Usage
- Alogliptin is prescribed for type 2 diabetes mellitus in adults aged 18 years and older to improve glycemic control. It is used as an adjunct to diet and exercise, in combination with other glucose-lowering medications (including insulin) when these alone do not provide adequate glycemic control. It is not indicated for type 1 diabetes or diabetic ketoacidosis.
- Pharmacological Classification: Dipeptidyl peptidase-4 (DPP-4) inhibitor.
- Mechanism of Action: Alogliptin works by inhibiting the enzyme DPP-4, which is responsible for the breakdown of incretin hormones. Incretins, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play a crucial role in glucose regulation by increasing insulin secretion and decreasing glucagon secretion, particularly after meals. By inhibiting DPP-4, alogliptin increases the levels of these incretins, leading to improved blood glucose control.
Alternate Names
- International Nonproprietary Name (INN): Alogliptin.
- Brand Names: Nesina, Vipidia, Vipdomet (combination with Metformin).
How It Works
- Pharmacodynamics: Alogliptin’s primary effect is to increase incretin levels, resulting in glucose-dependent insulin secretion and suppression of glucagon secretion, thus lowering blood glucose levels.
- Pharmacokinetics:
- Absorption: Alogliptin is well absorbed after oral administration, with an absolute bioavailability of approximately 100%. Food does not significantly affect its absorption.
- Metabolism: Minimally metabolized, primarily by CYP2C8 and CYP3A4 enzymes, with a small contribution from aldehyde oxidase.
- Elimination: Primarily excreted unchanged in the urine (approximately 60%), with about 20% eliminated in the feces. The elimination half-life is about 21 hours.
- Mode of Action: Alogliptin competitively binds to and inhibits DPP-4, preventing the degradation of GLP-1 and GIP. This leads to increased incretin concentrations, which in turn stimulate glucose-dependent insulin release from pancreatic beta-cells and suppress glucagon secretion from alpha-cells.
- Elimination pathways: Primarily renal excretion (about 60%) of the unchanged drug, with some fecal elimination (about 20%). Metabolism by CYP2C8, CYP3A4, and aldehyde oxidase plays a minor role.
Dosage
Standard Dosage
Adults:
- The standard dose is 25 mg orally once daily, with or without food.
- Maximum dose: 25 mg daily.
Children:
- Not established. Alogliptin is not recommended for use in pediatric patients.
Special Cases:
- Elderly Patients: No dose adjustment is necessary based on age alone. However, dose adjustments should be considered in elderly patients with moderate or severe renal impairment.
- Patients with Renal Impairment:
- Mild renal impairment (CrCl > 50 to ≤ 80 mL/min): No dosage adjustment is necessary.
- Moderate renal impairment (CrCl ≥ 30 to ≤ 50 mL/min): 12.5 mg once daily.
- Severe renal impairment (CrCl < 30 mL/min) or end-stage renal disease (ESRD): 6.25 mg once daily. Hemodialysis does not significantly remove alogliptin.
- Patients with Hepatic Dysfunction:
- Mild to moderate hepatic impairment (Child-Pugh A or B): No dosage adjustment necessary.
- Severe hepatic impairment (Child-Pugh C): Not studied, use with caution.
- Patients with Comorbid Conditions: When used in combination with insulin or an insulin secretagogue (e.g., sulfonylurea), a lower dose of insulin or the secretagogue may be required to minimize the risk of hypoglycemia.
Clinical Use Cases
Alogliptin is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. It is primarily indicated for the long-term management of type 2 diabetes.
Dosage Adjustments
As described above, dose modifications are necessary for patients with renal impairment. Dose adjustments may also be needed when alogliptin is used in combination with insulin or insulin secretagogues.
Side Effects
Common Side Effects
- Upper respiratory tract infection (cold-like symptoms)
- Headache
- Diarrhea
- Nausea
- Rash or itchy skin
Rare but Serious Side Effects
- Pancreatitis (symptoms include severe abdominal pain, nausea, and vomiting)
- Angioedema (swelling of face, lips, tongue, or throat)
- Severe allergic reactions (anaphylaxis, including rash, itching/swelling, severe dizziness, trouble breathing)
- Bullous pemphigoid (skin blistering)
- Stevens-Johnson syndrome (severe skin reaction)
- Acute renal failure
- Hepatic dysfunction
Long-Term Effects
Long-term effects of alogliptin are still being studied, but they may include an increased risk of certain cancers and cardiovascular complications.
Adverse Drug Reactions (ADR)
The ADRs mentioned above under “Rare but Serious Side Effects” necessitate immediate medical intervention.
