Selected Safety Information – Gulf
Selected Safety Information
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
JANUMET XR safely and effectively. See full prescribing
information for JANUMET XR.
JANUMET® XR (sitagliptin and metformin hydrochloride extendedrelease)
tablets, for oral use
Initial U.S. Approval: 2012
WARNING: LACTIC ACIDOSIS
See full prescribing information for complete boxed warning.
Postmarketing cases of metformin-associated lactic acidosis
have resulted in death, hypothermia, hypotension, and resistant
bradyarrhythmias. Symptoms included malaise, myalgias,
respiratory distress, somnolence, and abdominal pain.
Laboratory abnormalities included elevated blood lactate levels,
anion gap acidosis, increased lactate/pyruvate ratio, and
metformin plasma levels generally >5 mcg/mL. (5.1)
Risk factors include renal impairment, concomitant use of
certain drugs, age ≥65 years old, radiological studies with
contrast, surgery and other procedures, hypoxic states,
excessive alcohol intake, and hepatic impairment. Steps to
reduce the risk of and manage metformin-associated lactic
acidosis in these highrisk groups are provided in the Full
Prescribing Information. (5.1)
If lactic acidosis is suspected, discontinue JANUMET XR and
institute general supportive measures in a hospital setting.
Prompt hemodialysis is recommended. (5.1)
—————————-INDICATIONS AND USAGE —————————-
JANUMET XR is a combination of sitagliptin, a dipeptidyl peptidase-4
(DPP-4) inhibitor, and metformin hydrochloride (HCl), a biguanide
indicated as an adjunct to diet and exercise to improve glycemic control
in adults with type 2 diabetes mellitus. (1)
Limitations of Use:
Not for the treatment of type 1 diabetes. (1)
Has not been studied in patients with a history of pancreatitis. (1,
5.2)
———————– DOSAGE AND ADMINISTRATION ———————–
Take JANUMET XR orally once daily with a meal. Patients taking two
JANUMET XR tablets should take the tablets together. (2.1)
Individualize the dosage of JANUMET XR on the basis of the
patient’s current regimen, effectiveness, and tolerability. (2.1)
The maximum recommended daily dose is 100 mg of sitagliptin and
2000 mg of metformin HCl extended-release. (2.1)
The recommended starting dose in patients not currently treated with
metformin is 100 mg sitagliptin and 1000 mg metformin HCl once
daily, with gradual dose escalation recommended to reduce the
gastrointestinal effects due to metformin. (2.1)
The starting dose in patients already treated with metformin should
provide sitagliptin dosed as 100 mg and the dose of metformin
already being taken once daily. For patients taking metformin HCl 850
mg twice daily or 1000 mg twice daily, the recommended starting
dose of JANUMET XR is two 50 mg sitagliptin and 1000 mg
metformin HCl extended-release tablets once daily. (2.1)
Maintain the same total daily dose of sitagliptin and metformin when
changing between JANUMET and JANUMET XR. (2.1)
Prior to initiation, assess renal function with estimated glomerular
filtration rate (eGFR) (2.2)
o Do not use in patients with eGFR below 30 mL/min/1.73 m2.
o Discontinue if eGFR later falls below 30 mL/min/1.73 m2.
o Initiation is not recommended in patients with eGFR between 30 –
45 mL/min/1.73 m2.
o Assess risk/benefit of continuing if eGFR falls below
45 mL/min/1.73 m2.
o Limit dose of sitagliptin to 50 mg once daily if eGFR falls below
45 mL/min/1.73 m2.
