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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 at a 30% price reduction for RRP patients. Please remind Michael Liu, who works with Holley, that you are an RRP patient. Holley claims its artemisinin has been tested by HPLC, and this is the source of Dr. Schlegel's artemisinin, as described in Learn>Novel Therapies.

Sourcing of artesunate (and Artemix, before that) has been through Hepalin/Wellcare. No price drop is offered. Dr. Narendra Singh, an artemisinin expert at University of Washington's School of Bioengineering, has confirmed that he himself regularly tests Hepalin's ART products for purity and for dose, and this includes artemininin, artesunate and artemether. He confirmed things check out. Additionally, Hepalin claims it tests by HPLC, melting point, etc.

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.

Readers of this section are emphatically encouraged to also review Guidelines II, posted in August 2008

Also see the Forum post touching on this issue.

 

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. Other patients 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, each capsule of which also contains 50 mg of artemisinin plus 50 mg artesunate and 40 mg 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 using the guidelines in this section.

Since some of the toxicities seem to be associated primarily with artemether, which found in the Artemix although in a low dose, this writer decided against using it after a time. He has since provisionally concluded that use of Artemix was not optimal and has 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 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 you should be cautious about keeping the bottle unprotected in an open cupboard, etc.

Dosing at ~7 mg/kg a day of body weight for the artemisinin from Holley and 4 mg/kg a day 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 + artemisinin, substituting more artesunate for 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 want to take BOTH artemisinin 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.

It's been reported that the artemisinin and its analogues (including artesunate) have only about a 4 hour half-life, which is very short. This writer decided to take artemisinin and its analogues and, additionally, space the dosings throughout the day. You may wish to divide the total dosage, spacing the smaller dosings at 4 hour intervals. You needn't be obsessive, however. This writer "fudged" during sleep and you may wish to do likewise, or during school hours.

We would emphatically warn against taking all the capsules at once. This writer spaced them out throughout the day, mixing artemisinin and artesunate, but never taking more than 100 mg of artesunate at a time (the writer weighs about 75 kg). Thus he might have taken 200 mg of artemisinin + 100 mg of artesunate, or 100 mg of artemisinin + 50 mg of artesunate. He never took all the artesunate in the morning, for example, and the artemisinin in the evening.

There is some controversy about taking anti-oxidants with ART. It seems somewhat counter-intuitive to this writer. Until more is learned, you may wish not to take antioxidants within a day of dosing with artemisinin or artesunate. This includes vitamins C, E, A, etc. The writer may indeed use different guidelines in the future, but this is what was applicable here.

If taking statins or other medications, we again emphasize the need to coordinate our usage guidelines with your physician who may have also asked you to take Co-Q. This writer believes it's ok to take it with the ART, but he preferred a dose of only once a day only (e.g., 100 mg in the morning).)

ART superoxidizes iron. This writer decided NOT to take iron supplements in any form for a day before/after using artemisinin-like products. Used with anemia and certain other diseases affected by (or affecting) iron levels would seem to be counter-indicated although we know of one patient with borderline-anemia who has used it without any adverse tipping toward anemia.

NOTE: Sources at the University of Washington (Narendra Singh, an associate professor in Bioengineering) emphasizes the need to ensure stomach contents are almost empty when taking ART. He suggests waiting 3-4 hours after a meal to help ensure this. The purpose of giving 3-4 hour interval after a meal is to make sure the stomach is almost empty, as the drug interacts with the iron contents of food.

He suggests taking the ART with a fatty agent like a couple of spoons of yogurt (having fat, but no flavors or fruits), a little milk or spoonful of ice cream (without flavors or additives, e.g. Breyers natural vanilla).

This writer also drinks water with the dosing as some forms of ART (e.g., artemisinin) are water soluble.

Continuation dosing considerations:

Papilloma necrosis (its markers would be inflammation or hoarseness) seems not to occur following the use of artemisinin. Dr. Singh at the University of Washington, who has done research on ART, says it kills not through necrosis, requiring an inflammatory action (he said ART is an anti-inflammatory), but through apoptosis.

This writer has used it monthly (artemisinin and artesunate), based on his reasoning that ART's efficacy may require periodic refreshment. He has used it for 2-3 days a month only, however, on this once-a-month basis. He has done this for >2 1/2 years without a problem. Until more is learned, he plans on using it indefinitely.

NOTE: See Dr. Singh's recommendations above about the need for an empty stomach and taking ART with yogurt, ice-cream of milk. Same caveats regarding water apply here as with the "loading dose" described above.

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.

For whatever reason, this writer's voice became DRAMATICALLY stronger and clearer than it had been in ~30 years with RRP, with previous surgeries averaging twice per year.

For almost three years, since implementing these guidelines, there was no need for surgery (required up to four times 1-2 years previously). Up to recently, 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 was diagnosed (4/17/08), after >two years of remission, with a small papilloma on his left vocal cord and a small one posteriorally. His voice is still excellent and 3 1/2 months later, the papillomas are still relatively small. Of significance, his voice is still excellent (very strong), but he had surgery 7/31/08.

Following that surgery, he wrote Guidelines II, to which the reader is referred.

Mixing Variables and Treatment Modalities:

Please pay close attention to what is said here.

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.

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. 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 probably ill-advised for this reason.

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 (three systemic injections) 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).

Unless you know how another drug will interact with it, however, we think that it would be prudent to avoid adding a lot of unknown variables unless your physician says otherwise.

Use with Children:

Reports on safety in children deserve special mention.

We know ART functions as an agent that kills--or stuns (?)--HPV -infected cells. Dr. Singh says ART is an anti-inflammatory and kills through apoptosis, not necrosis. If that is true, the speculations below are unwarranted.

If inflammation does result, however, could it not cause a potential airway obstruction in very young children? Anyone using ART with kids needs to be especially careful. There may indeed be no cause for concern, based on Dr. Singh's comments, but we think that physician supervision and close monitoring is absolutely indicated and required in the case of toddlers and young children with small airways.

Side Effects:

RRP ISA strongly suggests that everyone wishing to use ART obtain a baseline blood test (e.g, the usual liver enzymes, renal function, etc.). The writer 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, which Dr. Singh, in email, also described as appearing quite safe. We cannot offer medical advice, but we can say that several 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 (on all pages associated with Learn>Novel Therapies. That should allay most anxiety concerns for both prospective patients and health care professionals.

The writer has not experienced significant 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 have not yet confirmed the wisdom of using the butyric acid potentiator from Holley. Dr. Singh confirmed in a phone call that it potentiates the artemisinin and artesunate up to tenfold--without toxic side-effects--and research may show that is a very good thing. This writer believes the dose of artemisinin and artesunate may be already high enough, however, though not too high. Raising it yet further might create unknown-effects, at least in this writer's mind.

Dr. Singh has also told him that butyric acid does not cause an "odor-problem" if you swallow the capsules whole, but he confirmed it smells terrible if the capsules are first opened.

We have explicitly asked Holley management and staff to steer RRP patients and doctors away from it--at least at this juncture--assuming the person(s) calling in have identified themselves RRP patients/physicians in order 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 (apoptopic 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 be (??) 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 seem 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 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 patients who have tried it, however--and this "novel therapy" appeared to show rather 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. If people wish to replicate it, that's up to them. These are not intended as guidelines for others, i..e., they are not offered as medical advice, which, as you know (see disclaimer), RRP ISA isn't able to give.

If you try this approach, please read this material several times over, so you thoroughly understand what is said here. Please let us know how it works.

We wish you the very best of luck.

                                                             Also see Guidelines II