Alogliptin

339.397

339.39

1592732-453-0

JHC049LO86

DTXSID90234130

C76906

A10BD09|A10BH04|A - Alimentary tract and metabolism

29335990

93.7

0.6

1.3±0.1 g/cm3

519.2°C at 760 mmHg

267.8℃

1.660

In water, 1491 mg/L at 25 deg C (est)

3.11X10-12 mm Hg at 25 deg C (est)

pKa = 9.47 (est)

White to off-white crystalline powder; soluble in dimethylsulfoxide; sparingly soluble in water, methanol; slightly soluble in ethanol; very slightly soluble in octanol, isopropyl acetate /Alogliptin benzoate/

3077

24/25

Stable if stored as directed; avoid strong oxidizing agents

P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

H302

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 alogliptin benzoate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Alogliptin benzoate/

|Warning|H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]|P201, P202, P264, P280, P281, P305+P351+P338, P308+P313, P337+P313, P405, and P501|Aggregated GHS information provided by 3 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, 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, federal, 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 ... .

Common adverse reactions (reported in ≥4% of patients treated with alogliptin 25 mg and more frequently than in patients who received placebo) are: nasopharyngitis, headache, and upper respiratory tract infection.|IDENTIFICATION AND USE: Alogliptin 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 not for treatment of type 1 diabetes or diabetic ketoacidosis. HUMAN EXPOSURE AND TOXICITY: During clinical trials patients receiving alogliptin 25 mg daily reported adverse reactions including pancreatitis (0.2%), hypersensitivity reactions (0.6%), a single event of serum sickness, nasopharyngitis (4.4%), hypoglycemia (1.5%), headache (4.2%) and upper respiratory tract infection (4.2%). In elderly patients the incidence of hypoglycemia with alogliptin increased to 5.4%. Postmarketing, patients taking alogliptin reported acute pancreatitis and serious hypersensitivity reactions. These reactions include anaphylaxis, angioedema and severe cutaneous adverse reactions, including Stevens-Johnson syndrome. There have been postmarketing reports of fatal and nonfatal hepatic failure in patients taking Nesina. ANIMAL STUDIES: In a fertility study in rats, alogliptin had no adverse effects on early embryonic development, mating or fertility at doses up to 500 mg/kg, or approximately 172 times the clinical dose based on plasma drug exposure (AUC). Alogliptin administered to pregnant rabbits and rats during the period of organogenesis was not teratogenic at doses of up to 200 mg/kg and 500 mg/kg, or 149 times and 180 times, respectively, the clinical dose based on plasma drug exposure (AUC). Doses of alogliptin up to 250 mg/kg (approximately 95 times clinical exposure based on AUC) given to pregnant rats from gestation Day 6 to lactation Day 20 did not harm the developing embryo or adversely affect growth and development of offspring. Placental transfer of alogliptin into the fetus was observed following oral dosing to pregnant rats. Alogliptin is secreted in the milk of lactating rats in a 2:1 ratio to plasma. No drug-related tumors were observed in mice after administration of 50, 150 or 300 mg/kg alogliptin for two years, or up to approximately 51 times the maximum recommended clinical dose of 25 mg, based on AUC exposure. Alogliptin was not mutagenic or clastogenic, with and without metabolic activation, in the Ames test with S. typhimurium and E. coli or the cytogenetic assay in mouse lymphoma cells. Alogliptin was negative in the in vivo mouse micronucleus study.

Liver injury due to alogliptin is rare. In large clinical trials, serum enzyme elevations were uncommon (1% to 3%) and no greater than with comparator arms or placebo. In these studies, no instances of clinically apparent liver injury with jaundice were reported. Since licensure, instances of serum enzyme elevations and acute hepatitis including acute liver failure attributed to alogliptin have been reported to the FDA and the sponsor. These cases have not been reported in the literature and the clinical features have not been defined. Cases of clinically apparent acute liver injury have been reported with other DPP-4 inhibitors such as sitagliptin and saxagliptin. The latency to onset was typically within 2 to 12 weeks of starting and the pattern of liver enzyme elevations was usually hepatocellular. Immunoallergic features were often present. Most cases were self-limited in course and rapidly reversed once the medication was stopped.

When alogliptin is used in combination with an insulin secretagogue (e.g., a sulfonylurea) or insulin, the incidence of hypoglycemia is increased compared with sulfonylurea or insulin monotherapy. Therefore, patients receiving alogliptin may require a reduced dosage of the concomitant insulin secretagogue or insulin to reduce the risk of hypoglycemia.

