Linagliptin

472.54

472.54

3X29ZEJ4R2

C83887

White to yellow solid; also reported as a crystalline solid

A10BD11|A10BH05|A10BD19|A - Alimentary tract and metabolism

29335990

114

1.9

1.39

202 °C

661.2°C at 760 mmHg

353.7±34.3 °C

1.717

H2O: <1 mg/mL;soluble in methanol; sparingly soluble in ethanol; very slightly soluble in isopropanol, alcohol

5.75X10-17 mm Hg at 25 deg C (est)

pKa1 = 1.9; pKa2 = 8.6

Slightly hygroscopic

Stable if stored as directed; avoid strong oxidizing agents

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including linagliptin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Personal protective equipment as follows: Breathing equipment: NIOSH/MSHA-approved respirator. Protection of hands: chemical-resistant rubber gloves. Eye protection: chemical safety goggles.

Suitable extinguishing agents: water spray, carbon dioxide, dry chemical powder or foam. Protective equipment: wear self-contained breathing apparatus and protective clothing to prevent contact with skin and eyes.

Accidental release measures: After Inhalation: cordon off area of spill; wear self-contained breathing apparatus, protective clothing and heavy rubber gloves Measures for cleaning/collecting absorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); decontaminate surfaces and equipment by scrubbing with alcohol; dispose of contaminated material /in accordance with prevailing country, fedreal, state and local regulations/.

Handling should only be performed by personnel trained and familiar with handling of potent active pharmaceutical ingredients.|Information for safe handling: avoid inhalation and contact with skin, eyes and clothing ... .

No dosage adjustment is necessary based on race, age, weight, sex, renal impairment, or hepatic impairment. Studies of efficacy and safety in pediatric populations were not included in the original drug approval but recent clinical trials show linagliptin to be well tolerated in patients 10 to 18 years old. Animal studies showed an increased risk of lymphoma in female rats at over 200 times the clinical dose. Aside from this effect, linagliptin was not shown to be mutagenic, clastogenic, or have an effect on fertility.|IDENTIFICATION AND USE: Linagliptin 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, but should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. HUMAN EXPOSURE AND TOXICITY: In a pooled dataset of 14 placebo-controlled clinical trials, adverse reactions that occurred in > or = 2% of patients receiving Tradjenta (Linagliptin) (n = 3625) were nasopharyngitis (7.0%), diarrhea (3.3%), and cough (2.1%). Other adverse reactions reported in clinical studies with treatment of Tradjenta (Linagliptin) were hypersensitivity (e.g., urticaria, angioedema, localized skin exfoliation, or bronchial hyperreactivity), and myalgia. Additional adverse reactions have been identified during postapproval use of Tradjenta (Linagliptin); acute pancreatitis, including fatal pancreatitis, hypersensitivity reactions including anaphylaxis, angioedema, exfoliative skin conditions, and rash. ANIMAL STUDIES: Linagliptin did not increase the incidence of tumors in male and female rats in a 2-year study at doses of 6, 18, and 60 mg/kg. Linagliptin did not increase the incidence of tumors in mice in a 2-year study at doses up to 80 mg/kg (males) and 25 mg/kg (females). Higher doses of Linagliptin in female mice (80 mg/kg) increased the incidence of lymphoma. In fertility studies in rats, Linagliptin had no adverse effects on early embryonic development, mating, fertility, or bearing live young up to the highest dose of 240 mg/kg. Linagliptin crossed the placenta into the fetus following oral dosing in pregnant rats and rabbits and available animal data have shown excretion of linagliptin in milk at a milk-to-plasma ratio of 4:1. Linagliptin was not mutagenic or clastogenic with or without metabolic activation in the Ames bacterial mutagenicity assay, a chromosomal aberration test in human lymphocytes, and an in vivo micronucleus assay.

