Fordia MR: Antidiabetic medicince

2021-07-04 06:22 PM

Fordia MR is indicated for the treatment of type 2 diabetes in adults, especially in overweight patients, when diet and exercise are not adequately controlled.

Producer

United International Pharma.

Ingredient

Each tablet: Metformin hydrochloride 500mg or 750mg.

Pharmacodynamic

Metformin hydrochloride (metformin HCl) is an oral biguanide for the treatment of type 2 diabetes. It improves glucose tolerance in patients with type 2 diabetes and lowers plasma glucose. normal time and after eating. Metformin HCl reduces hepatic glucose production and improves insulin sensitivity by increasing peripheral glucose uptake and consumption.

Metformin HCl has beneficial effects on serum lipid profiles in patients with type 2 diabetes. The drug reduces mean fasting serum concentrations of triglycerides, total cholesterol, and low density cholesterol without no adverse effects on other lipid concentrations. Increased fibrinolytic activity and decreased platelet aggregation have been observed in diabetic patients following treatment with metformin HCl.

Pharmacokinetics

Absorb

Following oral administration of a 500 mg controlled-release metformin tablet, metformin absorption was significantly delayed compared with an immediate-release tablet (Tmax 2.5 hours) with a Tmax of 7 hours. At steady state, similar to the immediate-release formulation, Cmax and AUC do not increase in a dose proportional manner. The AUC following a single dose of 2,000 mg of controlled-release metformin was similar to that observed with a 1,000 mg dose of immediate-release form.

The intra-individual variability of controlled-release Cmax and AUC was comparable to that observed for immediate-release metformin.
 
Administered controlled-release metformin tablets on an empty stomach, AUC decreased approximately 30% (C and Tmax were not affected).

Absorption of metformin controlled-release dosage forms is not altered by food. No accumulation was observed following repeated dosing up to 2,000 mg of controlled-release metformin.

Following a single oral dose of 1,500 mg of 750 mg controlled-release metformin, peak plasma concentrations of 1,193 ng/mL were achieved on average after 5 hours (range 4-12 hours).

Metformin 750 mg controlled release has been shown to be bioequivalent to metformin 500 mg controlled release at a dose of 1,500 mg of both Cmax and AUC in healthy subjects in both satiety and fasting.

Distribution

Binding to plasma proteins is negligible. Metformin divides into red blood cells. Peak blood concentrations are lower than those in plasma and occur at approximately the same time intervals. Red blood cells roughly represent the secondary distribution compartment. The average volume of distribution ranges from 63-276 liters.

Metabolism

Metformin is excreted unchanged in the urine. No metabolites have been found in humans.

Elimination

With metformin clearance >400 mL/min, metformin is eliminated by glomerular filtration and tubular secretion. Following oral administration, the half-life is expected to be approximately 6.5 hours.

When renal function is impaired, renal clearance is proportionally reduced to creatinine and thus the half-life of metformin is prolonged, leading to increased plasma concentrations of metformin.

Indications and uses

Fordia MR is indicated for the treatment of type 2 diabetes mellitus in adults, particularly in overweight patients, when diet and exercise are not adequately controlled. Fordia MR can be used alone or in combination with other oral antidiabetic agents, or with insulin.

Dosage and Administration

Recommended dose

The starting dose for patients not taking metformin is 500 mg once daily orally. If the patient does not experience gastrointestinal adverse reactions and the dose needs to be increased, an additional 500 mg may be given at intervals of 1 to 2 weeks. Dosage of metformin should be individually adjusted based on efficacy and tolerability and should not exceed the maximum recommended dose of 2000 mg/day.

Monotherapy and in combination with other oral antidiabetic drugs

If blood glucose is not controlled with Fordia MR 2,000 mg once daily, Fordia MR 1,000 mg twice daily should be considered, taken with food.

In patients already treated with conventional (immediate-release) metformin tablets, the starting dose of Fordia MR should be equivalent to the daily dose of the immediate-release metformin tablet. In patients treated with metformin at doses above 2,000 mg daily, switching to Fordia MR should not be recommended.

