AHFS Class:

• Amebicides 8:30.04

Generic Name(s):

• Iodoquinol

Iodoquinol is a luminal or contact amebicide and an antiprotozoal agent.

Amebiasis

Iodoquinol is used in as a luminal amebicide in the treatment of amebiasis caused by Entamoeba histolytica .100,102,105,106,107,110 A luminal amebicide generally is sufficient for the treatment of asymptomatic cyst passers who have only intraluminal infections; however, treatment of symptomatic intestinal amebiasis or extraintestinal disease involves the use of both a luminal and tissue amebicide to ensure eradication of tissue-invading trophozoites as well as cysts in the intestinal lumen.100,105,106,107

Asymptomatic Amebiasis

Oral iodoquinol is used alone for the treatment of asymptomatic intestinal amebiasis and is considered a drug of choice for the treatment of asymptomatic cyst passers.100,102,105,106,107 Other luminal amebicides that can be used for the treatment of asymptomatic cyst passers include oral paromomycin or oral diloxanide furoate (not commercially available in the US).100,102,105,106,107 Paromomycin may be preferred, rather than iodoquinol or diloxanide furoate, in children or pregnant women. 105,106

Some strains of Entamoeba are nonpathogenic (e.g., E. dispar , E. hartmanni ) and asymptomatic intraluminal infections with these organisms generally do not require treatment.100,105,106,107 A high percentage of Entamoeba recovered from the intestinal tracts of homosexual males appear to be nonpathogenic.105,107 However, some of these nonpathogenic strains are difficult to differentiate from pathogenic E. histolytica without specialized testing.105,106 Because of the risk of invasive amebiasis if asymptomatic E. histolytica infections are not treated, many clinicians suggest that asymptomatic cyst passers in areas nonendemic for E. histolytica receive treatment with a luminal amebicide.105,106 Treatment of asymptomatic cyst passers in endemic areas (e.g., Mexico, India, Southern and Western Africa, Far East, portions of Central and South America) is more controversial.105,106,107

Symptomatic Intestinal Amebiasis or Extraintestinal Amebiasis (Including Amebic Liver Abscess)

Because iodoquinol acts principally as a luminal amebicide, the drug should not be used alone for the treatment of symptomatic intestinal amebiasis or extraintestinal amebiasis (including hepatic abscess).100,102,106

The regimen of choice for symptomatic intestinal amebiasis or extraintestinal disease (including liver abscess) is treatment with a nitroimidazole derivative (oral metronidazole or oral tinidazole) followed by treatment with a luminal amebicide (oral iodoquinol or oral paromomycin).100,102,105,106,107 When used as follow-up after a tissue amebicide, iodoquinol eradicates encysted E. histolytica in the intestinal lumen.100,102,105,106,107 Paromomycin may be preferred for such follow-up treatment in children or pregnant women.105,106

Balantidiasis

Iodoquinol has been used for the treatment of balantidiasis† caused by Balantidium coli .100,102,106 Tetracycline is considered the drug of choice for treatment of balantidiasis; alternatives are iodoquinol or metronidazole.100,102,106

Blastocystis hominis Infections

Iodoquinol has been used in the treatment of infections caused by Blastocystis hominis †.100,102,106,108,109 However, the clinical importance of B. hominis as a cause of GI pathology is controversial100,102,106,108,109 and it is unclear when treatment of B. hominis infection is indicated.100,106,108 If B. hominis is identified in stool specimens from symptomatic patients, other possible causes, particularly Giardia or Cryptosporidium parvum , should be investigated before assuming that GI symptoms are related to B. hominis .100,108 Some clinicians suggest that treatment be reserved for certain individuals (e.g., immunocompromised patients) who are persistently symptomatic and in whom no other pathogen or process is found to explain the patient's GI symptoms.100,106 Other clinicians believe that B. hominis does not cause symptomatic disease and recommend only a careful search for other causes of the symptoms.100

Metronidazole, iodoquinol, co-trimoxazole, or nitazoxanide has been reported to be effective for treatment of B. hominis infections in some patients,100,102 but metronidazole resistance may be common.102

Dientamoeba fragilis Infections

Iodoquinol is used for the treatment of infections caused by Dientamoeba fragilis †.102,106 Drugs of choice for these infections are iodoquinol, paromomycin, tetracycline, or metronidazole.102,106

Other Uses

For topical uses of iodoquinol, see Iodoquinol 84:04.92.

