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Drugs for parasitic infections (april 2002)

The Medical Letter On Drugs and Therapeutics Published by The Medical Letter, Inc. • 1000 Main Street, New Rochelle, N.Y. 10801 • A Nonprofit Publication DRUGS FOR PARASITIC INFECTIONS
Parasitic infections are found throughout the world. With increasing travel, immigration, use of immunosuppressive drugs and the spread of AIDS, physicians anywhere may see in- fections caused by previously unfamiliar parasites. The table below lists first-choice and al- ternative drugs for most parasitic infections. The manufacturers of the drugs are listed on 30-40 mg/kg/d (max. 2g) in 3 doses 25-35 mg/kg/d in 3 doses x 7d 25-35 mg/kg/d in 3 doses x 7d 20 mg/kg/d in 3 doses x 10d mild to moderate intestinal disease3
500-750 mg tid x 7-10d 35-50 mg/kg/d in 3 doses x 7-10d 2 grams/d divided tid x 3d 50 mg/kg (max. 2g) qd x 3d severe intestinal and extraintestinal disease3
750 mg tid x 7-10d 35-50 mg/kg/d in 3 doses x 7-10d 60 mg/kg/d (max. 2 g) x 5d AMEBIC MENINGOENCEPHALITIS, PRIMARY
Amphotericin B6,7 1 mg/kg/d IV, uncertain duration 1 mg/kg/d IV, uncertain duration * Availability problems. See table on page 12.
1. For treatment of keratitis caused by Acanthamoeba, concurrent topical use of 0.1% propamidine isethionate (Brolene) plus neomycin-polymyxin B-gramicidin ophthalmic solution has been successful (SL Hargrave et al, Ophthalmology 1999; 106:952). In addition, 0.02% topical polyhexamethylene biguanide (PHMB)and/or chlorhexadine has been used successfully in a large number of patients (G Tabin et al, Cornea 2001; 20:757; YS Wysenbeek et al, Cornea 2000; 19:464).
PHMB is available from Leiters Park Avenue Pharmacy, San Jose, CA (800-292-6773).
2. The drug is not available commercially, but as a service can be compounded by Medical Center Pharmacy, New Haven, CT (203-688-6816) or Panorama Com- pounding Pharmacy 6744 Balboa Blvd, Van Nuys, CA 91406 (800-247-9767).
3. Treatment should be followed by a course of iodoquinol or paromomycin in the dosage used to treat asymptomatic amebiasis.
4. Nitazoxanide (an investigational drug in the US manufactured by Romark Laboratories, Tampa, Florida, 813-282-8544, www.romarklabs.com) 500 mg bid x 3d is also effective for treatment of amebiasis (JF Rossignol et al, J Infect Dis 2001; 184:381).
5. A nitro-imidazole similar to metronidazole, but not marketed in the US, tinidazole appears to be at least as effective as metronidazole and better tolerated. Orni- dazole, a similar drug, is also used outside the US.
6. A Naegleria infection was treated successfully with intravenous and intrathecal use of both amphotericin B and miconazole, plus rifampin (J Seidel et al, N Engl J Med 1982; 306:346). Other reports of successful therapy are questionable.
7. An approved drug, but considered investigational for this condition by the U.S. Food and Drug Administration.
8. Strains of Acanthamoeba isolated from fatal granulomatous amebic encephalitis are usually susceptible in vitro to pentamidine, ketoconazole (Nizoral), flucyto- sine (Ancobon) and (less so) to amphotericin B. Chronic Acanthamoeba meningitis has been successfully treated in 2 children with a combination of oraltrimethoprim/sulfamethoxazole, rifampin and ketoconazole (T Singhal et al, Pediatr Infect Dis J 2001; 20:623), and in an AIDS patient with fluconazole and sul-fadiazine combined with surgical resection of the CNS lesion (M Seijo Martinez et al, J Clin Microbiol 2000; 38:3892). Disseminated cutaneous infection in animmunocompromised patient has been treated successfully with IV pentamidine isethionate, topical chlorhexidine and 2% ketoconazole cream, followed byoral itraconazole (Sporanox) (CA Slater et al, N Engl J Med 1994; 331:85).
EDITOR: Mark Abramowicz, M.D. DEPUTY EDITOR: Gianna Zuccotti, M.D., M.P.H., Weill Medical College of Cornell University
CONSULTING EDITOR: Martin A. Rizack, M.D., Ph.D., Rockefeller University ASSOCIATE EDITORS: Donna Goodstein, Amy Faucard ASSISTANT EDITOR: Susie Wong
CONTRIBUTING EDITORS: Philip D. Hansten, Pharm. D., University of Washington; Neal H. Steigbigel, M.D., New York University School of Medicine
ADVISORY BOARD: William T. Beaver, M.D., Georgetown University School of Medicine; Jules Hirsch, M.D., Rockefeller University; James D. Kenney, M.D., Yale University School of Medicine;
Gerhard Levy, Pharm.D., State University of N.Y. at Buffalo; Gerald L. Mandell, M.D., University of Virginia School of Medicine; Hans Meinertz, M.D., University Hospital, Copenhagen; Dan M.
Roden, M.D., Vanderbilt School of Medicine; F. Estelle R. Simons, M.D., University of Manitoba
EDITORIAL FELLOWS: Elizabeth Stephens, M.D., Oregon Health Sciences University School of Medicine; Arthur M.F. Yee, M.D., Ph.D., Cornell University Medical Center
EDITORIAL ADMINISTRATOR: Marianne Aschenbrenner PUBLISHER: Doris Peter, Ph.D.
Founded 1959 by Arthur Kallet and Harold Aaron, M.D. Copyright 2002. The Medical Letter, Inc. (ISSN 1523-2859)
FORWARDING OR COPYING IS A VIOLATION OF U.S. AND INTERNATIONAL COPYRIGHT LAWS AMEBIC MENINGOENCEPHALITIS, PRIMARY (continued)
ANCYLOSTOMA caninum (Eosinophilic enterocolitis)
OR Pyrantel pamoate7 11 mg/kg (max. 1g) x 3d 11 mg/kg (max. 1g) x 3d OR Endoscopic removal Ancylostoma duodenale, see HOOKWORM
Treatment of choice: Surgical or endoscopic removal ASCARIASIS (Ascaris lumbricoides, roundworm)
100 mg bid x 3d or 500 mg once 100 mg bid x 3d or 500 mg once OR Pyrantel pamoate7 11 mg/kg once (max. 1 gram) 11 mg/kg once (max. 1 gram) BABESIOSIS (Babesia microti)
Drugs of choice:13 1.2 grams bid IV or 600 mg tid PO 20-40 mg/kg/d PO in 3 doses x 7d plus quinine
650 mg tid PO x 7d 25 mg/kg/d PO in 3 doses x 7d 750 mg bid x 7-10d 20 mg/kg bid x 7-10d 600 mg PO daily x 7-10d 12 mg/kg daily x 7-10d Balamuthia mandrillaris, see AMEBIC MENINGOENCEPHALITIS, PRIMARY
40 mg/kg/d (max. 2 g) in 4 doses 35-50 mg/kg/d in 3 doses x 5d 40 mg/kg/d in 3 doses x 20d BLASTOCYSTIS hominis infection
400 mg daily x 10d 400 mg daily x 10d Chagas' disease, see TRYPANOSOMIASIS
Clonorchis sinensis, see FLUKE infection
* Availability problems. See table on page 12.
