Rabacfosadine

Indications

TANOVEA is indicated for the treatment of lymphoma in dogs.

Dosage and Administration

Always provide the Client Information Sheet to the dog owner with each dose administration. Administer TANOVEA at 1 mg/kg body weight as a 30-minute intravenous infusion, once every three weeks, for up to five doses. Stepwise dose reductions to 0.8 mg/kg and 0.66 mg/kg or dose delays may be used to manage adverse reactions. TANOVEA is supplied as a sterile lyophilized powder for reconstitution before use. After reconstitution with 2 mL of 0.9% Sodium Chloride Injection, USP, the reconstituted solution contains 8.2 mg/mL of rabacfosadine. Reconstitution and administration of TANOVEA Wear chemotherapy-resistant gloves, goggles, and protective clothing in the preparation and administration of TANOVEA. Use aseptic technique in the preparation and administration of TANOVEA. Reconstitution instructions 1. Obtain the desired number of vials from the refrigerator. 2. Add 2 mL of 0.9% Sodium Chloride Injection, USP to the single-use vial. 3. Gently invert the vial several times until the drug has completely dissolved and the solution is particle free. 4. The solution should be clear without visible particulates. If particulates are observed, the solution should be discarded. Dilution for infusion and administration instructions 1. TANOVEA should be diluted for infusion within 4 hours of reconstitution. 2. Add the calculated volume of reconstituted TANOVEA (8.2 mg/mL) to 0.9% Sodium Chloride Injection, USP in a polyvinyl chloride (PVC) infusion bag or polypropylene infusion syringe to yield a total infusion volume of 2 mL/kg. 3. The volume of reconstituted TANOVEA should be calculated based on the exact weight of the dog. (See Table 1 . for example doses and administration volumes). 4. The infusion solution should be used within 24 hours of being added to the infusion bag or syringe and within 4 hours of being added to an intravenous transfer set. Protection from light is not needed. 5. Administer TANOVEA as a 30-minute intravenous infusion. Table 1. Example doses and volumes at 1 mg/kg. a TANOVEA can be administered to dogs less than 5 kg and greater than 40 kg. Always calculate the dose based on the exact weight of the dog. Dog weight (kg) Dog weight (lb) Dose (mg) Volume of reconstituted TANOVEA solution (mL) Volume 0.9% NaCl (mL) Total infusion volume (mL) Rate of infusion (mL/minute) 5 a 11 5 0.6 9.4 10 0.3 10 22 10 1.2 18.8 20 0.7 15 33 15 1.8 28.2 30 1.0 20 44 20 2.4 37.6 40 1.3 25 55 25 3.0 47.0 50 1.7 30 66 30 3.7 56.3 60 2.0 35 77 35 4.3 65.7 70 2.3 40 a 88 40 4.9 75.1 80 2.7 Compatibility of administration sets containing ethyl vinyl acetate (EVA) has not been evaluated.

Contraindications

Do not use in dogs with pulmonary fibrosis or a history of chronic pulmonary disease that could lead to fibrosis, such as chronic bronchitis (see WARNINGS ). Do not use in West Highland White Terriers due to a genetic predisposition for development of pulmonary fibrosis. Use with caution in other terrier breeds due to potential genetic predisposition for development of pulmonary fibrosis. Do not use in dogs that are pregnant, lactating, or intended for breeding. Rabacfosadine is cytotoxic and may cause birth defects and affect female and male fertility. TANOVEA has not been evaluated in pregnant, lactating, or breeding dogs.

