Interferon beta-1b is available through recombinant DNA technology. Interferon beta-1b has been shown to decrease both the number and severity of multiple sclerosis (MS) attacks (i.e., relapses) and to significantly slow the progression of physical disability associated with relapsing-remitting MS, such as clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. Early treatment of MS with proper therapy may delay cognitive and physical disability. The interferon beta medications are generally considered the initial treatment options for pediatric patients with MS. Interferon beta-1b has also been studied in the treatment of many other conditions. The FDA initially approved interferon beta-1b in 1993.
General Administration Information
For storage information, see specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Interferon beta-1b is administered only by subcutaneous injection.
-The initial injection should be performed under the supervision of a healthcare professional. Patients and caregivers should be properly trained in all aspects of interferon beta-1b injection prior to independent use. See the "Instructions for Use" for the product prescribed. Assess the physical and cognitive abilities of the patient to properly self-administer and dispose of syringes. Patients with severe neurological deficits should not administer interferon beta-1b without assistance from a trained caregiver.
-The manufacturers of Betaseron and of Extavia offer materials to assist with training on subcutaneous injection administration for patients and their health care partners. Information may be obtained by calling 1-800-788-1467 for Betaseron and 1-888-669-6682 for Extavia.
-Premedication with acetaminophen or ibuprofen and administration of interferon at bedtime may lessen the severity of flu-like symptoms.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if particulate matter is present in the reconstituted product or if the solution is not colorless.
Subcutaneous Administration
Reconstitution (Betaseron or Extavia pre-filled syringes)
-Add the manufacturer supplied diluent (0.54% Sodium Chloride injection solution, 1.2 mL) as instructed in the product directions to the vial by using the vial adapter to attach the prefilled syringe that contains the diluent. Gently swirl the vial to aid in dissolution; do NOT shake. If foaming occurs, allow the vial to sit undisturbed until the foam settles. The final concentration is 250 mcg/mL.
-The removable rubber cap of the diluent for the Extavia product contains natural rubber latex, which may cause allergic reactions and should not be handled by individuals with latex hypersensitivity.
-Storage: If not used immediately, the reconstituted injection may be stored in the refrigerator for up to 3 hours; do not freeze the reconstituted product. Discard any unused portion after 3 hours.
Subcutaneous injection
-Withdraw the desired amount of the reconstituted solution into the syringe by turning the vial and syringe to get the vial on top. Pull the plunger back to get the desired amount of product into the syringe. Turn the syringe to point the needle upward, and tap the syringe and release any air bubbles. Twist the vial adapter to remove it and the vial.
-Choose an injection site on the back of the upper arms; abdomen; buttocks; or front thighs. Do not inject within 2 inches of the navel or in a site where the skin is red, bruised, infected, broken, painful, uneven, or scabbed. Also, do not inject into the same site for consecutive injections. Rotate injection sites to minimize injection site reactions such as necrosis or localized infection.
-Inject subcutaneously. Take care not to inject intradermally.
-Use safe disposal procedures for needles and syringes; do not re-use needles or syringes.
Subcutaneous injection of Betaseron using the Betaconnect autoinjector
-The optional Betaconnect autoinjector is not supplied with Betaseron, but is available for patients with a prescription for Betaseron by calling the BETAPLUS patient support program toll-free number in the U.S. at 1-800-788-1467.
-The autoinjector has 3 adjustable injection depth settings; the healthcare provider should determine proper depth setting and injection technique.
-Betaconnect must be charged fully before the first use. Turn the injector on. Wait for the power-on self-test to finish. When finished, the injection button will glow blue, and the green light bar will display the charge status. If the on/off button blinks green continuously or the light bar blinks red, consult troubleshooting instructions.
-Only use the syringes that come in the Betaseron packaging with the autoinjector. Prepare the syringes as above.
-Press the blue lid release button on the side of the autoinjector and fully open the lid. Place the syringe inside the autoinjector leaving the needle cap on. Close the lid.
-The autoinjector is ready for injection when the injection button displays a steady blue light.
-Choose an injection site such as the abdomen, back of the upper arm, thigh, or buttock. Do not inject in the area near the navel or waistline. Rotate injection sites with each injection.
