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Antacids

This is the combination of Sodium Alginate and Potassium Bicarbonate. Sodium Alginate is a naturally occurring substance. It reacts with the acid in the stomach to form a gel. Potassium Bicarbonate also reacts with the acid in the stomach to form bubbles of carbon dioxide. These bubbles are trapped by the gel formed by Sodium Alginate and they allow the gel to float like a raft on top of the stomach contents. The raft prevents acid in the stomach from flowing back into the esophagus. This relieves the symptoms of reflux such as heartburn. The mode of action of this is physical and does not depend on absorption into the systemic circulation. The raft lasts for up to 4 hours on top of the stomach contents and is then broken down in the digestive system and excreted in the feces.

Tablet:

• Adults and children over 12 years: 1-2 tablets 3-4 times daily, after meals and before bedtime.
• Children 6-12 years: ½-1 tablet 3-4 times daily, after meals and before bedtime.

Suspension:

• Adults and children 12 years and above: 5-10 ml (1-2 teaspoonfuls) 3-4 times daily, after meals and before bedtime.
• Children 2-12 years: 2.5-5ml (½-1 teaspoonful) 3-4 times daily, after meals and before bedtime.

Use in children: This is not recommended under 2 years of age.
Elderly: No dose modifications are necessary for this age group.
Hepatic Impairment: No dose modifications are necessary.
Renal Insufficiency: Caution if a highly restricted salt diet is necessary.

In addition to the desired effect of the drug, some side effects may appear such as: nausea, constipation, diarrhea or headache. In these cases consult a physician In case too big dosage has been taken, there might appear a sensation of swelling. In this case it is advisable to consult a physician.

Sodium alginate and potassium bicarbonate is contraindicated in patients with known hypersensitivity to these.

Sodium Alginate and Potassium Bicarbonate should be prescribed with caution in patients with renal impairment and congestive cardiac failure. Care needs to be taken in treating patients with hypercalcemia, nephrocalcinosis and recurrent calcium-containing renal calculi. There is a possibility of reduced efficacy in patients with very low levels of gastric acid. If symptoms do not improve after seven days, the clinical situation should be reviewed.

A time interval of 2 hours should be considered between this intake and the administration of other medicinal products, especially tetracyclines, fluoroquinolones, iron salts, thyroid hormones, chloroquine, bisphosphonates, and estramustine.

This combination (Sodium Alginate and Potassium Bicarbonate) can be used during pregnancy, if clinically needed. No known effect on breast-fed infants. This combination can be used during breastfeeding.

Overdosage with this formulation is a rare case. In case of overdose please consult with a registered physician.

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

Antacids

This is the combination of Sodium Alginate and Potassium Bicarbonate. Sodium Alginate is a naturally occurring substance. It reacts with the acid in the stomach to form a gel. Potassium Bicarbonate also reacts with the acid in the stomach to form bubbles of carbon dioxide. These bubbles are trapped by the gel formed by Sodium Alginate and they allow the gel to float like a raft on top of the stomach contents. The raft prevents acid in the stomach from flowing back into the esophagus. This relieves the symptoms of reflux such as heartburn. The mode of action of this is physical and does not depend on absorption into the systemic circulation. The raft lasts for up to 4 hours on top of the stomach contents and is then broken down in the digestive system and excreted in the feces.

Tablet:

• Adults and children over 12 years: 1-2 tablets 3-4 times daily, after meals and before bedtime.
• Children 6-12 years: ½-1 tablet 3-4 times daily, after meals and before bedtime.

Suspension:

• Adults and children 12 years and above: 5-10 ml (1-2 teaspoonfuls) 3-4 times daily, after meals and before bedtime.
• Children 2-12 years: 2.5-5ml (½-1 teaspoonful) 3-4 times daily, after meals and before bedtime.

Use in children: This is not recommended under 2 years of age.
Elderly: No dose modifications are necessary for this age group.
Hepatic Impairment: No dose modifications are necessary.
Renal Insufficiency: Caution if a highly restricted salt diet is necessary.

In addition to the desired effect of the drug, some side effects may appear such as: nausea, constipation, diarrhea or headache. In these cases consult a physician In case too big dosage has been taken, there might appear a sensation of swelling. In this case it is advisable to consult a physician.

Sodium alginate and potassium bicarbonate is contraindicated in patients with known hypersensitivity to these.

Sodium Alginate and Potassium Bicarbonate should be prescribed with caution in patients with renal impairment and congestive cardiac failure. Care needs to be taken in treating patients with hypercalcemia, nephrocalcinosis and recurrent calcium-containing renal calculi. There is a possibility of reduced efficacy in patients with very low levels of gastric acid. If symptoms do not improve after seven days, the clinical situation should be reviewed.

A time interval of 2 hours should be considered between this intake and the administration of other medicinal products, especially tetracyclines, fluoroquinolones, iron salts, thyroid hormones, chloroquine, bisphosphonates, and estramustine.

This combination (Sodium Alginate and Potassium Bicarbonate) can be used during pregnancy, if clinically needed. No known effect on breast-fed infants. This combination can be used during breastfeeding.

Overdosage with this formulation is a rare case. In case of overdose please consult with a registered physician.

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

Anti-fibrinolytic drugs, Haemostatic drugs

This is a preparation of tranexamic acid (trans-4 aminomethyl-cyclohexanecarboxylic acid). Tranexamic acid is a substance endowed with a strong antifibrinolytic action and both in vivo and in vitro it has proved to be 10 times more active than conventional hemostatics, depending on the test. The antihemorrhagic action of tranexamic acid is essentially due to an inhibition of the plasminogen activation of both exogenous activators like streptokinase and endogenous ones like urokinase and the plasminogen tissue activator. This fact is particularly important for the clinical use of Tranexamic Acid, because it ensures an antihemorrhagic activity with an antifibrinolytic mechanism under a variety of conditions.

The acute toxicity of Tranexamic Acid is extremely low and chronic toxicity almost non-existent. Tranexamic Acid is well absorbed by oral route and the effect is already seen 15-30 minutes after administration. It is excreted mainly by renal route but more slowly than conventional hemostatics. These features make the Tranexamic Acid effect more lasting than those conventional hemostatics. Considerably lower single doses of Tranexamic Acid can thus be administered at greater intervals without the drug plasma levels dropping to inefficient levels of antifibrinolytic activity between one dose and the other.

Tranexamic Acid at therapeutic doses does not interfere with clotting processes and even a prolonged administration has not been seen to be accompanied by any tendency to thrombophilia.

Adults-

• The usual dose: 500-1000 mg 3 times daily.
• For prophylaxis: The mean recommended daily doses are 0.5-1 gm orally, 500 mg by the parenteral (intravenous or intramuscular) route.
• For therapy of hemorrhagic manifestations: the oral dose increases to 1-3 gm given in divided doses: in cases of particular seriousness and urgency, begin by injecting an ampoule (500 mg) slowly by intravenous route and administer the necessary subsequent oral doses.

Children-

• For prophylaxis: For every kg of body weight from 5-10 mg are orally administered daily in divided doses.
• For therapeutic purposes: The oral doses are doubled (from 10 to 20 mg/kg), while the intravenous and intramuscular treatment is begun with 10 mg/kg (=0.5 ml every 5 kg) by the slow intravenous route, continuing the oral administration up to the required dose. Where it is more convenient (e.g. in small babies) the ampoules, diluted in a little sweetened water, maybe orally administered instead of the Capsules.

Elderly patients: No reduction in dosage is necessary unless there is evidence of renal failure.

Known individual hypersensitivity to the product. Thromboembolic disease, arterial and venous thrombosis, endocavitary hemorrhages, serious kidney failure.

Tranexamic Acid is a synthetic Amino Acid that is incompatible with solutions containing penicillins (eg: Benzyl penicillin). Thrombolytic drugs like Streptokinase & Urokinase antagonise the antifibrinolytic action of Tranexamic Acid. The potential for thrombus formation may be increased by concomitant administration of estrogen containing drugs, like oral contraceptives. Direct admixture of Tranexamic Acid with whole blood should be avoided during Transfusion.

Since the transplacental passage of the drug and its possible effects on the fetus are unknown, Tranexamic Acid should not be administered during known and presumed pregnancy. Tranexamic Acid passes into breast milk to a concentration of approximately one hundredth of the concentration in the maternal blood. An antifibrinolytic effect in the infant is unlikely.

Store in a dry place at 15-30°C, away from light and keep out of children's reach.

Anti-fibrinolytic drugs, Haemostatic drugs

This is a preparation of tranexamic acid (trans-4 aminomethyl-cyclohexanecarboxylic acid). Tranexamic acid is a substance endowed with a strong antifibrinolytic action and both in vivo and in vitro it has proved to be 10 times more active than conventional hemostatics, depending on the test. The antihemorrhagic action of tranexamic acid is essentially due to an inhibition of the plasminogen activation of both exogenous activators like streptokinase and endogenous ones like urokinase and the plasminogen tissue activator. This fact is particularly important for the clinical use of Tranexamic Acid, because it ensures an antihemorrhagic activity with an antifibrinolytic mechanism under a variety of conditions.

The acute toxicity of Tranexamic Acid is extremely low and chronic toxicity almost non-existent. Tranexamic Acid is well absorbed by oral route and the effect is already seen 15-30 minutes after administration. It is excreted mainly by renal route but more slowly than conventional hemostatics. These features make the Tranexamic Acid effect more lasting than those conventional hemostatics. Considerably lower single doses of Tranexamic Acid can thus be administered at greater intervals without the drug plasma levels dropping to inefficient levels of antifibrinolytic activity between one dose and the other.

Tranexamic Acid at therapeutic doses does not interfere with clotting processes and even a prolonged administration has not been seen to be accompanied by any tendency to thrombophilia.

Adults-

• The usual dose: 500-1000 mg 3 times daily.
• For prophylaxis: The mean recommended daily doses are 0.5-1 gm orally, 500 mg by the parenteral (intravenous or intramuscular) route.
• For therapy of hemorrhagic manifestations: the oral dose increases to 1-3 gm given in divided doses: in cases of particular seriousness and urgency, begin by injecting an ampoule (500 mg) slowly by intravenous route and administer the necessary subsequent oral doses.

Children-

• For prophylaxis: For every kg of body weight from 5-10 mg are orally administered daily in divided doses.
• For therapeutic purposes: The oral doses are doubled (from 10 to 20 mg/kg), while the intravenous and intramuscular treatment is begun with 10 mg/kg (=0.5 ml every 5 kg) by the slow intravenous route, continuing the oral administration up to the required dose. Where it is more convenient (e.g. in small babies) the ampoules, diluted in a little sweetened water, maybe orally administered instead of the Capsules.

Elderly patients: No reduction in dosage is necessary unless there is evidence of renal failure.

Known individual hypersensitivity to the product. Thromboembolic disease, arterial and venous thrombosis, endocavitary hemorrhages, serious kidney failure.

Tranexamic Acid is a synthetic Amino Acid that is incompatible with solutions containing penicillins (eg: Benzyl penicillin). Thrombolytic drugs like Streptokinase & Urokinase antagonise the antifibrinolytic action of Tranexamic Acid. The potential for thrombus formation may be increased by concomitant administration of estrogen containing drugs, like oral contraceptives. Direct admixture of Tranexamic Acid with whole blood should be avoided during Transfusion.

