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Indicated for the treatment of osteoarthritis of knee, hip, spine, hand, and other locations as a dietary supplement. It is also beneficial in rheumatoid arthritis, sport injuries, migraine, different skin problems (e.g., psoriasis), vascular complications (e. g., atherosclerosis), kidney stones, and inflammatory bowel disease (e.g., ulcerative colitis, leaky gut syndrome).

Stimulation of Cartilage formation

Glucosamine is a natural amino-sugar, produced by the body and found in certain foods. It is the most fundamental building block required for biosynthesis of glycosaminoglycans (GAGs) like Hyaluronic Acid, Keratan Sulfate, and Chondroitin Sulfate. GAGs binds with protein and form proteoglycans, the essential building block of articular cartilage. When cartilage in a joint deteriorates,Osteoarthritis develops. It also helps to form ligaments, tendon, nails, and various other connective tissues.When we take artificially synthesized Glucosamine Sulfate supplement, it increases Glucosamine level in the body, thus facilitates production and repair of cartilage. Glucosamine also activates chondrocytes in the cartilage which help produce GAGs and proteoglycans.

Chondroitin Sulfate is a glycosaminoglycan (acid muco polysaccharide) found in connective tissue, especially in the articular cartilage of all mammals. Chondroitin Sulfate supplement acts similarly as Glucosamine Sulfate, since it also provide substrate for proteoglycans. Chondroitin also protects existing healthy cartilage from premature decline by preventing the MMP (Matrix metalloproteinase) enzyme that breakdowns the proteoglycans.

Combining Glucosamine with Chondroitin Sulfate shows synergistic effect. Data supports that this combination has been shown to be very much effective in severe cases of Osteoarthritis that treats both sign and symptoms of Osteoarthritis & modifies disease progression. It prevents Osteoarthritis in case of normal adults. In Osteoarthritic pain it is as effective as NSAIDs with significantly better tolerability and clinical compliance. It is also helpful during the repair phase of musculo-skeletal soft tissue injuries such as tendon or ligament strains

250/200 mg tablet: 1 to 2 tablets, three times daily. Dose may be adjusted according to the response of the drug and body weight. Doses can be tapered after 60 days as per requirement of the individual and for cost convenience. Typical dosage recommendation, based on body weight is as follows-

• Under 54 Kg: 1000 mg Glucosamine Sulfate & 800 mg Chondroitin Sulfate per day
• 54 Kg to 91 Kg: 1500 mg Glucosamine Sulfate & 1200 mg Chondroitin Sulfate per day
• Over 91 Kg: 2000 mg Glucosamine Sulfate & 1600 mg Chondroitin Sulfate per day.

750/600 mg tablet: 1 tablet two times daily or as directed by the physician.

Safety studies with Glucosamine Sulfate & Chondroitin Sulfate show no demonstrable side effects. Rarely occurring side effects (such as, mild & reversible intestinal flatulence) are almost like placebo.

There are no known contraindications for Glucosamine and Chondroitin. But proven hypersensitivity (e. g. allergic to shellfish or sulfur) to Glucosamine and Chondroitin is a contraindication.

Patients with Diabetes Mellitus are advised to monitor blood glucose levels regularly when taking Glucosamine. No special studies were formed in patients with renal or hepatic insufficiency. The toxicological and pharmacokinetic profile of Glucosamine and Chondroitin does not indicate limitations for these patients. However, administration to patients with severe hepatic or renal insufficiency should be under appropriate medical supervision. Children should not be supplemented with Glucosamine and Chondroitin.

There have been no reports of significant drug interactions of Glucosamine and Chondroitin with Antibiotics/ Antidepressants/ Antihypertensives/ Nitrates/ Antiarrythmics/ Anxiolytics/ Hypoglycemic agents/ Antisecretives/ Antiasthmatics. Chondroitin may enhance the blood thinning effects of anticoagulants like Warfarin, Heparin.

Women who are pregnant or who could become pregnant should not supplement with Glucosamine Sulfate or Chondroitin Sulfate. Glucosamine and Chondroitin has not been studied enough to determine their effects on a developing fetus. No studies have evaluated the use of Glucosamine and Chondroitin during pregnancy or lactation. It should be taken with caution and medical advice during pregnancy and lactation.

Store in a cool and dry place, protected from light.

Betaxolol ophthalmic solution has been shown to be effective in lowering intraocular pressure and is indicated in the treatment of ocular hypertension and chronic open-angle glaucoma. May be used alone or in combination with other intraocular pressure-lowering medication.

Drugs for miotics and glaucoma

Betaxolol is a selective (beta-1-adrenergic) receptor blocking agent that does not have significant membrane stabilizing (local anesthetic) activity and is free from intrinsic sympathomimetic action. When instilled into the eye, Betaxolol reduces elevated as well as normal intraocular pressure, whether or not accompanied by glaucoma. Optic nerve head damage and visual field loss are results of a sustained elevated intraocular pressure and poor ocular perfusion. The ocular hypotensive action of Betaxolol appears to be mediated by a reduction of aqueous production as demonstrated by tonography and aqueous flurophotometry. Betaxolol ophthalmic solution does not produce miosis or accommodative spasm which is frequently seen with miotic.

The onset of action with Betaxolol can generally be noted within 30 minutes and the maximal effect can usually be detected two hours after topical administration. A single dose provides a 12-hour reduction in intraocular pressure (IOP) and twice daily administration maintains the IOP below 22 mm Hg in most patients.

0.5% ophthalmic solution: The usual dose is 1 drop of Betaxolol Hydrochloride ophthalmic solution in the affected eye(s) twice daily. In some patients, the intraocular pressure-lowering response may require a few weeks to stabilize. Clinical follow-up should include a determination of the intraocular pressure during the first month of treatment. Thereafter, intraocular pressure should be determined on an individual basis at the judgment of the physician.

0.25% ophthalmic solution: The recommended dose is one to two drops of Betaxolol Hydrochloride ophthalmic solution in the affected eye(s) twice daily.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Ocular: Discomfort of short duration, occasional tearing has been reported. Rare instances of decreased corneal sensitivity, erythema, itching sensation, corneal punctuate staining, keratitis, edema and photophobia have been reported.

Systemic: Systemic reactions following administration of Betaxolol hydrochloride ophthalmic solution 0.5% have been rarely reported. These include:

• Cardiovascular: bradycardia, heart block, congestive heart failure.
• Respiratory: bronchospasm, respiratory failure.
• Others: Hives, toxic epidermal necrolysis, hair loss and glossitis.

Hypersensitivity to any component of this product. Betaxolol should not be used in patients with sinus bradycardia, atrioventricular block greater than first degree, cardiogenic shock, or patients with a history of overt cardiac failure.

In patients with angle-closure glaucoma, the immediate treatment objective is to re-open the angle by constriction of the pupil with miotic agent. Betaxolol has no effect on the pupil; therefore, Betaxolol should be used with a miotic to reduce elevated intraocular pressure in angle-closure glaucoma. Beta-adrenergic blocking agents should be administered with caution in patients subjected to spontaneous hypoglycemia or to diabetic patients as these agents may mask the signs and symptoms of acute hypoglycemia.

Patients who are receiving a beta-adrenergic blocking agent orally and Betaxolol Hydrochloride Ophthalmic Solution should be observed for a potential additive effect either on the intraocular pressure or on the known systemic effects of beta blockade. Close observation of the patient is recommended when a beta blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or bradycardia. Caution should be exercised in patients using concomitant adrenergic psychotropic drugs. In patients with angle-closure glaucoma, the immediate treatment objective is to reopen the angle by constriction of the pupil with a miotic agent. Betaxolol has little or no effect on the pupil. When Betaxolol Hydrochloride Ophthalmic Solution is used to reduce elevated intraocular pressure in angle-closure glaucoma, it should be used with a miotic and not alone.

There are no adequate & well controlled studies in pregnant women. Betaxolol ophthalmic solution should be used during pregnancy only if the potential benefit justifies the potential risk. It is not known whether Betaxolol is excreted in human milk. The risk of hypoglycemia & bradycardia in nursing infant has not been evaluated. Breast feeding is not recommended during treatment.

No information is available on overdosage. A topical overdosage of Betaxolol ophthalmic solution may be flushed from the eye(s) with warm tap water.

Store at room temperature. It is desirable that the content should not be used more than one month after first opening of the bottle.

Gliclazide is a medicine that reduces blood sugar levels (oral antidiabetic medicine belonging to the sulphonylurea group). Gliclazide is used in a certain form of diabetes (type 2 diabetes Mellitus) in adults, when diet, exercise and weight loss alone do not have an adequate effect on keeping blood sugar at the correct level.

Sulfonylureas

Gliclazide is a second generation sulfonylurea drug that has hypoglycaemic and potentially useful hematological properties. It stimulates the release of insulin from pancreatic β-cells by facilitating Ca⁺²  transport across the β-cell membranes and decreases hepatic glucose output.

Film-coated tablet: The usual initial dose is 40 to 80 mg daily. The dose can be increased up to 320 mg daily in divided doses when needed. The drug should be taken before meal. For children, Gliclazide is not used because it is contraindicated in juvenile-onset diabetes.