-Remove the needle cap. Activate the safety release by holding the injector against the skin at a 90-degree angle.
-Inject subcutaneously. Press and release the injection button to start the injection. The blue light bar displays the progress of the injection. Injection is complete when blue, flashing bar displays blue and 2 short beeps occur.
-The unit will automatically power off when the injection is complete.
-Press the blue lid release button to open the lid and remove the syringe.
-Keep the safety release clean using a dry or slightly damp cloth or alcohol wipe.
Interferon beta-1b may cause flu-like symptoms; gradual dose titration during treatment initiation may reduce these symptoms. Also, concurrent use of analgesics and/or antipyretics may help ameliorate symptoms on treatment days. Flu-like symptom complex occurred in 57% of 1407 patients who received interferon-1b. The incidence decreased over time with only 10% of patients reporting flu-like symptom complex at the end of the studies. The flu-like symptom complex denotes flu syndrome and/or a combination of at least 2 of the following: fever, chills, myalgia, malaise, and diaphoresis. The median duration was 7.5 days. Among 1407 treated patients, 31% had fever, 21% had chills, 6% had malaise, 23% had myalgia, 53% had asthenia, 42% had pain, 50% had headache, and < 2% had arthralgia and muscle cramps (leg cramps). Myasthenia (< 2%) was an adverse reaction that resulted in clinical intervention such as discontinuation, dosage adjustment, or the need for concomitant medication to treat the adverse reaction symptom. Anorexia was reported post-marketing.
An injection site reaction is the most commonly described adverse reaction to interferon beta-1b therapy and occurred in 78% of patients in trials. Injection site reactions included erythema, bleeding, atrophy, inflammation (42%), pain (16%), skin discoloration, swelling, injection site hypersensitivity (4%), injection site mass (2%), injection site edema (2%), and nonspecific reactions. The likelihood of an injection site reaction appears to decrease over time. During clinical trials, approximately 69% of patients experienced injection site reactions during the first 3 months of treatment as compared with approximately 40% at the end of the studies. Interferon beta-1b may cause tissue necrosis at the injection site. Injection site abscesses and cellulitis have been reported during postmarketing use of interferon beta-1b. Hospitalization for surgical drainage and intravenous antibiotics were required in some cases. Advise patients of the importance of injection site rotation and aseptic injection technique to minimize the risk of tissue necrosis; periodically evaluate patient understanding and use of aseptic self-injection techniques and procedures. Also, instruct patients to promptly report any break in the skin, which may be associated with blue-black discoloration, swelling, or fluid drainage. The decision to discontinue interferon beta-1b after a single site of necrosis is dependent on the extent of necrosis. If multiple lesions occur, discontinue therapy until healing occurs. Some patients have experienced healing while interferon beta-1b therapy continues; however, do not administer into the affected area until it is fully healed. Tissue necrosis at the injection site has been reported in 4% of patients in controlled clinical trials and may occur at single or multiple sites. Typically, it occurs within the first 4 months of therapy but has been reported after 1 year of treatment. The necrotic lesions are usually less than 3 cm in diameter and only involve the subcutaneous fat, although larger and deeper lesions have been reported. Vasculitis has also been reported. For some lesions, debridement and, infrequently, skin grafting have been required. Time to healing varies depending on the severity of the necrosis at the time treatment begins. In most reported cases, healing was associated with scarring.
Of 1407 patients who received interferon beta-1b in clinical trials, 40% had hypertonia as compared with 33% of 965 placebo-treated patients. Incoordination was noted in 17% of interferon beta-1b recipients as compared with 15% of placebo recipients. Dizziness has been reported in < 2% of patients receiving interferon beta-1b in clinical trials and psychotic symptoms have been reported during the post-marketing surveillance period.
Depression and suicide have been reported to occur with increased frequency in patients receiving interferon compounds including interferon beta-1b. Advise patients to report immediately any symptoms of depression and/or suicidal ideation. If a patient develops depression, consider interferon beta-1b cessation. Insomnia (21%) occurred among 1407 patients who received interferon beta-1b in clinical trials. Anxiety and nervousness have been reported in < 2% of patients receiving interferon beta-1b in clinical trials. Confusion and emotional lability have been reported post-marketing. Approximately 30% of both interferon beta-1b recipients and placebo recipients had depression of any severity. Among 1532 patients who participated in clinical trials, 3 suicides and 8 suicide attempts occurred in patients who received interferon beta-1b. As a comparison, 1 suicide and 4 suicide attempts occurred among the 965 patients who received placebo.
