Elephant specific information, if available, is in blue.

Chemistry – A diaminopyrimidine structurally related to trimethoprim, ormetoprim occurs as a white, almost tasteless powder. The chemistry of sulfadimethoxine is described in the previous monograph.

 

Storage/Stability/Compatibility – Unless otherwise instructed by the manufacturer, store tablets in tight, light resistant containers at room temperature.

 

Pharmacology – Sulfadimethoxine/ormetoprim shares mechanisms of action and probably the bacterial spectrum of activity with trimethoprim/sulfa. Alone, sulfonamides are bacte­riostatic agents, but in combination with either ormetoprim or trimethoprim, the potentiated sulfas are bactericidal. Potentiated sulfas sequentially inhibit enzymes in the folic acid pathway, thereby inhibiting bacterial thymidine synthesis. The sulfonamide blocks the conversion of para-aminobenzoic acid (PABA) to dihydrofolic acid (DFA) and ormetoprim blocks the conversion of DFA to tetrahydrofolic acid by inhibiting dihydrofolate re­ductase.

           

The potentiated sulfas have a fairly broad spectrum of activity. Gram positive bacteria that are generally susceptible include, most streptococci, many strains of staphylococcus, and Nocardia. Many gram negative organisms of the family Enterobacteriaceae are susceptible to the potentiated sulfas, but not Pseudomonas aeruginosa. Some protozoa (Pneumocystis carinii, Coccidia and Toxoplasma) are also inhibited by the combination. Potentiated sulfas reportedly have little activity against most anaerobes, but opinions on this vary.

           

Resistance will develop slower to the combination of drugs, than to either one alone. In gram negative organisms, resistance is usually plasmid-mediated.

 

Uses/Indications – The present approved indications for this combination are for the treatment of skin and soft tissue infections in dogs caused by susceptible strains of Staphylococcus aureus and E. coli. Because clinical experience with this drug is extremely limited at the time of this writing, further uses and indications may be forthcoming.

 

Pharmacokinetics – The pharmacokinetics of sulfadimethoxine are outlined in the previ­ous monograph. Pharmacokinetic data for ormetoprim is not available at the time of this writing, but the manufacturer claims that therapeutic levels are maintained over 24 hours at recommended doses.

 

Contraindications/Precautions/Reproductive Safety – The manufacturer states that ormetoprim/sulfadimethoxine should not be used in dogs or horses showing marked liver parenchymal damage, blood dyscrasias, or in those with a history of sulfonamide sensitiv­ity.

           

This combination should be used with caution in patients with pre-existing hepatic or thyroid disease.

           

Safety of ormetoprim/sulfadimethoxine has not been established in pregnant animals. Reports of teratogenicity (cleft palate) have been reported in some lab animals with trimethoprim/sulfa.

 

Adverse Effects/Warnings – Adverse effects with this combination have not been re­ported at recommended doses, but the number of evaluated patients is very small at the time of this writing. This combination would be expected to exhibit an adverse reaction profile in dogs similar to that seen with trimethoprim/sulfa, including: keratoconjunctivitis sicca (which may be irreversible), acute neutrophilic hepatitis with icterus, vomiting, anorexia, diarrhea, fever, hemolytic anemia, urticaria, polyarthritis, facial swelling, poly­dipsia, polyuria and cholestasis. Acute hypersensitivity reactions manifesting as Type I (anaphylaxis) or Type III reaction (serum sickness) can also be seen. Hypersensitivity re­actions appear to be more common in large breed dogs; Doberman Pinschers may possibly be more susceptible to this effect than other breeds. Other hematologic effects (anemias, agranulocytosis) are possible, but fairly rare in dogs.

           

Long-term (8 weeks) therapy at recommended doses with ormetoprim/sulfadimethoxine (27.5 mg/kg once daily) resulted in elevated serum cholesterol, thyroid and liver weights, mild follicular thyroid hyperplasia and enlarged basophilic cells in the pituitary. The manufacturer states that the principal treatment-related effect of extended or excessive us­age is hypothyroidism.

 

Overdosage/Acute Toxicity – In experimental studies in dogs, doses greater than 80 mg/kg resulted in slight tremors and increased motor activity in some dogs. Higher doses may result in depression, anorexia or seizures.

           

It is suggested that very high oral overdoses be handled by emptying the gut using stan­dard precautions and protocols and by treating symptoms supportively and symptomatically.

 

Drug Interactions; Drug/Laboratory Interactions – None have been noted for this combination, but it would be expected that the potential interactions outlined for the trimethoprim/sulfa monograph would also apply to this combination; refer to that mono­graph for more information.

 

Doses –

            Dogs:

For susceptible infections:

a)   Initially 55 mg/kg (combined drug) PO on the first day of therapy, then 27.5 mg/kg PO once daily for at least 2 days after remission of clinical signs. Not approved for treatment longer than 21 days. (Package insert; Primor®—SKB)

           

Elephants:

a) Sulfadimethoxine/ormetoprim (Primor; 1200:100mg of sulfadimethoxine/200 mg ormetoprim): 16.2 – 18.5 mg/kg po BID on day 1 then 9.25 mg/kg thereafter.  This regimen has been used for 30 days with positive therapeutic results and no adverse effects.  For more severe infections: 23.2 – 26.4 mg/kg po BID on day 1 then 13.2 mg/kg

thereafter.  Diarrhea may result at the higher dose but will resolve with the discontinuation of treatment (Schmidt,1986).

 

Elephant References:

a) Schmidt, M.J: Senior Research Veterinarian, Washington Park Zoo, Portland, Oregon, personal communication, 1986. In: Olsen,J.H., 1999. Antibiotic therapy in elephants. In: Fowler,M.E. and Miller R.E. (Editors), Zoo and Wild Animal Medicine: Current Therapy 4. W.B. Saunders, Philadelphia, PA,USA p. 537.

Monitoring Parameters –

1)   Clinical efficacy

2)   Adverse effects

 

Client Information – Animals must be allowed free access to water and must not become dehydrated while on therapy.

 

Dosage Forms/Preparations/FDA Approval Status/Withholding Times –

 

Veterinary-Approved Products:

Sulfadimethoxine/Ormetoprim Tablets (scored)

            120’s: 100 mg Sulfadimethoxine, 20 mg Ormetoprim

            240’s: 200 mg Sulfadimethoxine, 40 mg Ormetoprim

            600’s: 500 mg Sulfadimethoxine, 100 mg Ormetoprim

            1200’s: 1000 mg Sulfadimethoxine, 200 mg Ormetoprim

Primor®  (Pfizer); (Rx)  Approved for use in dogs.

 

Human-Approved Products: None