Administration

Iodoquinol is administered orally after a meal.110 Iodoquinol tablets may be crushed and mixed with applesauce or chocolate syrup.

Dosage

Amebiasis

Asymptomatic Amebiasis

Oral iodoquinol is used alone for the treatment of asymptomatic intestinal amebiasis caused by Entamoeba histolytica , including asymptomatic cyst passers (intraluminal infections).100,102,105,106,107

The usual adult dosage of oral iodoquinol for the treatment of asymptomatic amebiasis, including asymptomatic cyst passers (intraluminal infections), is 650 mg 3 times daily for 20 days.102,105,107,110

The usual dosage of oral iodoquinol for pediatric patients who are asymptomatic cyst passers is 30-40 mg/kg daily (maximum 2 g daily) administered in 3 divided doses for 20 days.102,107 The manufacturer recommends that children receive oral iodoquinol in a dosage of 10-13.3 mg/kg 3 times daily (up to 1.95 g daily) for 20 days.110

Symptomatic Intestinal Amebiasis or Extraintestinal Amebiasis (Including Amebic Liver Abscess)

In the treatment of mild to moderate or severe intestinal amebiasis or extraintestinal amebiasis (including hepatic abscess), oral iodoquinol is used as follow-up after a tissue amebicide (oral metronidazole or oral tinidazole).100,102,105,106,107

The usual adult dosage of oral iodoquinol for follow-up after a tissue amebicide (oral metronidazole or tinidazole) is 650 mg 3 times daily for 20 days.102,105,106,107,110

The usual pediatric dosage of oral iodoquinol for follow-up after a tissue amebicide (oral metronidazole or oral tinidazole) is 30-40 mg/kg daily (maximum 2 g daily) administered in 3 divided doses for 20 days.102,107 The manufacturer recommends that children receive oral iodoquinol in a dosage of 10-13.3 mg/kg 3 times daily (up to 1.95 g daily) for 20 days.110

Balantidiasis

For the treatment of balantidiasis† caused by Balantidium coli , some clinicians recommend that adults receive oral iodoquinol in a dosage of 650 mg 3 times daily for 20 days102 and that pediatric patients receive 30-40 mg/kg daily (maximum 2 g daily) given in 3 divided doses for 20 days.102

Blastocystis hominis Infections

When used in the treatment of symptomatic infections caused by Blastocystis hominis †, adults have received oral iodoquinol in a dosage of 650 mg 3 times daily for 20 days.102,109

Dientamoeba fragilis Infections

For the treatment of infections caused by Dientamoeba fragilis †, some clinicians recommend that adults receive oral iodoquinol in a dosage of 650 mg 3 times daily for 20 days102 and that pediatric patients receive 30-40 mg/kg daily (maximum 2 g daily) given in 3 divided doses for 20 days.102

Adverse Effects

The most serious adverse effect of iodoquinol is neurotoxicity, which is related to dose and duration of therapy. Optic neuritis,110 optic atrophy,110 and peripheral neuropathy110 have been reported in patients receiving prolonged, high dosage with 8-hydroxyquinolines.110 Permanent loss of vision has occurred. Dysesthesia and weakness are reported to occur commonly in adults. Large doses administered for short periods have caused acute cerebral manifestations, including agitation and retrograde amnesia. Large doses administered for prolonged periods have resulted in a syndrome of muscle pain, weakness, optic atrophy, and ataxia known as subacute myelo-optic neuropathy (SMON).

Adverse GI effects reported with iodoquinol usually are mild and include anorexia, nausea,110 vomiting,110 diarrhea,110 abdominal cramps,110 increased motility, constipation, epigastric burning and pain, and gastritis. Pruritus ani,110 which probably is related to increased concentrations of iodine, may also occur.

