Pronunciation: LIN-a-GLIP-tin
Class: Antidiabetic agent/Dipeptidyl peptidase-4 inhibitor

Trade Names

Tradjenta
- Tablets, oral 5 mg

Pharmacology

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.

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Pharmacokinetics

Absorption

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%.

Distribution

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.

Metabolism

A small fraction is metabolized to a pharmacologically inactive metabolite.

Elimination

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 Populations

Renal 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.

Contraindications

Hypersensitivity to linagliptin.

Dosage and Administration

Adults

PO 5 mg once daily.

General Advice

• 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.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

CYP3A4 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.

Adverse Reactions

CNS

Headache (6%).

EENT

Nasopharyngitis (6%).

GI

Pancreatitis.

Hypersensitivity

Hypersensitivity reactions, including angioedema, bronchial hyperreactivity, localized skin exfoliation, and urticaria.

Lab Tests

Uric acid increased (3%).

Metabolic

Hypoglycemia (8%); hyperlipidemia (3%); hypertriglyceridemia, weight increased (2%).

Musculoskeletal

Arthralgia, back pain (6%); myalgia.

Respiratory

Cough (2%).

Precautions

Monitor Periodically monitor blood glucose and A 1c .

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Type 1 diabetes/diabetic ketoacidosis

Do not use linagliptin in these settings.

Overdosage

Symptoms

No dose-related adverse reactions were reported with single doses of up to 600 mg.

Patient Information

• 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.

Copyright © 2009 Wolters Kluwer Health.