If switching from another oral antidiabetic agent to Fordia MR: discontinue those agents and initiate Fordia MR at the dose indicated above.

Fordia MR 750 mg is intended for use in patients already treated with metformin (immediate release or controlled release).

The dose of Fordia MR 750 mg should be equivalent to a daily dose of metformin tablets (immediate or controlled release), up to a maximum of 1,500 mg, taken with the evening meal.

Combination with insulin

Metformin and insulin can be used in combination to achieve better glycemic control. The usual starting dose of Fordia MR is 1 tablet of 500 mg once daily, the dose of insulin is adjusted based on blood glucose readings.

For patients already on metformin and insulin combination therapy, the dose of Fordia MR 750 mg should be equivalent to a daily dose of metformin tablets, up to a maximum of 1,500 mg, taken with evening meals, insulin dose adjusted. based on blood sugar.

Recommended use in patients with renal failure

Assess renal function prior to initiation of metformin therapy and periodically thereafter.

Metformin is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2.

Initiation of metformin therapy is not recommended in patients with an eGFR between 30 and 45 mL/min/1.73 m2.

In patients taking metformin and whose eGFR falls below 45 mL/min/1.73 m2, assess the risk-benefit of continuing treatment.

Discontinue metformin if the patient's eGFR falls below 30 mL/min/1.73 m2.

Discontinue metformin during iodinated contrast imaging tests

In patients with an eGFR between 30 and 60 mL/min/1.73 m2, in patients with a history of liver disease, alcoholism, or heart failure, or in patients who will be receiving anticoagulants. Intra-arterial iodinated contrast agents, discontinue metformin before or at the time of imaging with iodinated contrast media. Reassess eGFR at 48 hours, reinstitute metformin if renal function is stable.

Elderly

Because metformin has the potential to decrease renal function in the elderly, dose adjustment of metformin should be based on renal function, requiring frequent monitoring of renal function.

Children

Due to the lack of clinical data, Fordia MR should not be used in children.

Warning

Lactic acidosis

Postmarketing surveillance has documented metformin-associated lactic acidosis, including death, hypothermia, hypotension, and persistent bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied by atypical symptoms such as malaise, myalgia, respiratory distress, lethargy, and abdominal pain. Metformin-associated lactic acidosis is characterized by increased lactate levels in the blood (>5 mmol/L), an anion gap (no evidence of ketouria or ketosis), increased lactate/pyruvate ratio, In general, metformin plasma concentrations are increased by >5 µg/mL.

Risk factors for metformin-associated lactic acidosis include renal failure, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), age 65 years or older, taking Contrast imaging, surgery and other procedures, hypoxia (eg, acute congestive heart failure), heavy alcohol consumption, and liver failure.

Measures to reduce risk and manage metformin-associated lactic acidosis in high-risk patients are detailed in the package insert (Dosage and administration section, Contraindications, Contraindications). Warnings, Interactions and Use in Special Populations).

If metformin-associated lactic acidosis is suspected, metformin should be discontinued, the patient promptly referred to the hospital, and management instituted. In patients already treated with metformin, diagnosed with lactic acidosis, or suspected of having a high likelihood of developing lactic acidosis, prompt dialysis is recommended to correct the acidosis and remove accumulated metformin. metformin hydrochloride is dialyzable with a clearance of 170 mL/min under good hemodynamic conditions). Hemodialysis can reverse symptoms and restore recovery.

Educate patients and family members about the symptoms of lactic acidosis and, if these occur, discontinue the drug and report these symptoms to the physician.

For each risk factor for metformin-associated lactic acidosis, recommendations to help reduce the risk and manage metformin-associated lactic acidosis are as follows:

Renal failure

Metformin-associated lactic acidosis during postmarketing drug monitoring occurred mainly in patients with severe renal impairment. The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal failure because metformin is eliminated primarily by the kidneys. Clinical recommendations based on the patient's renal function include:

Before initiating therapy with metformin, it is necessary to estimate the patient's glomerular filtration rate (eGFR).

Metformin is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2.

