Tips from the Pharmacologist
(Click to Expand)Single Dose Fluconazole as a Treatment for Vaginal Candidiasis
U.S.-based clinicians are accustomed to treating vaginal candidiasis with clotrimazole cream. Of course, treatment with this cream must be done for several days and requires an additional accessory or an inserter. A number of years ago, a single 150 mg tablet of fluconazole taken once was demonstrated to cure this common infection. Not only is it much more convenient and compliance is 100%, the cost of a single tablet is about one- tenth the cost of a tube of clotrimazole. We have been encouraging prescribing medical professionals for perhaps two years or more to switch to fluconazole 150 mg tablets, not just because it is less expensive, but also because it is a tiny fraction of the weight of a 45 gm tube of clotrimazole and so requires almost no space by comparison. These are often important considerations when carrying medicines into other nations. So to be a good steward of your pharmacy budget, you and your team should consider an oral treatment which should be more acceptable for all patients except those having liver problems.
For almost 20 years, common intestinal worm infections were treated with mebendazole 100 mg b.i.d. for three days. Indeed, this was and is effective for treatment of common roundworms, pinworms, hookworms and whipworms. More recently, mebendazole 500 mg tablets have been formulated for the purpose of single tablet treatment programs with much fanfare that compliance would be 100%. True enough. However, the efficacy of single tablet treatment remained in question until a few years ago when a study reported that while roundworms (ascariasis) are effectively treated by the 500 mg single tablet dose, the efficacy of treatment of whipworms was greatly reduced and the efficacy of treating hookworms was very poor (7.6% cure rate vs. 96% cure rate using 100 mg tablets b.i.d. x three days). So where a population is known to be infected with whipworms and hookworms, use of the 100 mg dose of mebendazole b.i.d. x three day is mandatory.
Albendazole is an anthelmintic that is similar to mebendazole except that more is absorbed than mebendazole. A single 400 mg tablet is effective in the treatment of roundworms, pinworms andhookworms in children (two years and older) and adults. The advantage of albendazole is that it is also useful for treating non-intestinal worm infections. Both whipworm and cutaneous larva migrans infections can be treated with 400 mg for three days. Even neurocysticercosis (larval infection of Taenia solium) can be treated using the 400 mg albendazole b.i.d. for eight to 30 days. Even though most short-term medical teams lack the ability to diagnose tissue worm effectively, the use of albendazole will no doubt increase with time.
When ciprofloxacin was introduced, it had an enormous impact in improving the treatment of UTIs, skin infections and respiratory infections. While B.I. still ships out large quantities of generic Bactrim/Septra under our own name of Cotrimoxazole for use in many nations where such infections remain sensitive to this important combination, there are many countries where ciprofloxacin has replaced sulfamethoxazole + trimethoprim due to the development of resistance. Likewise, response rates to ciprofloxacin have begun to fall in some developing nations in the same way it had in developed countries. This is especially serious when treating lower respiratory infections when azithromycin is also not as effective. For these reasons, and to stay ahead of the problems of increased resistance in developing nations, B.I. added levofloxacin to its pharmaceutical armamentarium sometime in 2010. Let us know if you have a need or an interest in obtaining levofloxacin for use in your medical clinics.
Background: Ivermectin is a drug (related to macrolide antibiotics) that has been around for many years and has very broad use in veterinary medicine; many know of its use to prevent heartworms in dogs. For many years, Merck has donated this drug for the treatment and prevention of onchocerciasis (river-bend blindness) and more recently lymphatic filariasis (elephantiasis). Annual treatment is required because the drug does not kill the adult worms, but rather only the immature microfilaria. Because the human is primary host for these diseases, it is thought that by keeping the circulating microfilaria levels very low in treated subjects, transmission by the intermediate vectors (a fly for onchocerciasis, and mosquito for filariasis) would be greatly reduced or blocked altogether. Eventually the incidence and prevalence of these diseases should drop. The goal is for the eventual complete elimination of these diseases. Therefore, Merck is to be commended for its donations of ivermectin (Mectizan) in support of mass drug administration programs. However, Merck donates ivermectin for such programs only to countries where onchocerciasis and lymphatic filariasis are co-endemic.
