Learn

RRP ISA is not encouraging anyone to try Gardasil or artemisinin-like substances, nor are we able to  "recommend" them in the way a licensed physician might recommend medication/treatment.

That said, artemisinin itself may be acquired through Holley Pharmaceuticals (http://holleypharma.com/) at a 30% price reduction for RRP patients. Please remind Michael Liu, who works with Holley, that you are an RRP patient.

Sourcing of artesunate (http://www.hepalin.com/hepasunate50.htm) is through Hepalin/Wellcare. No price drop is offered,

All artemisinin or its analogues (abbreviated ART) are imported. RRP ISA cannot vouch for product purity or quality, and we are not "recommending" these two sources over any other. Those who choose to order are advised to do their own due diligence. After doing its own due diligence, these are the sources through whom staff at RRP ISA have ordered.

By way of a disclaimer, RRP ISA and its board shall be exempted from all product and dosing liability. No representations or suggestions of any kind regarding optimal dosing or toxic dosing have been made by RRP ISA.

Initial dosing considerations:

We can't say our dosing guidelines are optimal in all cases (much more study needs to be done), but what we can say is that it seems to have been very helpful for RRP ISA's executive director. He is the writer of this section. Another patient following these guidelines has also reported excellent results.

This writer initially used 3 artemisinin capsules from Holley (total of 300 mg/day) + 4 Artemix [from Hepalin/Wellcare, which also contains artemisinin plus artesunate and artemether] capsules (560mg) per day for a week, followed by a week off, followed by another 7 days of the same dosing. Artemisinin can only be absorbed continuously for 6-7 days; this pulses the dose in accord with that specification.  No serious side-effects were observed.

There is reason to suppose this pulsing of a week on, a week off and a week on again might be beneficial in the initial dosing of artemisinin and its analogues. This is the only time anyone will take ART for more than 3 days in a row.

Since some of the toxicities seem to be associated primarily with artemether, found in the Artemix though in a very low dose, this writer decided against using it after a time.

We have since concluded that use of Artemix was not optimal and have supplanted its use with artesunate instead.

Both artemisinin and artesunate are light sensitive, yet they come bottled in plastic bottle that, while opaque, still allow light to get in. If you wish to follow the guidelines used by the writer of this section, you will want to either be absolutely sure that between uses the bottle are in a dark, closed area or else wrap the bottles with tin foil so as to prevent light from entering. You can safely carry a daily dose of capsules around with you, but we are assuming that you should be cautious about keeping the bottle unprotected in an open cupboard, etc.

Dosing at ~7 mg/kg of body weight for the artemisinin from Holley and 4 mg/kg for the artesunate from Hepalin/Wellcare seemed to work without any side-effects for this writer. (This is commensurate with the initial dosing with the Artemix but it no longer includes the artemether.)

If you wish to follow the guidelines this writer has used, it is important that these levels not be exceeded. If you wish to do this, you will also need to take BOTH artimisinin and artesunate. Not just artemisinin.

The reason why artesunate was used is because in some ways it is much stronger than artemisinin alone. In other ways, artemisinin can apparently be described to be stronger.

There is reason to believe that the two together may, as in malaria treatment, be synergistic. They may potentiate one another and the use of just one or the other may (??) not be as effective as using both together.

Again, more studies need to be done to determine the optimum combination and dosing.

Now, artemisinin and its analogues (including artesunate) have only a 4 hour half-life, which is very short. One should take artemisinin and its analogues with food and, additionally, space the dosings throughout the day. You may wish to space them at 4 hour intervals but you needn't be obsessive. You may "fudge" during sleep and school hours. We would emphatically warn against taking all the capsules at once and definitely do space them out throughout the day as well.

Do not take anti-oxidants within a day of dosing with artemisinin or artesunate. This includes vitamins C, E, A, Co-Enzyme Q, etc. If taking statins, we again emphasize the need to coordinate our usage guidelines  with your physician who may have asked you to take Co-Q. For some people, that will mean ceasing to take statins during the time they are taking ART. (Since ongoing use of ART does not exceed three days a month, this should not lead to health problems. If your physician concurs, you may wish to discontinue both statins and Co-Q during the time you are using the artemisinin or its analogues.)

We strongly suggest that you do not take iron supplements in any form for ~two days before/after using artemisinin-like products. Use with anemia and certain other diseases affected by (or affecting) iron levels would seem to be counter-indicated although we know of a patient with borderline-anemia who has used it without any adverse tipping toward anemia.

