Jarod M. Hanson, DVM, PhD, DACVPM, DABT, is a veterinary virologist, toxicologist, public health consultant, and an adjunct faculty member at University of Maryland and an associate editor for ProMED-mail. Dr. Hanson earned his DVM from University of Minnesota and his PhD in infectious diseases from University of Georgia. He has developed and implemented population health and disease eradication programs for a variety of diseases and species, emphasizing a One Health approach to disease management.
Which of the following drugs would be appropriate for this patient?*
The following represents the best responses based on drug metabolism, pharmacokinetics, species, diagnostic differentials, clinical and laboratory data, and other pertinent findings.
Correct ResponseSafeGlucocorticoids (eg, prednisone) are considered first-line therapy to stop platelet destruction in patients with primary ITP. Prednisone suppresses multiple components of abnormal immune responses, but long-term administration of immunosuppressive dosages (≥2 mg/kg PO, IM, or IV every 24 hours) is associated with adverse effects (eg, iatrogenic hyperadrenocorticism, GI ulceration, ligamentous injury). Prednisone is thus often administered with adjunctive immunosuppressants to facilitate more rapid tapering while controlling clinical signs; however, no multiple-agent protocol for ITP has been consistently associated with a survival benefit or lower relapse rate as compared with prednisone alone.1
Correct ResponseDo Not UseCarprofen is a cyclooxygenase-inhibiting NSAID not indicated for immune suppression, which is necessary for patients with ITP. NSAIDs should not be administered concurrently with glucocorticoids because of increased risk for adverse effects (eg, GI ulceration). NSAIDs are also contraindicated in this patient because they inhibit platelet function, which could worsen clinically apparent mucosal bleeding secondary to thrombocytopenia.2
Correct ResponseProceed with CautionCyclosporine is a calcineurin inhibitor immunosuppressant typically coadministered with glucocorticoids to suppress lymphocyte proliferation in patients with ITP. Dogs should be given the modified, microemulsified formulation to ensure adequate bioavailability. Although a benefit for increased survival has not been consistently shown compared with glucocorticoids alone, cyclosporine may allow faster withdrawal of glucocorticoid therapy to reduce risk for adverse effects.1 GI adverse effects are most common; gingival hyperplasia and papillomatosis are less common.3 A possible predisposition to lymphoma has only been reported in one dog.4 Cyclosporine use in patients with ITP also receiving vincristine may cause predisposition to neutropenia; additional monitoring for myelosuppression is warranted when these drugs are administered concurrently.5
Correct ResponseProceed with CautionMycophenolate mofetil has been increasingly used as an adjunctive immunosuppressant (most often with glucocorticoids) and is metabolized to mycophenolic acid, which inhibits inosine monophosphate dehydrogenase necessary for purine synthesis and lymphocyte proliferation.6 GI adverse effects are common; myelosuppression, hepatotoxicity, and dermatologic reactions are less common but may require additional therapeutic monitoring.7 In humans, concurrent administration of mycophenolate mofetil and antacids impaired immunosuppressive efficacy, as mycophenolate mofetil requires an acidic environment for conversion into active metabolites.8 Although the significance of this interaction has not been evaluated in dogs, these drugs should be administered separately when used concurrently.
Correct ResponseProceed with CautionAzathioprine is an antimetabolite immunosuppressant often used in conjunction with glucocorticoids for treatment of immune-mediated diseases and has been associated with hepatotoxicity and myelosuppression, especially when initial therapeutic doses are administered for prolonged periods.1,9 Reported tapering schedules should therefore be followed, and CBC and liver values should be intermittently monitored during therapy. German shepherd dogs were overrepresented in a study of azathioprine-associated toxicoses, especially development of hepatotoxicity.9
Correct ResponseSafeVincristine is a vinca alkaloid chemotherapeutic agent that disrupts microtubules in rapidly dividing cells. Vincristine administered at low doses increases circulating platelets by accelerating fragmentation from megakaryocytes.10 These prematurely released platelets are functional when entering circulation, supporting vincristine as a first-line therapy for patients with ITP.11
Vincristine can cause extravasation injury; careful catheter placement is thus necessary prior to administration. Myelosuppression is also a known risk, and further dose reduction should be considered in dogs weighing >33.1 lb (15 kg), as the dosage for thrombocytopenia (0.02 mg/kg IV once) may fall in the oncologic range (0.5-0.75 mg/m2 IV once weekly). Risk for myelosuppression is also increased in dogs with the multidrug sensitivity gene (MDR1 gene, also known as ABCB1 gene) or when vincristine is used concurrently with cyclosporine.4,12
Correct ResponseDo Not UseMost patients with ITP and evidence of active hemorrhage lose blood across intact mucosal surfaces in the absence of overt ulceration. Antacids are often administered to increase gastric pH for protective purposes, as high-dose glucocorticoids increase risk for ulceration. Famotidine is an over-the-counter histamine type-2 receptor antagonist, and oral administration of this drug is ineffective for increasing gastric pH to a sustained level for therapeutic benefit.13,14 Famotidine is therefore not recommended when more effective oral acid-suppressing therapies are available.1,15
Correct ResponseProceed with CautionOmeprazole is an over-the-counter antacid proton pump inhibitor. Oral omeprazole administration results in higher gastric pH than famotidine and is therefore recommended for gastroprotection in patients with GI ulceration.13,16 Omeprazole administration could be considered in patients with ITP for GI bleeding; however, bleeding is believed to be related to thrombocytopenia, with ulceration being less likely. Omeprazole should be discontinued once melena resolves. In addition, acid suppression may impact drug metabolism and reduce immunosuppression efficacy if omeprazole is administered concurrently with mycophenolate.8
Correct ResponseSafeAmoxicillin is a beta lactam antibiotic recommended for empiric treatment of clinical bacterial UTI.17 This therapy should be initiated while urine culture is pending; however, sterile sample collection via cystocentesis is unlikely in this thrombocytopenic patient. Based on history of infection and therapeutic response, therapy should be initiated because the patient is showing clinical signs and will soon be immunosuppressed. Therapeutic monitoring involves assessing improvement in clinical signs and a urine culture to document infection clearance once the platelet count is recovered.
Correct ResponseDo Not UseTrimethoprim/sulfadiazine is a potentiated sulfonamide antibiotic that may be used for empiric treatment of clinical bacterial UTI17; however, this class of antibiotics is associated with possible idiosyncratic autoimmune adverse effects, including thrombocytopenia.18