Since the transplacental passage of the drug and its possible effects on the fetus are unknown, Tranexamic Acid should not be administered during known and presumed pregnancy. Tranexamic Acid passes into breast milk to a concentration of approximately one hundredth of the concentration in the maternal blood. An antifibrinolytic effect in the infant is unlikely.

Store in a dry place at 15-30°C, away from light and keep out of children's reach.

Iodine compounds (Anti-septic Preparations)

Povidone Iodine is a complex of iodine and an organic polymer, povidone. This polymerization makes Povidone Iodine superior to ordinary elemental iodine. It prolongs the germicidal activity of iodine by liberating elemental iodine slowly. Consequently it has a lower toxicity than elemental iodine. It gives rapid microbicidal activity against both Gram-positive and Gram-negative bacteria, protozoa, viruses and fungi/yeasts. It is also sporicidal. It is the only microbicide with this broad spectrum of activity. It is non-staining, exerts prolong germicidal action and is also active in the presence of soap, blood, serum, pus, mucosal secretions and water.

Cream or ointment:

• For the treatment of infection: Apply once or twice daily or at dressing changes for a maximum of 14 days.
• For the prevention of infection: Apply once or twice a week for as long as necessary. The affected skin should be cleaned and dried and can be covered with a dressing or bandage.

Solution: Apply full strength as often as needed as paint, spray, or wet soak. Maybe bandaged (where necessary).

Gargle & Mouthwash: Adults and children over 6 years of age: Use undiluted or diluted with an equal volume of warm water. Gargle or rinse with up to 10 mL for up to 30 seconds without swallowing. Repeat up to four times daily, for up to 14 consecutive days, or as advised by the Registered Dental Surgeon/Physician.

Surgical Scrub:

• For Preoperative and Postoperative washing by Operating Personnel: Wet hands and forearms with water. Pour about 5 mL of Povidone Iodine Surgical Scrub on the palm of the hand and spread over both hands and forearms. Without adding more water, rub the Scrub thoroughly over all areas for about five minutes. Use a brush if desired. Clean thoroughly under fingernails. Add a little water and develop copious suds. Rinse thoroughly under running water. Complete the wash by scrubbing with another 5 mL of Povidone Iodine Surgical Scrub in the same way.
• For Preoperative use on Patients: After the skin area is shaved, wet it with water. Apply Povidone Iodine Surgical Scrub (1 mL is sufficient to cover an area of 20-30 square inches), develop lather and scrub thoroughly for about five minutes. Rinse off by aid of sterile gauze saturated with water.
• For use in the Physician's Office: Use for washing whenever a germicidal soap is required.

Powder: Apply a light dusting of powder to the affected area. When dry, this forms a protective antiseptic layer over the area treated. Or use as advised by the Registered Physician. There are no special dosage recommendations for children or elderly patients.

Ophthalmic Solution: 1 drop 4 times daily or as required, depending upon the severity of the disease, to be instilled into the conjunctival sac.

Povidone Iodine may cause hypersensitivity reactions and irritation of the skin and mucous membranes. The application of povidone Iodine to severe burns or to large areas otherwise denuded of skin may produce systemic adverse effects such as metabolic acidosis, hypernatraemia, and impairment of renal function. It may interfere with thyroid function tests.

It can cause hypersensitivity reactions. Regular use in patients with thyroid disorders (in particular nodular colloid goitre, endemic goitre and Hashimoto's thyroiditis) or those receiving lithium therapy is to be avoided. In severely burnt patients serum iodide levels should be assessed due to possible hepatic and renal impairment. Povidone Iodine Powder should not be used in serious cavities and in Children under the age of 2 years.

Cream or ointment: In case of deep or puncture wounds or serious burns, consult Registered Physician. If redness, irritation, swelling or pain persists or increases or if infection occurs, discontinue use and consult Registered Physician.

Solution: In preoperative prepping, avoid 'pooling' beneath the patient. Prolonged exposure to wet solution may cause irritation or rarely, severe skin reactions. In case of deep or puncture wounds or serious burns, consult Registered Physician. If redness, irritation, swelling or pain persists or increases or if infection occurs, discontinue use and consult Registered Physician.

Gargle & Mouthwash: Regular use should be avoided as prolonged use may lead to the absorption of a significant amount of iodine. Do not use for more than 14 days. If sores or ulcers in the mouth do not heal within 14 days seek dental or medical advice. It is also not for use in children under 6 years of age. Regular use should be avoided in patients on concurrent lithium therapy.

Surgical Scrub: Special caution is needed when regular applications to broken skin are made to patients with pre-existing renal insufficiency. Regular use should be avoided in patients on concurrent lithium therapy. It can permanently discolor white gold jewellery and it is recommended that this type of jewellery should be removed before using this product.

Powder: Care must be taken when used on known iodine sensitivity, although do not normally react to Povidone-Iodine. Excess powder can be washed off readily with warm water. It should be used directly from the container. Not to be administered internally.

Ophthalmic Solution: Patients, who experience blurred vision after application of the eye drops, should not drive or use machinery until their vision has cleared. Contact lenses should not be worn during the instillation of the drug. After instillation, there should be an interval of at least 30 minutes before reinsertion.

It exhibits interaction with strong alkali, sodium thiosulphate, sodium metabisulphite and thiomersal. Use with concurrent lithium therapy has been shown to exhibithypothyroidic effect.

Povidone Iodine Cream, Solution & Powder are not recommended for use during pregnancy because of the possibility of absorption of sufficient iodine to affect the fetal thyroid. American Academy of Pediatrics considers that the use of Povidone-Iodine is usually compatible with breast feeding. Consult Registered Physician. Regular use of Gargle & Mouthwash and Surgical Scrub should also be avoided in pregnant and lactating women.

There is no experience regarding the safety of the Povidone eye drops in human pregnancy or lactation. Administration during pregnancy and lactation is therefore not recommended, except for compelling reasons.

Store below 25°C. Do not freeze. Store in a cool and dry place, protected from light. Keep out of the reach of children. Do not touch the ophthalmic solution dropper tip to any surface as this may contaminate this preparation. Do not use it after one month of the first opening.

Herbal and Nutraceuticals

Saccharomyces boulardii strain survives stomach acid to colonize in the intestinal tract while acting as a temporary flora to protect the beneficial organisms of the intestine. Additionally, it works with the body to re establish the microflora, thereby helping to maintain and support healthy immunity, digestion and gut health. It shows the following actions:

Anti-toxin activity: S. boulardii produces proteins that work to neutralize bacterial toxins. This may include the toxins produced by Clostridium diffcile.

Anti-microbial: S. boulardii adheres to pathogens, which decreases their adhesion to the intestinal wall and decreases invasion of enterocytes into the body. These pathogens are then removed during bowel movements.

Enzymatic activity: In healthy adults, S. boulardii increases the enzymatic activities (lactase, alpha glucosidase, alkaline phosphatase). The production of intestinal polyamines by S. boulardii is one of its most relevant and specific mechanisms of action. The polyamines spermidine, spermine, and putrescine enhance the expression of brush border enzymes (such as hydrolases, proteases, and transport molecules).

Immune Enhancement: S. boulardii helps prevent infection by stimulating the immune system along the GI lining by increasing the protective antibody IgA.

Anti-inflammatory: S. boulardii causes a decrease in pro-inflammatory cytokines.

Adult:

• For diarrhea associated with the use of antibiotics: 250-500 mg of Saccharomyces boulardii two to four times a day.
• For diarrhea caused by Clostridium difficile: 1 gram of Saccharomyces boulardii daily for 4 weeks along with antibiotic treatment.
• For reduction in symptoms of acute diarrhea: 250 mg of Saccharomyces boulardii twice a day for 5 days.
• For diarrhea in Crohn's disease: 250 mg of Saccharomyces boulardii three times daily has been used for up to 9 weeks.
• For diarrhea in ulcerative colitis: 250 mg of Saccharomyces boulardii three times daily.
• For treatment of infections due to Helicobacter pylori: 250 mg-500 mg Saccharomyces boulardii twice daily in addition to usual treatment.
• For diarrhea in Irritable bowel syndrome (IBS): 250 mg capsule twice daily.
• For traveler's diarrhea: The recommended dosage is 250 mg capsule per day.

Children:

• For reduction in symptoms of acute diarrhea: Children over three months are recommended to take two doses of 250 mg a day for five days. Children under three months are recommended to take 125 mg twice daily for five days.

Saccharomyces boulardii is likely safe for most adults when taken by mouth. It can cause gas in some people.

It is contraindicated in patients with a history of hypersensitivity to Saccharomyces boulardii or any other components of this product.

Taking Saccharomyces boulardii with medications for fungal infections (e.g. fluconazole, itraconazole, terbinafine and others) can reduce the effectiveness of it.

There is no available information about the safety of taking Saccharomyces boulardii in pregnancy and lactation.

Store below 25° C, away from direct sunlight & moisture. Keep out of reach of children.

Herbal and Nutraceuticals

Saccharomyces boulardii strain survives stomach acid to colonize in the intestinal tract while acting as a temporary flora to protect the beneficial organisms of the intestine. Additionally, it works with the body to re establish the microflora, thereby helping to maintain and support healthy immunity, digestion and gut health. It shows the following actions:

Anti-toxin activity: S. boulardii produces proteins that work to neutralize bacterial toxins. This may include the toxins produced by Clostridium diffcile.

Anti-microbial: S. boulardii adheres to pathogens, which decreases their adhesion to the intestinal wall and decreases invasion of enterocytes into the body. These pathogens are then removed during bowel movements.

Enzymatic activity: In healthy adults, S. boulardii increases the enzymatic activities (lactase, alpha glucosidase, alkaline phosphatase). The production of intestinal polyamines by S. boulardii is one of its most relevant and specific mechanisms of action. The polyamines spermidine, spermine, and putrescine enhance the expression of brush border enzymes (such as hydrolases, proteases, and transport molecules).

Immune Enhancement: S. boulardii helps prevent infection by stimulating the immune system along the GI lining by increasing the protective antibody IgA.

Anti-inflammatory: S. boulardii causes a decrease in pro-inflammatory cytokines.

Adult:

• For diarrhea associated with the use of antibiotics: 250-500 mg of Saccharomyces boulardii two to four times a day.
• For diarrhea caused by Clostridium difficile: 1 gram of Saccharomyces boulardii daily for 4 weeks along with antibiotic treatment.
• For reduction in symptoms of acute diarrhea: 250 mg of Saccharomyces boulardii twice a day for 5 days.
• For diarrhea in Crohn's disease: 250 mg of Saccharomyces boulardii three times daily has been used for up to 9 weeks.
• For diarrhea in ulcerative colitis: 250 mg of Saccharomyces boulardii three times daily.
• For treatment of infections due to Helicobacter pylori: 250 mg-500 mg Saccharomyces boulardii twice daily in addition to usual treatment.
• For diarrhea in Irritable bowel syndrome (IBS): 250 mg capsule twice daily.
• For traveler's diarrhea: The recommended dosage is 250 mg capsule per day.

Children:

• For reduction in symptoms of acute diarrhea: Children over three months are recommended to take two doses of 250 mg a day for five days. Children under three months are recommended to take 125 mg twice daily for five days.