The most common adverse gastrointestinal symptom reported during interferon beta-1b therapy of 1407 patients was abdominal pain (16%). Diarrhea, constipation, dyspepsia, and nausea have been reported in < 2% of patients receiving interferon beta-1b in clinical trials. Pancreatitis and vomiting have been reported during the post-marketing surveillance period.
Menstrual disorders were experienced by 12% of 783 premenopausal women treated with interferon beta-1b. However, 15% of 528 patients who received placebo reported menstrual disorders. With the exception of 1 event, all changes were mild to moderate in severity, and no patients withdrew from the studies due to menstrual irregularity. Among 1407 patients who received interferon beta-1b, 9% of premenopausal women had metrorrhagia. Dysmenorrhea and menorrhagia were each reported in < 2% of patients receiving interferon beta-1b in clinical trials.
Among 1407 patients who received interferon beta-1b therapy, peripheral edema (12%), chest pain (unspecified) (9%), and hypertension (6%) were the most common cardiovascular events reported. Cases of congestive heart failure (CHF), cardiomyopathy, and cardiomyopathy with CHF have been reported in patients without known predisposition to these events, and without other known etiologies being established. In some cases, these events have been temporally related to the administration of interferon beta-1b and upon rechallenge, CHF recurrence was observed. Palpitations, vasodilatation, and sinus tachycardia have occurred in < 2% of patients receiving interferon beta-1b during clinical trials. Hypertriglyceridemia has been reported during the post-marketing surveillance period.
Interferon beta-1b can cause various cytopenias. A complete blood count with differential and platelet count is recommended at regular intervals (1, 3, and 6 months) after therapy initiation and periodically thereafter in the absence of clinical symptoms. Patients with myelosuppression may need more intensive monitoring. Lymphopenia (lymphocytes less than 1,500/mm3) occurred commonly (86% of 1,407 patients) and lymphadenopathy was noted in 6% of the patients. Neutropenia (absolute neutrophil count (ANC) less than 1,500/mm3) has been reported in 13% of patients receiving interferon beta-1b. Leukopenia consisting of a WBC count less than 3,000/mm3 has been reported in 13% of patients; an interferon beta-1b dose reduction was needed in some patients. In clinical trials, 18% of patients had leukopenia. Other hematologic toxicities were reported rarely. Thrombocytopenia and hemolytic anemia have been reported during the postmarketing surveillance period.
Spontaneous fetal abortion has been reported during clinical trials with interferon beta-1b. Spontaneous abortions while on treatment were reported in 4 patients participating in the interferon beta-1b clinical trial. In rhesus monkeys, a dose-related abortifacient activity was observed with doses of 0.028 mg/kg/day to 0.42 mg/kg/day of interferon beta-1b, which is 2.8 to 40 times the recommended human dose based on body surface area comparison. The monkeys were given the drug throughout the period of organogenesis. Apprise women who become pregnant or desire to become pregnant while taking interferon beta-1b of the potential risk to the fetus. Use interferon beta-1b during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus; interferon beta-1b discontinuation is recommended.
Weight gain has been reported in < 2% of patients receiving interferon beta-1b in clinical trials. Hypothyroidism, hyperthyroidism, thyroid dysfunction, and weight loss were noted during the post-marketing period of interferon beta-1b. Thyroid function tests are recommended every 6 months for patients with a history of thyroid dysfunction, or as clinically indicated.
Allergic reactions to interferon beta-1b, including trouble with breathing or bronchospasm (wheezing), tongue edema, pruritus, urticaria, and rash (unspecified), have been reported. Of 1,407 patients who received interferon beta-1b, 6% had problems with breathing, 10% had a skin disorder (unspecified), and 21% had a rash. Anaphylactoid reactions, anaphylactic shock, or angioedema have occurred rarely. Discontinue interferon beta-1b if anaphylaxis occurs.