Continuation dosing considerations:

Papilloma necrosis (its markers would be inflammation or hoarseness) seems not to occur following the use of artemisinin. That suggests that while it may "knock the virus for a loop," it doesn't kill all cells infected with the virus that causes RRP. Our director has used it (artemisinin and artesunate) monthly, based on his reasoning that ART's efficacy may require periodic refreshment. Our director will use it for 2-3 days a month only, however, on this once-a-month basis. He has done this for nearly two years without a problem. He plans on doing it indefinitely.

The once a month continuation dosing schedule will commence after the initial dosing is over (that's a week on, a week off and another week on). Thus we have (day 1) an initial dosing schedule lasting around three weeks. On day 21 (three weeks), the clock for the continuation schedule begins. A month from that day, it's appropriate to take artemisinin and artesunate together again, but this time only for about three days. Wait yet another month and you may take it again for three days. This cycle can go on awhile--the writer's been doing it every month for two years--assuming you get the intended results.

For whatever reason (ART alone? When used with GARD?), this writer's voice is stronger and clearer than it's been in ~30 years with RRP. For two years, since implementing these guidelines, there was no need for surgery (required up to four times a year previously). In that time, there was no discernible regrowth of the RRP, which previously regrew to where it was ALWAYS visible on indirect laryngoscopy within a matter of a few months.

This writer has just been diagnosed (4/17/08) after two years of remission with a small papilloma. His voice is still excellent. He will be monitoring the situation.

Mixing Variables and Treatment Modalities:

This is important enough to also warrant a bold, colored font. Please pay close attention to what is said here.

The writer believes that patients should probably should not take I3C or DIM when they are taking ART. We simply don't know what I3C/DIM and ART will behave when mixed together in the stomach. Probably they are quite safe together, but safety studies have never been done. Speculating on how ART and DIM might interact or how one affects the other is really quite impossible.

Likewise, we wouldn't suggest taking cidofovir and ART together. We don't even know with precision how cidofovir works, much less what it does when ART is added to the mix. If you're on a course of cidofovir, we'd strongly suggest not doing any ART. Since cidofovir works over time, that means for as long as you're in treatment with that modality. 

The same thing is more than likely true with MMR and, possibly, even interferon. Our point is that you absolutely do not want to mix a lot of variables that could result in unknown drug interactions. Hitting RRP with "everything available" is very ill-advised unless you wish to play Russian Roulette.

ART is not a vitamin. While is may not be considered a drug in America, it is considered a medicine elsewhere in the world. It is very potent and it saves lives. You want to treat it with respect.

There should be no problem taking Gardasil with ART. There are no interlesional injections to contend with and Gardasil seems very well-tolerated (no liver issues like interferon or kidney issue like cidofovir when it enters the bloodstream). But we discourage people from taking other RRP treatments at the same time.

Unless you know how another drug will interact with it--and this is a wide-open unknown at this time--we think that it would be prudent to avoid it unless your physician says otherwise.

One other thing. The writer of this section has already confounded two variables by mixing Gardasil and ART. That makes a useful report of efficacy of one or the other all but impossible. If you proceed to add DIM, interferon, MMR or cidofovir, you should forget about saying anything about the use of ART and GARD together or separately.

It isn't just unsafe, but it makes for some very flawed reporting. Your self-report to others in the community, because of the confusion of so many different variables, will be meaningless. The credibility of that report will be lacking as well.

We need good reports at this time, however anecdotal. Please be mindful of this.

Use with Children:

Reports on safety in children deserve special mention. We know ART functions as an agent that kills--or stuns--HPV. If the level of HPV-cytotoxic activity is high enough, however, inflammation will result, potentially causing airway obstruction in very young children. This could be life-threatening and would not be reported in safety literature on kids without RRP because they don't have chronic HPV/RRP infections. Anyone using ART with kids needs to be especially careful. Physician supervision and close monitoring is absolutely indicated and required. We don't know if there will be inflammation or how serious it could be in kids with RRP. RRP ISA is not "recommending" any treatments, including ART, and we are adding a cautionary comment with respect to the use of ART in infants, toddlers and young children who, almost by definition, have very small airways.

Side Effects:

RRP ISA strongly suggest that everyone wishing to use ART obtain a baseline blood test (e.g, the usual liver enzymes, renal function, etc.). The writer, whose personal guidelines you may wish to replicate, has been taking ART monthly for two years with no ART-related abnormalities (baseline and testing two years later is substantially the same).

