Metformindosage

Administer once daily with the evening meal. Individualize the starting dosage based on the patient’s current regimen then adjust the dosage based on effectiveness and tolerability. Do not exceed a daily dosage of 5 mg saxagliptin/2,000 mg metformin HCl extended-release. Swallow whole. Never crush, cut, or chew. Limit the saxagliptin dosage to 2.5 mg daily for patients also taking strong cytochrome P450 3A4/5 inhibitors (e.g., ketoconazole). Assess renal function prior to initiation of saxagliptin and metformin hydrochloride extended-release tablets and periodically thereafter. o Do not use in patients with eGFR below 30 mL/min/1.73 m 2. o Initiation is not recommended in patients with eGFR between 30 to 45 mL/min/1.73 m 2. o Assess risk/benefit of continuing if eGFR falls below 45 mL/min/1.73 m 2. o Limit the saxagliptin component to 2.5 mg daily if eGFR is less than 45 mL/min/1.73 m 2. o Discontinue if eGFR falls below 30 mL/min/1.73 m 2. Saxagliptin and metformin hydrochloride extended-release tablets may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures.

2.1 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. 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. 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.

2.2 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. 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. 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 to 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.

2.3 Dosage Modifications with

Concomitant Use of Strong CYP3A4/5 Inhibitors The maximum recommended dosage of saxagliptin and metformin hydrochloride extended-release tablets is 2.5 mg of saxagliptin and 1,000 mg of metformin HCl given orally once daily when used concomitantly with strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitors (e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin).

2.4 Discontinuation for

Iodinated Contrast Imaging Procedures Discontinue saxagliptin and metformin hydrochloride extended-release tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR less than 60 mL/min/1.73 m 2; a history of liver disease, alcoholism or heart failure; or in any patient who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart saxagliptin and metformin hydrochloride extended-release tablets if renal function is stable.