Modified release preparation: Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The dose is determined by the doctor, depending on your blood and possibly urine sugar levels. Change in external factors (weight reduction, lifestyle, stress) or improvements in the blood sugar control may require changed gliclazide doses.

The recommended daily dose is one to four tablets (maximum 120 mg) in a single intake at breakfast time. This depends on the response to treatment. Gliclazide MR tablet is for oral use. Take your tablet(s) with a glass of water at breakfast time (and preferably at the same time each day). Swallow your whole tablet(s) in one piece. Do not chew or crush. You must always eat a meal after taking your tablet(s).

If a combination therapy of gliclazide with metformin, an alpha-glucosidase inhibitor, a thiazolidinedione, a dipeptidyl peptidase-4 inhibitor a GLP-1 receptor agonist or insulin is initiated your doctor will determine the proper dose of each medicine individually for you. If you notice that your blood sugar levels are high although you are taking the medicine as prescribed, you should contact your doctor or pharmacist.

If you take more Gliclazide tablets than you should: If you take too many tablets, contact your doctor or the nearest hospital Accident & Emergency department immediately. The signs of overdose are those of low blood sugar (hypoglycaemia). The symptoms can be helped by taking sugar (4 to 6 lumps) or sugary drinks straight away, followed by a substantial snack or meal. If the patient is unconscious immediately inform a doctor and call the emergency services. The same should be done if somebody, (for instance a child), has taken the product unintentionally. Unconscious patients must not be given food or drink. It should be ensured that there is always a pre-informed person that can call a doctor in case of emergency.

If you forget to take Gliclazide tablet: It is important to take your medicine every day as regular treatment works better. However, if you forget to take a dose of Gliclazide MR tablet, take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Gliclazide MR tablet: As the treatment for diabetes is usually lifelong, you should discuss with your doctor before stopping this medicinal product. Stopping could cause high blood sugar (hyperglycaemia) which increases the risk of developing complications of diabetes. If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, Gliclazide can cause side effects, although not everybody gets them. The most commonly observed side effect is low blood sugar (hypoglycaemia). If left untreated these symptoms could progress to drowsiness, loss of consciousness or possibly coma. If an episode of low blood sugar is severe or prolonged, even if it is temporarily controlled by eating sugar, you should seek immediate medical attention.

Liver disorders: There have been isolated reports of abnormal iiver function, which can cause yellow skin and eyes. If you get this, see your doctor immediately. The symptoms generally disappear if the medicine is stopped. Your doctor will decide whether to stop your treatment.

Skin disorders: Skin reactions such as rash, redness, itching, hives, blisters, angioedema (rapid swelling of tissues such as eyelids, face, lips, mouth, tongue or throat that may result in breathing difficulty) have been reported. Rash may progress to widespread blistering or peeling of the skin. If you develop this, stop taking, seek urgent advice from a doctor and tell him that you are taking this medicine. Exceptionally, signs of severe hypersensitivity reactions have been reported: initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature.

Blood disorders: Decrease in the number of cells in the blood (e.g. platelets, red and white blood cells) which may cause paleness, prolonged bleeding, bruising, sore throat and fever have been reported. These symptoms usually vanish when the treatment is discontinued.

Digestive disorders: Abdominal pain, nausea, vomiting, indigestion, diarrhoea, and constipation. These effects are reduced when Gliclazide is taken with a meal as recommended.

Eye disorders: Your vision may be affected for a short time especially at the start of treatment. This effect is due to changes in blood sugar levels.

As for another sulfonylurea, the following adverse events have been observed: cases of severe changes in the number of blood cells and allergic inflammation of the wall of blood vessels, reduction in blood sodium (hyponatraemia), symptoms of liver impairment (for instance jaundice) which in most cases disappeared after withdrawal of the sulfonylurea, but may lead to life-threatening liver failure in isolated cases.

Reporting of side effects: If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. By reporting side effects, you can help provide more information on the safety of this medicine.

Do not take Gliclazide:

• if you are allergic to gliclazide or to other medicines of the same group (sulfonylurea), or to other related medicines (hypoglycaemic sulfonamides)
• if you have insulin-dependent diabetes (type 1)
• if you have ketone bodies and sugar in your urine (this may mean you have diabetic ketoacidosis), a diabetic pre-coma or coma
• if you have severe kidney or liver disease
• if you are taking medicines to treat fungal infections
• if you are breastfeeding

Talk to your doctor before taking Gliclazide. You should observe the treatment plan prescribed by your doctor to achieve proper blood sugar levels. This means, apart from regular tablet intake, to observe the dietary regimen, have physical exercise and, where necessary, reduce weight During gliclazide treatment regular monitoring of your blood (and possibly urine) sugar level and also your glycated haemoglobin (HbA1c) is necessary. In the first few weeks of treatment, the risk of having reduced blood sugar levels (hypoglycaemia) may be increased. So particularly close medical monitoring is necessary.

Low blood sugar (Hypoglycaemia) may occur:

• if you take meals irregularly or skip meals altogether,
• if you are fasting
• if you are malnourished
• if you change your diet
• if you increase your physical activity and carbohydrate intake does not match this increase,
• if you drink alcohol, especially in combination with skipped meals,
• if you take other medicines or natural remedies at the same time,
• if you take too high doses of gliclazide,
• if you suffer from particular hormone-induced disorders (functional disorders of the thyroid gland, pituitary gland or adrenal cortex),
• if your kidney function or liver function is severely decreased.

if you have low blood sugar you may have the following symptoms: headache, intense hunger, nausea, vomiting, weariness, sleep disorders, restlessness, aggressiveness, poor concentration, reduced alertness and reaction time, depression, confusion, speech or visual disorders, tremor, sensory disturbances, dizziness and helplessness.

The following signs and symptoms may also occur: sweating, clammy skin, anxiety, fast or irregular heartbeat, high blood pressure, sudden strong pain in the chest that may radiate into nearby areas (angina pectoris).

If blood sugar levels continue to drop you may suffer from considerable confusion (delirium), develop convulsions, lose self-control, your breathing may be shallow and your heartbeat slowed down, you may become unconscious.

In most cases the symptoms of low blood sugar vanish very quickly when you consume .some form of sugar, (for instance, glucose tablets, sugar cubes, sweet juice, sweetened tea).

You should therefore always carry some form of sugar with you (glucose tablets, sugar cubes). Remember that artificial sweeteners are not effective. Please contact your doctor or the nearest hospital if taking sugar does not help or if the symptoms recur.

Symptoms of low blood sugar may be absent, less obvious or develop very slowly or you are not aware in time that your blood sugar level has dropped. This may happen if you are an elderly patient taking certain medicines (for instance those acting on the central nervous system and beta-blockers).

If you are in stressful situations (e.g. accidents, surgical operations, fever etc.) your doctor may temporarily switch you to insulin therapy.

Symptoms of high blood sugar (hyperglycaemia) may occur when gliclazide has not yet sufficiently reduced the blood sugar when you have not complied with the treatment plan prescribed by your doctor if you take St. John’s Wort (Hypericum perforatum) preparations or in special stress situations. These may include thirst, frequent urination, dry mouth, dry itchy skin, skin infections and reduced performance.

Blood glucose disturbances (low blood sugar and high bold sugar) can occur when Gliclazide is prescribed at the same time as medicines to a class of antibiotics called fluoroquinolone, especially in elderly patients. In this case, your doctor will remind you of the importance of monitoring your blood glucose.

If you have a family history of or know you have the hereditary condition glucose-6-phosphate dehydrogenase (G6PD) deficiency (abnormality of red blood cells), lowering of the haemoglobin level and breakdown of red blood cells (haemolytic anaemia) can occur. Contact your doctor before taking this medicinal product.

Gliclazide is not recommended for use in children due to lack of data.

Other medicines and Gliclazide: Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.

The blood sugar lowering effect of gliclazide may be strengthened and signs of low blood sugar levels may occur when one of the follow ng medicines is taken:

• other medicines used to treat high blood sugar (oral antidiabetics, GLP-1 receptor agonists or insulin),
• antibiotics (sulphonamides, clarithromycin)
• medicines to treat high blood pressure or heart failure (beta-blockers. ACE-inhibitors such as captopril, or enalapril)
• medicines to treat fungal infections (miconazole, fluconazole)
• medicines to treat ulcers in the stomach or duodenum (H2 receptor antagonists),
• medicines to treat depression (monoamine oxidase inhibitors)
• painkiller or antirheumatics (phenylbutazone, ibuprofen)
• medicines containing alcohol

The blood-glucose-lowering effect of gliclazide may be weakened and raised blood sugar levels may occur when one of the following medicines is taken:

• medicines to treat disorders of the central nervous system (chlorpromazine)
• medicines reducing inflammation (corticosteroids)
• medicines to treat asthma or used during labour (intravenous salbutamol, ritodrine and terbutaline)
• medicines to treat breast disorders, heavy menstrual bleeding and endometriosis (danazol)
• St John's Wort- Hypericum perforatum- preparations

Blood glucose disturbance (low blood sugar and high blood sugar) can occur when a medicine belonging to a class of antibiotics called fluoroquinolones is taken at the same time as gliclazide especially in elderly patients.

Gliclazide may increase the effects of medicines that reduce blood clotting (warfarin).

Consult your doctor before you start taking another medicinal product. If you go into hospital tell the medical staff you are taking gliclazide.

