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*'''Sulfadiazine and pyrimethamine combination, 'Re-Balance'''': administered PO daily for a minimum of 90 days. Due to availability and ease of administration, some use an off-label regimen of trimethoprimsulfa tablets with pyrimethamine tablets.  ''Mode of action'': trimethoprim, sulfadiazine, and pyrimethamine all inhibit enzymes of folic acid synthesis.  ''Efficacy'': 61.5% improvement by one clinical grade.(98 in furr)''Potential adverse effects'': bone marrow suppression (mild anaemia, leucopenia, neutropenia, thrombocytopenia), fever, anorexia, depression, acute worsening of ataxiam altered reproductive performance in stallions (19 in IVIS 4), congenital defects(20 in IVIS 4) and abortion.  Folic acid deficiency may also cause gastrointestinal disturbances such as glossitis.(18 in IVIS 4) Blood dyscrazias are typically self-limiting and resolve on withdrawal of treatment. (Furr)
 
*'''Sulfadiazine and pyrimethamine combination, 'Re-Balance'''': administered PO daily for a minimum of 90 days. Due to availability and ease of administration, some use an off-label regimen of trimethoprimsulfa tablets with pyrimethamine tablets.  ''Mode of action'': trimethoprim, sulfadiazine, and pyrimethamine all inhibit enzymes of folic acid synthesis.  ''Efficacy'': 61.5% improvement by one clinical grade.(98 in furr)''Potential adverse effects'': bone marrow suppression (mild anaemia, leucopenia, neutropenia, thrombocytopenia), fever, anorexia, depression, acute worsening of ataxiam altered reproductive performance in stallions (19 in IVIS 4), congenital defects(20 in IVIS 4) and abortion.  Folic acid deficiency may also cause gastrointestinal disturbances such as glossitis.(18 in IVIS 4) Blood dyscrazias are typically self-limiting and resolve on withdrawal of treatment. (Furr)
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*'''Ponazuril (Marquis, Bayer Animal Health)''': PO daily for 28 days, use in pregnant animals is off-label.  ''Mode of action'': ponazuril is a triazinetrione antiprotozoal that targets the “apicoplast” organelle and inhibits the respiratory chain.  ''Efficacy'': well absorbed PO, achieves steady state therapeutic concentration in CSF within 3 days(100 in Furr), clinical response within 10 days, 60% improvement by at least one clinical grade, 8% relapse within 90 days of stopping treatment(91 in Furr).  ''Potential adverse effects'': none in a multi-centre field study (IVIS 4), no systemic toxicity even at high doses.(101 in Furr)However, the manufacturer reports signs that may have been related to treatment including blisters on nose and mouth, skin rash or hives, loose stools, mild colic, and a seizure.(IVIS 4)
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*'''Ponazuril (Marquis, Bayer Animal Health)''': PO daily for 28 days, use in pregnant animals is off-label.  ''Mode of action'': ponazuril is a triazinetrione that targets the “apicoplast” organelle and inhibits the respiratory chain.  ''Efficacy'': well absorbed PO, achieves steady state therapeutic concentration in CSF within 3 days(100 in Furr), clinical response within 10 days, 60% improvement by at least one clinical grade, 8% relapse within 90 days of stopping treatment(91 in Furr).  ''Potential adverse effects'': none in a multi-centre field study (IVIS 4), no systemic toxicity even at high doses.(101 in Furr)However, the manufacturer reports signs that may have been related to treatment including blisters on nose and mouth, skin rash or hives, loose stools, mild colic, and a seizure.(IVIS 4)
 
    
 
    
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*'''Diclazuril''': PO, daily for 28 days, approved by FDA for use as top-dress tablet but not commercially available ''Mode of action'': chemically similar to ponazuril but mechanism of action unknown.  ''Efficacy'': one study reported clinical improvement in 58% of cases.(98 in Furr)  ''Potential adverse effects'': none found in one efficacy study.(Furr)  Reported problems in a multi-centre field study included worsening neurologic status and laminitis but these were not proven to be related to treatment. (IVIS 4)
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*'''Nitazoxanide, NTZ (Navigator, Idexx Pharmaceuticals)''': no longer commercially available in the US.  ''Mode of action'': a member of the 5-nitrothiazole class of antiparasitics that inhibits the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction essential for anaerobic energy metabolism.(IVIS 4)  ''Efficacy'': 60% success rate in an FDA-regulated study.(98 in Furr) ''Potential adverse effects'': adverse effects and death at high doses(98), fever, anorexia, diarrhoea, lethargy, depression and laminitis recorded at lower doses.  Toxic signs usally resolve upon cessation of treatment.(Furr)'''''Caution''': 'administration of nitazoxanide can disrupt the normal microbial flora of the gastrointestinal tract leading to enterocolitis.  Deaths due to enterocolitis have been observed while administering the recommended dose in field studies.''''''(IVIS 4)
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Prolonged, off-license treatment is often instigated after 1 month, based on repeated clinical examination.  Even successfully treated cases may remain immunoblot positive for long periods, thus aiming for seronegativity is unrealistic.(Furr)  A lack of response to treatment suggests that the diagnosis should be re-assessed.  Another month's worth of treatment is recommended for partial responders.(Furr)
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Diclazuril po, SID, chemically similar to ponazuril, one study imorvment in 58% cases if gven for 28days (98 in Furr), approved by FDA for use as top-dress tablet but not comemrically avialable, no adverse effects in effciacy study.(Furr)
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Diclazuril is a triazinetrione antiprotozoal agent similar to ponazuril with an unknown (but possibly similar) mechanism of action.  A multi-center clinical field study was performed.  Reported adverse reactions were not clearly linked to drug administration and included worsening neurologic status and laminitis. Results of efficacy studies were surprisingly similar for each of the four approved therapies when similar methodologies and means of assessing improvement were used. Regardless of drug, _60% of treated horses improved by at least one neurologic grade or became negative on CSF WB. Based on reported side effects, ponazuril and diclazuril seem to have the fewest reported adverse effects. (IVIS 4)
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NTZ (Navigator, Idexx Pharmaceuticals) member of 5-notrothiazol class of antimicrobials ad currently approved for tx of EPM, succes rate of about 60% in FDA-regulated study (98 in Furr). Adverse effects and death at high doses (98),, diarrhoea, depressiona and lamninits recorded at lower doses.  {Poor completion rate and study compliance sugegts unreproted toxicity.  Toxci signs usally resolve oin withdrawl of tx, no longer availbale in US.
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Even successfully treaed cases may remian immunoblot positive for long periods so trying ot treat unitl seronegatvie not relasiitc. Triaxine based rugs (ponazuril, diclazruil, NTZ) licensed to be used oinly for 28days.  Longer tx often needed as determined by repeat exam after 1mth.  No reposnee sugegsts misdx and case should be re-evaluated.  If some resposne bt rmeiansabnromal, continue tx for another mth.(Furr)
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Paste no longer commercially available. This drug is a 5-nitrothiazole antiparasitic drug that inhibits the pyruvate:ferredoxin oxidoreductase (PFOR) enzymedependent electron transfer reaction essential for anaerobic energy metabolism.  Reported side effects in these studies included inappetence and depression.
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Two field studies for efficacy and safety were conducted during the approval process for nitazoxanide.
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The most common adverse reactions were fever, anorexia/reduced appetite, and lethargy/depression.
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Following warning: “administration of nitazoxanide can disrupt the normal microbial flora of the gastrointestinal tract leading to enterocolitis.  Deaths due to enterocolitis have been observed while administering the recommended dose in field studies.”a(IVIS 4)
      
===Ancillary medication===
 
===Ancillary medication===
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