THIACETARSEMIDE SODIUM
Chemistry - A phenylarsenoxide, thiacetarsemide sodium is an organic arsenical compound. Thecommercially available injection is actually a combination of thiacetarsemide and p-arsenosobenzamide. It is available commercially in a 10 mg/ml (1%) solution and may also be knownas sodium thiacetarsemide.
Thiacetarsemide is effective against adult heartworms only and has no clinical efficacy againstmicrofilaria.
Uses, Indications - Thiacetarsemide is indicated for the removal of adult heartworms (D. Immitis)in dogs. The drug is also labeled to be given every 6 months to dogs when other larvacidal drugsare impractical to be administered. Use of thiacetarsamide is largely being supplanted bymelarsomine, as the latter drug has increased efficacy and a significantly lower incidence of seriousadverse effects.
Although not approved, thiacetarsemide has also been used to treat adult heartworms or hemobartenella in cats.
Animals with concurrent diabetes mellitus, gastrointestinal disease, renal disease (moderate) orhypoadrenocorticism should receive thiacetarsemide only with intensified monitoring.
Extreme care must be taken to avoid perivascular leakage (extravasation) when injecting this agent.
Fortunately most minor extravasation injuries are minor and result only in swelling and pain at thesite, but skin sloughing can occur. Topical treatment with hot packs and topical DMSO (or
DMSO/steroid product¯Synotic® q4-6h), and/or dexamethasone/saline infiltration has beensuggested should extravasation occur.
Microfilaricide therapy should not be started for approximately 4 weeks after thiacetarsemide oruntil the clinical complications of thiacetarsemide-related therapy have subsided.
No specific information was located regarding this drug's effects on developing fetuses. If possible, treatment with thiacetarsemide should be postponed until after parturition.
Because heartworm disease can cause significant heart, pulmonary, kidney and liver damage, treatment should be started as soon as possible to both reduce the long-term sequelae associatedwith the disease and to maximize the animal's health status to improve toleration of the therapy.
Vomiting after dosing is the most common adverse reaction seen with thiacetarsemide and usuallyoccurs after the first or second injection. Emesis alone is not an indication to halt therapy, unlessother signs or symptoms (e.g., anorexia, depression, etc.) develop.
Nephrotoxicity may occur after thiacetarsemide therapy, with tubular casts seen in the urinesediment most commonly noted. Casts alone are generally not an indication that therapy must behalted, but in conjunction with other symptoms may be an indicator to stop therapy. Azotemia isuncommon during thiacetarsemide therapy and treatment may usually be continued if BUN remainsbelow 100 mg/dl as long as the patient receives adequate fluid and electrolyte replacement duringand after treatment.
Hepatotoxicity can occur during thiacetarsemide therapy, but the mechanism of its hepatotoxiceffects are unknown. Approximately 20% of patients receiving thiacetarsemide acquire increasedserum ALT's and Alkaline Phosphatase, but there are no factors that have been determined to bepredictive for hepatotoxicity development. Signs and symptoms can occur within 1-3 days afterdosing and can be acute in onset. These can include: anorexia, vomiting, depression, bilirubinuria, hyperbilirubinemia/icterus, melena, stupor, coma or death. Bilirubinuria is often the first sign ofimpending hepatoxicity. Gross bilirubinuria seen after the first or second injection is usually anindication to stop therapy. Should bilirubinuria be seen after the third injection, therapy may usuallybe continued unless other signs/symptoms are seen. Should liver toxicity occur, thiacetarsemideshould be discontinued and supportive/symptomatic treatment for liver disease be instituted asnecessary.
Patients whose therapy is aborted because of the onset of acute adverse effects should not beretreated for 4 weeks. At that time, therapy may be reconsidered, often without a recurrence ofadversity.
After thiacetarsemide treatment, adult worms begin to die within days and continue to die over a 3week period with resultant degrees of pulmonary artery emboli developing. The caudal lung lobesare routinely affected. Dogs with pre-existing pulmonary emboli, periarterial granulomas or severepulmonary artery enlargement are at greatest risk to develop severe complications. Signs/symptomsof embolic disease generally begin 5-7 days after treatment is completed and usually peak at 10-14days. Early symptoms noted include coughing, fevers, anorexia and lethargy. Dyspnea, high feversor hemoptysis are signs of severe pulmonary emboli and/or preexisting pulmonary disease. Tominimize the morbidity/mortality associated with pulmonary embolic disease, animals should bekept on strict cage rest, usually for a month following therapy. Aspirin at doses of 5 - 10 mg/kg POonce daily (see Aspirin monograph for more information) has been recommended in animals withsevere pulmonary artery disease to reduce thiacetarsemide-induced pulmonary effects, but aspirinmay exacerbate pulmonary parenchymal disease in some animals and cause additional clottingproblems should thrombocytopenia develop (see below).