Iodism manifested by generalized furunculosis (iodine toxicoderma) and a variety of skin reactions, including papular and pustular acneiform eruptions, bullae, and vegetating or tuberous iododerma, have been reported in patients receiving iodoquinol. 110 Urticaria,110 pruritus,110 and discoloration of hair and nails also have been reported.

Other reported adverse effects of iodoquinol include enlargement of the thyroid,110 fever,110 chills,110 headache,110 vertigo,110 malaise, and, rarely, hair loss and agranulocytosis.

Precautions and Contraindications

Iodoquinol is contraindicated in patients with known hypersensitivity to iodine or 8-hydroxyquinolines.110 The drug also is contraindicated in patients with hepatic disease.110

Iodoquinol should be administered with caution to individuals with thyroid diseases.110 (See Laboratory Test Interferences: Thyroid Function Tests.)

Iodoquinol should be discontinued if hypersensitivity reactions occur.110 Patients receiving iodoquinol should be advised not to discontinue the medication prematurely and to notify their physician if rash occurs.

Long-term use of iodoquinol should be avoided since prolonged high dosage therapy with halogenated 8-hydroxyquinolines has been associated with optic neuritis, optic atrophy, and peripheral neuropathy.110 Iodoquinol should not be used for the treatment of nonspecific diarrhea.110

Pregnancy and Lactation

Pregnancy

Safe use of iodoquinol during pregnancy has not been established.110

Lactation

Safe use of iodoquinol during lactation has not been established.110

Laboratory Test Interferences

Thyroid Function Tests

Iodoquinol therapy may interfere with certain thyroid function tests by increasing protein-bound serum iodine concentrations.110 This effect may persist for as long as 6 months after cessation of iodoquinol therapy.110

Mechanism of Action

Iodoquinol is referred to as a luminal or contact amebicide because it acts primarily in the intestinal lumen. The precise mechanism of action is unknown.

Spectrum

Iodoquinol is amebicidal against Entamoeba histolytica .110 The drug is believed to act against both the trophozoite and encysted forms of the parasite;110 however, elimination of the cyst form probably results from destruction of the trophozoites.

Pharmacokinetics

The pharmacokinetics of iodoquinol have not been fully elucidated. Most of an oral dose of the drug is not absorbed from the GI tract and is excreted in feces. However, increased blood concentrations of iodine following ingestion of iodoquinol indicate that some systemic absorption does occur. Limited animal studies suggest that a portion of the drug is distributed into tissues and that free iodine appears in urine. One study in a limited number of individuals revealed no free iodoquinol, but only glucuronide and sulfate conjugates of the drug in urine following oral administration.

Chemistry and Stability

Chemistry

Iodoquinol is a halogenated 8-hydroxyquinoline. The drug occurs as a light yellowish to tan, microcrystalline powder that is odorless or has a faint odor110 and is practically insoluble in water110 and sparingly soluble in alcohol. Iodoquinol contains approximately 64% iodine.110

Stability

Iodoquinol tablets should be stored at 15-30°C110 in well-closed containers.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Only references cited for selected revisions after 1984 are available electronically.

100. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

102. Anon. Drugs for parasitic infections. From the Medical Letter website. 2008 Aug. [Web]

105. Ravdin JI. Amebiasis. Clin Infect Dis . 1995; 20:1453-66. [PubMed 7548493]

106. Aucott JN. Amebiasis and “nonpathogenic” intestinal protozoa. Infect Dis Clin North Am . 1993; 7:67-85.

107. Reed SL. Amebiasis: an update. Clin Infect Dis . 1992; 14:385-93. [PubMed 1554822]

108. Miller RA. Blastocystis hominis : an organism in search of a disease. Rev Infect Dis . 1988; 10:930-8. [PubMed 3055191]

109. Grossman I, Weiss LM, Simon D et al. Blastocystis hominis in hospital employees. Am J Gastroenterol . 1992; 87:729-32. [PubMed 1590309]

110. Glenwood. Yodoxin^® (iodoquinol) tablets prescribing information. From manufacturer's website. Accessed 2009 May 11.

111. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 8th ed. Baltimore, MD: Williams & Wilkins; 2008:843-4.