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
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Established tolerability profile in a 24-week study of treatment-naïve patients
Most commonly reported adverse reactions (≥5% and more commonly than with placebo)1,a
PERCENTAGE OF PATIENTS
IN TREATMENT-NAÏVE STUDYa,b | Saxagliptin 5 mg + metformin IR | Placebo + metformin IR |
---|---|---|
Headache | 7.5% | 5.2% |
Nasopharyngitis | 6.9% | 4.0% |
(n=320) | (n=328) |
aMetformin IR was initiated at a starting dose of 500 mg and titrated up to a maximum of 2000 mg daily.
bIn this study, saxagliptin 5 mg and metformin IR were administered as separate tablets.
Adverse reactions in placebo-controlled monotherapy trials of metformin XR occurring in >5% of metformin XR-treated patients and more commonly than in placebo-treated patients1
PERCENTAGE OF PATIENTS
Metformin XR | Placebo | |
---|---|---|
Diarrhea | 9.6% | 2.6% |
Nausea/Vomiting | 6.5% | 1.5% |
Overall incidence of adverse events with saxagliptin in monotherapy and add-on therapy studies was similar to placebo, 72% vs 71%, respectively.1
PERCENTAGE OF PATIENTS
IN MONOTHERAPY AND ADD-ON THERAPY STUDIESc | Saxagliptin 5 mg | Placebo |
---|---|---|
Upper Respiratory Tract Infection | 7.7% | 7.6% |
Urinary Tract Infection | 6.8% | 6.1% |
Headache | 6.5% | 5.9% |
(n=882) | (n=799) |
- Sinusitis: 2.6%, 2.9% vs 1.6%
- Abdominal pain: 1.7%, 2.4% vs 0.5%
- Gastroenteritis: 2.3%, 1.9% vs 0.9%
- Vomiting: 2.3%, 2.2% vs 1.3%
cPrespecified pooled analysis of 2 monotherapy studies, the add-on to metformin study, the add-on to glyburide study, and the add-on to a TZD study; 24-week data regardless of glycemic rescue.
Discontinuation of therapy due to adverse events occurred in 3.3%, 2.2%, and 1.8% of patients receiving saxagliptin 5 mg, 2.5 mg, and placebo, respectively.1
PERCENTAGE OF PATIENTS
Saxagliptin 5 mg | Saxagliptin 2.5 mg | Placebo | |
---|---|---|---|
Lymphopenia | 0.5% | 0.1% | 0.0% |
Rash | 0.3% | 0.2% | 0.3% |
Blood Creatinine Increase | 0.0% | 0.3% | 0.0% |
Blood Creatine Phosphokinase Increase | 0.2% | 0.1% | 0.0% |
(n=882) | (n=882) | (n=799) |
dReported in at least 2 patients treated with saxagliptin.
In the clinical trial database for saxagliptin to date, there have been 6 reports (0.12%) of tuberculosis among the patients treated with saxagliptin compared with no reports among the patients treated with comparator. Causality has not been established. In addition, 1 patient treated with saxagliptin developed suspected foodborne fatal salmonella sepsis. There have been no spontaneous reports of tuberculosis or opportunistic infections associated with saxagliptin use.
Saxagliptin 5 mg + metformin IR (n=320)
Placebo + metformin IR (n=328)
eReported hypoglycemic events were a combination of reports of either signs or symptoms consistent with hypoglycemia with or without documented glucose levels or reported low glucose levels without symptoms. A concurrent glucose measurement was not required or was normal in some patients. Therefore, it is not possible to conclusively determine that all these reports reflect true hypoglycemia.
fAdverse reactions of hypoglycemia were based on all reports of hypoglycemia.
gDefined as symptoms of hypoglycemia accompanied by a fingerstick glucose ≤50 mg/dL.
Incidence of diarrhea over 24 weeks2,3,h
PERCENTAGE OF PATIENTS
Saxagliptin 5 mg + metformin IR | Saxagliptin 2.5 mg + metformin IR | Placebo + metformin IR | |
---|---|---|---|
Uncontrolled on Metformin Monotherapy | 5.8% | 9.9% | 11.2% |
(n=191) | (n=192) | (n=179) | |
Treatment-Naïvei | 6.9% | -- | 7.3% |
(n=320) | (n=328) |
hIn these studies, saxagliptin and metformin IR were administered as separate tablets.
iMetformin IR was initiated at a starting dose of 500 mg and titrated up to a maximum of 2000 mg daily.