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Immunosuppressant

Rheumatoid arthritis is an autoimmune disease characterized by a dysregulation of pro-inflammatory cytokines including IL7, IL15, IL21, IL6, IFN-alpha, and IFN-beta. (3) Cytokines signalling results in tissue inflammation and joint damage by stimulating the recruitment and activation of immune cells via the janus kinase signalling pathway.

Tofacitinib is a partial and reversible janus kinase (JAK) inihibitor that will prevent the body from responding to cytokine signals. By inhibiting JAKs, tofacitinib prevents the phosphorylation and activation of STATs. The JAK-STAT signalling pathway is involved in the transcription of cells involved in hematopoiesis, and immune cell function. Tofacitinib works therapeutically by inhibiting the JAK-STAT pathway to decrease the inflammatory response. However, there is evidence to suggest that it may also achieve efficacy via other pathways as well.

Rheumatoid Arthritis: Tofacitinib 5 mg twice daily or Tofacitinib 11 mg once daily. Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinib 5 mg once daily.

Psoriatic Arthritis (in combination with nonbiologic DMARDs): Tofacitinib 5 mg twice daily or Tofacitinib 11 mg once daily.  Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinib 5 mg once daily.

Ulcerative Colitis: Tofacitinib 10 mg twice daily for at least 8 weeks; then 5 or 10 mg twice daily. Discontinue after 16 weeks of 10 mg twice daily, if adequate therapeutic benefit is not achieved. Use the lowest effective dose to maintain response.

The most commonly reported adverse reactions during the first 3 months in controlled clinical trials (occurring in greater than or equal to 2% of patients treated with Tofacitinib monotherapy or in combination with DMARDs) were upper respiratory tract infections, headache, diarrhea and nasopharyngitis.

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

It is not known whether Tofacitinib 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 Tofacitinib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug for the mother

Pediatric Use: The safety and effectiveness of Tofacitinib in pediatric patients have not been established.

Geriatric Use: The frequency of serious infection among Tofacitinib-treated subjects 65 years of age and older was higher than among those under the age of 65. As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.

Moderate and severe renal impairment or moderate hepatic impairment: half the total daily dosage recommended for patients with normal renal and hepatic function.

Store below 30°C. Protect from light & moisture. Keep all medicines out of the reach of children.

Immunosuppressant

Rheumatoid arthritis is an autoimmune disease characterized by a dysregulation of pro-inflammatory cytokines including IL7, IL15, IL21, IL6, IFN-alpha, and IFN-beta. (3) Cytokines signalling results in tissue inflammation and joint damage by stimulating the recruitment and activation of immune cells via the janus kinase signalling pathway.

Tofacitinib is a partial and reversible janus kinase (JAK) inihibitor that will prevent the body from responding to cytokine signals. By inhibiting JAKs, tofacitinib prevents the phosphorylation and activation of STATs. The JAK-STAT signalling pathway is involved in the transcription of cells involved in hematopoiesis, and immune cell function. Tofacitinib works therapeutically by inhibiting the JAK-STAT pathway to decrease the inflammatory response. However, there is evidence to suggest that it may also achieve efficacy via other pathways as well.

Rheumatoid Arthritis: Tofacitinib 5 mg twice daily or Tofacitinib 11 mg once daily. Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinib 5 mg once daily.

Psoriatic Arthritis (in combination with nonbiologic DMARDs): Tofacitinib 5 mg twice daily or Tofacitinib 11 mg once daily.  Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinib 5 mg once daily.

Ulcerative Colitis: Tofacitinib 10 mg twice daily for at least 8 weeks; then 5 or 10 mg twice daily. Discontinue after 16 weeks of 10 mg twice daily, if adequate therapeutic benefit is not achieved. Use the lowest effective dose to maintain response.

The most commonly reported adverse reactions during the first 3 months in controlled clinical trials (occurring in greater than or equal to 2% of patients treated with Tofacitinib monotherapy or in combination with DMARDs) were upper respiratory tract infections, headache, diarrhea and nasopharyngitis.

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

It is not known whether Tofacitinib 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 Tofacitinib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug for the mother

Pediatric Use: The safety and effectiveness of Tofacitinib in pediatric patients have not been established.

Geriatric Use: The frequency of serious infection among Tofacitinib-treated subjects 65 years of age and older was higher than among those under the age of 65. As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.

Moderate and severe renal impairment or moderate hepatic impairment: half the total daily dosage recommended for patients with normal renal and hepatic function.

Store below 30°C. Protect from light & moisture. Keep all medicines out of the reach of children.

Immunosuppressant

Rheumatoid arthritis is an autoimmune disease characterized by a dysregulation of pro-inflammatory cytokines including IL7, IL15, IL21, IL6, IFN-alpha, and IFN-beta. (3) Cytokines signalling results in tissue inflammation and joint damage by stimulating the recruitment and activation of immune cells via the janus kinase signalling pathway.

Tofacitinib is a partial and reversible janus kinase (JAK) inihibitor that will prevent the body from responding to cytokine signals. By inhibiting JAKs, tofacitinib prevents the phosphorylation and activation of STATs. The JAK-STAT signalling pathway is involved in the transcription of cells involved in hematopoiesis, and immune cell function. Tofacitinib works therapeutically by inhibiting the JAK-STAT pathway to decrease the inflammatory response. However, there is evidence to suggest that it may also achieve efficacy via other pathways as well.

Rheumatoid Arthritis: Tofacitinib 5 mg twice daily or Tofacitinib 11 mg once daily. Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinib 5 mg once daily.

Psoriatic Arthritis (in combination with nonbiologic DMARDs): Tofacitinib 5 mg twice daily or Tofacitinib 11 mg once daily.  Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinib 5 mg once daily.

Ulcerative Colitis: Tofacitinib 10 mg twice daily for at least 8 weeks; then 5 or 10 mg twice daily. Discontinue after 16 weeks of 10 mg twice daily, if adequate therapeutic benefit is not achieved. Use the lowest effective dose to maintain response.

The most commonly reported adverse reactions during the first 3 months in controlled clinical trials (occurring in greater than or equal to 2% of patients treated with Tofacitinib monotherapy or in combination with DMARDs) were upper respiratory tract infections, headache, diarrhea and nasopharyngitis.

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

It is not known whether Tofacitinib 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 Tofacitinib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug for the mother

Pediatric Use: The safety and effectiveness of Tofacitinib in pediatric patients have not been established.

Geriatric Use: The frequency of serious infection among Tofacitinib-treated subjects 65 years of age and older was higher than among those under the age of 65. As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.

Moderate and severe renal impairment or moderate hepatic impairment: half the total daily dosage recommended for patients with normal renal and hepatic function.

Store below 30°C. Protect from light & moisture. Keep all medicines out of the reach of children.

Immunosuppressant

Rheumatoid arthritis is an autoimmune disease characterized by a dysregulation of pro-inflammatory cytokines including IL7, IL15, IL21, IL6, IFN-alpha, and IFN-beta. (3) Cytokines signalling results in tissue inflammation and joint damage by stimulating the recruitment and activation of immune cells via the janus kinase signalling pathway.

Tofacitinib is a partial and reversible janus kinase (JAK) inihibitor that will prevent the body from responding to cytokine signals. By inhibiting JAKs, tofacitinib prevents the phosphorylation and activation of STATs. The JAK-STAT signalling pathway is involved in the transcription of cells involved in hematopoiesis, and immune cell function. Tofacitinib works therapeutically by inhibiting the JAK-STAT pathway to decrease the inflammatory response. However, there is evidence to suggest that it may also achieve efficacy via other pathways as well.

Rheumatoid Arthritis: Tofacitinib 5 mg twice daily or Tofacitinib 11 mg once daily. Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinib 5 mg once daily.

Psoriatic Arthritis (in combination with nonbiologic DMARDs): Tofacitinib 5 mg twice daily or Tofacitinib 11 mg once daily.  Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinib 5 mg once daily.

