Glibenclamide
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Sulfonylureas, Therapy Class:
Antidiabetic Agent, Approved Countries
India, the United States, Canada, the United Kingdom, Brazil, South Africa, Germany and Australia.
Glibenclamide is an Anti-diabetic Agent belonging to the pharmacological class of second-generation sulfonylureas.
Glibenclamide, or glyburide in the US, is approved for managing type 2 diabetes. In people with this condition, it helps to reduce and regulate increased blood sugar levels by inducing the pancreas to secrete insulin.
After being taken orally, Glibenclamide is rapidly absorbed. Between four and six hours, peak plasma concentrations occur. The plasma proteins, primarily albumin, are its major binding partners. It is mainly eliminated in the urine and faeces and is metabolized by the liver primarily by CYP2C9. Its half-life of elimination is roughly 10 hours.
The most common side effects of Glibenclamide include headache, nausea, and dizziness. It may also occasionally lead to hypoglycemia or low blood sugar.
Glibenclamide is available in the form of oral Tablets.
The molecule is available in India, the United States, Canada, the United Kingdom, Brazil, South Africa, Germany and Australia.
Glibenclamide is an Anti-diabetic Agent belonging to the pharmacological class of second-generation sulfonylureas.
These medications prevent pancreatic beta cells' ATP-sensitive potassium channels from opening. Sulfonylurea receptor 1 (SUR1) is the name for the ATP-sensitive potassium channels found on beta cells.Low glucose concentrations cause SUR1 to stay open, which permits potassium ion efflux to produce a membrane potential of -70 mV. High glucose concentrations typically cause SUR1 to close, the cell's membrane potential to lessen, the cell to depolarize, voltage-gated calcium channels to open, calcium ions to enter the cell, and an increase in intracellular calcium concentration that triggers the release of insulin-containing granules. By closing SUR1 and promoting enhanced insulin secretion, Glibenclamide circumvents this mechanism.
Glibenclamide is available in oral tablets.
Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.
As the physician recommends, take the medication orally once daily, generally with or without a meal.
- Glibenclamide is used in individuals with type 2 diabetes to help control and lower elevated blood sugar levels.
- It manages gestational diabetes in pregnant women when dietary and lifestyle changes are insufficient.
- Glibenclamide is sometimes used to manage insulin resistance in women with polycystic ovary syndrome, which can be associated with elevated blood sugar levels.
In Treatment of Type 2 diabetes mellitus
Glibenclamide helps increase the amount of insulin your body produces (in the pancreas). It works by boosting the amount of insulin your body generates following a meal and prevents excessive glucose (sugar) release into the blood. In doing so, it decreases your body's blood glucose levels.
To effectively manage diabetes, the blood glucose levels must be reduced. Controlling blood sugar levels will lower the likelihood of developing any significant consequences of diabetes, including kidney damage, eye damage, nerve problems, and amputation of limbs. The risk of cardiac disease and stroke can be decreased with proper diabetes management. Individuals can live longer if they take this medication consistently and follow a healthy diet and exercise routine.
Glibenclamide is indicated for use as an adjuvant to diet and exercise in persons with type 2 diabetes mellitus to enhance glycemic control. It can be used alone or in combination with metformin.
Orally: Glibenclamide (glyburide) is administered orally as tablets or micronized powder. It is commonly taken once daily with breakfast or the first main meal to maximize its effectiveness in regulating blood sugar levels throughout the day. It is best to take it regularly at a fixed time each day following the physician's prescribed schedule for regular and evenly spaced intervals because the dose and duration of therapy are individualized per specific conditions to achieve the most effective and successful treatment outcome.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Tablet: 1.25mg, 2.5mg, 5mg
Tablet, micronized:1.5mg, 3mg, 5mg, 6mg
Glibenclamide is available in the form of Oral Tablets.
Dose Adjustment in Adult Patients:
Type 2 Diabetes Mellitus
Regular tablets
Initial: 2.5-5 mg orally qDay
Maintenance: 1.25-20 mg orally per day or every 12 hours
Not more than 20 mg per day
Consider administering q12hr for doses >10 mg/day
Micronized tablets
Initial: 1.5 to 3 mg orally qDay
Maintenance: 0.75 to 12 mg orally qDay
Not more than 12 mg per day
Hypoglycemic individuals should start with 0.75 mg PO qDay.
Changing from insulin to glibenclamide therapy
Dosage for Glibenclamide: 2.5 to 5 mg/day (normal) or 1.5 to 3 mg/day (micronized)
Insulin dosage at the moment: 20–40 units. Stop using insulin and start taking 5 mg of ordinary or 3 mg of micronized Glibenclamide daily.