Warnings

USER SAFETY WARNINGS: NOT FOR USE IN HUMANS. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. Do not store near food or with medications intended for use in humans. Do not eat, drink, or smoke while handling the product. CHILDREN SHOULD NOT COME INTO CONTACT WITH TANOVEA. Children should not come into contact with feces, urine, vomit, and saliva of treated dogs for 5 days after each treatment. Drug Handling and Administration Pregnant women, women who may become pregnant, and nursing women should not handle, prepare, or administer TANOVEA. Rabacfosadine is cytotoxic and may cause birth defects and affect female and male fertility. Use standard measures for the safe handling of all chemotherapeutic drugs. Refer to Occupational Safety and Health Administration (OSHA) for appropriate guidelines, recommendations, and regulations for handling antineoplastic agents. Do not come into direct contact with TANOVEA. Wear chemotherapy-resistant gloves, goggles, and protective clothing when handling or administering TANOVEA. After removing and disposal of gloves, wash hands immediately and thoroughly with soap and water. Accidental Exposure to TANOVEA In the case of accidental self-injection: o Remove glove. o Let the wound bleed a few drops of blood. o Rinse the wound thoroughly with tap water. o Seek medical advice immediately and show the package insert, label, or client information sheet to the physician. In case of accidental skin contact: o Wash the affected area immediately and thoroughly with soap and water. In the case of accidental eye exposure: o Remove contact lenses. o Rinse the eyes with large amounts of tap water (use eyewash station if present) for 10 minutes while holding back the eyelid. o Seek medical advice immediately and show the package insert, label, or client information sheet to the physician. In the case of accidental ingestion: o Seek medical advice immediately and show the package insert, label, or client information sheet to the physician. Handling of Excreta and Soiled Items Do not come into direct contact with the treated dog's feces, urine, vomit, and saliva for 5 days after each treatment with TANOVEA. When cleaning up feces, urine, vomit, and saliva, wear disposable chemotherapy-resistant gloves to collect the contaminated substances with disposable absorptive material (such as paper towels) and place them into a plastic bag. Carefully remove the gloves and place them in the bag, and tie or fasten it securely before general disposal. Wash hands immediately and thoroughly with soap and water afterwards. Do not wash any items soiled with feces, urine, vomit, and saliva from the dog for 5 days after each treatment with other laundry. Wear disposable chemotherapy-resistant gloves when handling the dog's toys, food bowl, and water bowl. Wash food and water bowls separately from other items for 5 days after each treatment. Accidental Exposure to Excreta In the case of direct skin contact with feces, urine, vomit, and saliva of dogs for 5 days after each treatment: o Wash the affected skin immediately and thoroughly with soap and water. ANIMAL SAFETY WARNINGS: TANOVEA is associated with life-threatening or fatal pulmonary fibrosis. The pulmonary fibrosis may be an idiosyncratic toxicity. Monitoring for signs of pulmonary dysfunction is recommended (see ADVERSE REACTIONS ).

Precautions

TANOVEA is associated with dermatopathies (e.g., otitis, alopecia, dermatitis, erythema, pruritus, hyperpigmentation, skin ulcerations, and bacterial skin infections) which can worsen with subsequent treatment (see ADVERSE REACTIONS ). Careful monitoring for changes in the skin and ears is recommended. Dose reductions and/or dose delays should be considered to mitigate dermatologic adverse reactions. TANOVEA can cause neutropenia with a nadir around seven days post-treatment. Dogs should be frequently monitored for evidence of neutropenia during treatment with TANOVEA (see ADVERSE REACTIONS and TARGET ANIMAL SAFETY ). Extravasation of TANOVEA may cause pain and/or tissue injury. If extravasation is suspected, discontinue infusion immediately. Monitor the site for evidence of injury; consider local and systemic treatment measures as needed. The safety and effectiveness of TANOVEA has not been evaluated in conjunction with other chemotherapeutic agents or other modalities for the treatment of lymphoma. The effect of concomitant medications on the metabolism of TANOVEA has not been evaluated.