Saccharomyces boulardii is likely safe for most adults when taken by mouth. It can cause gas in some people.

It is contraindicated in patients with a history of hypersensitivity to Saccharomyces boulardii or any other components of this product.

Taking Saccharomyces boulardii with medications for fungal infections (e.g. fluconazole, itraconazole, terbinafine and others) can reduce the effectiveness of it.

There is no available information about the safety of taking Saccharomyces boulardii in pregnancy and lactation.

Store below 25° C, away from direct sunlight & moisture. Keep out of reach of children.

Benzodiazepine sedatives

Bromazepam is a powerful psychotropic agent. In lower dosage, it selectively reduces tension and anxiety. In higher dosage, it shows sedative and muscle-relaxant properties. Bromazepam binds to the GABA-A receptor producing a conformational change and potentiating its inhibitory effects. Other neurotransmitters are not influenced.

Standard dosage: Average dosage for outpatient therapy is 1.5-3 mg up to three times daily. Treatment of outpatients should begin with low doses, gradually increasing to the optimum level.

In severe cases, especially in hospital: 6-12 mg 2 or 3 times daily. The overall treatment generally should not be more than 8-12 weeks. In certain cases extension beyond the maximum treatment period may be necessary; if so, it should be taken with re-evaluation of the patient's status with special expertise.

Elderly and debilitated patients: Elderly patients and those with impaired hepatic functions require lower doses.

Children: Bromazepam is usually not indicated in children, but if the physician feels bromazepam treatment is appropriate, then the dose should be adjusted to their low bodyweight (about 0.1-0.3 mg/kg bodyweight)

Bromazepam tablets are for oral administration

Common side-effects include fatigue, drowsiness, muscle weakness, numbed muscle, reduced alertness, confusion, headache, ataxia etc. These phenomena occur predominantly at the start of therapy and usually disappear with prolonged administration. Anterograde amnesia may occur using therapeutic doses.

Bromazepam is contraindicated in patients with known hypersensitivity to bromazepam, severe respiratory insufficiency, severe hepatic insufficiency or sleep apnea syndrome.

The use of benzodiazepines and benzodiazepine like agents may lead to the development of physical and psychological dependence upon these products. This dependence depends on the dose and duration of treatment; it is also greater in predisposed patients with a history of alcohol. Once physical dependence has developed, termination of the treatment will be accompanied by withdrawal symptoms. These may consist of headache, muscle pain, extreme anxiety, tension, confusion and irritability. Since the risk of withdrawal phenomena and rebound phenomena is greater after abrupt discontinuation of the treatment, it is recommended that the dosage be decreased gradually. Bromazepam is not recommended for the primary treatment of sleeplessness caused by psychotic illness. Caution should be exercised while driving cars or using machineries.

If bromazepam is combined with other centrally active drugs, its sedative effects may be enhanced. These drugs are antidepressants, hypnotics, narcotics, antipsychotics, sedatives, antiepileptic drugs, sedative antihistamines and anesthetics. Co-administration of cimetidine may prolong the eliminiation half-life of bromazepam. Concomitant intake of bromazepam with alcohol should be avoided, because the sedative effect of bromazepam may be intensified by alcohol.

The safety of bromazepam during pregnancy has not been established. As bromazepam is excreted in breast milk, use should be avoided during lactation.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Minerals in bone formation, Specific mineral preparations

Calcium carbonate reacts with gastric acid to produce a salt and water. For calcium carbonate the postulated chemical reaction is: CaCO₃+2HCl = CaCl₂+H₂O+CO₂. Two grams of calcium carbonate will readily bring 100 ml of hydrochloric acid to a pH above 6. The increase in gastric pH diminishes the activity of pepsin in the gastric secretion. Up to 30% of the oral calcium load may be absorbed.

250 mg or 500 mg tablet: Calcium Carbonate is always used orally and when used as an antacid the recommended doses for adults are equivalent to 540-2000 mg Calcium Carbonate per day, doses for children being half of those for adults. As a dietary supplement, such as for the prevention of osteoporosis, 1250-3750 mg Calcium Carbonate (500-1500 mg calcium) daily is recommended in general, but again this will need to be tailored to the individual patient depending on any specific disease such as Calcium deficiency, malabsorption or parathyroid function. In pregnancy and lactation the recommended daily dose of calcium is 1200-1500 mg. In chronic renal failure the doses used vary from 2.5-9.0 gm Calcium Carbonate per day and need to be adjusted according to the individual patient. To maximize effective phosphate binding in this context the Calcium Carbonate should be given with meals.

1000 mg tablet: 2000-3000 mg tablet when symptoms occur; may be repeated hourly if needed or as directed by the physician.

Orally administered Calcium Carbonate may be irritating to the GI tract. It may also cause constipation. Hypercalcaemia is rarely produced by administration of calcium alone, but may occur when large doses are given to patients with chronic renal failure.

• Hypercalcaemia and hyperparathyroidism
• Hypercalciuria and nephrolithiasis
• Zollinger-Ellison syndrome
• Concomitant digoxin therapy (requires careful monitoring of serum calcium level)

When hypercalcaemia occurs, discontinuation of the drug is usually sufficient to return serum calcium concentrations to normal. Calcium salts should be used cautiously in patients with sarcoidosis, renal or cardiac disease, and in patients receiving cardiac glycosides.

Calcium Carbonate may enhance the cardiac effects of digoxin and other cardiac glycosides, if systemic hypercalcaemia occurs. Calcium Carbonate may interfere with the absorption of concomitantly administered tetracycline preparations and in chronic renal failure modification of vitamin D therapy may be required to avoid hypercalcaemia when Calcium Carbonate is used as the primary phosphate binder.

Calcium containing drugs have been widely used in pregnancy by way of oral calcium supplementation or antacid therapy. Calcium Carbonate can be used in lactating women too.

Use in children: Calcium carbonate has been extensively studied in children and infants with chronic renal failure and is both safe and effective.

Use in elderly: In case of elderly patients with renal failure when calcium carbonate is taken constipation may be troublesome one for this group. For this reason, monitoring of serum calcium and phosphate is of course indicated for elderly patients.

Store in a cool, dry place in controlled room temperature.

This tablet is indicated in-

• Osteoarthritis
• Rheumatoid arthritis
• Bone and Joint injuries

Stimulation of Cartilage formation

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

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

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

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

Use in adults: One tablet twice daily with food.

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

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

Contraindicated for those who shows hypersensitivity to Glucosamine or Diacerein.

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

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

This tablet is contraindicated during pregnancy and breastfeeding.

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

Ibandronic acid is indicated for the treatment of postmenopausal osteoporosis, to reduce the risk of fractures.

Treatment of Osteoporosis: Osteoporosis may be confirmed by the finding of low bone mass (T-score <-2.0 SD) and the presence or history of osteoporotic fracture, or a low bone mass (T-score <-2.5 SD) in the absence of documented pre-existing osteoporotic fracture.

Bisphosphonate preparations

The pharmacodynamic action of ibandronic acid is inhibition of bone resorption. In vivo, ibandronic acid prevents experimentally induced bone destruction caused by cessation of gonadal function, retinoids, tumors or tumor extracts. In young (fast growing) rats, the endogenous bone resorption is also inhibited, leading to increased bone mass compared with untreated animals. Animal models confirm that ibandronic acid is a highly potent inhibitor of osteoclastic activity. In growing rats, there was no evidence of impaired mineralization even at doses greater than 5,000 times the dose required for osteoporosis treatment. The high potency and therapeutic margin of ibandronic acid allows for more flexible dosing regimens and intermittent treatment with long drug-free intervals at comparatively low doses.

Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of bisphosphonates, which act on bone tissue and specifically inhibit osteoclast activity, It does not interfere with osteoclast recruitment. The selective action of ibandronic acid on bone tissue is based on the high affinity of this compound for hydroxyapatite, which represents the mineral matrix of the bone. Ibandronic acid reduces bone resorption, with no direct effect on bone formation. In postmenopausal women, it reduces the elevated rate of bone turnover towards premenopausal levels, leading to a progressive net gain in bone mass. Daily or intermittent administration of ibandronic acid results in reduced bone resorption as reflected in reduced levels of serum and urinary biochemical markers of bone turnover, increased BMD and a decreased incidence of fractures.

The recommended dose of Ibandronic acid for treatment is one 150 mg film-coated tablet once a month. The tablet should preferably be taken on the same date each month. Ibandronic acid should be taken 60 minutes before the first food or drink (other than water) of the day or any other oral medication or supplementation (including calcium):

• Tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the patient is sitting or standing in an upright position. Patients should not lie down for 60 minutes after taking Ibandronic acid.
• Plain water is the only drink that should be taken with Ibandronic acid. Please note that some mineral waters may have a higher concentration of calcium and therefore should not be used.
• Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration. Patients should receive supplemental calcium or vitamin D if dietary intake is inadequate. In case a once-monthly dose is missed, patients should be instructed to take one Ibandronic Acid 150 mg tablet the morning after the tablet is remembered unless the time to the next scheduled dose is within 7 days. Patients should then return to taking their dose once a month on their originally scheduled date. If the next scheduled dose is within 7 days, patients should wait until their next dose and then continue taking one tablet once a month as originally scheduled. Patients should not take two 150 mg tablets within the same week.

The main side effects of ibandronic acid are dyspepsia, nausea, diarrhea, abdominal pain, muscle aches, headaches, dizziness.

Ibandronic Acid is contraindicated in patients with known hypersensitivity to ibandronic acid or to any of the excipients. Ibandronic Acid is contraindicated in patients with uncorrected hypocalcemia. As with all bisphosphonates indicated in the treatment of osteoporosis, pre-existing hypocalcemia needs to be corrected before initiating therapy with Ibandronic Acid. As with several bisphosphonates, Ibandronic Acid is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia. Ibandronic Acid is contraindicated in patients who are unable to stand or sit upright for at least 60 minutes.

Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Ibandronic Acid therapy. Adequate intake of calcium and vitamin D is important in all patients. Orally administered bisphosphonates may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when Ibandronic Acid is given to patients with active upper gastrointestinal problems (e.g. known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers). Adverse experiences such as esophagitis, esophageal ulcers and esophageal erosions, in some cases severe and requiring hospitalization, rarely with bleeding or followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. The risk of severe esophageal adverse experiences appears to be greater in patients who do not comply with the dosing instruction and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Patients should pay particular attention and be able to comply with the dosing instructions.

Physicians should be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue Ibandronic Acid and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn. While no increased risk was observed in controlled clinical trials there have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications. Since NSAIDs and bisphosphonates are both associated with gastrointestinal irritation, caution should be taken during concomitant medication with Ibandronic Acid. Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Known risk factors for osteonecrosis of the jaw include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), and co-morbid disorders (e.g., anemia, coagulopathy, infection, pre-existing dental disease). Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment.

It is likely that calcium supplements, antacids and some oral medications containing multivalent cations (such as aluminium, magnesium, iron) are likely to interfere with the absorption of Ibandronic Acid. Therefore, patients must wait 60 minutes after taking Ibandronic Acid before taking other oral medications. Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (estrogen). No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma. In healthy male volunteers and postmenopausal women, i.v. ranitidine caused an increase in ibandronic acid bioavailability of about 20 %, probably as a result of reduced gastric acidity. However, since this increase is within the normal range of the bioavailability of ibandronic acid, no dosage adjustment is required when Ibandronic Acid is administered with H2-antagonists or other drugs which increase gastric pH.

In relation to disposition, no drug interactions of clinical significance are considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats. Furthermore, plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other drugs. Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other drugs. In a one-year study in postmenopausal women with osteoporosis (BM16549). the incidence of upper gastrointestinal events in patients concomitantly taking aspirin or NSAIDs was similar in patients taking Ibandronic Acid 2.5 mg daily or 150mg once monthly. Of over 1500 patients enrolled in study BM 16549 comparing monthly with daily dosing regimens of ibandronic acid, 14% of patients used histamine (H2) blockers or proton pump inhibitors. Among these patients, the incidence of upper gastrointestinal events in the patients treated with Ibandronic Acid 150 mg once monthly was similar to that in patients treated with Ibandronic Acid 2.5 mg daily.

Pregnancy: Ibandronic Acid should not be used during pregnancy. There was no evidence for a direct fetal toxic or teratogenic effect of ibandronic acid in daily orally treated rats and rabbits and there were no adverse effects on the development in F1 offspring in rats. Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those observed with bisphosphonates as a class. They include a decreased number of implantation sites, interference with natural delivery (dystocia), and an increase in visceral variations (renal pelvis ureter syndrome). Specific studies for the monthly regimen have not been performed. There is no clinical experience with Ibandronic Acid in pregnant women.

Nursing Mothers: Ibandronic Acid should not be used during lactation. In lactating rats treated with 0.08 mg/kg/day IV. ibandronic acid, the highest concentration of ibandronic acid in breast milk was 8.1 ng/ml and was seen in the first 2 hours after i.v. administration. After 24 hours, the concentration in milk and plasma was similar, and corresponded to about 5 % of the concentration measured after 2 hours.

No specific information is available on the treatment of overdosage with ibandronic acid. However, oral overdosage may result in upper gastrointestinal adverse events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer. Milk or antacids should be given to bind ibandronic acid. Owing to the risk of esophageal irritation, vomiting should not be induced and the patient should remain fully upright.

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

Ibandronic acid is indicated for the treatment of postmenopausal osteoporosis, to reduce the risk of fractures.

Treatment of Osteoporosis: Osteoporosis may be confirmed by the finding of low bone mass (T-score <-2.0 SD) and the presence or history of osteoporotic fracture, or a low bone mass (T-score <-2.5 SD) in the absence of documented pre-existing osteoporotic fracture.

Bisphosphonate preparations

The pharmacodynamic action of ibandronic acid is inhibition of bone resorption. In vivo, ibandronic acid prevents experimentally induced bone destruction caused by cessation of gonadal function, retinoids, tumors or tumor extracts. In young (fast growing) rats, the endogenous bone resorption is also inhibited, leading to increased bone mass compared with untreated animals. Animal models confirm that ibandronic acid is a highly potent inhibitor of osteoclastic activity. In growing rats, there was no evidence of impaired mineralization even at doses greater than 5,000 times the dose required for osteoporosis treatment. The high potency and therapeutic margin of ibandronic acid allows for more flexible dosing regimens and intermittent treatment with long drug-free intervals at comparatively low doses.

Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of bisphosphonates, which act on bone tissue and specifically inhibit osteoclast activity, It does not interfere with osteoclast recruitment. The selective action of ibandronic acid on bone tissue is based on the high affinity of this compound for hydroxyapatite, which represents the mineral matrix of the bone. Ibandronic acid reduces bone resorption, with no direct effect on bone formation. In postmenopausal women, it reduces the elevated rate of bone turnover towards premenopausal levels, leading to a progressive net gain in bone mass. Daily or intermittent administration of ibandronic acid results in reduced bone resorption as reflected in reduced levels of serum and urinary biochemical markers of bone turnover, increased BMD and a decreased incidence of fractures.

The recommended dose of Ibandronic acid for treatment is one 150 mg film-coated tablet once a month. The tablet should preferably be taken on the same date each month. Ibandronic acid should be taken 60 minutes before the first food or drink (other than water) of the day or any other oral medication or supplementation (including calcium):

• Tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the patient is sitting or standing in an upright position. Patients should not lie down for 60 minutes after taking Ibandronic acid.
• Plain water is the only drink that should be taken with Ibandronic acid. Please note that some mineral waters may have a higher concentration of calcium and therefore should not be used.
• Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration. Patients should receive supplemental calcium or vitamin D if dietary intake is inadequate. In case a once-monthly dose is missed, patients should be instructed to take one Ibandronic Acid 150 mg tablet the morning after the tablet is remembered unless the time to the next scheduled dose is within 7 days. Patients should then return to taking their dose once a month on their originally scheduled date. If the next scheduled dose is within 7 days, patients should wait until their next dose and then continue taking one tablet once a month as originally scheduled. Patients should not take two 150 mg tablets within the same week.

The main side effects of ibandronic acid are dyspepsia, nausea, diarrhea, abdominal pain, muscle aches, headaches, dizziness.

Ibandronic Acid is contraindicated in patients with known hypersensitivity to ibandronic acid or to any of the excipients. Ibandronic Acid is contraindicated in patients with uncorrected hypocalcemia. As with all bisphosphonates indicated in the treatment of osteoporosis, pre-existing hypocalcemia needs to be corrected before initiating therapy with Ibandronic Acid. As with several bisphosphonates, Ibandronic Acid is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia. Ibandronic Acid is contraindicated in patients who are unable to stand or sit upright for at least 60 minutes.

Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Ibandronic Acid therapy. Adequate intake of calcium and vitamin D is important in all patients. Orally administered bisphosphonates may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when Ibandronic Acid is given to patients with active upper gastrointestinal problems (e.g. known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers). Adverse experiences such as esophagitis, esophageal ulcers and esophageal erosions, in some cases severe and requiring hospitalization, rarely with bleeding or followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. The risk of severe esophageal adverse experiences appears to be greater in patients who do not comply with the dosing instruction and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Patients should pay particular attention and be able to comply with the dosing instructions.

Physicians should be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue Ibandronic Acid and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn. While no increased risk was observed in controlled clinical trials there have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications. Since NSAIDs and bisphosphonates are both associated with gastrointestinal irritation, caution should be taken during concomitant medication with Ibandronic Acid. Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Known risk factors for osteonecrosis of the jaw include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), and co-morbid disorders (e.g., anemia, coagulopathy, infection, pre-existing dental disease). Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment.

It is likely that calcium supplements, antacids and some oral medications containing multivalent cations (such as aluminium, magnesium, iron) are likely to interfere with the absorption of Ibandronic Acid. Therefore, patients must wait 60 minutes after taking Ibandronic Acid before taking other oral medications. Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (estrogen). No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma. In healthy male volunteers and postmenopausal women, i.v. ranitidine caused an increase in ibandronic acid bioavailability of about 20 %, probably as a result of reduced gastric acidity. However, since this increase is within the normal range of the bioavailability of ibandronic acid, no dosage adjustment is required when Ibandronic Acid is administered with H2-antagonists or other drugs which increase gastric pH.

In relation to disposition, no drug interactions of clinical significance are considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats. Furthermore, plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other drugs. Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other drugs. In a one-year study in postmenopausal women with osteoporosis (BM16549). the incidence of upper gastrointestinal events in patients concomitantly taking aspirin or NSAIDs was similar in patients taking Ibandronic Acid 2.5 mg daily or 150mg once monthly. Of over 1500 patients enrolled in study BM 16549 comparing monthly with daily dosing regimens of ibandronic acid, 14% of patients used histamine (H2) blockers or proton pump inhibitors. Among these patients, the incidence of upper gastrointestinal events in the patients treated with Ibandronic Acid 150 mg once monthly was similar to that in patients treated with Ibandronic Acid 2.5 mg daily.

Pregnancy: Ibandronic Acid should not be used during pregnancy. There was no evidence for a direct fetal toxic or teratogenic effect of ibandronic acid in daily orally treated rats and rabbits and there were no adverse effects on the development in F1 offspring in rats. Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those observed with bisphosphonates as a class. They include a decreased number of implantation sites, interference with natural delivery (dystocia), and an increase in visceral variations (renal pelvis ureter syndrome). Specific studies for the monthly regimen have not been performed. There is no clinical experience with Ibandronic Acid in pregnant women.

Nursing Mothers: Ibandronic Acid should not be used during lactation. In lactating rats treated with 0.08 mg/kg/day IV. ibandronic acid, the highest concentration of ibandronic acid in breast milk was 8.1 ng/ml and was seen in the first 2 hours after i.v. administration. After 24 hours, the concentration in milk and plasma was similar, and corresponded to about 5 % of the concentration measured after 2 hours.

No specific information is available on the treatment of overdosage with ibandronic acid. However, oral overdosage may result in upper gastrointestinal adverse events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer. Milk or antacids should be given to bind ibandronic acid. Owing to the risk of esophageal irritation, vomiting should not be induced and the patient should remain fully upright.

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

Ibandronic acid is indicated for the treatment of postmenopausal osteoporosis, to reduce the risk of fractures.

Treatment of Osteoporosis: Osteoporosis may be confirmed by the finding of low bone mass (T-score <-2.0 SD) and the presence or history of osteoporotic fracture, or a low bone mass (T-score <-2.5 SD) in the absence of documented pre-existing osteoporotic fracture.

Bisphosphonate preparations

The pharmacodynamic action of ibandronic acid is inhibition of bone resorption. In vivo, ibandronic acid prevents experimentally induced bone destruction caused by cessation of gonadal function, retinoids, tumors or tumor extracts. In young (fast growing) rats, the endogenous bone resorption is also inhibited, leading to increased bone mass compared with untreated animals. Animal models confirm that ibandronic acid is a highly potent inhibitor of osteoclastic activity. In growing rats, there was no evidence of impaired mineralization even at doses greater than 5,000 times the dose required for osteoporosis treatment. The high potency and therapeutic margin of ibandronic acid allows for more flexible dosing regimens and intermittent treatment with long drug-free intervals at comparatively low doses.

Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of bisphosphonates, which act on bone tissue and specifically inhibit osteoclast activity, It does not interfere with osteoclast recruitment. The selective action of ibandronic acid on bone tissue is based on the high affinity of this compound for hydroxyapatite, which represents the mineral matrix of the bone. Ibandronic acid reduces bone resorption, with no direct effect on bone formation. In postmenopausal women, it reduces the elevated rate of bone turnover towards premenopausal levels, leading to a progressive net gain in bone mass. Daily or intermittent administration of ibandronic acid results in reduced bone resorption as reflected in reduced levels of serum and urinary biochemical markers of bone turnover, increased BMD and a decreased incidence of fractures.

