A large number of individuals have asked for a simple explaination of how
the low dose oral interferon lozenges work. To get a hint at how important
interferon is to the human body and all the systems our internal interferon
production is to our overall health, visit http://www.lerner.ccf.org/labs/williams/ and check out how vital interferon and its production is to overall health.
This above link shows that interferon alpha modulates approximate 600 genes
which help control health and our internal communication which maintains
overall health.
The full explanation of how the oral interferon works is complex and varies
drastically between those issues that deals with viruses, tumors, and autoimmune
disorders since the different conditions, viruses, antibodies, and other
stimuli present in the body greatly impacts the way the body responds to
any given immune situation. Also, there is a big difference between the
way the injectable interferon and the oral interferon work; that is why
Amarillo Biosciences holds about 20 patents on the oral interferon and
is undergoing clinical trials for the oral interferon even though the injectable
is already approved. The low dose oral interferon alpha is still officially
considered to be an experimental, non-approved medication in the USA, Canada,
and in many other countries.
Based on my research, the following is a very simplistic explanation in
layman's terms of how it is thought the low dose oral interferon alpha
lozenges may work to help Behcet’s patients: Each low dose oral interferon
alpha lozenge contains natural human interferon just like that produced
by the body’s own cells. The lozenge is dissolved in the mouth by saliva
and the interferon from the lozenge binds to special dendritic cells in
the mucosal membranes of the mouth and throat. Interferon is a cytokine,
one of a large group of low-molecular-weight proteins secreted by various
cell types and involved in cell-to-cell communication - coordinating anti-body
and T cell immune interactions. The oral interferon essentially sets in
motion a modulation of the body's own production of some interferons, some
interleukins, and some immunoglobulin levels which are crucial to the immune
cascade. By modulating these levels, the interferon modulates the lop-sided,
over-reactive Behcet’s autoimmune cascade that causes the Behcet’s flares.
When these Behcet’s flares are brought under control, the body is again
able to sustain normal functions and recuperate over time.
When a "normal" body detects a virus or other "invader" that it thinks needs to be fought, it "normally" responds by creating interferon in the nasal secretions in very small amounts. It then distributes this interferon to the cells in the mucosal membranes of the nasal passages, throat, etc. performing its job of directing and controlling the immune response appropriate for the invader detected. This is the same interferon that is cultured and distributed in the lozenges in roughly the same quantity as that normally produced by the body in response to such an invader. It works the same way.
For example, Behcet's patients have a problem with their natural immune system. Somewhere along the line in the immune response, something goes awry. Some level of the immune cascade either over-reacts or reacts inappropriately to whatever their body has decided to recognize as an invader. (To a BD body, anything from foods to chemicals to physical or emotional stress can be interpreted as a invader.) These over-zealous, inappropriate reactions tend to zap things they shouldn't creating a major long term immune response rather than just a simple allergic reaction like sniffles or hives or else the immune system gets so hyped up that it not only zaps the invader but it manages to zap everything around it including the blood vessels, nerves, and tissues. That accounts for the multitude of symptoms encountered by a BD patient such as systemic vasculitis, lesions all over the place, neuro damage, and all the other weird symptoms a BD body can create.
Many doctors think of interferon treatments as a drastic last ditch step. That is par for the course because nearly all doctors only know of the injectable kind. When they inject IFN, they use dosages measured in the millions - 3 million units (3 MU) at a time is typical. It takes that much in an injection into your muscles to get what is necessary (circulating systemically) to reach the target problem.
The normal LDO-IFNa oral dosage is a tiny fraction of the injectable - usually only 900 IUs a day. That is 3,000,000 vs. 900 IUs. The injectable 3 MU are put into a body in a very unnatural fashion. Now even though they have had toxic side effects when injecting 3 million units at a time into our muscles, the tiny doses we take in the lozenges is miniscule and has not been shown to cause any side effects significantly different from placebo for the many hundreds of people (now over a 1500 from clinical trials) that have used LDO-IFNa during the last few years. The tiny oral dose can still work because it mimics the same kind and the same amount our body naturally creates in our nasal secretions during times when our body is fending off some kind of virus. It seems to work so well because it is absorbed through the mucosal membranes of our mouth and throat just like it does with the natural interferon in our nasal secretions. We don't need to pound our bodies with huge doses to make it effective; we just need to apply the natural kind to the body in a natural way.