Interferon beta-1b contains albumin and thus, may contain infectious agents, such as viruses, that can cause disease. The remote possibility of contamination or infection with viruses exists in patients receiving interferon beta-1b. Donor screening and manufacturing processes have reduced the risk of infectious agent transmission. Transmissibility of the Creutzfeldt-Jakob disease (CJD) virus by albumin-containing products is unknown but is considered extremely remote. No cases of viral disease or CJD transmission have been identified for albumin.
Among 1407 patients who received interferon beta-1b, 11% reported urinary urgency and 8% reported impotence (erectile dysfunction). .
The relationship between antibody formation to interferon beta-1b and clinical safety or efficacy is not known. Neutralizing antibody formation against interferon beta-1b has been noted in up to 42% of multiple sclerosis patients treated for more than 3 months. Antibodies cross-reacting with interferon beta-1a and natural interferon have also been found in patients with high titers of interferon beta-1b antibodies. Among 124 patients who received interferon beta-1b 0.25 mg every other day, 45% were found to have serum neutralizing activity at one or more of the time points tested. In another group of patients, neutralizing activity was observed in 16.5-25.2% of interferon beta-1b recipients. Among the 75 patients who had neutralizing activity measured at least once, 22.7% converted to negative status later in the study.
Seizures have been reported during the post-marketing period of interferon beta-1b; use caution when administering interferon beta-1b to patients with pre-existing seizure disorders. Seizures have been temporally associated with the use of beta interferons in clinical trials, but it is not known whether these events were related to a primary seizure disorder, the effects of multiple sclerosis alone, to the use of beta interferons, or to some combination of these and other potential precipitants of seizures such as fever.
Fatal capillary leak syndrome has been reported during the post-marketing period of interferon beta-1b. The administration of cytokines to patients with a pre-existing monoclonal gammopathy has been associated
with the development of capillary leak syndrome.
Interferon beta-1b may cause hepatotoxicity. Rare cases of severe hepatic injury including hepatic failure, some due to autoimmune hepatitis, has been reported. The more serious events often occurred in patients exposed to other drugs or substances known to be associated with hepatotoxicity or in the presence of comorbid medical conditions. Asymptomatic elevations of serum transaminases is common in patients receiving interferon beta-1b. Twelve percent of 1407 patients developed significant increases in ALT (> 5 times baseline) as compared with 4% of 965 placebo-treated patients; AST increased significantly in 4% of patients as compared with 1% of placebo-treated patients. Increased GGT has been reported during the post-marketing surveillance period. Liver function tests are recommended at regular intervals (1, 3, and 6 months) after therapy initiation and periodically thereafter in the absence of clinical symptoms. The occurrence of elevated hepatic enzymes should lead to close monitoring and investigation. Consider interferon beta-1b withdrawal if the transaminase concentrations significantly increase or if they are associated with clinical symptoms such as jaundice.
Alopecia, peripheral vascular disorder, peripheral vasodilation, and prostatic disorder have been reported in < 2% of patients receiving interferon beta-1b in clinical trials.
Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), have been reported with interferon beta-1b. Cases have been reported several weeks to years after treatment initiation. Some cases have been fatal. Discontinue therapy if clinical symptoms and laboratory parameters consistent with thrombotic microangiopathy develop, and manage as appropriate.
Lupus-like symptoms (i.e., drug-induced lupus erythematosus) have been observed in patients receiving interferon beta-1b. Signs and symptoms of drug-induced lupus reported in patients treated with interferon beta-1b included rash, serositis, polyarthritis, nephritis, and Raynaud's phenomenon. Cases have occurred with positive serologic testing (including positive anti-nuclear and/or anti-double-stranded DNA testing). Interferon beta-1b should be discontinued in patients developing new signs and symptoms characteristic of drug-induced lupus erythematosus.
Cases of pulmonary arterial hypertension (PAH), some requiring hospitalization, have been reported in patients treated with interferon beta products in the absence of other contributory factors. One reported case required a lung transplant. Cases of pulmonary hypertension have been reported at various time points during treatment, and may occur years after treatment initiation. Assess patients who develop unexplained symptoms (e.g., dyspnea or new or increasing fatigue) for PAH. Discontinue therapy if a diagnosis of PAH is confirmed, and manage as appropriate.