In large clinical trials, rates of serum enzyme elevations were similar with linagliptin therapy (

Trajenta is not indicated in combination with insulin due to an increase in cardiovascular risk, which cannot be excluded.|Insulin secretagogues and insulin are known to cause hypoglycemia. The use of Tradjenta in combination with an insulin secretagogue (e.g., sulfonylurea) was associated with a higher rate of hypoglycemia compared with placebo in a clinical trial. The use of Tradjenta in combination with insulin in subjects with severe renal impairment was associated with a higher rate of hypoglycemia. Therefore, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when used in combination with Tradjenta.|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.|Sulfonylureas and insulin are known to cause hypoglycemia. Therefore, caution is advised when linagliptin is used in combination with a sulfonylurea and/or insulin. A dose reduction of the sulfonylurea or insulin, may be considered.|Linagliptin is a weak to moderate inhibitor of cytochrome P-450 (CYP) isoenzyme 3A4; however, it does not inhibit or induce CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 4A11 in vitro. In vivo studies indicate that drug interactions are unlikely with substrates of CYP isoenzymes 3A4, 2C9, or 2C8. No adjustment of linagliptin dosage is recommended based on results of pharmacokinetic studies. Inducers of CYP3A4 (e.g., rifampin) decrease exposure to linagliptin, resulting in subtherapeutic and likely ineffective concentrations. The manufacturer states that alternatives to linagliptin are strongly recommended in patients who require therapy with potent CYP3A4 inducers.

Trajenta is not recommended for use in pregnancy.|A limited number of patients with history of congestive heart failure participated in clinical studies with Trajenta. In clinical trials, patients with a clinically significant history of cardiac disease or presence of active cardiac disease within 6 months were excluded. Use in this population is not recommended.|Tradjenta should 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.

Linagliptin is 99% protein bound at a concentration of 1nmol/L and 75-89% protein bound at a concentration of >30nmol/L.

Linagliptin's production and use as an antidiabetic drug(1) may result in its release to the environment through various waste streams(SRC). Antidiabetic compounds are among the most prescribed pharmaceuticals(2).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3,100(SRC), determined from a structure estimation method(2), indicates that linagliptin is expected to have slight mobility in soil(SRC). The pKa of linagliptin is 8.6(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of linagliptin from moist soil surfaces is not expected to be an important fate process because linagliptin exists as a cation and cations do not volatilize(SRC). Linagliptin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.6X10-17 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2014).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3,100(SRC), determined from a structure estimation method(2), indicates that linagliptin is expected to adsorb to suspended solids and sediment(SRC). A pKa of 8.6(3) indicates linagliptin will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces and bioconcentration are not expected to be important fate processes. Biodegradation data in water were not available(SRC, 2014).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), linagliptin, which has an estimated vapor pressure of 5.6X10-17 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase linagliptin may be removed from the air by wet and dry deposition(SRC). Linagliptin contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Linagliptin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Linagliptin contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

A pKa of 8.6(1) indicates linagliptin will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, bioconcentration is not expected to be an important fate process(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of linagliptin can be estimated to be 3,100(SRC). According to a classification scheme(2), this estimated Koc value suggests that linagliptin is expected to have slight mobility in soil. The pKa of linagliptin is 8.6(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

A pKa of 8.6(1) indicates linagliptin will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process. Linagliptin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.6X10-12 mm Hg(SRC), determined from a fragment constant method(2).

While data specific to linagliptin were not located(SRC, 2014), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are, therefore, discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Available animal data /in rats and rabbits/ have shown excretion of linagliptin in milk at a milk-to-plasma ratio of 4:1.

Occupational exposure to linagliptin may occur through inhalation and dermal contact with this compound at workplaces where linagliptin is produced or used. Exposure to linagliptin among the general population may be among those administered the drugs Jentadueto or Tradjenta, antidiabetics. (SRC)