Ulcerative Colitis: Tofacitinib 10 mg twice daily for at least 8 weeks; then 5 or 10 mg twice daily. Discontinue after 16 weeks of 10 mg twice daily, if adequate therapeutic benefit is not achieved. Use the lowest effective dose to maintain response.

The most commonly reported adverse reactions during the first 3 months in controlled clinical trials (occurring in greater than or equal to 2% of patients treated with Tofacitinib monotherapy or in combination with DMARDs) were upper respiratory tract infections, headache, diarrhea and nasopharyngitis.

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

It is not known whether Tofacitinib 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 Tofacitinib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug for the mother

Pediatric Use: The safety and effectiveness of Tofacitinib in pediatric patients have not been established.

Geriatric Use: The frequency of serious infection among Tofacitinib-treated subjects 65 years of age and older was higher than among those under the age of 65. As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.

Moderate and severe renal impairment or moderate hepatic impairment: half the total daily dosage recommended for patients with normal renal and hepatic function.

Store below 30°C. Protect from light & moisture. Keep all medicines out of the reach of children.

Combination Oral hypoglycemic preparations

This tablet combines two antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes. Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and Metformin HCl, a member of the biguanide class. Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated then GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, Sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. The pharmacologic mechanism of action of Metformin HCl is different from other classes of oral antihyperglycemic agents. Metformin HCl decreases hepatic glucose production, decreases intestinal absorption of glucose and increases peripheral glucose uptake and utilization.

Dose of film-coated tablet: The dosage of this tablet should be individualized on the basis of the patient's current regimen, efectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg sitagliptin and 2000 mg metformin. Initial combination therapy or maintenance of combination therapy should be individualized and left to the discretion of the health care provider.

This tablet should generally be given twice daily with meals, with gradual dose escalation, to reduce the gastrointestinal (GI) side efects due to metformin.

The starting dose of this tablet should be based on the patient’s current regimen. This tablet should be given twice daily with meals.

The recommended starting dose in patients not currently treated with metformin is 50 mg sitagliptin/500 mg metformin hydrochloride twice daily, with gradual dose escalation recommended to reduce gastrointestinal side efects associated with metformin.

The starting dose in patients already treated with metformin should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and the dose of metformin already being taken. For patients taking metformin 850 mg twice daily, the recommended starting dose of this tablet is 50 mg sitagliptin/1000 mg metformin hydrochloride twice daily.

No studies have been performed specifcally examining the safety and efcacy of Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP in patients previously treated with other oral antihyperglycemic agents and switched to Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.

Dose of extended-release tablet: Administer once daily with a meal preferably in the evening. Gradually escalate the dose to reduce the gastrointestinal side effects due to Metformin. May adjust the dosing based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of 100 mg Sitagliptin and 2000 mg Metformin extended-release. Maintain the same total daily dose of Sitagliptin and Metformin when changing between film-coated tablet and extended-release tablet, without exceeding the maximum recommended daily dose of 2000 mg Metformin extended-release.

Patients using two extended-release tablets (such as two 50/500 or two 50/1000 tablets) should take the two tablets together once daily. The 100 mg Sitagliptin/1000 mg Metformin HCI extended-release tablet should be taken as a single tablet once daily.

Patients treated with an insulin secretagogue or insulin: Co-administration of the combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.

The most common adverse reactions reported in ≥5% of patients simultaneously started on sitagliptin and metformin and more commonly than in patients treated with placebo were diarrhea, upper respiratory tract infection, and headache.

Adverse reactions reported in ≥5% of patients treated with sitagliptin in combination with sulfonylurea and metformin and more commonly than in patients treated with placebo in combination with sulfonylurea and metformin were hypoglycemia and headache.

Hypoglycemia was the only adverse reaction reported in ≥5% of patients treated with sitagliptin in combination with insulin and metformin and more commonly than in patients treated with placebo in combination with insulin and metformin.

Nasopharyngitis was the only adverse reaction reported in ≥5% of patients treated with sitagliptin monotherapy and more commonly than in patients given placebo.

The most common (>5%) adverse reactions due to initiation of metformin therapy are diarrhea, nausea/vomiting, fatulence, abdominal discomfort, indigestion, asthenia, and headache.

This tablet is contraindicated in patients with:

• Renal disease or renal dysfunction, e.g., as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females] or abnormal creatinine clearance which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
• History of a serious hypersensitivity reaction to this tablet or sitagliptin, such as anaphylaxis or angioedema.

This tablet should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function.

Lactic Acidosis-

• Lactic acidosis can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic insufciency, renal impairment, and acute congestive heart failure.
• Symptoms include malaise, myalgias, respiratory distress, increasing somnolence, and nonspecifc abdominal distress. Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate.
• If acidosis is suspected, discontinue this tablet and hospitalize the patient immediately.
• Regular monitoring of thyroid-stimulating hormone (TSH) levels is recommended in patients with hypothyroidism.
• Long-term treatment with metformin has been associated with a decrease in vitamin B12 serum levels which may cause peripheral neuropathy. Monitoring of the vitamin B12 level is recommended.

Others-

• Do not use this tablet in patients with hepatic disease.
• There have been postmarketing reports of acute renal failure, sometimes requiring dialysis. Before initiating this tablet and at least annually thereafter, assess renal function and verify as normal.
• There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue this tablet.
• Measure hematologic parameters annually.
• Warn patients against excessive alcohol intake.
• May need to discontinue this tablet and temporarily use insulin during periods of stress and decreased intake of fluids and food as may occur with fever, trauma, infection or surgery.
• Promptly evaluate patients previously controlled on this tablet who develop laboratory abnormalities or clinical illness for evidence of ketoacidosis or lactic acidosis.
• When used with an insulin secretagogue (e.g., sulfonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia.
• There have been postmarketing reports of serious allergic and hypersensitivity reactions in patients treated with sitagliptin (one of the components of this tablet ), such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. In such cases, promptly stop this tablet, assess for other potential causes, and institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes.
• There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP or any other anti-diabetic drug.

Cationic Drugs: Cationic drugs eliminated by renal tubular secretion: Use with caution.

Phenprocoumon: Metformin may decrease the anticoagulant effect of phenprocoumon. Therefore, close monitoring of the INR is recommended.

Levothyroxine: Levothyroxine can reduce the hypoglycemic effect of metformin. Monitoring of blood glucose levels is recommended, especially when thyroid hormone therapy is initiated or stopped, and the dosage of metformin must be adjusted if necessary.

Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women with Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP or its individual components; therefore, the safety of Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP in pregnant women is not known. This tablet should be used during pregnancy only if clearly needed.

It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this tablet is administered to a nursing woman.

Sitagliptin: In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy as indicated by the patient's clinical status. Sitagliptin is modestly dialyzable. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

Metformin hydrochloride: Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams. Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected. Pancreatitis may occur in the context of a metformin overdose.

Store below 25°C in a dry place away from light. Keep the medicines in a safe place, out of the reach of children. Do not use later than the date of expiry. To be dispensed only on the prescription of a registered physician.

Combination Oral hypoglycemic preparations

This tablet combines two antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes. Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and Metformin HCl, a member of the biguanide class. Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated then GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, Sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. The pharmacologic mechanism of action of Metformin HCl is different from other classes of oral antihyperglycemic agents. Metformin HCl decreases hepatic glucose production, decreases intestinal absorption of glucose and increases peripheral glucose uptake and utilization.

Dose of film-coated tablet: The dosage of this tablet should be individualized on the basis of the patient's current regimen, efectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg sitagliptin and 2000 mg metformin. Initial combination therapy or maintenance of combination therapy should be individualized and left to the discretion of the health care provider.

This tablet should generally be given twice daily with meals, with gradual dose escalation, to reduce the gastrointestinal (GI) side efects due to metformin.

The starting dose of this tablet should be based on the patient’s current regimen. This tablet should be given twice daily with meals.

The recommended starting dose in patients not currently treated with metformin is 50 mg sitagliptin/500 mg metformin hydrochloride twice daily, with gradual dose escalation recommended to reduce gastrointestinal side efects associated with metformin.

The starting dose in patients already treated with metformin should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and the dose of metformin already being taken. For patients taking metformin 850 mg twice daily, the recommended starting dose of this tablet is 50 mg sitagliptin/1000 mg metformin hydrochloride twice daily.

No studies have been performed specifcally examining the safety and efcacy of Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP in patients previously treated with other oral antihyperglycemic agents and switched to Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.

Dose of extended-release tablet: Administer once daily with a meal preferably in the evening. Gradually escalate the dose to reduce the gastrointestinal side effects due to Metformin. May adjust the dosing based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of 100 mg Sitagliptin and 2000 mg Metformin extended-release. Maintain the same total daily dose of Sitagliptin and Metformin when changing between film-coated tablet and extended-release tablet, without exceeding the maximum recommended daily dose of 2000 mg Metformin extended-release.

Patients using two extended-release tablets (such as two 50/500 or two 50/1000 tablets) should take the two tablets together once daily. The 100 mg Sitagliptin/1000 mg Metformin HCI extended-release tablet should be taken as a single tablet once daily.

Patients treated with an insulin secretagogue or insulin: Co-administration of the combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.

The most common adverse reactions reported in ≥5% of patients simultaneously started on sitagliptin and metformin and more commonly than in patients treated with placebo were diarrhea, upper respiratory tract infection, and headache.

Adverse reactions reported in ≥5% of patients treated with sitagliptin in combination with sulfonylurea and metformin and more commonly than in patients treated with placebo in combination with sulfonylurea and metformin were hypoglycemia and headache.

Hypoglycemia was the only adverse reaction reported in ≥5% of patients treated with sitagliptin in combination with insulin and metformin and more commonly than in patients treated with placebo in combination with insulin and metformin.

Nasopharyngitis was the only adverse reaction reported in ≥5% of patients treated with sitagliptin monotherapy and more commonly than in patients given placebo.

The most common (>5%) adverse reactions due to initiation of metformin therapy are diarrhea, nausea/vomiting, fatulence, abdominal discomfort, indigestion, asthenia, and headache.

This tablet is contraindicated in patients with:

• Renal disease or renal dysfunction, e.g., as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females] or abnormal creatinine clearance which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
• History of a serious hypersensitivity reaction to this tablet or sitagliptin, such as anaphylaxis or angioedema.

This tablet should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function.

Lactic Acidosis-

• Lactic acidosis can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic insufciency, renal impairment, and acute congestive heart failure.
• Symptoms include malaise, myalgias, respiratory distress, increasing somnolence, and nonspecifc abdominal distress. Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate.
• If acidosis is suspected, discontinue this tablet and hospitalize the patient immediately.
• Regular monitoring of thyroid-stimulating hormone (TSH) levels is recommended in patients with hypothyroidism.
• Long-term treatment with metformin has been associated with a decrease in vitamin B12 serum levels which may cause peripheral neuropathy. Monitoring of the vitamin B12 level is recommended.

Others-

• Do not use this tablet in patients with hepatic disease.
• There have been postmarketing reports of acute renal failure, sometimes requiring dialysis. Before initiating this tablet and at least annually thereafter, assess renal function and verify as normal.
• There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue this tablet.
• Measure hematologic parameters annually.
• Warn patients against excessive alcohol intake.
• May need to discontinue this tablet and temporarily use insulin during periods of stress and decreased intake of fluids and food as may occur with fever, trauma, infection or surgery.
• Promptly evaluate patients previously controlled on this tablet who develop laboratory abnormalities or clinical illness for evidence of ketoacidosis or lactic acidosis.
• When used with an insulin secretagogue (e.g., sulfonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia.
• There have been postmarketing reports of serious allergic and hypersensitivity reactions in patients treated with sitagliptin (one of the components of this tablet ), such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. In such cases, promptly stop this tablet, assess for other potential causes, and institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes.
• There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP or any other anti-diabetic drug.

Cationic Drugs: Cationic drugs eliminated by renal tubular secretion: Use with caution.

Phenprocoumon: Metformin may decrease the anticoagulant effect of phenprocoumon. Therefore, close monitoring of the INR is recommended.

Levothyroxine: Levothyroxine can reduce the hypoglycemic effect of metformin. Monitoring of blood glucose levels is recommended, especially when thyroid hormone therapy is initiated or stopped, and the dosage of metformin must be adjusted if necessary.

Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women with Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP or its individual components; therefore, the safety of Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP in pregnant women is not known. This tablet should be used during pregnancy only if clearly needed.

It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this tablet is administered to a nursing woman.

Sitagliptin: In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy as indicated by the patient's clinical status. Sitagliptin is modestly dialyzable. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

Metformin hydrochloride: Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams. Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected. Pancreatitis may occur in the context of a metformin overdose.

Store below 25°C in a dry place away from light. Keep the medicines in a safe place, out of the reach of children. Do not use later than the date of expiry. To be dispensed only on the prescription of a registered physician.

Dipeptidyl Peptidase-4 (DPP-4) inhibitor

Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. Concentrations of the active intact hormones are increased by Sitagliptin, thereby increasing and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, Sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.

The recommended dose of sitagliptin is 50 mg twice a day and 100 mg once daily. Sitagliptin can be taken with or without food.

The most common adverse reactions include headache, upper respiratory tract infection and nasopharyngitis. Hypoglycemia may occur in patients treated with the combination to Sitagliptin and sulfonylurea and add on to insulin.

History of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema.

If pancreatitis is suspected, sitagliptin should promptly be discontinued and appropriate management should be initiated.

Use in Patients with Renal Insufficiency: Dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with ESRD requiring hemodialysis or peritoneal dialysis.

Use with medications known to cause Hypoglycemia: When sitagliptin is used in combination therapy dosage adjustment of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.

Hypersensitivity Reactions: There have been post-marketing reports of serious hypersensitivity reactions in patients treated with sitagliptin. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. If a hypersensitivity reaction is suspected, discontinue sitagliptin, assess for other potential causes for the event, and institute alternative treatment for diabetes.

Effects of sitagliptin on other Drugs: Sitagliptin did not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptive.

Digoxin: Sitagliptin slightly increases the mean of Digoxin concentration. However, no dose adjustment of either drug is required.

Pregnancy Category B. Reproduction studies have been performed in rats and rabbits. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Sitagliptin is secreted in the milk of lactating rats at milk to plasma ratio of 4:1. It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when sitagliptin is administered to a nursing woman.

Pediatric Use: Safety and effectiveness of sitagliptin in pediatric patients under 18 years of age have not been established.

Geriatric Use: This drug is known to be substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly, and it may be useful to assess renal function in these patients prior to initiating dosing and periodically thereafter.

For patients with mild renal insufciency: (CrCl <50 ml/min or serum creatinine levels of <1.7 mg/DL in men and <1.5 mg/DL in women), no dosage adjustment for sitagliptin is required.

For patients with moderate renal insufciency: (CrCl <30 to <50 mL/min, or serum creatinine levels of >1.7 to <3.0 mg/dL in men and >1.5 to <2.5 mg/dL in women), the dose of sitagliptin is 50 mg once daily.

For patients with severe renal insufficiency: (CrCl <30 mL/min or serum creatinine levels of >3.0 mg/dL in men and 2.5 mg/dL in women) or with end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis, the dose of sitagliptin is 25 mg once daily. Sitagliptin may be administered without regard to the limiting of hemodialysis.

During controlled clinical trials in healthy subjects, single doses of up to 800 mg Sitagliptin were administered. Maximal mean increases in QTc of 8.0 msec were observed in one study at a dose of 800 mg Sitagliptin, a mean effect that is not considered clinically important. There is no experience with doses above 800 mg in clinical studies. In Phase I multiple-dose studies, there were no dose-related clinical adverse reactions observed with Sitagliptin with doses of up to 600 mg per day for periods of up to 10 days and 400 mg per day for up to 28 days.

In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy as dictated by the patient's clinical status. Sitagliptin is modestly dialyzable. In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour hemodialysis session. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

Store below 25°C in a dry place away from light. Keep the medicines in a safe place, out of the reach of children. Do not use later than the date of expiry. To be dispensed only on the prescription of a registered physician

Dipeptidyl Peptidase-4 (DPP-4) inhibitor

Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. Concentrations of the active intact hormones are increased by Sitagliptin, thereby increasing and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, Sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.

The recommended dose of sitagliptin is 50 mg twice a day and 100 mg once daily. Sitagliptin can be taken with or without food.

The most common adverse reactions include headache, upper respiratory tract infection and nasopharyngitis. Hypoglycemia may occur in patients treated with the combination to Sitagliptin and sulfonylurea and add on to insulin.

History of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema.

If pancreatitis is suspected, sitagliptin should promptly be discontinued and appropriate management should be initiated.

Use in Patients with Renal Insufficiency: Dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with ESRD requiring hemodialysis or peritoneal dialysis.

Use with medications known to cause Hypoglycemia: When sitagliptin is used in combination therapy dosage adjustment of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.

Hypersensitivity Reactions: There have been post-marketing reports of serious hypersensitivity reactions in patients treated with sitagliptin. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. If a hypersensitivity reaction is suspected, discontinue sitagliptin, assess for other potential causes for the event, and institute alternative treatment for diabetes.

Effects of sitagliptin on other Drugs: Sitagliptin did not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptive.

Digoxin: Sitagliptin slightly increases the mean of Digoxin concentration. However, no dose adjustment of either drug is required.

Pregnancy Category B. Reproduction studies have been performed in rats and rabbits. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Sitagliptin is secreted in the milk of lactating rats at milk to plasma ratio of 4:1. It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when sitagliptin is administered to a nursing woman.

Pediatric Use: Safety and effectiveness of sitagliptin in pediatric patients under 18 years of age have not been established.

Geriatric Use: This drug is known to be substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly, and it may be useful to assess renal function in these patients prior to initiating dosing and periodically thereafter.

For patients with mild renal insufciency: (CrCl <50 ml/min or serum creatinine levels of <1.7 mg/DL in men and <1.5 mg/DL in women), no dosage adjustment for sitagliptin is required.

For patients with moderate renal insufciency: (CrCl <30 to <50 mL/min, or serum creatinine levels of >1.7 to <3.0 mg/dL in men and >1.5 to <2.5 mg/dL in women), the dose of sitagliptin is 50 mg once daily.

For patients with severe renal insufficiency: (CrCl <30 mL/min or serum creatinine levels of >3.0 mg/dL in men and 2.5 mg/dL in women) or with end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis, the dose of sitagliptin is 25 mg once daily. Sitagliptin may be administered without regard to the limiting of hemodialysis.

During controlled clinical trials in healthy subjects, single doses of up to 800 mg Sitagliptin were administered. Maximal mean increases in QTc of 8.0 msec were observed in one study at a dose of 800 mg Sitagliptin, a mean effect that is not considered clinically important. There is no experience with doses above 800 mg in clinical studies. In Phase I multiple-dose studies, there were no dose-related clinical adverse reactions observed with Sitagliptin with doses of up to 600 mg per day for periods of up to 10 days and 400 mg per day for up to 28 days.

In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy as dictated by the patient's clinical status. Sitagliptin is modestly dialyzable. In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour hemodialysis session. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

Store below 25°C in a dry place away from light. Keep the medicines in a safe place, out of the reach of children. Do not use later than the date of expiry. To be dispensed only on the prescription of a registered physician

Fourth generation Cephalosporins

Cephalosporins are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins). Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins (PBPs).

Cefepime should be administered intravenously over approximately 30 minutes.

• Moderate to Severe Pneumonia due to S. pneumoniae, *P. aeruginosa, K. pneumoniae, or Enterobacter species: 1-2 gm IV 12 hourly for 10 days.
• Empiric therapy for febrile neutropenic patients: 2 gm IV 8 hourly for 7** days.
• Mild to Moderate Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E. coli, K. pneumoniae, or P. mirabilis*: 0.5-1 gm IV/IM*** 12 hourly for 7-10 days.
• Severe Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E. coli or K. pneumoniae*: 2 gm IV 12 hourly for 10 days.
• Moderate to Severe Uncomplicated Skin and Skin Structure Infections due to S. aureus or S. pyogenes: 2 gm IV 12 hourly for 10 days.
• Complicated Intra-abdominal Infections (used in combination with metronidazole) caused by E. coli, viridans group streptococci, P. aeruginosa, K. pneumoniae, Enterobacter species, or B. fragilis: 2 gm IV 12 hourly for 7-10 days.

Note:
*including cases associated with concurrent bacteremia.
**or until resolution of neutropenia. In patients whose fever resolves but who remain neutropenic for more than 7 days, the need for continued antimicrobial therapy should be re evaluated frequently.
*** IM route of administration is indicated only for mild to moderate, uncomplicated or complicated UTls due to E. coli when the IM route is considered to be a more appropriate route of drug administration.

Cefepime is contraindicated in patients who have shown immediate hypersensitivity reactions to cefepime or the cephalosporin class of antibiotics, penicillin, or other betalactum antibiotics.

Cefepime is contraindicated in patients who have shown immediate hypersensitivity reactions to cefepime or the cephalosporin class of antibiotics, penicillin, or other betalactum antibiotics.

Renal function should be monitored carefully if high doses of aminoglycosides are to be administered with Cefepime because of the increased potential of nephrotoxicity and ototoxicity of aminoglycoside antibiotics. Nephrotoxicity has been reported following concomitant administration of other cephalosporins with potent diuretics such as furosemide.

Pregnancy Category B. There are, however, no adequate and well-controlled studies of cefepime use in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Cefepime is excreted in human breast milk in very low concentrations (0.5 pg/ml). Caution should be exercised when cefepime is administered to a nursing woman.

Pediatric Use (2 months up to 16 years): The maximum dose for pediatric patients should not exceed the recommended adult dose. The usual recommended dosage in pediatric patients up to 40 kg in weight for uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, and pneumonia is 50 mg/kg/dose, administered every 12 hours (50 mg/kg/dose, every 8 hours for febrile neutropenic patients), for durations as given above.

Geriatric Use: Serious adverse events have occurred in geriatric patients with renal insufficiency given unadjusted doses of cefepime, including life-threatening or fatal occurrences of the following: encephalopathy, myoclonus, and seizures. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored.

Impaired Hepatic Function: No adjustment is necessary for patients with impaired hepatic function.

Impaired Renal Function: In patients with impaired renal function (creatinine clearance<60 ml/min), the dose of Cefepime should be adjusted to compensate for the slower rate of renal elimination.

Patients who receive an overdose should be carefully observed and given supportive treatment. In the presence of renal insufficiency, hemodialysis, not peritoneal dialysis, is recommended to aid the removal of cefepime from the body. Accidental overdosing has occurred when large doses were given to patients with impaired renal function. Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and neuromuscular excitability.

For IV the resulting solution should be injected directly into the vein over a period of three to five minutes or injected into the tubing of an administration set while the patient is receiving a compatible IV fluid.

Intravenous: Cefepime is compatible with Sterile Water for Injection. It is also compatible at concentrations between 1 mg/ml and 40 mg/ml with the following IV infusion fluids: 0.9% Sodium Chloride Injection, 5% and 10% Dextrose Injection, M/6 Sodium Lactate Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, Lactated Ringers and 5% Dextrose Injection.

Intramuscular: Cefepime is compatible with the following diluent such as: Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, Sterile Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol or 0.5% or 1% Lidocaine Hydrochloride.

500 mg (IV) vials for intravenous administration:

• Amount of WFI to be added: 5 ml
• Approximate available volume: 5.6 ml

500 mg (IM) vials for intramuscular administration:

• Amount of WFI to be added: 1.3 ml
• Approximate available volume: 1.8 ml 

1 gm (IV) vials for Intravenous administration:

• Amount of WFI to be added: 10 ml
• Approximate available volume: 11.3 ml

1 gm (IM) vials for intramuscular administration:

• Amount of WFI to be added: 2.4 ml
• Approximate available volume: 3.6 ml

2 gm (IV) vials for Intravenous administration:

• Amount of WFI to be added: 10 ml
• Approximate available volume: 12.5 ml 

Do not use later than the date of expiry. Keep all medicines out of the reach of children. To be dispensed only on the prescription of a registered physician.

Empagliflozin is indicated in:

• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• To reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors

Empagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia, assists weight loss, and reduces blood pressure.

The recommended dose of Empagliflozin is 10 mg once daily, taken in the morning, with or without food. In patients tolerating Empagliflozin, the dose may be increased to 25 mg once daily. In patients with volume depletion, correcting this condition prior to initiation of Empagliflozin is recommended.

The most common adverse reactions associated with Empagliflozin are urinary tract infections and female genital mycotic infections. Others common side effects includes dehydration, hypotension, weakness, dizziness and increased thirstiness.

Empagliflozin is contraindicated in patients with history of serious hypersensitivity reaction to Empagliflozin or any of its ingredients, severe renal impairment, end-stage renal disease, or dialysis.

Assessment of renal function is recommended prior to initiation of Empagliflozin and periodically thereafter. Empagliflozin should not initiated in patients with an eGFR less than 45 ml/min/1.73 m². No dose adjustment is needed in patients with an eGFR greater than or equal to 45 ml/min/1.73 m².

Diuretics: Co-administration of Empagliflozin with diuretics resulted in increased urine volume. 

Insulin or Insulin Secretagogues: Co-administration of Empagliflozin with insulin or insulin secretagogues increases the risk for hypoglycemia. 

Positive Urine Glucose Test: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control. 

Interference with 1,5-anhydroglucitol (1,5-AG) Assay: Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

There are no adequate and well-controlled studies of Empagliflozin in pregnant women. Empagliflozin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if Empagliflozin is excreted in human milk. It is not recommended when breastfeeding.

In the event of an overdose with Empagliflozin the usual supportive measures (e.g., remove unabsorbed material from the gastrointestinal tract, perform clinical monitoring, and institute supportive treatment) should be employed. Removal of Empagliflozin by hemodialysis has not been studied.

Keep in a cool & dry place (below 30° C), protected from light & moisture. Keep out of the reach of children.

Empagliflozin is indicated in:

• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• To reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors

Empagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia, assists weight loss, and reduces blood pressure.

The recommended dose of Empagliflozin is 10 mg once daily, taken in the morning, with or without food. In patients tolerating Empagliflozin, the dose may be increased to 25 mg once daily. In patients with volume depletion, correcting this condition prior to initiation of Empagliflozin is recommended.

The most common adverse reactions associated with Empagliflozin are urinary tract infections and female genital mycotic infections. Others common side effects includes dehydration, hypotension, weakness, dizziness and increased thirstiness.

Empagliflozin is contraindicated in patients with history of serious hypersensitivity reaction to Empagliflozin or any of its ingredients, severe renal impairment, end-stage renal disease, or dialysis.

Assessment of renal function is recommended prior to initiation of Empagliflozin and periodically thereafter. Empagliflozin should not initiated in patients with an eGFR less than 45 ml/min/1.73 m². No dose adjustment is needed in patients with an eGFR greater than or equal to 45 ml/min/1.73 m².

Diuretics: Co-administration of Empagliflozin with diuretics resulted in increased urine volume. 

Insulin or Insulin Secretagogues: Co-administration of Empagliflozin with insulin or insulin secretagogues increases the risk for hypoglycemia. 

Positive Urine Glucose Test: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control. 

Interference with 1,5-anhydroglucitol (1,5-AG) Assay: Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

There are no adequate and well-controlled studies of Empagliflozin in pregnant women. Empagliflozin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if Empagliflozin is excreted in human milk. It is not recommended when breastfeeding.

In the event of an overdose with Empagliflozin the usual supportive measures (e.g., remove unabsorbed material from the gastrointestinal tract, perform clinical monitoring, and institute supportive treatment) should be employed. Removal of Empagliflozin by hemodialysis has not been studied.

Keep in a cool & dry place (below 30° C), protected from light & moisture. Keep out of the reach of children.

Empagliflozin is indicated in:

• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• To reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors

Empagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia, assists weight loss, and reduces blood pressure.

The recommended dose of Empagliflozin is 10 mg once daily, taken in the morning, with or without food. In patients tolerating Empagliflozin, the dose may be increased to 25 mg once daily. In patients with volume depletion, correcting this condition prior to initiation of Empagliflozin is recommended.

The most common adverse reactions associated with Empagliflozin are urinary tract infections and female genital mycotic infections. Others common side effects includes dehydration, hypotension, weakness, dizziness and increased thirstiness.

Empagliflozin is contraindicated in patients with history of serious hypersensitivity reaction to Empagliflozin or any of its ingredients, severe renal impairment, end-stage renal disease, or dialysis.

Assessment of renal function is recommended prior to initiation of Empagliflozin and periodically thereafter. Empagliflozin should not initiated in patients with an eGFR less than 45 ml/min/1.73 m². No dose adjustment is needed in patients with an eGFR greater than or equal to 45 ml/min/1.73 m².

Diuretics: Co-administration of Empagliflozin with diuretics resulted in increased urine volume. 

Insulin or Insulin Secretagogues: Co-administration of Empagliflozin with insulin or insulin secretagogues increases the risk for hypoglycemia. 

Positive Urine Glucose Test: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control. 

Interference with 1,5-anhydroglucitol (1,5-AG) Assay: Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

There are no adequate and well-controlled studies of Empagliflozin in pregnant women. Empagliflozin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if Empagliflozin is excreted in human milk. It is not recommended when breastfeeding.

In the event of an overdose with Empagliflozin the usual supportive measures (e.g., remove unabsorbed material from the gastrointestinal tract, perform clinical monitoring, and institute supportive treatment) should be employed. Removal of Empagliflozin by hemodialysis has not been studied.

Keep in a cool & dry place (below 30° C), protected from light & moisture. Keep out of the reach of children.

Empagliflozin is indicated in:

• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• To reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors

Empagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia, assists weight loss, and reduces blood pressure.

The recommended dose of Empagliflozin is 10 mg once daily, taken in the morning, with or without food. In patients tolerating Empagliflozin, the dose may be increased to 25 mg once daily. In patients with volume depletion, correcting this condition prior to initiation of Empagliflozin is recommended.

The most common adverse reactions associated with Empagliflozin are urinary tract infections and female genital mycotic infections. Others common side effects includes dehydration, hypotension, weakness, dizziness and increased thirstiness.

Empagliflozin is contraindicated in patients with history of serious hypersensitivity reaction to Empagliflozin or any of its ingredients, severe renal impairment, end-stage renal disease, or dialysis.

Assessment of renal function is recommended prior to initiation of Empagliflozin and periodically thereafter. Empagliflozin should not initiated in patients with an eGFR less than 45 ml/min/1.73 m². No dose adjustment is needed in patients with an eGFR greater than or equal to 45 ml/min/1.73 m².

Diuretics: Co-administration of Empagliflozin with diuretics resulted in increased urine volume. 

Insulin or Insulin Secretagogues: Co-administration of Empagliflozin with insulin or insulin secretagogues increases the risk for hypoglycemia. 

Positive Urine Glucose Test: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control. 

Interference with 1,5-anhydroglucitol (1,5-AG) Assay: Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

There are no adequate and well-controlled studies of Empagliflozin in pregnant women. Empagliflozin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if Empagliflozin is excreted in human milk. It is not recommended when breastfeeding.

In the event of an overdose with Empagliflozin the usual supportive measures (e.g., remove unabsorbed material from the gastrointestinal tract, perform clinical monitoring, and institute supportive treatment) should be employed. Removal of Empagliflozin by hemodialysis has not been studied.

Keep in a cool & dry place (below 30° C), protected from light & moisture. Keep out of the reach of children.

Combination Oral hypoglycemic preparations

Empagliflozin is an inhibitor of Sodium-Glucose Co-Transporter 2 (SGLT2). SGLT2 is the predominant transporter, responsible for reabsorption of glucose from the kidney back into the circulation. By inhibiting SGLT2, Empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose and thereby increases urinary glucose excretion.

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

The dosage should be individualized based on effectiveness and tolerability. Take this combination twice daily with meals. Dose escalation should be gradual to reduce the gastrointestinal side effects due to Metformin Hydrochloride. Maximum recommended daily dose of Metformin Hydrochloride is 2000 mg and Empagliflozin is 25 mg.

Recommended individualized starting dose:

• In patients on Metformin Hydrochloride, switch to this combination containing Empagliflozin 5 mg with a similar total daily dose of Metformin Hydrochloride.
• In patients on Empagliflozin, switch to this combination containing Metformin Hydrochloride 500 mg with a similar total daily dose of Empagliflozin.
• In patients already treated with Empagliflozin and Metformin Hydrochloride separately switch to this combination containing the same total daily doses of each component.
• In patients with volume depletion not previously treated with Empagliflozin, correct this condition before initiating this combination.

Renal impaired patient: Assess renal function before initiating this combination. In patients with an eGFR below 45 mL/min/1.73 m² is contraindicated.

Pediatric patients under 18 years of age: Safety and effectiveness in pediatric patients under 18 years of age have not been established.

Most common adverse reactions associated with Empagliflozin (5% or greater incidence) were urinary tract infection and female genital mycotic infections. Most common adverse reactions associated with Metformin (>5%) are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache. The following important adverse reactions are given below:

• Very common: Hypoglycemia (when used with sulphonylurea or insulin), Gastrointestinal symptoms
• Common: Vaginal moniliasis, vulvovaginitis, balanitis and other genital infection. Urinary tract infection (including pyelonephritis and urosepsis), thirst, taste disturbance, pruritus (generalised), rash, Increased urination, serum lipids increased
• Uncommon: Volume depletion, urticaria, dysuria, blood creatinine increased/Glomerular filtration rate decreased, Haematocrit increased
• Rare: Diabetic ketoacidosis.

Lactic Acidosis: Postmarketing cases of Metformin Hydrochloride-associated lactic acidosis. If lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of this combination.

Hypotension: Before initiating this combination assess and correct volume status in patients with renal impairment, the elderly, in patients with low systolic blood pressure, and in patients on diuretics. Monitor for signs and symptoms of hypotension after initiating therapy and increase monitoring in clinical situations where volume contraction is expected.

Ketoacidosis: Before initiating this combination assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue this combination, evaluate and treat promptly.

Acute kidney injury & impairment in renal function: Consider temporarily discontinuing this combination in settings of reduced oral intake or fluid losses. If acute kidney injury occurs, discontinue this combination promptly and institute treatment.

Urosepsis, Pyelonephritis, Fournier’s gangrene & Genital mycotic infections: Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated.

Hypoglycemia: Consider lowering the dose of insulin secretagogue or insulin to reduce the risk of hypoglycemia when initiating this combination.

Vitamin B12 Deficiency: Metformin Hydrochloride may lower vitamin B12 levels. Monitor hematologic parameters annually.

Increased LDL-C: Monitor and treat as appropriate.

Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with this combination.

Diuretics: Co-administration of Empagliflozin with diuretics resulted in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.

Insulin or Insulin Secretagogues: Co-administration of Empagliflozin with insulin or insulin secretagogues increases the risk for hypoglycemia.

Positive Urine Glucose Test: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

Drugs that Reduce Metformin Clearance: Drugs that reduce Metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of Metformin.

Carbonic Anhydrase Inhibitors: Carbonic anhydrase inhibitors may increase risk of lactic acidosis.

Drugs Affecting Glycemic Control: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid produce hoperglycemia. When such drugs are administered to a patient receiving Empagliflozin and Metformin combination, the patient should be closely observed to maintain adequate glycemic control. When such drugs are withdrawn from a patient receiving Empagliflozin and Metformin combination, the patient should be observed closely for hypoglycemia.

Alcohol: Alcohol can potentiate the effect of Metformin on lactate metabolism. Warn patients against excessive alcohol intake.

Advise females of the potential risk to a fetus especially during the second and third trimesters. This is not recommended when breastfeeding.

In controlled clinical studies single doses of up to 800 mg Empagliflozin (equivalent to 32-times the highest recommended daily dose) in healthy volunteers and multiple daily doses of up to 100 mg Empagliflozin (equivalent to 4-times the highest recommended daily dose) in patients with type 2 diabetes did not show any toxicity. Hypoglycaemia has not been seen with Metformin doses of up to 85 g, although lactic acidosis has occurred in such circumstances. Lactic acidosis is a medical emergency and must be treated in hospital. In the event of an overdose, treatment should be initiated as appropriate to the patient's clinical status. The most effective method to remove lactate and Metformin is haemodialysis. The removal of Empagliflozin by haemodialysis has not been studied

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

Herbal and Nutraceuticals

1-2 Capsules 2-3 times daily or as directed by the registered physician.

No significant side effects have been observed in proper dosage.

It is contraindicated in pregnancy & lactation.

This drug should be used with caution in patient with ulceration in stomach and colon due to the secretion of gastric juice.

There has no information for Chirata Interactions.

Keep out of reach of children. Keep away from direct sunlight. Keep store in a cool and dry place.

Lidocaine Injection is indicated-

• As a local anaesthetic for use in infiltration blockade and intravenous regional analgesia.
• For the prevention and treatment of ventricular tachyarrhythmias

Local & Surface anesthesia

Lidocaine acts mainly by inhibiting sodium influx through sodium specific ion channels in the neuronal cell membrane, in particular the so called voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Lidocaine binds more readily to sodium channels in activated state, thus onset of neuronal blockade is faster in neurons that are rapidly firing. This is referred to as state dependent blockade.

The dosage is adjusted according to the response of the patient and site of administration.

Adult: For healthy adults, the maximum individual dose should not exceed 4.5mg/kg of body weight and in general it is recommended that the maximum total dose does not exceed 300 mg. Recommended doses given in the below serve only as a guide to the amount of anaesthetic required for most routine procedures.

Infiltration-

• Percutaneous: Total dose 5-300 mg
• Intravenous regional: Total dose 50-300 mg

Peripheral Nerve Blocks-

• Brachial: Total dose 225-300 mg
• Dental: Total dose 20-100 mg
• Intercostal: Total dose 30 mg
• Paravertebral: Total dose 30-50 mg

Pudenal (each side): 

• Paracervical Obstetrical analgesia: Total dose 100 mg

Sympathetic Nerve Blocks

• Cervical: Total dose 50 mg
• Lumbar: Total dose 50-100 mg

Central Neural Blocks

• Epidural: Total dose 200-300 mg [Dose determined by number of dermatomes to be anesthetized (2-3 mL/dermatome) periodically.]
• Thoracic: Total dose 200-300 mg

Lumbar

• Analgesia: Total dose 250-300 mg
• Anesthesia: Total dose 200-300 mg

Caudal

• Obstetrical analgesia: Total dose 200-300 mg
• Surgical anesthesia: Total dose 225-300 mg.

Antiarrhythmic treatment: An intravenous dose of 1 mg.kg^-1 may be given over 2 min and repeated after 5 min, but giving an infusion of 2-4 mg.min^-1 to produce a plasma level of 2-4 mg. l^-1 is a more satisfactory technique. To avoid a long delay in achieving a steady state, a loading dose of approximately 1 mg.kg^-1 is usually given intravenously over 2 min at the outset.

In common with other local anaesthetics, adverse reactions to lidocaine are rare and are usually the result of excessively high blood concentrations due to inadvertent intravascular injection, excessive dosage, rapid absorption or occasionally to hypersensitivity, idiosyncracy or diminished tolerance on the part of the patient. In such circumstances systemic effects occur involving the central nervous system and/or the cardiovascular system. CNS reactions are excitatory and/or depressant and may be characterized by nervousness, dizziness, blurred vision and tremors, followed by drowsiness, convulsions, unconsciousness and possibly respiratory arrest. Cardiovascular reactions are hypotension, myocardial depression, bradycardia and possibly cardiac arrest. Allergic reactions are extremely rare. They may be characterized by cutaneous lesions, urticaria, oedema or anaphylactoid reactions.

Known hypersensitivity to anaesthetics of the amide type.

Lidocaine for infiltration and nerve block should be employed only by clinicians who are well versed in diagnosis and management of dose-related toxicity. The safety and effectiveness of lidocaine depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Standard text books should be consulted for specific techniques and precautions for various regional anaesthetic procedures. Resuscitative equipment, oxygen and other resuscitative drugs should be available for immediate use.

It should be used cautiously in patients with epilepsy, impaired cardiac conduction, bradycardia, impaired respiratory function and in patients with impaired hepatic function, if the dose or site of administration is likely to result in high blood levels. The effect of local anaesthetics may be reduced if an injection is made into an inflamed or infected area. Repeated doses of lidocaine may cause significant increases in blood levels with each repeated dose because of slow accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Careful and constant monitoring of cardiovascular and respiratory vital signs and the patient's state of consciousness should be accomplished after each local anaesthetic injection.

Cimetidine can impair the metabolism of lidocaine absorbed into the circulation. Elimination will be delayed and the risk of adverse reactions increased. Significant increases in plasma lidocaine concentrations have occurred during concomitant therapy with beta blockers such as propranolol, metoprolol or nadolol. It prolongs the duration of action of suxamethonium.

Although there is no evidence from animal studies of harm to the foetus, as with all drugs, it should not be given during early pregnancy unless the benefits are considered to outweigh the risks. Caution should be exercised when it is administered to a nursing woman.

Dosages in children should be reduced, commensurate with age, body-weight and physical condition. Elderly patients may be more sensitive to systemic effects and may require dose reductions.

Keep below 25°C temperature, away from light & moisture. Keep out of the reach of children.

Lidocaine Jelly is indicated for-

• Surface anaesthesia of the male and female urethra
• Topical treatment of painful urethritis
• Anaesthetic lubrication for endotracheal intubation
• Adequate analgesia in endoscopy.

Local & Surface anesthesia

Lidocaine acts mainly by inhibiting sodium influx through sodium specific ion channels in the neuronal cell membrane, in particular the so called voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Lidocaine binds more readily to sodium channels in activated state, thus onset of neuronal blockade is faster in neurons that are rapidly firing. This is referred to as state dependent blockade.

Urethral anaesthesia:

• Surface anaesthesia of the male adult urethra: For adequate analgesia in males 400 mg is required.
• Surface anaesthesia of the female adult urethra: Instil 100-200 mg in small portions to fill the whole urethra. In order to obtain adequate anaesthesia, several minutes should be allowed prior to perform in the urological procedure.

Lubrication for endotracheal intubation: 100 mg applied on the surface of the tube just prior to insertion. Care should be taken to avoid introducing the product into the lumen of the tube.

Endoscopy: Instillation of 200-400 mg is recommended for adequate analgesia and a small amount should be applied on the instrument for lubrication. Debilitated, elderly patients and children should be given doses commensurate with their age and physical condition.

Note: The applicator is sterilized for 5 minutes in boiling water, cooled and attached to the tube. The jelly is instilled slowly as required. The applicator should be detached after each use and keep the tube tightly closed.

Nervousness, dizziness, blurred vision, tremors, drowsiness, convulsions, unconsciousness, respiratory arrest, hypotension, myocardial depression, bradycardia, cardiac arrest and anaphylactic reactions (cutaneous lesion, urticaria, oedema).

It is contraindicated in patients with a known history of hypersensitivity of local anaesthetics of the amide type.

Absorption from wound surfaces and mucous membranes is relatively high, especially in the bronchial tree. Lidocaine Jelly should be used with caution in patients with traumatised mucosa and/or sepsis in the region of the proposed application.

If the dose or site of administration is likely to result in high blood levels, Lidocaine, in common with other local anaesthetics, should be used cautiously in patients with epilepsy, impaired cardiac condition, bradycardia, impaired hepatic function and in severe shock.

The use of oropharyngeal topical anaesthetic agents may interfere with swallowing and thus enhance the danger of aspiration. This is particularly important in children because of their frequency of eating. Numbness of the tongue or buccal mucosa may increase the danger of biting trauma.

Lidocaine should be used with caution in patients receiving antiarrhythmic drugs, such as tocainide since the toxic effects are additive.

There is no, or inadequate, evidence of safety of the drug in human pregnancy but it has been in wide use for many years without apparent ill consequence. If drug therapy is needed in pregnancy, this drug can be used if there is no safer alternative. Lidocaine enters the mother's milk, but in such small quantities that there is generally no risk of affecting the child at therapeutic dose levels.

Store below 25°C in a dry place, away from light.

Lidocaine Injection is indicated-

• As a local anaesthetic for use in infiltration blockade and intravenous regional analgesia.
• For the prevention and treatment of ventricular tachyarrhythmias

Local & Surface anesthesia

Lidocaine acts mainly by inhibiting sodium influx through sodium specific ion channels in the neuronal cell membrane, in particular the so called voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Lidocaine binds more readily to sodium channels in activated state, thus onset of neuronal blockade is faster in neurons that are rapidly firing. This is referred to as state dependent blockade.

The dosage is adjusted according to the response of the patient and site of administration.

Adult: For healthy adults, the maximum individual dose should not exceed 4.5mg/kg of body weight and in general it is recommended that the maximum total dose does not exceed 300 mg. Recommended doses given in the below serve only as a guide to the amount of anaesthetic required for most routine procedures.

Infiltration-

• Percutaneous: Total dose 5-300 mg
• Intravenous regional: Total dose 50-300 mg

Peripheral Nerve Blocks-

• Brachial: Total dose 225-300 mg
• Dental: Total dose 20-100 mg
• Intercostal: Total dose 30 mg
• Paravertebral: Total dose 30-50 mg

Pudenal (each side): 

• Paracervical Obstetrical analgesia: Total dose 100 mg

Sympathetic Nerve Blocks

• Cervical: Total dose 50 mg
• Lumbar: Total dose 50-100 mg

Central Neural Blocks

• Epidural: Total dose 200-300 mg [Dose determined by number of dermatomes to be anesthetized (2-3 mL/dermatome) periodically.]
• Thoracic: Total dose 200-300 mg

Lumbar

• Analgesia: Total dose 250-300 mg
• Anesthesia: Total dose 200-300 mg

Caudal

• Obstetrical analgesia: Total dose 200-300 mg
• Surgical anesthesia: Total dose 225-300 mg.

Antiarrhythmic treatment: An intravenous dose of 1 mg.kg^-1 may be given over 2 min and repeated after 5 min, but giving an infusion of 2-4 mg.min^-1 to produce a plasma level of 2-4 mg. l^-1 is a more satisfactory technique. To avoid a long delay in achieving a steady state, a loading dose of approximately 1 mg.kg^-1 is usually given intravenously over 2 min at the outset.

In common with other local anaesthetics, adverse reactions to lidocaine are rare and are usually the result of excessively high blood concentrations due to inadvertent intravascular injection, excessive dosage, rapid absorption or occasionally to hypersensitivity, idiosyncracy or diminished tolerance on the part of the patient. In such circumstances systemic effects occur involving the central nervous system and/or the cardiovascular system. CNS reactions are excitatory and/or depressant and may be characterized by nervousness, dizziness, blurred vision and tremors, followed by drowsiness, convulsions, unconsciousness and possibly respiratory arrest. Cardiovascular reactions are hypotension, myocardial depression, bradycardia and possibly cardiac arrest. Allergic reactions are extremely rare. They may be characterized by cutaneous lesions, urticaria, oedema or anaphylactoid reactions.

