Glimepiride Prices(4,2,1 mg)

Glimepiride is a member of the Sulfonylouris drug category and is commonly used for diabetes - type-2.

Commercial names for glimepiride include Amaryl.

Green

Oral Tablets

Quantity	Per Unit	Price
30	0.44 $ 0.44	13. 12 $ 13. 12
50 (5 x10 each)	0. 31 $ 15. 53	$ 15. 53
90	0. 23 $ 20. 35	20. 35 $ 0. 21- $ 0. 22
100	$ 0. 21- $ 0. 22	$ 21. 38- $ 21. 56
180	0. 17 $ 0. 17 $ 0. 17 $ 0. 17 $ 0. 17 $ 0. 17 $ 0. 17	0. 14 $ 0. 14 $ 0. 14 $ 0. 14 $ 0. 14
500	0. 14 $ 69. 80	69. 80 $ 69. 80 $ 69. 80 $ 69. 80

See the brand version of this drug:

IMPORTANT: If there is a price range, consumers should normally expect to pay the lowest price. However, due to lack of stock and other unknown variables, no guarantee can be offered.

Quantity	Per Unit	Price
30	0. 49 $ 0. 49	$ 14. 60
50 (5 x10 each)	0.36 $ 18.00	0. 36 $ 18. 00
90	0. 26 $ 23. 69	23. 69 $ 0. 22- $ 0. 27
100	$ 0. 22- $ 0. 27	$ 21. 97- $ 26. 50
180	0. 16 $ $ 28.	28. 94 $ 0. 19 $ 0. 19 $ 0. 19 $ 0. 19
500	0. 19 $ 0. 19 $ 0. 19 $ 0. 19 $ 0. 19 $ 0. 19 $ 0. 19	94. 51 $ 0. 51

See the brand version of this drug:

IMPORTANT: If there is a price range, consumers should normally expect to pay the lowest price. However, due to lack of stock and other unknown variables, no guarantee can be offered.

Quantity	Per Unit	Price
30	0. $64	19. 12 Dollars
50 (5 x10 each)	0. 51 $25. 53	25. 53 $ 0. 27- $ 0. 31
90	$ 0. 27- $ 0. 31	$ 23. 96- $ 27. 61
100	$ 0. 26- $ 0. 42	$ 25. 82- $ 41. 56
180	0. 16 $ $ 28.	29. 49 $ 0. 34
500	$ 0. 34 $ 0. 35 $ 0. 35 $ 0. 35	$ 169. 81

See the brand version of this drug:

IMPORTANT: If there is a price range, consumers should normally expect to pay the lowest price. However, due to lack of stock and other unknown variables, no guarantee can be offered.

Glimepiride Coupons, Copay Cards, and Discounts

Glimepiride offers may be in the form of printable coupons, discounts, save or join cards, trial-type offers or free samples. Some bids may be printable from the website, while others may require registration, completion of a questionnaire, or a sample received by the physician.

The free printable discount drugs.com acts as a coupon and can save you up to 80% or more over the cost of prescription drugs, non-prescription drugs, and pets.

Note: This is a drug discount program, not an insurance program, and applies to all major chains, including Walgreens, CVS Pharmacy, Target, Walmart Pharmacy, Duane Reade, and 65, 000 pharmacies nationwide.

No manufacturer bids were found for this drug.

Patient Assistance Program & Glimepiride Payments Payments

Patient Help Programs (PAPS) are usually funded by pharmaceutical companies and offer free or reduced drug prices, participation programs to low-income and uninsured/underinsured individuals, and meet certain criteria. Eligibility requirements for each program may vary.

No patient help programs were found for this drug. However, your health care provider may have more information about specific programs available in your area.

Amaryl

Amaryl is a prescription medication used to treat symptoms of type 2 Diabetes 2. Amaryl can be used alone or with other medications.

Amaryl belongs to a category of drugs called anti-diabetic, sulfonylureas.

It is not known if Amaryl is safe and effective in children.

What are the possible side effects of Amaryl?

Amaryl can cause serious side effects, including

• Pale or yellow skin
• Dark urine,
• Delirium,
• Weakness and
• fever

If any of the above symptoms are present, seek medical assistance immediately.

The most common side effects of Amaryl include

• Headache,
• Dizziness,
• Weakness,
• nausea, and
• low blood sugar.

Tell your doctor if you have any side effects that concern you or do not recede.

These are not all side effects of Amaryl. Contact your physician or pharmacist for more information.

For medical advice on side effects, call your doctor at 1-800-FDA-1088 to report FDA side effects.

Description.