In patients with moderate hepatic impairment (Child-Pugh class B), alogliptin total exposure was approximately 10% lower than values in healthy individuals. Alogliptin has not been studied in patients with severe hepatic impairment (Child-Pugh class C). Caution should be exercised in patients with liver disease.|Nesina should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.

Alogliptin is 20% bound to plasma proteins.

Alogliptin'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 940(SRC), determined from a structure estimation method(2), indicates that alogliptin is expected to have low mobility in soil(SRC). The estimated pKa of alogliptin is 9.47(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 alogliptin from moist soil surfaces is not expected to be an important fate process because alogliptin exists as a cation and cations do not volatilize(SRC). Alogliptin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.1X10-12 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 940(SRC), determined from a structure estimation method(2), indicates that alogliptin is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 9.47(3) indicates alogliptin will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water or moist soil 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), alogliptin, which has an estimated vapor pressure of 3.1X10-12 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 alogliptin may be removed from the air by wet and dry deposition(SRC). Alogliptin contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

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

An estimated pKa of 9.47(1) indicates alogliptin 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 alogliptin can be estimated to be 940(SRC). According to a classification scheme(2), this estimated Koc value suggests that alogliptin is expected to have low mobility in soil. The estimated pKa of alogliptin is 9.47(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).

An estimated pKa of 9.47(1) indicates alogliptin 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. Alogliptin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.1X10-12 mm Hg(SRC), determined from a fragment constant method(2).

While data specific to alogliptin 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).

Alogliptin is secreted in the milk of lactating rats in a 2:1 ratio to plasma.

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

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.|FDA Label|Incresync is indicated as a second- or third-line treatment in adult patients aged 18 years and older with type-2 diabetes mellitus:as an adjunct to diet and exercise to improve glycaemic control in adult patients (particularly overweight patients) inadequately controlled on pioglitazone alone, and for whom metformin is inappropriate due to contraindications or intolerance;in combination with metformin (i.e. triple combination therapy) as an adjunct to diet and exercise to improve glycaemic control in adult patients (particularly overweight patients) inadequately controlled on their maximal tolerated dose of metformin and pioglitazone.In addition, Incresync can be used to replace separate tablets of alogliptin and pioglitazone in those adult patients aged 18 years and older with type-2 diabetes mellitus already being treated with this combination.After initiation of therapy with Incresync, patients should be reviewed after three to six months to assess adequacy of response to treatment (e.g. reduction in HbA1c). In patients who fail to show an adequate response, Incresync should be discontinued. In light of potential risks with prolonged pioglitazone therapy, prescribers should confirm at subsequent routine reviews that the benefit of Incresync is maintained (see section 4.4).|Vipidia is indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control in combination with other glucose lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control (see sections 4.4, 4.5 and 5.1 for available data on different combinations).|Treatment of type II diabetes mellitus

Alogliptin 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. Alogliptin has been reported to cause liver injury, but the characteristics and details of the injury have not been defined in the published literature.

Antidiabetic Agents

Hypoglycemic Agents|Nesina is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings. /Included in US product label/|A single-dose, open-label study was conducted to evaluate the pharmacokinetics of alogliptin 50 mg in patients with chronic renal impairment compared with healthy subjects. In patients with mild renal impairment (creatinine clearance (CrCl) =60 to <90 mL/min), an approximate 1.2-fold increase in plasma AUC of alogliptin was observed. Because increases of this magnitude are not considered clinically relevant, dose adjustment for patients with mild renal impairment is not recommended. In patients with moderate renal impairment (CrCl =30 to <60 mL/min), an approximate two-fold increase in plasma AUC of alogliptin was observed. To maintain similar systemic exposures of Nesina to those with normal renal function, the recommended dose is 12.5 mg once daily in patients with moderate renal impairment. In patients with severe renal impairment (CrCl =15 to <30 mL/min) and ESRD (CrCl <15 mL/min or requiring dialysis), an approximate three- and four-fold increase in plasma AUC of alogliptin were observed, respectively. Dialysis removed approximately 7% of the drug during a three-hour dialysis session. Nesina may be administered without regard to the timing of the dialysis. To maintain similar systemic exposures of Nesina to those with normal renal function, the recommended dose is 6.25 mg once daily in patients with severe renal impairment, as well as in patients with ESRD requiring dialysis.