Currently taking more than 40 units of insulin: Reduce insulin by 50% and start Glibenclamide at 5 mg/day (regular) or 3 mg/day (micronized); increase Glibenclamide by 1.25–2.5 mg (regular) or 0.75–1.5 mg/day (micronized); gradually reduce insulin as Glibenclamide dose increases based on patient response.
Glibenclamide should be used in treating Type 2 Diabetes Mellitus, along with appropriate nutritional limits.
Glibenclamide before or with meals is advised, as it enhances insulin release when glucose levels rise after eating. And also to eat meals at regular intervals and avoid skipping meals to help stabilize blood sugar levels.
Limit or avoid the intake of alcohol as it can interfere with blood sugar regulation, causing hypoglycemia (low blood sugar).
Avoid consuming sugary foods and beverages, including cereals, snacks, and sweetened beverages, as they can lead to blood sugar spikes.
It is advised to stay hydrated, maintain a rich, balanced diet low in saturated fats and cholesterol, and consume plenty of vegetables, whole grains, fruits, and lean proteins to help manage your overall health and blood sugar levels effectively.
The dietary restriction should be individualized as per patient requirements.
Glibenclamide may be contraindicated in the following conditions:
- Hypersensitivity or sulfa allergy to the drug or any of its excipients
- Diabetic ketoacidosis, either in a coma or not. Insulin should be used to treat the disease
- Type 1 diabetes
- Bosentan coadministration causes increased hepatotoxicity risk.
- Hypoglycemia is more likely in elderly, malnourished or debilitated patients, patients with adrenal and/or pituitary insufficiency, and those patients with severe hepatic and hepatic impairment. It is also more likely to occur when ethanol is consumed, multiple glucose-lowering agents are used, and after prolonged or intense exercise.
- Patients who have previously experienced allergic reactions to any compound with the sulfonamide structure SO2NH2 have expressed concerns about cross-reactivity between agents containing sulfonamide products; however, as our understanding of allergic mechanisms expands, it is possible that cross-reactivity between antibiotic and nonantibiotic sulfonamides will not occur, or will occur very rarely.
- When compared to treatment with diet alone or diet plus insulin, the use of oral hypoglycemic medications has been linked to an increased risk of cardiovascular death; however, more recent research has refuted this association.
- When treated with sulfonylurea medications, glucose 6-phosphate dehydrogenase (G6PD) deficiency can result in hemolytic anaemia; in these individuals, exercise caution and consider a nonsulfonylurea option.
- Clinical research providing solid proof of anti-diabetic medication's ability to lower macrovascular risk is lacking.
- Glibenclamide use is not advised in patients with chronic kidney illness; patients with renal impairment may experience slower glyburide metabolism and excretion, which can accumulate in advanced renal insufficiency and result in prolonged hypoglycemia.
- Caution should be taken while administrating to Pregnant and lactating populations.
- If the patient is under stress, it can be necessary to stop their medication and give them insulin.
- When switching patients to a different Glibenclamide formulation, titrate the dosage because the micronized tablet formulation is not bioequivalent to regular Glibenclamide tablets.
- In patients with type 2 diabetes mellitus, extended medication use may cause beta cell death, which could lead to a loss of treatment efficacy. If patients who were previously responding to treatment have this loss of effectiveness and no identifiable contributing variables are found, stop therapy.
- Any sulfonylurea can cause severe hypoglycemia.
Alcohol Warning
It is unsafe to consume Glibenclamide with alcohol.
Breast Feeding Warning
There is no sufficient scientific evidence regarding the use and safety of Glibenclamide in breastfeeding.
Pregnancy Warning
Safe to use during pregnancy only if the possible benefit outweighs the potential risk to the fetus. Use caution.
Food Warning
Increase intake of fibre-rich foods and minimize the carbohydrate or sugary intake.
The adverse reactions related to Glibenclamide can be categorized as:
- Common Adverse Effects: Hypoglycemia (low blood sugar), digestive issues (e.g., diarrhoea, abdominal discomfort)
- Less Common Adverse Effects: Skin reactions (e.g., photosensitivity, rashes), weight gain
- Rare Adverse Effects: Allergic Reactions, liver function abnormalities.
The clinically relevant drug interactions of Glibenclamide are briefly summarized here:
Certain medications, such as ACE inhibitors, disopyramide, fluoxetine, clarithromycin, and other highly protein-bound drugs, salicylates, sulfonamides, and chloramphenicol, may enhance the hypoglycemia effect of sulfonylureas, monoamine oxidase inhibitors, beta-adrenergic blocking medicines and probenecid. When a patient using Glibenclamide is given such medication, they should be closely monitored for hypoglycemia. When a patient using Glibenclamide has such drugs stopped, they should be closely monitored for any loss of control.