Linagliptin is indicated for the treatment of type II diabetes in addition to diet and exercise. It should not be used to treat type I diabetes or in diabetic ketoacidosis. An extended-release combination product containing empagliflozin, linagliptin, and metformin was approved by the FDA in January 2020 for the improvement of glycemic control in adults with type 2 diabetes mellitus when used adjunctively with diet and exercise.|FDA Label|Treatment of adult patients with type-2 diabetes mellitus:Jentadueto is indicated as an adjunct to diet and exercise to improve glycaemic control in adult patients inadequately controlled on their maximal tolerated dose of metformin alone, or those already being treated with the combination of linagliptin and metformin.Jentadueto is indicated in combination with a sulphonylurea (i.e. triple combination therapy) as an adjunct to diet and exercise in adult patients inadequately controlled on their maximal tolerated dose of metformin and a sulphonylurea.|Trajenta is indicated in the treatment of type 2 diabetes mellitus to improve glycaemic control in adults:as monotherapyin patients inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to intolerance, or contraindicated due to renal impairment.as combination therapyin combination with metformin when diet and exercise plus metformin alone do not provide adequate glycaemic control.in combination with a sulphonylurea and metformin when diet and exercise plus dual therapy with these medicinal products do not provide adequate glycaemic control.in combination with insulin with or without metformin, when this regimen alone, with diet and exercise, does not provide adequate glycaemic control.|Glyxambi, fixed dose combination of empagliflozin and linagliptin, is indicated in adults aged 18 years and older with type 2 diabetes mellitus:to improve glycaemic control when metformin and/or sulphonylurea (SU) and one of the monocomponents of Glyxambi do not provide adequate glycaemic control;when already being treated with the free combination of empagliflozin and linagliptin.|Treatment of type II diabetes mellitus

Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor which is used in combination with diet and exercise in the therapy of type 2 diabetes, either alone or in combination with other oral hypoglycemic agents. Linagliptin has been linked to rare instances of clinically apparent liver injury.

Antidiabetic Agents

Hypoglycemic Agents|Tradjenta tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. /Included in US product label/

/BOXED WARNING/ WARNING: RISK OF LACTIC ACIDOSIS. Lactic acidosis is a rare, but serious, complication that can occur due to metformin accumulation. The risk increases with conditions such as renal impairment, sepsis, dehydration, excess alcohol intake, hepatic impairment, and acute congestive heart failure. The onset is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate. If acidosis is suspected, Jentadueto should be discontinued and the patient hospitalized immediately. /Linagliptin and metformin hydrochloride combination product/|FDA is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis and pre-cancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with a class of drugs called incretin mimetics. These findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes. FDA has asked the researchers to provide the methodology used to collect and study these specimens and to provide the tissue samples so the Agency can further investigate potential pancreatic toxicity associated with the incretin mimetics. Drugs in the incretin mimetic class include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). These drugs work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal. They are used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. FDA has not reached any new conclusions about safety risks with incretin mimetic drugs. This early communication is intended only to inform the public and health care professionals that the Agency intends to obtain and evaluate this new information. ... FDA will communicate its final conclusions and recommendations when its review is complete or when the Agency has additional information to report. The Warnings and Precautions section of drug labels and patient Medication Guides for incretin mimetics contain warnings about the risk of acute pancreatitis. FDA has not previously communicated about the potential risk of pre-cancerous findings of the pancreas with incretin mimetics. FDA has not concluded these drugs may cause or contribute to the development of pancreatic cancer. At this time, patients should continue to take their medicine as directed until they talk to their health care professional, and health care professionals should continue to follow the prescribing recommendations in the drug labels. ...|There have been postmarketing reports of acute pancreatitis, including fatal pancreatitis, in patients taking Tradjenta. Take careful notice of potential signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue Tradjenta and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using Tradjenta.|There have been postmarketing reports of serious hypersensitivity reactions in patients treated with Tradjenta. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with Tradjenta, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue Tradjenta, assess for other potential causes for the event, and institute alternative treatment for diabetes. Angioedema has also been reported with other dipeptidyl peptidase-4 (DPP-4) inhibitors. Use caution in a patient with a history of angioedema to another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with Tradjenta.|For more Drug Warnings (Complete) data for Linagliptin (20 total), please visit the HSDB record page.

A 5mg oral dose of linagliptin results in >80% inhibition of dipeptidyl peptidase 4 (DPP-4) for ≥24 hours. Inhibition of DPP-4 increases the concentration of glucagon-like peptide 1 (GLP-1), leading to decreased glycosylated hemoglobin and fasting plasma glucose.

Compounds that suppress the degradation of INCRETINS by blocking the action of DIPEPTIDYL-PEPTIDASE IV. This helps to correct the defective INSULIN and GLUCAGON secretion characteristic of TYPE 2 DIABETES MELLITUS by stimulating insulin secretion and suppressing glucagon release. (See all compounds classified as Dipeptidyl-Peptidase IV Inhibitors.)|Substances which lower blood glucose levels. (See all compounds classified as Hypoglycemic Agents.)|Peptides which stimulate INSULIN release from the PANCREATIC BETA CELLS following oral nutrient ingestion, or postprandially. (See all compounds classified as Incretins.)

Oral bioavailability of linagliptin is 30%.|84.7% of linagliptin is eliminated in the feces and 5.4% is eliminated in the urine.|A single intravenous dose of 5mg results in a volume of distribution of 1110L. However an intravenous infusion of 0.5-10mg results in a volume of distribution of 380-1540L.|Total clearance of linagliptin is 374mL/min.|Available animal data have shown excretion of linagliptin in milk at a milk-to-plasma ratio of 4:1.|After oral administration of a single 5-mg dose to healthy subjects, peak plasma concentrations of linagliptin occurred at approximately 1.5 hours post dose (Tmax); the mean plasma area under the curve (AUC) was 139 nmol*h/L and maximum concentration (Cmax) was 8.9 nmol/L.|The absolute bioavailability of linagliptin is approximately 30%. High-fat meal reduced Cmax by 15% and increased AUC by 4%; this effect is not clinically relevant. Tradjenta may be administered with or without food.|Following administration of an oral (14C)-linagliptin dose to healthy subjects, approximately 85% of the administered radioactivity was eliminated via the enterohepatic system (80%) or urine (5%) within 4 days of dosing. Renal clearance at steady state was approximately 70 mL/min.|For more Absorption, Distribution and Excretion (Complete) data for Linagliptin (6 total), please visit the HSDB record page.

An oral dose of linagliptin is excreted primarily in the feces. 90% of an oral dose is excreted unchanged in the urine and feces. The predominant metabolite in the plasma is CD1790 and the predominant metabolite recovered after excretion was M489(1). Other metabolites are produced through oxidation, oxidative degradation, N-acetylation, glucuronidation, and cysteine adduct formation. Other metabolites have been identified through mass spectrometry though no structures were determined. Metabolism of linagliptin is mediated by cytochrome P450 3A4, aldo-keto reductases, and carbonyl reductases.|Following oral administration, the majority (about 90%) of linagliptin is excreted unchanged, indicating that metabolism represents a minor elimination pathway. A small fraction of absorbed linagliptin is metabolized to a pharmacologically inactive metabolite, which shows a steady-state exposure of 13.3% relative to linagliptin.

The terminal half life of linagliptin is 155 hours.|The effective half-life for accumulation of linagliptin, as determined from oral administration of multiple doses of linagliptin 5 mg, is approximately 12 hours.|Plasma concentrations of linagliptin decline in at least a biphasic manner with a long terminal half-life (>100 hours), related to the saturable binding of linagliptin to DPP-4.