JANUMET XR may need to be discontinued at time of, or prior to,
iodinated contrast imaging procedures. (2.3)
——————— DOSAGE FORMS AND STRENGTHS ———————
JANUMET XR Tablets:
sitagliptin 100 mg and metformin HCl 1000 mg extended-release
sitagliptin 50 mg and metformin HCl 500 mg extended-release
sitagliptin 50 mg and metformin HCl 1000 mg extended-release (3)
——————————- CONTRAINDICATIONS ——————————-
Severe renal impairment: eGFR below 30 mL/min/1.73 m2. (4)
Metabolic acidosis, including diabetic ketoacidosis. (4)
History of a serious hypersensitivity reaction (e.g., anaphylaxis or
angioedema) to JANUMET XR, sitagliptin, or metformin. (5.7, 6.2)
———————– WARNINGS AND PRECAUTIONS ———————–
Lactic Acidosis: See boxed warning. (5.1)
Pancreatitis: There have been postmarketing reports of acute
pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing
pancreatitis in patients treated with sitagliptin. If pancreatitis is
suspected, promptly discontinue JANUMET XR. (5.2)
Heart Failure: Has been observed with two other members of the
DPP-4 inhibitor class. Consider risks and benefits of JANUMET XR
in patients who have known risk factors for heart failure. Monitor
patients for signs and symptoms. (5.3)
Acute Renal Failure: Has been reported postmarketing sometimes
requiring dialysis. Before initiating JANUMET XR and at least
annually thereafter, assess renal function. (5.4)
Vitamin B12 Deficiency: Metformin may lower vitamin B12 levels.
Measure hematologic parameters annually and vitamin B12 at 2 to 3
year intervals and manage any abnormalities. (5.5)
Hypoglycemia with Concomitant Use with Insulin or Insulin
Secretagogues: Increased risk of hypoglycemia when used in
combination with insulin and/or an insulin secretagogue. A lower dose
of insulin or insulin secretagogue may be required. (5.6)
Hypersensitivity Reactions: There have been postmarketing reports
of serious allergic and hypersensitivity reactions in patients treated
with sitagliptin, such as anaphylaxis, angioedema, and exfoliative
skin conditions including Stevens-Johnson syndrome. Promptly stop
JANUMET XR, assess for other potential causes, institute
appropriate monitoring and treatment. (5.7)
Severe and Disabling Arthralgia: Has been reported in patients taking
DPP-4 inhibitors. Consider as a possible cause for severe joint pain
and discontinue drug if appropriate. (5.8)
Bullous Pemphigoid: There have been postmarketing reports
requiring hospitalization in patients taking DPP-4 inhibitors. Tell
patients to report development of blisters or erosions. If bullous
pemphigoid is suspected, discontinue JANUMET XR. (5.9)
—————————— ADVERSE REACTIONS ——————————
The most common adverse reactions reported in ≥5% of patients
simultaneously started on sitagliptin and metformin and more
commonly than in patients treated with placebo were diarrhea, upper
respiratory tract infection, and headache. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Merck
Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., LLC at 1-
877-888-4231 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch .
——————————- DRUG INTERACTIONS ——————————-
Carbonic anhydrase inhibitors may increase risk of lactic acidosis.
Consider more frequent monitoring. (7)
Drugs that reduce metformin clearance (such as ranolazine,
vandetanib, dolutegravir, and cimetidine) may increase the
accumulation of metformin. Consider the benefits and risks of
concomitant use. (7)
Alcohol can potentiate the effect of metformin on lactate metabolism.
Warn patients against excessive alcohol intake. (7)
———————– USE IN SPECIFIC POPULATIONS ———————–
Females and Males of Reproductive Potential: Advise
premenopausal females of the potential for an unintended pregnancy.
(8.3)
Geriatric Use: Assess renal function more frequently. (8.5)
Hepatic Impairment: Avoid use in patients with hepatic impairment.
(8.7)
See 17 for PATIENT COUNSELING INFORMATION and Medication
Guide
FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: LACTIC ACIDOSIS
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing
2.2 Recommendations for Use in Renal Impairment
2.3 Discontinuation for Iodinated Contrast Imaging Procedures
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Lactic Acidosis
5.2 Pancreatitis
5.3 Heart Failure
5.4 Acute Renal Failure
5.5 Vitamin B12 Deficiency
5.6 Hypoglycemia with Concomitant Use with Insulin or Insulin
Secretagogues
5.7 Hypersensitivity Reactions
5.8 Severe and Disabling Arthralgia
5.9 Bullous Pemphigoid
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.3 Females and Males of Reproductive Potential
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information
are not listed.
AE-JXR-00057 | Exp: 30 SEPT 2026