STELFONTA 1 Mg/mL: Product Information (Page 2 of 4)

PRECAUTIONS

STELFONTA has not been evaluated in dogs with signs of systemic disease due to the mast cell tumor(s).

STELFONTA is not intended for the treatment of metastatic mast cell tumors.

The safe and effective use of STELFONTA has not been evaluated for simultaneous treatment of more than one mast cell tumor.

The safe and effective use of STELFONTA has not been evaluated in dogs with a mast cell tumor volume >10 cm3.

Use STELFONTA with caution in tumors located within mucocutaneous regions (e.g., eyelids, vulva, prepuce, and anus) as tumor necrosis could cause a change in morphology of the mucocutaneous region resulting in loss of functional integrity.

Use STELFONTA with caution in mast cell tumors with significant ulceration as leakage of the drug from the ulcerated area may occur following treatment potentially reducing effectiveness.

The safe use of STELFONTA has not been evaluated in dogs with concurrent diseases that may result in delayed wound healing.

After treatment with STELFONTA, dogs may require additional care of the treated site to aid in the healing process. An Elizabethan collar or a non-constricting dry gauze bandage may be needed to prevent the dog from self-traumatizing the treated site.

After treatment with STELFONTA, separation from other household animals may be necessary to prevent grooming and trauma to the treated site.

The safe use of STELFONTA under conditions of use has not been evaluated in dogs younger than 3.5 years old.

The safe use of STELFONTA has not been evaluated in dogs that are pregnant, lactating, or intended for breeding.

ADVERSE REACTIONS

Human Exposure

There was one human exposure during the field study where the veterinarian had a needle stick injury to the thumb at completion of tumor treatment and was injected with an unknown amount of STELFONTA. The incident resulted in pain and necrosis of the center of the thumb at the point of needle stick. The wound healed over a period of three months. See Pictures 1 and 2 below. A separate needle stick injury was reported with a maximum potential dose of 0.1 mL tigilanol tiglate into the distal extremity of the left index finger, resulting in a localized burning sensation, local inflammation, bruising, muscular pain up the left arm, and localized tissue necrosis. Muscular pain resolved in the first 12-24 hours and the wound healed in 8 weeks. There have been other needle stick injuries reported, with at least one injection into a thumb, with minimal (stinging, pain, and swelling) to no adverse events associated with these accidental self-injections.

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Field Study

In a well-controlled, multi-center, randomized, double-masked field study evaluating the effectiveness and safety of STELFONTA for the treatment of cutaneous and subcutaneous mast cell tumors in dogs, 117 dogs treated with STELFONTA and 42 dogs receiving sham treatment (untreated control) were evaluated for safety. Eighty-one dogs were treated with STELFONTA on Day 0. Thirty-six previously untreated control dogs were treated with STELFONTA on Day 30. In addition, 18 dogs treated with STELFONTA on Day 0 had the same tumor re-treated with STELFONTA on Day 30 due to incomplete response. The most common adverse reactions included wound formation, injection site pain, lameness in the treated limb, vomiting, diarrhea, and hypoalbuminemia. Wound formation, vomiting, and diarrhea were mainly observed within the first 7 to 10 days after treatment. Injection site pain and lameness in the treated leg were mainly observed within the first 2 days after treatment. Hypoalbuminemia was mainly observed within the first 28 days after treatment. All dogs received concomitant medications as noted in the Effectiveness section. The adverse reactions during the study are summarized in Table 2 below.

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a There was a statistically significant decrease in albumin and albumin/globulin ratios at Day 7 in the STELFONTA group compared to the control group. The hypoalbuminemia ranged from 2.0 to 2.6 g/dL (reference range 2.7-3.9 g/dL). Note: If an animal experienced the same adverse reaction more than once, onlythe highest grade was tabulated.

Adverse reactions were graded using the Veterinary Co-operative Oncology Group – Common Terminology Criteria for Adverse Events (VCOG-CTCAE).1 Most adverse reactions were Grade 1 (mild) or 2 (moderate). Grade 3 (severe) and 4 (life-threatening) adverse reactions in dogs treated with STELFONTA included: lameness in the treated limb (6 dogs), injection site pain (4 dogs), wound formation (3 dogs), lethargy/depression (3 dogs), anorexia (2 dogs), infection at injection site (1 dog), pruritis (1 dog), and tachycardia (1 dog).

Adverse reactions associated with use of the required concomitant corticosteroids were similarly reported in STELFONTA and untreated control
dogs and included elevated alkaline phosphatase, polyuria, and polydipsia.

Wound Formation

Tumor observations were conducted at 2, 4, 8, and 24 hours and 4 days after treatment. The 81 dogs treated with STELFONTA on Day 0 were reported most frequently with swelling, bruising, pain and heat at all tumor observation timepoints. The following were reported at 24 hours post treatment:

  • Swelling: 97.5% (79/81 dogs)
  • Bruising: 91.4% (74/81 dogs)
  • Pain: 69.1% (56/81 dogs)
  • Heat: 53.1% (43/81 dogs)

At 24 hours post treatment, intact skin was reported in 71.6% (58/81 dogs) of STELFONTA® (tigilanol tiglate injection) treated dogs. On Day 4 intact skin was reported in 17.3% (14/81 dogs) of STELFONTA treated dogs. On Day 4, the following observations were reported with the highest frequency:

  • Necrosis: 55.6% (45/81 dogs)
  • Crater pockets: 37.0% (30/81 dogs)
  • Exudate: 37.0% (30/81 dogs)
  • Eschar: 28.4% (23/81 dogs)
  • Ulceration: 11.1% (9/81 dogs)

A wound healing assessment was performed on the effectiveness dataset which included 80 dogs in the STELFONTA group and 38 dogs in the untreated control group. Wounds developed in 92.5% (74/80) of STELFONTA treated dogs and 2.6% (1/38) of untreated control dogs by Day 7. On Day 28, the presence of wounds was 40% (32/80) in the STELFONTA group and 2.6% (1/38) in the untreated control group. On Day 42 and Day 84, the presence of wounds was 27.1% (16/59) and 1.8% (1/57), respectively, in the STELFONTA group.