Initiation of metformin therapy is not recommended in patients with an eGFR between 30 and 45 mL/min/1.73 m2.

Collect data on eGFR at least once a year in all metfformin patients. In patients at increased risk of renal failure (eg, the elderly), renal function should be assessed more frequently.

In patients taking metformin and whose eGFR falls below 45 mL/min/1.73 m2, assess the risk-benefit of continuing the regimen.

Drug interactions

Concomitant use of metformin with certain drugs may increase the risk of metformin-associated lactic acidosis, in patients with impaired renal function leading to significant hemodynamic changes, affecting acid-base balance or increase metformin accumulation. Therefore, consider monitoring the patient more frequently.

Patients 65 years and older

The risk of metformin-associated lactic acidosis increases with patient age because elderly patients are more likely to have liver, renal, or heart failure than younger patients. Renal function should be assessed more frequently in elderly patients.

Perform diagnostic tests using contrast

Intravascular administration of contrast in patients receiving metformin therapy may lead to acute decline in renal function and lactic acidosis. Discontinue metformin before or at the time of iodinated contrast imaging in patients with an eGFR between 30-60 mL/min/1.73 m2, who have a history of renal failure liver disease, alcoholics, heart failure, or patients who will receive intravenous iodinated contrast agents. Reassess eGFR 48 hours after screening and reinstitute metformin if renal function is stable.

Surgery or other procedures

Food and fluid retention during surgery or other procedures may increase the risk of volume depletion, hypotension, and renal failure. Metformin should be temporarily discontinued when the patient has limited food and fluid intake.

Inspiratory hypoxia

Postmarketing follow-up has documented a number of metformin-associated lactic acidosis occurring in the setting of acute congestive heart failure (especially when accompanied by hypoperfusion and hypoxemia). Cardiovascular collapse (shock), acute myocardial infarction, sepsis and other conditions associated with hypoxemia are associated with lactic acidosis and may also cause prerenal azotemia. When these events occur, discontinue metformin.

Drink alcohol

Alcohol has the potential to affect the effects of metformin on lactate metabolism and may therefore increase the risk of metformin-associated lactic acidosis. Warn patients not to drink alcohol while using metformin.

Liver failure

Patients with hepatic impairment may develop metformin-associated lactic acidosis due to impaired lactate elimination leading to increased blood lactate concentrations. Therefore, the use of metformin should be avoided in patients who have been diagnosed with liver disease through laboratory or clinical evidence.

Impaired absorption of vitamin B12 and folic acid from the gastrointestinal tract due to long-term treatment with metformin HCl.

Effects on ability to drive and use machines

Metformin monotherapy does not cause hypoglycaemia and therefore does not affect the ability to drive and use machines. However, patients should be warned about the risk of hypoglycaemia when receiving concomitant metformin and other antidiabetic agents (sulfonylureas, insulin, repaglinide). Metformin may cause headache and dizziness in rare cases and the ability to drive or use machines may therefore be impaired.

Elderly

Age is associated with a decline in renal function and metformin HCl is known to be excreted primarily by the kidneys. The risk of serious adverse events with metformin HCl is greater in patients with impaired renal function/severe renal impairment, especially in the elderly. Care should be taken in dose selection and should be based on careful and frequent monitoring of renal function. In general, the dose used in elderly patients should not be maximal. Metformin HCl should not be treated in patients 80 years of age or older unless creatinine clearance demonstrates that renal function is not impaired.

Babies and children

The use of metformin HCl immediate-release tablets has been performed in pediatric type 2 diabetic patients aged 10 to 16 years. Clinical studies have not been performed in children under 10 years of age.

Overdose

No reduction in blood sugar was observed after ingestion of 85 g of metformin HCl, although lactic acidosis did occur in that case. Metformin HCl is dialyzable with clearances up to 170 mL/min; hemodialysis may therefore be effective in eliminating accumulated drug in patients with suspected drug overdose.

Contraindications

Do not use Fordia MR in patients who:

The patient has a history of hypersensitivity to metformin hydrochloride.

Patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis.

Patients with severe renal impairment (eGFR less than 30 mL/min/1.73m2).