Interferon beta-1b s contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta or in patients with albumin hypersensitivity, or any other component of the formulation. For example, interferon beta-1b may also be inappropriate for patients with E. coli protein hypersensitivity, as the product contains trace amounts of E. coli protein as the drug is manufactured by bacterial fermentation of a strain of E. coli; also assess with caution in patients with mannitol hypersensitivity, as some products contain mannitol.
Use interferon beta-1b with caution in patients with active hepatic disease or a history of significant liver disease. Severe hepatic injury, including cases of hepatic failure, some of which have been due to autoimmune hepatitis, has rarely been reported in patients taking interferon beta-1b. Asymptomatic elevation of serum transaminases is common in patients treated with interferon beta-1b; some cases have recurred on rechallenge with interferon beta treatment. In some cases, events have occurred in the presence of other drugs that have been associated with hepatic injury. The potential hepatotoxicity risk of interferon beta therapies when used in combination with known hepatotoxic drugs or other products (e.g., ethanol ingestion) should be considered before their concurrent use. Monitor patients for signs and symptoms of hepatic injury. Monitoring of LFTs is recommended at regular intervals (e.g., 1, 3, and 6 months) following initiation of therapy and then periodically thereafter in the absence of clinical symptoms. Consider discontinuing treatment with interferon beta-1b if jaundice or other clinical signs of liver dysfunction appear.
Patients with hepatitis or other hepatic disease may not be appropriate candidates for interferon beta-1b receipt. Adverse hepatic events have been associated with the drug. Rare cases of severe hepatic injury including hepatic failure, some due to autoimmune hepatitis, have been reported. Consider the potential risk of hepatotoxicity when used in combination with known hepatotoxic drugs or other products (e.g., alcohol) prior to interferon beta-1b administration, or when adding new agents to the regimen if patients are currently receiving interferon beta-1b. Monitor for signs and symptoms of hepatic injury. Liver function tests are recommended at 1, 3, and 6 months after interferon beta-1b initiation and periodically thereafter in the absence of clinical symptoms. Consider discontinuing interferon beta-1b if serum transaminase levels significantly increase, or if they are associated with clinical symptoms such as jaundice.
Patients treated with interferon beta-1b and their caregivers should be advised to report immediately any symptoms of depression, suicidal ideation, and/or psychosis to their prescribing physicians. If a patient develops depression or other severe psychiatric symptoms, consider cessation of interferon beta-1b therapy. Depression and suicide have been reported to occur with increased frequency in patients receiving interferon beta products versus those receiving placebo. Additionally, there have been postmarketing reports of depression, suicidal ideation, and/or development of new or worsening of other pre-existing psychiatric disorders, including psychosis. For some of these patients, symptoms of depression improved upon cessation of interferon beta.
Interferon beta-1b should be used with caution in patients with a pre-existing seizure disorder; seizures have been reported during clinical trials and postmarketing surveillance. It is not known whether these events were related to a primary seizure disorder, the effects of MS alone, the use of beta interferons, other potential precipitants of seizures (e.g., fever), or to some combination of these.
Monitor patients with significant cardiac disease or pre-existing heart failure for worsening of their cardiac condition during initiation and continuation of treatment with interferon beta-1b. While beta interferons do not have any known direct cardiac toxicity, during the postmarketing period cases of congestive heart failure, (CHF), cardiomyopathy, and cardiomyopathy with CHF have been reported in patients without known predisposition to these events. In some cases, these events have been temporally related to the administration of interferon beta-1b. Recurrence upon rechallenge was observed in some patients. Consider discontinuation of interferon beta-1b if worsening of CHF occurs with no other etiology.
In controlled clinical trials, leukopenia was reported in more persons receiving interferon beta-1b versus placebo and lead to a reduction of interferon beta-1b dosage in some patients. Decreased peripheral blood counts in all cell lines are possible, including rare cases of pancytopenia and severe thrombocytopenia. Monitoring of complete blood cell counts (CBC), differential white blood cell counts, and platelet counts is recommended during therapy (e.g., 1, 3, and 6 months following introduction and periodically thereafter). Patients with bone marrow suppression or myelosuppression may require more intensive monitoring of blood cell counts.
Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), have been reported with interferon beta-1b. Cases have been reported several weeks to years after treatment initiation. Some cases have been fatal. Discontinue therapy if clinical symptoms and laboratory parameters consistent with thrombotic microangiopathy develop, and manage as appropriate.
Use interferon beta-1b with caution in patients with pulmonary hypertension. Cases of pulmonary arterial hypertension (PAH), some requiring hospitalization, have been reported in patients treated with interferon beta products in the absence of other contributory factors. Assess patients who develop unexplained symptoms (e.g., dyspnea or new or increasing fatigue) for PAH. Discontinue therapy if a diagnosis of PAH is confirmed, and manage as appropriate. Cases of PAH have been reported at various time points during treatment, and may occur years after treatment initiation.
Autoimmune disease of multiple target organs has been reported during interferon beta therapy, including thyroid disease (hyperthyroidism or hypothyroidism) and rare cases of autoimmune hepatitis. Monitor for clinical signs and symptoms and if a patient develops a new autoimmune disorder, consider stopping treatment. Cases of drug-induced systemic lupus erythematosus (SLE) have also been reported with interferon beta-1b. Signs and symptoms of drug-induced lupus have included rash, serositis, polyarthritis, nephritis, and Raynaud's phenomenon. Cases have occurred with positive serologic testing (including positive anti-nuclear and/or anti-double-stranded DNA antibody testing). If a treated patient develops new signs and symptoms characteristic of SLE, interferon beta-1b therapy should be stopped.
Injection site reactions, including injection site tissue necrosis, abscess, and cellulitis, can occur with the use of interferon beta-1b. Injection site necrosis (ISN) typically occurs within the first 4 months of therapy, although some cases have occurred over 1 year after initiation of therapy. The necrotic lesions are typically 3 cm or less in diameter, but larger areas have been reported. Generally the necrosis has extended only to subcutaneous fat, but has extended to the fascia overlying muscle. In some lesions where biopsy results are available, vasculitis has been reported. For some lesions, debridement, and/or skin grafting have been required. In most cases, healing was associated with scarring. Necrosis has occurred at single and at multiple injection sites. Some cases reported postmarketing required hospitalization for surgical drainage and intravenous antibiotics. Periodically evaluate patient understanding and use of aseptic self-injection techniques and procedures, particularly if injection site necrosis has occurred. Decisions to discontinue therapy following tissue necrosis at an injection site should be based on the extent of the necrosis. For patients who continue therapy, avoid administration near the affected area until it is fully healed. If multiple lesions occur, change injection site or discontinue interferon beta-1b until healing occurs.
There are no data available on interferon beta-1b use during human pregnancy from well-controlled studies. Observational studies of interferon beta-1b in women have generally not indicated a drug-associated risk of major birth defects. However, spontaneous abortions were reported in 4 patients while receiving interferon beta-1b during clinical trials. Increased risks for lower mean birth weight, shorter mean birth length, and preterm birth (less than 37 weeks) without spontaneous abortion were reported during a systemic review of 761 interferon-beta exposed pregnancies; no increased risk for congenital anomalies was found. The National Multiple Sclerosis Society consensus guidelines and the product labels recommend that women discontinue interferon beta therapy when trying to conceive and throughout gestation due to insufficient evidence regarding safety to the human fetus; however, most women who happen to conceive while taking interferon beta appear to have healthy newborns. If a patient does become pregnant while receiving interferon therapy, she should be made aware of the risks; discontinuation of interferon therapy during pregnancy is recommended. The risks and benefits of continuing interferon beta therapy during pregnancy require careful consideration of the patient's level of disease activity, personal preferences, and the potential fetal risks. During animal studies, a dose-related abortifacient effect was observed when interferon beta-1b was given to pregnant rhesus monkeys at exposures of 3 or more times the human therapeutic dose of 0.25 mg on a body surface area (mg/m2) basis. The effects of interferon beta-1b during labor and delivery are unknown.
