Questions And Answers On Antifungal Therapy

Q: Are oral antifungals contraindicated for patients who are currently taking statins or cholesterol-lowering medications?
Dr. Scher: The statins are not to be used with the azoles, but that is not the case with terbinafine. They can be used with terbinafine. There is a lot of fear among primary care physicians, including internists, in regard to the oral antifungals. However, I do not believe it is justified.
I have been using the oral antifungals since they became available. We have done the clinical trials on all of them. I have a very large onychomycosis practice and I can say these are safe drugs. If you use them carefully, I believe you will not get into any problems.

If you have any questions, talk to the internist. I talk to internists all the time. I talk to the hepatologists all the time. I don’t have a problem. I think the safety factor is overwhelmingly in favor of the patient.
When I recommend an oral antifungal, patients often ask if it will harm their liver or kidneys. The answer is no. What they should be asking me is, “What are the chances that I will have side effects?” Then I can answer their questions. I tell them there are no medications, including vitamins, that do not have potential side effects.
When it comes to prescribing oral antifungals, it is a question of knowing what you are doing, doing it carefully and getting advice if you have any question in your mind.

What About Topical Recommendations?
Q: If you use an oral antifungal for three months and you want to use a topical, since most cases of onychomycosis begin as tinea pedis, what topical would you use?
Dr. Joseph: Ciclopirox gel or cream is my topical of choice for the skin, but I don’t use it on the nail. If I am going to treat the nail with a topical, then I use the 8% ciclopirox lacquer.
Q: Isn’t it true that most of the nail fungi begin as a skin fungus?
Dr. Joseph: Yes.
Q: So would you use ciclopirox as your therapy?
Dr. Joseph: If I am using an oral, I would not use topical ciclopirox gel or cream because I know the oral is also going to work against the tinea pedis so I don’t need the topical. After patients are cured, I will follow up with them and keep them on a topical antifungal cream for the skin and lacquer for the nail to prevent re-infection because we want to keep the fungus off the skin and from getting up under the toenail again.
Q: Once there is a cure, would you use ciclopirox over ciclopirox lacquer 8%?
Dr. Joseph: I use ciclopirox lacquer 8% on nails and ciclopirox cream or gel on skin.
Q: Dr. Joseph, you said you would use ciclopirox as your drug of choice on the skin fungus. If you do not use ciclopirox, what else would you use?
Dr. Joseph: Take your choice. I like ciclopirox because we know ciclopirox is a broad-spectrum fungicidal, bacteriocidal, Candida-cidal, sporicidal antifungal that has a totally unique mechanism compared to other topical antifungals. It is a hydroxypyridone. It is also antiinflammatory so you get relief of the itch component.
While all of these antifungals are good, I also like ciclopirox because it is available in different formulations. I love the gel. I use it personally. Any of them will work. The point is to treat the tinea pedis as well.

What About Itraconazole And Fluconazole?
Q: Is there any use in podiatry for itraconazole?
Dr. Joseph: I used to use a lot of itraconazole. I used itraconazole and terbinafine equally for many years and found they both worked really well. With itraconazole, it just got to a point with me where I got tired of keeping up with the black box warnings and the drug interactions.
Dr. Scher: You have to have more than one drug in your armamentarium. If the patient is allergic to terbinafine, there is no reason why you cannot use itraconazole, provided there are no contraindications, the patient has a good liver and there are no serious drug interactions. I think there are special situations where itraconazole might be indicated. Even though fluconazole is not FDA-approved, it can be effective. You need to have more than one drug.
Once I clear my patients, I put them on a topical for the skin and I have them use the same topical on the nails. I think that works very well in helping to prevent recurrence.
Q: In regard to fluconazole, what do you think of the intermittent dosing?
Dr. Scher: I think fluconazole is a very good antifungal. It’s fine to use if there is no contraindication to it. The once-a-week regimen is effective.
Dr. Joseph: I agree.

