Linastar

Approved Indications:

• Type 2 Diabetes Mellitus (T2DM):
  Linagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It may be used:

o    As monotherapy in patients inadequately controlled by diet and exercise alone.

o    In combination therapy with:

§  Metformin

§  Sulfonylureas

§  Thiazolidinediones

§  Insulin

§  Sodium-glucose co-transporter-2 (SGLT2) inhibitors

Note:
Linagliptin is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

Adults:

• Recommended Dose: 5 mg orally once daily, with or without food.

Pediatric Use:

• Not approved. Safety and efficacy have not been established in patients under 18 years of age.

Geriatric Use:

• No dose adjustment necessary based solely on age.

Renal Impairment:

• No dosage adjustment required. Linagliptin can be used across all stages of renal impairment, including in patients on dialysis.

Hepatic Impairment:

• No dosage adjustment required in mild to moderate hepatic impairment. Use with caution in severe hepatic impairment due to limited data.

Route of Administration:

• Oral. The tablet should be swallowed whole, once daily, at the same time each day.

Missed Dose:

• If a dose is missed, take it as soon as remembered. If it is close to the next dose, skip the missed dose. Do not take two doses at once.

Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. DPP-4 is responsible for degrading incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones enhance glucose-dependent insulin secretion and suppress glucagon release. By inhibiting DPP-4, linagliptin increases incretin levels, thereby promoting insulin secretion, decreasing glucagon levels, and improving glycemic control in patients with type 2 diabetes mellitus.

• Absorption: Rapidly absorbed with a peak plasma concentration (Tmax) of approximately 1.5 hours after oral administration.
• Bioavailability: Approximately 30%.
• Distribution: Large volume of distribution (~1,110 L), indicating extensive tissue distribution. Plasma protein binding is concentration-dependent (~75–99%).
• Metabolism: Minimally metabolized. The major metabolic pathway involves CYP3A4; however, metabolism is clinically insignificant.
• Half-life: Terminal half-life is approximately 100–130 hours. Pharmacodynamic effect allows for once-daily dosing.
• Elimination: Approximately 80% excreted unchanged in feces; about 5% excreted in urine.
• Steady-State: Achieved within 4–5 days of once-daily dosing.

Pregnancy:

• FDA Pregnancy Category B (based on old classification system).
  Animal studies did not show harm to the fetus, but there are no adequate, well-controlled studies in pregnant women. Use only if clearly needed.

Lactation:

• It is unknown whether linagliptin is excreted into human breast milk. Animal studies show excretion into milk. Use with caution in breastfeeding women. Consider the potential risks and benefits.

• Class: Dipeptidyl Peptidase-4 (DPP-4) Inhibitor
• Subclass: Incretin-based antidiabetic agent
• Therapeutic Use: Oral hypoglycemic for type 2 diabetes mellitus

• Known hypersensitivity to linagliptin or any component of the formulation
• History of serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) to linagliptin or other DPP-4 inhibitors
• Patients with type 1 diabetes mellitus or diabetic ketoacidosis

• Pancreatitis: Cases of acute pancreatitis have been reported. Discontinue if pancreatitis is suspected.
• Hypoglycemia: Risk increases when used with insulin or sulfonylureas. Dose adjustment of these agents may be required.
• Arthralgia: Severe joint pain has been reported with DPP-4 inhibitors; symptoms may be reversible upon discontinuation.
• Bullous Pemphigoid: Rare skin condition reported; discontinue treatment if suspected.
• Hepatic Impairment: Use with caution in severe hepatic impairment due to limited clinical experience.
• Clinical Monitoring: Monitor blood glucose and HbA1c periodically. Be alert for signs of pancreatitis or hypersensitivity.

Common Adverse Effects (≥1%):

• Respiratory: Nasopharyngitis, cough
• Gastrointestinal: Diarrhea
• Musculoskeletal: Back pain, arthralgia
• Endocrine/Metabolic: Hypoglycemia (especially when used with sulfonylureas or insulin)

Serious and Rare Adverse Effects:

• Acute pancreatitis
• Bullous pemphigoid
• Anaphylaxis or severe hypersensitivity reactions
• Severe disabling joint pain

Onset & Severity:

• Most common side effects are mild to moderate and occur early during therapy.
• Serious side effects are rare but require immediate medical attention.

• Rifampin: Strong CYP3A4 inducer; may reduce linagliptin plasma levels and efficacy.
• Insulin/Sulfonylureas: Increased risk of hypoglycemia when used in combination.
• CYP3A4 inhibitors (e.g., ketoconazole): No significant clinical impact, as linagliptin is minimally metabolized.
• P-glycoprotein inducers/inhibitors: Potential to affect linagliptin levels, though generally not clinically significant.
• Alcohol: May increase risk of hypoglycemia, particularly when combined with insulin or insulin secretagogues.

• American Diabetes Association (ADA) 2024 Guidelines: Linagliptin remains an acceptable second-line therapy after metformin or for patients with renal impairment.
• FDA Safety Communication (2023): Reiterated risk of bullous pemphigoid and pancreatitis; patients should be educated on early symptoms.
• NICE UK (2023): Supports use in patients with contraindications to SGLT2 inhibitors or GLP-1 agonists, especially with renal impairment.

• Temperature: Store below 30°C (86°F)
• Light & Moisture: Store in original packaging to protect from light and moisture.
• Handling: Keep tablets dry; do not crush or chew.
• Reconstitution: Not applicable