Dosing and uses of Nesina (alogliptin)
Adult dosage forms and strengths
tablet
- 6.25mg
- 12.5mg
- 25mg
Diabetes Mellitus Type 2
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
25 mg PO qDay
Dosage modifications
Renal impairment
- Mild (CrCl ≥60mL/min): No dosage adjustment required
- Moderate (CrCl ≥30 to <60 mL/min): Decrease dose to 12.5 mg PO qDay
- Severe (CrCl ≥15 to <30 mL/min) or ESRD (CrCl <15 mL/min) or requiring hemodialysis: 6.25 mg PO qDay
- May administer without regard to the timing of dialysis
- Peritoneal dialysis: Not studied
Hepatic impairment
- Mild-to-moderate (Child-Pugh A and B): No dosage adjustment required
- Severe (Child-Pugh C): Not studied
Dosing Considerations
Limitations of use: Not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, as it would not be effective in these settings
Assess renal function before initiating alogliptin and periodically thereafter
Pediatric dosage forms and strengths
Safety and efficacy not established
Nesina (alogliptin) adverse (side) effects
>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
Warnings
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)
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 and lactation
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.
Pharmacology of Nesina (alogliptin)
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
Administration
Instructions
May take with or without food
