Tigilanol tiglate

Indications

STELFONTA ® injection is indicated for use in dogs for the treatment of: non-metastatic cutaneous mast cell tumors non-metastatic subcutaneous mast cell tumors located at or distal to the elbow or the hock

Dosage and Administration

ALWAYS PROVIDE THE CLIENT INFORMATION SHEET TO THE DOG OWNER BEFORE DOSE ADMINISTRATION. Carefully consider the potential benefits and risks of STELFONTA before deciding to use STELFONTA. It is crucial to follow the dosing and administration instructions to use the product safely and effectively (see Boxed Warning, Animal Warnings, Precautions, Clinical Pharmacology ). Concomitant medications Administer the following medications to decrease the potential for severe systemic adverse reactions from mast cell degranulation (see Effectiveness ). Do not underdose concomitant medications and confirm that the dog owner administered the medications as prescribed prior to the date of STELFONTA treatment. Corticosteroid (oral prednisone or prednisolone at anti-inflammatory dose): Start medication 2 days prior to STELFONTA treatment at a dose of 0.5 mg/kg orally every 12 hours for 7 days (2 days prior, the day of treatment, and 4 days after treatment), then 0.5 mg/kg orally every 24 hours for an additional 3 days (10 days total). H1 receptor blocking agent (oral diphenhydramine): Start medication on the day of STELFONTA treatment at a dose of 2 mg/kg orally every 12 hours and continue for a total of 8 days (the day of treatment and 7 days after treatment). H2 receptor blocking agent (oral famotidine): Start medication on the day of STELFONTA treatment at a dose of 0.5 mg/kg orally every 12 hours and continue for a total of 8 days (the day of treatment and 7 days after treatment). Fill out the medication schedule (drug name, dose, route of administration, date) on the Client Information Sheet to help the dog owner administer these medicaitons correctly. Consider administering analgesic medicaitons prior to, during, and after treatment with STELFONTA. Dosing Instructions Administer STELFONTA as an intratumoral injection at a dose of 0.5 mL per cm 3 of tumor volume, as determined by the following calculations: STEP 1. Calculate Tumor Volume: Measure the tumor dimensions (Length, Width and Height) with calipers on the day of STELFONTA injection. Determine the Tumor Volume using the midified ellipsoid formula to account for the tumor shape (cube volume x 1/2) as below: Confirm the Tumor Volume does not exceed 10 cm3. Do not use STELFONTA if tumor volume is >10 cm3. STEP 2. Ca lculate the mL of STELFONTA to inject: Confirm the dose of STELFONTA does not exceed 0.25 mL/kg body weight of body weight and do not use if the calculate dose exceeds this. Do not exceed 5 mL per dog, regardless of tumor volume or body weight. The minimum dose of STELFONTA is 0.1 mL, regardless of tumor volume or body weight. If the calculated dose is <0.1 mL, administer 0.1 mL. Confirm the calculate dose of STELFONTA using the online dosing calculator at www.stelfonta.com/calculator (or scan the QR code below). Administration of STELFONTA: Sedation may be necessary to safely and accurately administer STELFONTA to decrease the chance of accidental self-injection. Wear gloves, eye protection, and lab coat or gown in the preparation and administration of STELFONTA. Care should be taken to restrict injections to the tumor only. STELFONTA should not be injected into the margins, beyond the periphery, or deep to the tumor. Shave the tumor site. Avoid manipulation of the tumor. Draw the calculated volume of STELFONTA into a sterile Luer-lock syringe with a 23 gauge needle. Identify an appropriate injection point on the edge of the tumor. See Figure 1. Insertion of the needle depends on the tumor’s location, form, and appearance. If a tumor protrudes above the surface of the skin, insert the needle at an oblique angle of approximately 45°. Insert and embed the needle in the tumor through a single injection site and draw the syringe plunger back slightly to ensure STELFONTA is not injected into a blood vessel. While applying even pressure on the syringe plunger move the needle back and forth in a fanning manner to inject STELFONTA into the tumor. See Figure 1. The drug should fully perfuse the entire tumor. When the total dose of STELFONTA has been administered, pause to allow tissue dispersion before removing the needle from the tumor. Pull back on the syringe plunger to create a small negative pressure before removing the needle to minimize leakage from the injection site. After the needle is withdrawn, apply light pressure for 30 seconds over the needle exit hole using a gloved finger. If leakage does occur, rinse injection site with saline to wash STELFONTA from the skin surface. Do not readminister. To minimize risk of accidental self-injection, do not recap the needle. Disposeof the needle and syringe. image description image description image description image description

Contraindications

Do not inject STELFONTA into subcutaneous mast cell tumors located above the elbow or hock (e.g. on the body, head, or neck). This may result in accumulation of necrotic debris in the subcutaneous space increasing the risk of systemic adverse reactions, including death, from mast cell degranulation (see Adverse Reactions ).

