Trig pm pi

For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only Glimepiride, Pioglitazone and Metformin Hydrochloride (Extended Release) Tablets TRIGPM-1/2
Composition
Metformin
Following a single oral dose of Metformin Hydrochloride sustained release: Cmax is achieved with a value of 7 hours and a range of 4 to 8 hours. Metformin has an absolute oral bioavailability of 50 to 60%. Higher oral doses are proportionately less bioavailable than lower doses (observed in doses of 0.5 to 1.5g) when given with food, AUC increase by 50% from the sustained release Metformin tablet but there was no effect of food on Cmax and Tmax of Metformin.
Following absorption, Metformin is rapidly distributed and does not bind to plasma proteins. Metformin undergoes renal excretion and has plasma elimination half life of 6.2 hours after oral administration.
In patients with decreased renal function, the plasma and blood half life of Metformin is prolonged and the renal clearance is decreased in proportion to the decrease in creatinine clearance.
Indications
Pharmacology
TRIGPM is used as an adjunct to diet and exercise to improve glycemic Pharmacodynamics
control in patients with type 2 diabetes who do not achieve glycemic Glimepiride is an lnsulin Secretagogue. The primary mechanism of action control with diet and exercise alone. It is indicated as second-line therapy of Glimepiride, a second generation Sulphonylurea (sometimes referred when diet, exercise, and the single agents or dual therapy do not result in as third generation) appears to be via stimulation of the release of Insulin adequate glycemic control in patients with type 2 diabetes.
by closing the ATP sensitive potassium channel in the pancreatic beta cell membrane. In addition, effects of Glimepiride also may involve extrapancreatic processes. (Pioglitazone is a thiazolidinedione Dosage should be individualized on the basis of glycemic control and antidiabetic agent and acts primarily by decreasing Insulin resistance.) tolerance. The combination should be given once daily with meals and should be started at a low dose. The initial recommended dose is one Pioglitazone depends on the presence of Insulin for its mechanism of action. Pioglitazone is a potent and highly selective agonist for peroxisome proliferator activated receptor gamma (PPAR gamma). PPAR The maximum recommended dose of Glimepiride is 8 mg; Pioglitazone is receptors are found in tissue important for Insulin action such as adipose 45 mg and of Metformin extended release is 2550 mg once daily in tissue, skeletal muscle and liver. Activation of PPAR nuclear receptors modulates the transcription of a number of Insulin responsive genes involved in the control of glucose and lipid metabolism.
Contraindications
?
Hypersensitivity to the drugs or to any other ingredient of the Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves Insulin sensitivity by increasing Renal disease or renal dysfunction which may also result from peripheral glucose uptake and utilization. It thus lowers both basal and infarction, septicaemia and usage of radiocontrast materials.
postprandial plasma glucose without causing hypoglycemia.
Congestive heart failure requiring pharmacological treatment.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis, Pharmacokinetics
with or without coma. Diabetic ketoacidosis should be treated with Glimepiride
After oral administration, Glimepiride is completely (100%) absorbed from the GI tract. Significant absorption occurs within 1 hour of Warnings and Precautions
administration and peak drug levels at 2 to 3 hours. Glimepiride is The administration of older sulphonylureas has been reported to be completely metabolized by oxidative biotransformation after either an IV associated with increased cardiovascular mortality. This warning also or oral dose. The major metabolites are the cyclohexyl hydroxy methyl applies for Glimepiride since it belongs to this category.
derivative (M1) and the carboxyl derivative (M2). M1, but not M2, possesses about 1/3 of the pharmacological activity as compared to its Pioglitazone like other thiazolidinediones, can cause fluid retention parent in an animal model. When 14C-Glimepiride was given orally, when used alone or in combination with other antidiabetic agents, approximately 60% of the total radioactivity was recovered in the urine including Insulin. Fluid retention may lead to or exacerbate heart failure. in 7 days and M1 (predominant) and M2 accounted for 80-90% of that Patients should be observed for signs and symptoms of heart failure.