There have been reports of a severe hypoglycemia-causing interaction between oral hypoglycemic medications and miconazole. It is unknown if this interaction also happens with miconazole's topical, injectable, or vaginal formulations.
There have been reports of a potential interaction between Glibenclamide and fluoroquinolone antibiotics, which could intensify Glibenclamide's hypoglycemic effects. It is still being determined how these two interact.
There could be interactions between Glibenclamide and coumarin derivatives that either strengthen or lessen the effects of coumarin derivatives. It's yet to be discovered how these connections work.
Because rifampin can considerably enhance Glibenclamide's metabolic isozymes, such as CYP2C9 and 3A4, it may exacerbate the drug's ability to manage glucose.
Some medications frequently cause hyperglycemia, which can cause loss of control. These medications include corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. They also contain thiazides and other diuretics. When a patient using Glibenclamide is administered such a medication, they should be closely monitored for any loss of control. When a patient using Glibenclamide has such drugs stopped, they should be closely monitored for hypoglycemia.
Glibenclamide patients who received bosentan showed a higher frequency of elevated liver enzymes. As a result, using this combination is not advised.
Glibenclamide may raise the plasma levels of cyclosporine, which could make it more hazardous. Therefore, monitoring and modifying the dosage of cyclosporine when both drugs are coadministered is advised.
The most common side effects of Glibenclamide include:
- Low blood glucose, or hypoglycemia
- Vomiting
- Head Pain
- Fatigue
- Dizziness
- Pregnancy
Teratogenic Effects: Pregnancy Category C
When administered at doses 6250 times higher than the maximum authorized human dose, Glibenclamide has been demonstrated to impact the development of the long bones (femur and humerus) in rat pups. These effects, observed during lactation rather than organogenesis, include a reduction in bone length that affects several long bone structures, particularly the femur and humerus.
There isn't enough data or well-controlled research on pregnant women. Glibenclamide should be used during pregnancy if the possible benefit outweighs the risk to the fetus, as research on animal reproduction does not necessarily indicate human response. Many doctors advise using insulin to keep blood glucose levels as close to normal as possible during pregnancy because new data indicates that aberrant blood glucose levels during pregnancy are linked to a higher incidence of congenital disabilities.
Nonteratogenic Effects: There have been reports of prolonged, severe hypoglycemia (4 to 10 days) in newborns whose mothers were on sulfonylurea medication at delivery. That has been documented more often when agents with extended half-lives are used. Glibenclamide should be stopped at least two weeks before the expected delivery date if taken during pregnancy.
- Nursing Mothers
Certain sulfonylureas are known to be eliminated in human milk. However, it is unknown if Glibenclamide is also eliminated in this manner. Considering the significance of the medication to the mother, a choice should be taken, either stopping the drug's administration or breastfeeding a nursing newborn due to the possibility of hypoglycemia. Insulin therapy should be considered if Glibenclamide is stopped, and diet alone is insufficient to regulate blood glucose levels.
- Pediatric Use
As per FDA, safety and effectiveness in the pediatric population have yet to be established.
- Geriatrics
Glibenclamide (glyburide) safety and efficacy in elderly persons must be closely monitored. Individualized dosage and routine blood sugar monitoring are essential due to possible age-related changes in metabolism and greater susceptibility to hypoglycemia. To minimize drug interactions and improve diabetes care, elderly people may also require close medical supervision due to their multiple comorbidities and prescription regimens.
Dosage adjustment in geriatric patients
Type 2 Diabetes
Initial:0.75 mg/day for micronized tablets or 1.25 mg/day for non-micronized tablets
The dose may be increased by no more than 1.25–2.5 mg (regular) or 0.75–1.5 mg (micronized) each week, depending on the glycemic response.
A maintenance dose of 1.25–20 mg/day (regular) or 0.75–12 mg/day (micronized) may be given; patients taking more than 10 mg/day (regular) or more than 6 mg/day (micronized) may show that their response is better if their dose is divided every 12 hours.
Dosing considerations
The subject of how strictly glucose levels should be maintained is controversial because elderly people are more vulnerable to the hypoglycemic effects of glucose-lowering medications.
It can be challenging to diagnose hypoglycemia in older people.
Normalized glycemic management may be less crucial than other cardiovascular disease-related metrics like blood pressure and cholesterol.
Dosing should be conservative both at initial as well as maintenance dosing.
If a patient has renal insufficiency, continue with caution.
Dose Adjustment in Kidney Impairment Patient:
Use cautiously if CrCl is less than 50 mL/min.
Dose Adjustment in Hepatic Impairment Patients:
Avoid use in cases of severe liver illness and use cautious starting and maintenance dosages.
Signs and Symptoms
The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Glibenclamide.
Overconsumption of Glibenclamide may lead to hypoglycemia (low blood sugar) symptoms.