The oral IFN apparently does not travel to the site of problem tissues to tackle the problem directly; rather it appears to modulate or regulate our immune system to work correctly. Essentially, if you have any type of immune dysfunction and your immune system is going nuts and attacking your body lots of ways that it shouldn't while ignoring tasks that it should be tackling, the oral IFN triggers it to balance out and work right. It doesn't heal your lesions or battle the inflammations, it stops you from getting new ones and allows the old ones to heal. All over your body.
Amarillo Biosciences has been doing clinical trials, formal studies, and individual trials with oral IFN for a number of years throughout the world with a lot of people taking it on a long term basis for a number of diseases and disorders. The oral version has not shown nearly the number or severity of the toxic side effects normally associated with the injectable interferon. IFN has been shown to regulate the interleukin levels that have been demonstrated to be deficient in several immune disorders. (My Mosby's Pocket Dictionary defines interleukin as "one of a large group of cytokines produced mainly by T cells or in some cases by mononuclear phagocytes or other cells. Most interleukins direct other cells to divide and differentiate.")
IFN may sound like a toxic drug to your doctors but I consider the oral IFN to be a natural treatment. Consider this: You are thirsty. You drink 8 ounces of water and you are no longer thirsty. Try to visualize how much water would have to be injected with a syringe into your muscles before you had the same amount of thirst relief and how long would it take? That much water injected into your muscles would also cause some nasty problems with your body! It is not natural to your body to absorb it that way. Ditto with the interferon!
The kind and dose of interferon received via the lozenges is probably physiological compared to the toxic injections given to most folks. That is why it has the potential to work as well or better than the injectable interferon without the nasty side effects
NOTE: I am simply a Behcet’s patient that takes the oral interferon lozenges.
I am not a medical professional. Although I and my doctor have had extensive
communications with the pharmaceutical company that produces this medication,
I am speaking strictly from my own experience. If you have any questions,
please talk to your physician. Always follow the guidance of your personal
physician.
After personal experimentation and communicating with many other BDers that take these lozenges, as of 2002 I routinely take 3 lozenges twice a day. This dosage allows me, like many others, to lead a more normal lifestyle with very few restrictions. Six lozenges a day is now considered to be the normal dosage for patients with Behcet's although some patients have found that a higher dosage (prescribed by their physician) is even more beneficial; to the best of my knowledge, those on the higher dosage are not suffering from side effects due to the increased dosage. I tend to vary my dosage depending on whether or not I have been "mistreating" my body. If I have been exposed to things that used to trigger my BD flares such as eating a lot of foods that I know I am allergic to, have been exposed to harmful chemicals (exhaust, gasoline, ammonia), pushed my body very far physically (hiking, spending a day stacking firewood, etc.), and/or have been under a lot of emotional stress - then I may use a higher dosage. Also, I tend to forget to take them because I don't have symptoms to remind me and after slacking off for a while I may start feeling symptoms. When this happens, I increase my dosage for a day or two to bring my immune responses back under control, then go back to my normal dosage of 6 lozenges a day.
Dosages vary quite a bit between patients. A few do well on a lower dose but most need to take six lozenges a day although the dosage pattern also varies between patients. Only personal trials of different doses and schedules will let you determine what is best for you. Discuss this with your doctor and follow his advice. After nearly 3 years of talking with others using this treatment, it has become obvious that most do best on at least 6 lozenges a day and a few doctors prescribe higher dosages. The following dosage schedules are the most common: two lozenges three times a day, three lozenges twice a day (best for me), or two in the morning upon arising, one lozenge after lunch, two lozenges after supper, and one lozenge at bedtime (some Neuro-BD patients seem to have reduced their seizures using this latter dosage that I refer to as the 2-1-2-1 dose). One thing learned over the last three years is that a smaller dose may not only not be beneficial but it might possibly work against a Behcet's patient by stimulating their immune system; the full dosage of six lozenges a day appears to bring the level of interferon up to where it modulates the immune system like we BDers need. With immune disorders like Behcet's, the focus is to modulate the immune system so I no longer recommend that BD patients start with a tiny dose then work up. A mouse study for a different immune disorder appears to back this theory up. From personal experience, we discovered that one of our sons could not tolerate a very small dose of 1/2 or even a 1/4 lozenge twice a day but when he took the plunge and started right off with 2 lozenges two or three times a day - he did great. He also does well on a dose of 3 lozenges twice a day. Most patients need to experiment with their schedule to see what works best for them. The good news is that the doses that we take is so low that I don't think anyone could overdose on the dosages listed here.