Adverse Reactions

A randomized, placebo-controlled, masked, multicenter clinical field study evaluated the effectiveness and safety of TANOVEA for the treatment of lymphoma. One-hundred and twenty dogs received TANOVEA at a dose of 1 mg/kg, administered as a 30-minute intravenous infusion once every three weeks for one to five doses. Thirty-eight dogs received a placebo (saline) infusion. The Veterinary Cooperative Oncology Group - common terminology criteria for adverse events (VCOG-CTCAE) 1 definitions were used to grade the adverse reactions observed: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (death or euthanasia). Most adverse reactions were Grade 1 or 2. The adverse reactions observed in the study and number of dogs experiencing each adverse reaction is summarized in Table 2 below. The most common adverse reactions included diarrhea, decreased appetite, vomiting, lethargy, weight loss, and neutropenia. Though diarrhea, decreased appetite, vomiting, lethargy, and weight loss were observed in both groups, the incidence was higher in the TANOVEA group and there were more Grade 2 and 3 adverse reactions compared to the Placebo group. Table 2. Adverse Reactions Reported During the Field Study a Most neutropenias were Grade 1 or 2. However, eight instances of Grade 3 and three instances of Grade 4 neutropenia were reported. Neutropenia was reported seven days after treatment and returned to the normal range in all but two instances by the next cycle. b Represents combined terms of Otitis Externa and Otitis Not Otherwise Specified (NOS) c Pulmonary disorders included pulmonary fibrosis or possible pulmonary fibrosis (five dogs), pulmonary interstitial pattern (three dogs), pneumonia (three dogs), alveolar pattern on radiographs (two dogs), pneumomediastinum (one dog), pneumonitis (one dog), pulmonary infiltrates on radiographs (one dog). Some dogs were reported with more than one abnormality. d Masses included skin and subcutaneous masses e Glucosuria ranges from 1+ to 4+. In one dog, a 1+ ketonuria was reported at the same time as a 4+ glucosuria. f Digestive tract disorders NOS included regurgitation (three dogs) and abnormal stool color (three dogs). TANOVEA (n=120) Placebo (n=38) n % n % Diarrhea 105 87.5 19 50 Decreased appetite 82 68.3 15 39.5 Emesis 82 68.3 9 23.7 Lethargy 76 63.3 24 63.2 Weight loss 58 48.3 4 10.5 Neutropenia a 55 45.8 0 Polydipsia 40 33.3 6 15.8 Anorexia 34 28.3 7 18.4 Otitis b 31 25.8 0 Alopecia 30 25 2 5.3 Adipsia 29 24.2 5 13.2 Polyuria 29 24.2 2 5.3 Dermatitis 25 20.8 0 Increased appetite 24 20 6 15.8 Hypoalbuminemia 24 20 5 13.2 Anemia 20 16.7 3 7.9 Hematochezia 20 16.7 0 Dehydration 17 14.2 1 2.6 Nausea 15 12.5 2 5.3 Erythema 15 12.5 1 2.6 Pruritus 15 12.5 1 2.6 Hyperpigmentation 14 11.7 0 Leukopenia 14 11.7 0 Monocytosis 13 10.8 3 7.9 Elevated alanine aminotransferase (ALT) 13 10.8 2 5.3 Proteinuria 13 10.8 2 5.3 Pulmonary disorder c 13 10.8 0 Elevated creatine-kinase (CK) 12 10 1 2.6 Oliguria 12 10 1 2.6 Urinary tract infection 12 10 1 2.6 Cough 11 9.2 3 7.9 Increased blood urea nitrogen (BUN) or creatinine 11 9.2 2 5.3 Elevated aspartate aminotransferase (AST) 11 9.2 0 Neutrophilia 10 8.3 3 7.9 Hematuria 10 8.3 1 2.6 Mass d 10 8.3 0 Hyperthermia 9 7.5 4 10.5 Thrombocytopenia 9 7.5 3 7.9 Elevated symmetrical dimethylarginine (SDMA) 9 7.5 2 5.3 Hypocalcemia 9 7.5 2 5.3 Glucosuria e 9 7.5 0 Skin ulceration 9 7.5 0 Tachypnea 8 6.7 5 13.2 Dyspnea 7 5.8 5 13.2 Elevated total bilirubin 7 5.8 1 2.6 Hypokalemia 7 5.8 1 2.6 Bacterial skin infection 7 5.8 0 Desquamation 7 5.8 0 Leukocytosis 6 5 5 13.2 Pinnal irritation 6 5 1 2.6 Digestive tract disorders NOS f 6 5 0 Hypoproteinemia 6 5 0 The type and frequency of reported adverse reactions did not vary greatly by cycle of TANOVEA treatment. A single cycle was the day of treatment and the 20 days after treatment (total of 21 days). However, during Cycles 1 and 2 (after the first or second dose), the majority of adverse reactions were primarily related to gastrointestinal and constitutional signs (i.e. lethargy, weight loss), while dermatopathies began to occur more frequently in Cycles 3 through 5 (after the third through fifth dose). Serious Adverse Reactions Serious adverse events (SAEs) were reported in 20% of dogs in the TANOVEA group (24 of 120 dogs) and 13% of dogs in the placebo group (five of 38 dogs). In the 24 TANOVEA dogs, SAEs included pulmonary fibrosis (five dogs) and dermatopathy (six dogs) as described below. Other SAEs included three cases of progressive disease (Grade 5), three cases of unrelated neoplasia/comorbidities, and one case each of hepatopathy (Grade 3), renal insufficiency (Grade 3), neutropenia (Grade 4), nausea (Grade 3), lymph node abscess (Grade 3), colitis (Grade 3), and hematochezia (Grade 3). Pulmonary Fibrosis Five dogs in the TANOVEA group developed severe adverse reactions associated with pulmonary fibrosis. The clinical signs included dyspnea, tachypnea, and orthopnea. Four of these dogs also had pneumomediastinum, pneumothorax, and/or emphysema diagnosed radiographically. All five dogs had radiographic findings that could be associated with pulmonary fibrosis along with accompanying pulmonary clinical signs. All five dogs were euthanized (four dogs) or died (one dog) due to the pulmonary fibrosis (either during the study or after removal from the study). Two of these dogs had a histologic confirmation of fibrosis on necropsy. The median time from randomization to first detection of clinical signs was 87 days (range 84 to 140) and the median time from randomization to death was 127 days (range 112 to 172). At the time of withdrawal (due to adverse reactions), all five dogs had a complete response to treatment. Pulmonary fibrosis may be an idiosyncratic adverse reaction with an unknown mechanism of action. Dermatopathy Over half of the patients (67/120 dogs) treated with TANOVEA experienced one or more dermatologic adverse reactions during their treatment. These adverse reactions were predominantly Grade 1 and primarily included otitis, alopecia, dermatitis, erythema, pruritus, hyperpigmentation, skin ulcerations, and bacterial skin infections. Dermatologic adverse reactions typically presented by Cycle 3 (after the third dose), suggesting a cumulative effect of TANOVEA-associated dermatopathy. Dose reductions and dose delays were implemented to mitigate dermal adverse reactions. Six dogs in the TANOVEA group had Grade 3 or Grade 4 dermal adverse reactions which appeared in Cycle 2 (two dogs), Cycle 3 (three dogs), and Cycle 5 (one dog). Grade 3 adverse reactions included bacterial skin infections, skin ulcerations, desquamation, and dermatitis. Grade 4 adverse reactions included skin ulceration (severe erythema and ulceration of skin on limbs, ventrum, and foot pads) and desquamation (moist desquamation along the inguinal region and encompassing perivulvar area). Euthanasia Nine dogs in the TANOVEA group (8%) and two dogs in the placebo group (5%) were euthanized while on study. Reasons for euthanasia included four cases of progressive lymphoma (one with multiple comorbidities and pre-existing dermatopathy), two cases of pulmonary fibrosis, one case of probable hemangiosarcoma, one case of pyelonephritis/renal failure, and one case was unspecified. An additional three dogs died/were euthanized after withdrawal from the study due to suspected pulmonary fibrosis. One dog was euthanized after withdrawal from the study due to sepsis secondary to dermatopathy. Dose Reductions and Dose Delays Twenty-nine dogs in the TANOVEA group dogs received dose reductions (from 1 to 0.8 mg/kg), which were typically employed on the second to fourth dose of TANOVEA. Four dogs received a second stepwise reduction (from 0.8 to 0.66 mg/kg), which were employed on the third to fifth dose. The primary reason for dose reduction was gastrointestinal toxicity (diarrhea, vomiting, nausea), followed by dermatopathies, weight loss, anorexia/hyporexia, neutropenia, thrombocytopenia, and hypoalbuminemia. All dogs continued on the reduced dose(s) for the remainder of the study or until withdrawn. Fourteen dogs in the TANOVEA group had a dose delay, which typically was one week beyond the intended treatment day. The primary reason cited in all cases was dermatopathy, and one case also cited weight loss. Eight dogs had both a dose reduction and delay, primarily attributable to dermatopathies. Infusion Site Observations On the day of treatment, two incidences of bruising were reported in dogs in the TANOVEA group. Infusion site observations seven days after treatment in dogs in the TANOVEA group included pigmentation (seven incidences), scaling (five incidences), erythema (three incidences), and swelling (two incidences). Conditional Approval Experience: Rabacfosadine for injection was conditionally approved and marketed from 2016-2021 under the proprietary name TANOVEA-CA1. The adverse events voluntarily reported for TANOVEA-CA1 (i.e., reports not associated with the clinical study) were similar to those described in the ADVERSE REACTIONS section above.