Pertinent Points On Screening Techniques And Diagnostic Testing
Q: In regard to baseline screening, it has been my experience working with some MDs, if I have a patient who has high normal LFTs, the PCP will tell me to do more frequent testing. Those patients might have hepatitis C. These patients do not always present with an abnormal liver test. They could have a high normal value. So that is something to keep in mind.
Dr. Scher: That is a very good point.
Q: My question also concerns the serology. What about patients who previously had hepatitis and no longer have the acute condition yet they test high for hepatitis B and hepatitis C antibodies when you test their blood? What are your concerns regarding these patients?
Dr. Scher: I will not treat a patient who has a history of hepatitis without the written approval from a liver specialist. I will send that patient to a hepatologist and, if the hepatologist tells me it is okay to treat, I will do so. If the hepatologist says no, I will not treat that patient.
In my experience, most of the hepatologists will say it is all right to treat. Nevertheless, it is serious if you are treating the patient. I always work with the hepatologist if there is a history of hepatitis, no matter what the LFTs show. I would suggest you do the same thing. Consult the hepatologist and document it.
Q: Do you include a CBC with a differential in your first set of screening?
Dr. Joseph: I like to do this. In fact, I have seen a case of neutropenia. It was reversible of course.
Dr. Scher: I definitely get a CBC. It is not critical, but I do it anyway as well as a urinalysis. I have picked up about five diabetics and urinary tract infections by doing a urinalysis. I order a CBC, a urinalysis and what in our lab is called an SMA20, which includes the LFTs and ordinary blood chemistries. By the way, with the mechanized methodology in the laboratories, it does not cost any more to do 20 tests than to do five.
Q: When I take a nail sample, I usually send it out for a KOH and a culture. Sometimes I will get a negative KOH and then the culture will come back positive. Is that a positive reading?
Dr. Scher: It’s a positive reading. More often, it’s the other way around. The KOH is more dependable than a culture.
Q: Do you think the PAS stain might be of benefit?
Dr. Scher: Yes, the benefit is far better with much fewer false positives and we have published on this.18 Its sensitivity is extremely high and the only time you may get a false negative with a PAS stain is if you have a very early case. It is unlikely that you would see these cases in your office.
I like the PAS stain because it is fast. It takes me time to do the other tests and I do not have a lot of time and you probably don’t either. With a PAS, you clip the nail, put it in formalin, send it to the path lab and you will get a reading in about seven to 10 days, depending on how quick the turnover is. It is dependable.

Weighing In On Appropriate Use Of Matrixectomies
Q: Regarding the single nail of the HIV patient that you discussed on page 10, what is your opinion of performing a total matrixectomy with that nail?
Dr. Joseph: If I have an HIV-positive patient whose CD4 is low enough to have a fungal infection, if their CD4 count is that low, I don’t think I would perform a matrixectomy. Besides, we know we can treat and cure proximal white onychomycosis so why would I do the surgery in that case?
Q: How would you treat the same patient minus the HIV?
Dr. Joseph: If you have a really thick, bad, painful single nail, I would perform a matrixectomy in that case. I remember sitting on one panel and one very outspoken dermatologist said surgically removing a nail without trying an oral antifungal first is malpractice. I don’t go that far.
I think it’s very ingrained in our profession to do surgery, but that would be for an isolated nail or two that was really thick and painful. In this case, I don’t think I would have good results with the antifungal.

Dr. Scher: I essentially agree with Dr. Joseph on that with a slight modification. Onychomycosis is a medical disorder. It is not a surgical disorder. Now does that mean you should never take a nail off for onychomycosis? No, it does not mean that at all. Certainly, I don’t agree with whoever said it was malpractice to perform surgery without trying an antifungal first. It’s not malpractice.
I think you have to meet the criteria that Dr. Joseph just cited. You have to have a severely dystrophic nail, one that is causing pain and is unlikely to respond to oral therapy, but I don’t think you have to do a matrixectomy. I would suggest avulsing the nail. Then treat it with an oral antifungal. Once you have gotten rid of the fungal load, you have a very good chance of getting a normal, healthy nail without destroying the matrix and removing the patient’s nail forever. That would be the modification I would make.