Amaryl is an oral sulfur containing the active ingredient glimepiride. The chemical, glimepiride, is identified as 1-[[P-methylcircul)urea (C₂₄H₃₄N₄O₅S) with a molecular weight of 490.62. Glimepiride is a white to yellowish white, crystalline, odorless dust so practically odorless and practically insoluble in water. The structural type is as follows

Amaryl tablets contain the active ingredient glitepiride and the following inactive ingredients: lactose (water), glycol sodium starch, povidone, microcrystalline cellulose, and magnesium stearate. In addition, Amaryl 1 mg tablets contain iron oxide, Amaryl 2 mg tablets contain iron oxide yellow, and Amaryl 4 mg tablets with FD& C Blue #2 aluminum lake.

Indications.

Amaryl has been shown as a dietary and exercise supplement to improve glycemic control in adults with type 2 diabetes [see clinical studies].

Substantial Limitations of Use

Amaryl should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it is not effective in these conditions.

Medication and Administration

Recommended Dosage.

Amaryl should be given with breakfast or the first main meal of the day.

The recommended starting dose of Amaryl is 1 mg or 2 mg daily. Patients at high risk of hypoglycemia (elderly or patients with renal dysfunction) should be started at 1 mg daily [see Precautions and Prophylaxis in Special Populations, and Use].

After reaching a dose of 2 mg daily, further doses can be given in 1 mg or 2 mg steps based on the patient's glycemic response. Upgrades are infrequent, every 1-2 weeks. For patients at high risk of hypoglycemia, a preservative securitization regimen is recommended [see Precautions and Prophylaxis and Use in Special Populations].

The maximum recommended dose is 8 mg once daily.

Patients transported to Amaryl by sulfonylureas with longer half-lives (e.g., chloropropamide) should have overlapping drug activity for 1-2 weeks and be monitored appropriately for hypoglycemia.

When Collsevelam is co-administered with Glimeride, the maximum plasma concentration and overall exposure to glimepiride is reduced. Therefore, Amaryl should be administered at least 4 hours before Collsevelam.

How is it approved

Dosage and form of power

Amaryl is designed as the following tablets

• 1 mg (pink, flat face, notched on the side of the double partition, with the phrase "ama ryl" on one side)
• 2 mg (green, flat, notched with an elongated double diaphragm, with the footprint "ama ryl" on one side)
• 4 mg (blue, flat, epic, double dihedral with closed sides, footprint "Amma Ryl" on one side)

Storage and Handling

Amma Ryl tablets are available in the following packaging contents and sizes

100 bottles (NDC 0039-0221-10) of 1 mg (pink, flat, elongated with notched, double-dichotomized sides, imprinted "amma ryl" on one side)

2 mg (green, level, elongated, with closed sides in double dichotomies, engraved "ama ryl" on one side) 100 bottles (NDC 0039-0222-10)

4 mg (blue, flat, elongated, with double-dichotomized closed sides, engraved on one side "ama ryl") 100 bottles (NDC 0039-0223-10)

Store at 25°C (77°F) - determination is allowed at 20-25°C (68-77°F) (see USP controlled room temperature).

Dispense into properly closed cans with safety caps.

Sanofi-Aaventis U. S. LLC, Bridgewater, NJ 08807, Sanofi Inc. revised December 2016

Slide show

Sides.

The following serious side effects are detailed below elsewhere on the label.

[see Warnings and Precautions] [see Warnings and Precautions].

In clinical trials, the most common side effects of Amaryl were hypoglycemia, dizziness, sickness, headache, and nausea.

Clinical Trial Experience

Because clinical trials are conducted under very different conditions, the rates of side effects observed in clinical trials for one drug cannot be directly compared to rates in clinical trials for another drug and may not reflect the rates actually observed.

Patients with type 2 diabetes were treated with Amaryl in controlled clinical trials. In these studies, approximately 1,700 patients were treated with Amaryl for at least one year.

Table 1 summarizes side effects in addition to hypoglycemia, referring to 11 enriched placebo-controlled studies that were considered potentially or possibly relevant to the study studies. Treatment durations ranged from 13 weeks to 12 months. The terms mentioned represent those that occurred at a frequency of 5% or more among patients treated with Amaryl and more frequently than in placebo patients.

Table 1: 11 petals from 13 weeks to 12 months - controlled imaging study: side effects (except hypoglycemia) occurred more often than 5% of patients treated more frequently than virtual medicine*.