There are limited data regarding the use of interferon beta-1b during breast-feeding, and its excretion into human milk is unknown. Due to its poor oral bioavailability, any drug present in the breast milk is unlikely to be systemically absorbed by the nursing infant. The estimated relative infant dose would be 0.006% of the maternal dose, according to one review. An infant who was exclusively breastfed through 5 months of age had no adverse effects due to interferon beta exposure. The Multiple Sclerosis Centre of Excellence on Reproduction and Child Health considers interferon beta to be moderately safe for use during lactation since the molecular weight of the drug is likely to limit transfer to breast milk. Other reviews concur that interferon beta is likely compatible with breast-feeding. Glatiramer and interferon beta-1a are potential alternatives to consider for the treatment of multiple sclerosis. However, the standard of care is to have a patient start disease-modifying therapy of any type only after complete weaning of their infant. A discussion about the risks and benefits of postponing the resumption of interferon beta treatment in order to breastfeed is important, particularly for patients who experience highly-active disease or who had active multiple sclerosis in the year prior to conception. Consider the developmental and health benefits of breast-feeding along with the clinical need for interferon beta-1b and any potential adverse effects on the breastfed infant.
The removable rubber cap of the diluent (0.54% Sodium Chloride Solution) pre-filled syringe for the Extavia formulation contains natural rubber latex, which may cause allergic reactions and should not be handled by individuals with latex hypersensitivity.
For treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease:
NOTE: Interferon beta-1b has been designated as an orphan drug by the FDA for this indication.
Subcutaneous dosage:
Adults: 62.5 mcg subcutaneously every other day for 2 weeks, then 125 mcg subcutaneously every other day for 2 weeks, then 187.5 mcg subcutaneously every other day for 2 weeks, then 250 mcg subcutaneously every other day.
Maximum Dosage Limits:
-Adults
250 mcg every other day subcutaneously.
-Geriatric
250 mcg every other day subcutaneously.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Abacavir: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Abacavir; Lamivudine, 3TC: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Alemtuzumab: (Major) Concomitant use of interferon beta with alemtuzumab may increase the risk of immunosuppression. Avoid the use of these drugs together.
Atazanavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Atazanavir; Cobicistat: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Cabotegravir; Rilpivirine: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and rilpivirine can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving antiretroviral agents and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Chloroquine: (Moderate) Concurrent use of chloroquine and interferons is not recommended as there is an increased risk of retinal toxicity.
Darunavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Darunavir; Cobicistat: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Delavirdine: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
Dolutegravir; Lamivudine: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Dolutegravir; Rilpivirine: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and rilpivirine can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving antiretroviral agents and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Efavirenz: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and efavirenz can both cause hepatotoxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and efavirenz can both cause hepatotoxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and efavirenz can both cause hepatotoxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Emtricitabine: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and rilpivirine can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving antiretroviral agents and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and rilpivirine can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving antiretroviral agents and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Emtricitabine; Tenofovir alafenamide: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Entecavir: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Ethanol: (Major) Consider the potential risk of interferon beta products used in combination with known hepatotoxic drugs or other products (e.g., alcohol) prior to use. Monitor hepatic function during interferon beta treatment. Patients should be advised to avoid drinking alcohol to reduce the chance of injury to the liver during interferon beta treatment. Alcohol may also potentiate drowsiness and dizziness. Patients who develop dizziness, confusion, somnolence, and fatigue with interferon beta treatment should be cautioned to avoid driving or operating machinery.
Fosamprenavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Indinavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Lamivudine, 3TC: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Lamivudine, 3TC; Zidovudine, ZDV: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Lopinavir; Ritonavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Natalizumab: (Major) Natalizumab should be used with caution with interferon beta because of the potential for increased risk of progressive multifocal leukoencephalopathy (PML) and other serious infections with combined use. Ordinarily, multiple sclerosis (MS) patients receiving chronic immunomodulatory therapy should not be treated with natalizumab; however, in some multiple sclerosis clinical trials, patients were allowed to continue interferon beta therapy. Due to the risk for infection and PML, natalizumab is only approved for monotherapy of MS. The safety and efficacy of natalizumab as an add-on therapy to interferon beta treatments has not been established. Sequential therapy (e.g., interferon beta followed by natalizumab) does not appear to increase the risk for PML.
Nelfinavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Nevirapine: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
Nirmatrelvir; Ritonavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Ocrelizumab: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as interferon beta-1a or interferon beta-1b. Concomitant use of ocrelizumab with interferon beta may increase the risk of immunosuppression.
