Dosing and uses of Tradjenta (linagliptin)
Adult dosage forms and strengths
tablet
- 5mg
Diabetes Mellitus Type 2
Indicated for adults with diabetes mellitus type II along with diet and exercise to lower blood sugar; may be used as monotherapy or in combination with other common antidiabetic medications including metformin, sulfonylurea, pioglitazone, or insulin
5 mg PO qDay
Dosage modifications
Hepatic or renal impairment: No dosage adjustment required
Dosing Considerations
Not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings
Has not been studied in patients with a history of pancreatitis; unknown whether patients with a history of pancreatitis are at an increased risk of developing pancreatitis when taking linagliptin
Administration
May administer with or without food
When used in combination with other antidiabetic agents, a lower dose of the insulin secretagogue (eg, sulfanylurea) or insulin may be required to reduce the risk of hypoglycemia
Pediatric dosage forms and strengths
Safety and efficacy not established
Tradjenta (linagliptin) adverse (side) effects
1-10%
Nasopharyngitis (4.3%)
Hyperlipidemia (2.8%; with pioglitazone)
Cough (2.4%; with metformin and sulfonylurea)
Hypertriglyceridemia (2.4%; with sulfonylurea)
Weight gain (2.3%; with pioglitazone)
Hypoglycemia
- 7.6% overall incidence
- 22.9% incidence compared with placebo plus metformin and a sulfonylurea
- Incidence similar to placebo with monotherapy or combined with metformin or pioglitazone
Postmarketing Reports
Acute pancreatitis, including fatal pancreatitis
Rash
Mouth ulceration, stomatitis
Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions
Severe disabling arthralgia
Warnings
Contraindications
Hypersensitivity (eg, anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity)
Type 1 diabetes mellitus
Diabetic ketoacidosis
Cautions
Use in combination with an insulin secretagogue (eg, sulfonylurea) was associated with a higher rate of hypoglycemia compared with placebo in a clinical triaL
Rifampin decreased linagliptin exposure suggesting that the levels may be reduced when administered in combination with a strong P-gp or CYP 3A4 inducer; alternative treatment is strongly recommended when linagliptin is to be administered with P-gp or CYP 3A4 inducers
Serious hypersensitivity reactions reported including anaphylaxis, angioedema, and exfoliative skin conditions
Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate
Pancreatitis
- Postmarketing reports of acute pancreatitis, including fatal pancreatitis; monitor for signs and symptoms of pancreatitis, and discontinue if suspected
- Unknown if patients with history of pancreatitis are at increased risk for the development of pancreatitis while using linagliptin
Pregnancy and lactation
Pregnancy category: B
Lactation: Unknown whether distributed in breast milk; caution advised
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Tradjenta (linagliptin)
Mechanism of action
Dipeptidyl peptidase 4 (DPP-4) inhibitor; increases and prolongs incretin hormone activity which is inactivated by DPP-4 enzyme
Incretins regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and reducing glucagon secretion from pancreatic alpha cells
Absorption
Bioavailability: 30%
Peak Plasma Time: 1.5 hr
Peak Plasma Concentration: 8.9 nmol/L
AUC: 139 nmol•h/L
Distribution
Protein Bound: 75-99%; concentration dependent
Vd: 1,110 L
Metabolism
Small fraction metabolized to inactive metabolite
Excretion
Half-Life: 12 hr
Terminal Half-Life: >100 hr
Enterohepatic system (80%), urine (5%)
Renal clearance: 70 mL/min
Administration
Instructions
May administer with or without food
When used in combination with other antidiabetic agents, a lower dose of the insulin secretagogue (eg, sulfanylurea) or insulin may be required to reduce the risk of hypoglycemia