The recommended dose of Ibandronic acid for treatment is one 150 mg film-coated tablet once a month. The tablet should preferably be taken on the same date each month. Ibandronic acid should be taken 60 minutes before the first food or drink (other than water) of the day or any other oral medication or supplementation (including calcium):

• Tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the patient is sitting or standing in an upright position. Patients should not lie down for 60 minutes after taking Ibandronic acid.
• Plain water is the only drink that should be taken with Ibandronic acid. Please note that some mineral waters may have a higher concentration of calcium and therefore should not be used.
• Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration. Patients should receive supplemental calcium or vitamin D if dietary intake is inadequate. In case a once-monthly dose is missed, patients should be instructed to take one Ibandronic Acid 150 mg tablet the morning after the tablet is remembered unless the time to the next scheduled dose is within 7 days. Patients should then return to taking their dose once a month on their originally scheduled date. If the next scheduled dose is within 7 days, patients should wait until their next dose and then continue taking one tablet once a month as originally scheduled. Patients should not take two 150 mg tablets within the same week.

The main side effects of ibandronic acid are dyspepsia, nausea, diarrhea, abdominal pain, muscle aches, headaches, dizziness.

Ibandronic Acid is contraindicated in patients with known hypersensitivity to ibandronic acid or to any of the excipients. Ibandronic Acid is contraindicated in patients with uncorrected hypocalcemia. As with all bisphosphonates indicated in the treatment of osteoporosis, pre-existing hypocalcemia needs to be corrected before initiating therapy with Ibandronic Acid. As with several bisphosphonates, Ibandronic Acid is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia. Ibandronic Acid is contraindicated in patients who are unable to stand or sit upright for at least 60 minutes.

Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Ibandronic Acid therapy. Adequate intake of calcium and vitamin D is important in all patients. Orally administered bisphosphonates may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when Ibandronic Acid is given to patients with active upper gastrointestinal problems (e.g. known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers). Adverse experiences such as esophagitis, esophageal ulcers and esophageal erosions, in some cases severe and requiring hospitalization, rarely with bleeding or followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. The risk of severe esophageal adverse experiences appears to be greater in patients who do not comply with the dosing instruction and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Patients should pay particular attention and be able to comply with the dosing instructions.

Physicians should be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue Ibandronic Acid and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn. While no increased risk was observed in controlled clinical trials there have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications. Since NSAIDs and bisphosphonates are both associated with gastrointestinal irritation, caution should be taken during concomitant medication with Ibandronic Acid. Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Known risk factors for osteonecrosis of the jaw include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), and co-morbid disorders (e.g., anemia, coagulopathy, infection, pre-existing dental disease). Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment.

It is likely that calcium supplements, antacids and some oral medications containing multivalent cations (such as aluminium, magnesium, iron) are likely to interfere with the absorption of Ibandronic Acid. Therefore, patients must wait 60 minutes after taking Ibandronic Acid before taking other oral medications. Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (estrogen). No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma. In healthy male volunteers and postmenopausal women, i.v. ranitidine caused an increase in ibandronic acid bioavailability of about 20 %, probably as a result of reduced gastric acidity. However, since this increase is within the normal range of the bioavailability of ibandronic acid, no dosage adjustment is required when Ibandronic Acid is administered with H2-antagonists or other drugs which increase gastric pH.

In relation to disposition, no drug interactions of clinical significance are considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats. Furthermore, plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other drugs. Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other drugs. In a one-year study in postmenopausal women with osteoporosis (BM16549). the incidence of upper gastrointestinal events in patients concomitantly taking aspirin or NSAIDs was similar in patients taking Ibandronic Acid 2.5 mg daily or 150mg once monthly. Of over 1500 patients enrolled in study BM 16549 comparing monthly with daily dosing regimens of ibandronic acid, 14% of patients used histamine (H2) blockers or proton pump inhibitors. Among these patients, the incidence of upper gastrointestinal events in the patients treated with Ibandronic Acid 150 mg once monthly was similar to that in patients treated with Ibandronic Acid 2.5 mg daily.

Pregnancy: Ibandronic Acid should not be used during pregnancy. There was no evidence for a direct fetal toxic or teratogenic effect of ibandronic acid in daily orally treated rats and rabbits and there were no adverse effects on the development in F1 offspring in rats. Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those observed with bisphosphonates as a class. They include a decreased number of implantation sites, interference with natural delivery (dystocia), and an increase in visceral variations (renal pelvis ureter syndrome). Specific studies for the monthly regimen have not been performed. There is no clinical experience with Ibandronic Acid in pregnant women.

Nursing Mothers: Ibandronic Acid should not be used during lactation. In lactating rats treated with 0.08 mg/kg/day IV. ibandronic acid, the highest concentration of ibandronic acid in breast milk was 8.1 ng/ml and was seen in the first 2 hours after i.v. administration. After 24 hours, the concentration in milk and plasma was similar, and corresponded to about 5 % of the concentration measured after 2 hours.

No specific information is available on the treatment of overdosage with ibandronic acid. However, oral overdosage may result in upper gastrointestinal adverse events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer. Milk or antacids should be given to bind ibandronic acid. Owing to the risk of esophageal irritation, vomiting should not be induced and the patient should remain fully upright.

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

Ibandronic acid is indicated for the treatment of postmenopausal osteoporosis, to reduce the risk of fractures.

Treatment of Osteoporosis: Osteoporosis may be confirmed by the finding of low bone mass (T-score <-2.0 SD) and the presence or history of osteoporotic fracture, or a low bone mass (T-score <-2.5 SD) in the absence of documented pre-existing osteoporotic fracture.

Bisphosphonate preparations

The pharmacodynamic action of ibandronic acid is inhibition of bone resorption. In vivo, ibandronic acid prevents experimentally induced bone destruction caused by cessation of gonadal function, retinoids, tumors or tumor extracts. In young (fast growing) rats, the endogenous bone resorption is also inhibited, leading to increased bone mass compared with untreated animals. Animal models confirm that ibandronic acid is a highly potent inhibitor of osteoclastic activity. In growing rats, there was no evidence of impaired mineralization even at doses greater than 5,000 times the dose required for osteoporosis treatment. The high potency and therapeutic margin of ibandronic acid allows for more flexible dosing regimens and intermittent treatment with long drug-free intervals at comparatively low doses.

Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of bisphosphonates, which act on bone tissue and specifically inhibit osteoclast activity, It does not interfere with osteoclast recruitment. The selective action of ibandronic acid on bone tissue is based on the high affinity of this compound for hydroxyapatite, which represents the mineral matrix of the bone. Ibandronic acid reduces bone resorption, with no direct effect on bone formation. In postmenopausal women, it reduces the elevated rate of bone turnover towards premenopausal levels, leading to a progressive net gain in bone mass. Daily or intermittent administration of ibandronic acid results in reduced bone resorption as reflected in reduced levels of serum and urinary biochemical markers of bone turnover, increased BMD and a decreased incidence of fractures.

The recommended dose of Ibandronic acid for treatment is one 150 mg film-coated tablet once a month. The tablet should preferably be taken on the same date each month. Ibandronic acid should be taken 60 minutes before the first food or drink (other than water) of the day or any other oral medication or supplementation (including calcium):

• Tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the patient is sitting or standing in an upright position. Patients should not lie down for 60 minutes after taking Ibandronic acid.
• Plain water is the only drink that should be taken with Ibandronic acid. Please note that some mineral waters may have a higher concentration of calcium and therefore should not be used.
• Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration. Patients should receive supplemental calcium or vitamin D if dietary intake is inadequate. In case a once-monthly dose is missed, patients should be instructed to take one Ibandronic Acid 150 mg tablet the morning after the tablet is remembered unless the time to the next scheduled dose is within 7 days. Patients should then return to taking their dose once a month on their originally scheduled date. If the next scheduled dose is within 7 days, patients should wait until their next dose and then continue taking one tablet once a month as originally scheduled. Patients should not take two 150 mg tablets within the same week.

The main side effects of ibandronic acid are dyspepsia, nausea, diarrhea, abdominal pain, muscle aches, headaches, dizziness.

Ibandronic Acid is contraindicated in patients with known hypersensitivity to ibandronic acid or to any of the excipients. Ibandronic Acid is contraindicated in patients with uncorrected hypocalcemia. As with all bisphosphonates indicated in the treatment of osteoporosis, pre-existing hypocalcemia needs to be corrected before initiating therapy with Ibandronic Acid. As with several bisphosphonates, Ibandronic Acid is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia. Ibandronic Acid is contraindicated in patients who are unable to stand or sit upright for at least 60 minutes.

Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Ibandronic Acid therapy. Adequate intake of calcium and vitamin D is important in all patients. Orally administered bisphosphonates may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when Ibandronic Acid is given to patients with active upper gastrointestinal problems (e.g. known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers). Adverse experiences such as esophagitis, esophageal ulcers and esophageal erosions, in some cases severe and requiring hospitalization, rarely with bleeding or followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. The risk of severe esophageal adverse experiences appears to be greater in patients who do not comply with the dosing instruction and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Patients should pay particular attention and be able to comply with the dosing instructions.

Physicians should be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue Ibandronic Acid and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn. While no increased risk was observed in controlled clinical trials there have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications. Since NSAIDs and bisphosphonates are both associated with gastrointestinal irritation, caution should be taken during concomitant medication with Ibandronic Acid. Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Known risk factors for osteonecrosis of the jaw include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), and co-morbid disorders (e.g., anemia, coagulopathy, infection, pre-existing dental disease). Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment.

It is likely that calcium supplements, antacids and some oral medications containing multivalent cations (such as aluminium, magnesium, iron) are likely to interfere with the absorption of Ibandronic Acid. Therefore, patients must wait 60 minutes after taking Ibandronic Acid before taking other oral medications. Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (estrogen). No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma. In healthy male volunteers and postmenopausal women, i.v. ranitidine caused an increase in ibandronic acid bioavailability of about 20 %, probably as a result of reduced gastric acidity. However, since this increase is within the normal range of the bioavailability of ibandronic acid, no dosage adjustment is required when Ibandronic Acid is administered with H2-antagonists or other drugs which increase gastric pH.

In relation to disposition, no drug interactions of clinical significance are considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats. Furthermore, plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other drugs. Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other drugs. In a one-year study in postmenopausal women with osteoporosis (BM16549). the incidence of upper gastrointestinal events in patients concomitantly taking aspirin or NSAIDs was similar in patients taking Ibandronic Acid 2.5 mg daily or 150mg once monthly. Of over 1500 patients enrolled in study BM 16549 comparing monthly with daily dosing regimens of ibandronic acid, 14% of patients used histamine (H2) blockers or proton pump inhibitors. Among these patients, the incidence of upper gastrointestinal events in the patients treated with Ibandronic Acid 150 mg once monthly was similar to that in patients treated with Ibandronic Acid 2.5 mg daily.

Pregnancy: Ibandronic Acid should not be used during pregnancy. There was no evidence for a direct fetal toxic or teratogenic effect of ibandronic acid in daily orally treated rats and rabbits and there were no adverse effects on the development in F1 offspring in rats. Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those observed with bisphosphonates as a class. They include a decreased number of implantation sites, interference with natural delivery (dystocia), and an increase in visceral variations (renal pelvis ureter syndrome). Specific studies for the monthly regimen have not been performed. There is no clinical experience with Ibandronic Acid in pregnant women.

Nursing Mothers: Ibandronic Acid should not be used during lactation. In lactating rats treated with 0.08 mg/kg/day IV. ibandronic acid, the highest concentration of ibandronic acid in breast milk was 8.1 ng/ml and was seen in the first 2 hours after i.v. administration. After 24 hours, the concentration in milk and plasma was similar, and corresponded to about 5 % of the concentration measured after 2 hours.