Contraindications
- History of serious hypersensitivity reaction to alogliptin (including anaphylaxis, angioedema, and severe cutaneous adverse reactions).
- Type 1 diabetes mellitus.
- Diabetic ketoacidosis.
Drug Interactions
- CYP450 Interactions: Alogliptin is primarily metabolized by CYP2C8 and CYP3A4 but has a low propensity for drug interactions involving these enzymes.
- Other Interactions: May enhance the hypoglycemic effects of insulin and insulin secretagogues. Additive hypoglycemia may also occur when used with other antidiabetic agents.
- Medications: Additive effects with other antidiabetic medications. Some specific drug interactions with other medications have been reported, though their clinical significance is not always clear.
- OTC Drugs and Supplements: No significant interactions known.
- Food and Lifestyle Factors: No known interactions with food or alcohol. However, alcohol can affect blood sugar levels, which may indirectly interfere with alogliptin’s effectiveness.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category B. Alogliptin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Insufficient data in humans. Animal studies do not indicate direct or indirect harmful effects.
- Breastfeeding: It is unknown whether alogliptin is excreted in human milk. As a precaution, alogliptin is generally not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: DPP-4 inhibitor, increasing incretin levels, leading to increased insulin secretion and decreased glucagon secretion.
- Side Effects: Common: Upper respiratory tract infection, headache, diarrhea. Serious: pancreatitis, angioedema, severe allergic reactions.
- Contraindications: Hypersensitivity to alogliptin, type 1 diabetes.
- Drug Interactions: May enhance hypoglycemic effects of insulin and other antidiabetic agents.
- Pregnancy & Breastfeeding: Category B; not recommended while breastfeeding.
- Dosage: 25 mg once daily (adjustments needed for renal impairment).
- Monitoring Parameters: HbA1c, fasting blood glucose, postprandial glucose, renal function.
Popular Combinations
- Metformin: Alogliptin is often combined with metformin for synergistic glucose-lowering effects.
- Pioglitazone or other thiazolidinediones.
- Sulfonylureas (with dose adjustments to reduce hypoglycemia risk).
- Insulin (with dose adjustments to reduce hypoglycemia risk).
Precautions
- General Precautions: Assess renal function before and during treatment. Monitor for signs of pancreatitis, angioedema, and hepatic dysfunction.
- Specific Populations: See dosage adjustments sections for pregnant women, breastfeeding mothers, children, and elderly patients.
- Lifestyle Considerations: Advise patients on the importance of diet and exercise for diabetes management.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Alogliptin?
A: The recommended dosage for adults with normal renal function or mild renal impairment is 25 mg orally once daily. For patients with moderate renal impairment, the dose is 12.5 mg once daily, and for those with severe renal impairment or ESRD, it is 6.25 mg once daily.
Q2: Can Alogliptin be used in patients with type 1 diabetes?
A: No, Alogliptin is not indicated for patients with type 1 diabetes. It is specifically for type 2 diabetes.
Q3: What are the common side effects of Alogliptin?
A: Common side effects include upper respiratory tract infections (cold-like symptoms), headache, diarrhea, nausea, and skin rash or itching.
Q4: Does Alogliptin interact with other medications?
A: Alogliptin can interact with other medications, particularly insulin and sulfonylureas, increasing the risk of hypoglycemia. Dose adjustments of these medications may be necessary.
Q5: Can Alogliptin be taken during pregnancy?
A: Alogliptin should only be used during pregnancy if the potential benefit outweighs the potential risk to the fetus. Discuss the risks and benefits with your doctor.
Q6: Is it safe to take Alogliptin while breastfeeding?
A: Alogliptin’s safety during breastfeeding has not been established. As a precaution, it is generally not recommended. Consult with your doctor about potential risks and alternative therapies.
Q7: How does Alogliptin work to lower blood sugar?
A: Alogliptin inhibits DPP-4, increasing the levels of incretin hormones. These hormones increase insulin secretion and decrease glucagon secretion, resulting in lower blood sugar levels.
Q8: What should I monitor while my patient is taking Alogliptin?
A: Monitor HbA1c levels, fasting and postprandial glucose levels, and renal function during treatment with Alogliptin. Be vigilant for signs of pancreatitis or allergic reactions.
Q9: Can Alogliptin be used as monotherapy?
A: Yes, Alogliptin can be used as monotherapy, but it is often used in combination with other antidiabetic medications like Metformin when diet and exercise alone are insufficient for blood sugar control.
