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Janumet/Janumet XR

Generic Name: Sitagliptin and Metformin HCL
Drug Category: DPP-4 Inhibitor/Biguanide
Litigation Alert Level: High
This drug has been approved for use by males and females over the age of 18 years old for a maximum duration of 2 years.

Approved Uses

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both sitagliptin and metformin is appropriate.

JANUMET/JANUMET XR should not be used in patients with type 1 diabetes.

JANUMET/JANUMET XR has not been studied in patients with a history of pancreatitis. There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients taking JANUMET/JANUMET XR.

The maximum recommended daily dose is 100 mg of sitagliptin and 2000 mg of metformin hydrochloride.

An association between dipeptidyl peptidase-4 (DPP-4) inhibitor treatment and heart failure has been observed in cardiovascular outcomes trials for two other members of the DPP-4 inhibitor class.

There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypothermia, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate/pyruvate ratio; metformin plasma levels were generally >5 mcg/mL. Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. 

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

JANUMET/JANUMET XR is contraindicated in patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis.

Several of the postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia).

Do not use in patients with eGFR below 30 mL/min/1.73 m2. JANUMET/JANUMET XR is not recommended in patients with eGFR between 30 and less than 45 mL/min/1.73 m2.

Discontinue JANUMET/JANUMET XR at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Reevaluate eGFR 48 hours after the imaging procedure; restart JANUMET/JANUMET XR if renal function is stable.

JANUMET/JANUMET XR should be temporarily discontinued while patients have restricted food and fluid intake.

There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years.

Alcohol potentiates the effect of metformin on lactate metabolism and this may increase the risk of metformin-associated lactic acidosis. Warn patients against excessive alcohol intake while receiving JANUMET/JANUMET XR.

Certain individuals (those with inadequate Vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal Vitamin B12 levels. In these patients, routine serum Vitamin B12 measurements at two- to three-year intervals may be useful.

Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use.

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with sitagliptin, one of the components of JANUMET/JANUMET XR. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome.

JANUMET/JANUMET XR is contraindicated in patients with:

  • Severe renal impairment (eGFR below 30 mL/min/1.73 m2)
  • Acute or chronic metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with JANUMET/JANUMET XR or any other anti-diabetic drug.

Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol. Elderly, debilitated, or malnourished patients, and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking β-adrenergic blocking drugs.

Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with JANUMET/JANUMET XR may increase the risk of lactic acidosis.

Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis.

Co-administration of JANUMET/JANUMET XR with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.

Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving JANUMET/JANUMET XR the patient should be closely observed to maintain adequate glycemic control.

Published data from post-marketing studies do not report a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin is used during pregnancy. However, these studies cannot definitely establish the absence of any risk because of methodological limitations, including small sample size and inconsistent comparator groups.

There is no information regarding the presence of JANUMET/JANUMET XR  in human milk, the effects on the breastfed infant, or the effects on milk production. Limited published studies report that metformin is present in human milk.

GoToSource: (JANUMET)
GoToSource: (JANUMET XR)

Off-label Uses

• Dosage greater than 100 mg sitagliptin and 2000 mg metformin per day. GoToSource

• Use in patients under the age of 18. GoToSource

• Type 1 diabetes or diabetic ketoacidosis. GoToSource

Adverse Events

Lactic acidosis (elevated lactic acid level in blood). GoToSource

Pancreatitis (inflammation of pancreas) including fatal and non-fatal hemorrhagic or necrotizing pancreatitis and six-fold increase of developing pancreatic cancer. GoToSource

Upper respiratory tract infections, depression and increased creatinine levels. GoToSource 

Urinary tract infection and stevens–johnson syndrome (severe drug reaction). GoToSource

Heart failure. GoToSource

Kidney failure and rhabdomyolysis. GoToSource

Vitamin B12 deficiency. GoToSource

Bullous pemphigoid (blistering skin disorder). GoToSource

Hypoglycemia (low blood sugar). GoToSource

Severe joint pain. GoToSource

Litigation

Lawsuits filed for acute pancreatitis, hemorrhagic pancreatitis, acute necrotizing pancreatitis and cancer. 

The material contained in GoToPills is for informational purposes only and not intended to replace the judgment, evaluation and treatment of physicians, pharmacists and other healthcare providers. GoToPills does not provide medical advice, diagnoses or treatment. Always seek the advice of your physician or other qualified health provider regarding a medical condition or treatment.

 

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Site Last Updated March 29, 2024