Linagliptin and Metformin

Indication

Linashin-MET is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes when treatment with both linagliptin and metformin is appropriate.

Dosage and Administration

Initial dose for patients currently not receiving Metformin: Linagliptin 2.5 mg / Metformin 500 mg twice daily. Initial dose for patients currently receiving Metformin: Linagliptin 2.5 mg in combination with one-half of current Metformin dose twice daily.

Initial dose for patients currently receiving Linagliptin and Metformin as individual components: switch to combination product containing the same doses of each component twice daily.

Maintenance dose: Individualize dose based on effectiveness and patient tolerability.

Maximum daily dose: 5 mg Linagliptin / 2000 mg Metformin It is not recommended for use in children and adolescents under 18 years. It may be taken with meals to reduce the chance of upset stomach.

Continue to take Linashin-MET as long as your physician prescribes it. Physician may prescribe this medicine along with other oral anti-diabetes medicine or insulin according to your medical condition.

Composition

Each film-coated tablet contains:

Linagliptin INN ... 2.5 mg.

Metformin Hydrochloride B.P ... 500 mg.

Description

Linagliptin is described chemically as 1H-Purine-2, 6-dione,8-[(3R)-3-amino-1-piperidinyl]-7-(2-butyn-1-yl) -3, 7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl) methyl]. The empirical formula is C25H28N8O2 and the molecular weight is 472.54.

Metformin hydrochloride is an oral antihyperglycemic drug. Chemically, it is (1, 1-dimethyl biguanide hydrochloride) and its empirical formula is C4H12N5Cl. Molecular weight is 165.62.

Clinical Pharmacology

Linagliptin is a competitive, reversible inhibitor of dipeptidyl peptidase-4, an enzyme that degrades the incretin hormones glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), resulting in increased concentrations of active incretin hormones, stimulating the relea...read more

The primary effect of metformin is to active enzyme AMP-activated protein kinase and reduce hepatic glucose production. Metformin acts the following three mechanisms: increase peripheral utilization of glucose; inhibit hepatic gluconeogenesis and reduce absorption of glucose from the intestine. Metf...read more

Pharmacokinetics

The absolute bioavailability of linagliptin is approximately 30%. High-fat meal reduced Cmax by 15% and increased AUC by 4%: this effect is not clinically relevant. Plasma protein binding of linagliptin is concentration-dependent, decreasing from about 99% at 1 nmol/L to 75%-89% at ≥ 30 nmol/L, refl...read more

Metformin is absorbed mainly from the small intestine. Food decreases rate and extent of absorption. It does not bound to plasma protein, not metabolized and its half-life is 1.5 – 3 hours. It is excreted by the kidney as the active compound. As a consequence of blockage of gluconeogenesis, metformi...read more

Contraindication

Linashin-MET is contraindicated in patients with hyper-sensitivity to metformin and linagliptin; Type I diabetes, diabetes coma and ketoacidosis; impairment of liver function and renal function (estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2), chronic liver disease, cardiac fail...read more

Precaution

It is used with caution in patients with lactic acidosis, underlying liver disease, macrovascular outcomes; debilitated, malnourished or elderly patients and patients with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycaemic effects. Hypoglycaemia ...read more

Regular monitoring of folic acid and vitamin B12 levels are recommended during long term therapy because it may decrease their absorption.

It is not known if Linashin-MET will harm unborn baby or pass into breast milk. So, consult with physician about the best way to control blood sugar if you are pregnant/breastfeeding or plan to become pregnant/ breastfeed. Regular monitoring of renal function should be advised. If pancreatitis or bu...read more

Adverse Effects

Headache, diarrhea, vomiting, nausea, abdominal discomfort, acute pancreatitis including fatal and non-fatal haemorrhage and necrotizing pancreatitis, cough, naso-pharyngitis, hypoglycaemia, hyperlipidemia, hypertriglyceridemia, back pain, myalgia, severe and disabling arthralgia.

Drug Interaction

Carbonic Anhydrase Inhibitors: Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with Linashin-MET may in...read more

Alcohol may potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake while receiving Linashin-MET.

Insulin Secretagogues or Insulin: Co-administration of Linashin-MET with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.

Rifampin decreased linagliptin exposure, suggesting that the efficacy of linagliptin may be reduced when administered in combination with a strong P-gylcoprotein or CYP 3A4 inducer. Therefore, use of alternative treatments (not containing linagliptin) is strongly recommended when concomitant treatme...read more

Certain drugs (thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid) tend to produce hyperglycemia and may lead to loss of glycemic control.

Storage

Store below 30°C in cool, dry place. Protect from light and moisture. Keep out of reach and sight of children.

Presentation

10 x 10’s Blisters.