Saxagliptin
Dosing in kidney impairment
Recommendations for Dosage and Administration in Renal Impairment Assess renal function prior to initiation of saxagliptin and metformin hydrochloride extended-release tablets and then as clinically indicated [ see Use in Specific Populations ]. The recommended dosage of saxagliptin and metformin hydrochloride extended-release tablets in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 45 mL/minute/1.73 m 2 is the same as the recommended dosage in patients with normal renal function [ see Dosage and Administration ].
In patients taking saxagliptin and metformin hydrochloride extended-release tablets whose eGFR later falls below 45 mL/minute/1.73 m 2 , assess the benefit risk of continuing therapy and limit dose of the saxagliptin component to 2.5 mg once daily. Initiation of saxagliptin and metformin hydrochloride extended-release tablets in patients with an eGFR between 30 – 45 mL/minute/1.73 m 2 is not recommended.
Saxagliptin and metformin hydrochloride extended-release tablets are contraindicated in patients with an eGFR below 30 mL/minute/1.73 m 2 . Discontinue saxagliptin and metformin hydrochloride extended-release tablets if the patient’s eGFR later falls below 30 mL/minute/1.73 m 2 [ see Contraindications and Warnings and Precautions ].
Dosing in liver impairment
Hepatic Impairment Use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis. Saxagliptin and metformin hydrochloride extended-release tablets are not recommended in patients with hepatic impairment [ see Warnings and Precautions ].
Preparation and administration
Recommended Dosage and Administration Individualize the starting dosage of saxagliptin and metformin hydrochloride extended-release tablets based on the patient’s current regimen and the available strengths of saxagliptin and metformin hydrochloride extended-release tablets [ see Dosage Forms and Strengths ]. Administer saxagliptin and metformin hydrochloride extended-release tablets once daily with the evening meal, with gradual dose titration to reduce the gastrointestinal side effects associated with metformin HCl [ see Adverse Reactions ].
The recommended starting dosage of saxagliptin and metformin hydrochloride extended-release tablets in patients who need 5 mg of saxagliptin and who are not currently treated with metformin HCl is one saxagliptin and metformin hydrochloride extended-release tablet containing 5 mg saxagliptin and 500 mg metformin HCl extended-release once daily with gradual dose escalation to reduce the gastrointestinal side effects due to metformin HCl.
In patients treated with metformin HCl, the recommended starting dosage of saxagliptin and metformin hydrochloride extended-release tablets should provide metformin HCl at the dose already being taken, or the nearest therapeutically appropriate dose. Following a switch from metformin HCl immediate-release to saxagliptin and metformin hydrochloride extended-release tablets, closely monitor glycemic control and adjust the dosage accordingly.
Patients who need 2.5 mg saxagliptin in combination with metformin HCl extended-release may be treated with saxagliptin and metformin hydrochloride extended-release tablets 2.5 mg/1,000 mg. Patients who need 2.5 mg saxagliptin who are either metformin HCl naive or who require a dose of metformin HCl higher than 1,000 mg should use the individual components.
Gradually titrate the dosage of saxagliptin and metformin hydrochloride extended-release tablets, as needed, after assessing therapeutic response and tolerability, up to a maximum recommended dosage of saxagliptin and metformin hydrochloride extended-release tablets (5 mg for saxagliptin and 2,000 mg for metformin HCl extended-release orally once daily).
Inform patients that saxagliptin and metformin hydrochloride extended-release tablets must be swallowed whole and never crushed, cut, or chewed. Occasionally, the inactive ingredients of saxagliptin and metformin hydrochloride extended-release tablets will be eliminated in the feces as a soft, hydrated mass that may resemble the original tablet.
If a dose is missed, advise patients not to take an extra dose. Resume treatment with the next dose.