Treatment of scabies: The dosage recommended for treatment of scabies with ivermectin is a 200 mcg/kg taken once. A 70 kg adult dose would be 14 mg, or 2.5 tablets of 6 mg each. Tablets are scored for ease of administration to patients having various weights. Children as small as 15 kg (90 cm in height) can be treated with ivermectin. There are no studies on safety of using ivermectin in infants.
Safety, side effects, pregnancy, nursing mothers: Ivermectin is generally very well tolerated in well adults. Most side effects occur as a result of actions of the drug on the parasites; dying microfilaria can cause severe reactions. Such reactions do not occur in treating scabies. Ivermectin is not mutagenic by the Ames assay and by other tests. No studies have been conducted on carcinogenicity. The drug is not embryo toxic, but at repeated maternally toxic doses, it is teratogenic in mice, rats and rabbits. Therefore, it is rated a Pregnancy Category C drug. Even though very little drug is secreted into breast milk, the nursing of infants should be avoided for several days after treatment. There have been no known deaths caused by overdoses of ivermectin.
Therapeutic response: The response rate to treatment of scabies with ivermectin may be characterized as better than that with topical 1% lindane lotion, but somewhat less than with topical 5% premethrin. Those failing to respond two weeks after treatment can be retreated at the same dose and again after another two weeks if necessary. The need for retreatment is not unexpected in massive or incrusted infections. Finally, long-term cure depends upon good hygienic practices, especially washing all clothes and bedding of an infected family in hot water and bleach at the time of treatment, regardless of the choice of drug used for treatment.
Cost per treatment: For adults, the cost per treatment is between 30 to 45 cents (15 cents/tablet), which is only about 5-7% of the cost of treatment with 5% premethrin.
Final tip from the pharmacologist on ivermectin: While ivermectin is active against many intestinal helminthes other than hookworms, I do not advise using ivermectin for treating intestinal worms other than Strongyloides (threadworm) for two reasons. First, the administration of albendazole and mebendazole is much easier because the dose is the same for adults and children of all weights. Second, the incidence of side effects (intestinal discomfort) is less with mebendazole or albendazole than with ivermectin. Finally, don’t be tempted to use Blessings International ivermectin for your dog because it cost less; Blessings International ivermectin is intended for use only outside the USA.
For many years, Blessings International has desired to have these newer macrolid antibiotics in its formulary. Among other indications, both of these drugs are very useful for treating moderately severe lower respiratory infections in ambulatory patients which are resistant to older antibiotics. And with Azithromycin, the duration of treatment of moderate acute bacterial exacerbations of chronic obstructive pulmonary disease is much shorter, being three days (500 mg QD x 3d) instead of the typical 10 days for Clarithromycin (500 mg b.i.d. x 10 d). Community-acquired pneumonia can be treated with 500 mg of Azithromycin once on day one followed by 250 mg on day two through day five. I would encourage every team to consider having at least a supply of one of these drugs for every trip. Twice-daily treatment with Clarithromycin 500 mg, Amoxicillin 1 gram and Omeprazole 20 mg for treatment of duodenal ulcers caused by H. pylori infections.
Everyone is a creature of habit. When amoxicillin is the antibiotic chosen to treat an adult infection, it is well known that the standard dose is 500 mg t.i.d. (every eight hours or three times daily). Yet people in underdeveloped nations and here in the U.S. are apt to be much more compliant when a b.i.d. dose schedule is possible. Well this is very readily achieved by prescribing 750 mg of amoxicillin b.i.d. (every 12 hours or twice daily). Of course, this cannot be achieved using 500 mg capsules. However, it is easily and readily accomplished using three 250 mg capsules b.i.d. B.I. encourages medical teams to take only 250 mg capsules of amoxicillin instead of both 250 mg and 500 mg capsules because the 250 mg dose size can easily be used for treating both the school-aged children and adults.