DRUG UPDATE

APRIL 2018

SEGLUROMET (ertugliflozin+metformin)

HIGHLIGHTS OF PRESCRIBING INFORMATION

INDICATIONS AND USAGE

SEGLUROMET is a combination of ertugliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, and metformin, a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled on a regimen containing ertugliflozin or metformin, or in patients who are already treated with both ertugliflozin and metformin. (1)

Limitations of Use:

• Not for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. (1)

DOSAGE AND ADMINISTRATION

Individualize the starting dose based on the patient’s current regimen. (2.1)

Maximum recommended dose is 7.5 mg ertugliflozin/1,000 mg metformin twice daily. (2.1)

Take twice daily with meals, with gradual dose escalation. (2.1)

 Assess renal function before initiating SEGLUROMET (2.2):

o Do not use in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m².

o Initiation is not recommended in patients with an eGFR of 30 to less than 60 mL/minute/1.73 m².

o Continued use is not recommended in patients with an eGFR persistently between 30 and less than 60 mL/min/1.73 m².

SEGLUROMET may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures. (2.3)

DOSAGE FORMS AND STRENGTHS

Tablets:

•              Ertugliflozin 2.5 mg and metformin hydrochloride 500 mg (3)

•              Ertugliflozin 2.5 mg and metformin hydrochloride 1,000 mg (3)

•              Ertugliflozin 7.5 mg and metformin hydrochloride 500 mg (3)

•              Ertugliflozin 7.5 mg and metformin hydrochloride 1,000 mg (3)

CONTRAINDICATIONS

•              Severe renal impairment, end stage renal disease, or dialysis. (4, 5.1, 5.4)

•              Metabolic acidosis, including diabetic ketoacidosis. (4, 5.1)

•              History of serious hypersensitivity reaction to ertugliflozin or metformin. (4)

WARNINGS AND PRECAUTIONS

Lactic Acidosis: See boxed warning. (5.1)

Hypotension: May occur particularly in patients with renal impairment, the elderly, or patients on diuretics. Before initiating, assess and correct volume status. Monitor for signs and symptoms during therapy. (5.2)

 Ketoacidosis: Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue, evaluate, and treat promptly. Before initiating, consider risk factors for ketoacidosis. Patients may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis. (5.3)

Acute Kidney Injury and Impairment in Renal Function: Consider temporarily discontinuing in settings of reduced oral intake or fluid losses. If acute kidney injury occurs, discontinue and promptly treat. Monitor renal function. (5.4)

 Urosepsis and Pyelonephritis: Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated. (5.5)

Lower Limb Amputation: Before initiating, consider factors that may increase risk of amputation. Monitor patients for infections or ulcers of lower limbs, and discontinue if these occur. (5.6)

Hypoglycemia: Consider a lower dose of insulin or insulin secretagogue to reduce risk of hypoglycemia when used in combination. (5.7)

Genital Mycotic Infections: Monitor and treat if indicated. (5.8)

Vitamin B12 Deficiency: Metformin may lower vitamin B12 levels. Measure hematological parameters annually. (5.9)

Increased LDL-C: Monitor and treat as appropriate. (5.10)

ADVERSE REACTIONS

•              The most common adverse reactions associated with ertugliflozin (incidence ≥5%) were female genital mycotic infections. (6.1)

•              Most common adverse reactions associated with metformin (incidence ≥5%): diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

•              Carbonic anhydrase inhibitors may increase risk of lactic acidosis. Consider more frequent monitoring. (7.2)

•              Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin. Consider the benefits and risks of concomitant use. (7.2)

•              Alcohol can potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake. (7.2)

USE IN SPECIFIC POPULATIONS

•              Pregnancy: Advise females of the potential risk to a fetus, especially during the second and third trimesters. (8.1)

•              Lactation: Breastfeeding not recommended. (8.2)

•              Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy. (8.3)

•              Geriatrics: Higher incidence of adverse reactions related to reduced intravascular volume. (5.2, 8.5)

•              Renal impairment: Higher incidence of adverse reactions related to reduced intravascular volume and renal function. (5.1, 5.4, 8.6)

•              Hepatic impairment: Avoid use in patients with hepatic impairment. 

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