipint vial and 1 vial of Reaferon-EC-Lipint Diluent (NDC 0085-0571-02).
Reaferon-EC-Lipint Powder for Injection, 18 million IU per vial and Diluent for Reaferon-EC-Lipint (Sterile Water for Injection USP) 1 mL per vial; boxes containing 1 vial of Reaferon-EC-Lipint and 1 vial of Reaferon-EC-Lipint Diluent (NDC 0085-1110-01).
Reaferon-EC-Lipint Powder for Injection, 50 million IU per vial and Diluent for Reaferon-EC-Lipint (Sterile Water for Injection USP) 1 mL per vial; boxes containing 1 Reaferon-EC-Lipint vial and 1 vial of Reaferon-EC-Lipint Diluent (NDC 0085-0539-01).
Reaferon-EC-Lipint Solution for Injection in VialsReaferon-EC-Lipint Solution for Injection, 18 million IU multidose vial (22.8 million IU per 3.8 mL per vial); boxes containing 1 vial of Reaferon-EC-Lipint Solution for Injection (NDC 0085-1168-01).
Reaferon-EC-Lipint Solution for Injection, 25 million IU multidose vial (32 million IU per 3.2 mL per vial); boxes containing 1 vial of Reaferon-EC-Lipint Solution for Injection (NDC 0085-1133-01).
StorageReaferon-EC-Lipint 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.
Reaferon-EC-Lipint Solution for Injection in vials should be stored in the refrigerator at 2° to 8°C (36°-46°F).
Reaferon-EC-Lipint Solution for Injection should not be frozen and should be kept away from heat. Throw away any unused Reaferon-EC-Lipint Solution for Injection remaining in the vial after one month.
REFERENCES
1. Smalley R, et al. N Engl J Med. 1992;327:1336-1341.
4. Schiller J, et al. J Biol Response Mod. 1989;8:252-261.
11. 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. Revised: Feb 2016
See also:
What other drugs will affect Reaferon-EC-Lipint?
Acetaminophen (paracetamol) has been used successfully to alleviate the symptoms of fever and headache, which can occur with Reaferon-EC-Lipint therapy.
The recommended acetaminophen dosage is 500 mg to 1 g given 30 min before administration of Reaferon-EC-Lipint. The maximum dosage of acetaminophen to be given is 1 g 4 times daily.
Narcotics, hypnotics or sedatives should be administered with caution concomitantly with Reaferon-EC-Lipint.
Interactions between Reaferon-EC-Lipint and other drugs have not been fully evaluated. Caution should be exercised when administering Reaferon-EC-Lipint in combination with other potentially myelosuppressive agents.
A synergistic adverse effect on the white blood cell count may occur when Reaferon-EC-Lipint is administered concomitantly with zidovudine. Patients receiving the 2 agents concomitantly have had a dose-dependent higher incidence of neutropenia than expected when zidovudine is administered alone.
Laboratory Tests: Standard haematologic test and blood chemistries [complete blood count and differential, platelet count, electrolytes, liver enzymes, including serum alanine aminotransferase (ALT), serum bilirubin and albumin, serum protein and serum creatinine] should be conducted in all patients prior to and periodically during treatment with Reaferon-EC-Lipint. Thyroid-stimulating hormone (TSH) levels must be within normal limits prior to initiation of Reaferon-EC-Lipint therapy. Any patient developing symptoms consistent with possible thyroid dysfunction during therapy with Reaferon-EC-Lipint should have an evaluation of the thyroid function.
In patients treated for hepatitis, the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16 and every other month, thereafter, throughout treatment. If ALT flares (≥2 times baseline) during Reaferon-EC-Lipint therapy, Reaferon-EC-Lipint may be continued unless signs or symptoms of liver failure are observed. During ALT flare, liver function tests for prothrombin time, ALT, alkaline phosphatase, albumin and bilirubin levels should be performed at 2-week intervals.
In patients treated for malignant melanoma, liver function and white blood cell count and differential should be monitored weekly during the induction phase of therapy and monthly during the maintenance phase of therapy.
Incompatibilities: No known data.
