Professional Information

Sitagliptin / Metformin Hydrochloride

Pronouncation: (sit-a-GLIP-tin/MET-fore-min HYE-droe-KLOR-ide)
Class: Antidiabetic combination

Trade Names:
Janumet
- Tablets 50 mg sitagliptin/500 mg metformin hydrochloride
- Tablets 50 mg sitagliptin/1,000 mg metformin hydrochloride

Pharmacology

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Sitagliptin

Slows the inactivation of incretin hormones.

Metformin

Decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

Indications and Usage

Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus not adequately controlled on metformin or sitagliptin alone, or in patients already being treated with both of these agents.

Contraindications

Renal disease or renal function impairment; acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Temporarily discontinue treatment in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials; use of such products may alter renal function.

Dosage and Administration

Base dosage selection of sitagliptin and metformin on the patient's current dose of these agents (max, sitagliptin 100 mg and metformin 2,000 mg daily).

Patients Inadequately Controlled on Metformin Monotherapy
Adults

PO Start with sitagliptin 50 mg twice daily plus the current dose of metformin. For patients taking metformin 850 mg twice daily, the recommended starting dosage is sitagliptin 50 mg plus metformin 1,000 mg twice daily.

Patients Inadequately Controlled on Sitagliptin Monotherapy
Adults

PO Start with sitagliptin 50 mg plus metformin 500 mg twice daily. Titrate patient up to sitagliptin 50 mg plus metformin 1,000 mg twice daily. Patients taking sitagliptin monotherapy whose dose has been adjusted for renal function impairment should not be switched to sitagliptin plus metformin.

Patients Switching from Sitagliptin Coadministered with Metformin
Adults

PO Initiate therapy with the dose of sitagliptin and metformin already being taken.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Alcohol

The effects of metformin on lactic acidosis may be potentiated.

Cationic drugs (eg, amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin)

May compete with metformin for renal tubular transport.

Cimetidine

Metformin plasma levels may be increased.

Digoxin

Digoxin AUC and C _max may be increased slightly.

Drugs that produce hyperglycemia (eg, calcium channel blockers, corticosteroids, diuretics [eg, thiazides], estrogens, isoniazid, nicotinic acid, oral contraceptives, phenothiazines, phenytoin, sympathomimetics, thyroid products)

Closely monitor patient to maintain adequate glycemic control.

Furosemide

Metformin AUC and C _max may be increased while the AUC and C _max of furosemide may be decreased.

Glyburide

Glyburide AUC and C _max may be decreased.

Nifedipine

Metformin AUC and C _max may be increased.

Parenteral iodinated contrast media

Risk of metformin-induced lactic acidosis may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (at least 5%).

EENT

Nasopharyngitis (at least 5%).

GI

Abdominal discomfort, diarrhea, flatulence, indigestion, nausea, vomiting (more than 5%); abdominal pain (1%).

Miscellaneous

Asthenia (more than 5%).

Precautions

Warnings

Lactic acidosis, which is fatal in about 50% of cases, can occur. The risk increases with conditions such as acute CHF, dehydration, excess alcohol intake, hepatic and renal function impairment, and sepsis. Symptoms include increased somnolence, malaise, myalgia, nonspecific abdominal distress, and respiratory distress. Abnormal laboratory findings include elevated blood lactate, increased anion gap, and low pH.

Monitor

Measure blood glucose and A _1c levels periodically; initially and periodically monitor hematologic parameters and renal function.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution because of possible age-related reduction in renal function.

Renal Function

Metformin accumulation and lactic acidosis risk increases with the degree of renal function impairment.

Hepatic Function

Avoid metformin in patients with clinical or laboratory evidence of hepatic disease.

Changes in clinical status

Patients with type 2 diabetes previously well controlled who develop laboratory abnormalities or clinical illness should be evaluated promptly for ketoacidosis or lactic acidosis.

Hypoxic states

Immediately discontinue therapy in any condition characterized by hypoxemia (eg, acute CHF, MI).

Loss of blood glucose control

Patients exposed to stress (eg, fever, infection, surgery, trauma) may experience a loss in glycemic control. It may be necessary to withhold sitagliptin/metformin and temporarily administer insulin until an acute episode has been resolved.

Surgical patients

Temporarily suspend treatment for any surgical procedure, except in procedures not associated with restricted intake of food and fluids, and do not restart until oral intake has resumed and renal function has been evaluated as healthy.

Vitamin B ₁₂ levels

Metformin may decrease vitamin B ₁₂ levels.

Overdosage

Symptoms