Glucocorticoids (Predniso(lo)ne 0.5 - 1 mg/kg PO bid in decreasing doses over 7-14 days) havealso been recommended to treat symptoms associated with pulmonary thromboembolism afterthiacetarsemide therapy, but its use is controversial (see Drug Interactions section below).
Thrombocytopenia is common and is seen from 5-21 days after therapy is completed. Plateletcounts usually reach their nadir at 10-14 days. Aspirin therapy should be cut back or stopped ifplatelet counts decrease below 50, 000/mm3 or if hemoptysis develops. Vincristine (0.4 mg/m2 IVonce) has been suggested to be given if platelet counts approach 50, 000/ mm3 to stimulate plateletproduction. Disseminated Intravascular Coagulation (DIC) is possible and often precedes death.
Storage, Stability, Compatibility
Thiacetarsemide should be stored in the refrigerator (2°-8°C)and protected from light or freezing. The manufacturer recommends discarding opened containersfrom the refrigerator after 3 months. If the solution develops a yellow or orange color or ifprecipitates are seen, the solution should be discarded.Pharmacology - THIACETARSEMIDE SODIUM
The exact mechanism of action of thiacetarsemide is not known. It is believed theadulticidal activity of the compound is due to an arsenical moiety that reacts with sulfhydryl groupsin essential enzyme systems and is not due directly to the elemental arsenic. There is evidence thatworm mortality is increased the greater the length of time it is exposed at effective concentrations tothe compound and is not increased by obtaining higher thiacetarsemide blood levels.Thiacetarsemide is effective against adult heartworms only and has no clinical efficacy againstmicrofilaria.
Uses, Indications - Thiacetarsemide is indicated for the removal of adult heartworms (D. Immitis)in dogs. The drug is also labeled to be given every 6 months to dogs when other larvacidal drugsare impractical to be administered. Use of thiacetarsamide is largely being supplanted bymelarsomine, as the latter drug has increased efficacy and a significantly lower incidence of seriousadverse effects.
Although not approved, thiacetarsemide has also been used to treat adult heartworms or hemobartenella in cats.
Pharmacokinetics - THIACETARSEMIDE SODIUM
After IV injection in dogs, thiacetarsemide has an elimination half-life ofabout 43 minutes and a clearance of approximately 200 ml/kg/min, but significant interpatientvariation exists. Thiacetarsemide is metabolized and excreted via the bile into the feces and also inthe urine. Approximately 85% of the dose is recovered within 48 hours, primarily in the feces(66%). The drug is widely distributed in the body, but concentrates in the liver and to a lesserextent, the kidneys. Adult heartworms concentrate the drug in quantities greater than the liver.Contraindications, Precautions, Reproductive Safety
Because of the serious consequencesthat may occur as a result of thiacetarsemide treatment, animals with significantantly impairedhepatic, renal (azotemia, protein-losing nephropathy), cardiopulmonary (e.g., right heart failure, venacaval syndrome, pulmonary thromboembolism, allergic pneumonitis) systems or in DIC shouldgenerally not be given (at least temporarily) thiacetarsemide. The manufacturer recommendssurgically removing worms from the vena cava if they are blocking this vessel before startingtherapy.Animals with concurrent diabetes mellitus, gastrointestinal disease, renal disease (moderate) orhypoadrenocorticism should receive thiacetarsemide only with intensified monitoring.
Extreme care must be taken to avoid perivascular leakage (extravasation) when injecting this agent.
Fortunately most minor extravasation injuries are minor and result only in swelling and pain at thesite, but skin sloughing can occur. Topical treatment with hot packs and topical DMSO (or
DMSO/steroid product¯Synotic® q4-6h), and/or dexamethasone/saline infiltration has beensuggested should extravasation occur.
