Interferon Alfa

Risk Factor: CM
Class: Immunologic agents / Immunomodulators


Contents of this page:

Fetal Risk Summary

Interferon alfa is a family of at least 23 structurally similar subtypes of human proteins and glycoproteins that have antiviral, antineoplastic, and immunomodulating properties (1). Five preparations are available in the United States: interferon alfa-n3, interferon alfa-NL (orphan drug status), interferon alfa-2a, interferon alfa-2b, and peginterferon alfa-2B. Interferon alfa-2c has been used in pregnancy, but this product is not available in the United States. No reports describing the placental transfer of interferon alfa have been located.

Shepard reviewed four studies in which human interferon alfa (subtype not specified) was administered by various parenteral routes to rats and rabbits during pregnancy (2,3,4 and 5). No teratogenicity or adverse developmental changes were observed in the offspring.

Interferon alfa-2a produced a statistically significant increase in abortions in rhesus monkeys given 20500 times the human dose (6). No teratogenic effects, however, were observed in this species when doses of 125 million IU/kg/day were administered during the early to midfetal period (day 22 to day 70 of gestation) (6). Interferon alfa-2b also had abortifacient effects in rhesus monkeys treated with 7.530 million IU/kg (90360 times the human dose) (7). Reproduction studies have not been conducted with interferon alfa-n3 (8).

Administration of interferon alfa to female sheep before conception resulted in an increased number of pregnant ewes and embryonic survival (9). This effect may have been the result of enhanced biochemical communication between the mother and conceptus (9). A study published in 1986 demonstrated that human fetal blood and organs, placenta, membranes, amniotic fluid, and decidua contain significant concentrations of interferon alfa (10). In contrast, maternal blood and blood and tissues from nonpregnant adults contained little or none of these proteins. The investigators concluded that one of the effects of interferon alfa may involve the preservation of the fetus as a homograft (10). Other effects and actions of endogenous interferons (alfa, beta, and gamma) in relation to animal and human pregnancies and the presence of these proteins in various maternal and fetal tissues have been summarized in two reviews (11,12).

A number of reports have described the use of interferon alfa in all phases of pregnancy for the treatment of leukemia (13,14,15,16,17,18,19 and 20). The first reported case involved a woman with chronic myelogenous leukemia (CML) who was treated before conception and throughout a normal pregnancy with 4 million units/m2 (6.4 million units) of interferon alfa-2a every other day (13). She delivered a term, healthy, 3487-g female infant whose growth and development continued to be normal at 15 months of age. The newborn had an elevated white blood cell count (40,000/mm3) that normalized at 48 hours of age with no signs or symptoms of infection. Since this report, 10 other pregnancies have been described in which interferon alfa was used for CML or hairy cell leukemia (14,15,16,17,18,19 and 20). In one case, a woman was treated with interferon alfa-2c (not available in the United States) (16). In two of the pregnancies, the concentrations of interferon alfa in the newborns were <0.6 and <1 U/mL, respectively, while those in the mothers were 20.8 and 58 U/mL, respectively (18). Normal pregnancy outcomes were observed in all of the above cases and there were no fetal or newborn toxic effects attributable to interferon alfa (13,14,15,16,17,18,19 and 20). In addition, four infants have been followed for periods ranging from 6 to 44 months and all had normal growth and development (14).

A 1995 Reference reported the use of interferon alfa-2a for the treatment of multiple myeloma before and during approximately the first 6 weeks of pregnancy (21). The woman delivered a normal male infant at 38 weeks' gestation.

As noted above, interferon alfa does not appear to cross the placenta to the fetus. A study published in 1995 specifically evaluated this in two HIV-seropositive women who were undergoing abortions at 19 and 24 weeks (22). Both women were given a single IM injection of 5 million U interferon alfa-2a. Peak blood concentrations of the drug were reached at 3 hours in both women, 100 U and 400 U, respectively. Fetal blood and amniotic fluid samples were drawn at 1 hour from one fetus and at 4 hours from the other. Concentrations in the four samples were all below the detection limit of the assay (<2 U).

A number of pregnant women have been treated with interferon alfa (usually interferon alfa-2a) for essential thrombocythemia (23,24,25,26,27,28,29,30 and 31), although not without controversy (32,33 and 34). In some of these cases, the women were receiving interferon therapy at the time of conception (23,24,26,28,29) and, in most, the treatment was continued throughout pregnancy (26,28,29). No adverse effects in the fetuses or in the newborns attributable to the drug therapy were reported.

An HIV-infected pregnant woman was treated with IM interferon alfa, 2 million units twice weekly, and oral and IV glycyrrhizin during the 3rd trimester (35). Two weeks after interferon alfa was started, an elective cesarean section was performed at 37 weeks' gestation. The healthy, 2320-g female was alive and well at 4 years of age without evidence of HIV infection.

Two reports have described the use of interferon alfa for the treatment of chronic hepatitis C (36,37). In both cases treatment was started before conception and continued into the 2nd trimester. Interferon alfa treatment throughout the 1st trimester also occurred in a woman with advanced Hodgkin's disease (38). Normal newborns resulted in all three of these pregnancies.

In summary, based on a limited number of human cases, the maternal administration of interferon alfa does not appear to pose a significant risk to the developing embryo and fetus. There does not seem to be a difference in risk among the subtypes but, in many cases, the actual product used was not specified. Although very high doses are abortifacient in rhesus monkeys, doses used clinically apparently do not have this effect. No teratogenic or other reproductive toxicity, other than that noted above, has been observed in animals, and no toxicity of any type attributable to interferon alfa has been observed in humans. However, because of the antiproliferative activity of these agents, they should be used cautiously during gestation until more data are available to assess their risk.

Breast Feeding Summary

Interferon alfa is excreted into breast milk. A study published in 1996 measured interferon alfa milk concentrations in two women who had been treated with the drug throughout the 2nd and 3rd trimesters for CML (18). Both women were receiving 8 million units SC 3 times a week at the time of delivery. Immediately postpartum, milk concentrations in the two patients were 1.4 and 6 U/mL (time of the last dose in relationship to milk sampling not specified), while the serum levels in the mothers were 20.8 and 58 U/mL, respectively. The authors did not specify if the infants were allowed to breast-feed.

Breast feeding was allowed in a second Reference (25). The woman was being treated with interferon alfa-2a, 3 million units SC 3 times weekly, for essential thrombocythemia. Nursing was halted 2 weeks postpartum because of the onset of bilateral mastitis.

References

  1. American Hospital Formulary Service. Drug Information 1997. Bethesda, MD:American Society of Health-System Pharmacists, 1997:775804.
  2. Matsumoto T, Nakamura K, Imai M, Aoki H, Okugi M, Shimoi H, Hagita K. Reproduction studies of human interferon
  3. Matsumoto T, Nakamura K, Imai M, Aoki H, Okugi M, Shimoi H, Hagita K. Reproduction studies of human interferon a (interferon alpha). (III) Teratological study in rats. Iyakuhin Kenkyu 1986;17:41738. As cited by Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD:Johns Hopkins University Press, 1992:2201.
  4. Matsumoto T, Nakamura K, Imai M, Aoki H, Okugi M, Shimoi H, Hagita K. Perinatal studies of human interferon a (interferon alpha). (IV) Teratological study in rats. Iyakuhin Kenkyu 1986;17:43957. As cited by Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD:Johns Hopkins University Press, 1992:2201.
  5. Shibutani Y, Hamada Y, Kurokawa M, Inoue K, Shichi S. Toxicity studies of human lymphoblastoid interferon a. Teratogenicity study in rats. Iyakuhin Kenkyu 1987;18:6078. As cited by Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD:Johns Hopkins University Press, 1992:2201.
  6. Product information. Roferon-A. Roche Laboratories, 2001.
  7. Product information. Intron A. Schering, 2001.
  8. Product information. Alferon N. Interferon Sciences, 2001.
  9. Nephew KP, McClure KE, Day ML, Xie S, Roberts RM, Pope WF. Effects of intramuscular administration of recombinant bovine interferon-alphaI1 during the period of maternal recognition of pregnancy. J Anim Sci 1990;68:276670.
  10. Chard T, Craig PH, Menabawey M, Lee C. Alpha interferon in human pregnancy. Br J Obstet Gynaecol 1986;93:11459.
  11. Chard T. Interferon in pregnancy. J Develop Physiol 1989;11:2716.
  12. Roberts RM, Cross JC, Leaman DW. Interferons as hormones of pregnancy. Endocrine Reviews 1992;13:43252.
  13. Baer MR. Normal full-term pregnancy in a patient with chronic myelogenous leukemia treated with a-interferon. Am J Hematol 1991;37:66.
  14. Baer MR, Ozer H, Foon KA. Interferon-a therapy during pregnancy in chronic myelogenous leukaemia and hairy cell leukaemia. Br J Haematol 1992;81:1679.
  15. Crump M, Wang X-H, Sermer M, Keating A. Successful pregnancy and delivery during a-interferon therapy for chronic myeloid leukemia. Am J Hematol 1992;40:23843.
  16. Reichel RP, Linkesch W, Schetitska D. Therapy with recombinant interferon alpha-2c during unexpected pregnancy in a patient with chronic myeloid leukaemia. Br J Haematol 1992;82:4723.
  17. Delmer A, Rio B, Bauduer F, Ajchenbaum F, Marie J-P, Zittoun R. Pregnancy during myelosuppressive treatment for chronic myelogenous leukaemia. Br J Haematol 1992;82:7834.
  18. Haggstrom J, Adriansson M, Hybbinette T, Harnby E, Thorbert G. Two cases of CML treated with alpha-interferon during second and third trimester of pregnancy with analysis of the drug in the new-born immediately postpartum. Eur J Haematol 1996;57:1012.
  19. Lipton JH, Derzko CM, Curtis J. Alpha-interferon and pregnancy in a patient with CML. Hematol Oncol 1996;14:11922.
  20. Kuroiwa M, Gondo H, Ashida K, Kamimura T, Miyamoto T, Niho Y, Tsukimori K, Nakano H, Ohga S. Interferon-alpha therapy for chronic myelogenous leukemia during pregnancy. Am J Hematology 1998;59:1012.
  21. Sakata H, Karamitsos J, Kundaria B, DiSaia PJ. Case report of interferon alfa therapy for multiple myeloma during pregnancy. Am J Obstet Gynecol 1995;172:2179.
  22. Pons J-C, Lebon P, Frydman R, Delfraissy J-F. Pharmacokinetics of interferon-alpha in pregnant women and fetoplacental passage. Fetal Diagn Ther 1995;10:710.
  23. Pardini S, Dore F, Murineddu M, Bontigli S, Longinotti M, Grigliotti B, Spano B. a2b-Interferon therapy and pregnancyreport of a case of essential thrombocythemia. Am J Hematol 1993;43:789.
  24. Petit JJ, Callis M, Fernandez de Sevilla A. Normal pregnancy in a patient with essential thrombocythemia treated with interferon-a2b. Am J Hematol 1992;40:80.
  25. Thornley S, Manoharan A. Successful treatment of essential thrombocythemia with alpha interferon during pregnancy. Eur J Haematol 1994;52:634.
  26. Williams JM, Schlesinger PE, Gray AG. Successful treatment of essential thrombocythaemia and recurrent abortion with alpha interferon. Br J Haematol 1994;88:6478.
  27. Vianelli N, Gugliotta L, Tura S, Bovicelli L, Rizzo N, Gabrielli A. Interferon-a2a treatment in a pregnant woman with essential thrombocythemia. Blood 1994;83:8745.
  28. Shpilberg O, Shimon I, Sofer O, Dolitski M, Ben-Bassat I. Transient normal platelet counts and decreased requirement for interferon during pregnancy in essential thrombocythaemia. Br J Haematol 1996;92:4913.
  29. Pulik M, Lionnet F, Genet P, Petitdidier C, Jary L. Platelet counts during pregnancy in essential thrombocythaemia treated with recombinant a-interferon. Br J Haematol 1996;93:495.
  30. Delage R, Demers C, Cantin G, Roy J. Treatment of essential thrombocythemia during pregnancy with interferon-a. Obstet Gynecol 1996;87:8147.
  31. Schmidt HH, Neumeister P, Kainer F, Karpf EF, Linkesch W, Sill H. Treatment of essential thrombocythemia during pregnancy: antiabortive effect of interferon-a? Ann Hematol 1998;77:2912.
  32. Randi ML, Barbone E, Girolami A. Normal pregnancy and delivery in essential thrombocythemia even without interferon therapy. Am J Hematol 1994;45:270.
  33. Petit J. Normal pregnancy and delivery in essential thrombocythemia even without interferon therapy. In reply. Am J Hematol 1994;45:271.
  34. Frezzato M, Rodeghiero F. Pregnancy in women with essential thrombocythaemia. Br J Haematol 1996;93:977.
  35. Sagara Y. Management of pregnancy of HIV infected woman. Early Hum Dev 1992;29:2312.
  36. Ruggiero G, Andreana A, Zampino R. Normal pregnancy under inadvertent alpha-interferon therapy for chronic hepatitis C. J Hepatol 1996;24:646.
  37. Trotter JF, Zygmunt AJ. Conception and pregnancy during interferon-alpha therapy for chronic hepatitis C. J Clin Gastroenterol 2001;32:768.
  38. Ferrari VD, Jirillo A, Lonardi F, Pavanato G, Bonciarelli G. Pregnancy during alpha-interferon therapy in patients with advanced Hodgkin's disease. Eur J Cancer 1995;31A;21212.

blog comments powered by Disqus

Questions and Answers

what is an interferon beta and interferon alfa?, i have a virology class and i want to know what interferons are. i'm studying DNA virus, like hepatitis C and herpes.

Interferon definition: a group of proteins called cytokines produced by white blood cells, fibroblasts, or T-cells as part of an immune response to a viral infection or other immune trigger. The name of the proteins come from their ability to interfere with the production of new virus particles.

Description: There are 3 types of interferon's: alfa, beta, and gamma. Alfa and beta interferon's, which are grouped together at type I interferon, are produced by white blood cells and a type of connective tissue cell called a fibroblast. Gamma interferon (or type II interferon) is manufactured T-cells. Production occurs when when the T-cells are activated such as during an infection.

The alfa and beta interferon's share some biological activities, but also have activities that are distinct from one another. These similarities and differences reflect the common and different binding of the interferon's to various targets (receptors) on the surface of human cells.

Could epathitis C be treated in differents ways other than using interferon alfa?,

maybe. my dad has it and he's being treated. I'll ask him he's a doctor. yea he says yes

Why is intron A (Interferon alfa-2b) taken by injection?, I'm doing a project on the treatments for diabetes c. Therefore, i am writing about intron A and ribavarine So I'm just wondering why is intron A taken by injection and not a pill? (A site source would also be handy)

Not 100% and you may want to wait for someone with a better idea, but...

Interferons are proteins, and proteins take a beating in the digestive process. Of you were to give someone an oral dose of an interferon, my guess is that most of the interferon consumed would look nothing like its original self by the time it hit the bloodstream. Recombinant products aren't cheap to produce to begin with, so this would seem to be incredibly wasteful. Instead, give an IM injection of the stuff, and it sees the bloodstream in its intended form, at a much lower dose than would be needed for an oral formula.

Just my two cents.

Is there anybody using interferon alfa-2b 30M?, Is there anybody that use interferon alfa-2b for malign melanom cancer? I want to learn what feel use this vaccinate... My level, 3 days of week, and 30 million units and along 10 month.

no

hi my treatment (interferon alfa 2 a combined with ribavarin) has responded well at the 3th month. But now ?, after 10 month i would like to quit it
i know that it sounds ridiculous to quit only 1 month before the very end
do you think might be problematic not to do only 4 more injections?
thanks massimo

You would be well advised to continue with the treatment unless the interferon or ribavirin is causing severe reactions. I've heard of some that take neutrafil to treat anemia, but they generally continue treatment. The thing you must understand is that this treatment in NOT a cure. You can "clear" HCV but there is no cure. Clear means that there is no detectable level of virus.
The key word in that sentence is detectable. You understand how MRSA and other bacteria are becoming more resistant to antibiotics because people don't finish all their meds? With HCV it's not the same, but there are similarities.
#1 Just because one blood test did not find any HCV does not mean that your liver has cleared. HCV clears from the liver last, so blood tests don't always reveal your true status.You may still have the infection in your liver.
#2 HCV mutates- first it mutates some as your body fights it, then it will mutate in an effort to stop the treatment from killing it. If you stop treatment before it is all cleared from your liver you may end up with a more resistant strain of HCV.
There are new treatments in trial and the extra resistance may end up as a moot point, but then again it may mean longer treatment if this treatment doesn't clear the HCV from your system.
I know it isn't pleasant to be on tx & riba, it's miserable to feel like you have the flu about half the time. I only address these issues because I'm a non-responder. After the first 12 weeks my HCV viral count had gone up, my gastro / Hep Dr. let me stay on for 12 more weeks. When my viral count came back it was obvious that my HCV was thriving on the tx & riba. My initial diagnosis was type 1 undifferentiated which means that there was to much mutation to be able to determine the sub-group. Now I'm waiting for the release of the newer treatments (protease inhibitors) in hope that they'll come up with something that will work for me. Treat your HCV all the way, get clear, don't join me in Limbo. Best of luck.

Alfa Interferon.....Positive For FIV Cats?, Can anyone refer me to websites or other sorces for information on treating FIV postive cats currently showing symptoms? Info on Interferon would be greatly appreciated.

Thank you.

Join feral_cats@yahoogroups, they will have a ton of info on FIV and FELV, especially email Gesine - she is the moderator for the group and she can direct you to the list's files.
And I think there might be a group also for FIV cats and also for FELV cats (Feline leukemia)

Can long term methadone use wreck your body?, i know someone who is on methadone(maintance) and also has hepatitis c, has been offered interferon alfa and ribavirn treatment for this but is'nt sure about the long term effects of methadone use

In a word...yes;

i have cin1 cervical dysplasia caused by hpv.can i same how cure my cin 1?, My doctor gave me interferon alfa,7 shots every other night.and told me to wait and see.But i want to know what else can i do ti improve my health?i have hpv high risk type 31.have any one has some expirience or knows something more??

I have had CIN III that was treated with surgery. There are some things you an do to help, but there are no guarantees. You can eat foods rich in antioxidants, take a multivitamin, no smoking (big no-no) and lower your stress level. Your immune system plays a vital role in HPV and cervical dysplasia. Most people can fight off HPV and cause it to go dormant, if it is not active it won't cause you any problems. However, if your immune system is weakened at all it can come out and cause havoc. So take care of yourself and try to boost your immune system. The good thing is CIN I is mild and many times can regress on its own, but you need to keep your appts. and listen to your doc. Good luck!

New Hep-C patient. Need details on dieing from it.?, Been testing Hep-C pos for about 15 yrs, just got a viral load result of 11.5 mill., genome A or 1 (cant remember which) Considering just comfort measures 'til death because of the terrible experience hubby had 5 yrs ago with interferon alfa 2b with riboviron. Have suffered with great overal body pain (and other symptoms) of fibro myalgia, also have been dealing with insulin dependent diabetes for ~10 yrs., chronic allergies (which aggravate the flu like symptoms of fibro) and I have a miriad of other symptoms & probs from "endocrine system shut-down" (Dr's words) from a full body blast of radiation the level of Chernobyl. So, the question is, what do I have to contend with on my way to death from this latest slap in my life-pod's face. Please--no Bible-thumpers' "pray!..." answers.

Those that tend to have symptoms of HCV, tend to have a better time on antiviral chemo.

The trick to successful treatment is WATER. Lots of WATER.

There is no reason why you could not TRY treatment. If you can't handle it, then you just don't do it!

I would rather LIVE longer with the HCV not active anymore than suffer a death I could prevent.....

I did a full years worth of interferon and ribavirin and amantadine.
Sides were lessened dramatically due to a gallon of water a day.

Other meds can also help you through like antidepressants (if your not on them already...hcv does cause depression too) and anti-anxiety meds.

Your symptoms are CLEARLY a sign that your HCV is doing what it does best.....the fibro...I HAD fibro....but not anymore as the treatment cured the HCV that caused the fibro to begin with!

The only thing the treatment did not get rid of for me was the "brain fog".

My rashes...gone.
My bone and joint pain (fibro) gone.
My energy level? OUTSTANDING! I can stay up all day! I sleep anywhere between 5 hours a night to the standard (depending on my housework)
I used to sleep 18 hour days prior to chemo!

The endocrine system for me is messed up. HCV does that....the treatment doesn't help either...but I'm alive and feeling pretty good! TONS better.

HCV is not a death sentence. Treat the HCV and rid of some of your problems.....otherwise, you will end up treating all the "bi-directionals" of HCV......

I dont know about you, but I am not a pill taker. I am sooo glad they found out what was wrong with me after almost a lifelong infection......

Now that I have said that, what to expect if you opt not even to try the treatment is.....
liver cell death/cirrhosis/cancer (possible cancer that is)
kidney and heart failure.

HCV is not just a liver disease....if you have HCV it resides and causes all organs to malfunction.....

What happens is you basically bloat because the kidneys will shut down. Your skin will seep liquids. You will be a deep yellow color. You will eventually slip into a light comatose state and pass away from heart failure without even knowing it.

I REALLY hope you at least TRY the treatment...get on the right meds (anti's) and have the anti-anxiety meds ready to go....

If you need to talk, HOLLER okay? heppystephy at yahoo dot com



How to Pass a Drug Test?