No specific information is available on the treatment of overdosage with ibandronic acid. However, oral overdosage may result in upper gastrointestinal adverse events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer. Milk or antacids should be given to bind ibandronic acid. Owing to the risk of esophageal irritation, vomiting should not be induced and the patient should remain fully upright.

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

Ibandronic acid is indicated for the treatment of postmenopausal osteoporosis, to reduce the risk of fractures.

Treatment of Osteoporosis: Osteoporosis may be confirmed by the finding of low bone mass (T-score <-2.0 SD) and the presence or history of osteoporotic fracture, or a low bone mass (T-score <-2.5 SD) in the absence of documented pre-existing osteoporotic fracture.

Bisphosphonate preparations

The pharmacodynamic action of ibandronic acid is inhibition of bone resorption. In vivo, ibandronic acid prevents experimentally induced bone destruction caused by cessation of gonadal function, retinoids, tumors or tumor extracts. In young (fast growing) rats, the endogenous bone resorption is also inhibited, leading to increased bone mass compared with untreated animals. Animal models confirm that ibandronic acid is a highly potent inhibitor of osteoclastic activity. In growing rats, there was no evidence of impaired mineralization even at doses greater than 5,000 times the dose required for osteoporosis treatment. The high potency and therapeutic margin of ibandronic acid allows for more flexible dosing regimens and intermittent treatment with long drug-free intervals at comparatively low doses.

Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of bisphosphonates, which act on bone tissue and specifically inhibit osteoclast activity, It does not interfere with osteoclast recruitment. The selective action of ibandronic acid on bone tissue is based on the high affinity of this compound for hydroxyapatite, which represents the mineral matrix of the bone. Ibandronic acid reduces bone resorption, with no direct effect on bone formation. In postmenopausal women, it reduces the elevated rate of bone turnover towards premenopausal levels, leading to a progressive net gain in bone mass. Daily or intermittent administration of ibandronic acid results in reduced bone resorption as reflected in reduced levels of serum and urinary biochemical markers of bone turnover, increased BMD and a decreased incidence of fractures.

The recommended dose of Ibandronic acid for treatment is one 150 mg film-coated tablet once a month. The tablet should preferably be taken on the same date each month. Ibandronic acid should be taken 60 minutes before the first food or drink (other than water) of the day or any other oral medication or supplementation (including calcium):

• Tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the patient is sitting or standing in an upright position. Patients should not lie down for 60 minutes after taking Ibandronic acid.
• Plain water is the only drink that should be taken with Ibandronic acid. Please note that some mineral waters may have a higher concentration of calcium and therefore should not be used.
• Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration. Patients should receive supplemental calcium or vitamin D if dietary intake is inadequate. In case a once-monthly dose is missed, patients should be instructed to take one Ibandronic Acid 150 mg tablet the morning after the tablet is remembered unless the time to the next scheduled dose is within 7 days. Patients should then return to taking their dose once a month on their originally scheduled date. If the next scheduled dose is within 7 days, patients should wait until their next dose and then continue taking one tablet once a month as originally scheduled. Patients should not take two 150 mg tablets within the same week.

The main side effects of ibandronic acid are dyspepsia, nausea, diarrhea, abdominal pain, muscle aches, headaches, dizziness.

Ibandronic Acid is contraindicated in patients with known hypersensitivity to ibandronic acid or to any of the excipients. Ibandronic Acid is contraindicated in patients with uncorrected hypocalcemia. As with all bisphosphonates indicated in the treatment of osteoporosis, pre-existing hypocalcemia needs to be corrected before initiating therapy with Ibandronic Acid. As with several bisphosphonates, Ibandronic Acid is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia. Ibandronic Acid is contraindicated in patients who are unable to stand or sit upright for at least 60 minutes.

Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Ibandronic Acid therapy. Adequate intake of calcium and vitamin D is important in all patients. Orally administered bisphosphonates may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when Ibandronic Acid is given to patients with active upper gastrointestinal problems (e.g. known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers). Adverse experiences such as esophagitis, esophageal ulcers and esophageal erosions, in some cases severe and requiring hospitalization, rarely with bleeding or followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. The risk of severe esophageal adverse experiences appears to be greater in patients who do not comply with the dosing instruction and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Patients should pay particular attention and be able to comply with the dosing instructions.

Physicians should be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue Ibandronic Acid and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn. While no increased risk was observed in controlled clinical trials there have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications. Since NSAIDs and bisphosphonates are both associated with gastrointestinal irritation, caution should be taken during concomitant medication with Ibandronic Acid. Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Known risk factors for osteonecrosis of the jaw include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), and co-morbid disorders (e.g., anemia, coagulopathy, infection, pre-existing dental disease). Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment.

It is likely that calcium supplements, antacids and some oral medications containing multivalent cations (such as aluminium, magnesium, iron) are likely to interfere with the absorption of Ibandronic Acid. Therefore, patients must wait 60 minutes after taking Ibandronic Acid before taking other oral medications. Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (estrogen). No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma. In healthy male volunteers and postmenopausal women, i.v. ranitidine caused an increase in ibandronic acid bioavailability of about 20 %, probably as a result of reduced gastric acidity. However, since this increase is within the normal range of the bioavailability of ibandronic acid, no dosage adjustment is required when Ibandronic Acid is administered with H2-antagonists or other drugs which increase gastric pH.

In relation to disposition, no drug interactions of clinical significance are considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats. Furthermore, plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other drugs. Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other drugs. In a one-year study in postmenopausal women with osteoporosis (BM16549). the incidence of upper gastrointestinal events in patients concomitantly taking aspirin or NSAIDs was similar in patients taking Ibandronic Acid 2.5 mg daily or 150mg once monthly. Of over 1500 patients enrolled in study BM 16549 comparing monthly with daily dosing regimens of ibandronic acid, 14% of patients used histamine (H2) blockers or proton pump inhibitors. Among these patients, the incidence of upper gastrointestinal events in the patients treated with Ibandronic Acid 150 mg once monthly was similar to that in patients treated with Ibandronic Acid 2.5 mg daily.

Pregnancy: Ibandronic Acid should not be used during pregnancy. There was no evidence for a direct fetal toxic or teratogenic effect of ibandronic acid in daily orally treated rats and rabbits and there were no adverse effects on the development in F1 offspring in rats. Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those observed with bisphosphonates as a class. They include a decreased number of implantation sites, interference with natural delivery (dystocia), and an increase in visceral variations (renal pelvis ureter syndrome). Specific studies for the monthly regimen have not been performed. There is no clinical experience with Ibandronic Acid in pregnant women.

Nursing Mothers: Ibandronic Acid should not be used during lactation. In lactating rats treated with 0.08 mg/kg/day IV. ibandronic acid, the highest concentration of ibandronic acid in breast milk was 8.1 ng/ml and was seen in the first 2 hours after i.v. administration. After 24 hours, the concentration in milk and plasma was similar, and corresponded to about 5 % of the concentration measured after 2 hours.

No specific information is available on the treatment of overdosage with ibandronic acid. However, oral overdosage may result in upper gastrointestinal adverse events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer. Milk or antacids should be given to bind ibandronic acid. Owing to the risk of esophageal irritation, vomiting should not be induced and the patient should remain fully upright.

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

Ibandronic acid is indicated for the treatment of postmenopausal osteoporosis, to reduce the risk of fractures.

Treatment of Osteoporosis: Osteoporosis may be confirmed by the finding of low bone mass (T-score <-2.0 SD) and the presence or history of osteoporotic fracture, or a low bone mass (T-score <-2.5 SD) in the absence of documented pre-existing osteoporotic fracture.

Bisphosphonate preparations

The pharmacodynamic action of ibandronic acid is inhibition of bone resorption. In vivo, ibandronic acid prevents experimentally induced bone destruction caused by cessation of gonadal function, retinoids, tumors or tumor extracts. In young (fast growing) rats, the endogenous bone resorption is also inhibited, leading to increased bone mass compared with untreated animals. Animal models confirm that ibandronic acid is a highly potent inhibitor of osteoclastic activity. In growing rats, there was no evidence of impaired mineralization even at doses greater than 5,000 times the dose required for osteoporosis treatment. The high potency and therapeutic margin of ibandronic acid allows for more flexible dosing regimens and intermittent treatment with long drug-free intervals at comparatively low doses.

Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of bisphosphonates, which act on bone tissue and specifically inhibit osteoclast activity, It does not interfere with osteoclast recruitment. The selective action of ibandronic acid on bone tissue is based on the high affinity of this compound for hydroxyapatite, which represents the mineral matrix of the bone. Ibandronic acid reduces bone resorption, with no direct effect on bone formation. In postmenopausal women, it reduces the elevated rate of bone turnover towards premenopausal levels, leading to a progressive net gain in bone mass. Daily or intermittent administration of ibandronic acid results in reduced bone resorption as reflected in reduced levels of serum and urinary biochemical markers of bone turnover, increased BMD and a decreased incidence of fractures.

The recommended dose of Ibandronic acid for treatment is one 150 mg film-coated tablet once a month. The tablet should preferably be taken on the same date each month. Ibandronic acid should be taken 60 minutes before the first food or drink (other than water) of the day or any other oral medication or supplementation (including calcium):

• Tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the patient is sitting or standing in an upright position. Patients should not lie down for 60 minutes after taking Ibandronic acid.
• Plain water is the only drink that should be taken with Ibandronic acid. Please note that some mineral waters may have a higher concentration of calcium and therefore should not be used.
• Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration. Patients should receive supplemental calcium or vitamin D if dietary intake is inadequate. In case a once-monthly dose is missed, patients should be instructed to take one Ibandronic Acid 150 mg tablet the morning after the tablet is remembered unless the time to the next scheduled dose is within 7 days. Patients should then return to taking their dose once a month on their originally scheduled date. If the next scheduled dose is within 7 days, patients should wait until their next dose and then continue taking one tablet once a month as originally scheduled. Patients should not take two 150 mg tablets within the same week.

The main side effects of ibandronic acid are dyspepsia, nausea, diarrhea, abdominal pain, muscle aches, headaches, dizziness.

Ibandronic Acid is contraindicated in patients with known hypersensitivity to ibandronic acid or to any of the excipients. Ibandronic Acid is contraindicated in patients with uncorrected hypocalcemia. As with all bisphosphonates indicated in the treatment of osteoporosis, pre-existing hypocalcemia needs to be corrected before initiating therapy with Ibandronic Acid. As with several bisphosphonates, Ibandronic Acid is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia. Ibandronic Acid is contraindicated in patients who are unable to stand or sit upright for at least 60 minutes.

Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Ibandronic Acid therapy. Adequate intake of calcium and vitamin D is important in all patients. Orally administered bisphosphonates may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when Ibandronic Acid is given to patients with active upper gastrointestinal problems (e.g. known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers). Adverse experiences such as esophagitis, esophageal ulcers and esophageal erosions, in some cases severe and requiring hospitalization, rarely with bleeding or followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. The risk of severe esophageal adverse experiences appears to be greater in patients who do not comply with the dosing instruction and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Patients should pay particular attention and be able to comply with the dosing instructions.