Amaryl n = 745%.	Placebo n = 294%.
Headache	8.2	7.8
Accidental Injury†	5.8	3.4
Influenza syndrome	5.4	4.4
Motion sickness	5.0	3.4
Dizziness	5.0	2.4
*Amaryl doses ranged from 1 to 16 mg daily† Insufficient information determined whether any of the random injury incidents were related to hypoglycemia

Hypoglycemia

In a randomized, double-blind, placebo-controlled 14-week monotherapy study, patients already treated with sulfonylurea were randomized to Amaryl 1 mg, 4 mg, 4 mg, 8 mg, or 8 mg after 3 weeks. . Patients randomized with Amaryl 4 mg or 8 mg received forced securitization from an initial dose of 1 mg at these final doses. Clinical Study]. The overall impact of possible hypoglycemia (defined by the presence of at least one symptom that the investigators believed to be related to hypoglycemia - no concurrent glucose measurement) was 4% at 1 mg of Amaryl, 17% at 4 mg of Amaryl, and 16% at 8 mg of placebo and 0%. All of these events were treated with self-treatment.

In a randomized, double-blind, placebo-controlled 22-week monotherapy study, patients received daily initial doses of either 1 mg Amaryl or placebo. The dose of Amaryl was fixed so that fasting plasma had a target of 90-150 mg/dL. Final daily doses of Amaryl were 1, 2, 3, 4, 6, or 8 mg [reference clinical study]. The total effect of possible hypoglycemia (as defined above) of Amaryl versus placebo was 19.7% versus 3.2%. All of these events were self-healing.

Weight gain: Amaryl, like all sulfonylureas, can cause weight gain [see clinical studies].

Allergic reactions: In clinical studies, allergic reactions such as itching, erythema, ur measles, and morbid or macular occurred in less than 1% of patients treated with Amaryl. These may regress despite continued treatment with Amaryl. There have been reports after market traffic for more serious allergic reactions (e.g., shortness of breath, hypotension, shock, etc.) [see Precautions and precautions].

Laboratory Tests

Increased serum alanine aminotransferase (ALT): in 11 Amaryl-enriched placebo-controlled studies, 1.9% of patients treated with Amaryl and 0.8% of placebo-treated patients had ALTU above twice the upper limit of the reference range.

Post-Market Traffic Experience

The following adverse reactions have been identified during post-approval use of Amaryl. Because these reactions have been spontaneously mentioned by populations of uncertain size, it is not always possible to reliably assess their frequency or establish a causal relationship to drug exposure.

• Severe hypersensitivity reactions such as anaphylaxis, angioedema, Stevens-Johnson syndrome [reference paragraph warning and precautions] anemia in patients with or without G6PD deficiency [reference paragraph warning and precautions].
• Liver function (e.g., biliary congestion and yellow und), as well as hepatitis can be determined. and photosensitive reactions and allergic vasculitis, cardiorespiratory anemia and permeability (including severe cases of platelets less than 10, 000/µl) and thrombotic purplish
• hepatic porphyria and disulfiram-like reactions and syndrome of inappropriate antidiuretic hormone secretion (SIADH).
• Dysfunction

Drug interactions

Drugs that affect glucose metabolism

Some medications affect glucose metabolism and may require close monitoring of amaryl dose indications and especially hypoglycemia or deterioration of glycemic control.

The following are examples of drugs that may increase the glycosyliotic effects of sulfonylureas, including amaryl, increased hypoglycemic sensitivity, and/or hypoglycemia. Steroids and androgens, fluoxetine, nonsteroidal anti-inflammatory drugs, salicylics, sulfonamides, chloramphenicol, pentoxylines from proteins such as coumarins, propene aminekides and monoaminexidase inhibitors. When these medications are administered to patients taking Amaryl, patients are closely monitored for hypoglycemia. When these drugs are withdrawn from patients taking Amaryl, they closely monitor the patient and degrade glycemic control.

The following are examples of medications that can reduce the effects of sulfonylglucose reduction, including Amaryl, and lead to deterioration of glycemic control: danazol, glycon, somatotropin, protease inhibitors, informal antipsychotics (e.g., barbiturates, diazos, rifabin, rifabin, rifabin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetic acids. When these medications are administered to patients taking Amaryl, they closely monitor the patient and worsen glycemic control. When these medications are withdrawn from patients taking Amaryl, they closely monitor the patient for hypoglycemia.

Beta-blockers, clonidine, and reserpine can lead to enhanced or weakened glycosimetic effects of Amaryl.

Alcohol intake, both acute and chronic, can promote or weaken the glycosimetic activity of amaryl in unpredictable ways.

Signs of hypoglycemia may be reduced or absent in patients taking beta-blockers and sympathomimetics such as clonidine, guanetidine, and reserpine.

Miconazole.

An interaction is now possible between oral miconazole and sulfonyluris leading to severe hypoglycemia. It is not known if this interaction occurs with other dosage forms of miconazole.