9. A free-living leptomyxid ameba that causes subacute to chronic granulomatous CNS disease. In vitro pentamidine isethionate 10 µg/ml is amebastatic (CF Den- ney et al, Clin Infect Dis 1997; 25:1354). One patient, according to Medical Letter consultants, was successfully treated with clarithromycin (Biaxin) 500 mgt.i.d., fluconazole (Diflucan) 400 mg once daily, sulfadiazine 1.5 g q6h and flucytosine (Ancobon) 1.5 g q6h.
10. A recently described free-living ameba not previously known to be pathogenic to humans. It was successfully treated with azithromycin, IV pentamidine, itraconazole and flucytosine (BB Gelman et al, JAMA 2001; 285:2450).
11. Most patients have a self-limited course and recover completely. Analgesics, corticosteroids, and careful removal of CSF at frequent intervals can relieve symptoms (FD Pien and BC Pien, Int J Infect Dis 1999; 3:161; V Lo Re and SJ Gluckman, Clin Infect Dis 2001; 33:e112). In a recent report, mebendazole and aglucocorticosteroid appeared to shorten the course of infection (H-C Tsai et al, Am J Med 2001; 111:109). No drug is proven to be effective and some patientshave worsened when given thiabendazole, albendazole, mebendazole or ivermectin.
12. Mebendazole has been used in experimental animals.
13. Exchange transfusion has been used in severely ill patients and those with high (>10%) parasitemia (JC Hatcher et al, Clin Infect Dis 2001; 32:1117). Combina- tion therapy with atovaquone and azithromycin is as effective as clindamycin/quinine and may be better tolerated (PJ Krause et al, N Engl J Med 2000;343:1454). Concurrent use of pentamidine and trimethoprim-sulfamethoxazole has been reported to cure an infection with B. divergens, the most common Ba-besia species in Europe (D Raoult et al, Ann Intern Med 1987; 107:944).
14. Use of tetracyclines is contraindicated in pregnancy and in children less than 8 years old.
15. No drugs have been demonstrated to be effective. Albendazole 25 mg/kg/d x 10d started up to 3d after possible infection might prevent clinical disease and is recommended for children with known exposure (ingestion of racoon stool or contaminated soil) (MMWR Morb Mortal Wkly Rep 2002; 50:1153). Mebendazole,thiabendazole, levamisole (Ergamisol) and ivermectin could also be tried. Steroid therapy may be helpful, especially in eye and CNS infections. Ocular bay-lisascariasis has been treated successfully using laser photocoagulation therapy to destroy the intraretinal larvae.
16. Clinical significance of these organisms is controversial, but metronidazole 750 mg tid x 10d or iodoquinol 650 mg tid x 20d has been reported to be effective (DJ Stenzel and PFL Borenam, Clin Microbiol Rev 1996; 9:563). Metronidazole resistance may be common (K Haresh et al, Trop Med Int Health 1999; 4:274).
Trimethoprim-sulfamethoxazole is an alternative regimen (UZ Ok et al, Am J Gastroenterol 1999; 94:3245).
The Medical Letter • April 2002 CUTANEOUS LARVA MIGRANS (creeping eruption, dog and cat hookworm)
Drug of choice:18 400 mg daily x 3d 400 mg daily x 3d 200 µg/kg daily x 1-2d 200 µg/kg daily x 1-2d Drug of choice:19 800 mg bid x 7-10d 25 mg/kg bid x 7-10d CYSTICERCOSIS, see TAPEWORM infection
DIENTAMOEBA fragilis infection
30-40 mg/kg/d (max. 2g) in 3 doses 25-35 mg/kg/d in 3 doses x 7d 25-35 mg/kg/d in 3 doses x 7d 40 mg/kg/d (max. 2g) in 4 doses x 500-750 mg tid x 10d 20-40 mg/kg/d in 3 doses x 10d Diphyllobothrium latum, see TAPEWORM infection
DRACUNCULUS medinensis (guinea worm) infection
25 mg/kg/d (max. 750 mg) in 3 doses Echinococcus, see TAPEWORM infection
Entamoeba histolytica, see AMEBIASIS
ENTAMOEBA polecki infection
35-50 mg/kg/d in 3 doses x 10d ENTEROBIUS vermicularis (pinworm) infection
Drug of choice:21 11 mg/kg base once (max. 1 gram); 11 mg/kg base once (max. 1 gram); repeat in 2 weeks repeat in 2 weeks 100 mg once; repeat in 2 weeks 100 mg once; repeat in 2 weeks 400 mg once; repeat in 2 weeks 400 mg once; repeat in 2 weeks Fasciola hepatica, see FLUKE infection
Wuchereria bancrofti, Brugia malayi, Brugia timori
Day 1: 50 mg, p.c.
Day 1: 1 mg/kg p.c.
Day 2: 1 mg/kg tid Day 3: 100 mg tid Day 3: 1-2 mg/kg tid Days 4 through 14: 6 mg/kg/d in Days 4 through 14: 6 mg/kg/d in Day 1: 50 mg p.c.
Day 1: 1 mg/kg p.c.
Day 2: 1 mg/kg tid Day 3: 100 mg tid Day 3: 1-2 mg/kg tid Days 4 through 21: 9 mg/kg/d in Days 4 through 21: 9 mg/kg/d in * Availability problems. See table on page 12.
17. Three days of treatment with nitazoxanide (see footnote 4) may be useful for treating cryptosporidial diarrhea in immunocompetent patients. The recommend- ed dose in adults is 500 mg bid, in children 4-11 years old, 200 mg bid, and in children 1-3 years old, 100 mg bid (JA Rossignol et al, J Infect Dis 2001; 184:103).
A small randomized, double-blind trial in symptomatic HIV-infected patients found paromomycin similar to placebo (RG Hewitt et al, Clin Infect Dis 2000;3:1084).
18. G Albanese et al, Int J Dermatol 2001; 40:67.
19. HIV infected patients may need higher dosage and long-term maintenance. In cases of cotrimoxazole intolerance, ciprofloxacin 500 mg bid x 7d has been effective (R-I Verdier et al, Ann Intern Med 2000; 132:885).
20. Not curative, but decreases inflammation and facilitates removing the worm. Mebendazole 400-800 mg/d for 6d has been reported to kill the worm directly.
21. Since all family members are usually effected, treatment of the entire household is recommended.
22. Endosymbiotic Wolbachia bacteria may have a role in filarial development and host response, and may represent a new target for therapy (HF Cross et al, Lan- cet 2001; 358:1873). Doxycycline 100 mg daily x 6 weeks has eradicated Wolbachia and led to sterility of adult worms in onchocerciasis (A Hoerauf et al, Lancet2000; 355:1241).
