STEGLATRO 15MG 30 TABLETS

DESCRIPTION
STEGLATRO (ertugliflozin) tablets for oral use contain ertugliflozin L-pyroglutamic acid, a SGLT2 inhibitor.
The chemical name of ertugliflozin L-pyroglutamic acid is (1S,2S,3S,4R,5S)-5-(4-chloro-3-(4- ethoxybenzyl)phenyl)-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol, compound with (2S)-5- oxopyrrolidine-2-carboxylic acid. The molecular formula is C27H32ClNO10 and the molecular weight is 566.00.
The chemical structure is:
 
 
Ertugliflozin L-pyroglutamic acid is a white to off-white powder that is soluble in ethyl alcohol and acetone, slightly soluble in ethyl acetate and acetonitrile and very slightly soluble in water.
STEGLATRO is supplied as film-coated tablets, containing 6.48 or 19.43 mg of ertugliflozin Lpyroglutamic acid, which is equivalent to 5 and 15 mg of ertugliflozin.
Inactive ingredients are microcrystalline cellulose, lactose monohydrate, sodium starch glycolate, and magnesium stearate.
The film coating contains: hypromellose, lactose monohydrate, macrogol, triacetin, titanium dioxide and iron oxide red.
 
. Name of the medicinal product
Steglatro® 5 mg film-coated tablets
Steglatro® 15 mg film-coated tablets
2. Qualitative and quantitative composition
Steglatro 5 mg film-coated tablets
Each tablet contains 5 mg ertugliflozin (as ertugliflozin L-pyroglutamic acid).
Excipient(s) with known effect
Each tablet contains 28 mg of lactose (as monohydrate).
Steglatro 15 mg film-coated tablets
Each tablet contains 15 mg ertugliflozin (as ertugliflozin L-pyroglutamic acid).
Excipient(s) with known effect
Each tablet contains 85 mg of lactose (as monohydrate).
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Film-coated tablet (tablet).
Steglatro 5 mg film-coated tablets
Pink, 6.4 x 6.6 mm, triangular-shaped, film-coated tablets debossed with “701” on one side and plain on the other side.
Steglatro 15 mg film-coated tablets
Red, 9.0 x 9.4 mm, triangular-shaped, film-coated tablets debossed with “702” on one side and plain on the other side.
4. Clinical particulars
4.1 Therapeutic indications
Steglatro is indicated in adults aged 18 years and older with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control:
• as monotherapy in patients for whom the use of metformin is considered inappropriate due to intolerance or contraindications.
• in addition to other medicinal products for the treatment of diabetes.
(For study results with respect to combinations and effects on glycaemic control see sections 4.4, 4.5, and 5.1.)
4.2 Posology and method of administration
Posology
The recommended starting dose of ertugliflozin is 5 mg once daily. In patients tolerating ertugliflozin 5 mg once daily, the dose can be increased to 15 mg once daily if additional glycaemic control is needed.
When ertugliflozin is used in combination with insulin or an insulin secretagogue, a lower dose of insulin or the insulin secretagogue may be required to reduce the risk of hypoglycaemia (see sections 4.4, 4.5, and 4.8).
In patients with volume depletion, correcting this condition prior to initiation of ertugliflozin is recommended (see section 4.4).
If a dose is missed, it should be taken as soon as the patient remembers. Patients should not take two doses of Steglatro on the same day.
Special populations
Renal impairment
Assessment of renal function is recommended prior to initiation of Steglatro and periodically thereafter (see section 4.4).
Initiation of this medicinal product is not recommended in patients with an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2 or CrCl less than 60 ml/min (see section 4.4).
Steglatro should be discontinued when eGFR is persistently less than 45 ml/min/1.73 m2 or CrCl is persistently less than 45 ml/min.
Steglatro should not be used in patients with severe renal impairment, with end-stage renal disease (ESRD), or receiving dialysis, as it is not expected to be effective in these patients.
Hepatic impairment
No dose adjustment of ertugliflozin is necessary in patients with mild or moderate hepatic impairment. Ertugliflozin has not been studied in patients with severe hepatic impairment and is not recommended for use in these patients (see section 5.2).
Elderly (≥ 65 years old)
No dose adjustment of ertugliflozin is recommended based on age. Renal function and risk of volume depletion should be taken into account (see sections 4.4 and 4.8). There is limited experience with Steglatro in patients ≥ 75 years of age.
Paediatric population
The safety and efficacy of ertugliflozin in children under 18 years of age have not been established. No data are available.
Method of administration
Steglatro should be taken orally once daily in the morning, with or without food. In case of swallowing difficulties, the tablet could be broken or crushed as it is an immediate-release dosage form.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
General
Steglatro should not be used in patients with type 1 diabetes mellitus.
Hypotension/Volume depletion
Ertugliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction. Therefore, symptomatic hypotension may occur after initiating Steglatro (see section 4.8), particularly in patients with impaired renal function (eGFR less than 60 ml/min/1.73 m2 or CrCl less than 60 ml/min), elderly patients (≥ 65 years), patients on diuretics, or patients on anti-hypertensive therapy with a history of hypotension. Before initiating Steglatro, volume status should be assessed and corrected if indicated. Monitor for signs and symptoms after initiating therapy.
Due to its mechanism of action, ertugliflozin induces an osmotic diuresis and increases serum creatinine and decreases eGFR. Increases in serum creatinine and decreases in eGFR were greater in patients with moderate renal impairment (see section 4.8).
In case of conditions that may lead to fluid loss (e.g., gastrointestinal illness), careful monitoring of volume status (e.g., physical examination, blood pressure measurements, laboratory tests including haematocrit) and electrolytes is recommended for patients receiving ertugliflozin. Temporary interruption of treatment with ertugliflozin should be considered until the fluid loss is corrected.
Diabetic ketoacidosis
Rare cases of DKA, including life-threatening and fatal cases, have been reported in clinical trials and post-marketing in patients treated with sodium glucose co-transporter-2 (SGLT2) inhibitors, and cases have been reported in clinical trials with ertugliflozin. In a number of cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14 mmol/l (250 mg/dl). It is not known if DKA is more likely to occur with higher doses of ertugliflozin.
The risk of diabetic ketoacidosis must be considered in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness. Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level.
In patients where DKA is suspected or diagnosed, treatment with ertugliflozin should be discontinued immediately.