Senvelgo (Canada)

Company: Boehringer Ingelheim Animal Health

Velagliflozin Oral Solution 15 mg/mL

Veterinary Use Only

For cats

DIN 02543427

Description

Senvelgo™ (velagliflozin oral solution) is a clear, colourless to slightly yellow, to slightly brown, multi-dose preparation consisting of 15 mg/mL velagliflozin intended for oral use in cats. Senvelgo is a sodium-glucose co-transporter 2 (SGLT-2) inhibitor.

Non-medicinal ingredients: ethanol (96%), propylene glycol, citric acid monohydrate, sodium hydroxide, honey flavour, and purified water.

Senvelgo Indications

For the reduction of hyperglycemia in cats with non-insulin dependent diabetes mellitus.

Active Ingredient

Each mL contains 15 mg velagliflozin (as velagliflozin L-proline monohydrate).

Directions for use: Read entire package insert before use.

The recommended dosing regimen is once daily orally, 1 mg/kg body weight.

The solution should be drawn using the dosing syringe provided in the carton. The syringe fits onto the bottle and has a kilogram body weight scale in 0.5 kg increments. The product may be administered either directly into the mouth or with a small amount of food. The medication should be given at approximately the same time every day.

If a dose is missed, it should be given as soon as possible on the same day.

After administration close bottle tightly with the cap. The syringe can be cleaned with a clean, dry cloth.

Prior to starting treatment:

Ensure the cat is alert, active, eating and drinking and a complete work up for diabetes mellitus (exam, body weight, complete blood count, serum chemistry, fructosamine, Spec fPL, TT4, IGF-1, urinalysis, urine culture) and concurrent conditions has been done immediately before starting treatment, including evaluating for ketonuria (see Contraindications).

Monitoring of cats receiving Senvelgo:

Monitor the cat for hyporexia/anorexia, lethargy, dehydration, illness and weight loss. Immediately discontinue Senvelgo should any of those signs occur and assess the cat for diabetic ketoacidosis, no matter the blood glucose concentration.

During the first 2 weeks after starting treatment: evaluate the cat for ketonuria every 1 to 3 days and any time the cat shows signs of illness. If ketonuria is present, discontinue Senvelgo and treat with insulin (see below).

Two to three days after starting treatment: examine, weigh and measure blood glucose and assess a urine dip stick, especially for ketones.

One week and 1 month after starting treatment: examine, weigh, and do a complete blood count, serum chemistry, blood glucose curve, urinalysis, and serum fructosamine (1 month) to assess the cat. If there is poor glycemic control after 4 weeks of treatment or continued unintended weight loss, Senvelgo should be discontinued and insulin therapy initiated.

Thereafter the owner should assess the cat every 30 days. If there are changes to the cat’s condition, immediately reassess. Senvelgo should be discontinued if the cat’s condition deteriorates and/or glycemic control worsens after initial improvement.

Diabetic ketoacidosis or euglycemic ketoacidosis requires the following actions:

● Discontinue Senvelgo

● Initiate insulin therapy immediately, regardless of blood glucose concentration

● Administer dextrose or other carbohydrate source, if the cat has euglycemic ketoacidosis

● Provide appropriate nutritional support to prevent or treat hepatic lipidosis

Contraindications

Senvelgo is contraindicated in cats

● with insulin dependent diabetes mellitus,

● previously treated with insulin or receiving insulin (see DKA Adverse Events),

● with ketonuria

● with evidence of diabetic ketoacidosis, or

● severe dehydration requiring intravenous fluid supplementation.

Do not initiate treatment or continue treatment in cats with anorexia, dehydration, lethargy, clinical pancreatitis, or any condition or treatment that can cause insulin resistance.

Do not use in cases of hypersensitivity to the active substance or to any of the excipients.

Cautions:

Based on the mode of action of SGLT-2 inhibitors (such as velagliflozin), adequate endogenous insulin production is a requirement for successful management of diabetes mellitus with this veterinary medicinal product.

Cats treated with Senvelgo may be at an increased risk of diabetic ketoacidosis or euglycemic ketoacidosis. As diabetic ketoacidosis and euglycemic ketoacidosis in cats treated with Senvelgo may result in death, the ketoacidosis must be immediately treated including insulin administration and discontinuation of Senvelgo (see Monitoring).

Due to the mode of action of SGLT-2 inhibitors, high blood glucose levels will not be present in cases of DKA (euglycemic ketoacidosis). Therefore, the diagnosis of euglycemic DKA needs to be based on the presence of urine ketone bodies, and/or clinical signs.

Presence of acetoacetate and acetone ketone bodies can be checked by cat owners at home by dipping a urine test strip into the cat’s urine. Ketone body beta-hydroxybutyric acid (BHA) can be measured in the blood. Not all three ketones may be present in a cat with DKA.

The safety and efficacy of a combined treatment with insulin or other blood glucose lowering treatments and velagliflozin in cats has not been investigated. Due to the mode of action of insulin there is an increased risk for hypoglycemia, therefore combined treatment is not recommended.

Due to the mode of action, SGLT-2 inhibitors may cause an increase in serum creatinine, blood urea nitrogen (BUN), phosphorus, and sodium within weeks of starting therapy, followed by a stabilization of values. Routine evaluation of renal function, body weight and hydration status in patients with renal disease is recommended.

Use of velagliflozin in cats with chronic renal insufficiency has not been fully investigated.

Initial mild weight loss may be seen with Senvelgo associated with its mode of action (glucosuria and caloric wasting). If weight loss doesn’t improve or stabilize within 7 days consider evaluating for concurrent disease and discontinuing Senvelgo.

Senvelgo administration is associated with an increased risk of developing a urinary tract infection due to the persistent glucosuria. Routine urine culture is recommended.

Remission of diabetes mellitus in cats treated with Senvelgo has not been evaluated.

Glucosuria is not a reliable indicator for monitoring diabetic control while a cat is receiving a SGLT-2 inhibitor or shortly after discontinuation. Glucosuria may persist for 2-3 days after stopping Senvelgo.

Senvelgo contains propylene glycol. When cats are administered Senvelgo at the 1 mg/kg/day dose, cats receive 40 mg/kg/day of propylene glycol. Propylene glycol above 80 mg/kg/day can cause Heinz bodies to form without anemia. Use caution when administering Senvelgo to cats receiving other products that contain propylene glycol.

Use of Senvelgo following previous treatment with other oral anti-diabetic drugs has not been evaluated.

The safety of this product has not been established during breeding, pregnancy and lactation.

Warnings: Keep out of reach of children. Caution should be taken to avoid accidental ingestion and contact with eyes. This product can cause eye irritation; in case of contact with eyes immediately rinse thoroughly with water. In case of ingestion or contact with the eyes seek medical advice.

Adverse Reactions

A total of 408 patients from the USA, EU and Japan with diabetes mellitus were included in clinical trials to evaluate the safety and efficacy of velagliflozin, of which 343 patients received velagliflozin. Many adverse reactions observed were expected, based on the pharmacodynamic effect of SGLT-2 inhibitors. The osmotic diuresis accompanying glucosuria may lead to polyuria and/or polydipsia and weight loss. Minimal inhibition of SGLT-1 located in the intestine may lead to a softening of stool.

Adverse Reactions Observed in 3 Clinical Field Studies (USA, EU and Japan) in 343 cats

¹ This term includes cases with azotemia, chronic renal failure, increased BUN, increased SDMA, increased creatinine, increased protein:creatinine ratio, increased renal parameters, renal failure and renal insufficiency.

Electrolytes changes that are observed with velagliflozin are hypercalcemia, and hyperphosphatemia.

Velagliflozin may cause transient hypoglycemia but no adverse effects were observed.

In three clinical field efficacy studies, serious adverse events observed were diabetic ketoacidosis, euglycemic ketoacidosis, chronic renal insufficiency, dehydration and anorexia.

Diabetic Ketoacidosis

In the EU field study there were 4 cats (6.6%) treated with velagliflozin that developed euglycemic ketoacidosis. In 3 of the cats the euglycemic ketoacidosis occurred within the first week of treatment. In the fourth cat it occurred on study day 80. In the US field study 33 cats (13.1%) had diabetic ketoacidosis, diabetic ketonuria or ketosis. Most of the cats developed ketonuria before study day 7.

The risk for ketoacidosis is greatest within the first 14 days of starting treatment. Eighty-four percent of cats that developed ketoacidosis did so within the first 14 days of treatment. The incidence of clinical DKA within the first two weeks after starting treatment with velagliflozin was 5.1% in insulin naïve cats and 12.1% in cats pre-treated with insulin.

In the EU field study 13 (21.3%) velagliflozin treated cats and 10 (15.2%) insulin treated cats were treated for cystitis.

Death and Euthanasia

In the EU field study, 4 (6.6%) velagliflozin treated cats and 5 (7.6%) insulin treated cats died or were euthanized. In the velagliflozin group 1 cat died of advanced renal failure, one cat had yellow mucous membranes, decreased appetite, decreased weight and diarrhea, the third cat had decreased appetite, polydipsia, diarrhea and the fourth cat was dehydrated, lethargic and recumbent.

In the US field study, 17/252 (6.7%) cats died or were euthanized during the study or shortly after their removal from the study. The cats had acute renal failure (1), diabetic ketoacidosis (3), pancreatitis and hyperlipidemia (3), urinary incontinence/inappropriate urination (3), progressive diabetes mellitus (1), neoplasia (3), heart failure (1), pneumonia (1) or behaviour change-aggressive (1).

Clinical Pharmacology

Key Scientific Information: Velagliflozin as velagliflozin L-proline monohydrate is a sodium-glucose co-transporter 2 (SGLT-2) inhibitor. The chemical name is 2 - (4 - cyclopropylbenzyl) - 4 - ((2S,3R,4R,5S,6R) - 3,4,5 - trihydroxy - 6 - hydroxymethyltetrahydropyran - 2 - yl) - benzonitrile (S)-pyrrolidine-2-carboxylic acid monohydrate.

The chemical structure is: