Onglyza (saxagliptin HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Saxagliptin hydrochloride, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is an antidiabetic agent.
Saxagliptin inhibits dipeptidyl peptidase-4 (DPP-4), an enzyme that inactivates incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Both saxagliptin and its active metabolite (5-hydroxy saxagliptin) are more selective for inhibition of DPP-4 than for DPP-8 or DPP-9. Saxagliptin increases circulating levels of GLP-1 and GIP in a glucose-dependent manner.
GLP-1 and GIP stimulate insulin secretion from pancreatic beta-cells in a glucose-dependent manner (i.e., when glucose concentrations are normal or elevated). GLP-1 also decreases glucagon secretion from pancreatic alpha-cells, leading to reduced hepatic glucose production.
Saxagliptin lowers fasting plasma glucose concentrations and reduces glucose excursions following a glucose load or meal in patients with type 2 diabetes mellitus.
Saxagliptin monotherapy usually is not associated with substantial changes in body weight.
Saxagliptin did not produce a clinically meaningful prolongation of the QT interval corrected for rate (QTc) or heart rate at daily dosages up to 40 mg (8 times the maximum recommended human dose) in a randomized, double-blind, placebo-controlled, crossover, active-comparator study using moxifloxacin in healthy individuals.
Following oral administration of a single dose of saxagliptin under fasted conditions, the median time to peak plasma concentration was 2 hours for saxagliptin and 4 hours for 5-hydroxy saxagliptin. The peak plasma concentration and AUC of saxagliptin and its active metabolite increase proportionally in the 2.5--400 mg dosage range. Administration of saxagliptin with a high-fat meal increased the AUC by 27% and delayed the time to peak plasma concentration by approximately 20 minutes.
In vitro binding of saxagliptin and 5-hydroxy saxagliptin to serum proteins is negligible. Metabolism of saxagliptin is principally mediated by cytochrome P-450 (CYP) 3A4 and 3A5 isoenzymes. Mean plasma half-life of saxagliptin or 5-hydroxy saxagliptin is 2.5 or 3.1 hours, respectively.
Saxagliptin is eliminated by both renal and hepatic pathways; following administration of a single radiolabeled dose, 75% of the dose was excreted in urine (including 24% as unchanged drug and 36% as 5-hydroxy saxagliptin). A total of 22% of administered radioactivity was recovered in feces, representing the fraction of the saxagliptin dose excreted in bile and/or unabsorbed drug from the GI tract. There are no differences in the pharmacokinetics of saxagliptin based on gender, race, or body mass index.
Females have approximately 25% higher exposure to the active metabolite than males, although this is thought unlikely to be of clinical significance; gender does not affect clearance of saxagliptin or its active metabolite.
Bioequivalence between the fixed combination of saxagliptin and extended-release metformin hydrochloride and each agent (saxagliptin and extended-release metformin hydrochloride) given concurrently as separate tablets has been demonstrated; however, the relative bioavailability of the fixed combination of saxagliptin and extended-release metformin hydrochloride and concomitantly administered saxagliptin and immediate-release metformin hydrochloride has not been established. Metformin immediate-release and extended-release tablets have a similar extent of absorption, but peak plasma concentrations of metformin following administration of the drug as extended-release tablets are approximately 20% lower than peak concentrations following administration of the same dose as immediate-release tablets.
USES: Saxagliptin is used with a proper diet and exercise program to control high blood sugar in people with type 2 diabetes. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke.
Saxagliptin works by increasing levels of natural substances called incretins. Incretins help to control blood sugar by increasing insulin release, especially after a meal. They also decrease the amount of sugar your liver makes.
Generic name: saxagliptin HCl
Pronunciation: (SAX-a-GLIP-tin)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Onglyza
Indications
The following indications are listed for Onglyza:
- Type 2 Diabetes Mellitus
Also known as: Adult Onset Diabetes, Adult Onset Diabetes Mellitus, Adult Onset Dm, Diabetes Mellitus Type 2, Diabetes Mellitus Type Ii, Ketosis-Resistant Diabetes Mellitus, Ketosis-Resistant Dm, Maturity Onset Diabetes, Maturity Onset Diabetes Mellitus, Non-Insulin Dependent Diabetes Mellitus, Non-Insulin-Dependent Diabetes Mellitus, Type Ii Diabetes Mellitus.
Dosing
Dosage of saxagliptin hydrochloride (anhydrous) is expressed in terms of saxagliptin.
When saxagliptin is administered as monotherapy, the drug should be administered orally once daily without regard to meals. Saxagliptin tablets should be swallowed whole; they should not be cut, chewed, or crushed. If a dose of saxagliptin is missed, resume treatment with the next dose and do not take an extra dose.
When saxagliptin is administered in fixed combination with extended-release metformin, the combination should be administered orally once daily with the evening meal; dosage should be titrated gradually to minimize adverse GI effects of the metformin component. The fixed-combination tablets should be swallowed whole, and not cut, chewed, or crushed. If a dose is missed, resume treatment with the next dose and do not take an extra dose. Patients receiving saxagliptin in fixed combination with extended-release metformin hydrochloride should be advised that occasionally, the inactive ingredients of the fixed-combination tablet will be eliminated in the feces as a soft mass that may resemble the original tablet.
Store saxagliptin tablets alone or in fixed combination with extended-release metformin hydrochloride at 20--25degreesC; excursions permitted to 15--30degreesC.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*History of serious hypersensitivity to saxagliptin or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in at least 5% of patients in clinical trials receiving saxagliptin and more frequently than with placebo include upper respiratory tract infection, urinary tract infection, and headache.
Adverse effects reported in at least 5% of patients in clinical trials receiving saxagliptin in fixed combination with extended-release metformin and more frequently than placebo include headache and nasopharyngitis.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of saxagliptin have not been established in patients younger than 18 years of age.
Data on the use of saxagliptin in pregnant women are insufficient to determine a drug-associated risk for major birth defects or miscarriage. Poorly controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications. In addition, poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.
No adverse developmental effects independent of maternal toxicity were observed when saxagliptin was administered to pregnant rats and rabbits during the period of organogenesis and in pregnant and lactating rats during the prenatal and postnatal period.
Saxagliptin is distributed into milk in rats at a milk-to-plasma ratio of approximately 1:1. Data are lacking regarding the presence of saxagliptin in human milk and on the effects of the drug on the breast-fed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for saxagliptin and any potential adverse effects on the breast-fed infant from the drug or the underlying maternal condition.
The manufacturer states that no specific dosage adjustment of saxagliptin is necessary for age alone. Because geriatric patients are more likely to have decreased renal function, care should be taken in dosage selection based on renal function.
Of the 11,301 patients enrolled in clinical trials with saxagliptin, 4751 (42%) were >=65 years of age and 1210 (10.7%) were >=75 years of age. No substantial differences in safety and efficacy in patients >=65 years of age relative to younger adults have been observed, but increased sensitivity cannot be ruled out.
Saxagliptin and its active metabolite are eliminated in part by the kidneys; renal function should be assessed periodically since geriatric patients are more likely to have decreased renal function.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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