My personal experience has shown that keeping a perfect schedule (i.e. set times of day, every 6 hours, every 4 hours, etc.) does not work best for me. I am speaking only from personal experience, but I do best by following my body's natural schedule of sleeping and eating. I take my first dose (if I remember it!) after breakfast or after lunch. I always take my final dose when I go to bed.
Some BD patients seem to do best when they are careful to not spread out their doses more than 8 hours apart. It is my understanding the lozenges tend to do their good stuff for about an 8 hour time period so this may explain it. I used to be careful to never exceed the 8 hour limit; I used to follow the 2-1-2-1 dose myself for that very reason. If I took the first dose at 8 a.m. and the last dose at 8 p.m., then there was a 12 hour period between the doses - essentially letting my body run amuck for around 4 hours prior to the following dose. I used to get more mini break-through flares when I let that happen so I switched to the four times a day dosage and did much better. Now, possibly because the progression of my disease appears to have been halted or simply because my immune system is learning to over-react less often and behave more like a normal immune system should, I do very well on the 3 lozenges twice a day dose. Keep in mind this is my own personal decision. Each patient will have to see what works best for them. Please follow the advice of your personal physician.
The good news here is that there is no reason to "wean" down slowly from a higher dosage to a lower dosage. It is not like taking steroids where the body stops making the necessary substance naturally. The body continues to make interferon whether or not a person is on these lozenges and a "weaning" process is not necessary.
I think one of the beauties of this medication will be the fact that it can be taken on an “as needed” basis only for those that only suffer occasional flares. I have had trouble remembering to take my lozenges because I am no longer experiencing any pain to remind me. I have no rebound effect when I forget to take them and start skipping doses - my normal Behcet's just starts creeping back in and I promptly go back to taking my lozenges on a more regular basis!
Please keep in mind that this is a new, experimental medication. One of the things that we are working to figure out right now is the correct dose for Behcet's patients. It may easily take more for us than it does for someone with Sjogren's or fibromyalgia. The 'normal' dose listed on clinical trials for those patients is the dose determined to help those types of patients and a simple dosing schedule easy to maintain during clinical trials.
Remember, the people receiving the injectable interferon are usually taking 3 million IUs per day; if you are taking 6 lozenges a day - you are still only taking 900 units per day or .03% (no that is not a typo) of the injectable dose.
When I use more than one at a time - I dissolve the lozenges simultaneously. The directions on the box states otherwise but when taking more than a single lozenge, we need to do them simultaneously.
I try to not eat much for a little while before I take my lozenges, especially greasy foods. Common sense tells me that first coating my mouth with foods will reduce the ability of the interferon to make contact with the cells in my mucosal membranes. After I finish taking my lozenge(s), I wait 15 minutes before I eat or drink anything so as to not wash it right back out. They work through contact with the mucosal membranes in your oral pharyngeal cavity – not through what is absorbed through your stomach or intestines so you don’t want to wash the traces from your mouth too soon.
I will mention here that the lozenges come prepackaged in little individual foil squares and are easy to store and convenient to carry in a pocket or purse. The directions on the box say to keep refrigerated but I was told that this is not necessary for short term usage. I do keep my boxes of packets in the refrigerator but I also carry some little foil packets in my purse for times that I am away from home. If traveling, I take as many as needed in my suitcase. I do not open a packet until I am ready to use the lozenge as moisture is not good for them. If I open one and do not use it right away, I am careful to securely reseal the packet until I am ready to use it. Try to not "cook" them by leaving them in a car baking in the hot sun or by placing your purse containing lozenges directly under the heater outlets in the car. Also, exposure of open lozenges to moisture can reduce their efficacy. Keep them sealed. If you have broken the seals, then keep them dry and sealed as well as possible until time to use them.
