For US Health Care Professionals
WARNING FOR KOMBIGLYZE XR: LACTIC ACIDOSIS
US Full Prescribing Information including Boxed WARNING about lactic acidosis, and Medication Guide
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 impairment, renal impairment, and acute congestive heart failure.
The onset of lactic acidosis 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, KOMBIGLYZE™ XR (saxagliptin and metformin HCl extended-release) should be discontinued and the patient hospitalized immediately. [See Warnings and Precautions]
Click here for Important Safety Information including complete Boxed WARNING about lactic acidosis
A TREATMENT FOR ADULTS WITH TYPE 2 DIABETES MELLITUS, IN ADDITION TO DIET AND EXERCISE
STARTING THE KOMBIGLYZE XR DIALOGUE WITH YOUR PATIENTS
IMPORTANT TALKING POINTS AND RESOURCES FOR YOUR ADULT PATIENTS WITH TYPE 2 DIABETES MELLITUS
Managing patients with type 2 diabetes mellitus requires more than just the right prescription. It also requires ongoing patient discussion and support. This section contains important topics to discuss with patients for whom KOMBIGLYZE XR may be appropriate and links to additional resources for you and your patients.
1
Discuss whether KOMBIGLYZE XR is appropriate for your patients
- KOMBIGLYZE XR is for adult patients who need greater glycemic control through a combination of saxagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin, a biguanide1
- Talk to patients about their risk for lactic acidosis. Serious side effects can happen to patients taking KOMBIGLYZE XR. See the Boxed WARNING for KOMBIGLYZE XR
- Instruct patients to read the Medication Guide carefully before taking KOMBIGLYZE XR and each time they get a refill
- Contraindicated in patients with severe renal impairment (eGFR below 30 mL/min/1.73 m2)
2
Discuss the convenience of individualized, once-daily dosing
- The dosage of KOMBIGLYZE XR should be individualized based on the patient’s current regimen, effectiveness, and tolerability. Maximum daily recommended dose is 5 mg saxagliptin and 2000 mg metformin XR that can be taken as two 2.5/1000 mg tablets once a day1
- Strong CYP3A4/5 inhibitors (eg, ketoconazole): Coadministration with KOMBIGLYZE XR significantly increases saxagliptin concentrations. Recommend limiting saxagliptin dosage to 2.5 mg once daily
- Assess renal function prior to initiation of KOMBIGLYZE XR and periodically thereafter. If eGFR falls below 45 mL/minute/1.73 m2, assess the benefit risk of continuing therapy and limit dose of the saxagliptin component to 2.5 mg once daily. Discontinue KOMBIGLYZE XR if eGFR falls below 30 mL/minute/1.73 m2
- KOMBIGLYZE XR should generally be taken once daily with the evening meal with gradual dose titration to reduce the gastrointestinal side effects associated with metformin1
3
Encourage patients to access money-saving* offers and helpful patient support resources
- Affordability is an important factor for diabetes patients and their health care professionals. Explore money-saving offers for eligible* patients who have been prescribed KOMBIGLYZE XR
- Share helpful resources, listed below, to provide educational and treatment support for your patients
*Subject to eligibility. Restrictions apply. Not available for government-insured patients.
DOWNLOADABLE RESOURCES
Help reinforce the patient dialogue with these downloadable patient support resources:
DOWNLOADABLE RESOURCES
Help reinforce the patient dialogue with these downloadable patient support resources:
KOMBIGLYZE XR PATIENT BROCHURE —explains how KOMBIGLYZE XR may help lower blood sugar with descriptions of how KOMBIGLYZE XR works in the body, and the results of two clinical studies. It also shows how patients can save money on their prescriptions of KOMBIGLYZE XR, and the support available through the Fit2Me™ program that helps patients design appropriate meal plans and activities that they enjoy
MANAGING YOUR TYPE 2 DIABETES SHEET —diet and lifestyle suggestions to help your patients manage their type 2 diabetes, such as taking a short walk after meals or drinking one less soda per day. Includes descriptions of basic terms such as A1C, and a goal-setting guide
WHAT ARE YOUR NUMBERS TELLING YOU? BROCHURE —descriptions and illustrations to help patients understand type 2 diabetes, and how measurements such as A1C, FPG, and PPG are used to track their blood glucose levels. It also describes other health care specialties that you may recommend such as ophthalmologists, dietitians, and podiatrists
WHAT ARE YOUR NUMBERS TELLING YOU? BROCHURE IN SPANISH —the same brochure described above to give to your Spanish-speaking patients
PATIENT SUPPORT SITES
Your patients want to learn about their type 2 diabetes mellitus. You can help them understand.
