Laverdia-CA1 (Verdinexor) Tablets 2.5mg (50 tablets)

Laverdia-CA1 is a conditionally approved treatment for dogs with blood cancer.

It's the first prescription treatment for the condition that comes in tablet form, and it can be administered at home. It works to prevent certain proteins from leaving the nucleus of cancer cells, in turn allowing these proteins to control the growth and prevent the spread of cancer cells in dogs.

Indications

LAVERDIA-CA1 is indicated for treatment of lymphoma in dogs.

Always provide the Client Information Sheet to the dog owner with each dose administration or refill. Refer to the dosign tables on the package insert. Fed the dog immediately before giving LAVERDIA-CA1.

Caution:

Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Use only as directed. It is a violation of Federal law to use this product other than as directed in the labeling.

Contraindications:

Do not use in dogs that are pregnant, lactating or intended for breeding. LAVERDIA-CA1 is a possible teratogen and can affect female and male fertility. Laboratory studies in the rat have shown reduced fertility, embryotoxicity, teratogenicity, and maternal toxicity. Administration of LAVERDIA-CA1 caused degeneration/atrophy and vacuolation in the seminiferous tubules and oligospermia in the epididymides in male dogs in the margin of safety study (see Target Animal Safety).

Warnings:

User Safety Warnings:

NOT FOR USE IN HUMANS. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. CHILDREN SHOULD NOT COME INTO CONTACT WITH LAVERDIA-CA1. Children should not come in contact with the feces, urine, vomit, or saliva of treated dogs.

Pregnant women, women who may become pregnant, and nursing women should not handle or administer LAVERDIA-CA1 or come in contact with the feces, urine, vomit, or saliva from LAVERDIA-CA1-treated dogs. LAVERDIA-CA1 may cause birth defects and can affect female fertility based on animal studies.

LAVERDIA-CA1 can affect male fertility based on animal studies and studies in humans.

Wear protective disposable chemotherapy resistant gloves when handling LAVERDIA-CA1 to avoid exposure to drug.

Wear protective disposable chemotherapy resistant gloves to prevent direct contact with moistened, broken, or crushed LAVERDIA-CA1 tablets.

Wear protective disposable chemotherapy resistant gloves to prevent contact with feces, urine, vomit, and saliva during treatment and for 3 days after the dog has received the last treatment. Place all waste material in a plastic bag and seal before general disposal. Wash hands immediately and thoroughly with soap and water if contact occurs with the feces, urine, vomit, or saliva from LAVERDIA-CA1 treated dogs.

Any items that come in contact with feces, urine, vomit, or saliva should not be washed with other laundry during treatment and for 3 days after the last treatment with LAVERDIA-CA1.

Wear protective disposable chemotherapy resistant gloves when handling the dog's toys, food bowl, and water bowl. Wash food and water bowls separately from other items during treatment and for 3 days after the dog has received the last treatment.

If LAVERDIA-CA1 is accidentally ingested, or if there is significant contact with feces, urine, vomit, or saliva of dogs during treatment or within 3 days after the last treatment without proper precautions, seek medical advice immediately. It is important to show the treating physician a copy of the package insert, label, or client information sheet.

• It is recommended that LAVERDIA-CA1 be administered under the supervision of, or in consultation with, a veterinarian experienced in the use of cancer therapeutic agents.
• 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 eat, drink or smoke while handling the product.
• Do not store near food in or near a food preparation area, or with medications intended for use in humans.

• In case of contact with the skin, wash the affected area immediately and thoroughly with soap and water.

• Rinse the eyes with large amounts of tap water (use eyewash station if present) for 10 minutes while holding back the eyelid.
• Remove contact lenses.
• Seek medical advice immediately and show the package insert or label to the physician.

• Seek medical advice immediately and show the package insert or label to the physician.

Animal Safety Warnings:

LAVERDIA-CA1 can cause severe anorexia. Patients should be carefully monitored for inappetence, vomiting, diarrhea and dehydration, and supportive care should be provided as clinically indicated (see Adverse Reactions). In the study used to support reasonable expectation of effectiveness, low doses of corticosteroids (prednisone) were found to reduce the incidence of anorexia and gastrointestinal adverse reactions associated with verdinexor.

Keep LAVERDIA-CA1 in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

Precautions:

Safe use of LAVERDIA-CA1 has not been evaluated in dogs with concurrent serious infections; concurrent renal, cardiovascular, or hepatic disease; in dogs with diabetes mellitus; in dogs with clinically relevant hypercalcemia; or in dogs with concurrent malignancy.