Known hypersensitivity to anaesthetics of the amide type.

Lidocaine for infiltration and nerve block should be employed only by clinicians who are well versed in diagnosis and management of dose-related toxicity. The safety and effectiveness of lidocaine depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Standard text books should be consulted for specific techniques and precautions for various regional anaesthetic procedures. Resuscitative equipment, oxygen and other resuscitative drugs should be available for immediate use.

It should be used cautiously in patients with epilepsy, impaired cardiac conduction, bradycardia, impaired respiratory function and in patients with impaired hepatic function, if the dose or site of administration is likely to result in high blood levels. The effect of local anaesthetics may be reduced if an injection is made into an inflamed or infected area. Repeated doses of lidocaine may cause significant increases in blood levels with each repeated dose because of slow accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Careful and constant monitoring of cardiovascular and respiratory vital signs and the patient's state of consciousness should be accomplished after each local anaesthetic injection.

Cimetidine can impair the metabolism of lidocaine absorbed into the circulation. Elimination will be delayed and the risk of adverse reactions increased. Significant increases in plasma lidocaine concentrations have occurred during concomitant therapy with beta blockers such as propranolol, metoprolol or nadolol. It prolongs the duration of action of suxamethonium.

Although there is no evidence from animal studies of harm to the foetus, as with all drugs, it should not be given during early pregnancy unless the benefits are considered to outweigh the risks. Caution should be exercised when it is administered to a nursing woman.

Dosages in children should be reduced, commensurate with age, body-weight and physical condition. Elderly patients may be more sensitive to systemic effects and may require dose reductions.

Keep below 25°C temperature, away from light & moisture. Keep out of the reach of children.

Local & Surface anesthesia

Lidocaine acts mainly by inhibiting sodium influx through sodium specific ion channels in the neuronal cell membrane, in particular the so called voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Lidocaine binds more readily to sodium channels in activated state, thus onset of neuronal blockade is faster in neurons that are rapidly firing. This is referred to as state dependent blockade.

Skin rash or irritation, drowsiness, wheezing or difficulty breathing, chest pain, severe rash or itching, increased sweating, numbness.

Should not be given to patients with myasthenia gravis, epilepsy, impaired cardiac condition or liver damage.

Patient should be careful driving or operating machinery after use of Lidocaine 10% Spray. Patient may be drowsy and reflexes may be slow. Patient should not eat or drink anything for at least 1 hour after using Lidocaine 10% Spray in the mouth or throat area. Should be careful not to spray Lidocaine 10% Spray near the eyes. If any of the spray does go in the eye, should rinse immediately with lots of water for at least 15 minutes and doctor should be called.

No study available. Can be given to a pregnant woman as per doctor's judgment. Small amount of Lidocaine may pass to a lactating baby, but the amount is insignificant to cause any harm

The first signs that too much Lidocaine 10% Spray has been used usually take the form of light-headedness, drowsiness, dizziness and sometimes blurred vision. In the event of serious over dosage trembling, seizures or unconsciousness may occur.

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

Lidocaine Injection is indicated-

• As a local anaesthetic for use in infiltration blockade and intravenous regional analgesia.
• For the prevention and treatment of ventricular tachyarrhythmias

Local & Surface anesthesia

Lidocaine acts mainly by inhibiting sodium influx through sodium specific ion channels in the neuronal cell membrane, in particular the so called voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Lidocaine binds more readily to sodium channels in activated state, thus onset of neuronal blockade is faster in neurons that are rapidly firing. This is referred to as state dependent blockade.

The dosage is adjusted according to the response of the patient and site of administration.

Adult: For healthy adults, the maximum individual dose should not exceed 4.5mg/kg of body weight and in general it is recommended that the maximum total dose does not exceed 300 mg. Recommended doses given in the below serve only as a guide to the amount of anaesthetic required for most routine procedures.

Infiltration-

• Percutaneous: Total dose 5-300 mg
• Intravenous regional: Total dose 50-300 mg

Peripheral Nerve Blocks-

• Brachial: Total dose 225-300 mg
• Dental: Total dose 20-100 mg
• Intercostal: Total dose 30 mg
• Paravertebral: Total dose 30-50 mg

Pudenal (each side): 

• Paracervical Obstetrical analgesia: Total dose 100 mg

Sympathetic Nerve Blocks

• Cervical: Total dose 50 mg
• Lumbar: Total dose 50-100 mg

Central Neural Blocks

• Epidural: Total dose 200-300 mg [Dose determined by number of dermatomes to be anesthetized (2-3 mL/dermatome) periodically.]
• Thoracic: Total dose 200-300 mg

Lumbar

• Analgesia: Total dose 250-300 mg
• Anesthesia: Total dose 200-300 mg

Caudal

• Obstetrical analgesia: Total dose 200-300 mg
• Surgical anesthesia: Total dose 225-300 mg.

Antiarrhythmic treatment: An intravenous dose of 1 mg.kg^-1 may be given over 2 min and repeated after 5 min, but giving an infusion of 2-4 mg.min^-1 to produce a plasma level of 2-4 mg. l^-1 is a more satisfactory technique. To avoid a long delay in achieving a steady state, a loading dose of approximately 1 mg.kg^-1 is usually given intravenously over 2 min at the outset.

In common with other local anaesthetics, adverse reactions to lidocaine are rare and are usually the result of excessively high blood concentrations due to inadvertent intravascular injection, excessive dosage, rapid absorption or occasionally to hypersensitivity, idiosyncracy or diminished tolerance on the part of the patient. In such circumstances systemic effects occur involving the central nervous system and/or the cardiovascular system. CNS reactions are excitatory and/or depressant and may be characterized by nervousness, dizziness, blurred vision and tremors, followed by drowsiness, convulsions, unconsciousness and possibly respiratory arrest. Cardiovascular reactions are hypotension, myocardial depression, bradycardia and possibly cardiac arrest. Allergic reactions are extremely rare. They may be characterized by cutaneous lesions, urticaria, oedema or anaphylactoid reactions.

Known hypersensitivity to anaesthetics of the amide type.

Lidocaine for infiltration and nerve block should be employed only by clinicians who are well versed in diagnosis and management of dose-related toxicity. The safety and effectiveness of lidocaine depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Standard text books should be consulted for specific techniques and precautions for various regional anaesthetic procedures. Resuscitative equipment, oxygen and other resuscitative drugs should be available for immediate use.

It should be used cautiously in patients with epilepsy, impaired cardiac conduction, bradycardia, impaired respiratory function and in patients with impaired hepatic function, if the dose or site of administration is likely to result in high blood levels. The effect of local anaesthetics may be reduced if an injection is made into an inflamed or infected area. Repeated doses of lidocaine may cause significant increases in blood levels with each repeated dose because of slow accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Careful and constant monitoring of cardiovascular and respiratory vital signs and the patient's state of consciousness should be accomplished after each local anaesthetic injection.

Cimetidine can impair the metabolism of lidocaine absorbed into the circulation. Elimination will be delayed and the risk of adverse reactions increased. Significant increases in plasma lidocaine concentrations have occurred during concomitant therapy with beta blockers such as propranolol, metoprolol or nadolol. It prolongs the duration of action of suxamethonium.

Although there is no evidence from animal studies of harm to the foetus, as with all drugs, it should not be given during early pregnancy unless the benefits are considered to outweigh the risks. Caution should be exercised when it is administered to a nursing woman.

Dosages in children should be reduced, commensurate with age, body-weight and physical condition. Elderly patients may be more sensitive to systemic effects and may require dose reductions.

Keep below 25°C temperature, away from light & moisture. Keep out of the reach of children.