How To Address Interdigital Pustular Tinea
Q: I’ve had a couple of interesting cases of raging interdigital pustular tinea with a lot of oozing coming from multiple toes. I typically will put these patients on a topical, something like a topical terbinafine and I’ll put them on an oral, perhaps fluconazole 200 mg once a week for maybe four weeks. It has worked quite well. Do you have any other suggestions that I might try?
Dr. Joseph: Jim Leyden, MD, has done some nice work in discussing the differences in interdigital tinea. He classified interdigital tinea in two ways: dermatophytosis simplex and dermatophytosis complex. The complex was exactly what you are talking about. The simplex was when you have a little scaling in between the toes. Leyden found the complex was directly related to environment.19
He did a study in which he took people with dermatophytosis simplex and just wrapped their feet in plastic wrap. Within a couple of days, they had this raging, seeping mess of interdigital tinea. To cure it, he reversed the environment and he dried out the interspaces. By drying out the interspaces, Leyden was able to revert the condition back to a simplex.19
On top of using the antifungals you are talking about and everything else, I think you really have to pay attention to the environment in these cases.
Dr. Scher: I agree with that and I was going to cite Dr. Leyden as well. In a patient like that, you may have to give an antibiotic also. I know Dr. Leyden feels that the bacterial component is very significant.

Addressing Cost Concerns
Q: Often patients may not have insurance coverage for oral antifungal medications. How do you deal with this if patients can’t afford it?
Dr. Scher: The cost is a factor. There is no question about it. In terms of cost-effectiveness, there are studies that show you get more bang for your buck with the oral antifungal than you do with the topical. First of all, the oral antifungals work much better, the recurrence rates are lower and you do not have to treat for as long a period of time. However, that is a problem if you have a patient who has to pay out of pocket. I don’t have a solution for that.
Dr. Joseph: I agree. It is a problem. Most companies have patient-in-need programs where people can get the drug at a deeply discounted cost. I think you have to treat it. Despite all the talking we’ve done over the years about onychomycosis, as a profession, we are still just clipping toenails. That is not a treatment for fungus and we have to change our thinking about onychomycosis. You can get your patient on a medication if he or she truly needs that medication.

Fielding Questions On Dosing And Duration Of Oral Therapy
Q: What is your starting dosage for oral antifungals?
Dr. Joseph: I use 250 mg once a day for three months with terbinafine. If I use itraconazole, I do use the pulse therapy. If I use fluconazole, it is 300 mg once a week.
Q: If you use the terbinafine for three months and the patient is happy with the therapy and says, “I think the nail still has fungus,” do you extend treatment to a fourth month?
Dr. Joseph: I don’t routinely start the extra fourth month. I will start the patient with the three months and see what happens. We know this drug accumulates in the nail bed and in the nail for at least three to six months after you stop the therapy. I watch the patients. If the patient continues to progress at months four and five, I see no reason to give a further dose. If the patient at month five starts to regress or stops progressing, then I will booster him or her a little bit. That has been my approach.
Dr. Scher: You can do it that way. I tend to treat longer and maybe I have a more difficult patient population, but I can’t get some of my patients better with only three months. I would like to suggest you read a recent article in the Archives of Dermatology by Zaias, who treats intermittently with terbinafine for about one year until the healthy nail grows out.20 Now he does not mean continuously for a whole year. He breaks it up in various kinds of formulas, but he says you treat until the patient’s nail is perfectly normal.
We do tend to undertreat a lot and I think part of the reason is everybody says, “Well, it’s not worth it, because they are only going to get the onychomycosis back anyway.”
Q: I have been to many lectures and it seems that podiatrists are a little bit more conservative than dermatologists. Most podiatrists would only go three months and most of the dermatologists were more aggressive, noting that they would go four and even five months with terbinafine. Why is that?
Dr. Scher: What Dr. Joseph is doing is fine because he is following that patient’s progress. There are a couple of things that I do. I take a Polaroid before treatment and then I can tell whether that patient is getting better or not.
If you don’t want to take a Polaroid, you can make a notch. Just take a scalpel and make a small notch at the most proximal area and then treat that patient. If you treat that patient for three months and the active fungal area stays distal to the notch, you can probably stop. On the other hand, if during that treatment or at the end of three months, there is an indication that the fungus is coming proximal to the notch, then you have to treat longer. Every case is different and this is not an easy condition to treat.