Physicians should be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue Ibandronic Acid and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn. While no increased risk was observed in controlled clinical trials there have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications. Since NSAIDs and bisphosphonates are both associated with gastrointestinal irritation, caution should be taken during concomitant medication with Ibandronic Acid. Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Known risk factors for osteonecrosis of the jaw include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), and co-morbid disorders (e.g., anemia, coagulopathy, infection, pre-existing dental disease). Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment.

It is likely that calcium supplements, antacids and some oral medications containing multivalent cations (such as aluminium, magnesium, iron) are likely to interfere with the absorption of Ibandronic Acid. Therefore, patients must wait 60 minutes after taking Ibandronic Acid before taking other oral medications. Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (estrogen). No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma. In healthy male volunteers and postmenopausal women, i.v. ranitidine caused an increase in ibandronic acid bioavailability of about 20 %, probably as a result of reduced gastric acidity. However, since this increase is within the normal range of the bioavailability of ibandronic acid, no dosage adjustment is required when Ibandronic Acid is administered with H2-antagonists or other drugs which increase gastric pH.

In relation to disposition, no drug interactions of clinical significance are considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats. Furthermore, plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other drugs. Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other drugs. In a one-year study in postmenopausal women with osteoporosis (BM16549). the incidence of upper gastrointestinal events in patients concomitantly taking aspirin or NSAIDs was similar in patients taking Ibandronic Acid 2.5 mg daily or 150mg once monthly. Of over 1500 patients enrolled in study BM 16549 comparing monthly with daily dosing regimens of ibandronic acid, 14% of patients used histamine (H2) blockers or proton pump inhibitors. Among these patients, the incidence of upper gastrointestinal events in the patients treated with Ibandronic Acid 150 mg once monthly was similar to that in patients treated with Ibandronic Acid 2.5 mg daily.

Pregnancy: Ibandronic Acid should not be used during pregnancy. There was no evidence for a direct fetal toxic or teratogenic effect of ibandronic acid in daily orally treated rats and rabbits and there were no adverse effects on the development in F1 offspring in rats. Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those observed with bisphosphonates as a class. They include a decreased number of implantation sites, interference with natural delivery (dystocia), and an increase in visceral variations (renal pelvis ureter syndrome). Specific studies for the monthly regimen have not been performed. There is no clinical experience with Ibandronic Acid in pregnant women.

Nursing Mothers: Ibandronic Acid should not be used during lactation. In lactating rats treated with 0.08 mg/kg/day IV. ibandronic acid, the highest concentration of ibandronic acid in breast milk was 8.1 ng/ml and was seen in the first 2 hours after i.v. administration. After 24 hours, the concentration in milk and plasma was similar, and corresponded to about 5 % of the concentration measured after 2 hours.

No specific information is available on the treatment of overdosage with ibandronic acid. However, oral overdosage may result in upper gastrointestinal adverse events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer. Milk or antacids should be given to bind ibandronic acid. Owing to the risk of esophageal irritation, vomiting should not be induced and the patient should remain fully upright.

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

This Kit is indicated for the treatment and prevention of osteoporosis in women (especially after menopause) & men. It increases bone mineral density (BMD) and reduces the incidence of vertebral fractures.

Minerals in bone formation, Specific mineral preparations

One tablet of Ibandronic Acid 150 mg once monthly of the same date of each month is recommended. To maximize the clinical benefit of Ibandronic Acid, two tablets of Calcium Orotate per day are usually recommended in divided dosage.

To maximize absorption and clinical benefit, Ibandronic Acid tablet of this Kit should be taken at least 60 minutes before the first food or drink (other than water) of the day or before taking any oral medication or supplementation, including calcium, antacids, or vitamins.

To facilitate delivery to the stomach and thus reduce the potential for esophageal irritation, Ibandronic Acid tablet should be swallowed whole with a full glass of plain water (250 ml) while the patient is standing or sitting in an upright position. Patients should not lie down for 60 minutes after taking Ibandronic Acid tablet.

Ibandronic Acid 150 mg tablet of this Kit should be taken on the same date of each month (i.e., the patients Ibandronic Acid day)

If the once monthly dose is missed, and the patients next scheduled Ibandronic Acid day is more than 7 days away, the patient should be instructed to take one Ibandronic Acid 150 mg tablet in the morning following the date that it is remembered. The patient should then return to taking one Ibandronic Acid 150 mg tablet every month in the morning of their chosen day, according to their original schedule.

If the once monthly dose is missed, and the patients next scheduled Ibandronic Acid day is only 1 to 7 days away, the patient must wait until the subsequent month’s scheduled Ibandronic Acid day to take their tablet. The patient should then return to taking one Ibandronic Acid 150 mg tablet every month in the morning of their chosen day according to their original schedule.

The Patient must not take two Ibandronic Acid 150 mg tablets within the same week.

Start taking Calcium Orotate tablets from the next day of Ibandronic Acid day (from day-2 and onwards).

Ibandronic Acid: Common side effects include Hypertension, Dyspepsia, Nausea, Diarrhea, Abdominal Pain, Arthralgia, Back Pain, Localized Osteoarthritis, Myalgia, Muscle Cramp, Influenza, Nasopharyngitis, Bonchitis, Urinary Tract Infection, Upper Respiratory Tract Infection, Headache, Dizziness, Skin Rash, Insomnia etc.

Calcium Orotate: Bloating and swelling in the abdomen are common side effects of Calcium Orotate, loss of appetite, upset stomach, constipation, nausea, vomiting, unusual weight loss, mood changes, bone/muscle pain, headache, increased thirst/urination, weakness, unusual tiredness, formation of kidney stones may occur infrequently.

Ibandronic Acid: Abnormalities of the esophagus, hypocalcemia, known hypersensitivity to Ibandronic Acid or any of its components.

Calcium Orotate: Incomplete bowel movements, Kidney stone, Kidney disease and lung disease.

Ibandronic Acid:

• Ibandronic Acid of this Kit may cause local irritation of the upper gastrointestinal mucosa.
• Adequate intake of Calcium is important in all patient hypocalcaemia
• Severe and occasionally incapacitating bone joint, and/or muscle pain has been reported in patients taking Ibandronic Acid.
• Ibandronic Acid is not recommended for use in patients with severe renal impairment (Creatinine clearance of <30 ml/min).

Calcium Orotate: Before taking Calcium Orotate, precaution is needed if the patient is allergic to Calcium Orotate. Any Calcium supplement taken without food may increase the risk of kidney stones. Therefore, it is advisable that Calcium Orotate be taken with food.

Ibandronic Acid: Products containing calcium and other multivalent cautions (such as aluminium, magnesium, iron) are likely to interfere with absorption of Ibandronic Acid. Ibandronic Acid should be taken at least 60 minutes before any oral medications. Aspirin, NSAIDs, and bisphosphonates are all associated with gasrointestinal irritation, caution should be exercised in the concomitant use of aspirin of NSNADs with Ibandronic Acid.

Calcium Orotate: Calcium can decrease the absorption of the other drugs such as bisphosphonates (e.g., alendronate/risedronate), quinolone antibiotics (e.g., ciprofloxacin, levofloxacin), and tetracycline antibiotic (e.g., doxycycline, levofloxacin).

There are no adequate and well-controlled studies in pregnant women for this kit. This kit should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus. It is not known whether this kit is excreted in human milk. Caution should be exercised when this kit is administered to a nursing woman.

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

Renal and hepatic impaired patient: No dose adjustment is necessary for patients with mild or moderate renal impairment where creatinine clearance is equal to or greater than 30 ml/min. No dose adjustment is required for patients with hepatic impairment.

Store in a cool & dry place, protected from light. Keep all medicines out of reach of children.

Bisphosphonate preparations

Alendronate is a bisphosphonate that binds to bone hydroxyapatite and specifically inhibits the activity of osteoclasts, the bone-resorbing cells. Alendronate reduces bone resorption with no direct effect on bone formation, although the latter process is ultimately reduced because bone resorption and formation are coupled during bone turnover.

Animal studies have indicated the following mode of action. At the cellular level, alendronate shows preferential localization to sites of bone resorption, specifically under osteoclasts. The osteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption. Alendronate does not interfere with osteoclast recruitment or attachment, but it does inhibit osteoclast activity. Studies in mice on the localization of radioactive [3H] alendronate in bone showed about 10-fold higher uptake on osteoclast surfaces than on osteoblast surfaces. Bones examined 6 and 49 days after [3H] alendronate administration in rats and mice, respectively, showed that normal bone was formed on top of the alendronate, which was incorporated inside the matrix. While incorporated in bone matrix, alendronate is not pharmacologically active. Thus, alendronate must be continuously administered to suppress osteoclasts on newly formed resorption surfaces. Histomorphometry in baboons and rats showed that alendronate treatment reduces bone turnover (i.e., the number of sites at which bone is remodeled). In addition, bone formation exceeds bone resorption at these remodeling sites, leading to progressive gains in bone mass.

Treatment of Osteoporosis in Postmenopausal Women: The recommended dosage is one 70 mg tablet once weekly or one bottle of 70 mg oral solution once weekly or one 10 mg tablet once daily.

Prevention of Osteoporosis in Postmenopausal Women: The recommended dosage is one 35 mg tablet once weekly or one 5 mg tablet once daily.

Treatment to Increase Bone Mass in Men with Osteoporosis: The recommended dosage is one 70 mg tablet once weekly or one bottle of 70 mg oral solution once weekly or one 10 mg tablet once daily.

Treatment of Glucocorticoid-Induced Osteoporosis: The recommended dosage is one 5 mg tablet once daily, except for postmenopausal women not receiving estrogen, for whom the recommended dosage is one 10 mg tablet once daily.

Treatment of Paget's Disease of Bone: The recommended treatment regimen is 40 mg once a day for six months.

The commonest symptomatic side effects are constipation, diarrhoea, oesophageal ulcer, flatulence, dysphagia, musculoskeletal pain, headache, rarely rash, erythema, transient decrease in serum calcium and phosphate, nausea, vomiting, peptic ulceration, hypersensitivity reactions including urticaria and angio-oedema.

Alendronic acid is contraindicated in patients with the following conditions: 

• Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia.
• Inability to stand or sit upright for at least 30 minutes.
• Do not administer Alendronic acid oral solution to patients at increased risk of aspiration.
• Hypocalcemia.
• Hypersensitivity to any component of this product. Hypersensitivity reactions including urticaria and angioedema have been reported.

The incidence of upper gastrointestinal side effects are increased with the concomitant use of non-steroidal anti-inflammatory agents and aspirin. Absorption of Alendronate is reduced in the presence of antacids and calcium supplements.

Alendronic acid should not be given to pregnant women or nursing mother.

Pediatric Use: Alendronic acid is not indicated for use in pediatric patients.

Renal Impairment: Alendronic acid is not recommended for patients with creatinine clearance less than 35 mL/min. No dosage adjustment is necessary in patients with creatinine clearance values between 35-60 mL/min.

Hepatic Impairment: As there is evidence that alendronate is not metabolized or excreted in the bile, no studies were conducted in patients with hepatic impairment. No dosage adjustment is necessary.

Store in a well-closed container at room temperature, 15-30°C

Alendronic Acid & Vitamin D3 is indicated in:

• Treatment of osteoporosis in postmenopausal women.
• Treatment of osteoporosis in men.
• Treatment of osteoporosis as it increases the bone mass and reduces the incidence of fractures, including those of the hip and spine.