23. Most symptoms caused by the adult worm. Single-dose combination of albendazole (400 mg) with either ivermectin (200 µg/kg) or diethylcarbamazine (6 mg/kg) is effective for reduction or suppression of W. bancrofti microfilaremia (MM Ismail et al, Trans R Soc Trop Med Hyg 2001; 95:332; TB Nutman, Curr OpinInfect Dis 2001; 14:539).
24. Antihistamines or corticosteroids may be required to decrease allergic reactions due to disintegration of microfilariae in treatment of filarial infections, espe- cially those caused by Loa loa.
25. For patients with no microfilariae in the blood, full doses can be given from day one.
26. In heavy infections with Loa loa, rapid killing of microfilariae can provoke an encephalopathy. Apheresis has been reported to be effective in lowering microfilarial counts in patients heavily infected with Loa loa (EA Ottesen, Infect Dis Clin North Am 1993; 7:619). Albendazole or ivermectin have also been usedto reduce microfilaremia; albendazole is preferred because of its slower onset of action (AD Klion et al, J Infect Dis 1993; 168:202; M Kombila et al, Am J TropMed Hyg 1998; 58:458). Albendazole may be useful for treatment of loiasis when diethylcarbamazine is ineffective or cannot be used but repeated courses maybe necessary (AD Klion et al, Clin Infect Dis 1999; 29:680). Diethylcarbamazine, 300 mg once weekly, has been recommended for prevention of loiasis (TB Nut-man et al, N Engl J Med 1988; 319:752).
The Medical Letter • April 2002 Drug of choice:24 Drug of choice:24 Drug of choice:24,28 Tropical Pulmonary Eosinophilia (TPE)
6 mg/kg/d in 3 doses x 21d 6 mg/kg/d in 3 doses x 21d Onchocerca volvulus (River blindness)
150 µg/kg once, repeated every 6 to 150 µg/kg once, repeated every 6 to 12 months until asymptomatic 12 months until asymptomatic FLUKE, hermaphroditic, infection
Clonorchis sinensis (Chinese liver fluke)
75 mg/kg/d in 3 doses x 1d 75 mg/kg/d in 3 doses x 1d Fasciola hepatica (sheep liver fluke)
Drug of choice:30 30-50 mg/kg x 10-15 doses 30-50 mg/kg on alternate days x Fasciolopsis buski, Heterophyes heterophyes, Metagonimus yokogawai (intestinal flukes)
75 mg/kg/d in 3 doses x 1d 75 mg/kg/d in 3 doses x 1d Metorchis conjunctus (North American liver fluke)31
75 mg/kg/d in 3 doses x 1d 75 mg/kg/d in 3 doses x 1d 60 mg/kg/d in 3 doses x 1d 60 mg/kg/d in 3 doses x 1d Opisthorchis viverrini (Southeast Asian liver fluke)
75 mg/kg/d in 3 doses x 1d 75 mg/kg/d in 3 doses x 1d Paragonimus westermani (lung fluke)
75 mg/kg/d in 3 doses x 2d 75 mg/kg/d in 3 doses x 2d 30-50 mg/kg on alternate days 30-50 mg/kg on alternate days GIARDIASIS (Giardia lamblia)
15 mg/kg/d in 3 doses x 5d 100 mg tid x 5d (max. 300 mg/d) 2 mg/kg tid x 5d (max. 300 mg/d) 50 mg/kg once (max. 2 g) 100 mg qid x 7-10d 6 mg/kg/d in 4 doses x 7-10d 25-35 mg/kg/d in 3 doses x 7d 25-35 mg/kg/d in 3 doses x 7d 200 µg/kg/d x 2d 200 µg/kg/d x 2d OR Surgical removal OR Albendazole7, 36 * Availability problems. See table on page 12.
27. Diethylcarbamazine has no effect. Ivermectin, 200 µg/kg once, has been effective.
28. Diethylcarbamazine is potentially curative due to activity against both adult worms and microfilariae. Ivermectin is only active against microfilariae.
29. Annual treatment with ivermectin 150 µg/kg can prevent blindness due to ocular onchocerciasis (D Mabey et al, Ophthalmology 1996; 103:1001).
30. Unlike infections with other flukes, Fasciola hepatica infections may not respond to praziquantel. Triclabendazole, a veterinary fasciolide, may be safe and effective but data are limited (CS Graham et al, Clin Infect Dis 2001; 33:1). It is available from Victoria Pharmacy, Zurich, Switzerland, 41-1-211-24-32. It shouldbe given with food for better absorption.
31. JD MacLean et al, Lancet 1996; 347:154.
32. Triclabendazole may be effective in a dosage of 5 mg/kg once daily for 3 days or 10 mg/kg twice in one day (M Calvopiña et al, Trans R Soc Trop Med Hyg 1998; 92:566). See footnote 30.
33. In one study, nitazoxanide (see footnote 4) was as effective as metronidazole and has been used successfully in high doses to treat a case of Giardia resistant to metronidazole and albendazole (JJ Ortiz et al, Aliment Pharmacol Ther 2001; 15:1409; P Abboud et al, Clin Infect Dis 2001; 32:1792). Albendazole 400 mg daily x5d may be effective (A Hall and Q Nahar, Trans R Soc Trop Med Hyg 1993; 87:84; AK Dutta et al, Indian J Pediatr 1994; 61:689). Bacitracin zinc or bacitracin120,000 U bid for 10 days may also be effective (BJ Andrews et al, Am J Trop Med Hyg 1995; 52:318). Combination treatment with standard doses of metroni-dazole and quinacrine given for 3 weeks has been effective for a small number of refractory infections (TE Nash et al, Clin Infect Dis 2001; 33:22).
34. Not absorbed; may be useful for treatment of giardiasis in pregnancy.
35. F Chappuis et al, Clin Infect Dis 2001; 33:e17; P Nontasut et al, Southeast Asian J Trop Med Public Health 2000; 31:374.
36. One patient has been successfully treated with albendazole (ML Eberhard and C Busillo, Am J Trop Med Hyg 1999; 61:51).
The Medical Letter • April 2002 HOOKWORM infection (Ancylostoma duodenale, Necator americanus)
100 mg bid x 3d or 500 mg once 100 mg bid x 3d or 500 mg once Pyrantel pamoate7 11 mg/kg (max. 1g) x 3d 11 mg/kg (max. 1g) x 3d Hydatid cyst, see TAPEWORM infection
Hymenolepis nana, see TAPEWORM infection
ISOSPORIASIS (Isospora belli)
Drug of choice:37 160 mg TMP, 800 mg SMX bid x 10d TMP 5 mg/kg, SMX 25 mg/kg bid 20 mg Sb/kg/d IV or IM x 20-28d40 20 mg Sb/kg/d IV or IM x 20-28d40 Drug of choice:39 20 mg Sb/kg/d IV or IM x 20-27d40 20 mg Sb/kg/d IV or IM x 20-28d40 0.5 to 1 mg/kg IV daily or every 2d 0.5 to 1 mg/kg IV daily or every 2d 3 mg/kg/d (days 1-5) and 3 mg/kg/d 3 mg/kg/d (days 1-5) and 3 mg/kg/d 2-4 mg/kg daily or every 2d IV or IM 2-4 mg/kg daily or every 2d IV or IM for up to 15 doses43 for up to 15 doses43 Topically 2x/d x 10-20d LICE infestation (Pediculus humanus, P. capitis, Phthirus pubis)45
Loa loa, see FILARIASIS
* Availability problems. See table on page 12.