Gliclazide with food and drink: Gliclazide can be taken with food and non-alcoholic drinks. Drinking alcohol is not recommended as it can alter the control of your diabetes in an unpredictable manner.

Driving and using machines: Your ability to concentrate or react may be impaired if your blood sugar is too low (hypoglycaemia), or too high (hyperglycaemia) or if you develop visual problems as a result of such conditions. Bear in mind that you could endanger yourself or others (for instance when driving a car or using machines). Please ask your doctor whether you can drive a car if you:

• have frequent episodes of low blood sugar (hypoglycaemia)
• have few or no warning signals of low blood sugar (hypoglycaemia)

Gliclazide contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Gliclazide is not recommended for use during pregnancy. If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. You must not take Gliclazide while you are breastfeeding.

Keep out of the reach and sight of children. Do not use this medicine after the expiry date which is stated on the carton and the blister. The expiry date refers to the last day of that month. Store below 30°C. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Gliclazide is a medicine that reduces blood sugar levels (oral antidiabetic medicine belonging to the sulphonylurea group). Gliclazide is used in a certain form of diabetes (type 2 diabetes Mellitus) in adults, when diet, exercise and weight loss alone do not have an adequate effect on keeping blood sugar at the correct level.

Sulfonylureas

Gliclazide is a second generation sulfonylurea drug that has hypoglycaemic and potentially useful hematological properties. It stimulates the release of insulin from pancreatic β-cells by facilitating Ca⁺²  transport across the β-cell membranes and decreases hepatic glucose output.

Film-coated tablet: The usual initial dose is 40 to 80 mg daily. The dose can be increased up to 320 mg daily in divided doses when needed. The drug should be taken before meal. For children, Gliclazide is not used because it is contraindicated in juvenile-onset diabetes.

Modified release preparation: Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The dose is determined by the doctor, depending on your blood and possibly urine sugar levels. Change in external factors (weight reduction, lifestyle, stress) or improvements in the blood sugar control may require changed gliclazide doses.

The recommended daily dose is one to four tablets (maximum 120 mg) in a single intake at breakfast time. This depends on the response to treatment. Gliclazide MR tablet is for oral use. Take your tablet(s) with a glass of water at breakfast time (and preferably at the same time each day). Swallow your whole tablet(s) in one piece. Do not chew or crush. You must always eat a meal after taking your tablet(s).

If a combination therapy of gliclazide with metformin, an alpha-glucosidase inhibitor, a thiazolidinedione, a dipeptidyl peptidase-4 inhibitor a GLP-1 receptor agonist or insulin is initiated your doctor will determine the proper dose of each medicine individually for you. If you notice that your blood sugar levels are high although you are taking the medicine as prescribed, you should contact your doctor or pharmacist.

If you take more Gliclazide tablets than you should: If you take too many tablets, contact your doctor or the nearest hospital Accident & Emergency department immediately. The signs of overdose are those of low blood sugar (hypoglycaemia). The symptoms can be helped by taking sugar (4 to 6 lumps) or sugary drinks straight away, followed by a substantial snack or meal. If the patient is unconscious immediately inform a doctor and call the emergency services. The same should be done if somebody, (for instance a child), has taken the product unintentionally. Unconscious patients must not be given food or drink. It should be ensured that there is always a pre-informed person that can call a doctor in case of emergency.

If you forget to take Gliclazide tablet: It is important to take your medicine every day as regular treatment works better. However, if you forget to take a dose of Gliclazide MR tablet, take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Gliclazide MR tablet: As the treatment for diabetes is usually lifelong, you should discuss with your doctor before stopping this medicinal product. Stopping could cause high blood sugar (hyperglycaemia) which increases the risk of developing complications of diabetes. If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, Gliclazide can cause side effects, although not everybody gets them. The most commonly observed side effect is low blood sugar (hypoglycaemia). If left untreated these symptoms could progress to drowsiness, loss of consciousness or possibly coma. If an episode of low blood sugar is severe or prolonged, even if it is temporarily controlled by eating sugar, you should seek immediate medical attention.

Liver disorders: There have been isolated reports of abnormal iiver function, which can cause yellow skin and eyes. If you get this, see your doctor immediately. The symptoms generally disappear if the medicine is stopped. Your doctor will decide whether to stop your treatment.

Skin disorders: Skin reactions such as rash, redness, itching, hives, blisters, angioedema (rapid swelling of tissues such as eyelids, face, lips, mouth, tongue or throat that may result in breathing difficulty) have been reported. Rash may progress to widespread blistering or peeling of the skin. If you develop this, stop taking, seek urgent advice from a doctor and tell him that you are taking this medicine. Exceptionally, signs of severe hypersensitivity reactions have been reported: initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature.

Blood disorders: Decrease in the number of cells in the blood (e.g. platelets, red and white blood cells) which may cause paleness, prolonged bleeding, bruising, sore throat and fever have been reported. These symptoms usually vanish when the treatment is discontinued.

Digestive disorders: Abdominal pain, nausea, vomiting, indigestion, diarrhoea, and constipation. These effects are reduced when Gliclazide is taken with a meal as recommended.

Eye disorders: Your vision may be affected for a short time especially at the start of treatment. This effect is due to changes in blood sugar levels.

As for another sulfonylurea, the following adverse events have been observed: cases of severe changes in the number of blood cells and allergic inflammation of the wall of blood vessels, reduction in blood sodium (hyponatraemia), symptoms of liver impairment (for instance jaundice) which in most cases disappeared after withdrawal of the sulfonylurea, but may lead to life-threatening liver failure in isolated cases.

Reporting of side effects: If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. By reporting side effects, you can help provide more information on the safety of this medicine.

Do not take Gliclazide:

• if you are allergic to gliclazide or to other medicines of the same group (sulfonylurea), or to other related medicines (hypoglycaemic sulfonamides)
• if you have insulin-dependent diabetes (type 1)
• if you have ketone bodies and sugar in your urine (this may mean you have diabetic ketoacidosis), a diabetic pre-coma or coma
• if you have severe kidney or liver disease
• if you are taking medicines to treat fungal infections
• if you are breastfeeding

Talk to your doctor before taking Gliclazide. You should observe the treatment plan prescribed by your doctor to achieve proper blood sugar levels. This means, apart from regular tablet intake, to observe the dietary regimen, have physical exercise and, where necessary, reduce weight During gliclazide treatment regular monitoring of your blood (and possibly urine) sugar level and also your glycated haemoglobin (HbA1c) is necessary. In the first few weeks of treatment, the risk of having reduced blood sugar levels (hypoglycaemia) may be increased. So particularly close medical monitoring is necessary.

Low blood sugar (Hypoglycaemia) may occur:

• if you take meals irregularly or skip meals altogether,
• if you are fasting
• if you are malnourished
• if you change your diet
• if you increase your physical activity and carbohydrate intake does not match this increase,
• if you drink alcohol, especially in combination with skipped meals,
• if you take other medicines or natural remedies at the same time,
• if you take too high doses of gliclazide,
• if you suffer from particular hormone-induced disorders (functional disorders of the thyroid gland, pituitary gland or adrenal cortex),
• if your kidney function or liver function is severely decreased.

if you have low blood sugar you may have the following symptoms: headache, intense hunger, nausea, vomiting, weariness, sleep disorders, restlessness, aggressiveness, poor concentration, reduced alertness and reaction time, depression, confusion, speech or visual disorders, tremor, sensory disturbances, dizziness and helplessness.

The following signs and symptoms may also occur: sweating, clammy skin, anxiety, fast or irregular heartbeat, high blood pressure, sudden strong pain in the chest that may radiate into nearby areas (angina pectoris).

If blood sugar levels continue to drop you may suffer from considerable confusion (delirium), develop convulsions, lose self-control, your breathing may be shallow and your heartbeat slowed down, you may become unconscious.

In most cases the symptoms of low blood sugar vanish very quickly when you consume .some form of sugar, (for instance, glucose tablets, sugar cubes, sweet juice, sweetened tea).

You should therefore always carry some form of sugar with you (glucose tablets, sugar cubes). Remember that artificial sweeteners are not effective. Please contact your doctor or the nearest hospital if taking sugar does not help or if the symptoms recur.

Symptoms of low blood sugar may be absent, less obvious or develop very slowly or you are not aware in time that your blood sugar level has dropped. This may happen if you are an elderly patient taking certain medicines (for instance those acting on the central nervous system and beta-blockers).

If you are in stressful situations (e.g. accidents, surgical operations, fever etc.) your doctor may temporarily switch you to insulin therapy.

Symptoms of high blood sugar (hyperglycaemia) may occur when gliclazide has not yet sufficiently reduced the blood sugar when you have not complied with the treatment plan prescribed by your doctor if you take St. John’s Wort (Hypericum perforatum) preparations or in special stress situations. These may include thirst, frequent urination, dry mouth, dry itchy skin, skin infections and reduced performance.

Blood glucose disturbances (low blood sugar and high bold sugar) can occur when Gliclazide is prescribed at the same time as medicines to a class of antibiotics called fluoroquinolone, especially in elderly patients. In this case, your doctor will remind you of the importance of monitoring your blood glucose.

