Siglimet XR 50/500

Indications

This medication is recommended as a supplementary treatment alongside dietary adjustments and physical activity to enhance glycemic management in adult patients diagnosed with type 2 diabetes mellitus when combining both sitagliptin and metformin is deemed suitable. It’s important to note:

• This treatment is not appropriate for individuals with type 1 diabetes or those requiring management of diabetic ketoacidosis, as it won’t be effective in these circumstances.
• Its safety and efficacy haven’t been studied extensively in patients with a history of pancreatitis. The potential risk of pancreatitis development while using this medication in such patients remains uncertain.

Pharmacology

This tablet blends two antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in type 2 diabetes patients. Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and Metformin HCl, a member of the biguanide class. Sitagliptin works by slowing the inactivation of incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which play a role in regulating glucose homeostasis. By prolonging active incretin levels, Sitagliptin enhances insulin release and reduces glucagon levels in a glucose-dependent manner.

Metformin HCl operates differently from other oral antihyperglycemic agents. It decreases hepatic glucose production, reduces intestinal glucose absorption, and boosts peripheral glucose uptake and utilization.

Dosage & Administration:

The dosage of this tablet should be personalized based on the patient’s current regimen, effectiveness, and tolerance, without exceeding the maximum recommended daily dose of 100 mg sitagliptin and 2000 mg metformin. It’s generally administered twice daily with meals, with gradual dose escalation to mitigate gastrointestinal side effects related to metformin.

For patients not currently treated with metformin, the starting dose is typically 50 mg sitagliptin/500 mg metformin hydrochloride twice daily, with gradual escalation to minimize gastrointestinal side effects. Patients already on metformin should receive 50 mg sitagliptin twice daily (100 mg total daily dose) in addition to their current metformin dose.

Extended-release tablets are administered once daily with a meal, preferably in the evening, with dose adjustments based on effectiveness and tolerance. It’s crucial to maintain the total daily dose of sitagliptin and metformin when switching between film-coated and extended-release tablets.

Interaction

Caution is advised when using this medication with cationic drugs eliminated by renal tubular secretion. Close monitoring of INR is recommended when co-administering with phenprocoumon. Levothyroxine may diminish the hypoglycemic effect of metformin, necessitating blood glucose level monitoring, especially during initiation or cessation of thyroid hormone therapy.

Contraindications

This tablet is contraindicated in patients with renal disease or dysfunction, acute or chronic metabolic acidosis, and a history of serious hypersensitivity reactions to the medication or its components. Temporary discontinuation is recommended in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials due to potential acute renal function alteration.

Side Effects

Common adverse reactions include diarrhea, upper respiratory tract infection, headache, and hypoglycemia, particularly when combined with other antidiabetic agents. Nasopharyngitis may occur with sitagliptin monotherapy. Gastrointestinal disturbances are common upon initiating metformin therapy.

Pregnancy & Lactation

This medication falls under Pregnancy Category B, and its safety during pregnancy hasn’t been established. Use during pregnancy should be limited to cases where clearly indicated. Caution is advised when administering to nursing mothers due to unknown excretion of sitagliptin in human milk.

Precautions & Warnings

Lactic acidosis is a potential risk, particularly in conditions predisposing to its occurrence. Regular TSH monitoring is recommended in patients with hypothyroidism. Long-term metformin treatment may lower vitamin B12 levels, necessitating monitoring. Use is cautioned in patients with hepatic disease, and renal function should be assessed before and periodically during treatment. Acute pancreatitis has been reported postmarketing, requiring prompt discontinuation if suspected. Other precautions include avoiding excessive alcohol intake and temporarily switching to insulin during periods of stress or decreased food intake.

Overdose Effects

Usual supportive measures are recommended in case of overdose, including gastrointestinal decontamination and clinical monitoring. Prolonged hemodialysis may be considered for metformin overdose. Therapeutic Class: Combination Oral Hypoglycemic Preparations

Storage Conditions

Store below 25°C in a dry place away from light, and keep out of reach of children. Do not use beyond the expiry date. Dispense only on the prescription of a registered physician.