Janumet XR

Name: Janumet XR

Descriptions

Metformin and sitagliptin combination is used to treat high blood sugar levels caused by type 2 diabetes. Metformin reduces the absorption of sugar from the stomach, reduces the release of stored sugar from the liver, and helps your body use sugar better. Sitagliptin helps to control blood sugar levels by increasing substances in the body that make the pancreas release more insulin. It also signals the liver to stop producing sugar (glucose) when there is too much sugar in the blood. This medicine does not help patients who have insulin-dependent or type 1 diabetes.

This medicine is available only with your doctor's prescription.

This product is available in the following dosage forms:

  • Tablet, Extended Release
  • Tablet

Janumet XR FDA Warning

WARNING: LACTIC ACIDOSIS

Lactic acidosis is a rare, but serious complication that can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic insufficiency, renal impairment, and acute congestive heart failure.

The onset is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress.

Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate.

If acidosis is suspected, this medication should be discontinued and the patient hospitalized immediately.

Side effects

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Sitagliptin And Metformin Immediate-Release Coadministration In Patients With Type 2 Diabetes Inadequately Controlled On Diet And Exercise

Table 1 summarizes the most common (≥5% of patients) adverse reactions reported (regardless of investigator assessment of causality) in a 24-week placebo-controlled factorial study in which sitagliptin and metformin immediate-release were coadministered to patients with type 2 diabetes inadequately controlled on diet and exercise.

Table 1: Sitagliptin and Metformin Immediate-Release Coadministered to Patients with Type 2 Diabetes Inadequately Controlled on Diet and Exercise:
Adverse Reactions Reported (Regardless of Investigator Assessment of Causality) in ≥5% of Patients Receiving Combination Therapy (and Greater than in Patients Receiving Placebo) *

  Number of Patients (%)
Placebo Sitagliptin 100 mg once daily Metformin Immediate-Release 500 mg or 1000 mg twice daily † Sitagliptin 50 mg twice daily + Metformin Immediate-Release 500 mg or 1000 mg twice daily†
N = 176 N = 179 N = 364† N = 372†
Diarrhea 7 (4.0) 5 (2.8) 28 (7.7) 28 (7.5)
Upper Respiratory Tract Infection 9 (5.1) 8 (4.5) 19 (5.2) 23 (6.2)
Headache 5 (2.8) 2 (1.1) 14 (3.8) 22 (5.9)
* Intent-to-treat population.
†Data pooled for the patients given the lower and higher doses of metformin.

Sitagliptin Add-On Therapy In Patients With Type 2 Diabetes Inadequately Controlled On Metformin Immediate-Release Alone

In a 24-week placebo-controlled trial of sitagliptin 100 mg administered once daily added to a twice daily metformin immediate-release regimen, there were no adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo. Discontinuation of therapy due to clinical adverse reactions was similar to the placebo treatment group (sitagliptin and metformin immediate-release, 1.9%; placebo and metformin immediate-release, 2.5%).

Gastrointestinal Adverse Reactions

The incidences of pre-selected gastrointestinal adverse experiences in patients treated with sitagliptin and metformin immediate-release were similar to those reported for patients treated with metformin immediate-release alone. See Table 2.

Table 2: Pre-selected Gastrointestinal Adverse Reactions (Regardless of Investigator Assessment of Causality) Reported in Patients with Type 2 Diabetes Receiving Sitagliptin and Metformin Immediate-Release

  Number of Patients (%)
Study of Sitagliptin and Metformin Immediate-Release in Patients Inadequately Controlled on Diet and Exercise Study of Sitagliptin Add-on in Patients Inadequately Controlled on Metformin Immediate-Release Alone
Placebo Sitagliptin 100 mg once daily Metformin Immediate-Release 500 mg or 1000 mg twice daily * Sitagliptin 50 mg bid + Metformin Immediate-Release 500 mg or 1000 mg twice daily * Placebo and Metformin Immediate-Release ≥1500 mg daily Sitagliptin 100 mg once daily and Metformin Immediate-Release ≥1500 mg daily
N = 176 N = 179 N = 364 N = 372 N = 237 N = 464
Diarrhea 7 (4.0) 5 (2.8) 28 (7.7) 28 (7.5) 6 (2.5) 11 (2.4)
Nausea 2 (1.1) 2 (1.1) 20 (5.5) 18 (4.8) 2 (0.8) 6 (1.3)
Vomiting 1 (0.6) 0 (0.0) 2 (0.5) 8 (2.2) 2 (0.8) 5 (1.1)
Abdominal Pain† 4 (2.3) 6 (3.4) 14 (3.8) 11 (3.0) 9 (3.8) 10 (2.2)
* Data pooled for the patients given the lower and higher doses of metformin.
† Abdominal discomfort was included in the analysis of abdominal pain in the study of initial therapy.