Diabetic pre-coma.

Acute conditions with the potential to alter kidney function such as:

Loss of water.

Severe infection.

Shock.

Intravenous administration of contrast agents containing iodine.

Acute or chronic conditions that can cause tissue hypoxia include:

Decompensated heart failure.

Respiratory failure.

Recent myocardial infarction.

Shock.

Liver failure, acute alcohol poisoning, alcoholism.

Use in pregnant and lactating women

Pregnant

There are no adequate and well-controlled studies performed in humans. Fordia MR should not be used during pregnancy unless clearly needed.

Breastfeeding Women

Studies in rats have shown that metformin HCl is excreted in milk. Because of the potential for hypoglycemia in the nursing infant, consideration should be given to discontinuing the drug or stopping breastfeeding, given the importance of the drug to the mother.

Interactive

Should not be used at the same time

Alcohol: Increased risk of lactic acidosis in acute alcohol poisoning, especially in cases of:

Starvation or malnutrition.

Liver failure.

Avoid the use of alcohol and alcohol-containing preparations.

Iodine Contrast: Intravenous injection of iodinated contrast material during an X-ray can lead to kidney failure. This can cause drug accumulation and increase the risk of lactic acidosis. Metformin should be discontinued 48 hours prior to injection of iodinated contrast and reinstituted metformin at least 48 hours after radiographs when renal function has been reassessed.

Use caution when used concurrently

Drugs with the potential to increase blood glucose [eg, glucocorticoids, thyroid products and tetracosactide (systemic and topical), ß-agonists, danazol, chlorpromazine at high doses of 100 mg daily, and diuretics] : More frequent blood glucose monitoring is recommended, especially at the beginning of treatment. If necessary, adjust the dose of metformin during treatment.

ACE inhibitors

ACE inhibitors can lower blood sugar. Therefore, dose adjustment of metformin hydrochloride may be necessary when these drugs are co-administered or treatment is discontinued.

Antifreeze

Metformin accelerates the elimination of vitamin K antagonists. Therefore, prothrombin time should be closely monitored in patients receiving metformin and a vitamin K antagonist concomitantly.

Beta blockers

Concomitant use of metformin and beta-blockers may lead to a risk of hypoglycaemia. In addition, some signs of hypoglycemia, especially tachycardia, may be masked. Blood glucose should be monitored while adjusting the dose of each drug.

Calcium channel blockers

Calcium channel blockers may affect glycemic control in patients with diabetes; Blood sugar should be regularly monitored.

Cimetidine

Reduced metformin clearance has been reported during concomitant treatment with cimetidine, and dose reduction should be considered.

Diuretics, especially loop diuretics

May increase risk of lactic acidosis due to decreased renal function.

Other hypoglycemic drugs

Metformin monotherapy did not cause hypoglycaemia; however, caution should be exercised when used in combination with other hypoglycemic agents (sulfonylurea, glitinide, insulin).

Nifedipine

Nifedipine increases the absorption of metformin. Metformin affects the pharmacokinetics of nifedipine.

Thyrotropin

Decreased thyrotropin (TSH) levels have been reported in diabetic patients with hypothyroidism at the start of metformin therapy.

Side effects

The most common adverse effects of metformin are gastrointestinal. These effects are dose related and usually occur at the start of treatment but are usually transient.

Common, ADR>1/100

Gastrointestinal: Diarrhea (10-53%), nausea, vomiting (7-25%), flatulence (12%), dyspepsia (7%), abdominal distention, abnormal stools, constipation, heartburn taste disorder.

Central nervous system: Headache (6%), dizziness, chills.

Musculoskeletal: Muscle weakness (9%).

Respiratory: Shortness of breath, upper respiratory tract infection.

Skin: Rash

Uncommon, 1/1000<ADR<1/100

Metabolic acidosis (very rare), megaloblastic anemia, pneumonia.

Preservation

Store in a dry place, at a temperature not exceeding 30°C, protected from light.

Presentation and packaging

Controlled release film-coated tablets: box of 1 blister x 10 tablets, box of 6 blisters x 10 tablets.