LAVERDIA-CA1 can cause hematologic and serum chemistry abnormalities. Dogs should be frequently monitored for evidence of hematologic and serum chemistry abnormalities when initiating and maintaining treatment with LAVERDIA-CA1 (see ADVERSE REACTIONS and TARGET ANIMAL SAFETY).

The safety and effectiveness of LAVERDIA-CA1 has not been evaluated in conjunction with other chemotherapeutic agents or other treatment modalities for lymphoma.

The effect of concomitant medications on the metabolism of LAVERDIA-CA1 has not been evaluated.

The safe use of LAVERDIA-CA1 has not been evaluated in dogs younger than 7 months of age.

The primary metabolism of LAVERDIA-CA1 in vitro and in vivo is thought to be inactivation by glutathione (GSH) conjugation. Therefore, administration of LAVERDIA-CA1 with drugs which undergo substantial GSH conjugation (e.g., acetaminophen) should be minimized.

Adverse Reactions:

In the field study supporting reasonable expectation of effectiveness, 58 dogs were treated with verdinexor (not commercial formulation) at doses between 1.0 mg/kg and 1.75 mg/kg administered 2 to 3 times a week (see Reasonable Expectation of Effectiveness).

All dogs experienced at least one adverse reaction. The most common adverse reactions across all dose groups included: anorexia, vomiting, diarrhea, weight loss and lethargy. Most adverse reactions were considered Veterinary Cooperative Oncology Group – common terminology criteria for adverse events (VCOG-CTCAE)1 Grade 1 (mild) or 2 (moderate). Twenty-one dogs experienced a VCOG-CTCAE Grade 3 (severe), 4 (life-threatening), or 5 (death) adverse reaction.

Of the 58 dogs treated with verdinexor, adverse reactions occurring in ?10% of dogs associated with verdinexor treatment included:

• General: lethargy, fever, weakness, generalized pain
• Gastrointestinal: anorexia, vomiting, diarrhea
• Renal: polyuria, polydipsia, hematuria, proteinuria, low urine specific gravity, urinary tract infection
• Hepatic: elevated liver enzymes, bilirubinuria
• Cardiorespiratory: cough/dyspnea
• Metabolic: weight loss
• Hematologic: thrombocytopenia, anemia, lymphopenia, neutrophilia, leukopenia, eosinopenia, neutropenia, monocytosis, leukocytosis, prolonged partial thromboplastin time, elevated blood urea nitrogen, hypercalcemia, hyperphosphatemia
• Skin: subcutaneous edema/swelling, pyoderma

Adverse reactions occurring in <10% of dogs associated with verdinexor treatment included:

• Renal: protein losing nephropathy, urinary incontinence
• Hepatic: hepatomegaly, elevated bilirubin, icterus
• Cardiorespiratory: heart murmur, arrhythmia,heart block
• Hematologic: hypoglubulinemia, hypoproteinemia, hypoalbuminemia, prolonged prothrombin time
• Neurologic: seizure, tremor, disorientation
• Ocular: corneal opacity
• Skin: bruising, erythema, alopecia
• Other: nasal discharge, epistaxis, lymphadenitis

Thrombocytopenia (VCOG-CTCAE Grade 1 and 2) was observed in verdinexor treated dogs in the study supporting reasonable expectation of effectiveness. Two dogs with thrombocytopenia during the study were reported with bruising and one dog with thrombocytopenia was reported with epistaxis. In human studies of a closely related compound, idiosyncratic reductions in platelets (severe or medically significant but not immediately life-threatening in 10-20% of patients) were reported.

One dog was reported with a protein losing nephropathy (PLN). Two additional dogs, though not reported, may have had a PLN. One dog was reported with hypoalbuminemia and proteinuria on study day 21 which progressed until study end (study day 194). Another dog was reported with proteinuria at study day 7 which persisted (and worsened) to the end of the study (study day 105). At the start of the study the dog had hyperalbuminemia; by study day 105 the dog had hypoalbuminemia.

Information For Dog Owners:

Always provide the Client Information Sheet with each prescription 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, how to handle and administer the product, and how to clean up any feces, urine, vomit, or saliva from dogs treated with LAVERDIA-CA1 (verdinexor tablets). The Client Information Sheet also contains warnings for humans and what to do in case of accidental human exposure to LAVERDIA-CA1.

Storage:

Store the bottles at controlled room temperature 20° to 25°C (68° – 77°F).