If you have a family history of or know you have the hereditary condition glucose-6-phosphate dehydrogenase (G6PD) deficiency (abnormality of red blood cells), lowering of the haemoglobin level and breakdown of red blood cells (haemolytic anaemia) can occur. Contact your doctor before taking this medicinal product.

Gliclazide is not recommended for use in children due to lack of data.

Other medicines and Gliclazide: Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.

The blood sugar lowering effect of gliclazide may be strengthened and signs of low blood sugar levels may occur when one of the follow ng medicines is taken:

• other medicines used to treat high blood sugar (oral antidiabetics, GLP-1 receptor agonists or insulin),
• antibiotics (sulphonamides, clarithromycin)
• medicines to treat high blood pressure or heart failure (beta-blockers. ACE-inhibitors such as captopril, or enalapril)
• medicines to treat fungal infections (miconazole, fluconazole)
• medicines to treat ulcers in the stomach or duodenum (H2 receptor antagonists),
• medicines to treat depression (monoamine oxidase inhibitors)
• painkiller or antirheumatics (phenylbutazone, ibuprofen)
• medicines containing alcohol

The blood-glucose-lowering effect of gliclazide may be weakened and raised blood sugar levels may occur when one of the following medicines is taken:

• medicines to treat disorders of the central nervous system (chlorpromazine)
• medicines reducing inflammation (corticosteroids)
• medicines to treat asthma or used during labour (intravenous salbutamol, ritodrine and terbutaline)
• medicines to treat breast disorders, heavy menstrual bleeding and endometriosis (danazol)
• St John's Wort- Hypericum perforatum- preparations

Blood glucose disturbance (low blood sugar and high blood sugar) can occur when a medicine belonging to a class of antibiotics called fluoroquinolones is taken at the same time as gliclazide especially in elderly patients.

Gliclazide may increase the effects of medicines that reduce blood clotting (warfarin).

Consult your doctor before you start taking another medicinal product. If you go into hospital tell the medical staff you are taking gliclazide.

Gliclazide with food and drink: Gliclazide can be taken with food and non-alcoholic drinks. Drinking alcohol is not recommended as it can alter the control of your diabetes in an unpredictable manner.

Driving and using machines: Your ability to concentrate or react may be impaired if your blood sugar is too low (hypoglycaemia), or too high (hyperglycaemia) or if you develop visual problems as a result of such conditions. Bear in mind that you could endanger yourself or others (for instance when driving a car or using machines). Please ask your doctor whether you can drive a car if you:

• have frequent episodes of low blood sugar (hypoglycaemia)
• have few or no warning signals of low blood sugar (hypoglycaemia)

Gliclazide contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Gliclazide is not recommended for use during pregnancy. If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. You must not take Gliclazide while you are breastfeeding.

Keep out of the reach and sight of children. Do not use this medicine after the expiry date which is stated on the carton and the blister. The expiry date refers to the last day of that month. Store below 30°C. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Gliclazide is a medicine that reduces blood sugar levels (oral antidiabetic medicine belonging to the sulphonylurea group). Gliclazide is used in a certain form of diabetes (type 2 diabetes Mellitus) in adults, when diet, exercise and weight loss alone do not have an adequate effect on keeping blood sugar at the correct level.

Sulfonylureas

Gliclazide is a second generation sulfonylurea drug that has hypoglycaemic and potentially useful hematological properties. It stimulates the release of insulin from pancreatic β-cells by facilitating Ca⁺²  transport across the β-cell membranes and decreases hepatic glucose output.

Film-coated tablet: The usual initial dose is 40 to 80 mg daily. The dose can be increased up to 320 mg daily in divided doses when needed. The drug should be taken before meal. For children, Gliclazide is not used because it is contraindicated in juvenile-onset diabetes.

Modified release preparation: Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The dose is determined by the doctor, depending on your blood and possibly urine sugar levels. Change in external factors (weight reduction, lifestyle, stress) or improvements in the blood sugar control may require changed gliclazide doses.

The recommended daily dose is one to four tablets (maximum 120 mg) in a single intake at breakfast time. This depends on the response to treatment. Gliclazide MR tablet is for oral use. Take your tablet(s) with a glass of water at breakfast time (and preferably at the same time each day). Swallow your whole tablet(s) in one piece. Do not chew or crush. You must always eat a meal after taking your tablet(s).

If a combination therapy of gliclazide with metformin, an alpha-glucosidase inhibitor, a thiazolidinedione, a dipeptidyl peptidase-4 inhibitor a GLP-1 receptor agonist or insulin is initiated your doctor will determine the proper dose of each medicine individually for you. If you notice that your blood sugar levels are high although you are taking the medicine as prescribed, you should contact your doctor or pharmacist.

If you take more Gliclazide tablets than you should: If you take too many tablets, contact your doctor or the nearest hospital Accident & Emergency department immediately. The signs of overdose are those of low blood sugar (hypoglycaemia). The symptoms can be helped by taking sugar (4 to 6 lumps) or sugary drinks straight away, followed by a substantial snack or meal. If the patient is unconscious immediately inform a doctor and call the emergency services. The same should be done if somebody, (for instance a child), has taken the product unintentionally. Unconscious patients must not be given food or drink. It should be ensured that there is always a pre-informed person that can call a doctor in case of emergency.

If you forget to take Gliclazide tablet: It is important to take your medicine every day as regular treatment works better. However, if you forget to take a dose of Gliclazide MR tablet, take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Gliclazide MR tablet: As the treatment for diabetes is usually lifelong, you should discuss with your doctor before stopping this medicinal product. Stopping could cause high blood sugar (hyperglycaemia) which increases the risk of developing complications of diabetes. If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, Gliclazide can cause side effects, although not everybody gets them. The most commonly observed side effect is low blood sugar (hypoglycaemia). If left untreated these symptoms could progress to drowsiness, loss of consciousness or possibly coma. If an episode of low blood sugar is severe or prolonged, even if it is temporarily controlled by eating sugar, you should seek immediate medical attention.

Liver disorders: There have been isolated reports of abnormal iiver function, which can cause yellow skin and eyes. If you get this, see your doctor immediately. The symptoms generally disappear if the medicine is stopped. Your doctor will decide whether to stop your treatment.

Skin disorders: Skin reactions such as rash, redness, itching, hives, blisters, angioedema (rapid swelling of tissues such as eyelids, face, lips, mouth, tongue or throat that may result in breathing difficulty) have been reported. Rash may progress to widespread blistering or peeling of the skin. If you develop this, stop taking, seek urgent advice from a doctor and tell him that you are taking this medicine. Exceptionally, signs of severe hypersensitivity reactions have been reported: initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature.

Blood disorders: Decrease in the number of cells in the blood (e.g. platelets, red and white blood cells) which may cause paleness, prolonged bleeding, bruising, sore throat and fever have been reported. These symptoms usually vanish when the treatment is discontinued.

Digestive disorders: Abdominal pain, nausea, vomiting, indigestion, diarrhoea, and constipation. These effects are reduced when Gliclazide is taken with a meal as recommended.

Eye disorders: Your vision may be affected for a short time especially at the start of treatment. This effect is due to changes in blood sugar levels.

As for another sulfonylurea, the following adverse events have been observed: cases of severe changes in the number of blood cells and allergic inflammation of the wall of blood vessels, reduction in blood sodium (hyponatraemia), symptoms of liver impairment (for instance jaundice) which in most cases disappeared after withdrawal of the sulfonylurea, but may lead to life-threatening liver failure in isolated cases.

Reporting of side effects: If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. By reporting side effects, you can help provide more information on the safety of this medicine.

Do not take Gliclazide:

• if you are allergic to gliclazide or to other medicines of the same group (sulfonylurea), or to other related medicines (hypoglycaemic sulfonamides)
• if you have insulin-dependent diabetes (type 1)
• if you have ketone bodies and sugar in your urine (this may mean you have diabetic ketoacidosis), a diabetic pre-coma or coma
• if you have severe kidney or liver disease
• if you are taking medicines to treat fungal infections
• if you are breastfeeding

Talk to your doctor before taking Gliclazide. You should observe the treatment plan prescribed by your doctor to achieve proper blood sugar levels. This means, apart from regular tablet intake, to observe the dietary regimen, have physical exercise and, where necessary, reduce weight During gliclazide treatment regular monitoring of your blood (and possibly urine) sugar level and also your glycated haemoglobin (HbA1c) is necessary. In the first few weeks of treatment, the risk of having reduced blood sugar levels (hypoglycaemia) may be increased. So particularly close medical monitoring is necessary.

Low blood sugar (Hypoglycaemia) may occur:

• if you take meals irregularly or skip meals altogether,
• if you are fasting
• if you are malnourished
• if you change your diet
• if you increase your physical activity and carbohydrate intake does not match this increase,
• if you drink alcohol, especially in combination with skipped meals,
• if you take other medicines or natural remedies at the same time,
• if you take too high doses of gliclazide,
• if you suffer from particular hormone-induced disorders (functional disorders of the thyroid gland, pituitary gland or adrenal cortex),
• if your kidney function or liver function is severely decreased.

if you have low blood sugar you may have the following symptoms: headache, intense hunger, nausea, vomiting, weariness, sleep disorders, restlessness, aggressiveness, poor concentration, reduced alertness and reaction time, depression, confusion, speech or visual disorders, tremor, sensory disturbances, dizziness and helplessness.