Linagliptin is a competitive, reversible DPP-4 inhibitor. Inhibition of this enzyme slows the breakdown of GLP-1 and glucose-dependant insulinotropic polypeptide (GIP). GLP-1 and GIP stimulate the release of insulin from beta cells in the pancreas while inhibiting release of glucagon from pancreatic beta cells. These effects together reduce the breakdown of glycogen in the liver and increase insulin release in response to glucose.|Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta-cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha-cells, resulting in a reduction in hepatic glucose output.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma and seizures if the occur. 3. Obtain finger stick blood glucose levels every 1-2 hours until stabilized. /Antidiabetic agents/|For more Antidote and Emergency Treatment (Complete) data for Linagliptin (6 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ An open-label pharmacokinetic study evaluated the pharmacokinetics of linagliptin 5 mg in male and female patients with varying degrees of chronic renal impairment. The study included 6 healthy subjects with normal renal function (creatinine clearance [CrCl] =80 mL/min), 6 patients with mild renal impairment (CrCl 50 to <80 mL/min), 6 patients with moderate renal impairment (CrCl 30 to <50 mL/min), 10 patients with type 2 diabetes mellitus and severe renal impairment (CrCl <30 mL/min), and 11 patients with type 2 diabetes mellitus and normal renal function. Creatinine clearance was measured by 24-hour urinary creatinine clearance measurements or estimated from serum creatinine based on the Cockcroft-Gault formula. Under steady-state conditions, linagliptin exposure in patients with mild renal impairment was comparable to healthy subjects. In patients with moderate renal impairment under steady-state conditions, mean exposure of linagliptin increased (AUCt,ss by 71% and Cmax by 46%) compared with healthy subjects. This increase was not associated with a prolonged accumulation half-life, terminal half-life, or an increased accumulation factor. Renal excretion of linagliptin was below 5% of the administered dose and was not affected by decreased renal function. Patients with type 2 diabetes mellitus and severe renal impairment showed steady-state exposure approximately 40% higher than that of patients with type 2 diabetes mellitus and normal renal function (increase in AUCt,ss by 42% and Cmax by 35%). For both type 2 diabetes mellitus groups, renal excretion was below 7% of the administered dose.|/HUMAN EXPOSURE STUDIES/ In a randomized, placebo-controlled, active-comparator, 4-way crossover study, 36 healthy subjects were administered a single oral dose of linagliptin 5 mg, linagliptin 100 mg (20 times the recommended dose), moxifloxacin, and placebo. No increase in QTc was observed with either the recommended dose of 5 mg or the 100-mg dose. At the 100-mg dose, peak linagliptin plasma concentrations were approximately 38-fold higher than the peak concentrations following a 5-mg dose.|/SIGNS AND SYMPTOMS/ In a pooled dataset of 14 placebo-controlled clinical trials, adverse reactions that occurred in > or = 2% of patients receiving Tradjenta (Linagliptin) (n = 3625) were nasopharyngitis (7.0%), diarrhea (3.3%), and cough (2.1%). ... Other adverse reactions reported in clinical studies with treatment of Tradjenta (Linagliptin) were hypersensitivity (e.g., urticaria, angioedema, localized skin exfoliation, or bronchial hyperreactivity), and myalgia.|/SIGNS AND SYMPTOMS/ Adverse reactions have been identified during postapproval use of Tradjenta: acute pancreatitis, including fatal pancreatitis; hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions; and rash.|For more Human Toxicity Excerpts (Complete) data for Linagliptin (11 total), please visit the HSDB record page.

(R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione

Jentadueto is a combination of linagliptin and metformin hydrochloride. Jentadueto tablets are available in the following dosage forms and strengths: 2.5 mg linagliptin/500 mg metformin hydrochloride; 2.5 mg linagliptin/850 mg metformin hydrochloride tablets; 2.5 mg linagliptin/1000 mg metformin hydrochloride tablets.|Oral: Tablet, film coated: 5 mg, Tradjenta (Boehringer Ingelheim, comarketed by Lilly)

In this work, two reversed-phase liquid chromatographic (RP-LC) methods have been developed for the determination of linagliptin (LNG) based on isocratic elution using a mobile phase consisting of potassium dihydrogen phosphate buffer pH (4.6)-acetonitrile(20:80, v/v) at a flow rate of 1 mL min(-1). Two detection techniques have been applied either UV detection at 299 nm in the first method or fluorometric detection at 239 nm for excitation and 355 nm for emission in the second method. Chromatographic separation in the two methods was achieved on a Symmetry cyanide column (150 mm x 4.6 mm, 5 um). Linearity, accuracy and precision were found to be acceptable over the concentration ranges of 2.5-80 ug mL(-1) for LNG in bulk and 2.5-15 ug mL(-1) for LNG in plasma with the first method and 5-160 ug mL(-1) for LNG in bulk with the second method. The optimized methods were validated and proved to be specific, robust and accurate for the quality control of the cited drug in its pharmaceutical preparation.

Human drugs -> Jentadueto -> EMA Drug Category|Drugs used in diabetes -> Human pharmacotherapeutic group|Human drugs -> Trajenta -> EMA Drug Category|Human drugs -> Glyxambi -> EMA Drug Category|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients