Ertugliflozin

Oral
Type 2 diabetes mellitus

eGFR 30-<60 mL/minute/1.73 m²: Not recommended; eGFR <30 mL/minute/1.73 m², ESRD or undergoing dialysis: Contraindicated.

Severe (Child-Pugh class C): Not recommended.

tab: May be taken with or without food.

Diabetic ketoacidosis. Severe renal impairment (eGFR <30 mL/minute/1.73 m²), ESRD, or patients on haemodialysis.

Patient with history of genital mycotic infections, hypotension, CV disease; risk factors predisposing to ketoacidosis (e.g. pancreatic insulin deficiency, history of pancreatitis, dose decreases of insulin, caloric restriction, dehydration, alcohol abuse, acute febrile illness, pancreatic surgery); risk factors for amputation (e.g. prior amputation, peripheral vascular disease, neuropathy, diabetic foot ulcers); risk factors for acute kidney injury (e.g. hypovolaemia, chronic renal insufficiency, CHF); undergoing bariatric surgery. Uncircumcised males. Not recommended for treatment of type 1 diabetes mellitus. Temporarily discontinue therapy ≥4 days before surgery or any event that may precipitate ketoacidosis. Hepatic and mild to moderate renal impairment. Elderly. Pregnancy and lactation.

Significant: Bone fractures, genital mycotic infections (e.g. vulvovaginal candidiasis, vulvovaginitis, candidal balanitis, balanoposthitis), hypotension, volume depletion, lower limb amputation (mainly of the toe), acute renal injury, impaired renal function (e.g. decreased eGFR, increased serum creatinine), increased LDL-cholesterol (LDL-C), serious UTIs including urosepsis and pyelonephritis.
Investigations: Increased Hb and BUN; changed serum lipids, weight decreased.
Metabolism and nutrition disorders: Hypoglycaemia, thirst.
Musculoskeletal and connective tissue disorders: Back pain.
Nervous system disorders: Headache.
Renal and urinary disorders: Increased urination.
Reproductive system and breast disorders: Vulvovaginal pruritus.
Respiratory, thoracic and mediastinal disorders: Nasopharyngitis.
Potentially Fatal: Rarely, diabetic ketoacidosis, Fournier’s gangrene (necrotising fasciitis of the genitalia or perineum).

This drug may increase your risk of lower limb amputations; it is important to adhere with your routine preventive foot care.

Monitor blood glucose, HbA_1c (at least twice yearly in patients with stable glycaemic control; quarterly in patients not meeting treatment goals); renal function at baseline and periodically during therapy; phosphate and LDL-C; volume status (e.g. blood pressure, haematocrit, electrolytes). Assess for signs of genital mycotic infections, UTIs, lower limb and feet sores, ulcers, or infection; hypersensitivity reactions. Confirm signs and symptoms of ketoacidosis (e g. nausea, vomiting, abdominal pain, malaise, shortness of breath) by measuring blood ketones and arterial pH.

Increased risk of hypoglycaemia with insulin and sulphonylurea. May increase risk of hypotension and dehydration with diuretics.

May give positive test result for glucosuria. May interfere with glycaemic control monitoring using 1,5-anhydroglucitol (1,5-AG) assay.

Description:
Mechanism of Action: Ertugliflozin is a potent, selective, and reversible inhibitor of sodium-glucose co-transporter 2 (SGLT2), the main transporter responsible for filtered glucose reabsorption in the renal proximal convoluted tubules. It reduces renal reabsorption of filtered glucose and lowers renal threshold for glucose, resulting in increased urinary glucose excretion.
Pharmacokinetics:
Absorption: Bioavailability: Approx 100%. Time to peak plasma concentration: Approx 1 hour (fasting); 2 hours (with high-fat, high-calorie meal).
Distribution: Volume of distribution: 85.5 L. Plasma protein binding: Approx 94%.
Metabolism: Extensively metabolised primarily by uridine diphosphate glucuronosyltransferases (UGT)1A9 and UGT2B7 via O-glucuronidation into inactive metabolites; undergoes minimal metabolism by CYP450 isoenzyme.
Excretion: Via urine (approx 50%; 1.5% as unchanged drug); faeces (approx 41%; approx 34% as unchanged drug). Elimination half-life: Approx 17 hours.

Source: National Center for Biotechnology Information. PubChem Database. Ertugliflozin, CID=44814423, https://pubchem.ncbi.nlm.nih.gov/compound/Ertugliflozin (accessed on Apr. 27, 2020)

Store between 15-30°C. Protect from moisture.

Antidiabetic Agents

A10BK04 - ertugliflozin ; Belongs to the class of sodium-glucose co-transporter 2 (SGLT2) inhibitors. Used in the treatment of diabetes.

Anon. Ertugliflozin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/04/2020.

Buckingham R (ed). Ertugliflozin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/04/2020.

FDA Revises Labels of SGLT2 Inhibitors for Diabetes to Include Warnings About Too Much Acid in The Blood and Serious Urinary Tract Infections. U.S. FDA. https://www.fda.gov/. Accessed 22/04/2020.

Joint Formulary Committee. Ertugliflozin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/04/2020.

Steglatro 5, 15 mg Film-Coated Tablets (Merck Sharp & Dohme [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my/. Accessed 02/04/2020.

Steglatro Tablet, Film Coated (Merck Sharp & Dohme Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 02/04/2020.