The following signs and symptoms may also occur: sweating, clammy skin, anxiety, fast or irregular heartbeat, high blood pressure, sudden strong pain in the chest that may radiate into nearby areas (angina pectoris).

If blood sugar levels continue to drop you may suffer from considerable confusion (delirium), develop convulsions, lose self-control, your breathing may be shallow and your heartbeat slowed down, you may become unconscious.

In most cases the symptoms of low blood sugar vanish very quickly when you consume .some form of sugar, (for instance, glucose tablets, sugar cubes, sweet juice, sweetened tea).

You should therefore always carry some form of sugar with you (glucose tablets, sugar cubes). Remember that artificial sweeteners are not effective. Please contact your doctor or the nearest hospital if taking sugar does not help or if the symptoms recur.

Symptoms of low blood sugar may be absent, less obvious or develop very slowly or you are not aware in time that your blood sugar level has dropped. This may happen if you are an elderly patient taking certain medicines (for instance those acting on the central nervous system and beta-blockers).

If you are in stressful situations (e.g. accidents, surgical operations, fever etc.) your doctor may temporarily switch you to insulin therapy.

Symptoms of high blood sugar (hyperglycaemia) may occur when gliclazide has not yet sufficiently reduced the blood sugar when you have not complied with the treatment plan prescribed by your doctor if you take St. John’s Wort (Hypericum perforatum) preparations or in special stress situations. These may include thirst, frequent urination, dry mouth, dry itchy skin, skin infections and reduced performance.

Blood glucose disturbances (low blood sugar and high bold sugar) can occur when Gliclazide is prescribed at the same time as medicines to a class of antibiotics called fluoroquinolone, especially in elderly patients. In this case, your doctor will remind you of the importance of monitoring your blood glucose.

If you have a family history of or know you have the hereditary condition glucose-6-phosphate dehydrogenase (G6PD) deficiency (abnormality of red blood cells), lowering of the haemoglobin level and breakdown of red blood cells (haemolytic anaemia) can occur. Contact your doctor before taking this medicinal product.

Gliclazide is not recommended for use in children due to lack of data.

Other medicines and Gliclazide: Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.

The blood sugar lowering effect of gliclazide may be strengthened and signs of low blood sugar levels may occur when one of the follow ng medicines is taken:

• other medicines used to treat high blood sugar (oral antidiabetics, GLP-1 receptor agonists or insulin),
• antibiotics (sulphonamides, clarithromycin)
• medicines to treat high blood pressure or heart failure (beta-blockers. ACE-inhibitors such as captopril, or enalapril)
• medicines to treat fungal infections (miconazole, fluconazole)
• medicines to treat ulcers in the stomach or duodenum (H2 receptor antagonists),
• medicines to treat depression (monoamine oxidase inhibitors)
• painkiller or antirheumatics (phenylbutazone, ibuprofen)
• medicines containing alcohol

The blood-glucose-lowering effect of gliclazide may be weakened and raised blood sugar levels may occur when one of the following medicines is taken:

• medicines to treat disorders of the central nervous system (chlorpromazine)
• medicines reducing inflammation (corticosteroids)
• medicines to treat asthma or used during labour (intravenous salbutamol, ritodrine and terbutaline)
• medicines to treat breast disorders, heavy menstrual bleeding and endometriosis (danazol)
• St John's Wort- Hypericum perforatum- preparations

Blood glucose disturbance (low blood sugar and high blood sugar) can occur when a medicine belonging to a class of antibiotics called fluoroquinolones is taken at the same time as gliclazide especially in elderly patients.

Gliclazide may increase the effects of medicines that reduce blood clotting (warfarin).

Consult your doctor before you start taking another medicinal product. If you go into hospital tell the medical staff you are taking gliclazide.

Gliclazide with food and drink: Gliclazide can be taken with food and non-alcoholic drinks. Drinking alcohol is not recommended as it can alter the control of your diabetes in an unpredictable manner.

Driving and using machines: Your ability to concentrate or react may be impaired if your blood sugar is too low (hypoglycaemia), or too high (hyperglycaemia) or if you develop visual problems as a result of such conditions. Bear in mind that you could endanger yourself or others (for instance when driving a car or using machines). Please ask your doctor whether you can drive a car if you:

• have frequent episodes of low blood sugar (hypoglycaemia)
• have few or no warning signals of low blood sugar (hypoglycaemia)

Gliclazide contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Gliclazide is not recommended for use during pregnancy. If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. You must not take Gliclazide while you are breastfeeding.

Keep out of the reach and sight of children. Do not use this medicine after the expiry date which is stated on the carton and the blister. The expiry date refers to the last day of that month. Store below 30°C. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Dexamethasone is a synthetic glucocorticoid which decreases inflammation by inhibiting the migration of leukocytes and reversal of increased capillary permeability. It suppresses normal immune response.

In general, glucocorticoid dosage depends on the severity of the condition and the response of the patient. If no favourable response is noted within a couple of days, continuation of glucocorticoid therapy is undesirable. In chronic conditions requiring long-term therapy the lowest dosage that provides adequate, but not necessarily complete, relief should be used.

For tablet:

• In adult patients, daily oral dosages vary from 1 mg to 10 mg and in children from 0.03-0.20 mg/kg body weight,according to the individual response.
• In some patients higher dosages may be temporarily required,to control the disease. As soon as circumstances permit,dosage should be decreased.
• For a short dexamethasone suppression test 1 mg dexamethasone is given at 11 p.m. and plasmacortisol measured the next morning.
• Patients who do not show a decrease in cortisol can be exposed to a longer test: 0.5 mg dexamethasone is given at 6-hour intervals
• for 48 hours followed by 2 mg every 6 hours for a further 48 hours. 24-hour urine collections are made before, during and at the end of the test for the determination of 17 alpha-hydroxycorticoids.

For injection:

• Dexamethasone can be given by intravenous (IV), intramuscular (IM) or local injection. Dexamethasone injections can also be diluted with an infusion fluid or be injected directly into the infusion line.
• Intravenous injections of massive doses should be given slowly, over a period of several minutes.
• Intramuscular administration should be given by deep intramuscular injection,to prevent atrophy of the subcutaneous adipose tissues.
• Intra-articular injections should be given under strictly aseptic conditions as glucocorticoids decrease the resistance to infection. When diluted with these infusion fluids, Dexamethasone will keep its potency for at least 24 hours (at room temperature and in daylight conditions). As infusion fluids, Sodium chloride 0.9%, Anhydrous glucose 5%, Invert sugar 10%, Sorbitol 5%, Ringer's solution, Hartman's solution (Ringer-lactate) etc.can be used.
• The dosage of Dexamethasone depends on the severity of the condition and the response of the patient.
• For systemic therapy in adults, daily doses of 0.05-0.20 mg/kg body weight are usually sufficient. For emergencies (e.g. anaphylaxis, acute severe asthma, cerebral edema) substantially higher doses are required. An initial dose of 10-20 mg IV is followed by 6 mg IV or IM every 6 hours,until a satisfactory result has been obtained. Thereafter the dosage has to be tapered off gradually.

For local therapy, the following doses are recommended:

• Intra-articularly: 2-4 mg in large and 0.8-1 mg in small joints
• Intrabursally: 2-4 mg;in tendon sheaths:0.4-1 mg
• The frequency of these injections may vary from every 3-5 days to every 2-3 weeks

The following adverse reactions have been associated with prolonged systemic glucocorticoid therapy.

Endocrine and metabolic disturbances: Cushing-like syndrome, hirsutism, menstrual irregularities, premature epiphyseal closure, secondary adrenocortical and pituitary unresponsiveness, decreased glucose tolerance, negative nitrogen and calcium balance.

Fluid and electrolyte disturbances: Sodium and fluid retention, hypertension, potassium loss, hypokalaemic alkalosis.

Musculo-skeletal effects: Myopathy, abdominal distension, osteoporosis, aseptic necrosis of femoral and humeral heads.

Gastro-intestinal effects: Gastric and duodenal ulceration, perforation and haemorrhage.

Dermatological effects: Impaired wound healing, skin atrophy, striae, petechiae and ecchymoses, bruising, facial erythema, increased sweating, acne.

Central Nervous System effects: Psychic disturbances ranging from euphoria to frank psychotic manifestations,convulsions,in children pseudotumor cerebri (benign intracranial hypertension) with vomiting and papilloedema.

Ophthalmic effects: Glaucoma, increased intraocular pressure, posterior subcapsular cataracts.

Immunosuppressive effects: Increased susceptibility to infections, decreased responsiveness to vaccination and skin tests.

General: The lowest possible dose of corticosteroids should be used to control the condition under treatment.The reduction should be gradual.

Cardio-renal: These agents should be used with caution in patients with congestive heart failure,hypertension, or renal insufficiency.

Endocrine: Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage.

Gastrointestinal: Steroids should be used with caution in active or latent peptic ulcers, diverticulitis, intestinal anastomoses, and nonspecific ulcerative colitis, since they may increase the risk of a perforation.

Musculoskeletal: Special consideration should be given to patients at increased risk of osteoporosis (e.g.,postmenopausal women) before initiating corticosteroid therapy.