Sitagliptin In Combination With Metformin Immediate-Release And Glimepiride

In a 24-week placebo-controlled study of sitagliptin 100 mg as add-on therapy in patients with type 2 diabetes inadequately controlled on metformin immediate-release and glimepiride (sitagliptin, N=116; placebo, N=113), the adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients treated with sitagliptin and more commonly than in patients treated with placebo were: hypoglycemia (Table 3) and headache (6.9%, 2.7%).

Sitagliptin In Combination With Metformin Immediate-Release And Rosiglitazone

In a placebo-controlled study of sitagliptin 100 mg as add-on therapy in patients with type 2 diabetes inadequately controlled on metformin immediate-release and rosiglitazone (sitagliptin, N=181; placebo, N=97), the adverse reactions reported regardless of investigator assessment of causality through Week 18 in ≥5% of patients treated with sitagliptin and more commonly than in patients treated with placebo were: upper respiratory tract infection (sitagliptin, 5.5%; placebo, 5.2%) and nasopharyngitis (6.1%, 4.1%). Through Week 54, the adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients treated with sitagliptin and more commonly than in patients treated with placebo were: upper respiratory tract infection (sitagliptin, 15.5%; placebo, 6.2%), nasopharyngitis (11.0%, 9.3%), peripheral edema (8.3%, 5.2%), and headache (5.5%, 4.1%).

Sitagliptin In Combination With Metformin Immediate-Release And Insulin

In a 24-week placebo-controlled study of sitagliptin 100 mg as add-on therapy in patients with type 2 diabetes inadequately controlled on metformin immediate-release and insulin (sitagliptin, N=229; placebo, N=233), the only adverse reaction reported regardless of investigator assessment of causality in ≥5% of patients treated with sitagliptin and more commonly than in patients treated with placebo was hypoglycemia (Table 3).

Hypoglycemia

In all (N=5) studies, adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia; a concurrent glucose measurement was not required although most (77%) reports of hypoglycemia were accompanied by a blood glucose measurement ≤70 mg/dL. When the combination of sitagliptin and metformin immediate-release was coadministered with a sulfonylurea or with insulin, the percentage of patients reporting at least one adverse reaction of hypoglycemia was higher than that observed with placebo and metformin immediate-release coadministered with a sulfonylurea or with insulin (Table 3).

Table 3: Incidence and Rate of Hypoglycemia* (Regardless of Investigator Assessment of Causality) in Placebo-Controlled Clinical Studies of Sitagliptin in Combination with Metformin Immediate-Release Coadministered with Glimepiride or Insulin

Add-On to Glimepiride + Metformin Immediate-Release (24 weeks) Sitagliptin 100 mg + Metformin Immediate-Release + Glimepiride Placebo + Metformin Immediate-Release + Glimepiride
  N = 116 N = 113
  Overall (%) 19 (16.4) 1 (0.9)
  Rate (episodes/patient-year) † 0.82 0.02
  Severe (%)‡ 0 (0.0) 0 (0.0)
Add-On to Insulin + Metformin Immediate-Release (24 weeks) Sitagliptin 100 mg + Metformin Immedia Placebo + Metformin Immediate-Release + Insulin
  N = 229 N = 233
  Overall (%) 35 (15.3) 19 (8.2)
  Rate (episodes/patient-year) † 0.98 0.61
  Severe (%)‡ 1 (0.4) 1 (0.4)
* Adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia; a concurrent glucose measurement was not required: Intent-to-treat population.
† Based on total number of events (i.e., a single patient may have had multiple events).
‡ Severe events of hypoglycemia were defined as those events requiring medical assistance or exhibiting depressed level/loss of consciousness or seizure.

The overall incidence of reported adverse reactions of hypoglycemia in patients with type 2 diabetes inadequately controlled on diet and exercise was 0.6% in patients given placebo, 0.6% in patients given sitagliptin alone, 0.8% in patients given metformin immediate-release alone, and 1.6% in patients given sitagliptin in combination with metformin immediate-release. In patients with type 2 diabetes inadequately controlled on metformin immediate-release alone, the overall incidence of adverse reactions of hypoglycemia was 1.3% in patients given add-on sitagliptin and 2.1% in patients given add-on placebo.

In the study of sitagliptin and add-on combination therapy with metformin immediate-release and rosiglitazone, the overall incidence of hypoglycemia was 2.2% in patients given add-on sitagliptin and 0.0% in patients given add-on placebo through Week 18. Through Week 54, the overall incidence of hypoglycemia was 3.9% in patients given add-on sitagliptin and 1.0% in patients given add-on placebo.

Vital Signs And Electrocardiograms

With the combination of sitagliptin and metformin immediate-release, no clinically meaningful changes in vital signs or in electrocardiogram parameters (including the QTc interval) were observed.

Pancreatitis

In a pooled analysis of 19 double-blind clinical trials that included data from 10,246 patients randomized to receive sitagliptin 100 mg/day (N=5429) or corresponding (active or placebo) control (N=4817), the incidence of acute pancreatitis was 0.1 per 100 patient-years in each group (4 patients with an event in 4708 patient-years for sitagliptin and 4 patients with an event in 3942 patient-years for control). [See WARNINGS AND PRECAUTIONS]

Sitagliptin

The most common adverse experience in sitagliptin monotherapy reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo was nasopharyngitis.

Metformin Extended-Release

In a 24-week clinical trial in which extended-release metformin or placebo was added to glyburide therapy, the most common (>5% and greater than placebo) adverse reactions in the combined treatment group were hypoglycemia (13.7% vs. 4.9%), diarrhea (12.5% vs. 5.6%), and nausea (6.7% vs. 4.2%).

Laboratory Tests

Sitagliptin

The incidence of laboratory adverse reactions was similar in patients treated with sitagliptin and metformin immediate-release (7.6%) compared to patients treated with placebo and metformin (8.7%). In most but not all studies, a small increase in white blood cell count (approximately 200 cells/microL difference in WBC vs. placebo; mean baseline WBC approximately 6600 cells/microL) was observed due to a small increase in neutrophils. This change in laboratory parameters is not considered to be clinically relevant.

Metformin hydrochloride

In controlled clinical trials of metformin of 29 weeks duration, a decrease to subnormal levels of previously normal serum Vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease, possibly due to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of metformin or Vitamin B12 supplementation. [See WARNINGS AND PRECAUTIONS]

Postmarketing Experience

Additional adverse reactions have been identified during postapproval use of sitagliptin with metformin, sitagliptin, or metformin. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis, and exfoliative skin conditions including Stevens-Johnson syndrome [see Use In Specific Populations]; upper respiratory tract infection; hepatic enzyme elevations; acute pancreatitis, including fatal and nonfatal hemorrhagic and necrotizing pancreatitis [see INDICATIONS AND USAGE; WARNINGS AND PRECAUTIONS]; worsening renal function, including acute renal failure (sometimes requiring dialysis) [see Use In Specific Populations]; severe and disabling arthralgia [see Use In Specific Populations]; bullous pemphigoid [see Use In Specific Populations]; constipation; vomiting; headache; myalgia; pain in extremity; back pain; pruritus; cholestatic, hepatocellular, and mixed hepatocellular liver injury.

Read the entire FDA prescribing information for Janumet XR (Sitagliptin and Metformin HCl)

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Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of metformin and sitagliptin combination in the pediatric population. Safety and efficacy have not been established.

Before Using Janumet XR

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of metformin and sitagliptin combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of metformin and sitagliptin combination in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require an adjustment in the dose for patients receiving metformin and sitagliptin combination.

Pregnancy

Pregnancy Category Explanation
All Trimesters B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Acetrizoic Acid
  • Diatrizoate
  • Ethiodized Oil
  • Iobenzamic Acid
  • Iobitridol
  • Iocarmic Acid
  • Iocetamic Acid
  • Iodamide
  • Iodipamide
  • Iodixanol
  • Iodohippuric Acid
  • Iodopyracet
  • Iodoxamic Acid
  • Ioglicic Acid
  • Ioglycamic Acid
  • Iohexol
  • Iomeprol
  • Iopamidol
  • Iopanoic Acid
  • Iopentol
  • Iophendylate
  • Iopromide
  • Iopronic Acid
  • Ioseric Acid
  • Iosimide
  • Iotasul
  • Iothalamate
  • Iotrolan
  • Iotroxic Acid
  • Ioxaglate
  • Ioxitalamic Acid
  • Ipodate
  • Metrizamide
  • Metrizoic Acid
  • Tyropanoate Sodium