recovered in faeces and M1 and M2 (predominant) accounted for about 70% of that recovered in faeces. No parent drug was recovered from Lactic acidosis is a rare, but serious, metabolic complication that can occur due to Metformin accumulation during treatment with this formulation. When it occurs, it is fatal in approximately 50% of cases. Pioglitazone
The risk of lactic acidosis increases with the degree of renal insufficiency Following oral administration, in the fasting state, Pioglitazone is first including both intrinsic renal disease and renal hypoperfusion.
measurable in serum within 30 minutes, with peak concentration observed within 2 hours. Food slightly delays the time to peak serum Patients with CHF requiring pharmacological management, in particular concentration to 3 to 4 hours but does not after the extent of absorption.
those with CHF requiring pharmacological management, in particular The mean apparent column of distribution (Vd/F) of Pioglitazone those with unstable or acute CHF who are at risk of hypo-perfusion and following single-dose administration is 0.63 ± 0.41 (mean ± SD) L/kg of hypoxemia, are at increased risk of lactic acidosis.
body weight. Pioglitazone is extensively protein bound (> 99%) in human serum, principally to serum albumin. Pioglitazone also binds to The combination should be discontinued in the presence of any other serum proteins, but with lower affinity. Metabolites M-III and M-IV condition associated with hypoxemia, dehydration or sepsis. Avoid use in also are extensively bound (> 98%) to serum albumin. Following oral patients with impaired hepatic function.
administration, approximately 15% to 30% of the Pioglitazone dose is recovered in the urine. This combination should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure. Vitamin Renal elimination of Pioglitazone is negligible, and the drug is excreted B12 levels should be routinely monitored in patients who are on primarily as metabolites and their conjugates. It is presumed that most of metformin. Periodic monitoring of fasting blood glucose levels, the oral dose is excreted into the bile either unchanged or as metabolites Glycosylated Hemoglobin and haematologic parameters should be and eliminated in the feces. The mean serum half-life of Pioglitazone and done. This combination may cause hypoglycemia especially in the elderly, total Pioglitazone ranges from 3 to 7 hours and 16 to 24 hours, debilitated or malnourished patients, in those with adrenal, pituitary or hepatic insufficiency. Impaired renal function, deficient caloric intake, or For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only Glimepiride, Pioglitazone and Metformin Hydrochloride (Extended Release) Tablets TRIGPM-1/2
after severe or prolonged exercise or ingestion of alcohol. Alertness and Pregnancy
reactions may be impaired due to hypoglycemia, thus care should be Most experts suggest Insulin be used to maintain the blood glucose levels taken while operating vehicle of machinery. When a patient stabilized on as close to normal as possible. The use of Glimepiride, Pioglitazone and any diabetic regimen is exposed to stress such as fever, trauma, infection Metformin combination is contraindicated during pregnancy.
or surgery, a loss of control may occur.
Lactation
At such times it may be necessary to add Insulin temporarily. The Glimepiride should not be used by breast-feeding mothers. Hence, the effectiveness of any oral antidiabetic combination may decrease in use of Glimepiride, Pioglitazone and Metformin combination is patients over a period of time and is known as 'secondary failure' quite contraindicated in lactating mothers, and if the diet alone is inadequate inherent in the group of Sulphonylureas and may be corrected by adding for controlling blood glucose, Insulin therapy should be considered. Insulin. TRIGPM is not suitable for the Treatment of Type 1 diabetes mellitus.