Combined preparations: Inhibiting bone resorption

Alendronate Sodium is a bisphosphonate that acts as a specific inhibitor of osteoclast mediated bone resorption. Alendronate is effective when administered at least 30 minutes before breakfast. It transiently distributes to soft tissues following administration but is then rapidly distributed to bone or excreted in the urine. Protein binding in human plasma is approximately 78%. There is no evidence that Alendronate is metabolised in animals or humans. At the cellular level, Alendronate shows preferential localization to sites of bone resorption, specially under osteoclasts. It inhibits osteoclast activity. In addition, bone formation exceeds bone resorption, leading to progressive gains in bone mass. Vitamin D is required for normal bone formation. Vitamin D insufficiency develops when both sunlight exposure and dietary intake are inadequate. Insufficiency is associated with negative calcium balance, increased parathyroid hormone levels, bone loss, and increased risk of skeletal fracture.

Treatment of Osteoporosis in Postmenopausal Women: The recommended dosage is-

• 70 mg alendronate and 2800 IU vitamin D3 or
• 70 mg alendronate and 5600 IU vitamin D3 tablet once weekly.
• For most osteoporotic women, the appropriate dose is 70 mg alendronate and 5600 IU vitamin D3 once weekly.

Treatment to Increase Bone Mass in Men with Osteoporosis: The recommended dosage is-

• 70 mg alendronate and 2800 IU vitamin D3 or
• 70 mg alendronate and 5600 IU D3 tablet once weekly.
• For most osteoporotic men, the appropriate dose is 70 mg alendronate and 5600 IU vitamin D3 once weekly.

To permit adequate absorption, Alendronate & Colecalciferol must be taken at least 30 minutes before the first food, beverage or medication of the day with plain water only. Other beverages (including mineral water), food and some medications are likely to reduce the absorption of Alendronate. To facilitate delivery to the stomach and thus to reduce the potential for esophageal irritation, Alendronate & Colecalciferol tablet should only be swallowed upon rising for the day with a full glass of water. Patients should not lie down for at least 30 minutes after taking Alendronate until after their first food of the day. Alendronate & Colecalciferol should not be taken at bed time.

Usually mild and generally do not require discontinuation of therapy. Side effects include esophageal reactions, abdominal pain and distension, diarrhoea or constipation, flatulence, musculoskeletal pain, headache, rash, erythema and transient decreases in serum calcium and phosphate.

Hypocalcaemia and other disturbances of mineral metabolism should be corrected before initiation of therapy. Alendronate can cause local irritation of the upper gastro-intestinal mucosa. Caution should be used when Alendronate is given to patients with active upper gastrointestinal problems such as dysphagia, esophageal disease, gastritis, duodenitis or ulcers. Patients should stop taking medicine and consult their physician if they develop esophageal diseases.

Calcium supplement, antacids and some oral medications will interfere with absorption of Alendronate if taken at the same time. Intravenous ranitidine makes the bioavailability of oral Alendronate double. Incidence of upper gastro-intestinal adverse events associated with NSAID and aspirin appears to be greater with concomitant administration of Alendronate. Mineral oils, orlistat, and bile acid sequestrants (e.g., cholestyramine, colestipol) may impair the absorption of vitamin D. Anticonvulsants, cimetidine, and thiazides may increase the catabolism of vitamin D.

Pregnancy category C. Overdoses of vitamin D have shown teratogenic effects in pregnant animals. Alendronic Acid & Vitamin D3 (Colecalciferol) should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus. Cholecalciferol and some of its active metabolites pass into breast milk. It is not known whether alendronate is excreted in human milk. Caution should be exercised when administered to lactating women.

Dosing in elderly and renal insufficiency: No dosage adjustment is necessary for the elderly or for patients with mild-to-moderate renal insufficiency (creatinine clearance 35 to 60 mL/min). Alendronic Acid + Vitamin D3 (Colecalciferol) is not recommended for patients with more severe renal insufficiency (creatinine clearance<35 mL/min) due to lack of experience.

Hypocalcemia, hypophosphatemia, and upper gastrointestinal adverse events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer, may result from oral overdosage.  Signs and symptoms of vitamin D toxicity include hypercalcemia, hypercalciuria, anorexia, nausea, vomiting, polyuria, polydipsia, weakness, and lethargy.

Store in a cool and dry place. Protect from light & moisture. Keep out of the reach of children.

Ibandronic acid is indicated for the treatment of postmenopausal osteoporosis, to reduce the risk of fractures.

Treatment of Osteoporosis: Osteoporosis may be confirmed by the finding of low bone mass (T-score <-2.0 SD) and the presence or history of osteoporotic fracture, or a low bone mass (T-score <-2.5 SD) in the absence of documented pre-existing osteoporotic fracture.

Bisphosphonate preparations

The pharmacodynamic action of ibandronic acid is inhibition of bone resorption. In vivo, ibandronic acid prevents experimentally induced bone destruction caused by cessation of gonadal function, retinoids, tumors or tumor extracts. In young (fast growing) rats, the endogenous bone resorption is also inhibited, leading to increased bone mass compared with untreated animals. Animal models confirm that ibandronic acid is a highly potent inhibitor of osteoclastic activity. In growing rats, there was no evidence of impaired mineralization even at doses greater than 5,000 times the dose required for osteoporosis treatment. The high potency and therapeutic margin of ibandronic acid allows for more flexible dosing regimens and intermittent treatment with long drug-free intervals at comparatively low doses.

Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of bisphosphonates, which act on bone tissue and specifically inhibit osteoclast activity, It does not interfere with osteoclast recruitment. The selective action of ibandronic acid on bone tissue is based on the high affinity of this compound for hydroxyapatite, which represents the mineral matrix of the bone. Ibandronic acid reduces bone resorption, with no direct effect on bone formation. In postmenopausal women, it reduces the elevated rate of bone turnover towards premenopausal levels, leading to a progressive net gain in bone mass. Daily or intermittent administration of ibandronic acid results in reduced bone resorption as reflected in reduced levels of serum and urinary biochemical markers of bone turnover, increased BMD and a decreased incidence of fractures.

The recommended dose of Ibandronic acid for treatment is one 150 mg film-coated tablet once a month. The tablet should preferably be taken on the same date each month. Ibandronic acid should be taken 60 minutes before the first food or drink (other than water) of the day or any other oral medication or supplementation (including calcium):

• Tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the patient is sitting or standing in an upright position. Patients should not lie down for 60 minutes after taking Ibandronic acid.
• Plain water is the only drink that should be taken with Ibandronic acid. Please note that some mineral waters may have a higher concentration of calcium and therefore should not be used.
• Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration. Patients should receive supplemental calcium or vitamin D if dietary intake is inadequate. In case a once-monthly dose is missed, patients should be instructed to take one Ibandronic Acid 150 mg tablet the morning after the tablet is remembered unless the time to the next scheduled dose is within 7 days. Patients should then return to taking their dose once a month on their originally scheduled date. If the next scheduled dose is within 7 days, patients should wait until their next dose and then continue taking one tablet once a month as originally scheduled. Patients should not take two 150 mg tablets within the same week.

The main side effects of ibandronic acid are dyspepsia, nausea, diarrhea, abdominal pain, muscle aches, headaches, dizziness.

Ibandronic Acid is contraindicated in patients with known hypersensitivity to ibandronic acid or to any of the excipients. Ibandronic Acid is contraindicated in patients with uncorrected hypocalcemia. As with all bisphosphonates indicated in the treatment of osteoporosis, pre-existing hypocalcemia needs to be corrected before initiating therapy with Ibandronic Acid. As with several bisphosphonates, Ibandronic Acid is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia. Ibandronic Acid is contraindicated in patients who are unable to stand or sit upright for at least 60 minutes.

Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Ibandronic Acid therapy. Adequate intake of calcium and vitamin D is important in all patients. Orally administered bisphosphonates may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when Ibandronic Acid is given to patients with active upper gastrointestinal problems (e.g. known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers). Adverse experiences such as esophagitis, esophageal ulcers and esophageal erosions, in some cases severe and requiring hospitalization, rarely with bleeding or followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. The risk of severe esophageal adverse experiences appears to be greater in patients who do not comply with the dosing instruction and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Patients should pay particular attention and be able to comply with the dosing instructions.

Physicians should be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue Ibandronic Acid and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn. While no increased risk was observed in controlled clinical trials there have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications. Since NSAIDs and bisphosphonates are both associated with gastrointestinal irritation, caution should be taken during concomitant medication with Ibandronic Acid. Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Known risk factors for osteonecrosis of the jaw include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), and co-morbid disorders (e.g., anemia, coagulopathy, infection, pre-existing dental disease). Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment.

It is likely that calcium supplements, antacids and some oral medications containing multivalent cations (such as aluminium, magnesium, iron) are likely to interfere with the absorption of Ibandronic Acid. Therefore, patients must wait 60 minutes after taking Ibandronic Acid before taking other oral medications. Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (estrogen). No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma. In healthy male volunteers and postmenopausal women, i.v. ranitidine caused an increase in ibandronic acid bioavailability of about 20 %, probably as a result of reduced gastric acidity. However, since this increase is within the normal range of the bioavailability of ibandronic acid, no dosage adjustment is required when Ibandronic Acid is administered with H2-antagonists or other drugs which increase gastric pH.

In relation to disposition, no drug interactions of clinical significance are considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats. Furthermore, plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other drugs. Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other drugs. In a one-year study in postmenopausal women with osteoporosis (BM16549). the incidence of upper gastrointestinal events in patients concomitantly taking aspirin or NSAIDs was similar in patients taking Ibandronic Acid 2.5 mg daily or 150mg once monthly. Of over 1500 patients enrolled in study BM 16549 comparing monthly with daily dosing regimens of ibandronic acid, 14% of patients used histamine (H2) blockers or proton pump inhibitors. Among these patients, the incidence of upper gastrointestinal events in the patients treated with Ibandronic Acid 150 mg once monthly was similar to that in patients treated with Ibandronic Acid 2.5 mg daily.

Pregnancy: Ibandronic Acid should not be used during pregnancy. There was no evidence for a direct fetal toxic or teratogenic effect of ibandronic acid in daily orally treated rats and rabbits and there were no adverse effects on the development in F1 offspring in rats. Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those observed with bisphosphonates as a class. They include a decreased number of implantation sites, interference with natural delivery (dystocia), and an increase in visceral variations (renal pelvis ureter syndrome). Specific studies for the monthly regimen have not been performed. There is no clinical experience with Ibandronic Acid in pregnant women.

Nursing Mothers: Ibandronic Acid should not be used during lactation. In lactating rats treated with 0.08 mg/kg/day IV. ibandronic acid, the highest concentration of ibandronic acid in breast milk was 8.1 ng/ml and was seen in the first 2 hours after i.v. administration. After 24 hours, the concentration in milk and plasma was similar, and corresponded to about 5 % of the concentration measured after 2 hours.

No specific information is available on the treatment of overdosage with ibandronic acid. However, oral overdosage may result in upper gastrointestinal adverse events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer. Milk or antacids should be given to bind ibandronic acid. Owing to the risk of esophageal irritation, vomiting should not be induced and the patient should remain fully upright.

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