Management
There is no specific antidote or treatment for excessive intake of Glibenclamide. However, immediate medical attention is essential. Glibenclamide should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake.
If there are mild hypoglycemia symptoms but no loss of consciousness or neurological signs, oral glucose and changes in medication dosage and/or meal schedules should be administered with vigour. Close observation should be maintained until the doctor specifies that the patient is not in danger. Rarely, severe hypoglycemia reactions can result in coma, seizures, or other neurological impairment; nevertheless, these reactions are medical emergencies that call for prompt treatment. The patient should get a quick intravenous infusion of concentrated (50%) glucose solution if hypoglycemia coma is identified or suspected. A more diluted (10%) glucose solution should then be continuously infused at a rate that will keep the blood glucose level over 100 mg/dL.
Patients must be constantly observed for at least 24 to 48 hours, as hypoglycemia may recur after apparent clinical recovery.
Pharmacodynamics:
Glibenclamide increases intracellular potassium and calcium ion concentrations by causing beta cells' ATP-sensitive potassium channels to close, promoting insulin production. Glibenclamide has a broad therapeutic index since patients can begin taking it at doses as little as once daily, and it has a lengthy duration of effect. As with tolbutamide, another sulfonylurea, Glibenclamide, should be used cautiously due to an elevated risk of cardiovascular mortality.
Pharmacokinetics:
Absorption
After oral treatment, Glibenclamide is efficiently absorbed. Reaching peak plasma concentrations usually takes 4–6 hours, so the body can easily use it for the desired therapeutic purpose.
Bioavailability: Variable, depending on the oral dosage form
Onset: 15 to 60 min after a single dose (increase in serum insulin levels)
Duration: <24 hr
Vd: 9-10 L
Peak serum time: 2-4 hr (adults)
Distribution
Glibenclamide is mainly bound to plasma proteins and accumulates all over the body. It can enter target tissues and is found in the circulation, regulating blood sugar.
Protein-bound: 99%
Metabolism
CYP3A4 is the primary metabolizer of Glibenclamide, with CYP2C9, CYP2C19, CYP3A7, and CYP3A5 following in order of preference.3,2 These enzymes metabolize glyburide to produce 4-trans-hydroxy cyclohexyl glyburide (M1), 4-cis-hydroxy cyclohexyl glyburide (M2a), 3-cis-hydroxy cyclohexyl glyburide (M2b), 3-trans-hydroxycyclohexyl glyburide (M3), 2-trans-hydroxy cyclohexyl glyburide (M4), and ethyl hydroxy cyclohexyl glyburide (M5).2. Not only is the parent molecule considered to be active but also the metabolites M1 and M2b.
Elimination
Glibenclamide gets eliminated 50% in the urine and 50% in the faeces, compared to other sulfonylureas. The primary metabolite of Glibenclamide that is destroyed is 4-trans-hydroxyglyburide.
Half-life: 10 hr (DiaBeta) and 4 hr (Glynase, PresTab)
Excretion: Urine (50%), faeces (50%)
- Rambiritch V, Maharaj B, Naidoo P. Glibenclamide in the patients with poorly controlled type 2 diabetes: a 12-week, prospective, single-center, open-label, dose-escalation study. Clin Pharmacol. 2014 Apr 4;6:63-9. Doi: 10.2147/CPAA.S54809. PMID: 24741335; PMCID: PMC3983009.
- Riefflin A, Ayyagari U, et al. The effect of Glibenclamide on insulin secretion at normal glucose concentrations. Diabetologia. 2015 Jan;58(1):43-9. doi: 10.1007/s00125-014-3399-1. Epub 2014 Oct 9. PMID: 25297572.
- Landgraf, R., Bilo, H. & Müller, P. A comparison of repaglinide and Glibenclamide in treating type 2 diabetic patients previously treated with sulphonylureas. E J Clin Pharmacol 55, 165–171 (1999). https://doi.org/10.1007/s002280050613
- Zhao J, Song C, Li D, et al; GATE-ICH Study Group. Efficacy and the safety of glibenclamide therapy after intracerebral haemorrhage (GATE-ICH): A multicentre, prospective, randomized, controlled, open-label, blinded-endpoint, phase 2 clinical trial. EClinicalMedicine. 2022 Sep 23;53:101666. Doi 10.1016/j.eclinm.2022.101666. PMID: 36177443; PMCID: PMC9513728.
https://www.singhealth.com.sg/patient-care/medicine/glibenclamide
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021995s045lbl.pdf
https://www.ncbi.nlm.nih.gov/books/NBK545313/
https://pubmed.ncbi.nlm.nih.gov/5004340/
Published on: 21 Oct 2023 5:30 AM GMT