Interaction with Cytochrome P450 2C9

There is a possible interaction between glimepiride and inhibitors (such as fluconazole) and inducers (such as rifabin) of cytochrome P450 2C9. Fluconazole suspends glimepiride metabolism, causing an increase in plasma dimepiride concentrations, which may lead to hypoglycemia. Rifampin induces the metabolism of dimepiride and causes a decrease in the concentration of dimepiride in the plasma, which may lead to deterioration of glycemic control.

Concurrent administration of Colesevelam

Collsevelam can reduce maximum plasma concentrations and overall exposure to glimepiride when these two substances are collocated. However, if glimepiride is administered 4 hours before Colesevelam, absorption is not reduced. Therefore, Amaryl should be administered at least 4 hours prior to Colcevelam.

Warning.

Included as part of the Precautions section.

Prophylaxis

Hypoglycemia

All sulfonylureas, including Amaryl, can cause severe hypoglycemia [see Unwanted Effects]. The patient's ability to concentrate and react can be reduced as a result of hypoglycemia. These impairments may be a risk in situations where these abilities are particularly important, such as driving or handling other machinery. Severe hypoglycemia can lead to loss of sensation and seizures, which can lead to temporary or permanent discounts in brain function or death.

Patients should be trained to recognize and manage hypoglycemia. Be careful to initiate and increase Amaryl doses in patients who may be predisposed to hypoglycemia (elderly patients, patients with renal dysfunction, patients taking other antidiabetic medications). Weak or malnourished patients and patients with adrenal, subtype or hepatic dysfunction are particularly susceptible to the hypoglycemic effects of glucose-reducing agents. Hypoglycemia is more likely to occur when caloric intake is inadequate, after severe or prolonged exercise, or when alcohol is taken.

Early warning signs of hypoglycemia may be different or less severe in patients with autonomic neuropathy, the elderly, and those taking medications that inhibit beta-adrenergic effects or other sympathetic factors. These conditions can lead to severe hypoglycemia before the patient feels hypoglycemic.

Hypersensitivity Reactions

There have been reports of hypersensitivity reactions following the release of Amaryl for patients treated with Amaryl, including severe reactions such as anaphylaxis, angioedema, and Stevens-Johnson syndrome. If a hypersensitivity reaction is suspected, discontinue Amaryl immediately, evaluate other possible reactions, and initiate alternative treatment for diabetes.

Hemolytic anemia

In patients with 6-phosphate glucose (G6PD) dehydrogenase deficiency, sulfonylureas can cause hemolytic anemia. Because Amaryl is a sulfonylurea, caution should be exercised in patients with G6PD deficiency and the use of non-sulfonylureas should be investigated as an alternative. There have also been reports of hemolytic anemia in patients receiving Amaryl after marketing and no known G6PD deficiency [action not required for reference].

Increased risk of cardiovascular mortality with sulfonylureas

Administration of oral hypoglycemic agents has been reported to be associated with increased cardiovascular mortality compared to treatment with diet or diet and insulin alone. This warning is based on a study conducted by the University Group Group Diabetes Program (UGDP). This is a long-term prospective clinical trial designed to evaluate the efficacy of drugs to reduce blood glucose in preventing or delaying vascular complications in non-insulin diabetics. The study involved 823 patients who were randomly distributed into one of four treatment groups of UGDP. It reported more patients treated over time with stable doses, with patients treated for 5 to 8 years than those who received diet alone. Although there was no significant increase in overall mortality, the use of tolbutamide was discontinued based on increased cardiovascular mortality, thereby limiting the opportunity for the study to show an increase in overall mortality. Despite disputes regarding the interpretation of these results, the results of the UGDP study provide an adequate basis for this warning. Patients should be informed of the potential risks and benefits of Amaryl and alternative treatment modalities. Although this study included only one drug in the sulfonylur category (tolbutamide), it is prudent to consider that this warning may apply to other oral glucose medications in this category. Action and Chemical Structure.

Primary Consequences.

There are no clinical trials that convincingly demonstrate a reduction in macrovascular risk with Amaryl or other antidiabetic drugs.

Non-clinical toxicology

Carcinogenesis, mutation, and fertility damage

Studies in rats at doses of up to 5000 parts per million (ppm) for 30 months (approximately 340 times the maximum recommended human dose based on surface basis) showed no evidence of carcinogenesis. In mice, administration of glimepiridis for 24 months resulted in increased formation of dose-related benign pancreatic adenomas, which were thought to be the result of chronic irritation of the pancreas. In mice, no adenoma formation was observed at doses of 320 ppm on complete food or 46-54 mg/kg body weight/day. This is approximately 35 times the maximum recommended dose for males of 8 mg once daily based on the surface.

Glimepiride was non-mutagenic in a series of in vitro and in vivo mutation studies (AMES test, somatic mutation, chromosome bypass, unscheduled DNA synthesis and mouse microtestis test).