Pediatric use
The use of Glimepiride, Pioglitazone and Metformin is not studied in
Drug Interactions
The hypoglycemic action of sulphonylurea drugs may be potentiating by certain drugs that are highly protein bound, and classes like nonsteroidal Geriatric use
anti-inflammatory drugs. The others which can do the same are Insulin Metformin is known to be excreted by the kidneys. and because risk of and other oral antidiabetics, ACE inhibitors, allopurinon, anabolic serious adverse reactions to the drug is greater in patients with impaired steroids and male sex hormones, chloramphenicol, coumarins, renal function, hence Glimepiride, Pioglitazone and Metformin should cyclophosphamide, disopuramide, fenfluramine, fibrates, fluxetine, be used only in patients with normal renal function. Because aging is guanethidine, iposphamide, β-blockers, MAO motors, miconazole, associated with reduced renal function the use of Glimepiride, para-amino salicylic acid, pentoxifyline (high dose parenteral), Pioglitazone and Metformin combination should be with caution as age phenylbutazone, azapropazone, oxphenbutazone, probenecid, increases. Care should be taken in the dose selection and regular renal Quinolones, salicylates, sulfinpyrazone, sulphonamides, tetracyclines, tritoqualine, trofosfamide. Weaking of the blood sugar lowering effect and, thus, raised blood sugar levels may occur when one of the following Overdosage
medicines are taken concomitantly, for example: acetaxolamide, Overdosage of sulfonylureas, including Glimepiride, can produce barbiturates, corticosteroids, diazoxide, diuretics, adrenaline and other hypoglycemia. Mild hypoglycemic symptoms without loss of sympathomimetic agents, glucagon, laxatives (after protracted use); consciousness or neurologic findings should be treated aggressively with nicotinic acid (in high doses), destrogen and progestogen, oral glucose and adjustments in drug dosage and/or meal patterns. phenothiazines, phenytoin, rifampicin, thyroid hormones. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but 2 receptor antagonists, clonidine and reserpine may lead to either protentiation or weakening of the blood sugar lowering effect. Cationic constitute medical emergencies requiring immediate hospitalization. If drugs (e.g., amiloride, digoxin, morphine, procainamide, Quinidine, hypoglycemic coma is diagnosed or suspected, the patient should be Quinine, ranitidine, triamterene, trimethoprim and cancomycin) which given a rapid intravenous injection of concentrated (50%) glucose are eliminated by renal tubular secretion could have the potential for solution. This should be followed by a continuous infusion of a more interaction with Metformin by competing for common renal tubular dilute (10%) glucose solution at a rate that will maintain the blood transport systems Concomitant cimetidine leads to 60% increase in peak glucose at a level above 100 mg/dl. Patients should be closely monitored renal clearance in a single dose study. Nifedipine was reported to cause increases in plasma Metformin C Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly.
In vivo drug-drug interaction studies have suggested that Pioglitazone may be a weak inducer of Cyp Storage:
administration of Pioglitazone with oral contraceptives (i.e., 1 mg Store in a cool, dry place. Protect from light norethindrone plus 0.035 mg ethinyl estradiol once daily) resulted in an 11% decrease in ethinyl estradiol AUC. Higher-dosage oral Medicine:
contraceptive formulations may be needed to increase contraceptive efficacy during Pioglitazone use. Alternatively, the use of an alternative or additional method of contraception can be considered. Ketoconazole Presentation:
appears to significantly inhibit the metabolism of Pioglitazone.
Adverse Effects
Gastrointestinal disturbances: Nausea, diarrhea, gastric pain, constipation, vomiting, metallic taste in mouth. These reactions are Biocon Limited
generally dose related and disappear when the dose is reduced. Dermatological effects: Rash, pruritus, urticaria, erythema & flushing.
Electronics city, Bangalore –560 100.
Miscellaneous: Headache and dizziness.
Hypoglycemia: Glimepiride appears to be associated with a incidence of WINDLAS Biotech Limited
hypoglycaemia. Glimepiride may have the potential to produce adverse cardiovascular effects; however Glimepiride has been established agent for the treatment of type 2 diabetes for a number of years adverse cardiovascular effects. Side effects such as headache, upper respiratory tract infection, myalgia, sinusitis and pharyngitis have been reported with Pioglitazone therapy. Cases of anaemia have been Biocon Limited,
reported infrequently in patients treated with Pioglitazone.
20th K.M. Hosur Road, Electronics City,Bangalore - 560100.
Renal Impairment
The use of Glimepiride, Pioglitazone and Metformin is contraindicated in
To report adverse events and/or product complaints visit our website patients with renal impairtment.Hepatic Impairment The use of www.biocon.com or call toll free No: 1800 102 9465 or e mail us at
Glimepiride, Pioglitazone and Metformin is contraindicated in patients

Source: http://biocon.com/docs/prescribing_information/diabetology/trigpm_pi.pdf