Description

TANOVEA (rabacfosadine for injection) is an acyclic nucleotide phosphonate. The molecular weight of rabacfosadine is 526.5 g/mole. The empirical formula is C 21 H 35 N 8 O 6 P. The structural formula is: TANOVEA is supplied as a sterile, white to off-white lyophilized powder in the form of a cake contained in a 3 mL amber glass vial. Each single-use vial contains 16.4 mg of rabacfosadine, present as the succinate salt, along with 20 mg of mannitol and 1.6 mg of citrate as excipients. Structural Formula

Information for Owners

Always provide the Client Information Sheet and review it with the dog owner or person responsible for care of the dog. Advise dog owners about possible adverse reactions, when to contact a veterinarian, and how to clean up any feces, urine, vomit, or saliva from dogs treated with TANOVEA. The Client Information Sheet also contains warnings for humans and what to do in case of accidental human exposure to TANOVEA.

Storage

Unopened vials: Store the vials refrigerated at 2 °C to 8 °C (36 °F to 46 °F). Retain in the original package to protect from light. After reconstitution: Store at 20 °C to 25 °C (68 °F to 77 °F). TANOVEA should be diluted for infusion within 4 hours of reconstitution. The infusion solution should be used within 24 hours of being added to the infusion bag or syringe and within 4 hours of attachment to an intravenous administration set. Protection from light is not needed. Disposal: Dispose of any unused product or waste materials in accordance with proper procedures for cytotoxic drugs.

FDA adverse event reports

The FDA Center for Veterinary Medicine publishes the adverse event reports it receives through openFDA. The counts below are the reports naming rabacfosadine as an active ingredient for each species this label names, as returned on 2026-09-16, coded by the VeDDRA reaction term the reporter chose. Reactions are counted per report, so one report can appear under several terms.

These are counts, not rates. Reporting is voluntary, the number of animals treated is not known, and a widely used product accumulates reports for that reason alone. A report records that an event followed a dose; it does not establish that the product caused it. The counts say nothing about how one product compares with another.