There was no effect of glimepiride on male mouse fertility in animals exposed up to 2500 mg/kg body weight ( >(1, 700 times the maximum recommended human dose, based on surface) Glimepiride had no effect on fertility in male and female rats administered up to 4000 mg/kg body weight (approximately 4, 000 times the maximum recommended human dose).

Use in specific populations

Pregnancy

Pregnancy Category

Inadequate and well-controlled amalyl studies in pregnant women. Animal studies showed no increase in birth defects, but there was a 50-fold increase in fetal deaths in rats and rabbits at the guigilide dose (rats) and a 0.1-fold increase at the maximum recommended human dose (rabbits) (body). This embryotoxicity, observed only at doses that cause hypoglycemia in the mother, is believed to be directly related to the pharmacological (hypoglycemic) activity of glimepiride, as well as other sulfonylureas. Amaryl should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data suggest that treatment of diabetes during pregnancy should maintain blood glucose as close as possible, as abnormal blood glucose during pregnancy is associated with a higher incidence of birth defects.

Non-tooth-forming effects

Long-term severe hypoglycemia (4-10 days) has been reported in neonates born to mothers who received sulfonylureas during delivery.

Nursing mothers.

It is not known if amaryl is excreted in breast milk. During pre-Nival studies in rats, there was considerable heritable inheritance in milk and neonatal serum. Offspring of rats exposed to high levels of digipyride during pregnancy and breastfeeding exhibited skeletal deformities consisting of shortening, hypertrophy, and bending of bones during the postnatal period. These skeletal deformities were determined as a result of breastfeeding by mothers exposed to glimepiride. Based on these animals, a decision should be made whether to stop or discontinue breastfeeding based on the possibility of hypoglycemia in breastfed infants and considering the importance of maternal amaryllis.

Pediatric Uses

As discussed below, the pharmacokinetics, efficacy, and safety of Amaryl have been evaluated in pediatric patients with type 2 diabetes. Due to side effects on body weight and hypoglycemia, Amaryl is not recommended in pediatric patients.

Pharmacokinetics of a single 1 mg Amaryl dose were evaluated in 30 patients aged 10-17 years with type 2 diabetes (males = 7, females = 23). The mean (±SD) AUC (339 ± 203 ngâ-hr/ml), CMAX (102 ± 48 ngâ-hr/ml) and T½ (3. 1 ± 1. 7 h) of glimepiride were comparable to historical data in adults (AUC(0)-last) 315 ± 96 ngâ-hr/ml, cmax 103 ± 34 ngâ-hr/ml and t½5. 3±4. 1 hr).

The safety and efficacy of Amaryl in pediatric patients were evaluated in a 24-week single-case study in which 272 patients (8-17 years) with type 2 diabetes were randomized to Amaryl (n = 135) or metformin (n = 137). Untreated patients (those on diet and exercise only for at least 2 weeks of randomization) and previously treated patients (those previously or currently treated with another oral antidiabetic for at least 3 months) were eligible to participate. Patients who received oral antidiabetic medications when they entered the study discontinued these medications prior to the rage without a rinse period; Amaryl was started at a dose of 1 mg and fixed to 2, 4, or 8 mg by week 12 (final dose of 4 mg) and aimed at self-regulated fasting blood glucose< 126 mg/dL. Metformin was initiated at 500 mg twice daily and titrated at Week 12 up to 1000 mg twice daily (mean last dose 1365 mg).

After 24 weeks, the overall mean treatment difference in HBA1C between Amaryl and metformin was 0. 2% (95% confidenc e-0. 3% to +0. 6%). Based on these results, the test did not achieve its primary goal. That is, to show a similar reduction in Hba1c using Amaryl compared to metformin.

Table 2: Change from initial HBA values and body weight in pediatric patients treated with Amaryl or metformin

Metformin	Amaryl
Patients without treatment*.	n = 69	n = 72
HBA1C (%)
Base price (average)	8.2	8.3
Change per initial value (indicated mean LS)	-1. 2	-1. 0
Difference in indicated treatment‡ (95% CI)	0. 2 (-0. 3; 0. 6)
Previously cured patients*.	n = 57	n = 55
HBA1C (%)
Base price (average)	9.0	8.7
Change per initial value (indicated mean LS)	-0. 2	0.2
Difference in indicated treatment‡ (95% CI)	0. 4 (-0. 4; 1. 2)
Body weight (kg)*	n = 126	n = 129
Base price (average)	67. 3	66. 5
Change per initial value (indicated mean LS)	0.7	2.0
Adjusted treatment difference‡ (95% de)	1. 3 (0. 3; 2. 3)
*Population intended to be treated last observation moved forward due to missing data (Amaryl, n = 127 - metformin, n = 126)† in favor of metformin adapted to the original HBA 1C and Tanner phase

The profile of adverse effects in pediatric patients treated with Amaryl was similar to that observed in adults [action not required for reference].