Warnings

Human Safety Warnings NOT FOR USE IN HUMANS. KEEP THIS AND ALL MEDICATIONS OUT OF REACH OF CHILDREN. Caution is required during treatment to avoid accidental self-injection. Dogs undergoing treatment with STELFONTA should be adequately restrained and sedation used if necessary. Use a Luer-lock syringe to administer STELFONTA. Do not recap the needle. Accidental self-injection may result in local inflammatory reactions, including swelling, redness and severe wound formation. In case of accidental self-injection, immediately rinse the area with water, seek medical advice immediately, and show the package insert to the physician. Wear personal protective equipment consisting of disposable gloves, protective eye wear, and a lab coat or gown when handling STELFONTA. STELFONTA is an irritant and accidental exposure to skin, eye, or by ingestion should be avoided. In case of dermal or ocular exposure, repeatedly wash the exposed skin or eye with water. If wearing contacts, rinse the eyes first then remove contacts and continue to rinse with water. If symptoms such as local signs of redness and swelling occur, or if there has been ingestion, seek the advice of a physician and show them the package insert. Limited data is available on the potential teratogenic effects of STELFONTA. Therefore, STELFONTA should not be administered by women who are pregnant or planning to become pregnant. People with known hypersensitivity to tigilanol tiglate or to any of the excipients should avoid contact with STELFONTA. Animal Safety Warnings Dogs should be monitored during and for 5-7 days after intratumoral treatment with STELFONTA for signs of systemic mast cell degranulation such as vomiting, diarrhea, lethargy, anorexia/hyporexia, altered breathing, hypotension, urticaria, edema at or away from the treated site, or bruising at or away from the treated site. If signs are observed, appropriate treatment should be started immediately. Always administer the concomitant medications (prednisone or prednisolone, diphenhydramine, and famotidine), as directed in the Dosage and Administration section, with STELFONTA in order to decrease the potential for severe systemic adverse reactions, including death, from mast cell degranulation (see Adverse Reactions ). Treatment with STELFONTA causes tumor necrosis which is part of the mechanism of action of the drug. Bruising, heat, pain, and swelling may begin at the site within 2 hours of treatment. By day 7 after treatment, wound formation including full thickness dermal necrosis with exudate, peripheral tissue edema, erythema, skin discoloration, tissue sloughing, and necrotic eschar may occur. STELFONTA can induce a substantial local inflammatory reaction which may result in severe pain and swelling, bruising, cellulitis, extensive wound formation, and severe tissue sloughing extending away from the treated site. Consider administering analgesic medications prior to, during, and after treatment with STELFONTA in addition to the use of corticosteroids and both H1 and H2 receptor blocking agents. Amputation of an extremity has been reported in some cases (see Post-Approval Experience ). Some dogs require wound care and pain management for an extended period. Do not inject STELFONTA into normal subcutaneous tissue or adjacent tissues (e.g. beyond tumor margins) because severe edema, erythema and necrosis of the injected tissue may occur.

Precautions

STELFONTA is not intended for the treatment of metastatic mast cell tumors. 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. Some discharge from the site following treatment is expected. Wear disposable gloves to clean the site with warm water as necessary. After treatment with STELFONTA, dogs may require additional care of the treated site to aid in the healing process, especially if there is extensive wound formation (see Animal Safety Warnings and Post-Approval Experience ). Tongue lesions have been reported (see Post-Approval Experience ). Do not allow the dog to lick the site for the first few days after treatment. Discourage excessive licking for the remainder of the healing period. 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. STELFONTA has not been evaluated in dogs with signs of systemic disease due to the mast cell tumor(s). The safe and effective use of STELFONTA has not been evaluated for sumultaneous treatment of more than one mast cell tumor. The safe use of STELFONTA has not been evaluated in dogs with concurrent diseases that may result in delayed wound healing. 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. 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 1 below. 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 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. 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 cm 3 ) 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. Post-Approval Experience (2024) The following adverse events are based on post-approval adverse drug experience reporting for STELFONTA. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data. The following adverse events reported in dogs are listed in decreasing order of reporting frequency: Injection site reactions (wound formation, swelling, pain, necrosis, skin sloughing, bleeding, bruising and erythema). These injection site reactions varied in severity and ranged from localized to extending away from the injection site. Other signs reported include anorexia, lameness, lethargy, diarrhea, vomiting, fever, tachypnea/dyspnea, and ulceration or necrosis of tongue. In some cases, when STELFONTA was used to treat a mast cell tumor on an extremity, the entire extremity became swollen, painful, and developed tissue sloughing. Some of these cases resulted in amputation. In some cases, death (including euthanasia) has been reported as an outcome of the adverse events reported above.

Description

The active ingredient for tigilanol tiglate injection is a phorbol ester that activates alpha, beta I, beta II, and gamma isoforms of protein kinase C. The chemical name is (4S,5S,6R,7S,8R,9R,10S,11R,12R,13S,14R)-12-(2E)-2-methylbut-2-enoatyl-13- [(2S)-2-methylbutyroyl]-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tigliaen-3-one. The molecular formula is C30H42O10 and its molecular weight is 562.65 g mol-1. Each mL of STELFONTA contains 1 mg tigilanol tiglate and sterile water for injection (60% v/v), propylene glycol (40% v/v), sodium acetate (<0.1% w/v), and glacial acetic acid (<0.1% w/v). The chemical structure for tigilanol tiglate is: image description

Information for Owners

Owners should be given the Client Information Sheet (CIS) to read before STELFONTA is administered. Owners should be advised to observe their dog for potential side effects, including signs of systemic mast cell degranulation, excessive pain and swelling, and excessive wound formation. Advise dog owners about the possibility of severe side effects, including amputation and death, 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. Discuss the importance of the concomitant medications and ensure that the owner is aware of the schedule of medications that should be administered. The owner should use the Medication Schedule on the CIS to keep track of the medications they have administered. Discuss with owners that they should not allow the dog to lick the site for the first few days after treatment and they should discourage excessive licking for the remainder of the healing period. An Elizabethan Collar may be utilized to prevent self-trauma of the treatment site. After treatment the owner may need to separate the dog from other household animals to prevent grooming and trauma to the treated site. image description image description image description

Storage

Store STELFONTA vials refrigerated at 2°C to 8°C (35°F to 46°F). Do not freeze. Keep the vial in the carton at all times to protect the vial from light. For single use only. Dispose of any unused product in accordance with disposal for routine medical waste.

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 tigilanol tiglate 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.