Linagliptin
FDA Drug Information • Also known as: Linagliptin, Tradjenta
- Brand Names
- Linagliptin, Tradjenta
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
11 DESCRIPTION TRADJENTA tablets for oral use contain linagliptin, an inhibitor of the DPP-4 enzyme. The chemical name of linagliptin is 1H-Purine-2,6-dione, 8-[(3R)-3-amino-1-piperidinyl]-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]- The molecular formula is C 25 H 28 N 8 O 2 and the molecular weight is 472.54 g/mol. The structural formula is: Linagliptin is a white to yellowish, not or only slightly hygroscopic solid substance. It is very slightly soluble in water (0.9 mg/mL). Linagliptin is soluble in methanol (ca. 60 mg/mL), sparingly soluble in ethanol (ca. 10 mg/mL), very slightly soluble in isopropanol (<1 mg/mL), and very slightly soluble in acetone (ca. 1 mg/mL). Each film-coated tablet of TRADJENTA contains 5 mg of linagliptin free base and the following inactive ingredients: copovidone, corn starch, magnesium stearate, mannitol, and pregelatinized starch. In addition, the film coating contains the following inactive ingredients: hypromellose, polyethylene glycol, red ferric oxide, talc, and titanium dioxide. Chemical Structure
What Is Linagliptin Used For?
1 INDICATIONS AND USAGE TRADJENTA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus . TRADJENTA is a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus ( 1 ) Limitations of Use Not recommended in patients with type 1 diabetes mellitus as it would not be effective ( 1 ) Has not been studied in patients with a history of pancreatitis ( 1 ) Limitations of Use TRADJENTA is not recommended in patients with type 1 diabetes mellitus as it would not be effective. TRADJENTA has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using TRADJENTA [see Warnings and Precautions (5.1) ].
Dosage and Administration
2 DOSAGE AND ADMINISTRATION The recommended dosage of TRADJENTA is 5 mg orally once daily ( 2.1 ) TRADJENTA can be taken with or without food ( 2.1 ) 2.1 Recommended Dosage and Administration The recommended dosage of TRADJENTA is 5 mg taken orally once daily, with or without food.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: Pancreatitis [see Warnings and Precautions (5.1) ] Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Severe and Disabling Arthralgia [see Warnings and Precautions (5.4) ] Bullous Pemphigoid [see Warnings and Precautions (5.5) ] Heart Failure [see Warnings and Precautions (5.6) ] Most common adverse reaction (incidence ≥5% and more often than placebo) was nasopharyngitis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety evaluation of TRADJENTA 5 mg once daily in patients with type 2 diabetes mellitus is based on 14 placebo-controlled trials, 1 active-controlled trial, and one trial in patients with severe renal impairment. In the 14 placebo-controlled studies, a total of 3,625 patients were randomized and treated with TRADJENTA 5 mg daily and 2,176 with placebo. The mean exposure in patients treated with TRADJENTA across studies was 29.6 weeks. The maximum follow-up was 78 weeks. TRADJENTA 5 mg once daily was studied as monotherapy in three placebo-controlled trials of 18 and 24 weeks' duration and in five additional placebo-controlled studies lasting ≤18 weeks. The use of TRADJENTA in combination with other antihyperglycemic agents was studied in six placebo-controlled trials: two with metformin (12 and 24 weeks' treatment duration); one with a sulfonylurea (18 weeks' treatment duration); one with metformin and sulfonylurea (24 weeks' treatment duration); one with pioglitazone (24 weeks' treatment duration); and one with insulin (primary endpoint at 24 weeks). In a pooled dataset of 14 placebo-controlled clinical trials, adverse reactions that occurred in ≥2% of patients receiving TRADJENTA (n = 3,625) and more commonly than in patients given placebo (n = 2,176), are shown in Table 1. Table 1 Adverse Reactions Reported in ≥2% of Patients Treated with TRADJENTA and Greater than Placebo in Placebo-Controlled Clinical Studies of TRADJENTA Monotherapy or Combination Therapy Adverse Reactions TRADJENTA 5 mg (%) n = 3,625 Placebo (%) n = 2,176 Nasopharyngitis 7.0 6.1 Diarrhea 3.3 3.0 Cough 2.1 1.4 Rates for other adverse reactions for TRADJENTA 5 mg vs placebo when