Neuro-psychiatric: An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with myasthenia gravis or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). Psychic derangements may appear ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations.

Pregnancy Category C.There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Glucocorticoids appear in breast milk.Mothers taking high dosages of corticosteroids should be advised not to breast-feed

In order to minimize the potential growth effects of corticosteroids, pediatric patients should be titrated to the lowest effective dose.

Overdosage is unlikely, however, treatment of overdosage is by supportive and symptomatic therapy

Tablet: Store in a cool & dry place, protected from light & moisture.
Injection: Store below 30° C, protected from light.Do not freeze. Keep medicines out of the reach of children

Dexamethasone is a synthetic glucocorticoid which decreases inflammation by inhibiting the migration of leukocytes and reversal of increased capillary permeability. It suppresses normal immune response.

In general, glucocorticoid dosage depends on the severity of the condition and the response of the patient. If no favourable response is noted within a couple of days, continuation of glucocorticoid therapy is undesirable. In chronic conditions requiring long-term therapy the lowest dosage that provides adequate, but not necessarily complete, relief should be used.

For tablet:

• In adult patients, daily oral dosages vary from 1 mg to 10 mg and in children from 0.03-0.20 mg/kg body weight,according to the individual response.
• In some patients higher dosages may be temporarily required,to control the disease. As soon as circumstances permit,dosage should be decreased.
• For a short dexamethasone suppression test 1 mg dexamethasone is given at 11 p.m. and plasmacortisol measured the next morning.
• Patients who do not show a decrease in cortisol can be exposed to a longer test: 0.5 mg dexamethasone is given at 6-hour intervals
• for 48 hours followed by 2 mg every 6 hours for a further 48 hours. 24-hour urine collections are made before, during and at the end of the test for the determination of 17 alpha-hydroxycorticoids.

For injection:

• Dexamethasone can be given by intravenous (IV), intramuscular (IM) or local injection. Dexamethasone injections can also be diluted with an infusion fluid or be injected directly into the infusion line.
• Intravenous injections of massive doses should be given slowly, over a period of several minutes.
• Intramuscular administration should be given by deep intramuscular injection,to prevent atrophy of the subcutaneous adipose tissues.
• Intra-articular injections should be given under strictly aseptic conditions as glucocorticoids decrease the resistance to infection. When diluted with these infusion fluids, Dexamethasone will keep its potency for at least 24 hours (at room temperature and in daylight conditions). As infusion fluids, Sodium chloride 0.9%, Anhydrous glucose 5%, Invert sugar 10%, Sorbitol 5%, Ringer's solution, Hartman's solution (Ringer-lactate) etc.can be used.
• The dosage of Dexamethasone depends on the severity of the condition and the response of the patient.
• For systemic therapy in adults, daily doses of 0.05-0.20 mg/kg body weight are usually sufficient. For emergencies (e.g. anaphylaxis, acute severe asthma, cerebral edema) substantially higher doses are required. An initial dose of 10-20 mg IV is followed by 6 mg IV or IM every 6 hours,until a satisfactory result has been obtained. Thereafter the dosage has to be tapered off gradually.

For local therapy, the following doses are recommended:

• Intra-articularly: 2-4 mg in large and 0.8-1 mg in small joints
• Intrabursally: 2-4 mg;in tendon sheaths:0.4-1 mg
• The frequency of these injections may vary from every 3-5 days to every 2-3 weeks

The following adverse reactions have been associated with prolonged systemic glucocorticoid therapy.

Endocrine and metabolic disturbances: Cushing-like syndrome, hirsutism, menstrual irregularities, premature epiphyseal closure, secondary adrenocortical and pituitary unresponsiveness, decreased glucose tolerance, negative nitrogen and calcium balance.

Fluid and electrolyte disturbances: Sodium and fluid retention, hypertension, potassium loss, hypokalaemic alkalosis.

Musculo-skeletal effects: Myopathy, abdominal distension, osteoporosis, aseptic necrosis of femoral and humeral heads.

Gastro-intestinal effects: Gastric and duodenal ulceration, perforation and haemorrhage.

Dermatological effects: Impaired wound healing, skin atrophy, striae, petechiae and ecchymoses, bruising, facial erythema, increased sweating, acne.

Central Nervous System effects: Psychic disturbances ranging from euphoria to frank psychotic manifestations,convulsions,in children pseudotumor cerebri (benign intracranial hypertension) with vomiting and papilloedema.

Ophthalmic effects: Glaucoma, increased intraocular pressure, posterior subcapsular cataracts.

Immunosuppressive effects: Increased susceptibility to infections, decreased responsiveness to vaccination and skin tests.

General: The lowest possible dose of corticosteroids should be used to control the condition under treatment.The reduction should be gradual.

Cardio-renal: These agents should be used with caution in patients with congestive heart failure,hypertension, or renal insufficiency.

Endocrine: Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage.

Gastrointestinal: Steroids should be used with caution in active or latent peptic ulcers, diverticulitis, intestinal anastomoses, and nonspecific ulcerative colitis, since they may increase the risk of a perforation.

Musculoskeletal: Special consideration should be given to patients at increased risk of osteoporosis (e.g.,postmenopausal women) before initiating corticosteroid therapy.

Neuro-psychiatric: An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with myasthenia gravis or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). Psychic derangements may appear ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations.

Pregnancy Category C.There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Glucocorticoids appear in breast milk.Mothers taking high dosages of corticosteroids should be advised not to breast-feed

In order to minimize the potential growth effects of corticosteroids, pediatric patients should be titrated to the lowest effective dose.

Overdosage is unlikely, however, treatment of overdosage is by supportive and symptomatic therapy

Tablet: Store in a cool & dry place, protected from light & moisture.
Injection: Store below 30° C, protected from light.Do not freeze. Keep medicines out of the reach of children

Dexamethasone is a synthetic glucocorticoid which decreases inflammation by inhibiting the migration of leukocytes and reversal of increased capillary permeability. It suppresses normal immune response.

Eye:

• As 0.1% drop: The frequency of instillation of drops and the duration of treatment will vary depending upon the severity of the underlying condition and the response to treatment. Severe inflammations require one to two drops instilled into the eye every thirty to sixty minutes until a satisfactory response occurs. Subconjunctival or systemic steroid therapy should be considered if there is no response. When a favourable response has been observed reduce the dosage towards one drop every four hours.
• As 0.05% ointment: Apply 0.5-1 inch ribbon of ointment into the conjunctival sac(s) up to 4 times daily. Reduce to once daily dosing once conditon has improved.

Ear: Instill two or three drops to the ear at two or three hour interval. The frequency of dosage and duration of the treatment may vary with the type of lesion and severity.

Glaucoma with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, perforation of the globe. Rarely, stinging and burning may occur.

Epithelial herpes simplex keratitis (dendritic keratitis), acute infections stages of vaccinia, varicella, and many other viral diseases of the cornea and conjunctiva, Mycobacterial infection of the eye, Fungal diseases of ocular or auricular structures, perforation of a drum membrane. Hypersensitivity to any ingredient of this product.

The possibility of persistent fungal infections of the cornea should be considered after prolonged corticosteroid dosing. There have been reports of bacterial keratitis associated with the use of multiple dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.

None relevant to topical use.

Pregnancy category C. There is no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Caution should be exercised when Dexamethasone ophthalmic solution is administered to a nursing woman.

Pediatric Use: Safety and efficacy in pediatric patients below the age of 18 have not been established.

Long-term intensive topical use may lead to systemic effects. Oral ingestion of the contents of the bottle (up to 10 ml) is unlikely to lead to any serious adverse effects.

Store below 30° C in a cool and dry place protected from light. Keep out of reach of children. Do not touch the dropper tip to surfaces since this may contaminate the solution. Do not use after 30 days of first opening.

Timolol Maleate Ophthalmic Solution is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

Drugs for miotics and glaucoma

Timolol is a non-selective β-adrenergic receptor blocker. It does not have significant intrinsic sympathomimetic activity, direct myocardial depressant activity or local anaesth activity. Exact mechanism of ocular hypotensive effect is unclear, but it is thought to be related to reduction of aqueous humour formation. β-blockade also causes lowering of BP.

Eye drops Solution: Initially, instill 1 drop of 0.25% solution bid into the affected eye(s), may increase to 1 drop of 0.5% solution bid if there is inadequate response; decrease to 1 drop once daily if controlled. Do not exceed 1 drop bid of 0.5% solution.

Gel-forming eye drops: 0.25% or 0.5% Gel-forming eye drops: Instill 1 drop into the affected eye(s) once daily.

Burning and stinging sensation of the eyes, bradycardia, hypotension, arrhythmia and AV or SA nodal block, CHF, pulmonary oedema, Raynaud's phenomenon, headache, dizziness, fatigue, asthenia, abdominal discomfort, nausea, constipation, hypoglycaemia.

Timolol is contraindicated in patients with bronchial asthma, a history of bronchial asthma, severe chronic obstructive pulmonary disease, sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, cardiogenic shock, hypersensitivity to any component of this product.

