LINAGLIP-M

COMPOSITION:

Linaglip –M 500                                              

Each film coated tablet contains: Linagliptin    2.5 mg and Metformin Hydrochloride USP 500 mg

Linaglip –M 850

Each film coated tablet contains: Linagliptin    2.5 mg and Metformin Hydrochloride USP 850 mg

Linaglip –M 1000

Each film coated tablet contains: Linagliptin    2.5 mg and Metformin Hydrochloride USP 1000 mg

CLINICAL PHARMACOLOGY:

Mechanism of Action

Linagliptin 

Linagliptin, a DPP-4 inhibitor, enhances insulin release and decreases glucagon levels to regulate blood glucose, particularly post-meal. 

Metformin  

Metformin lowers basal and postprandial glucose by reducing hepatic glucose production, intestinal absorption, and improving insulin sensitivity.

Pharmacokinetics

Metformin

Metformin, a biguanide, is absorbed in the small intestine with 50–60% bioavailability, delayed by food. It is excreted unchanged by the kidneys, with a half-life of 6.5 hours and extensive tissue uptake, particularly in the liver and GI tract.

Linagliptin

Linagliptin, a DPP-4 inhibitor, is rapidly absorbed (Tmax 1.5 hours) with ~30% bioavailability, unaffected by food. It has a long half-life (100–200 hours), minimal metabolism, high protein binding (>99%), and is primarily excreted via bile and feces.

INDICATIONS AND USAGE: 

Linagliptin+Metformin tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both Linagliptin and Metformin is appropriate.

Linagliptin+Metformin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.

Linagliptin+Metformin have not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using Linagliptin+Metformin.

 DOSAGE AND ADMINISTRATION:

Recommended Dosing: Linagliptin+Metformin should be individualized, with a maximum dose of 2.5 mg Linagliptin/1000 mg Metformin twice daily, taken with meals. Dose escalation should be gradual to minimize gastrointestinal side effects.

Recommended starting dose: 

For patients not on Metformin, initiate with 2.5 mg Linagliptin/500 mg Metformin twice daily. For those already on Metformin, add 2.5 mg Linagliptin to their current Metformin dose.The combination should not be used if eGFR <30 mL/min/1.73 m², and initiation is not recommended for eGFR between 30-45 mL/min/1.73 m². Renal function should be assessed regularly.

WARNINGS AND PRECAUTIONS:

Warning:

Metformin-associated lactic acidosis, which can be fatal, may present with symptoms like malaise, myalgias, respiratory distress, and elevated blood lactate levels. 

Precautions:

Risk factors include renal impairment, age over 65, hypoxia, alcohol use, and hepatic dysfunction. If suspected, discontinue Metformin, provide supportive care, and initiate hemodialysis.

ADVERSE REACTIONS: 

Common adverse reactions in patients treated with Linagliptin+Metformin include nasopharyngitis and diarrhea. Hypoglycemia was more frequent in patients on the Linagliptin+Metformin and SU combination compared to SU and Metformin alone. Other reported side effects include hypersensitivity (urticaria, angioedema, and bronchial hyperreactivity), cough, decreased appetite, nausea, vomiting, pruritus, and pancreatitis.

DRUG INTERACTIONS: 

Carbonic anhydrase inhibitors, alcohol, and drugs reducing Metformin clearance (e.g., Cimetidine, Dolutegravir) may increase lactic acidosis risk. Strong P-glycoprotein/CYP3A4 inducers (e.g., Rifampin) can reduce efficacy; alternative treatments are advised.

USE IN SPECIFIC POPULATIONS:

Pregnancy: Linagliptin+Metformin tablets should be used during pregnancy only if clearly needed. 

Nursing mothers: Caution should be exercised when Linagliptin+Metformin is administered to a nursing woman.

Geriatric Use:  Assess renal function more frequently. 

Pediatric Use: The safety and efficacy of metformin and linagliptin in pediatric patients have not been established, and their use requires careful consideration and monitoring.

Hepatic Impairment: Avoid use in patients with hepatic impairment.

CONTRAINDICATIONS: 

Linagliptin+Metformin are contraindicated in patients with severe renal impairment (eGFR below 30 mL/min/1.73 m²), acute or chronic metabolic acidosis, and a history of hypersensitivity reactions to Linagliptin or Metformin. This includes conditions like anaphylaxis, angioedema, exfoliative skin reactions, urticaria, bronchial hyperreactivity, and hypersensitivity to Metformin.

OVERDOSAGE: 

In case of Linagliptin+Metformin overdose, contact Poison Control and provide supportive care based on clinical status. While Linagliptin is not dialyzable, hemodialysis can help remove accumulated Metformin effectively

STORAGE:

Store between 15°-30°C .Store in a safe place out of reach of children.

PRESENTATION:

Cartons containing 10 Alu-Alu blister strips of 10 tablets (10 x 10’s)