Exudate from the treated site including serous, serosanguinous, sanguineous, seropurulent, and purulent discharges were seen mainly on Day 7 and to a lesser extent on Day 14. Sloughing of the treated site was observed from Day 7 to Day 42, with decreasing frequency after Day 7. Peripheral pitting or non-pitting edema and erythema of the surrounding area were observed from Day 7 to Day 28, with decreasing intensity and frequency after Day 7. Necrotic eschar and epithelialization of the treated site was observed from Day 7 to Day 84, with decreasing frequency after Day 14. Granulation or hyper-granulation of the treated site was observed from Day 7 to Day 84, with decreasing frequency after Day 14.

The average wound size at Day 7 for a STELFONTA treated dog was 3.3 cm x 2.4 cm (original average tumor size 1.9 x 1.6 x 0.9 cm). On Day 28, the average wound size was 2.0 x 1.4 cm.

The largest total wound for a STELFONTA treated dog was reported seven days after treatment. The treated tumor was located on the left caudal stifle and the original tumor size measured 2.4 x 2.1 x 1.4 cm. The wound area initially consisted of three individual wounds recorded on the treated limb (both medial and lateral sides): 7.5 x 4.5 cm, 7.0 x 3.5 cm, and 11.5 x 7.0 cm. The wounds had reduced to 3.5 x 1.4 cm, 3.9 x 1.5 cm, and 9.7 x 4.3 cm 28 days after treatment, and 0.5 x 0.7 cm and 2.5 x 2.9 cm 42 days after treatment and were no longer present at 84 days after treatment.

One dog treated with STELFONTA was reported with an extensive wound formation (wound size 25.0 x 9.5 cm) with severe tissue slough (Grade 3) nine days after treatment of a mast cell tumor on the left metacarpal area (original tumor size 2.5 x 1.9 x 1.3 cm). The wound extended proximally up the leg to the shoulder and required bandaging of the leg and antibiotics. Scar contracture formed, requiring treatment under sedation to release the scar tissue. Clinical pathology abnormalities included elevated band neutrophils, anemia, and hypoalbuminemia. The wound had not fully healed by the end of the study 89 days after treatment. See pictures below comparing progression of this extensive
wound formation versus commonly observed wound progression.

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One dog treated with STELFONTA was reported with a bacterial infection and cellulitis in the right rear leg 9 days after treatment of a mast cell tumor on the right rear paw. There was bruising of the upper thigh and necrotic skin on the caudal right thigh and cranial aspect of the hock. Bloody discharge under the necrotic tissue revealed rod bacteria and toxic neutrophils. The dog was treated with intravenous fluids and antibiotics.

Systemic Mast Cell Degranulation and Death

Two dogs from two separate pilot studies died from a suspected mast cell degranulation reaction. Both dogs were treated with STELFONTA for a subcutaneous mast cell tumor located above the hock and did not receive the concomitant medications as prescribed.

In a pilot field study, one dog with a large (10 cm³) subcutaneous mast cell tumor on the right hip was treated with STELFONTA. The dog had a partial Response Evaluation Criteria in Solid Tumors Guideline (RECIST)2 response to the initial STELFONTA injection and was re-treated with STELFONTA, 30 days following the initial injection. The patient did not receive any of the recommended concomitant medications of prednisolone, chlorpheniramine and famotidine from 24 hours after the second STELFONTA injection. On Day 2 following the second STELFONTA injection, the dog became anorexic, painful, and lethargic and had marked swelling of the right hind limb extending to the chest with hemorrhagic, ruptured blisters near the hock joint. Blood work showed anemia, hypoproteinemia, liver enzyme elevations, and white blood cell changes (leukocytosis, neutrophilia, monocytosis, and thrombocytopenia). The dog was hospitalized, received a blood transfusion, and was administered intravenous fluids, prednisolone, chlorpheniramine and tramadol. Pitting edema progressed to the neck by four days following treatment. Despite supportive care, the dog died five days following treatment likely due to degranulation of the mast cell tumor and internal necrotic discharge of the tumor.

In a separate pilot field study, one dog with a moderate (2.53 cm3) subcutaneous mast cell tumor on the left caudal hindlimb was treated with STELFONTA. The dog was treated with chlorpheniramine and meloxicam on treatment day (Day 0) and Day 1 only. The dog did not receive further concomitant medication. On Day 3 the dog was lethargic and there was significant edema at the injection site. While intravenous fluid and antibiotic therapy was initiated on Day 3, the dog rapidly deteriorated and died on the following day likely due to degranulation of the mast cell tumor. Pathology findings included widespread cellulitis, panniculitis (likely of bacterial origin), and septic peritonitis.

To report suspected adverse reactions, to obtain a Safety Data Sheet (SDS), or for technical assistance, call 800-338-3659. For additional information about adverse drug experience reporting for animal drugs, contact the FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae.

INFORMATION FOR DOG OWNERS
Owners should be given the Client Information Sheet to read before STELFONTA is administered and should be advised to observe their dog for potential side effects, including signs of degranulation and excessive wound formation, as described in the sheet. Advise dog owners about possible adverse reactions, when to contact a veterinarian, and how to care for the treated tumor site. Some discharge from the site following treatment is expected. The site can be cleaned with warm water as necessary. Advise owners to wear disposable gloves when cleaning the area.

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