ALOGLIPTIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALOGLIPTIN (ALOGLIPTIN).
Alogliptin is a selective, reversible inhibitor of dipeptidyl peptidase-4 (DPP-4). By inhibiting DPP-4, it increases the levels of active incretin hormones (GLP-1 and GIP), which stimulate insulin secretion in a glucose-dependent manner and suppress glucagon release, thereby improving glycemic control.
| Metabolism | Alogliptin is minimally metabolized; approximately 60-70% excreted unchanged in urine. Metabolism involves hepatic microsomal enzymes, primarily CYP2D6 and CYP3A4, but to a minor extent. |
| Excretion | Approximately 60-71% of the dose is excreted unchanged in urine via active renal tubular secretion, with about 20% eliminated as metabolites (primarily N-demethylated and N-acetylated derivatives) in urine, and less than 2% in feces. Renal excretion is the major route. |
| Half-life | Terminal elimination half-life is approximately 12-21 hours. This supports once-daily dosing. In patients with renal impairment, half-life is prolonged (e.g., up to 32 hours in severe impairment), necessitating dose adjustment. |
| Protein binding | 20% bound to plasma proteins, primarily albumin. Binding is concentration-independent. |
| Volume of Distribution | Volume of distribution is approximately 33 L (0.47 L/kg assuming 70 kg). This suggests distribution into total body water, but not extensive tissue binding. |
| Bioavailability | Oral bioavailability is approximately 100%, indicating complete absorption with minimal first-pass metabolism. |
| Onset of Action | Oral: Onset of action occurs within 1 hour, with peak plasma concentrations reached at 1-2 hours post-dose. Pharmacodynamic effects (DPP-4 inhibition, increased incretin levels) begin within 1-2 hours. |
| Duration of Action | Oral: Duration of DPP-4 inhibition exceeds 24 hours, allowing once-daily dosing. Clinically, the drug provides sustained glycemic control over 24 hours, with a duration of action that covers the postprandial and fasting periods. |
25 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | eGFR 30-59 mL/min: 12.5 mg orally once daily; eGFR 15-29 mL/min: 6.25 mg orally once daily; eGFR <15 mL/min or dialysis: 6.25 mg orally once daily |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A and B); not recommended for severe hepatic impairment (Child-Pugh C) |
| Pediatric use | Safety and efficacy not established; no recommended dosing available |
| Geriatric use | No dose adjustment recommended based on age alone; monitor renal function and adjust dose accordingly |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALOGLIPTIN (ALOGLIPTIN).
| Breastfeeding | It is unknown if alogliptin is excreted in human breast milk. No M/P ratio available. Due to potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account importance to the mother. |
| Teratogenic Risk | Alogliptin is classified as FDA Pregnancy Category B. Animal studies showed no teratogenic effects at exposures up to 100 times the human clinical dose. However, no adequate and well-controlled studies in pregnant women exist. Use only if clearly needed. First trimester risk cannot be ruled out; limited human data. |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of serious hypersensitivity reaction to alogliptin or any excipient","Type 1 diabetes mellitus","Diabetic ketoacidosis"]
| Precautions | ["Pancreatitis: Cases of acute pancreatitis have been reported; discontinue if pancreatitis is suspected.","Hypersensitivity reactions: Including anaphylaxis, angioedema, and severe cutaneous adverse reactions.","Heart failure: Consider risk factors; monitor for signs and symptoms.","Severe and disabling arthralgia has been reported.","Acute renal failure: Not recommended in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²) or end-stage renal disease.","Hypoglycemia when used in combination with insulin or sulfonylureas."] |
| Food/Dietary | No specific food interactions; can be taken with or without food. Avoid excessive alcohol intake due to potential hypoglycemia risk when used with other agents. |
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| Fetal Monitoring | Monitor blood glucose and HbA1c for glycemic control. No specific fetal monitoring required beyond standard prenatal care. Liver function tests periodically due to rare hepatotoxicity reports. |
| Fertility Effects | No human studies on fertility. Animal studies at high doses showed no impairment of fertility. Clinical significance in humans is unknown. |
| Clinical Pearls | Alogliptin is a DPP-4 inhibitor with minimal risk of hypoglycemia when used as monotherapy; dosing adjustments required for renal impairment (creatinine clearance <60 mL/min). Monitor for acute pancreatitis and severe arthralgia. No significant weight loss or gain. Use with caution in patients with history of pancreatitis. |
| Patient Advice | Take alogliptin with or without food once daily. · Do not skip meals, especially if taking other diabetes medications that cause hypoglycemia. · Contact healthcare provider immediately if you experience persistent severe abdominal pain (sign of pancreatitis). · Report any joint pain that is new or worsening. · Store at room temperature away from moisture and heat. |