Alogliptin + Metformin

Oral
Type 2 diabetes mellitus

Severe (GFR <30 mL/min): Contraindicated.

Contraindicated.

Should be taken with food.

Acute or chronic metabolic acidosis (e.g. diabetic ketoacidosis, lactic acidosis), diabetic pre-coma, alcoholism or acute alcohol intoxication, acute or chronic disease that may cause hypoxia (e.g. cardiac or respiratory failure, recent MI, shock), conditions which may alter renal function (e.g. severe infection, dehydration). Intravascular administration of iodinated contrast agents. Hepatic and severe renal impairment (GFR <30 mL/min).

Patient with history of heart failure, and pancreatitis; abnormal serum transaminases, and those who are exposed to stress-related states (e.g. infection, fever, trauma, surgery). Not intended for the treatment of diabetic ketoacidosis or type 1 diabetes mellitus. Renal impairment (eGFR 30-60 mL/min). Pregnancy and lactation.

Significant: Bullous pemphigoid, severe arthralgia, hypoglycaemia, heart failure, acute pancreatitis, vitamin B12 deficiency. Rarely, serious hypersensitivity reactions (e.g. anaphylaxis, angioedema, Stevens-Johnson syndrome, exfoliative skin conditions).
Gastrointestinal disorders: Diarrhoea, abdominal pain, GERD, gastroenteritis, vomiting, gastritis.
Musculoskeletal and connective tissue disorders: Back pain.
Nervous system disorders: Headache.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Upper respiratory infection, nasopharyngitis.
Skin and subcutaneous tissue disorders: Pruritus, rash.
Vascular disorders: Hypertension.
Potentially Fatal: Lactic acidosis. Hepatotoxicity, including fatal and non-fatal hepatic failure.

Monitor glycosylated Hb (HbA_1c), serum glucose, LFT and renal function, haematologic parameters prior to initiation of therapy and periodically thereafter. Monitor vitamin B₁₂; signs or symptoms of heart failure, pancreatitis.

Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, oral contraceptives, sympathomimetics, phenytoin, nicotininc acid, Ca channel blockers and isoniazid may produce hyperglycaemia which may lead to loss of glycaemic control.
Alogliptin: Increased risk of hypoglycaemia when used in combination with sulfonylureas or insulin.
Metformin: Concomitant cationic drugs that interfere with renal tubular transport systems (e.g. ranolazine, vandetanib, dolutegravir, cimetidine) may increase metformin levels. Increased risk of lactic acidosis with topiramate or other carbonic anhydrase inhibitors (e.g. zonisamide, acetazolamide, dichlorphenamide), ACE inhibitor, angiotensin II receptor antagonists, NSAIDs, loop diuretics. May impair vitamin B12 absorption.
Potentially Fatal: Intravascular admin of iodinated contrast agents may cause renal dysfunction, leading to metformin-induced lactic acidosis.

Food decreases the extent and slightly delays absorption of metformin. Alcohol may potentiate the effect of metformin on lactate metabolism.

Description: Alogliptin inhibits dipeptidylpeptidase-4 (DPP-4), an enzyme that inactivates incretin hormones. Inhibition of DPP-4 result in an increase in the levels of incretin hormones [e.g. glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] which regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic β-cells and decreasing glucagon secretion from pancreatic α-cells, leading to reduced hepatic glucose production.
Metformin is a biguanide antidiabetic agent that reduces hepatic glucose production by decreasing gluconeogenesis and glycogenolysis, decreases intestinal absorption of glucose and enhances insulin sensitivity by increasing peripheral utilisation and uptake of glucose.
Pharmacokinetics:
Absorption: Alogliptin: Absorbed from the gastrointestinal tract. Bioavailability: Approx 100%. Time to peak plasma concentration: Approx 1-2 hours.
Metformin: Slowly and incompletely absorbed from the gastrointestinal tract. Reduced if taken with food. Absolute bioavailability: Approx 50-60%. Time to peak plasma concentration: 1-2 hours.
Distribution: Alogliptin: Volume of distribution: 417 L. Plasma protein binding: 20%.
Metformin: Partitions into erythrocytes; concentrates in kidney, liver, and gastrointestinal tract. Crosses the placenta and enters breast milk in small amounts. Volume of distribution: 654 ± 358 L.
Metabolism: Alogliptin: Minimally metabolised in the liver by CYP2D6 and CYP34A to active and inactive metabolites.
Excretion: Alogliptin: Mainly via urine (76%, 60-71% as unchanged drug); faeces (13%). Terminal elimination half-life: Approx 21 hours.
Metformin: Via urine (90% as unchanged drug). Plasma elimination half-life: Approx 2-6 hours.

Source: National Center for Biotechnology Information. PubChem Database. Alogliptin, CID=11450633, https://pubchem.ncbi.nlm.nih.gov/compound/Alogliptin (accessed on Jan. 20, 2020)

Source: National Center for Biotechnology Information. PubChem Database. Metformin, CID=4091, https://pubchem.ncbi.nlm.nih.gov/compound/Metformin (accessed on Jan. 20, 2020)

Store at 25°C. Protect from moisture.

Antidiabetic Agents

A10BD13 - metformin and alogliptin ; Belongs to the class of combinations of oral blood glucose lowering drugs. Used in the treatment of diabetes.

Alogliptin and Metformin Hydrochloride Tablet, Film Coated (Perrigo New York Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 02/02/2018.

Anon. Alogliptin and Metformin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/02/2018.

Anon. Alogliptin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/02/2018.

Anon. Metformin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/02/2018.

Buckingham R (ed). Alogliptin Benzoate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/02/2018.

Buckingham R (ed). Metformin Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/02/2018.

Joint Formulary Committee. Alogliptin with Metformin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/02/2018.

McEvoy GK, Snow EK, Miller J et al (eds). Alogliptin Benzoate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 02/02/2018.