Class: Antidiabetic agent/Dipeptidyl peptidase-4 inhibitor
- Tablets, oral 5 mg
Inhibits dipeptidyl peptidase-4, an enzyme that degrades the incretin hormone's glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Results in increased concentrations of active incretin hormones, stimulating the release of insulin and decreasing levels of glucagon in the circulation.
T max is 1.5 h. The bioavailability is approximately 30%. Administration with a high-fat meal decreased C max by 15% and increased AUC by 4%.
Vd is approximately 1,110 L. Plasma protein binding is concentration-dependent, decreasing from 99% at 1 nmol/L to 75% to 89% at 30 nmol/L or more.
A small fraction is metabolized to a pharmacologically inactive metabolite.
Half-life is approximately 12 h. Approximately 85% of a dose is eliminated via enterohepatic system (80%) and in urine (5%). Renal Cl is 70 mL/min.
Special PopulationsRenal Function Impairment
Exposure of linagliptin is increased in moderate and severe renal impairment, but renal Cl was below 5% and 7% of the administered dose, respectively. No dosage adjustment is required.Hepatic Function Impairment
Mean AUC and C max of linagliptin decreased in patients with mild or moderate hepatic impairment, and C max decreased in patients with severe hepatic impairment. However, no dosage adjustment is necessary.Elderly
No clinically meaningful impact on the pharmacokinetics of linagliptin.Children
Pharmacokinetic studies have not been performed.Gender/Race/BMI/Weight
No clinically meaningful effects on the pharmacokinetics of sitagliptin were observed.
Indications and Usage
Adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus as monotherapy or combination therapy.
Hypersensitivity to linagliptin.
Dosage and AdministrationAdults
PO 5 mg once daily.
- May be taken with or without food.
- When used in combination with a sulfonylurea, a lower dose of the sulfonylurea may be required to reduce the risk of hypoglycemia.
Store between 59° and 86°F.
Drug InteractionsCYP3A4 strong inducers (eg, rifampin), P-glycoprotein strong inducers (eg, rifampin)
Linagliptin exposure may be reduced, decreasing the therapeutic effect. Alternative therapy to linagliptin is recommended.Food
High-fat meals reduced the linagliptin C max and AUC by 15% and 4%, respectively, which is not expected to be clinically important. Linagliptin may be taken with or without food.Ritonavir
Linagliptin exposure, pharmacologic effects, and risk of adverse reactions may be increased. Use with caution. Monitor the clinical response and adjust therapy as needed.Sulfonylureas (eg, glyburide)
The risk of hypoglycemia may be increased. Monitor blood glucose and adjust the sulfonylurea dose as needed.
Hypersensitivity reactions, including angioedema, bronchial hyperreactivity, localized skin exfoliation, and urticaria.
Uric acid increased (3%).
Hypoglycemia (8%); hyperlipidemia (3%); hypertriglyceridemia, weight increased (2%).
Arthralgia, back pain (6%); myalgia.
Periodically monitor blood glucose and A 1c .
Category B .
Safety and efficacy not established.
Type 1 diabetes/diabetic ketoacidosis
Do not use linagliptin in these settings.
No dose-related adverse reactions were reported with single doses of up to 600 mg.
- Educate patient, family, or caregiver regarding type 2 diabetes and its management.
- Instruct patient that this drug is not a substitute for diet and exercise and to follow the prescribed regimen.
- Emphasize the importance of regular daily blood glucose monitoring and periodic glycosylated Hgb tests.
- Review symptoms of hypoglycemia and hyperglycemia and action plans to undertake in the event that either occurs. Instruct patient to report hypoglycemic or hyperglycemic episodes to a health care provider.
- Advise patient that during periods of stress (eg, fever, trauma, infection, surgery), medication requirements may change and to seek medical advice promptly.
- Advise patients not to double their next dose if a dose is missed.
- Instruct patients to inform their health care provider if they develop any unusual symptoms, or if any known symptom persists or worsens.
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