TRADJENTA was used in combination with specific antidiabetic agents were: urinary tract infection (3.1% vs 0%) and hypertriglyceridemia (2.4% vs 0%) when TRADJENTA was used as add-on to sulfonylurea; hyperlipidemia (2.7% vs 0.8%) and weight increased (2.3% vs 0.8%) when TRADJENTA was used as add-on to pioglitazone; and constipation (2.1% vs 1%) when TRADJENTA was used as add-on to basal insulin therapy. Other adverse reactions reported in clinical studies with treatment of TRADJENTA were hypersensitivity (e.g., urticaria, angioedema, localized skin exfoliation, or bronchial hyperreactivity) and myalgia. Following 104 weeks' treatment in a controlled trial comparing TRADJENTA with glimepiride in which all patients were also receiving metformin, adverse reactions reported in ≥5% of patients treated with TRADJENTA (n = 776) and more frequently than in patients treated with a sulfonylurea (n = 775) were back pain (9.1% vs 8.4%), arthralgia (8.1% vs 6.1%), upper respiratory tract infection (8.0% vs 7.6%), headache (6.4% vs 5.2%), cough (6.1% vs 4.9%), and pain in extremity (5.3% vs 3.9%). In the clinical trial program, pancreatitis was reported in 15.2 cases per 10,000 patient year exposure while being treated...
Drug Interactions
7 DRUG INTERACTIONS Strong P-glycoprotein/CYP3A4 inducer: The efficacy of TRADJENTA may be reduced when administered in combination (e.g., with rifampin). Use of alternative treatments is strongly recommended. ( 7.1 ) 7.1 Inducers of P-glycoprotein or CYP3A4 Enzymes Rifampin decreased linagliptin exposure, suggesting that the efficacy of TRADJENTA may be reduced when administered in combination with a strong P-gp or CYP3A4 inducer. Therefore, use of alternative treatments is strongly recommended when linagliptin is to be administered with a strong P-gp or CYP3A4 inducer [see Clinical Pharmacology (12.3) ] . 7.2 Insulin Secretagogues or Insulin Insulin and insulin secretagogues are known to cause hypoglycemia. The risk of hypoglycemia is increased when linagliptin is used in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin. Coadministration of TRADJENTA with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower dosages of the insulin secretagogue or insulin to reduce the risk of hypoglycemia [see Warnings and Precautions (5.2) ] .
Contraindications
4 CONTRAINDICATIONS TRADJENTA is contraindicated in patients with hypersensitivity to linagliptin or any of the excipients in TRADJENTA, reactions such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity have occurred [see Warnings and Precautions (5.3) and Adverse Reactions (6) ]. Hypersensitivity to linagliptin or any of the excipients in TRADJENTA ( 4 , 5.3 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary The limited data with TRADJENTA use in pregnant women are not sufficient to inform of drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations ]. In animal reproduction studies, no adverse developmental effects were observed when linagliptin was administered to pregnant rats during the period of organogenesis at doses similar to the maximum recommended clinical dose, based on exposure [see Data ] . The estimated background risk of major birth defects is 6% to 10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20% to 25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Data Animal Data No adverse developmental outcome was observed when linagliptin was administered to pregnant Wistar Han rats and Himalayan rabbits during the period of organogenesis at doses up to 240 mg/kg/day and 150 mg/kg/day, respectively. These doses represent approximately 943-times (rats) and 1,943-times (rabbits) the 5 mg maximum clinical dose, based on exposure. No adverse functional, behavioral, or reproductive outcome was observed in offspring following administration of linagliptin to Wistar Han rats from gestation day 6 to lactation day 21 at a dose 49-times the maximum...
Overdosage
10 OVERDOSAGE In the event of an overdose with TRADJENTA, consider contacting the Poison Help Line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Removal of linagliptin by hemodialysis or peritoneal dialysis is unlikely.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-4383 NDC: 50090-4383-0 90 TABLET, FILM COATED in a BOTTLE
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.