Health Journey Support is:
- An online health library to share with your patients, containing videos and printable brochures, including information on type 2 diabetes mellitus
- A source of educational materials across AstraZeneca therapeutic areas, from diagnosis to treatment and wellness. Helping patients through the health journey every step of the way
Important Safety Information for KOMBIGLYZE XR
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 high risk groups are provided in the Full Prescribing Information.
If lactic acidosis is suspected, discontinue KOMBIGLYZE XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
Contraindications
- Severe renal impairment (eGFR below 30 mL/min/1.73 m2)
- Prior serious hypersensitivity reaction to saxagliptin or hypersensitivity to metformin hydrochloride
- Metabolic acidosis, including diabetic ketoacidosis
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Indication and Limitations of Use
Warnings and Precautions
Pancreatitis: There have been post-marketing reports of acute pancreatitis in patients taking saxagliptin, and in the SAVOR cardiovascular outcomes trial. Observe for pancreatitis. If pancreatitis is suspected, discontinue KOMBIGLYZE XR.
Heart Failure: In the SAVOR cardiovascular outcomes trial, more patients treated with saxagliptin were hospitalized for heart failure compared to placebo. Patients with a prior history of heart failure or renal impairment had a higher risk for hospitalization for heart failure. Consider the risks and benefits of KOMBIGLYZE XR in patients who have known risk factors for heart failure. Monitor for signs and symptoms. If heart failure develops, consider discontinuation of KOMBIGLYZE XR.
Vitamin B12 Deficiency: Metformin may lower vitamin B12 levels. Measure hematological parameters annually.
Hypoglycemia: When saxagliptin was used in combination with a sulfonylurea or with insulin, the incidence of confirmed hypoglycemia was increased over that of placebo. Consider lowering the dose of these agents when coadministered with KOMBIGLYZE XR.
Hypoglycemia could occur when caloric intake is deficient, strenuous exercise is not compensated by caloric supplementation, or when KOMBIGLYZE XR is used with other glucose-lowering agents or ethanol.
Hypersensitivity: Serious reactions have been reported in patients treated with saxagliptin, including anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with saxagliptin, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue KOMBIGLYZE XR. Use caution in patients with a history of angioedema to another DPP-4 inhibitor.
Severe and Disabling Arthralgia has been reported in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years. Patients experienced relief of symptoms upon discontinuation. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider discontinuing drug if appropriate.
Bullous Pemphigoid: There have been postmarketing reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If suspected, discontinue KOMBIGLYZE XR.
Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with KOMBIGLYZE XR.
Adverse Reactions
Most common adverse reactions reported in ≥5% of patients treated with saxagliptin and more commonly than in patients treated with placebo were upper respiratory tract infection (7.7%, 7.6%), urinary tract infection (6.8%, 6.1%), and headache (6.5%, 5.9%).
Adverse reactions reported in >5% of patients treated with metformin XR and more commonly than in patients treated with placebo were diarrhea (9.6% vs 2.6%) and nausea/vomiting (6.5% vs 1.5%).
Adverse reactions reported in ≥5% of treatment-naive patients treated with coadministered saxagliptin and metformin IR and more commonly than in patients treated with metformin IR alone were headache (7.5% vs 5.2%) and nasopharyngitis (6.9% vs 4.0%).
Drug Interactions
Strong CYP3A4/5 inhibitors (eg, ketoconazole): Coadministration with KOMBIGLYZE XR significantly increases saxagliptin concentrations. Recommend limiting saxagliptin dosage to 2.5 mg once daily.
Use in Specific Populations
Assess renal function prior to initiation of KOMBIGLYZE XR and periodically thereafter. If eGFR falls below 45 mL/minute/1.73 m2, assess the benefit risk of continuing therapy and limit dose of the saxagliptin component to 2.5 mg once daily. Discontinue KOMBIGLYZE XR if eGFR falls below 30 mL/minute/1.73 m2.
Indication and Limitations of Use
- KOMBIGLYZE 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 saxagliptin and metformin is appropriate
- KOMBIGLYZE XR is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis
Please see US Full Prescribing Information for KOMBIGLYZE XR (5/500•5/1000•2.5/1000 mg tablets), including Boxed WARNING about lactic acidosis, and Medication Guide.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.
This product information is intended for US Health Care Professionals only.
KOMBIGLYZE XR is a registered trademark and AZ&Me is a trademark of the AstraZeneca group of companies.
KOMBIGLYZE XR is a registered trademark of the AstraZeneca group of companies.
Fingertip Formulary is a registered trademark of Fingertip Formulary, LLC.
©2017 AstraZeneca. All rights reserved. US-8577; US-15269 Last Updated 11/17
Indication and Limitations of Use for KOMBIGLYZE® XR (saxagliptin and metformin HCl extended-release) tablets
KOMBIGLYZE 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 saxagliptin and metformin is appropriate.
KOMBIGLYZE XR is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