37. Immunosuppressed patients: TMP/SMX qid x 10d followed by bid x 3 weeks. In sulfonamide-sensitive patients, pyrimethamine 50-75 mg daily in divided doses has been effective. HIV-infected patients may need long-term maintenance. Ciprofloxacin 500 mg bid x 7d has also been effective (R-I Verdier et al, Ann InternMed 2000; 132:885).
38. Treatment dosage and duration vary based on the disease symptoms, host immune status, species, and the area of the world where infection was acquired.
Cutaneous infection is due to L. mexicana, L. tropica, L. major, L. braziliensis; mucocutaneous is mostly due to L. braziliensis, and visceral is due to L. donovani(Kala-azar), L. infantum, L. chagasi. Dosage range listed includes many, but not all possibilities.
39. For treatment of kala-azar, oral miltefosine 100 mg daily for 4 weeks was 97% effective after 6 months in one study. Gastrointestinal adverse effects are com- mon and the drug is contraindicated in pregnancy (TK Jha et al, N Engl J Med 1999; 341:1795). In an uncontrolled trial, oral miltefosine was effective for thetreatment of American cutaneous leishmaniasis at a dosage of about 2.25 mg/kg/day for 3-4 wks. "Motion sickness" was the most frequent adverse effect (JSoto et al, Clin Infect Dis 2001; 33:e57).
40. May be repeated or continued. A longer duration may be needed for some forms of visceral leishmaniasis (BL Herwaldt, Lancet 1999; 354:1191).
41. Three preparations of lipid-encapsulated amphotericin B have been used for treatment of visceral leishmaniasis. Largely based on clinical trials in patients in- fected with L. infantum, the FDA approved liposomal amphotericin B (AmBisome) for treatment of visceral leishmaniasis (A Meyerhoff, Clin Infect Dis 1999;28:42; JD Berman, Clin Infect Dis 1999; 28:49). Amphotericin B lipid complex (Abelcet) and amphotericin B cholesteryl sulfate (Amphotec) have also been usedwith good results. Limited data in a few patients suggest that liposomal amphotericin B may also be effective for mucocutaneous disease (VS Amato et al, JAntimicrob Chemother 2000; 46:341; RNR Sampaio and PD Marsden, Trans R Soc Trop Med Hyg 1997; 91:77). Some studies indicate that L. donovani resistantto pentavalent antimonial agents may respond to lipid-encapsulated amphotericin B (S Sundar et al, Ann Trop Med Parasitol 1998; 92:755).
42. The dose for immunocompromised patients with HIV is 4 mg/kg/d (days 1-5) and 4 mg/kg/d on days 10,17,24,31,38. The relapse rate is high, suggesting that maintenance therapy may be indicated.
43. For L. donovani: 4 mg/kg once/day x 15 doses; for cutaneous disease: 2 mg/kg once/day x 7 or 3 mg/kg once/day x 4 doses.
44. Topical paromomycin can only be used in geographic regions where cutaneous leishmaniasis species have low potential for mucosal spread. A formulation of 15% paromomycin and 12% methylbenzethonium chloride (Leshcutan) in soft white paraffin for topical use, has been reported to be effective in some patientsagainst cutaneous leishmaniasis due to L. major (O Ozgoztasi and I Baydar, Int J Dermatol 1997; 36:61; BA Arana et al, Am J Trop Med Hyg 2001; 65:466).
45. For infestation of eyelashes with crab lice, use petrolatum. For pubic lice, treat with 5% permethrin or ivermectin as for scabies (see page 9).
46. A second application is recommended one week later to kill hatching progeny. Some lice are resistant to pyrethrins and permethrin (RJ Pollack, Arch Pediatr Adolesc Med 1999; 153:969).
47. RJ Roberts et al, Lancet 2000; 356:540.
48. Ivermectin is effective against adult lice but has no effect on nits (TA Bell, Pediatr Infect Dis J 1998; 17:923).
The Medical Letter • April 2002 MALARIA, Treatment of (Plasmodium falciparum, P. ovale, P. vivax, and P. malariae)
650 mg q8h x 3-7d50 25mg/kg/d in 3 doses x 3-7d50 plus
doxycycline7,14 100 mg bid x 7d 2 mg/kg/d x 7d
or plus
tetracycline7,14
6.25 mg/kg qid x 7d 3 tablets at once on last day of <1 yr: ⁄14 tablet 1-3 yrs: 1⁄2 tablet4-8 yrs: 1 tablet9-14 yrs: 2 tablets 20-40 mg/kg/d in 3 doses x 5d 2 adult tablets bid x 3d 11-20 kg: 1 adult tablet/day x 3d 21-30 kg: 2 adult tablets/day x 3d31-40 kg: 3 adult tablets/day x 3d>40 kg: 2 adult tablets bid x 3d 750 mg followed by 500 mg <45 kg: 15 mg/kg PO followed by 10 mg/kg PO 8-12 hours later 500 mg q6h x 3 doses; repeat in 1 <40 kg: 8 mg/kg q6h x 3 doses; repeat in 1 week58 750 mg followed by 500 mg 15 mg/kg followed 8-12 hrs later by 650 mg q8h x 3-7d50 25 mg/kg/d in 3 doses x 3-7d50 750 mg followed by 500 mg 15 mg/kg followed 8-12 hrs later by Halofantrine57, 61* 500 mg q6h x 3 doses 8 mg/kg q6h x 3 doses 25 mg base/kg in 3 doses over 2.5 mg base/kg in 3 doses over * Availability problems. See table on page 12.
49. Chloroquine-resistant P. falciparum occur in all malarious areas except Central America west of the Panama Canal Zone, Mexico, Haiti, the Dominican Republic, and most of the Middle East (chloroquine resistance has been reported in Yemen, Oman, Saudi Arabia and Iran).
50. In Southeast Asia, relative resistance to quinine has increased and the treatment should be continued for 7 days.
51. Fansidar tablets contain 25 mg of pyrimethamine and 500 mg of sulfadoxine. Resistance to pyrimethamine-sulfadoxine has been reported from Southeast Asia, the Amazon basin, sub-Saharan Africa, Bangladesh and Oceania.
52. For use in pregnancy.
53. Atovaquone plus proguanil is available as a fixed-dose combination tablet: adult tablets (250 mg atovaquone/100 mg proguanil, Malarone) and pediatric tablets (62.5 mg atovaquone/25 mg proguanil, Malarone Pediatric). To enhance absorption, it should be taken within 45 minutes after eating (S Looareesuwan et al,Am J Trop Med Hyg 1999; 60:533). Although approved for once daily dosing, to decrease nausea and vomiting the dose for treatment is usually divided in two.
54. For treatment of multiple-drug-resistant P. falciparum in Southeast Asia, especially Thailand, where resistance to mefloquine and halofantrine is frequent, a 7- day course of quinine and tetracycline is recommended (G Watt et al, Am J Trop Med Hyg 1992; 47:108). Artesunate plus mefloquine (C Luxemburger et al,Trans R Soc Trop Med Hyg 1994; 88:213), artemether plus mefloquine (J Karbwang et al, Trans R Soc Trop Med Hyg 1995; 89:296), mefloquine plus doxycyclineor atovaquone/proguanil may also be used to treat multiple-drug-resistant P. falciparum.
55. At this dosage, adverse effects including nausea, vomiting, diarrhea, dizziness, disturbed sense of balance, toxic psychosis and seizures can occur. Mefloquine is teratogenic in animals and should not be used for treatment of malaria in pregnancy. It should not be given together with quinine, quinidine or halofantrine,and caution is required in using quinine, quinidine or halofantrine to treat patients with malaria who have taken mefloquine for prophylaxis. The pediatricdosage has not been approved by the FDA. Resistance to mefloquine has been reported in some areas, such as the Thailand-Myanmar and -Cambodia bordersand in the Amazon basin, where 25 mg/kg should be used.
56. In the US, a 250-mg tablet of mefloquine contains 228 mg mefloquine base. Outside the US, each 275-mg tablet contains 250 mg base.
57. May be effective in multiple-drug-resistant P. falciparum malaria, but treatment failures and resistance have been reported, and the drug has caused lengthen- ing of the PR and QTc intervals and fatal cardiac arrhythmias. It should not be used for patients with cardiac conduction defects or with other drugs that mayaffect the QT interval, such as quinine, quinidine and mefloquine. Cardiac monitoring is recommended. Variability in absorption is a problem; halofantrineshould not be taken one hour before to two hours after meals because food increases its absorption. It should not be used in pregnancy.
58. A single 250-mg dose can be used for repeat treatment in mild to moderate infections (JE Touze et al, Lancet 1997; 349:255).
59. K Na-Bangchang, Trop Med Int Health 1999; 4:602.
60. P. vivax with decreased susceptibility to chloroquine is a significant problem in Papua-New Guinea and Indonesia. There are also a few reports of resistance from Myanmar, India, Thailand, the Solomon Islands, Vanuatu, Guyana, Brazil, Colombia and Peru.
61. JK Baird el al, J Infect Dis 1995; 171:1678.
62. Primaquine phosphate can cause hemolytic anemia, especially in patients whose red cells are deficient in glucose-6-phosphate dehydrogenase. This deficiency is most common in African, Asian and Mediterranean peoples. Patients should be screened for G-6-PD deficiency before treatment. Primaquineshould not be used during pregnancy.
The Medical Letter • April 2002 MALARIA, Treatment of (continued)
All Plasmodium except Chloroquine-resistant P. falciparum49 and Chloroquine-resistant P. vivax60
1 gram (600 mg base), then 500 mg 10 mg base/kg (max. 600 mg base), (300 mg base) 6 hrs later, then 500 then 5 mg base/kg 6 hrs later, then mg (300 mg base) at 24 and 48 hrs 5 mg base/kg at 24 and 48 hrs Drug of choice:64 10 mg/kg loading dose (max. 600 Same as adult dose mg) in normal saline slowly over 1to 2 hrs, followed by continuous in-fusion of 0.02 mg/kg/min until oraltherapy can be started 20 mg/kg loading dose IV in 5% dex- Same as adult dose trose over 4 hrs, followed by 10mg/kg over 2-4 hrs q8h (max. 1800mg/d) until oral therapy can bestarted 3.2 mg/kg IM, then 1.6 mg/kg daily x Same as adult dose Prevention of relapses: P. vivax and P. ovale only
26.3 mg (15 mg base)/d x 14d or 79 0.3 mg base/kg/d x 14d mg (45 mg base)/wk x 8 wks MALARIA, Prevention of 68
adult dose of300 mg base71 250 mg once/week71 <15 kg: 5 mg/kg7115-19 kg: 1⁄4 tablet7120-30 kg: 1⁄2 tablet7131-45 kg: 3⁄4 tablet71>45 kg: 1 tablet71 2 mg/kg/d, up to 100 mg/day73 250 mg/100 mg (1 adult tablet) 11-20 kg: 62.5 mg/25 mg53,74 21-30 kg: 125 mg/50 mg53,7431-40 kg: 187.5 mg/75 mg53,74>40 kg: 250 mg/100 mg53,74 0.5 mg/kg base daily * Availability problems. See table on page 12.
63. If chloroquine phosphate is not available, hydroxychloroquine sulfate is as effective; 400 mg of hydroxychloroquine sulfate is equivalent to 500 mg of chloro- quine phosphate.
64. Exchange transfusion has been helpful for some patients with high-density (>10%) parasitemia, altered mental status, pulmonary edema or renal complications (KD Miller et al, N Engl J Med 1989; 321:65).
65. Continuous EKG, blood pressure and glucose monitoring are recommended, especially in pregnant women and young children. For problems with quinidine availability, call the manufacturer (Eli Lilly, 800-821-0538) or the CDC Malaria Hotline (770-488-7788). Quinidine may have greater antimalarial activity thanquinine. The loading dose should be decreased or omitted in those patients who have received quinine or mefloquine. If more than 48 hours of parenteraltreatment is required, the quinine or quinidine dose should be reduced by 1/3 to 1/2.
66. Artemether-Quinine Meta-Analysis Study Group, Trans R Soc Trop Med Hyg 2001; 95:637. Not available in the US.
67. Relapses have been reported with this regimen, and should be treated with a second 14-day course of 30 mg base/day. In Southeast Asia and Somalia the higher dose (30 mg base/day) should be used initially.
68. No drug regimen guarantees protection against malaria. If fever develops within a year (particularly within the first two months) after travel to malarious areas, travelers should be advised to seek medical attention. Insect repellents, insecticide-impregnated bed nets and proper clothing are important adjuncts formalaria prophylaxis.
69. In pregnancy, chloroquine prophylaxis has been used extensively and safely.
70. For prevention of attack after departure from areas where P. vivax and P. ovale are endemic, which includes almost all areas where malaria is found (except Haiti), some experts prescribe in addition primaquine phosphate 26.3 mg (15 mg base)/d or, for children, 0.3 mg base/kg/d during the last two weeks of prophy-laxis. Others prefer to avoid the toxicity of primaquine and rely on surveillance to detect cases when they occur, particularly when exposure was limited ordoubtful. See also footnotes 62 and 67.
71. Beginning one to two weeks before travel and continuing weekly for the duration of stay and for four weeks after leaving.
72. The pediatric dosage has not been approved by the FDA, and the drug has not been approved for use during pregnancy. However, it has been reported to be safe for prophylactic use during the second or third trimester of pregnancy and possibly during early pregnancy as well (CDC Health Information for Interna-tional Travel, 2001-2002, page 113; BL Smoak et al, J Infect Dis 1997; 176:831). Mefloquine is not recommended for patients with cardiac conduction abnormali-ties. Patients with a history of seizures or psychiatric disorders should avoid mefloquine (Medical Letter 1990; 32:13). Resistance to mefloquine has been re-ported in some areas, such as Thailand; in these areas, doxycycline should be used for prophylaxis. In children less than eight years old, proguanil plussulfisoxazole has been used (KN Suh and JS Keystone, Infect Dis Clin Pract 1996; 5:541).
73. Beginning 1-2 days before travel and continuing for the duration of stay and for 4 weeks after leaving. Use of tetracyclines is contraindicated in pregnancy and in children less than eight years old. Doxycycline can cause gastrointestinal disturbances, vaginal moniliasis and photosensitivity reactions.
74. GE Shanks et al, Clin Infect Dis 1998; 27:494; B Lell et al, Lancet 1998; 351:709. Beginning 1 to 2 days before travel and continuing for the duration of stay and for 1 week after leaving. In one study of malaria prophylaxis, atovaquone/proguanil was better tolerated than mefloquine in nonimmune travelers (D Over-bosch et al, Clin Infect Dis 2001; 33:1015).
75. Several studies have shown that daily primaquine beginning one day before departure and continued until 7 days after leaving the malaria area provides effective prophylaxis against chloroquine-resistant P. falciparum (JK Baird et al, Clin Infect Dis 2001; 33:1990). Some studies have shown less efficacy againstP. vivax. Nausea and abdominal pain can be diminished by taking with food.
The Medical Letter • April 2002 MALARIA, Prevention of (continued)
500 mg (300 mg base) once/week71 5 mg/kg base once/week, up to adult dose of 300 mg base71 <2 yrs: 50 mg once/day2-6 yrs: 100 mg once/day7-10 yrs: 150 mg once/day>10 yrs: 200 mg once/day 2 adult tablets bid x 3d74 11-20 kg: one adult tablet/day x 3d74 21-30 kg: 2 adult tablets/day x 3d7431-40 kg: 3 adult tablets/day x 3d74>40 kg: 2 adult tablets bid x 3d74 OR Pyrimethamine- Carry a single dose (3 tablets) for <1 yr: 1⁄4 tablet self treatment of febrile illness 1-3 yrs: 1⁄2 tablet when medical care is not immedi- 4-8 yrs: 1 tablet 9-14 yrs: 2 tablets Ocular (Encephalitozoon hellem, Encephalitozoon cuniculi, Vittaforma corneae [Nosema corneum])
plus fumagillin77* Intestinal (Enterocytozoon bieneusi, Encephalitozoon [Septata] intestinalis)
E. bieneusi78
E. intestinalis Disseminated (E. hellem, E. cuniculi, E. intestinalis, Pleistophora sp., Trachipleistophora sp. and Brachiola vesicularum)
Drug of choice:79 Mites, see SCABIES
11 mg/kg once, repeat twice, 2 wks 11 mg/kg once, repeat twice, 2 wks Naegleria species, see AMEBIC MENINGOENCEPHALITIS, PRIMARY
Necator americanus, see HOOKWORM infection
Onchocerca volvulus, see FILARIASIS
Opisthorchis viverrini, see FLUKE infection
Paragonimus westermani, see FLUKE infection
Pediculus capitis, humanus, Phthirus pubis, see LICE
Pinworm, see ENTEROBIUS
* Availability problems. See table on page 12.
76. Proguanil (Paludrine − Wyeth Ayerst, Canada; AstraZeneca, United Kingdom), which is not available alone in the US but is widely available in Canada and Eu- rope, is recommended mainly for use in Africa south of the Sahara. Prophylaxis is recommended during exposure and for four weeks afterwards. Proguanilhas been used in pregnancy without evidence of toxicity (PA Phillips-Howard and D Wood, Drug Saf 1996; 14:131).
77. Ocular lesions due to E. hellem in HIV-infected patients have responded to fumagillin eyedrops prepared from Fumidil-B, a commercial product (Mid-Continent Agrimarketing, Inc., Olathe, Kansas, 800-547-1392) used to control a microsporidial disease of honey bees (MC Diesenhouse, Am J Ophthalmol 1993; 115:293).
For lesions due to V. corneae, topical therapy is generally not effective and keratoplasty may be required (RM Davis et al, Ophthalmology 1990; 97:953).
78. Oral fumagillin (see footnote 77, Sanofi Recherche, Gentilly, France) has been effective in treating E. bieneusi (J-M Molina et al, AIDS 2000; 14:1341), but has been associated with thrombocytopenia. Highly active antiretroviral therapy (HAART) may lead to microbiologic and clinical response in HIV-infected patientswith microsporidial diarrhea (NA Foudraine et al, AIDS 1998; 12:35; A Carr et al, Lancet 1998; 351:256). Octreotide (Sandostatin) has provided symptomatic re-lief in some patients with large volume diarrhea.
79. J-M Molina et al, J Infect Dis 1995; 171:245. There is no established treatment for Pleistophora.
80. Albendazole or pyrantel pamoate may be effective (HP Krepel et al, Trans R Soc Trop Med Hyg 1993; 87:87).
The Medical Letter • April 2002 PNEUMOCYSTIS carinii pneumonia (PCP)81
TMP 15 mg/kg/d, SMX 75 mg/kg/d, Same as adult dose oral or IV in 3 or 4 doses x 14-21d 30 mg base PO daily x 21 days 600 mg IV q6h x 21 days, or 300-450 mg PO q6h x 21 days 5 mg/kg PO tid x 21 days 100 mg PO daily x 21 days 3-4 mg/kg IV daily x 14-21 days Same as adult dose 750 mg bid PO x 21d Primary and secondary prophylaxis82
1 tab (single or double strength) TMP 150 mg/m2, SMX 750 mg/m2 in 2 doses on 3 consecutive days per 50 mg bid, or 100 mg daily 2 mg/kg (max. 100 mg) daily or 4 mg/kg (max. 200 mg each week) 50 mg daily or 200 mg each week 50 mg or 75 mg each week 300 mg inhaled monthly via Respir- ≥5 yrs: same as adult dose gard II nebulizer Roundworm, see ASCARIASIS
Sappinia Diploidea, See AMEBIC MENINGOENCEPHALITIS, PRIMARY
SCABIES (Sarcoptes scabiei)
200 µg/kg PO once 200 µg/kg PO once Topically once/daily x 2 Topically once/daily x 2 40 mg/kg/d in 2 doses x 1d 40 mg/kg/d in 2 doses x 1d 60 mg/kg/d in 3 doses x 1d 60 mg/kg/d in 3 doses x 1d 40 mg/kg/d in 2 doses x 1d 40 mg/kg/d in 2 doses x 1d 20 mg/kg/d in 2 doses x 1d87 60 mg/kg/d in 3 doses x 1d 60 mg/kg/d in 3 doses x 1d Sleeping sickness, see TRYPANOSOMIASIS
Drug of choice:88 200 µg/kg/d x 1-2d 200 µg/kg/d x 1-2d 50 mg/kg/d in 2 doses 50 mg/kg/d in 2 doses (max. 3 grams/d) x 2d89 (max. 3 grams/d) x 2d89 * Availability problems. See table on page 12.
81. In severe disease with room air PO ≤ 70 mmHg or Aa gradient ≥ 35 mmHg, prednisone should also be used (S Gagnon et al, N Engl J Med 1990; 323:1444; E Caumes et al, Clin Infect Dis 1994; 18:319).
82. Primary/secondary prophylaxis in patients with HIV can be discontinued after CD4 count increases to >200 x 106/L for more than 3 months (HIV/AIDS Treatment Information Service, US Department of Health and Human Services 2001; www.hivatis.org).
83. An alternative trimethoprim/sulfamethoxazole regimen is one DS tab 3x/week. Weekly therapy with sulfadoxine 500 mg/pyrimethamine 25 mg/leucovorin 25 mg was effective PCP prophylaxis in liver transplant patients (J Torre-Cisneros et al, Clin Infect Dis 1999; 29:771).
84. Plus leucovorin 25 mg with each dose of pyrimethamine.
85. Effective for crusted scabies in immunocompromised patients (M Larralde et al, Pediatr Dermatol 1999; 16:69; A Patel et al, Australas J Dermatol 1999; 40:37; O Chosidow, Lancet 2000; 355:819).
86. Oxamniquine has been effective in some areas in which praziquantel is less effective (FF Stelma et al, J Infect Dis 1997; 176:304). Oxamniquine is contraindicat- ed in pregnancy.
87. In East Africa, the dose should be increased to 30 mg/kg, and in Egypt and South Africa to 30 mg/kg/d x 2d. Some experts recommend 40-60 mg/kg over 2-3 days in all of Africa (KC Shekhar, Drugs 1991; 42:379).
88. In immunocompromised patients or disseminated disease, it may be necessary to prolong or repeat therapy or use other agents. A veterinary parenteral for- mulation of ivermectin was used in one patient (PL Chiodini et al, Lancet 2000; 355:43).
89. This dose is likely to be toxic and may have to be decreased.
The Medical Letter • April 2002 — Adult (intestinal stage)
Diphyllobothrium latum (fish), Taenia saginata (beef), Taenia solium (pork), Dipylidium caninum (dog)
Hymenolepis nana (dwarf tapeworm)
— Larval (tissue stage)
Echinococcus granulosus (hydatid cyst)
Drug of choice:90 400 mg bid x 1-6 months 15 mg/kg/d (max. 800 mg) x 1-6 400 mg bid x 8-30d; can be repeated 15 mg/kg/d (max. 800 mg) in 2 doses x 8-30d; can be repeated as neces-sary 50-100 mg/kg/d in 3 doses x 30d 50-100 mg/kg/d in 3 doses x 30d Toxocariasis, see VISCERAL LARVA MIGRANS
Drugs of choice:94 25-100 mg/d x 3-4 wks 2 mg/kg/d x 3d, (max. 25 mg/d) x 4 1-1.5 grams qid x 3-4 wks 100-200 mg/kg/d x 3-4 wks 3-4 grams/d x 3-4 wks 50-100 mg/kg/d x 3-4 wks Steroids for severe 200-400 mg tid x 3d, then 400-500 200-400 mg tid x 3d, then 400-500 400 mg bid x 8-14d 400 mg bid x 8-14d Drug of choice:98 2 grams once or 500 mg bid x 7d 15 mg/kg/d orally in 3 doses x 7d 2 grams once or 500 mg bid 50 mg/kg once (max. 2 g) * Availability problems. See table on page 12.
90. Patients may benefit from or require surgical resection of cysts. Praziquantel is useful preoperatively or in case of spill during surgery. Percutaneous drainage with ultrasound guidance plus albendazole therapy has been effective for management of hepatic hydatid cyst disease (MS Khuroo et al, N Engl J Med 1997;337:881; O Akhan and M Ozman, Eur J Radiol 1999; 32:76).
91. Surgical excision or the PAIR (Puncture, Aspirate, Inject, Re-aspirate) technique is the only reliable means of cure. Reports have suggested that in non- resectable cases use of albendazole or mebendazole can stabilize and sometimes cure infection (W Hao et al, Trans R Soc Trop Med Hyg 1994; 88:340; WHOGroup, Bull WHO 1996; 74:231).
92. Initial therapy of parenchymal disease with seizures should focus on symptomatic treatment with anticonvulsant drugs. Treatment of parenchymal disease with albendazole and praziquantel is controversial and randomized trials have not been conclusive. Obstructive hydrocephalus is treated with surgical removalof the obstructing cyst or CSF diversion. Prednisone 40 mg daily may be given in conjunction with surgery. Arachnoiditis, vasculitis or cerebral edema is treat-ed with prednisone 60 mg daily or dexamethasone 4-16 mg/d combined with albendazole or praziquantel (AC White, Jr, Annu Rev Med 2000; 51:187). Patientswith subarachnoid cysts or giant cysts in the fissures should receive albendazole for at least 30 days (JV Proano et al, N Engl J Med 2001; 345:879). Any cysti-cercocidal drug may cause irreparable damage when used to treat ocular or spinal cysts, even when corticosteroids are used. An ophthalmic exam should al-ways be done before treatment to rule out intraocular cysts.
93. In ocular toxoplasmosis with macular involvement, corticosteroids are recommended for an anti-inflammatory effect on the eyes.
94. To treat CNS toxoplasmosis in HIV-infected patients, some clinicians have used pyrimethamine 50 to 100 mg daily (after a loading dose of 200 mg) with sulfa- diazine and, when sulfonamide sensitivity developed, have given clindamycin 1.8 to 2.4 g/d in divided doses instead of the sulfonamide (JS Remington et al,Lancet 1991; 338:1142; BJ Luft et al, N Engl J Med 1993; 329:995). Atovaquone plus pyrimethamine appears to be an effective alternative in sulfa-intolerant pa-tients (JA Kovacs et al, Lancet 1992; 340:637). Treatment is followed by chronic suppression with lower dosage regimens of the same drugs. For primary pro-phylaxis in HIV patients with <100 CD4 cells, either trimethoprim-sulfamethoxazole, pyrimethamine with dapsone or atovaquone with or without pyrimetha-mine can be used. Primary/Secondary prophylaxis may be discontinued when the CD4 count increases to >200 x 106/L for more than 3 months (HIV/AIDS Treat-ment Information Service US Department of Health and Human Services 2001; (www.hivatis.org). See also footnote 95.
95. Plus leucovorin 10 to 25 mg with each dose of pyrimethamine.
96. Congenitally infected newborns should be treated with pyrimethamine every two or three days and a sulfonamide daily for about one year (JS Remington and G Desmonts in JS Remington and JO Klein, eds, Infectious Disease of the Fetus and Newborn Infant, 5th ed, Philadelphia:Saunders, 2001, page 290).