Geriatric use

In clinical trials of AMARYL, 1053 of 3491 patients (30%) were >65 years of age. No complete difference in safety or efficacy was observed between these patients and younger patients, but susceptibility of some elderly patients cannot be excluded.

There were no significant differences in glimepiride pharmacokinetics between patients with type 2 diabetes ≤ 65 years (n=49) and those >65 years of age (n = 42) [reference clinical pharmacology].

Glimepiride is excreted substantially by the kidneys. Elderly patients are more likely to suffer from renal dysfunction. Additionally, hypoglycemia can be difficult to recognize in the elderly [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]. Use caution when starting Amaryl and increase the Amaryl dose in this patient population.

Renal dysfunction

To minimize the risk of hypoglycemia, the recommended dose of Amaryl is 1 mg daily for all patients with type 2 diabetes and renal dysfunction [see Dosage and Administration and Warnings and Precautions].

A multidose titration study was conducted in 16 patients with type 2 diabetes and renal impairment using doses ranging from 1 mg to 8 mg daily for 3 months. Initial creatinine clearance ranged from 10 to 60 ml/min.Amaryl pharmacokinetics were evaluated in the multidose titration studies and results were consistent with those observed in patients involved in the dose studies. In both studies, the relative overall clearance of Amaryl increased as renal function decreased. Both studies also showed decreased removal of the two major metabolites in patients with renal impairment [see Clinical Pharmacology].

Overdose.

Amaryl overdose, like other sulfonylureas, can cause severe hypoglycemia. Mild episodes of hypoglycemia can be treated with oral glucose. Severe hypoglycemic reactions are urgent medical cases requiring immediate treatment.com Severe hypoglycemia with sleep, seizures or neurologic damage can be treated with glucagon or intravenous glucose. Ongoing observation and additional carbohydrate intake may be necessary as hypoglycemia may reappear after apparent clinical rehabilitation [see Precautions and Preventive Measures].

Contraindications.

Amaryl is contraindicated in patients with a history of hypersensitivity reactions to

• Glade or any of the product's ingredients [see Warnings and Precautions].

Sulfonamide Derivatives: Patients who have developed allergic reactions to sulfonamide derivatives may develop allergic reactions to Amaryl. Patients with a history of allergic reactions to sulfonamide derivatives should not use Amaryl.

Reported hypersensitivity reactions include skin rashes with or without itching as well as more severe reactions (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome, shortness of breath) [see Precautions and Preventive Measures and Side Effects].

Clinical Pharmacology

Mechanism of Action

Glimepiride decreases blood glucose primarily by stimulating the release of insulin from pancreatic beta cells. Sulfonylureas are committed to the receptor sulfonyl on the fictitious membrane of pancreatic beta cells, leading to closure of potassium sensitivity potassium, thereby stimulating insulin release.

Pharmacodynamics.

In healthy subjects, the time to achieve maximal effect (minimal glycemic concentration) was approximately 2-3 hours after a one-time oral administration of Amaryl; the effects of Amaryl on HBA1c, fasting plasma glucose, and postprandial glucose have been evaluated in clinical trials [see Clinical Studies].

Pharmacokinetics

Absorption.

Oral mass studies have studied glimepiride in healthy individuals and in patients with type 2 diabetes mellitus having multiple oral doses and showing a maximum drug concentration (CMAX) two to three hours after the dose. When glimepiride was administered with meals, mean CMAX and AUC (area under the curve) decreased by 8% and 9%, respectively.

Glimepiride does not accumulate in serum after multiple doses; the pharmacokinetics of glimepiride do not differ between healthy individuals and patients with type 2. Green's clearance after oral administration does not change over the dose range of 1 mg to 8 mg, indicating linear pharmacokinetics.

In healthy subjects, the intradiarrheal variability of glimepiride pharmacokinetic parameters was 15-23% and 24-29%, respectively.

Assignment.

After intravenous administration to healthy individuals, the volume of distribution (VD) was 8.8 L (113 ml/kg) and total body clearance (CL) was 47.8 ml/min. Protein commitment was greater than 99.5%.

Metabolism.

Glimepiride is completely metabolized by oxidative biomembranes after intravenous or oral administration. The major metabolites are the cycling hydroxymethyl derivative (M1) and the carboxylic derivative (M2). cyatochrome P450 2C9 is involved in the biomedical principle of glimepiride in M1. M1 is further metabolized to M2 by one or more cell soluble enzymes. M2 is inactive M2 is inactive. In animals, M1 has about one-third of the glimepiride pharmacologic activity, but it is not clear whether M1 has a clinically significant effect on blood glucose for humans.

