alogliptin (Rx)

>10%

Hypoglycemia (1.5-35%); higher when added to insulin

1-10%

Nasopharyngitis (4.4%)

Headache (4.2%)

Upper respiratory tract infection (4.2%)

<1%

Hypersensitivity (0.6%)

Pancreatitis (0.2%)

Postmarketing reports

Severe and disabling arthralgia

Anaphylaxis, angioedema, rash, urticaria

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome

Hepatic enzyme elevations

Fulminant hepatic failure

Bullous pemphigoid

Rhabdomyolysis

Constipation

Nausea

Ileus

Contraindications

Hypersensitivity to alogliptin, including anaphylaxis, angioedema, or severe cutaneous adverse reactions including Stevens-Johnson syndrome

Cautions

Pancreatitis reported; if pancreatitis suspected, discontinue therapy and initiate appropriate management

Caution with sensitivity to another DPP-4 inhibitor; discontinue if serious hypersensitivity reaction suspected (see Contraindications)

Postmarketing cases of bullous pemphigoid requiring hospitalization reported with DPP-4 inhibitor use; patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of DPP-4 inhibitor; tell patients to report development of blisters or erosions while receiving therapy; if bullous pemphigoid suspected, therapy should be discontinued and referral to a dermatologist considered for diagnosis and appropriate treatment

Fatal and nonfatal hepatic failure reported; type 2 DM is also known to cause fatty liver disease and liver enzyme elevation; monitor carefully and interrupt alogliptin treatment if LFTs elevated, do not restart alogliptin without another explanation for the liver test abnormalities; do not restart therapy if liver injury is confirmed and no alternative etiology can be found

Insulin and insulin secretagogues (eg, sulfonylureas) are known to cause hypoglycemia; therefore, a lower dose of insulin of insulin secretagogue may be needed to minimize hypoglycemia risk

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with alogliptin or any other antidiabetic drug

DPP-4 inhibitors may cause disabling joint arthralgia; resolves within a month upon discontinuing the drug

Congestive heart failure (CHF) risk

• The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial enrolled 5,380 patients with type 2 diabetes and recent acute coronary syndrome
• Hospitalization for CHF was observed in 106 (3.9%) patients treated with alogliptin and 89 (3.3%) patients treated with placebo; although the difference was not statistically significant (hazard ratio, 1.19), heart failure was not an end point of the study
• Health care professionals should consider discontinuing medications containing alogliptin in patients who develop heart failure and monitor their diabetes control
• If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation
• Lancet. 2015 May 23;385(9982):2067-76

Pregnancy Category: B

Lactation: Unknown whether distributed in breast milk

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.

Mechanism of Action

Selective dipeptidyl peptidase-4 (DPP-4) inhibitor; slows inactivation of incretin hormones (eg, GLP-1, GIP), thereby reducing fasting and postprandial glucose concentrations in a glucose-dependent manner

Absorption

Bioavailability: ~100%

Peak plasma time: 1-2 hr

Distribution

Protein bound: 20%

Vd: 417 L

Metabolism

Does not undergo extensive metabolism and 60-71% of the dose is excreted unchanged in the urine

Active metabolite: N-demethylated (<1% of parent compound)

Inactive metabolite: N-acetylated alogliptin (<6% of parent compound)

Minor substrate of CYP3A4 and CYP2D6

Elimination

Half-life: 21 hr

Renal clearance: 9.6 L/hr

Total body clearance: 14 L/hr

Excretion: 76% urine; 13% feces

Instructions

May take with or without food