97. For prophylactic use during pregnancy. If it is determined that transmission has occurred in utero, therapy with pyrimethamine and sulfadiazine should be started. Pyrimethamine is a potential teratogen and should be used only after the first trimester.
98. Sexual partners should be treated simultaneously. Metronidazole-resistant strains have been reported and should be treated with metronidazole 2-4 g/d x 7- 14d. Desensitization has been recommended for patients allergic to metronidazole (MD Pearlman et al, Am J Obstet Gynecol 1996; 174:934). High dose tinida-zole has also been used for the treatment of metronidazole-resistant trichomoniasis (JD Sobel et al, Clin Infect Dis 2001; 33:1341).
The Medical Letter • April 2002 Pyrantel pamoate7 11 mg/kg base once (max. 1 g) 11 mg/kg once (max. 1 gram) TRICHURIASIS (Trichuris trichiura, whipworm)
100 mg bid x 3d or 500 mg once 100 mg bid x 3d or 500 mg once T. cruzi (American trypanosomiasis, Chagas' disease)
5-7 mg/kg/d in 2 divided doses Up to 12 yrs: 10 mg/kg/d in 2 doses 8-10 mg/kg/d in 3-4 doses x 90-120d 15-20 mg/kg/d in 4 doses x 90d; 12.5-15 mg/kg/d in 4 doses x 90d T. brucei gambiense (West African trypanosomiasis, sleeping sickness)
Drug of choice:100 4 mg/kg/d IM x 10d 4 mg/kg/d IM x 10d 100-200 mg (test dose) IV, then 1 20 mg/kg on days 1,3,7,14, and 21 gram IV on days 1,3,7,14, and 21 T. b. rhodesiense (East African trypanosomiasis, sleeping sickness)
100-200 mg (test dose) IV, then 1 20 mg/kg on days 1,3,7,14, and 21 gram IV on days 1,3,7,14, and 21 late disease with CNS involvement (T.b. gambiense or T.b. rhodesiense)
2-3.6 mg/kg/d IV x 3d; after 1 wk 18-25 mg/kg total over 1 month; ini- 3.6 mg/kg per day IV x 3d; repeat tial dose of 0.36 mg/kg IV, increas- again after 10-21 days ing gradually to max. 3.6 mg/kg atintervals of 1-5d for total of 9-10doses VISCERAL LARVA MIGRANS103 (Toxocariasis)
100-200 mg bid x 5d 100-200 mg bid x 5d Whipworm, see TRICHURIASIS
Wuchereria bancrofti, see FILARIASIS
* Availability problems. See table on page 12.
99. Available from CDC. The addition of gamma interferon to nifurtimox for 20 days in a limited number of patients and in experimental animals appears to have shortened the acute phase of Chagas' disease (RE McCabe et al, J Infect Dis 1991; 163:912).
100. For treatment of T.b. gambiense, pentamidine and suramin have equal efficacy but pentamidine is better tolerated.
101. Eflornithine is highly effective in T.b. gambiense and variably effective in T.b. rhodesiense infections. It is available in limited supply only from the WHO, and is given 400 mg/kg/d IV in 4 divided doses for 14 days.
102. In frail patients, begin with as little as 18 mg and increase the dose progressively. Pretreatment with suramin has been advocated for debilitated patients.
Corticosteroids have been used to prevent arsenical encephalopathy (J Pepin et al, Trans R Soc Trop Med Hyg 1995; 89:92). Up to 20% of patients withT. gambiense fail to respond to melarsoprol (MP Barrett, Lancet 1999; 353:1113). A shortened course consisting of 10 daily injections of 2.2 mg/kg gave asimilar outcome to the usual 26-treatment schedule (C Burri et al, Lancet 2000; 355:1419).
103. Optimum duration of therapy is not known; some Medical Letter consultants would treat for up to 20 days. For severe symptoms or eye involvement, cor- ticosteroids can be used in addition.
The Medical Letter • April 2002 MANUFACTURERS OF SOME ANTIPARASITIC DRUGS
albendazole − Albenza (GlaxoSmithKline) metronidazole − Flagyl (Searle), others § artemether − Artenam (Arenco, Belgium) § miltefosine − (Zentaris) § artesunate − (Guilin No. 1 Factory, People's Republic § niclosamide − Yomesan (Bayer, Germany) † nifurtimox − Lampit (Bayer, Germany) atovaquone − Mepron (GlaxoSmithKline) * nitazoxanide − Cryptaz (Romark) atovaquone/proguanil — Malarone § ornidazole − Tiberal (Roche, France) oxamniquine − Vansil (Pfizer) bacitracin − many manufacturers paromomycin − Humatin (Monarch); Leshcutan (Teva § bacitracin-zinc − (Apothekernes Laboratorium A.S., Pharmaceutical Industries, Ltd., Israel; (topical for- mulation not available in US) § benznidazole − Rochagan (Roche, pentamidine isethionate − Pentam 300, NebuPent † bithionol − Bitin (Tanabe, Japan) permethrin − Nix (GlaxoSmithKline), Elimite (Allergan) chloroquine HCl and chloroquine phosphate − Aralen praziquantel − Biltricide (Bayer) primaquine phosphate USP crotamiton − Eurax (Westwood-Squibb) § proguanil − Paludrine (Wyeth Ayerst, Canada; As- dapsone − (Jacobus) traZeneca, United Kingdom); in combination with † diethylcarbamazine citrate USP − atovaquone as Malarone (GlaxoSmithKline) (University of Iowa School of Pharmacy) § propamidine isethionate − Brolene (Aventis, Canada) § diloxanide furoate − Furamide (Boots, United King- pyrantel pamoate − Antiminth (Pfizer) pyrethrins and piperonyl butoxide − RID (Pfizer), oth- § eflornithine (Difluoromethylornithine, DFMO) − Ornidyl pyrimethamine USP − Daraprim (GlaxoSmithKline) furazolidone − Furoxone (Roberts) § quinine dihydrochloride § halofantrine − Halfan (GlaxoSmithKline) quinine sulfate − many manufacturers iodoquinol − Yodoxin (Glenwood), others † sodium stibogluconate − Pentostam (GlaxoSmithKline, ivermectin − Stromectol (Merck) malathion − Ovide (Medicis) * spiramycin − Rovamycine (Aventis) mebendazole − Vermox (McNeil) † suramin sodium − (Bayer, Germany) mefloquine − Lariam (Roche) thiabendazole − Mintezol (Merck) § meglumine antimonate − Glucantime (Aventis, France) § tinidazole − Fasigyn (Pfizer) † melarsoprol − Mel-B (Specia) * triclabendazole − Egaten (Novartis, Switzerland) trimetrexate − Neutrexin (US Bioscience) Available in the US only from the manufacturer.
Not available in the US.
Available under an Investigational New Drug (IND) protocol from the CDC Drug Service, Centers for Disease Control and Preven-tion, Atlanta, Georgia 30333; 404-639-3670 (evenings, weekends, or holidays: 404-639-2888).
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