Excretion.

When 14 doses of C-glimepiride were administered orally to three healthy men, approximately 60% of the total radioactivity was recovered in the urine in 7 days; M1 and M2 represent 80-90% of the radioactivity recovered in the urine. The M1 to M2 ratio in urine was approximately 3:2 in two subjects and 4:1 in one subject. Approximately 40% of the total radioactivity was recovered in feces; M1 and M2 represent approximately 70% of the radioactivity recovered in feces (M1 to M2 ratio of 1:3). No parent drug was recovered by urine or feces. There was no significant biliary excretion of metabolites of Gymepiride or M1 after intravenous administration in patients

Geriatric patients

A comparison of glimepiride pharmacokinetics in patients with type 2 diabetes ≤ 65 years and those >65 years of age were evaluated in a multi-dose study using 6 mg of Amaryl daily; there were no significant differences in glimepiride pharmacokinetics between the two age groups. The mean stable state AUC of the older patients was about 13% lower than that of the younger patients - the mean weight-adapted clearance of the older patients was about 11% higher than that of the younger patients.

Sex.

There were no differences between men and women in glimepiride pharmacokinetics when adapting to differences in body weight.

Although no studies have been conducted to assess the effect of breed on glimepiride pharmacokinetics, in a placebo-controlled study of Amaryl in patients with type 2 diabetes, the reduction in HBA was comparable for whites (n = 536) (n = 63) and Spanish (n = 63).

Renal dysfunction

Hepatic dysfunction

The effect of hepatic dysfunction on Amaryl pharmacokinetics is unknown because Amaryl pharmacokinetics have not been adequately evaluated in patients with hepatic dysfunction.

Obesity.

The pharmacokinetics of glimepiride and its metabolites were measured in a dose study involving 28 patients with type 2 diabetes who were of normal weight or were obese.TMAX, clearance and volume of quinepiride distribution in morbidly obese patients was similar to patients in the normal weight group, but morbid obesity had a higher than normal weight CMAX and AUC were lower. Mean CMAX, AUC0-24, and AUC0-∞ of glimepiride for normality for morbidly obese patients were 547±218 ng/ml versus 410±124 ng/ml, 3210±1030 h ng/ml versus 2820±1110 h - ng/ml ml and 4000±1320 h ng/ml vs. 3280±1360 h ng/ml, respectively.

Drug Interactions

Aspirin: In a randomized, double-blind, cross-over, two-cycle study, healthy individuals received either placebo or 1 gram of aspirin three times a day for a total of five days of treatment. On day 4 of each study period, a single dose of 1 mg Amaryl was administered. Amaryl doses were separated from the 14-day riding period; Co administration of Aspirin and Amaryl resulted in a 34% reduction in mean AUC for Glimepiride and a 4% reduction in mean CMAX for Glimepiride.

Collsevelam: Concomitant administration of Cousinvelam and Glimepiridis reduced AUC0-∞ and CMAX of Glimepiride by 18% and 8%, respectively. When glimepiride was administered 4 hours prior to colcevelam, there were no significant changes in AUC0 -∞ and Cmax of glimepiride o f-6% and 3%, respectively [see Drug Dosing and Administration and Interactions].

Cimetidine and ranitidine: in a randomized, open-label, 3-way crossway study, healthy individuals received 4 mg Amaryl only, Amaryl containing ranitidine (150 mg twice for 4 days - Amaryl was given on day 3) Amaryl and cimetidine (800 mg daily for 4 days - Amaryl was Amaryl was given on day 3). cimetidine or ranitidine co-titration with one single oral dose of 4 mg Amaryl did not significantly alter dimethylation absorption and mood.

Propranolol: In a randomized, double-blind, cross-over, two-peripheral study, healthy individuals received placebo or 40 mg of pranolol three times daily for a total treatment period of five days; on Day 4 or each study period, a single dose of 2 mg amaryl was administered. Amaryl doses were separated from the 14-day riding period. The combination of propranolol and amaryl significantly increased CMAX, AUC, and glimepiride by 23%, 22%, and 15%, respectively, and decreased the CL/F of glimepiride by 18%. M1 and M2 recovery from urine was unchanged.

Warfarin: in an open, twice-way study, healthy people received 4 mg Amaryl daily for 10 days. a single dose of 25 mg warfarin was administered 6 days before the start of Amaryl administration and 4 days before the Amaryl regime. Concurrent administration of Amaryl did not alter the pharmacokinetics of r- and S-varfarin. No changes in warfarin binding in plasma proteins were observed. Amaryl produced a statistically significant reduction in the pharmacodynamic response to warfarin. The reduction in mean area under the prothrombin (PT) curve and the maximum PT during treatment with Amaryl were 3.3% and 9.9%, respectively, and are unlikely to be clinically significant.