I do not let those little lozenges stop moving in my mouth when I dissolve them. I swish them from side to side and over and under my tongue until they have dissolved, then I swish that saliva around for about 5 more minutes after that. I can't prevent my swallow reflex from kicking in but I have learned to "dry swallow" until I am ready to swallow my saliva. I just keep my saliva in the front of my mouth while my throat goes through its swallow reflex. It has become second nature at this point. I then tip my head back, gargle it a time or two (my own quirky way of coating my throat – I was never told to do this), then swallow it a little at a time. Even if there is a possibility of a slight allergic reaction to any of the ingredients in it, by keeping the lozenges moving around, it will hopefully prevent any localized reactions. Also, I feel like the more the mucosal membranes come in contact with the medication, the more I will get out of it. I am careful to completely coat my mouth: under my tongue, between my gums and teeth, the roof of my mouth, etc. I also tend to swish this around for a little longer than the 3 or 4 minutes recommended (I shoot for 5 minutes) because I want to get every little smidgen of good out of it. I have been informed several times that this is not necessary but I am trying to honestly report my own experiences and practices! I have talked to other Behcet's patients that have found great success with this treatment following this same routine - even the extended swishing.
Skeptical at first, we found that most Behcet’s patients treated with the injectable IFN were receiving as much as 3 MU (million international units) per injection on a daily basis. The oral interferon is provided in small tablet size lozenges of only 150 IU (international units) each and in some of the previous trials single lozenges were taken three times a day for a total of just 450 IU per day. This low dosage for the oral interferon was about 1/20,000th of that frequently taken by Behcet’s patients on the injectable variety! Now it made sense that it would not be as toxic as the injectable.
Here is information about how to order the low dose oral interferon alpha lozenges (brand name = Veldona). This email was written with an American Behcet’s Disease patient in mind as that is the disease I have and the majority of patients/physicians I work with have Behcet’s. If your physician is ordering the lozenges for a different medical disorder, simply substitute the name of the other disorder where it states Behcet’s in the documentation. If you are not an American, please check the local importation regulations as they vary from country to country. Please be sure to read all of the information in this email, especially the words of caution toward the end.
NOTE: This treatment is experimental and has not been approved in any country specifically for the treatment of Behcet’s Disease therefore it is necessary to carefully provide all information requested to help prevent problems with customs or other regulatory officials. Please note that the doctor must be authorized to legally write prescriptions within the country into which the lozenges will be imported.
Fax the documentation listed below plus the prescription (making certain the patient's name, physician's name, and mailing addresses are complete and legible) directly to Mr. Don McTaggart at 905/332-4492 in Canada. (The lozenges are manufactured in Canada.) This telephone number is a combination voice/fax line; their fax machine will automatically pick up if a fax tone is detected, otherwise it will be answered as usual. The address for Mr. McTaggart is:
Don McTaggart & Associates
Consulting Services, Inc.
1945 Kerns Road
Burlington, Ontario L7P 3J1
Canada
and the prescription and documentation can be mailed to this address if you have difficulty with this fax number.
Importation regulations vary widely from country to country but by including the following information, most shipments will not be held up by customs officials. If any problems are encountered with customs, it may help to email to Mr. Don McTaggart at dmctaggart1@cogeco.ca to request help.
What is needed:
1) The prescription should read: "560 interferon alpha lozenges @ 150 IU each; dissolve three lozenges in the mouth two times a day. May be refilled three (3) times." This is a three month supply. By marking the prescription for 3 refills, future orders within the coming year can be ordered via an email request to Mr. Don McTaggart at the email address listed above. It should not be necessary to duplicate the prescription, letters, and other documentation during this time period.
2) Include a letter, from the attending physician (on the physician's office letterhead stationary) that reads: "I, Dr. [name of doctor], will monitor the treatment of patient [name of patient] while the patient takes interferon orally for Behcet’s Disease."
