Interferon Alfa, Human Recombinant
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Cytokine used to alleviate clinical effects of certain viral diseases; little scientific info available to document safety/efficacy in small animals
Cautions: Preexisting autoimmune disease, severe cardiac disease, pulmonary disease, "brittle" diabetes, Herpes infections, hypersensitivity to the drug, or CNS disorders
Adverse Effects: In cats, adverse effects are apparently uncommon with PO; higher dosages given parenterally may cause malaise; fever, allergic reactions, myelotoxicity & myalgia are possible
Interferon alfa use in veterinary medicine has primarily been centered on its SC, or oral/buccal administration in cats to treat a variety of virus-induced diseases. Despite rapid antibody development when injected parenterally and little, if any, absorption after oral administration, the drug does appear to have some efficacy for certain diseases, either via direct antiviral action or more likely, an immunomodulatory effect. Interferon-alfa has been used in dogs for the adjunctive treatment of viral- or immunosuppression-related conditions, such as papillomas, pododermatitis, or digital keratomas. Some work has been done in dogs evaluating it as an adjunctive treatment for certain neoplastic diseases (e.g., hemangiosarcoma).
In summarizing the in vitro, controlled study and clinical efficacy status in vivo for human interferon-alfa use in virus infected cats, one author (Hartmann 2008) reports: High dose SC administration to cats does not appear to be clinically effective for FIV or FeLV infections. Low dose oral treatment does appear to have some efficacy for FIV in cats. Low dose oral therapy does not appear to be effective for FeLV, FHV-1, or FCV (feline calicivirus), and is contraindicated in FIP. Topical administration to FHV-1 infected cats may have some efficacy (see Topical Ophthalmology section). Feline Interferon-Omega has recently become available in several countries and it may be useful in treating viral diseases in both cats and dogs. A separate monograph for that agent follows this one.
The pharmacologic effects of the interferons are widespread and complex. Suffice it to say, that interferon alfa has antiviral, antiproliferative, and immunomodulating effects. Its antiproliferative and antiviral activities are thought to be due to its effects on the synthesis of RNA, DNA, and cellular proteins (oncogenes included). The mechanisms for its antineoplastic activities are not well understood, but are probably related these effects as well.
Interferon alfa is poorly absorbed after oral administration due to its degradation by proteolytic enzymes and studies have not detected measurable levels in the systemic circulation, however, there may be some absorption via upper GI mucosa. It may have some immunomodulating effect via stimulation of local lymphoid tissues.
Interferon alfa is widely distributed throughout the body, although it does not penetrate into the CNS well. It is unknown if it crosses the placenta. Interferon alfa is freely filtered by the glomeruli, but is absorbed by the renal tubules where it is metabolized by brush border or lysosomes. Hepatic metabolism is of minor importance. The plasma half-life in cats has been reported as 2.9 hours.
When used parenterally, consider the risks versus benefits in patients with preexisting autoimmune disease, severe cardiac disease, pulmonary disease, "brittle" diabetes, Herpes infections, hypersensitivity to the drug, or CNS disorders.
One author states that low dose oral therapy is contraindicated in cats with FIP (Hartmann 2008).
When used orally in cats, adverse effects are apparently uncommon. Higher dosages given parenterally to cats may cause malaise; fever, allergic reactions, myelotoxicity, and myalgia are possible. Cats given human interferon-alfa parenterally may develop significant antibodies to it after 3–7 weeks of treatment with resultant loss of efficacy.
When used systemically in humans, adverse effects have included anemia, leukopenias, thrombocytopenia, hepatotoxicity, neurotoxicity, taste sensation changes, anorexia, nausea, vomiting, diarrhea, dizziness, "flu-like" syndrome, transient hypotension, skin rashes, and dry mouth. Except for the "flu-like "syndrome, most adverse effects are dose-related and may vary depending on the condition treated.
Safety during pregnancy has not been established; high parenteral doses in monkeys did not cause teratogenic effects, but did increase abortifacient activity. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.)
It is not known whether this drug is excreted in milk.
No information was located. Determine dosages carefully.
The following drug interactions have either been reported or are theoretical in humans or animals receiving interferon and may be of significance in veterinary patients:
Acyclovir, Zidovudine, Vidarabine: Additive or synergistic antiviral effects may occur when interferon alfa is used in conjunction with zidovudine (AZT) or acyclovir. This effect does not appear to occur with vidarabine, although increased toxicities may occur. The veterinary significance of these potential interactions is unclear.