Ofatumumab: (Moderate) Concomitant use of ofatumumab with interferon beta may increase the risk of immunosuppression. Ofatumumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as interferon beta. Consider the duration and mechanism of action of drugs with immunosuppressive effects when switching therapies for multiple sclerosis patients.
Ozanimod: (Moderate) Concomitant use of ozanimod with interferon beta may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies. Ozanimod can generally be started immediately after discontinuation of interferon beta.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with interferon beta. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Pretomanid: (Major) Avoid coadministration of pretomanid with interferon beta, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Protease inhibitors: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Rilpivirine: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and rilpivirine can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving antiretroviral agents and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and interferon beta. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ritonavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Saquinavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Stavudine, d4T: (Major) Patients receiving stavudine with interferons (with or without ribavirin) should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation compared to patients not receiving HAART. Additionally, stavudine has been associated with fatal and nonfatal lactic acidosis and hepatomegaly with or without steatosis and should be used cautiously in patients with hepatic disease. Discontinuation of stavudine should be considered as medically appropriate. Dose reduction or discontinuation of interferon, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Tipranavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Vigabatrin: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Zidovudine, ZDV: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance.
Interferon beta-1b acts similarly to native interferon beta. Interferon beta belongs to the class of interferons, which are species-specific proteins produced in response to viruses as well as a variety of other natural and synthetic stimuli. Interferon beta is a Type I interferon. Interferon beta has 30% amino-acid homology with interferon alpha but only 1% homology with interferon gamma. Both interferon beta and interferon alpha are encoded on chromosome 9. Interferon beta binds to the type 1 interferon receptor with greater affinity than interferon alpha. In addition, interferon beta may bind to a distinct receptor that does not interact with interferon alpha. Interferon beta is produced by various cells including fibroblasts and macrophages, and has both antiviral and immune regulatory activities. Interferon beta increases the levels of 2,5-oligo-adenylate (2-5A) synthetase, an intracellular enzyme that is capable of degrading viral RNA. This activity may contribute to the antiviral and antiproliferative effects of interferon beta. Interferon beta has antiviral activity against herpes virus, human papillomavirus, hepatitis B, hepatitis C, and human immunodeficiency syndrome virus. There is some evidence that interferon beta has greater in vitro antiproliferative effects against many solid tumor cell lines than interferon alpha. The immunoregulatory effects of interferon beta include decreased expression of class II major histocompatibility complex (MHC) antigens, inhibition of T-helper cells, and decrease expression of pro-inflammatory cytokines, and upregulation of interleukin-10, which is an immunosuppressive cytokine that inhibits T-helper cells and interferon gamma and tumor necrosis factor release. The biologic responses of interferon beta therapy may be evaluated via the following markers: Beta2-microglobulin, neopterin, and tryptophan, and inhibition of concanavalin-stimulated proliferation of peripheral blood mononuclear cells.
Interferon beta inhibits the expression of pro-inflammatory cytokines including interleukin (IL)-1beta, tumor necrosis factor- alpha and beta, interferon gamma (INF-G) and IL-6. Interferon gamma is believed to be a major factor responsible for triggering the autoimmune reaction leading to multiple sclerosis. It is thought that INF-G stimulates cytotoxic T-cells and induces macrophages to produce proteinases that degrade the myelin sheath around the spinal cord. INF-G causes upregulation of class II MHC antigens on nervous system tissue; cytotoxic T-cells recognize these antigens as receptor sites and attack the tissue. The result is a progressive neurologic dysfunction. Interferon beta downregulates INF-G production and INF-G-stimulated class II MHC expression. Interferon beta reduces T-cell migration across the blood-brain barrier. Interferon beta has also been found to increase production of nerve growth factor (NGF), which promotes oligodendrocyte survival and differentiation and axonal recovery. This may have a favorable effect on remyelination.
Interferon beta-1b is administered by subcutaneous injection.
-Route-Specific Pharmacokinetics
Intravenous Route
After single IV doses, mean serum clearance was 9.4-28.9 mL/minute/kg, and the elimination half-life ranged between 8 minutes and 4.3 hours.
Subcutaneous Route
After subcutaneous injection of higher than recommended doses, peak serum concentrations were achieved between 1 and 8 hours in healthy volunteers. Bioavailability was approximately 50% after subcutaneous administration.