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Aspirin
  • Balofloxacin
  • Besifloxacin
  • Bupropion
  • Ciprofloxacin
  • Dasabuvir
  • Dofetilide
  • Dolutegravir
  • Eliglustat
  • Enoxacin
  • Fleroxacin
  • Flumequine
  • Gatifloxacin
  • Gemifloxacin
  • Ioversol
  • Lanreotide
  • Levofloxacin
  • Lomefloxacin
  • Moxifloxacin
  • Nadifloxacin
  • Norfloxacin
  • Octreotide
  • Ofloxacin
  • Ombitasvir
  • Paritaprevir
  • Pasireotide
  • Pazufloxacin
  • Pefloxacin
  • Pioglitazone
  • Prulifloxacin
  • Ritonavir
  • Rufloxacin
  • Simeprevir
  • Sparfloxacin
  • Thioctic Acid
  • Tosufloxacin
  • Vandetanib

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acebutolol
  • Atenolol
  • Betaxolol
  • Bisoprolol
  • Bitter Melon
  • Carteolol
  • Carvedilol
  • Celiprolol
  • Esmolol
  • Fenugreek
  • Furazolidone
  • Glucomannan
  • Guar Gum
  • Iproniazid
  • Isocarboxazid
  • Labetalol
  • Levobunolol
  • Linezolid
  • Methylene Blue
  • Metipranolol
  • Metoprolol
  • Moclobemide
  • Nadolol
  • Nebivolol
  • Nialamide
  • Oxprenolol
  • Patiromer
  • Penbutolol
  • Phenelzine
  • Pindolol
  • Practolol
  • Procarbazine
  • Propranolol
  • Psyllium
  • Ranolazine
  • Rasagiline
  • Rifampin
  • Safinamide
  • Selegiline
  • Sotalol
  • Timolol
  • Tranylcypromine
  • Verapamil

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Alcohol, excessive use or
  • Congestive heart failure, acute or unstable or
  • Dehydration, severe or
  • Heart attack, acute or
  • Heart or blood vessel problems or
  • Hypoxemia (decreased oxygen in the blood) or
  • Liver disease or
  • Poorly nourished condition or
  • Sepsis (severe infection) or
  • Shock (low blood pressure, blood circulation is poor) or
  • Weakened physical condition—Use with caution. May increase risk of serious side effects.
  • Anemia (low blood cells) or
  • Kidney disease or
  • Vitamin B12 deficiency—Use with caution. May make these conditions worse.
  • Angioedema (swelling of the face, lips, tongue, throat, arms, or legs), history with this medication or other dipeptidyl peptidase-4 (DPP-4) inhibitors—Use with caution. May increase the risk of this condition occurring again.
  • Diabetic ketoacidosis or metabolic acidosis (high ketones and acid in the blood) or
  • Kidney disease, severe or
  • Type 1 diabetes—Should not be used in patients with these conditions.
  • Fever or
  • Infection of any type or
  • Surgery (major) or
  • Trauma—These conditions may cause temporary problems with blood sugar control and your doctor may want to treat you with insulin.
  • Hypercholesterolemia (high cholesterol in the blood) or
  • Hypertriglyceridemia (high triglycerides and fats in the blood) or
  • Obesity or
  • Pancreas problems, history of—Use with caution. May increase risk for pancreatitis (swelling of the pancreas).
  • Radiologic procedures (eg, X-rays, CT scans, and MRIs) that require dyes to be injected in your vein—This medicine should be stopped before you have one of these procedures.

Uses of Janumet XR

  • It is used to lower blood sugar in patients with high blood sugar (diabetes).

What are some things I need to know or do while I take Janumet XR?

  • Tell all of your health care providers that you take Janumet XR. This includes your doctors, nurses, pharmacists, and dentists.
  • Do not drive if your blood sugar has been low. There is a greater chance of you having a crash.
  • Check your blood sugar as you have been told by your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Low blood sugar can happen. The chance of low blood sugar may be raised when this medicine is used with other drugs for high blood sugar (diabetes). Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call your doctor right away if you have any of these signs. Follow what you have been told to do if you get low blood sugar. This may include taking glucose tablets, liquid glucose, or some fruit juices.
  • It may be harder to control your blood sugar during times of stress like when you have a fever, an infection, an injury, or surgery. A change in level of physical activity or exercise and a change in diet may also affect your blood sugar. Talk with your doctor.
  • Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
  • Follow the diet and workout plan that your doctor told you about.
  • If you have been taking Janumet XR for a long time or at high doses, it may not work as well and you may need higher doses to get the same effect. This is known as tolerance. Call your doctor if this medicine stops working well. Do not take more than ordered.
  • A skin reaction called bullous pemphigoid has happened with drugs like this one. Sometimes, people have had to go to the hospital. Call your doctor right away if you have blisters or if your skin starts to break down.
  • Heart failure has happened in people taking drugs like this one. Tell your doctor if you have ever had heart failure or kidney problems. Call your doctor right away if you feel very tired or you have shortness of breath, a big weight gain, or swelling in the arms or legs.
  • If you are 65 or older, use Janumet XR with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Indications and Usage for Janumet XR

JANUMET® XR is 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 extended-release is appropriate. [See Clinical Studies (14).]