1. For cutaneus T-cell lymphoma and severe cases of oral/cutaneus papillomas: 1.5–2 million Units/m2 SC 3 times weekly (White 2000)
2. As an immunostimulant for the adjunctive treatment of certain dermatologic conditions (e.g., pododermatitis, papillomas, digital keratomas): 1000 Units PO once daily (given as 1000 Unit/mL solution). (Yu 2008)
For treatment of virus infections:
1. FeLV-infected cats: Low dose: 30 Units per cat PO daily; 7 days on, 7 days off); Hi dose: 10,000–1,000,000 Units/kg SC once daily. Little in the way of large, controlled trials to determine which, if any, immunomodulating therapies (interferon or other agents) are likely to benefit FeLV-infected cats. (Levy 2004)
2. For FIV: 30 Units per cat PO daily; 7 days on, 7 days off (Barr & Phillips 2000)
3. For chronic FHV-1 infections: 30 Units per cat PO daily; 7 days on, 7 days off; repeat cycle. May also use topical ophthalmic therapy: one drop of 25–50 Units/mL of saline in affected eye(s) q4–6 hours. (Powell 2002)
4. For acute life-threatening FHV-1 infections in kittens: 10,000 Units/kg SC daily for up to 3 weeks (Lappin 2003)
Owners should be made aware of the "investigational" nature of this compound and understand that efficacy and safety have not necessarily been established
Prepared from genetically engineered cultures of E. coli with genes from human leukocytes, interferon alfa-2a is commercially available as a sterile solution or sterile powder. Human interferon alfa is a complex protein that contains 165 or 166 amino acids.
Interferon may also be known as: IFN-alpha, interferon-alpha, Ro-22-8181 (interferon alfa-2a), Sch-30500 (interferon alfa-2b); there are many internationally registered trade names available.
Commercially available products should be stored in the refrigerator; do not freeze the accompanying diluent. Do not expose solutions to room temperature for longer than 24 hours. Do not vigorously shake solutions.
An article proposing using this product in cats for the treatment of FeLV states that after dilution of 3 million Units in one liter of sterile saline the resultant solution remains active for years if frozen or for months if refrigerated. However, data corroborating this is apparently not available.
To prepare a 3 Unit/mL solution for oral administration: Using the 3 million Unit vial (see below), dilute the entire contents into 100 mL of sterile water; mix well. Resulting solution contains approximately 30,000 Units/mL. Take 0.1 mL of this solution and add to one liter of sterile saline that has 4 mL of 25% albumin added to it. Albumin is optional but adds stability. Solution is now 3 Units/mL. Divide into aliquots of 15 mL and freeze, preferably at -70°C. Thaw as needed and keep refrigerated. Discard unused portion after 60 days. Discard unused 30,000 Units/mL solution within 2–3 hours of making initial dilutions.
Preparation of solution for 30 Units/mL oral administration: Using the 3 million Unit vial (see below), dilute the entire contents into a 1 L bag of sterile normal saline; mix well. Resulting solution contains approximately 3,000 Units/mL. Divide into aliquots of either 1 or 10 mL and freeze. By diluting further 100 fold (1 mL of 3000 Units/mL solution with 100 mL of sterile saline, or 10 mL with 1000 mL of sterile saline) a 30 Units/mL solution will result. Some have advised aliquoting the diluted solution into 1 mL volumes for freezing up to a year; defrost as necessary. Once defrosted, the drug can be refrigerated up to one week. Freezing the most dilute solutions is associated with loss in activity unless protein such as albumin (see above) is added during dilution (Greene et al. 2006).
Dosage Forms/Regulatory Status
Veterinary-Labeled Products: None
Interferon Alfa-2a (recombinant rIFN-A; IFLrA) Injection: Prefilled syringes: 3 million I.U./syringe (0.5 mL single-use syringes); 6 million I.U./syringe (0.5 mL single-use syringes); 9 million I.U./syringe (0.5 mL single-use syringes); Roferon-A® (Hoffman La-Roche); (Rx)
Interferon Alfa-2b (recombinant (IFN-alpha2; rIFN-a2; a-2-interferon) Powder for Injection: 5 million Units/vial; 10 million Units/vial; 18 million Units/vial; 25 million Units/vial & 50 million Units/vial in vials with a mL, 2 mL or 5 mL diluent/vial; Intron A® (Schering); (Rx)
Interferon Alfa-2b (recombinant (IFN-alpha2; rIFN-a2; a-2-interferon) Injection: 3 million Units/dose; 5 million Units/dose, & 10 million Units/dose in multidose pens; Intron A® (Schering); (Rx)
Interferon Alfa-2b (recombinant (IFN-alpha2; rIFN-a2; a-2-interferon) Solution for Injection: 3 million Units/vial, 5 million Units/vial; 10 million Units/vial; 18 million Units/vial & 25 million Units/vial in vials, Pak-3, -5, -10 (vials & syringes); & in multidose vials (22.8 million Units/3.8 mL/vial or 32 million Units/3.2 mL/vial); Intron A® (Schering); (Rx)
Interferon Alfa-N3 (human leukocyte derived) Injection: 5 million Units/mL (8 mg NaCl, 1.74 mg Na phosphate dibasic, 0.2 mg K phosphate monobasic, 0.2 mg KCl) in 1 mL vials; Alferon N ® (Interferon Sciences Inc.); (Rx)