Microfilaricide therapy should not be started for approximately 4 weeks after thiacetarsemide oruntil the clinical complications of thiacetarsemide-related therapy have subsided.
No specific information was located regarding this drug's effects on developing fetuses. If possible, treatment with thiacetarsemide should be postponed until after parturition.
Adverse Effects, Warnings
Adverse effects that can develop with thiacetarsemide therapy can besevere and life-threatening. With the exception of azotemic patients, there is apparently nocorrelation between any patient factors (age, sex, breed) and the incidence of adverse effects.Because heartworm disease can cause significant heart, pulmonary, kidney and liver damage, treatment should be started as soon as possible to both reduce the long-term sequelae associatedwith the disease and to maximize the animal's health status to improve toleration of the therapy.
Vomiting after dosing is the most common adverse reaction seen with thiacetarsemide and usuallyoccurs after the first or second injection. Emesis alone is not an indication to halt therapy, unlessother signs or symptoms (e.g., anorexia, depression, etc.) develop.
Nephrotoxicity may occur after thiacetarsemide therapy, with tubular casts seen in the urinesediment most commonly noted. Casts alone are generally not an indication that therapy must behalted, but in conjunction with other symptoms may be an indicator to stop therapy. Azotemia isuncommon during thiacetarsemide therapy and treatment may usually be continued if BUN remainsbelow 100 mg/dl as long as the patient receives adequate fluid and electrolyte replacement duringand after treatment.
Hepatotoxicity can occur during thiacetarsemide therapy, but the mechanism of its hepatotoxiceffects are unknown. Approximately 20% of patients receiving thiacetarsemide acquire increasedserum ALT's and Alkaline Phosphatase, but there are no factors that have been determined to bepredictive for hepatotoxicity development. Signs and symptoms can occur within 1-3 days afterdosing and can be acute in onset. These can include: anorexia, vomiting, depression, bilirubinuria, hyperbilirubinemia/icterus, melena, stupor, coma or death. Bilirubinuria is often the first sign ofimpending hepatoxicity. Gross bilirubinuria seen after the first or second injection is usually anindication to stop therapy. Should bilirubinuria be seen after the third injection, therapy may usuallybe continued unless other signs/symptoms are seen. Should liver toxicity occur, thiacetarsemideshould be discontinued and supportive/symptomatic treatment for liver disease be instituted asnecessary.
Patients whose therapy is aborted because of the onset of acute adverse effects should not beretreated for 4 weeks. At that time, therapy may be reconsidered, often without a recurrence ofadversity.
After thiacetarsemide treatment, adult worms begin to die within days and continue to die over a 3week period with resultant degrees of pulmonary artery emboli developing. The caudal lung lobesare routinely affected. Dogs with pre-existing pulmonary emboli, periarterial granulomas or severepulmonary artery enlargement are at greatest risk to develop severe complications. Signs/symptomsof embolic disease generally begin 5-7 days after treatment is completed and usually peak at 10-14days. Early symptoms noted include coughing, fevers, anorexia and lethargy. Dyspnea, high feversor hemoptysis are signs of severe pulmonary emboli and/or preexisting pulmonary disease. Tominimize the morbidity/mortality associated with pulmonary embolic disease, animals should bekept on strict cage rest, usually for a month following therapy. Aspirin at doses of 5 - 10 mg/kg POonce daily (see Aspirin monograph for more information) has been recommended in animals withsevere pulmonary artery disease to reduce thiacetarsemide-induced pulmonary effects, but aspirinmay exacerbate pulmonary parenchymal disease in some animals and cause additional clottingproblems should thrombocytopenia develop (see below).
Glucocorticoids (Predniso(lo)ne 0.5 - 1 mg/kg PO bid in decreasing doses over 7-14 days) havealso been recommended to treat symptoms associated with pulmonary thromboembolism afterthiacetarsemide therapy, but its use is controversial (see Drug Interactions section below).
Thrombocytopenia is common and is seen from 5-21 days after therapy is completed. Plateletcounts usually reach their nadir at 10-14 days. Aspirin therapy should be cut back or stopped ifplatelet counts decrease below 50, 000/mm3 or if hemoptysis develops. Vincristine (0.4 mg/m2 IVonce) has been suggested to be given if platelet counts approach 50, 000/ mm3 to stimulate plateletproduction. Disseminated Intravascular Coagulation (DIC) is possible and often precedes death.