Patients with inadequate cardiac function, DM, myasthenia gravis, cerebrovascular insufficiency, history of atopy. Avoid abrupt withdrawal as it may exacerbate angina symptoms or precipitate MI in patients with coronary artery disease, or precipitate thyroid crisis in patients with thyrotoxicosis. Patients undergoing major surgery. May mask signs of hyperthyroidism and hypoglycaemia. Ophth soln should not be used as monotherapy for angle-closure glaucoma. Renal and hepatic impairment. Pregnancy and lactation.

Although Timolol used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with Timolol Maleate and epinephrine has been reported occasionally. Drug interactions of Timolol Maleate have been noticed with concomitant administration of beta-adrenergic blocking agents (both oral and topical), calcium antagonists, catecholamine-depleting drugs, digitalis, quinidin, clonidine, injectable epinephrine.

Pregnancy: There are no adequate and well-controlled studies in pregnant women. Timolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Timolol has been detected in breast milk following oral and ophthalmic drug administration. Because of the potential for serious adverse reactions from Timolol in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

There have been reports of inadvertent overdosage with Timolol Ophthalmic Solution resulting in systemic effects similar to those seen with systemic beta-adrenergic blocking agents such as dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest.

Store between 15-30° C. Avoid freezing and protect from light.

This eye drop is indicated for the reduction of elevated intraocular pressure (IOP) in patients with glaucoma or ocular hypertension.

Drugs for miotics and glaucoma

This eye drops is comprised of two components: Brimonidine Tartrate & Timolol Maleate. Brimonidine Tartrate is a selective alpha-2 adrenergic receptor agonist having a dual mechanism of action. It decreases aqueous humor production and increases nonpressure dependent uveoscleral outflow. Timolol Maleate is a β-adrenergic receptor antagonist that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. It lowers IOP by reducing aqueous humor production. Therefore the combination of both drugs gives a rapid onset of action, with peak ocular hypotensive effect seen within two hours of administration.

Instill 1 drop in the affected eye(s) twice daily.

The most common side effects are allergic conjunctivitis, conjunctival folliculosis, conjunctival hyperaemia, eye pruritus and ocular burning or stinging.

Contraindicated in patients with hypersensitivity to any component of this product. Also contraindicated in bronchial asthma, severe chronic obstructive pulmonary disease, sinus bradycardia, second or third-degree atrioventricular block, overt cardiac failure and cardiogenic shock.

Like other topically applied ophthalmic agents, it may be absorbed systemically. Due to the presence of Timolol, the same types of cardiovascular and pulmonary adverse reactions as seen with systemic beta-blockers may occur. Cautions should be exercised in treating patients with severe or unstable and uncontrolled cardiovascular or pulmonary diseases.

Specific drug interaction studies have not been conducted.

There are no adequate and well-controlled studies in pregnant women. Combipres should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Timolol has been detected in human milk but it is not known whether Brimonidine Tartrate is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue taking into account the importance of the drug to the mother.

Use in children: Safety and effectiveness in children below the age of 2 years have not been established.

Use in elderly patients: No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

Store at a cool & dry place, protect from light. Do not use longer than 30 days after the first opening of the bottle. Keep out of the reach of children.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Biguanides

Metformin is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Metformin immediate release tablet: Dosage of Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses.

• Adult: The usual starting dose of Metformin is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. For those patients requiring additional glycemic control, Glucomin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given three times a day with meals.
• Children: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.

Metformin extended release tablet: Swallow Metformin XR tablet whole and never crush, cut or chew.

• Adult: The usual starting dose of Metformin XR is 500 mg once daily with the evening meal. Dose should be increased in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal, alternatively increased to 1000 mg twice daily taken with meal. Patient receiving Metformin immediate release tablet may be switched to Metformin extended release tablet up to a maximum recommended daily dose.
• Children: Metformin extended release tablet has not been studied in children.
• Renal impaired patient: Do not use Metformin in patients with eGFR below 30 mL/min/1.73 m². Asses risk/benefit of counting if eGFR falls below 45 mL/min/1.73 m².

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Metformin Hydrochloride is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Metformin may lower vitamin B12 level. It also increases risk of hypoglycemia when use in combination with insulin or insulin secretagogue.

Co-administration with Carbonic anhydrase (Topiramate, Zonisamide) may increase risk of lactic acidosis. Drugs (Ranolazine, Dolutegravir, Cimetidine) that reduce Metformin clearance may increase the accumulation of Metformin. Alcohol can potentiate the effect of Metformin on lactate metabolism.

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital abnormalities and perinatal mortality. When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breastfeeding: Metformin is excreted into human breast milk. No adverse efects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding should be made, taking into account the benefit of breastfeeding and the potential risk to adverse effects on the child.

Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Pediatric population: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin-treated children, especially prepubescent children, is recommended.

Children aged between 10 and 12 years: Particular caution is recommended when prescribing to children aged between 10 and 12 years.

Renal function: As metformin is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function,
• At least two to four times a year in patients with creatinine clearance at the lower limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicate in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Hypoglycemia has not been seen with Metformin doses up to 85 gm, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Metformin is hemodialysis.

Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Meglitinide Analogues

Repaglinide binds to specific receptors in the cell membrane leading to the closure of ATP dependent K⁺ channels and the depolarisation of cell membrane. This in turn, leads to Ca⁺⁺ influx, increased intracellular Ca⁺⁺ and the stimulation of insulin secretion.

The most common side effects of Repaglinide are hypoglycemia and related symptoms. Others include upper respiratory tract infections, diarrhea, constipation, nausea and vomiting. Hypersensitivity reactions include rashes and urticaria.

Repaglinide is contraindicated in patients with:

• Diabetic ketoacidosis, with or without coma.
• Type 1 diabetes mellitus and
• Known hypersensitivity to the drug or its inactive ingredients.

Insulin should be substituted during concurrent illness (such as myocardial infarction, coma, infection, and trauma) and during surgery. All oral blood glucose-lowering drugs are capable of producing hypoglycemia. Repaglinide should be administered with meals to lessen the risk of hypoglycemia.

The dose of Repaglinide may need to be adjusted, if taken with other medications. The possible interactions of Repaglinide with other drugs are:

• Inhibitors of the cytochrome P450 enzyme system (azole antifungals and macrolides) may lead to lower Repaglinide clearance and longer half life.
• Inducers of the cytochrome P450 enzyme system (Rifampin, Phenobarbital, Carbamazepine, Troglitazone, etc.) may accelerate Repaglinide metabolism and shorten its effect.
• Cimetidine has no significant effect on Repaglinide absorption or clearance.
• Repaglinide has no significant effect on Digoxin, Theophyllin, or Warfarin.
• Highly protein bound drugs (e.g., NSAIDs) may increase the plasma level of unbound Repaglinide and potentiate its glucose lowering effect. Thus, co-administration of these drugs with Repaglinide may increase the risk of hypoglycaemia.
• The risk of hypoglycaemia may also be increased when hypoglycaemic agents are co-administered with certain drugs such as salicylates, sulphonamides, Chloramphenicol, coumarins, Probenecid, monoamine oxidase (MAO) inhibitors, and adrenergic blockers.

Safety in pregnant women has not been established. Repaglinide should be used during pregnancy only if it is clearly needed. It is not known whether Repaglinide is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Repaglinide, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Patients receiving up to 80 mg of Repaglinide developed few adverse effects other than lowering of blood glucose. Hypoglycemia did not occur when meals were given with these high doses. Severe hypoglycemic reactions with coma, seizure or other neurological impairment occur infrequently.

Do not store above 30°C. Keep away from light and out of the reach of children.

Meglitinide Analogues

Repaglinide binds to specific receptors in the cell membrane leading to the closure of ATP dependent K⁺ channels and the depolarisation of cell membrane. This in turn, leads to Ca⁺⁺ influx, increased intracellular Ca⁺⁺ and the stimulation of insulin secretion.

The most common side effects of Repaglinide are hypoglycemia and related symptoms. Others include upper respiratory tract infections, diarrhea, constipation, nausea and vomiting. Hypersensitivity reactions include rashes and urticaria.

Repaglinide is contraindicated in patients with:

• Diabetic ketoacidosis, with or without coma.
• Type 1 diabetes mellitus and
• Known hypersensitivity to the drug or its inactive ingredients.

Insulin should be substituted during concurrent illness (such as myocardial infarction, coma, infection, and trauma) and during surgery. All oral blood glucose-lowering drugs are capable of producing hypoglycemia. Repaglinide should be administered with meals to lessen the risk of hypoglycemia.

The dose of Repaglinide may need to be adjusted, if taken with other medications. The possible interactions of Repaglinide with other drugs are:

• Inhibitors of the cytochrome P450 enzyme system (azole antifungals and macrolides) may lead to lower Repaglinide clearance and longer half life.
• Inducers of the cytochrome P450 enzyme system (Rifampin, Phenobarbital, Carbamazepine, Troglitazone, etc.) may accelerate Repaglinide metabolism and shorten its effect.
• Cimetidine has no significant effect on Repaglinide absorption or clearance.
• Repaglinide has no significant effect on Digoxin, Theophyllin, or Warfarin.
• Highly protein bound drugs (e.g., NSAIDs) may increase the plasma level of unbound Repaglinide and potentiate its glucose lowering effect. Thus, co-administration of these drugs with Repaglinide may increase the risk of hypoglycaemia.
• The risk of hypoglycaemia may also be increased when hypoglycaemic agents are co-administered with certain drugs such as salicylates, sulphonamides, Chloramphenicol, coumarins, Probenecid, monoamine oxidase (MAO) inhibitors, and adrenergic blockers.