Neurotoxicities, including irreversible hearing loss, have been reported in the literature but this was thought to mostly be associated with relatively high dosages of artemether. Unlike artemisinin and artesunate, artemether penetrates the blood-brain barrier. You don't need it to do that with RRP. Artemisinin is different and has been used VERY widely for malaria. Many consider it and artesunate the treatment of choice, although multiple agents are usually used. It is widely regarded as safe.

Artemisinin and artesunate appear safe for children, at least when used at this dose level. We cannot offer medical advice, but we can say that sources, including the World Health Organization, have reported a wide safety margin for children. As in most things, you need to do your own due diligence. We suggest reading from the material cited here. That should allay most anxiety concerns for both prospective patients and health care professionals.

The writer o9f this section has not experienced side effects at the dosing levels mentioned here. While he indicates he had no significant side effects, however, you could be different, and in no case should you take medications, including ART, without your physician's knowledge.

We definitely are not in favor of using the butyric acid potentiator from Holley. It potentiates the artemisinin and artesunate, but you absolutely do NOT want to potentiate the latter. We believee the dose of artemisinin and artesunate is already high enough, though not too high. Raising it yet further could get you in trouble.RRP ISA believes butyric acid's safety is very dubious when used with these dosing guidelines. 

We have explicitly asked Holley management and staff to steer RRP patients and doctors away from it, assuming the person(s) calling in have identified themselves as such to get the 30% discount.

For more on side-effects, see Learn>Novel Therapies>Artemisinin Safety and Pharmacokinetics.


Gardasil as a therapeutic agent:

In addition to the artemisinin-like products, we have also discussed in website and message board why it might be prudent to consider taking the three-shot series of Gardasil injections (not interlesional, but using the standard prophylactic protocol). Again, the writer of this section has done that and if you wish to replicate what he did, you'd want to get the series as well.

While we are in no way proposing that Gardasil can definitively treat existing cases of HPV disease such as RRP--this was thought unlikely by many experts, based on genital studies of Gardasil and also based on the adjuvant and VLP (viral like particle) composition of the vaccine--many unanswered questions do exist about Gardasil that cannot completely rule out a therapeutic possibility in the respiratory tract (see Dr. Steinberg's remarks on Learn>Novel Therapies).

There is evidence that VLPs like Gardasil can be used successfully in some kinds of laryngeal RRP treatment (Schlegel, Frazer), and genital HPV is arguably not the same as respiratory HPV. This has been thoroughly discussed elsewhere [e..g., the 2007 RRP Focus Session>RRP ISA,. etc.]

RRP ISA has suggested that the effect of ART might be (???) enhanced (cytotoxic effects for infected cells) if the Gardasil vaccine somehow "turned on the lights," allowing patients to "see" those infected cells. Could it mobilize the local immune system? RRP ISA believe that may (??) what is occurring.

It is understood that the metaphor of "turning on the lights” is very simplistic, especially in describing early and chronic infections, but a synergistic effect between Gardasil and ART cannot be ruled out (or verified) until more data is collected.

What we CAN say is that the conclusions resulting from Merck's genital studies were seriously flawed in that the assumed that the respiratory tract functions similarly to the genital tract. That assumption, as extrapolated from HIV/AIDS epidemiological data, is manifestly untrue [for more, see the argument in the 2007 RRP Focus Session>RRP ISA and also see Dr. Steinberg's remarks under Learn>Novel Therapies].

Concluding remarks:

Your replicating this approach may complement, but emphatically must not take the place of, regular medical care by a qualified physician. If you need surgery, get it. Same with any other issue that is medically recommended, etc.

We can't say these dosing guidelines are optimal, because very limited research has been done with RRP patients.  We still invite the research community to systematically study this approach. As stated elsewhere, we have allocated a generous grant for a worthy project along these lines.

Based on a showing of efficacy with the two patients who have tried it, however--and these appeared to be very dramatic results--we refuse to wait any longer in disseminating these guidelines.

ART is not regulated by the FDA in the United States, so RRP ISA is ostensibly operating under the same rules that allow us to offer guidelines on the use of I3C or DIM. These are, again, intended to be guidelines on what the writer of this section did, i.e., where he got ART and how he used it. It people wish to replicate it, that's up to them. These are not intended as guideline for others, i..e., itis not offered as medical advice, which, as you know (see disclaimer), RRP ISA isn't able to give.

If you try this approach, please let us know how it works. We wish you the very best of luck.