3) Include a request written by the physician (again on the physician's office letterhead stationary) for a "personal use exemption" with a brief explanation of the grounds for this request such as: "Other available treatments have failed to control the progression/symptoms of this patient’s Behcet’s Disease. This patient has suffered from severe and/or life threatening manifestations and I feel treatment with oral interferon alpha is warranted in this situation. I am requesting a personal use exemption for this patient, [name of patient]." This is a separate letter from the "I will monitor" letter.
4) Write a letter in which the PATIENT seeking to import the product affirms in writing that it is for the patient's own use and provides the name and address of the licensed doctor responsible for his or her treatment with the product. Be sure to include the handwritten signature of the patient. Example: "I, [name of patient], am importing the low dose oral interferon for my own use. My doctor is [name of doctor and doctor’s address]. [signature and address of patient]"
5) The patient should send a photocopy of proof of citizenship for the country they live in (where the lozenges are being shipped). This can be either a passport, a drivers license, or other such identification.
All of these letters can be very simple letters with just a few sentences as listed above; I recommend using the exact wording suggested. An invoice for approximately US$240 per 560 lozenges (this is the current price as of November 2008) will be included with the shipment of lozenges which should be paid promptly. (Half of that fee covers the actual cost of the lozenges; half of that fee covers the expenses incurred by the distributor to package and ship the lozenges and for the time required to file all applicable letters for customs and other officials.) Most banks can assist with handling payments in American dollars from other countries.
NOTE: I am not a doctor or other health professional and I am not responsible for any liability arising out of any trial of this medication. I have become involved with helping others secure trials of this medication only from the dedication I feel to this product for the tremendous positive result I experienced from taking it myself for my Behcet’s Disease. I do not receive any payments for recommending this treatment or assisting patients and doctors interested in using it for Behcet's Disease.
The low dose oral interferon is not effective for all Behcet’s Disease patients but from my personal communications with other Behcet’s patients that have tried it, those that are not artificially immune suppressed by other meds have enjoyed a significant improvement of their symptoms. I have personally held my Behcet's symptoms in check since October 1999 due to this treatment and after 9.5 years, I was able to slowly spread my doses out until I am now (as of June 2008) off all medications and I am officially in remission. Some patients respond very quickly to the oral interferon (within days) but some take days, weeks, or even months before feeling improvements - especially if they are waiting for immunosuppressants to clear from their systems. Some do not feel any improvements at all but again I think this was usually due to artificial immunosuppression.
CAUTION --- I do NOT recommend starting with a lower dose as previously suggested several years ago. Smaller doses are better for fighting viruses because they tend to stimulate the immune system, but the "larger" dose of three lozenges at a time is more effective at modulating the immune system - exactly what we need for Behcet's Disease and other immune disorders of a hyper-reactive nature. We surely don't want to stimulate our already hyper-reactive immune systems so I would highly recommend NOT trying a smaller dosage if you have Behcet's or a similar disease/disorder.
CAUTION --- Taking the lozenges while under the influence of immunosuppressants (Cell-Cept, Methotrexate, Imuran, etc.), anti-TNF meds (Enbrel, Remicade, etc.), or immune suppressing NSAIDS (ibuprofen, aspirin, naproxen, sulindac, etc.) does NOT appear to work well. (Tylenol and steroids are OK.) The immune suppressing activity of immunosuppressants seems to counter the immune modulating activity of the interferon so neither works and you are left with Behcet’s running rampant in your body. Some of those strong immunosuppressants can suppress the immune system for many months after discontinuing those medications so there can be a period when neither really works. I do not advocate taking them together or until all the effects of the previous meds have worked their way out of the body. Surprisingly, steroids do not seem to be a problem when taken with the lozenges so being on steroids when starting lozenges is not an issue. As the patient weans very slowly off the steroids, the oral interferon kicks in and modulates the immune system so many are able to wean completely off their steroids while on the lozenges.
Please email me at tutt@infiniteoptions.net if you have any other questions.
Take care,
Dot Tutt
Oral Interferon Liaison