Dosing and uses of PrandiMet (metformin-repaglinide)
Adult dosage forms and strengths
metformin/repaglinide
tablet
- 500mg/1mg
- 500mg/2mg
Type 2 Diabetes Mellitus
Indicated as adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a meglitinide and metformin, or who have inadequate glycemic control on a meglitinide alone or metformin alone
Currently using comcomitant repaglinide and metformin
- Start initial PrandiMet dose similar to patient's current repaglinide/metformin dosage, but do not exceed; titrate as necessary to acheive targeted glycemic control
Inadequately controlled with either metformin or a meglitinide monotherapy
- 500 mg/1 mg PO q12hr ac initially
- May gradually increase dose based on glycemic response
Dosage modifications
Hepatic impairment: Do not administer
Renal impairment
- Obtain eGFR before starting metformin
- eGFR <30 mL/min/1.73 m²: Contraindicated
- eGFR 30-45 mL/min/1.73 m²: Not recommended to initiate treatment
- Monitor eGFR at least annually or more often for those at risk for renal impairment (eg, elderly)
- If eGFR falls below 45mL/min/1.73 m² while taking metformin, risks and benefits of continuing therapy should be evaluated
- If eGFR falls below 30 mL/min/1.73 m²: while taking metformin, discontinue the drug
Oral Administration
May be administered PO q8-12hr
Generally given within 15 minutes prior to meals, but timing can vary from immediately preceding the meal up to 30 minutes before the meaL
Not to exceed 1000 mg/4 mg per meaL
Not to exceed cumulative daily dose of 2500 mg/10 mg
Pediatric dosage forms and strengths
Safety and efficacy not established; not recommended for use in children
Geriatric dosage forms and strengths
Currently using comcomitant repaglinide and metformin
Start initial PrandiMet dose similar to patient's current repaglinide/metformin dosage, but do not exceed; titrate as necessary to acheive targeted glycemic controL
Do not administer to patients >80 years before assessing renal function and determined to be normaL
Inadequately controlled with either metformin or meglitinide monotherapy
500 mg/1 mg PO q12hr ac initially
May gradually and conservatively increase dose based on glycemic response
Do not administer to patients >80 years before assessing renal function and determined to be normaL
Warnings
Black box warnings
Lactic acidosis is a rare but potentially severe consequence of therapy with metformin; characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma concentrations >5 mcg/mL are generally found
Patients with CHF requiring pharmacologic management, in particular those with unstable or acute CHF who are at risk of hypoperfusion and hypoxemia, are at an increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient’s age
Do not start in patients aged 80 years or older unless CrCl demonstrates that renal function is not reduced because these patients are more susceptible to developing lactic acidosis. Metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis
Should generally be avoided in patients with clinical or laboratory evidence of hepatic disease; caution patients against excessive alcohol intake, either acute or chronic, during metformin therapy because alcohol potentiates the effects of metformin on lactate metabolism
The onset of lactic acidosis often is subtle and accompanied by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, increasing somnolence, nonspecific abdominal distress); with marked acidosis, hypothermia, hypotension, and resistant bradyarrhythmias may occur; instruct patients to recognize symptoms and notify their physician immediately if they occur; withdraw metformin until the situation is clarified
Serum electrolytes, ketones, blood glucose, and if indicated, blood pH, lactate levels, and even blood metformin levels may be usefuL
Once a patient is stabilized on any dose level of metformin, GI symptoms, which are common during initiation of therapy, are unlikely to be drug related; later occurrences of GI symptoms could be due to lactic acidosis or other serious disease
Lactic acidosis is a medical emergency necessitating hospitalization and should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia); discontinue metformin immediately if lactic acidosis suspected
Metformin is highly dialyzable (clearance up to 170 mL/min under good hemodynamic conditions); prompt hemodialysis is recommended to correct the acidosis and to remove the accumulation
Contraindications
Severe renal disease: eGFR <30 ml/min/1.73 m²
Acute or chronic metabolic acidosis, including diabetic ketoacidosis
Concomitant gemfibrozil and itraconazole
Hypersensitivity to repaglinide or metformin
Cautions
Risk of lactic acidosis due to accumulation of metformin
Hepatic impairment
Avoid excessive alcohoL
Risk of hypoglycemia: elderly; patients taking beta blockers
May decrease levels of Vit B12
Suspend temporarily for any surgical procedure until patient is no longer NPO and normal renal function has resumed
During loss of blood sugar control: suspend PrandiMet temporarily and administer insulin
Discontinue during hypoxic states: acute CHF, MI or other event
Iodinated contrast imaging procedures
- Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast
- Reevaluate eGFR 48 hr after the imaging procedure; restart metformin if renal function is stable
Pregnancy and lactation
Pregnancy category: C
Lactation: not known if excreted in breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