Clinical Trials

Monotherapy

A total of 304 patients with type 2 diabetes! Patients interrupted treatment with sulfonylurea, invaded a 3-week placebo hemolytic period, followed by randomization in one of four treatment groups: placebo (n = 74), amaryl 1 mg (n = 78), amaryl 4 mg (n = 76) and amaryl 8 mg (n = 76). All patients randomized on Amaryl began taking 1 mg daily. Patients randomized on Amaryl 4 mg or 8 mg had blinded, forced titration of the Amaryl dose at weekly intervals, first at 4 mg and then at 8 mg, if the dose was tolerated until the randomized dose was reached. patients randomized on the 4 mg dose reached the specified dose at week 2 Patients randomized at the 8 mg dose reached the specified dose at week 3. Week 14. Approximately 66% of placebo patients completed testing compared to 81% of patients treated with 1 mg of glimepiride and 92% of patients treated with 4 mg or 8 mg of glimepiride. Compared to placebo, treatment with 1 mg, 4 mg, or 8 mg of amaryl daily resulted in a statistically significant improvement in HBA1C compared to placebo (Table 3).

Table 3: Monotherapy Studies* with Amaryl vs. Placebo in Patients Treated with 14-Sulfonyluria

Placebo (n = 74)	Amaryl
	1 mg (n = 78)	4 mg (n = 76)	8 mg (n = 76)
HBA1C (%)
n = 59	n = 65	n = 65	n = 68
Base price (average)	8.0	7.9	7.9	8.0
Change with original value (average mean†)	1.5	0.3	-0. 3	-0. 4
Difference from placebo (customized mean†) 95% confidence interval	-1. 2* (-1. 5, -0. 8)	-1. 8* (-2. 1, -1. 4)	-1. 8* (-2. 2, -1. 5)
Mean starting weight (kg)
n = 67	n = 76	n = 75	n = 73
Base price (average)	85. 7	84. 3	86. 1	85. 5
Change with original value (average mean†)	-2. 3	-0. 2	0.5	1.0
Difference from placebo (customized mean†) 95% confidence interval	2. 0‡ (1. 4, 2. 7)	2. 8‡ (2. 1, 3. 5)	3. 2‡ (2. 5, 4. 0)
*Intention to treat using the most recent observation in the study†Mean least squares adapted to original values‡P≤0. 001

A total of 249 patients who were previously untreated or had limited treatment with antidiabetic therapy were randomized to receive 22 weeks of treatment with Amaryl (n = 123) or multicenter placebo (n = 126). The study was double-blind, placebo-controlled, dosing-tested. The initial dose of Amaryl was 1 mg daily and was fixed up or down over 2 weeks until the target FPG of 90-150 mg/dL was achieved. blood glucose levels for both FPG and PPG were analyzed in the laboratory. after 10 weeks of dose adjustment, patients were kept at the optimal dose (1, 2, 3, 4, 6 or 8 mg) were maintained for the remaining 12 weeks of testing. Amaryl treatment resulted in statistically significant improvements in HBA1C and FPG compared to placebo (Table 4).

Table 4: 22-Monotherapy Studies Comparing Amaryl vs. Placebo in Patients Unknown During Treatment or Not Receiving Recent Treatment with Antidiabetic Therapy*.

Placebo (n = 126)	Amaryl (n = 123)
HBA1C (%)	n = 97	n = 106
Base price (average)	9.1	9.3
Changed from original value (customized mean)	-1. 1*	-2. 2*
Difference from placebo (customized mean)	-1. 1*
95% confidence interval	(-1. 5, -0. 8)
Body weight (kg)	n = 122	n = 119
Base price (average)	86. 5	87. 1
Changed from original value (customized mean)	-0. 9	1.8
Difference from placebo (customized mean)	2.7
95% confidence interval	(1. 9, 3. 6)
*Populations targeted for treatment using the most recent observations in the study†.

Patient Information

Inform patients of the importance of compliance with dietary instructions, a regular exercise program, and regular blood glucose testing.

Inform patients about potential side effects of Amaryl, including hypoglycemia and weight gain.

Explain symptoms and treatment of hypoglycemia and conditions that predispose to hypoglycemia. Patients should be informed that their ability to concentrate and react may be impaired as a result of hypoglycemia. This may be a risk in situations where these abilities are particularly important, such as driving or handling other machinery.

Patients with diabetes should be informed to notify their health care provider if they are pregnant, thinking about, or breastfeeding.