Important Limitations of Use

Janumet XR should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Janumet XR has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using Janumet XR. [See Warnings and Precautions (5.2).]

Janumet XR Dosage and Administration

Recommended Dosing

The dose of Janumet XR should be individualized on the basis of the patient's current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg sitagliptin and 2000 mg metformin. Initial combination therapy or maintenance of combination therapy should be individualized and left to the discretion of the healthcare provider.

  • In patients not currently treated with metformin, the recommended total daily starting dose of Janumet XR is 100 mg sitagliptin and 1000 mg metformin hydrochloride (HCl) extended-release. Patients with inadequate glycemic control on this dose of metformin can be titrated gradually, to reduce gastrointestinal side effects associated with metformin, up to the maximum recommended daily dose.
  • In patients already treated with metformin, the recommended total daily starting dose of Janumet XR is 100 mg sitagliptin and the previously prescribed dose of metformin.
  • For patients taking metformin immediate-release 850 mg twice daily or 1000 mg twice daily, the recommended starting dose of Janumet XR is two 50 mg sitagliptin/1000 mg metformin hydrochloride extended-release tablets taken together once daily.
  • Maintain the same total daily dose of sitagliptin and metformin when changing between JANUMET (sitagliptin and metformin HCl immediate-release) and Janumet XR. Patients with inadequate glycemic control on this dose of metformin can be titrated gradually, to reduce gastrointestinal side effects associated with metformin, up to the maximum recommended daily dose.

Janumet XR should be administered with food to reduce the gastrointestinal side effects associated with the metformin component. Janumet XR should be given once daily with a meal preferably in the evening. Janumet XR should be swallowed whole. The tablets must not be split, crushed, or chewed before swallowing. There have been reports of incompletely dissolved Janumet XR tablets being eliminated in the feces. It is not known whether this material seen in feces contains active drug. If a patient reports repeatedly seeing tablets in feces, the healthcare provider should assess adequacy of glycemic control [see Patient Counseling Information (17.1)].

The 100 mg sitagliptin/1000 mg metformin hydrochloride extended-release tablet should be taken as a single tablet once daily. Patients using two Janumet XR tablets (such as two 50 mg sitagliptin/500 mg metformin hydrochloride extended-release tablets or two 50 mg sitagliptin/1000 mg metformin hydrochloride extended-release tablets) should take the two tablets together once daily.

No studies have been performed specifically examining the safety and efficacy of Janumet XR in patients previously treated with other oral antihyperglycemic agents and switched to Janumet XR. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.

Recommendations for Use in Renal Impairment

Assess renal function prior to initiation of Janumet XR and periodically thereafter.

Janumet XR is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2. Discontinue Janumet XR if the patient's eGFR later falls below 30 mL/min/1.73 m2 [see Contraindications (4) and Warnings and Precautions (5.1)].

Initiation of Janumet XR in patients with an eGFR between 30 and 45 mL/min/1.73 m2 is not recommended.

In patients taking Janumet XR whose eGFR later falls below 45 mL/min/1.73 m2, assess the benefit risk of continuing therapy and limit dose of the sitagliptin component to 50 mg once daily.

Discontinuation for Iodinated Contrast Imaging Procedures

Discontinue 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. Re-evaluate eGFR 48 hours after the imaging procedure; restart Janumet XR if renal function is stable [see Warnings and Precautions (5.1)].

Drug Interactions

Carbonic Anhydrase Inhibitors

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 XR may increase the risk of lactic acidosis. Consider more frequent monitoring of these patients.

Drugs that Reduce Metformin Clearance

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 [see Clinical Pharmacology (12.3)]. Consider the benefits and risks of concomitant use.

Alcohol

Alcohol is known to potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake while receiving Janumet XR.

Insulin Secretagogues or Insulin

Coadministration of 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. [See Warnings and Precautions (5.7).]

Use of Metformin with Other Drugs

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 XR the patient should be closely observed to maintain adequate glycemic control.

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