Safety in pregnant women has not been established. Repaglinide should be used during pregnancy only if it is clearly needed. It is not known whether Repaglinide is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Repaglinide, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Patients receiving up to 80 mg of Repaglinide developed few adverse effects other than lowering of blood glucose. Hypoglycemia did not occur when meals were given with these high doses. Severe hypoglycemic reactions with coma, seizure or other neurological impairment occur infrequently.

Do not store above 30°C. Keep away from light and out of the reach of children.

Meglitinide Analogues

Repaglinide binds to specific receptors in the cell membrane leading to the closure of ATP dependent K⁺ channels and the depolarisation of cell membrane. This in turn, leads to Ca⁺⁺ influx, increased intracellular Ca⁺⁺ and the stimulation of insulin secretion.

The most common side effects of Repaglinide are hypoglycemia and related symptoms. Others include upper respiratory tract infections, diarrhea, constipation, nausea and vomiting. Hypersensitivity reactions include rashes and urticaria.

Repaglinide is contraindicated in patients with:

• Diabetic ketoacidosis, with or without coma.
• Type 1 diabetes mellitus and
• Known hypersensitivity to the drug or its inactive ingredients.

Insulin should be substituted during concurrent illness (such as myocardial infarction, coma, infection, and trauma) and during surgery. All oral blood glucose-lowering drugs are capable of producing hypoglycemia. Repaglinide should be administered with meals to lessen the risk of hypoglycemia.

The dose of Repaglinide may need to be adjusted, if taken with other medications. The possible interactions of Repaglinide with other drugs are:

• Inhibitors of the cytochrome P450 enzyme system (azole antifungals and macrolides) may lead to lower Repaglinide clearance and longer half life.
• Inducers of the cytochrome P450 enzyme system (Rifampin, Phenobarbital, Carbamazepine, Troglitazone, etc.) may accelerate Repaglinide metabolism and shorten its effect.
• Cimetidine has no significant effect on Repaglinide absorption or clearance.
• Repaglinide has no significant effect on Digoxin, Theophyllin, or Warfarin.
• Highly protein bound drugs (e.g., NSAIDs) may increase the plasma level of unbound Repaglinide and potentiate its glucose lowering effect. Thus, co-administration of these drugs with Repaglinide may increase the risk of hypoglycaemia.
• The risk of hypoglycaemia may also be increased when hypoglycaemic agents are co-administered with certain drugs such as salicylates, sulphonamides, Chloramphenicol, coumarins, Probenecid, monoamine oxidase (MAO) inhibitors, and adrenergic blockers.

Safety in pregnant women has not been established. Repaglinide should be used during pregnancy only if it is clearly needed. It is not known whether Repaglinide is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Repaglinide, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Patients receiving up to 80 mg of Repaglinide developed few adverse effects other than lowering of blood glucose. Hypoglycemia did not occur when meals were given with these high doses. Severe hypoglycemic reactions with coma, seizure or other neurological impairment occur infrequently.

Do not store above 30°C. Keep away from light and out of the reach of children.

Indicated for the treatment of osteoarthritis of knee, hip, spine, and other locations. Also indicated as dietary supplement.

Stimulation of Cartilage formation

Glucosamine is a naturally occurring compound for the body's production of joint lubricants and shock absorbers necessary to maintain healthy cartilage and joint function. Glucosamine hydrochloride is a prodrug for glucosamine that is well absorbed after oral administration and diffuses into several tissues, including bones and articular cartilages. The active ingredient in the treatment of osteoarthritis is glucosamine. The hydrochloride acid salt is the delivery vehicle. Once it has entered the stomach, after oral administration the salt's job is done and it is the glucosamine that is released to perform its function.

Data supports Glucosamine as the first anti-osteoarthritic drug that treats both sign and symptoms of osteoarthritis & modifies disease progression. It is as effective as NSAIDs with significantly better tolerability and clinical compliances.

500 mg tablet three times daily or as directed by the physician. A single dose of 1500 mg daily may also be effective. Obese individuals may need higher doses, based on body weight.

Safety studies with Glucosamine show no demonstrable toxicity. Rarely occurring side effects like mild & reversible intestinal flatulence are almost like placebo.

There are no known contraindications for Glucosamine. But proven hypersensitivity to Glucosamine is a contraindication.

Diabetics are advised to monitor blood glucose levels regularly while taking Glucosamine. No special studies were formed in patients with renal and/or hepatic insufficiency. The toxicological and pharmacokinetic profile of the product does not indicate limitations for these patients. However, administration to these patients with severe hepatic or renal insufficiency should be under appropriate medical supervision.

There have been no reports of significant drug interactions of Glucosamine with antibiotics, antidepressants, antihypertensives, nitrates, antiarrhythmics, anxiolytic, hypoglycaemic agents, anti-secretives.

Women who are pregnant or who could become pregnant should not supplement with glucosamine. Glucosamine has not been studied enough to determine their effects on a developing fetus. And no studies have evaluated the use of Glucosamine during pregnancy or lactation. It should be taken with caution and medical advice during pregnancy and lactation.

Should be stored in cool and dry place.

This tablet is indicated in-

• Osteoarthritis
• Rheumatoid arthritis
• Bone and Joint injuries

Stimulation of Cartilage formation

Glucosamine: Glucosamine (2-amino-2-deoxy-alpha-D-glucose) is a natural amino sugar, produced by the body and found in certain foods. It is the most fundamental building block required for biosynthesis of glycosaminoglycans (GAGs) like Hyaluronic Acid, Keratan Sulfate and Chondroitin Sulfate. GAGs binds with protein and form proteoglycans, the essential building block of articular cartilage. When cartilage in a joint deteriorates, Osteoarthritis develops. It also helps to form ligaments, tendon, nails and various other connective tissues. When we take artificially synthesized Glucosamine Sulfate supplement, it increases Glucosamine level in the body, thus facilitates production and repair of cartilage. Glucosamine also activates chondrocytes in the cartilage which help produce GAGs and proteoglycans.

In humans, about 90 percent of glucosamine, administered as an oral dose of glucosamine sulfate, is absorbed from the digestive tract. Predominantly metabolized by liver & excreted through urine.

Diacerein: This is used for the treatment of Osteoarthritis. It has also analgesic, antipyretic and anti-inflammatory activity. It release in vitro and directly inhibits InterLeukin-1(IL-1) synthesis, which is the main cytokine involved in cartilage destruction. Due to specific mode of action, it have been shown to have disease-modifying effect in experimental models of osteoarthritis and in human subjects with finger joint and knee osteoarthritis.

Oral bioavailability of Diacerein 56%. Concurrent intake of food delays the time to peak concentration but associated with a 25% increase in absorption. Therefore, diacerein is best given with food. Mainly binds with protein albumin. Diacerein is metabolized extensively (100%) in liver following oral dosing. Urinary excretion of diacerein in the form of its metabolites has ranged between 35% and 60%.

Use in adults: One tablet twice daily with food.

Use in children and adolescents: The safety and effectiveness of children and adolescents under the age of 18 years have not been established.

No serious adverse effect has been reported. Nausea, vomiting, diarrhea, epigastria pain, headache, skin rashes & intense yellow coloring of urine may be occurred.

Contraindicated for those who shows hypersensitivity to Glucosamine or Diacerein.

Caution should be practised when administering this tablet in case of patients who are allergic to Glucosamine or Diacerein.

Decrease absorption of Diacerein with aluminium and/ or magnesium hydroxide antacids. Increase risk of diarrhea with laxatives or antibiotics.

This tablet is contraindicated during pregnancy and breastfeeding.

Store in cool & dry place below 30ºC, protect from light & moisture. Keep out of reach of children.

This pain-relieving cream is applied topically and provides powerful pain relief of osteoarthritis pain, sprains, simple backache, tendonitis, minor arthritis pain.

Topical Analgesics

Glucosamine is sugar protein that is believed to help in developing and renewing cartilage and keep it lubricated for better joint movement and flexibility.

Chondroitin helps to maintain fluid and flexibility in the joints. The combination of chondroitin and glucosamine is widely used to aid in maintaining healthy joints. It is also used as a nutritional supplement in people with osteoarthritis or other inflammatory joint disorders.

Camphor is a strong smelling compound, chemically manufactured from turpentine oil. When applied to the skin, it stimulates nerve endings to relieve pain, itching and to relieve osteoarthritis.

Peppermint Oil is a strong smelling ingredient can be applied to the skin to treat muscle pain, nerve pain and joint pain.

For the management of osteoarthritis the recommended dose is twice daily into painful muscle and joints for 2-4 week. Apply gently to painful muscles and joints, until this pain relieving cream disappears. Repeat as necessary.

There are no known systemic side effects unless people have an allergy or skin sensitivity to camphor or one of the inactive ingredients.

Do not apply on broken or irritated skin or if excessive irritation develops. Do not bandage tightly or use a heating pad. Do not swallow. Avoid eye contact or mucous membranes.

This medicine is not known to interact significantly with other medicines.

It should not be used during pregnancy & lactation.

Store in a cool and dry place, away from light. keep out of reach of children.