/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, Kazano (alogliptin and metformin hydrochloride) should be discontinued and the patient hospitalized immediately. /Alogliptin 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 fatal and nonfatal hepatic failure in patients taking Nesina, although some of the reports contain insufficient information necessary to establish the probable cause.|There have been postmarketing reports of serious hypersensitivity reactions in patients treated with Nesina. These reactions include anaphylaxis, angioedema and severe cutaneous adverse reactions, including Stevens-Johnson syndrome. If a serious hypersensitivity reaction is suspected, discontinue Nesina, assess for other potential causes for the event and institute alternative treatment for diabetes.|For more Drug Warnings (Complete) data for Alogliptin (18 total), please visit the HSDB record page.

Peak inhibition of DPP-4 occurs within 2-3 hours after a single-dose administration to healthy subjects. The peak inhibition of DPP-4 exceeded 93% across doses of 12.5 mg to 800 mg. Inhibition of DPP-4 remained above 80% at 24 hours for doses greater than or equal to 25 mg. Alogliptin also demonstrated decreases in postprandial glucagon while increasing postprandial active GLP-1 levels compared to placebo over an 8-hour period following a standardized meal. Alogliptin does not affect the QTc interval.

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.)

The pharmacokinetics of NESINA was also shown to be similar in healthy subjects and in patients with type 2 diabetes. When single, oral doses up to 800 mg in healthy subjects and type 2 diabetes patients are given, the peak plasma alogliptin concentration (median Tmax) occurred 1 to 2 hours after dosing. Accumulation of aloglipin is minimal. The absolute bioavailability of NESINA is approximately 100%. Food does not affect the absorption of alogliptin.|Renal excretion (76%) and feces (13%). 60% to 71% of the dose is excreted as unchanged drug in the urine.|Following a single, 12.5 mg intravenous infusion of alogliptin to healthy subjects, the volume of distribution during the terminal phase was 417 L, indicating that the drug is well distributed into tissues.|Renal clearance = 9.6 L/h (this value indicates some active renal tubular secretion); Systemic clearance = 14.0 L/h.|The primary route of elimination of (14C) alogliptin-derived radioactivity occurs via renal excretion (76%) with 13% recovered in the feces, achieving a total recovery of 89% of the administered radioactive dose. The renal clearance of alogliptin (9.6 L/hr) indicates some active renal tubular secretion and systemic clearance was 14.0 L/hr.|Alogliptin does not undergo extensive metabolism and 60% to 71% of the dose is excreted as unchanged drug in the urine.|The absolute bioavailability of NESINA is approximately 100%. Administration of NESINA with a high-fat meal results in no significant change in total and peak exposure to alogliptin. NESINA may therefore be administered with or without food.|Following a single, 12.5 mg intravenous infusion of alogliptin to healthy subjects, the volume of distribution during the terminal phase was 417 L, indicating that the drug is well distributed into tissues. Alogliptin is 20% bound to plasma proteins.|For more Absorption, Distribution and Excretion (Complete) data for Alogliptin (6 total), please visit the HSDB record page.

Alogliptin does not undergo extensive metabolism. Two minor metabolites that were detected are N-demethylated alogliptin (<1% of parent compound) and N-acetylated alogliptin (<6% of parent compound). The N-demethylated metabolite is active and an inhibitor of DPP-4. The N-acetylated metabolite is inactive. Cytochrome enzymes that are involved with the metabolism of alogliptin are CYP2D6 and CYP3A4 but the extent to which this occurs is minimal. Approximately 10-20% of the dose is hepatically metabolized by cytochrome enzymes.|Two minor metabolites were detected following administration of an oral dose of [14C] alogliptin, N-demethylated, M-I (<1% of the parent compound), and N-acetylated alogliptin, M-II (<6% of the parent compound). M-I is an active metabolite and is an inhibitor of DPP-4 similar to the parent molecule; M-II does not display any inhibitory activity toward DPP-4 or other DPP-related enzymes. In vitro data indicate that CYP2D6 and CYP3A4 contribute to the limited metabolism of alogliptin. Alogliptin exists predominantly as the (R)-enantiomer (>99%) and undergoes little or no chiral conversion in vivo to the (S)-enantiomer. The (S)-enantiomer is not detectable at the 25 mg dose.

Terminal half-life = 21 hours|At the maximum recommended clinical dose of 25 mg, Nesina was eliminated with a mean terminal half-life of approximately 21 hours.

Alogliptin inhibits dipeptidyl peptidase 4 (DPP-4), which normally degrades the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide 1 ( GLP-1). The inhibition of DPP-4 increases the amount of active plasma incretins which helps with glycemic control. GIP and GLP-1 stimulate glucose dependent secretion of insulin in pancreatic beta cells. GLP-1 has the additional effects of suppressing glucose dependent glucagon secretion, inducing satiety, reducing food intake, and reducing gastric emptying.|Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Alogliptin is a DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus. Alogliptin selectively binds to and inhibits DPP-4 but not DPP-8 or DPP-9 activity in vitro at concentrations approximating therapeutic exposures.

/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/|In the event of an overdose, it is reasonable to institute the necessary clinical monitoring and supportive therapy as dictated by the patient's clinical status. ... Alogliptin is minimally dialyzable; over a three-hour hemodialysis session, approximately 7% of the drug was removed. Therefore, hemodialysis is unlikely to be beneficial in an overdose situation. ...|For more Antidote and Emergency Treatment (Complete) data for Alogliptin (7 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new class of anti-diabetic drug which exerts its glucose-lowering action by suppressing the degradation of a gut incretin hormone glucagon-like peptide-1 (GLP-1). To elucidate whether treatment with stronger DPP-4 inhibitor on top of angiotensin II type 1 receptor blocker (ARB) provides greater renal protective effects ... a crossover study with two DPP-4 inhibitors, sitagliptin and alogliptin, in twelve type 2 diabetic patients with incipient nephropathy taking ARBs /was performed/. This study consisted of three treatment periods: sitagliptin 50 mg/day for 4 weeks (first period), alogliptin 25 mg/day for 4 weeks (second period), and sitagliptin 50 mg/day for 4 weeks (third period). Significant changes in body mass index, blood pressure, serum lipids, serum creatinine, estimated glomerular filtration rate, and HbA1c were not observed among the three treatment periods. Reduced urinary levels of albumin and an oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG), increased urinary cAMP levels, and elevated plasma levels of stromal cell-derived factor-1alpha (SDF-1alpha) which is a physiological substrate of DPP-4 were observed after the switch from sitagliptin to a stronger DPP-4 inhibitor alogliptin. Given a large body of evidence indicating anti-oxidative action of cAMP and up-regulation of cellular cAMP production by SDF-1alpha, the present results suggest that more powerful DPP-4 inhibition on top of angiotensin II type 1 receptor blockade would offer additional protection against early-stage diabetic nephropathy beyond that attributed to glycemic control, via reduction of renal oxidative stress by SDF-1alpha-cAMP pathway activation.|/HUMAN EXPOSURE STUDIES/ In a randomized, placebo-controlled, four-arm, parallel-group study, 257 subjects were administered either alogliptin 50 mg, alogliptin 400 mg, moxifloxacin 400 mg or placebo once daily for a total of seven days. No increase in QTc was observed with either dose of alogliptin. At the 400 mg dose, peak alogliptin plasma concentrations were 19-fold higher than the peak concentrations following the maximum recommended clinical dose of 25 mg.|/HUMAN EXPOSURE STUDIES/ The highest doses of Nesina administered in clinical trials were single doses of 800 mg to healthy subjects and doses of 400 mg once daily for 14 days to patients with type 2 diabetes (equivalent to 32 times and 16 times the maximum recommended clinical dose of 25 mg, respectively). No serious adverse events were observed at these doses. ...|/SIGNS AND SYMPTOMS/ There have been postmarketing reports of fatal and nonfatal hepatic failure in patients taking Nesina, although some of the reports contain insufficient information necessary to establish the probable cause.|For more Human Toxicity Excerpts (Complete) data for Alogliptin (11 total), please visit the HSDB record page.

2-((6-((3R)-3-aminopiperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl) benzonitrile

Table: Alogliptin benzoate Preparations [Table#8203]|Table: Alogliptin benzoate Combinations Preparations [Table#8204]

... A reversed-phase liquid chromatographic (RP-LC) method has been developed for the determination of alogliptin (ALG) 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) with UV detection at 215 nm. Chromatographic separation 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 range of 5-160 ug mL(-1) for ALG in bulk. The optimized method was validated and proved to be specific, robust and accurate for the quality control of ALG in pharmaceutical preparations

Human drugs -> Incresync -> EMA Drug Category|Drugs used in diabetes, Combinations of oral blood glucose lowering drugs -> Human pharmacotherapeutic group|Human drugs -> Vipidia -> EMA Drug Category|Drugs used in diabetes, Dipeptidyl peptidase 4 (DPP-4) inhibitors -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans