Bovine Colostrum, Vitamin A, D, E, K & Zinc Powder

Each serve (3 g) of INSTAMUNE® provides:

Bovine Colostrum (with 30% IgG)-1000 mg Zinc-3.3 mg

Vitamin K-10 mcg

Vitamin A-1200 IU

Vitamin D-90 IU

Vitamin E-4 IU

Powder

90 grams per pack

4.1 Therapeutic indication

For children & adults to boost immunity.

4.2 Posology and method of administration

Recommended usage level:

Take one spoonful (3 g) with ½ cup of Milk/Water.

4.3 Contraindications

Known allergy to bovine colostrum or any of the ingredient of this product.

4.4 Special warnings and precautions for use

• Allergen Information: Product may contain Milk.
• This product shall be given only under medical advice by Physician / Certified Dietician / Nutritionist.
• This product is not to be used as a substitute for a varied diet.
• This product is not intended to diagnose, treat, cure or prevent any disease.

4.5 Drugs interactions

Bovine colostrum is generally well-tolerated, and no significant herb or drug interactions have been widely reported.

However, individuals with a known allergy to cow’s milk should avoid it.

4.6 Use in special populations

General Precautions: Due to the lack of comprehensive studies, it’s generally recommended to be cautious and it’s essential to consult with a healthcare provider before incorporating bovine colostrum into your diet during pregnancy or lactation.

4.7 Effects on ability to drive and use machines

There is no specific evidence to suggest that bovine colostrum has any direct effects on driving ability or use of machines. No effect anticipated.

4.8 Undesirable effects

• Colostrum is a high-protein, low fat and reduced lactose dairy product, as a result lactose-intolerant individuals generally experience no problems and some even report that colostrum helps with their condition. Colostrum used naturally contains low levels of lactose and during processing these are reduced further. If you can drink milk without any problem, then you can probably take colostrum.
• Some individuals may experience a mild gastrointestinal distress or a bloated feeling, which can be avoided by lowering the dose.
• If this reaction continues however then it is best to discontinue the colostrum treatment. However, as with all health supplements, it is always advisable to consult with your doctor in the first instance.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com

Website: https://www.zuventus.co.in/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

• Not to exceed the recommended daily usage.
• Overdosing on bovine colostrum is not well-documented, but taking it in excessive amounts could potentially lead to some side effects. Gastrointestinal Issues: High doses of bovine colostrum might cause nausea, bloating, diarrhea, or other digestive discomforts.
• In case of accidental overdose, contact a Healthcare Professional.

5.1 Pharmacodynamic properties

Bovine colostrum is a nutrient-rich fluid produced by cows in the first few days after giving birth. It’s packed with proteins, antibodies, and growth factors that help newborn calves thrive. For humans, bovine colostrum is often used in supplements due to its potential health benefits, such as boosting immunity, fighting infections, and promoting gut health.

This “early” milk has a nutrient profile and immunological composition significantly different from “mature” milk. In addition to macronutrients found in milk such as protein, carbohydrate, and fat, and micronutrients including vitamins and minerals, BC contain:

–Oligosaccharides,

–Growth factors,

– Antimicrobial compounds, &

– Immune-regulating constituents

either not present in milk or present in substantially lower concentrations.

Colostrum supports the human in two main ways.

1. Its multiple immune factors and natural antibiotics provide strong support for the immune system.

2.Its many growth factors offer a broad- spectrum boost to encourage optimum health and healing.

• The immunoglobulin, growth factors, antibodies play a role in prevention of infection that is in passive immunity.
• The vital nutrients help for tissue development, growth and energy.
• The growth factors present in the colostrum provide a novel treatment option for gastrointestinal conditions.

5.3 Pharmacokinetic properties

• Colostrum survives human GIT & works on mucosal surfaces: Bovine colostrum contains special glycoproteins and protease inhibitors which are extremely effective at protecting the destruction of colostrum’s active components (immunoglobulins and growth factors) by adult human digestive acids pancreatic enzymes and human stomach acids. This allows them to remain active as they pass into the bowel.
• The major benefit of immune factors from colostrum was shown to be their protective activity in the intestine on the walls of the bowel, and bronchials, (mucosal surfaces).
• The preservation of the biological activity of IgG (immunoglobulin) in the digestive secretions of adults receiving bovine immune colostrum orally indicates – passive enteral (intestinal) immunization for the prevention and treatment of acute intestinal diseases.
• Bovine colostrum has been shown to be safe, natural, effective & biologically transferable for human use.

6.1 Animal Toxicology or Pharmacology

Not available

Bovine Colostrum: Universal Donor of Colostrum to Human

• Only bovine colostrum has been shown to be safe, natural, effective & biologically transferable for human use.
• Colostrum is a nontoxic, non-allergenic food supplement that has no negative interactions with drugs, food, or other supplements.
• Bovine colostrum is not a drug: It is a safe, natural, non-allergenic food, taken by humans to treat and heal different conditions
• Help create new levels of vitality & well-being.

8.1 Incompatibilities

Not Applicable

8.2 Shelf-life

Refer on pack

8.3 Packaging information

Pack net weight:90 g Approximately Serving Size: 1 (3 g) No. of servings per pack: 30

8.4 Storage and handing instructions

Store below 30°C.

Protect from moisture.

Product is required to be stored out of reach of children.

• NOT FOR MEDICINAL USE.
• Not to be used as a substitute for a varied diet.
• Not intended to diagnose, treat, cure or prevent any disease.
• This product shall be given only under medical advice by Physician / Certified Dietician / Nutritionist.
• Not to exceed the recommended daily usage.

25th September 2024

Ferrous ascorbate, Folic Acid, Methylcobalamin and Zinc sulphate

Each Film-coated tablet contains:

Ferrous ascorbate equivalent to Elemental iron 100mg

Folic Acid IP 1.5mg

Methylcobalamin IP 1.5 mg

Zinc sulphate monohydrate eq. 22.5 mg

to Elemental Zinc

Excipients q.s.

Colour: Red Oxide of Iron and Titanium Dioxide IP

Film coated tablet

Ferrous Ascorbate 100 mg, Folic Acid 1.5 mg, Methylcobalamin 1.5 mg, Zinc Sulphate 22.5mg

4.1 Therapeutic indications

For the treatment of iron deficiency anemia.

4.2 Posology and method of administration

Adults

One tablet should be taken once daily by mouth.

Pediatric Population

There is no relevant use of Feronia HP Tablets in the pediatric population.

4.3 Contraindications

• Hypersensitivity to the active substances or any of the excipients.
• Paroxysmal nocturnal hemoglobinuria, hemosiderosis, haemochromatosis, active peptic ulcer, repeated blood transfusion, regional enteritis and ulcerative colitis.
• Feronia HP Tablets must not be used in the treatment of anemias other than those due to iron deficiency.
• Copper deficiency: Zinc may inhibit the absorption of Copper

4.4 Special warnings and precautions for use

CAUTION: Tablets are hygroscopic in nature. Exposure to humid conditions may soften the tablets affecting their appearance and shape. Cutting of strip should be avoided while dispensing/usage.

The label will state “Important warning: Contains Iron. Keep out of reach and sight of children, as overdose may be fatal”.

This will appear on the front of the pack within a rectangle in which there is no other information.

Some post-gastrectomy patients show poor absorption of iron. Care is needed when treating iron deficiency anemia in patients with treated or controlled peptic ulceration. Caution should be exercised when administering folic acid to patients who may have folate dependent tumors.

Since anemia due to combined iron and vitamin B12 or folate deficiencies may be microcytic in type, patients with microcytic anemia resistant to therapy with iron alone should be screened for vitamin B12 or folate deficiency.

Accumulation of zinc may occur in cases of renal failure.

Pregnancy

Safety is not established in pregnant women; therefore Feronia HP is not recommended in pregnancy.

Lactation

Safety is not established in lactating women; therefore Feronia HP is not recommended during lactation.

Pediatric population

Feronia HP Tablets should be kept out of the reach of children.

4.5 Interaction with other medicinal products and other forms of interaction

• Iron reduces the absorption of penicillamine. Iron compounds impair the bioavailability of fluoroquinolones, levodopa, carbidopa, thyroxine and bisphosphonates.
• Absorption of both iron and antibiotic may be reduced if Feronia HP is given with tetracycline.
• Concurrent administration of antacids may reduce absorption of iron. Co- trimoxazole, chloramphenicol, sulphasalazine, aminopterin, methotrexate, pyrimethamine or sulphonamides may interfere with folate metabolism. Serum levels of anticonvulsant drugs may be reduced by administration of folate.
• Oral chloramphenicol delays plasma iron clearance, incorporation of iron into red blood cells and interferes with erythropoiesis.
• Some inhibition of iron absorption may occur if it is taken with cholestyramine, trientine, tea, eggs or milk.
• Administration of oral iron may increase blood pressure in patients receiving methyldopa.
• Coffee may be a factor in reducing iron bioavailability. Neomycin may alter the absorption of iron.
• The absorption of zinc may be reduced by calcium supplements, tetracyclines and phosphorus-containing compounds, agents which increase gastric pH, such as H2 blockers, may decrease zinc absorption while zinc may reduce the absorption of penicillamine, tetracyclines, fluoroquinolones.

Food

Studies of the co-administration of zinc with food performed in healthy volunteers showed that the absorption of zinc was significantly delayed by many foods (including bread, hard boiled eggs, coffee and milk). Substances in food, especially phytates and fibres, bind zinc and prevent it from entering the intestinal cells. However, protein appears to interfere the least.

4.6 Fertility, pregnancy and lactation

Pregnancy

Safety is not established in pregnant women; therefore Feronia HP is not recommended in pregnancy. Breast-feeding Safety is not established in lactating women; therefore Feronia HP is not recommended during lactation. Fertility No fertility data is available.

4.7 Effects on ability to drive and use machines

Feronia HP Tablets has no influence on the ability to drive and use machines.

4.8 Undesirable effects

Very rare (<1/10,000)

Very rare (<1/10,000):

Rarely allergic reactions may occur.

Not known (cannot be estimated from the available data)

Not known: Gastrointestinal disorders Gastro-intestinal discomfort, anorexia, nausea, vomiting, constipation, diarrhea.

Not known: Renal and urinary disorders Darkening of the stools may occur. Blood amylase, lipase and alkaline phosphatase increased

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to:medico@zuventus.com

Website: http://www.zuventus.co.in/safety.aspx

4.9 Overdose

Symptoms

Symptoms and signs of abdominal pain, vomiting and diarrhea appear within 60 minutes. Cardiovascular collapse with coma may follow. Some improvement may occur after this phase which, in some patients, is followed by recovery. In others, after about 16 hours, deterioration may occur involving diffuse vascular congestion, pulmonary edema, convulsions, anuria, hypothermia, severe shock, metabolic acidosis, coagulation abnormalities and hypoglycemia.

Management

Vomiting should be induced immediately, followed as soon as possible by parenteral injection of desferrioxamine mesylate, and then gastric lavage. In the meantime, it is helpful to give milk and/or 5% sodium bicarbonate solution by mouth.

Dissolve 2g desferrioxamine mesylate in 2 to 3ml of water for injections and give intramuscularly. A solution of 5g desferrioxamine in 50 to 100ml of fluid may be left in the stomach. If desferrioxamine is not available, leave 300ml of 1 % to 5 % sodium bicarbonate in the stomach. Fluid replacement is essential.

Recovery may be complicated by long-term sequelae such as hepatic necrosis, pyloric stenosis or acute toxic encephalitis which may lead to CNS damage.

Treatment of overdose should be with gastric lavage or induced emesis as quickly as possible to remove unabsorbed zinc. Heavy metal chelation therapy should be considered if plasma zinc levels are markedly elevated (> 10 mg/l).

Pediatric population

Acute overdose of oral iron requires emergency treatment. In young children 200-250mg/kg Ferrous Ascorbate is considered to be extremely dangerous.

5.1 Mechanism of Action/ Pharmacodynamic properties

Iron absorption occurs predominantly in the duodenum and upper jejunum. Iron is oxidized to the Fe3+ state no matter its original form when taken in orally. Gastric acidity as well as solubilizing agents such as ascorbate prevent precipitation of the normally insoluble Fe3+. Intestinal mucosal cells in the duodenum and upper jejunum absorb the iron. The iron is coupled to transferrin (Tf) in the circulation which delivers it to the cells of the body. A feedback mechanism exists that enhances iron absorption in people who are iron deficient. In contrast, people with iron overload dampen iron absorption. A number of dietary factors influence iron absorption. Ascorbate increase iron uptake in part by acting as weak chelators to help to solubilize the metal in the duodenum. Iron is readily transferred from these compounds into the mucosal lining cells.

Zinc supplementation improves immunity.

Zinc deficiency also has direct effects on the gastrointestinal tract such as impaired intestinal brush border, increased secretion in response to bacterial enterotoxins and perturbations in intestinal permeability. Zinc supplementation improves the transport of water and electrolytes across the intestinal mucosa in experimental zinc deficiency.

Zinc plays a fundamental role in cellular metabolism and is postulated to modulate host resistance to various infections.

5.2 Pharmacokinetic properties

Absorption

Iron is absorbed chiefly in the duodenum and jejunum. Folic Acid is absorbed mainly from the proximal part of the small intestine.

Distribution

The amounts of Folic Acid absorbed from normal diets are rapidly distributed in body tissues.

Biotransformation

Absorption being aided by the acid secretion of the stomach and being more readily affected when the iron is in the ferrous state.

Folic acid rapidly appears in the blood, where it is extensively bound to plasma proteins.

When larger amounts are absorbed, a high proportion is metabolized in the liver to other active forms of folate and a proportion is stored as reduced and methylated folate.

Elimination

Larger amounts of folate are rapidly excreted in the urine and about 4 to 5 micrograms is excreted in the urine daily.

Zinc is absorbed in the small intestine and its absorption kinetics suggest a tendency to saturation at increasing doses. Fractional zinc absorption is negatively correlated with zinc intake. It ranges from 30 to 60% with usual dietary intake (7-15 mg/d) and decreases to 7% with pharmacological doses of 100 mg/d.

In the blood, about 80% of absorbed zinc is distributed to erythrocytes, with most of the remainder being bound to albumin and other plasma proteins. The liver is the main storage for zinc and hepatic zinc levels are increased during maintenance therapy with zinc. The plasma elimination half-life of zinc in healthy subjects is around 1 hour after a dose of 45 mg. The elimination of zinc results primarily from fecal excretion with relatively little from urine and sweat. The fecal excretion is in the greatest part due to the passage of unabsorbed zinc but it is also due to endogenous intestinal secretion.

This Product (tablet) contains: Ferrous Ascorbate, Folic Acid, Methylcobalamin and Zinc sulphate as active ingredients, for the treatment of iron deficiency anemia.

Ferrous Ascorbate is an iron supplement used to treat or prevent low blood levels of iron (such as those caused by anemia or during pregnancy). Ascorbic acid (vitamin C) improves the absorption of iron from the stomach.

Molecular Formula- C₁₂H₁₄FeO₁₂ Molecular Weight: 406.08g/mol

Folic acid is used to treat anemia caused by folate deficiency. Folic acid is also used as a supplement by women during pregnancy to reduce the risk of neural tube defects (NTDs) in the baby.

Molecular Formula-C₁₉H₁₉N₇O₆

Molecular Weight- 441.4 g/mol

Zinc is an essential trace element for humans, animals, plants and for microorganisms and is necessary for prenatal and postnatal development. Zinc is also an essential nutrient element for coral growth as it is an important cofactor for many enzymes.

Molecular Formula-ZnSO₄

Molecular Weight- 179.47 g/mol

Methylcobalamin a form of vitamin B12.

Methylcobalamin is equivalent physiologically to vitamin B12, and can be used to prevent or treat pathology arising from a lack of vitamin B12 intake. Methylcobalamin is also used in the treatment of peripheral neuropathy, diabetic neuropathy, and as a preliminary treatment for amyotrophic lateral sclerosis.

Molecular formula: C63H91CoN13O14P

Molecular weight: 1344.405 g·mol−1

8.1 Incompatibilities

Not applicable.

8.2 Shelf-life

Refer on pack.

8.3 Packaging information

3 blister strips of 10 tablets each

8.4 Storage and handing instructions

Store at a temperature not exceeding 25°C. Protect from light.

Keep out of reach of children.

Patient Counselling Information

• WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor immediately.
• Feronia HP Tablet is given to fulfil your nutritional requirement and to prevent any related diseases.
• Avoid taking antacids 2 hours before or after taking Feronia HP Tablet as they may make it harder for your body to absorb the medicine.
• Let your doctor know if you are taking any other medications like antihypertensive, antibiotics, or medicines for heart disease or bone disorders.

Sept 2024

Ferrous Ascorbate, Folic Acid, Cyanocobalamin, Pyridoxine Hydrochloride & Cholecalciferol Tablets

Each film coated tablet contains:

Ferrous Ascorbate IP

equivalent to Elemental Iron 100 mg

Folic Acid IP 1.5 mg

Cyanocobalamin IP 7.5 mcg

(Vitamin B12)

Pyridoxine Hydrochloride IP 1.5 mg

(Vitamin B6)

Cholecalciferol IP 1000 IU (Vitamin D3) (As stabilized form) Excipients q.s. Colours: Lake of Sunset Yellow,

Lake of Erythrosine & Titanium Dioxide IP

Film coated tablet

Ferrous ascorbate (100mg), Folic Acid (1.5mg), Cyanocobalamin (7.5 mcg), Pyridoxine Hydrochloride (1.5 mg), Cholecalciferol IP (1000 IU)

4.1 Therapeutic indications

Treatment and prevention of anemia with multivitamin deficiency

4.2 Posology and method of administration

Adults

One tablet to be taken daily orally

Pediatric Population

There is no relevant use of Feronia-D3 Tablets in the pediatric population.

4.3 Contraindications

• Hypersensitivity to the active substances or any of the excipients.
• Paroxysmal nocturnal hemoglobinuria, hemosiderosis, haemochromatosis, active peptic ulcer, repeated blood transfusion, regional enteritis and ulcerative colitis.
• Hypercalcaemia and/or hypercalciuria
• Nephrolithiasis (Renal calculi)
• Hypervitaminosis
• Severe renal impairment

4.4 Special warnings and precautions for use

• CAUTION: Tablets are hygroscopic in nature. Exposure to humid conditions may soften the tablets affecting their appearance and shape. Cutting of strip to be avoided while dispensing /usage.
• Important warning: Contains Iron. Keep out of reach and sight of children, as overdose may be fatal.
• Some post-gastrectomy patients show poor absorption of iron. Care is needed when treating iron deficiency anemia in patients with treated or controlled peptic ulceration. Caution should be exercised when administering folic acid to patients who may have folate dependent tumors.
• Since anemia due to combined iron and vitamin B12 or folate deficiencies may be microcytic in type, patients with microcytic anemia resistant to therapy with iron alone should be screened for vitamin B12 or folate deficiency.
• Cholecalciferol should be used with caution in patients with impairment of renal function and the effect on calcium and phosphate levels should be monitored. The risk of soft tissue calcification should be taken into account. In patients with severe renal insufficiency, vitamin D in the form of Cholecalciferol is not metabolised normally and other forms of vitamin D should be used. Cholecalciferol should not be taken by patients with a tendency to form calcium-containing renal calculi.
• Caution is required in patients receiving treatment for cardiovascular disease

Pediatric population

Feronia D3 Tablets should be kept out of the reach of children.

4.5 Interaction with other medicinal products and other forms of interaction

• Iron reduces the absorption of penicillamine. Iron compounds impair the bioavailability of fluoroquinolones, levodopa, carbidopa, thyroxine and bisphosphonates.
• Absorption of both iron and antibiotic may be reduced if Feronia D3 is given with tetracycline.
• Absorption of both iron and zinc are reduced if taken concomitantly. Concurrent administration of antacids may reduce absorption of iron. Co- trimoxazole, chloramphenicol, sulphasalazine, aminopterin, methotrexate, pyrimethamine or sulphonamides may interfere with folate metabolism. Serum levels of anticonvulsant drugs may be reduced by administration of folate.
• Oral chloramphenicol delays plasma iron clearance, incorporation of iron into red blood cells and interferes with erythropoiesis.
• Patients treated with cardiac glycosides may be susceptible to high calcium levels and should have ECG parameters and calcium levels monitored. It is recommended to reduce the dose or interrupt treatment if the calcium content in the urine exceeds 7.5 mmol/24 hours (300 mg/24 hours).
• Simultaneous administration of benzothiadiazine derivatives (thiazide diuretics) increases the risk of hypercalcaemia because they decrease the calcium excretion in the urine. The calcium levels in plasma and urine should therefore be monitored for patients undergoing long-term treatment.
• If Cholecalciferol is combined with metabolites or analogues of vitamin D careful monitoring of serum calcium levels is recommended.
• Some inhibition of iron absorption may occur if it is taken with cholestyramine, trientine, tea, eggs or milk.
• Administration of oral iron may increase blood pressure in patients receiving methyldopa.
• Coffee may be a factor in reducing iron bioavailability. Neomycin may alter the absorption of iron.
• Anti-convulsants e.g. phenytoin, phenobarbital, primidone may diminish the effect of Cholecalciferol due to hepatic enzyme induction.
• Rifampicin may reduce the effectiveness of Cholecalciferol due to hepatic enzyme induction.
• Isoniazid may reduce the effectiveness of Colecalciferol due to inhibition of the metabolic activation of Colecalciferol.
• Drugs leading to fat malabsorption, e.g. orlistat, liquid paraffin, cholestyramine, may impair the absorption of Cholecalciferol.
• The cytotoxic agent actinomycin and imidazole antifungal agents interfere with vitamin D activity.
• Concomitant use of glucocorticoids can decrease the effect of vitamin D.

4.6 Fertility, pregnancy and lactation

Pregnancy

The use of Feronia D3 Tablets may be considered during pregnancy, if necessary.

The development of anemia despite prophylaxis with Feronia D3 Tablets calls for investigation. During pregnancy women should follow the advice of their medical practitioner as their requirements may vary depending on the severity of their disease and their response to treatment.

Breast-feeding

It is unknown whether Ferrous Ascorbate and Folic Acid / metabolites are excreted in human milk.

A risk to the newborns/infants cannot be excluded.

Cholecalciferol and its metabolites are excreted in breast milk. Overdose in infants induced by nursing mothers has not been observed. However, when prescribing additional vitamin D to a breast-fed child the practitioner should consider the dose of any additional vitamin D given to the mother.

Fertility

No fertility data is available.

4.7 Effects on ability to drive and use machines

Feronia D3 Tablets has no influence on the ability to drive and use machines. Cholecalciferol has no known side effects that are likely to affect the ability to drive and use or operate machines.

4.8 Undesirable effects

Very rare (<1/10,000)

Very rare (<1/10,000): Rarely allergic reactions may occur. Not known (cannot be estimated from the available data) Not known: Gastrointestinal disorders Gastro-intestinal discomfort, anorexia, nausea, vomiting, constipation, diarrhea. Not known: Renal and urinary disorders Darkening of the stools may occur. Rarely Hypercalcemia, Hypercalciuria

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to:medico@zuventus.com

Website: Website: https://www.zuventus.com/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Symptoms

Symptoms and signs of abdominal pain, vomiting and diarrhea appear within 60 minutes. Cardiovascular collapse with coma may follow. Some improvement may occur after this phase which, in some patients, is followed by recovery. In others, after about 16 hours, deterioration may occur involving diffuse vascular congestion, pulmonary edema, convulsions, anuria, hypothermia, severe shock, metabolic acidosis, coagulation abnormalities and hypoglycemia.

Acute or chronic overdose of Cholecalciferol can cause hypercalcaemia, an increase in the serum and urinary concentrations of calcium. The symptoms of hypercalcaemia are not very specific and consist of nausea, vomiting, diarrhoea often in the early stages and later constipation, anorexia, fatigue, headache, muscle and joint pain, muscle weakness, polydipsia, polyuria formation of renal calculi, nephrocalcinosis, kidney failure, calcification of soft tissues, changes in ECG measurements, arrhythmias and pancreatitis. In rare and isolated cases there are reports that hypercalcaemia is fatal.

Management

Vomiting should be induced immediately, followed as soon as possible by parenteral injection of desferrioxamine mesylate, and then gastric lavage. In the meantime, it is helpful to give milk and/or 5% sodium bicarbonate solution by mouth.

Dissolve 2g desferrioxamine mesylate in 2 to 3ml of water for injections and give intramuscularly. A solution of 5g desferrioxamine in 50 to 100ml of fluid may be left in the stomach. If desferrioxamine is not available, leave 300ml of 1 % to 5 % sodium bicarbonate in the stomach. Fluid replacement is essential.

Recovery may be complicated by long-term sequelae such as hepatic necrosis, pyloric stenosis or acute toxic encephalitis which may lead to CNS damage.

A normalisation of hypercalcaemia due to vitamin D intoxication lasts several weeks. The recommendation for the treatment of hypercalcaemia is the avoidance of any further administration of vitamin D, including supplements, dietary intakes and the avoidance of sunlight. A low calcium or calcium-free diet can also be considered.

Rehydration and the treatment with diuretics e.g. furosemide to ensure adequate diuresis should be considered. Additional treatment with calcitonin or corticosteroids can also be considered.

Phosphate infusions should not be administered to lower hypercalcaemia of hypervitaminosis D because of the dangers of metastatic calcification.

Pediatric population

Acute overdose of oral iron requires emergency treatment. In young children 200-250mg/kg Ferrous Ascorbate is considered to be extremely dangerous.

5.1 Mechanism of Action/ Pharmacodynamic properties

Iron absorption occurs predominantly in the duodenum and upper jejunum. Iron is oxidized to the Fe3+ state no matter its original form when taken in orally. Gastric acidity as well as solubilizing agents such as ascorbate prevent precipitation of the normally insoluble Fe3+. Intestinal mucosal cells in the duodenum and upper jejunum absorb the iron. The iron is coupled to transferrin (Tf) in the circulation which delivers it to the cells of the body. A feedback mechanism exists that enhances iron absorption in people who are iron deficient. In contrast, people with iron overload dampen iron absorption. A number of dietary factors influence iron absorption. Ascorbate increase iron uptake in part by acting as weak chelators to help to solubilize the metal in the duodenum. Iron is readily transferred from these compounds into the mucosal lining cells.

Cholecalciferol is produced within the skin under the influence of UV radiation including sunlight. In its biologically active form, Cholecalciferol stimulates intestinal calcium absorption, incorporation of calcium into the osteoid, and release of calcium from bone tissue. In the small intestine it promotes rapid and delayed calcium uptake. The passive and active transport of phosphate is also stimulated. In the kidney, it inhibits the excretion of calcium and phosphate by promoting tubular resorption. The production of parathyroid hormone (PTH) in the parathyroids is inhibited directly by the biologically active form of Cholecalciferol. PTH secretion is inhibited additionally by the increased calcium uptake in the small intestine under the influence of biologically active Cholecalciferol.

Elimination: Cholecalciferol and other forms of vitamin D are excreted in feces and urine.

• Iron participates in the second activation step of vitamin D, necessary to make this hormone functional.
• This conversion is done by a renal 25-hydroxyvitamin D 1α-hydroxylase (1α-OHase) enzyme which comprises a CYP-450, a ferredoxin, and a ferredoxin reductase.
• Therefore, less available iron could compromise production of the active form of vitamin D.

5.2 Pharmacokinetic properties

Folic Acid is absorbed mainly from the proximal part of the small intestine.

Distribution

The amounts of Folic Acid absorbed from normal diets are rapidly distributed in body tissues.

Biotransformation

Absorption being aided by the acid secretion of the stomach and being more readily affected when the iron is in the ferrous state.

Folic acid rapidly appears in the blood, where it is extensively bound to plasma proteins.

When larger amounts are absorbed, a high proportion is metabolized in the liver to other active forms of folate and a proportion is stored as reduced and methylated folate.

Elimination

Larger amounts of folate are rapidly excreted in the urine and about 4 to 5 micrograms is excreted in the urine daily.

The pharmacokinetics of Cholecalciferol have been widely studied and are well-known. Cholecalciferol from nutritional sources is almost completely absorbed from within the gastro-intestinal tract in the presence of dietary lipids and bile acids. Cholecalciferol is stored in fat cells and its biological half-life is approximately 50 days.

Cholecalciferol is metabolised by microsomal hydroxylase to form 25-hydroxycolecalciferol (25(OH)D3, calcidiol), the primary storage form of vitamin D3. 25(OH)D3 undergoes a secondary hydroxylation within the kidney to form the predominant active metabolite 1,25-hydroxycolecalciferol (1,25(OH)2D3, calcitriol). The metabolites circulate in the blood bound to a specific α -globin.

After a single oral dose of Cholecalciferol, the maximum serum concentrations of the primary storage form are reached after approximately 7 days. 25(OH)D3 is then slowly eliminated with an apparent half-life in serum of about 50 days. Cholecalciferol and its metabolites are excreted mainly in the bile and feces.

After high doses of Cholecalciferol, serum concentrations of 25(OH)D3 may be increased for months. Overdose-induced hypercalcemia may persist for weeks

This Product (tablet) contains: Ferrous Ascorbate, Folic Acid Cyanocobalamin, Pyridoxine and Cholecalciferol as active ingredients, for the treatment and prevention of Anemia with multivitamin deficiency.

Ferrous Ascorbate is an iron supplement used to treat or prevent low blood levels of iron (such as those caused by anemia or during pregnancy). Ascorbic acid (vitamin C) improves the absorption of iron from the stomach.

Vitamin D promotes calcium absorption in the gut and maintains adequate serum calcium and phosphate concentrations to enable normal bone mineralization and to prevent hypocalcemic tetany.

Folic acid is used to treat anemia caused by folate deficiency. Folic acid is also used as a supplement by women during pregnancy to reduce the risk of neural tube defects (NTDs) in the baby.

Molecular Formula-C₁₉H₁₉N₇O₆

Molecular Weight- 441.4 g/mol

8.1 Incompatibilities

Not applicable.

8.2 Shelf-life

Refer on pack.

8.3 Packaging information

3 Blister strips of 10 tablets each

8.4 Storage and handing instructions

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

• WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor immediately.
• Feronia -D3 Tablet is given to fulfill your nutritional requirement and to prevent any related diseases.
• Avoid taking antacids 2 hours before or after taking Feronia-D3 Tablet as they may make it harder for your body to absorb the medicine.
• Let your doctor know if you are taking any other medications like antihypertensive, antibiotics, or medicines for heart disease or bone disorders.

25^th Sept 2024

Efonidipine Hydrochloride Ethanolate Tablets 10 mg / 20 mg / 40 mg

EFNOCAR-10

Each film coated tablet contains:

Efonidipine Hydrochloride Ethanolate 10 mg

Excipients q.s.

Colour: Titanium Dioxide IP

EFNOCAR-20

Each film coated tablet contains:

Efonidipine Hydrochloride Ethanolate 20 mg

Excipients q.s.

Colour: Titanium Dioxide IP

EFNOCAR-40

Each film coated tablet contains:

Efonidipine Hydrochloride Ethanolate 40 mg

Excipients q.s.

Colour: Titanium Dioxide IP

Film coated tablet

10/ 20/40 mg

4.1 Therapeutic Indication

Efonidipine is indicated for the management of

• Essential hypertension and renal parenchymal hypertension
• Angina

4.2 Posology and method of administration

Adults

• Essential hypertension and renal parenchymal hypertension: 20-40 mg orally once daily. A dose of up to 80 mg/day has been reported to be safe and effective in clinical trials.
• Angina: 40 mg/day.

Elderly

Efonidipine should be started with a low dose (20mg/day) and the patient's condition should be monitored. The dose should be halved in case the patient is intolerant to the higher dose.

In Children

Efonidipine is not recommended in infants and children as safety is not established in this group of patients.

4.3 Contraindications

• In patients with known hypersensitivity to Efonidipine or any other component of the formulation
• In pregnant women

4.4 Special warnings and precautions for use

• Should be administered with caution in patients with hepatic impairment.
• Should be administered with caution in patients with low BP and/or sinus node dysfunction.
• The drug should be withdrawn gradually to prevent rebound hypertension or worsening of angina.
• Administration of the drug may cause hypotension. Under such circumstances appropriate measures should be taken to either reduce the dose or withdraw the drug.
• Should not be taken with grapefruit juice as there may be excessive lowering of blood pressure.
• Dizziness may occur while taking antihypertensive agents. Hence, working on aerial platform, working with dangerous machinery and/or driving should be avoided.
• To be sold by retail on the prescription of Cardiologist / Nephrologist / Endocrinologist and Specialist in General / Internal medicine / Critical Care medicine only.

4.5 Drugs interactions

Concomitant administration of other antihypertensive agent/s may enhance the antihypertensive effect of efonidipine.

• Administration of calcium channel blockers (CCBs) with Cimetidine may cause elevated levels of CCBs.
• Increased levels of CCBs observed when taken concomitantly with grapefruit juice which may result in excessive lowering of blood pressure.
• Efonidipine when taken along with Tacrolimus may cause increased blood levels of Tacrolimus.

4.6 Use in special populations

Pregnancy

Efonidipine should not be administered in pregnant women.

Nursing Mothers

Efonidipine should not be administered in lactating women.

4.7 Effects on ability to drive and use machines

If patients taking Efonidipine suffer from dizziness, headache, fatigue or nausea the ability to react may be impaired. Caution is recommended especially at the start of treatment.

4.8 Undesirable effects

The common side effects are hot flushes, palpitations, facial flushing and headache. In addition, elevation in serum total cholesterol, ALT (SGPT), AST (SGOT) and BUN may occur.

Tabulated list of adverse reactions

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to:medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting

4.9 Overdose

In humans, experience with intentional overdose is limited. The stomach should be emptied by aspiration and gastric lavage if the patient reports immediately or up to two hours after overdosage.

Clinically significant hypotension due to Efonidipine overdosage calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade.

5.1 Mechanism of Action

Efonidipine, a new generation dihydropyridine (DHP) calcium channel blocker, inhibits both L-type and T-type calcium channels.

5.2 Pharmacodynamic properties

• Efonidipine exhibits antihypertensive effect through vasodilatation by blocking L-type and T-type calcium channels.
• Efonidipine has a negative chronotropic effect. Working on sino atrial node cells by inhibiting T-type calcium channel activation, Efonidipine prolongs the late phase-4 depolarization of the sino atrial node action potential and suppresses an elevated HR. The negative chronotropic effect of Efonidipine decreases heart rate, myocardial oxygen demand and increases coronary blood flow.
• Efonidipine increases coronary blood flow by blocking L & T-type calcium channels and attenuates myocardial ischaemia.
• By reducing synthesis and secretion of aldosterone, Efonidipine prevents hypertrophy and remodeling of cardiac myocytes.
• Efonidipine increases glomerular filtration rate without increasing intra-glomerular pressure and filtration fraction. This prevents hypertension induced renal damage.
• Efonidipine prevents Rho-kinase and NF-kB induced renal parenchymal fibrosis and provides long term renal protection.
• Efonidipine suppresses renin secretion from the Juxta Glomerular apparatus in the kidneys. •Efonidipine enhances sodium excretion from the kidneys by suppressing aldosterone synthesis and secretion from the adrenal glands. Aldosterone induced renal parenchymal fibrosis is suppressed by Efonidipine. •Efonidipine prevents NF-kB induced hypertrophy and inflammation in the renal vasculature and protects the kidneys.
• Efonidipine protects against endothelial dysfunction due to its anti-oxidant activity and by restoring nitric oxide bioavailability.
• Efonidipine has anti-atherogenic activity and protects the blood vessels from atherosclerosis.
• Efonidipine lowers blood pressure in cerebral resistance vessels and prevents hypertension induced brain damage.

5.3 Pharmacokinetic properties

Absorption

Peak plasma concentration is achieved in about 1.5 to 3.67 hours after administration. The bioavailability of Efonidipine is ~25% and half-life is approximately 4 hours.

Efonidipine 40mg when administered to healthy volunteers under fasting conditions shows the following pharmacokinetic profile:

The dissociation constant of Efonidipine from dihydropyridine receptors is very low (0.0042/min/nM), signifying very slow dissociation from the receptors. This explains the long duration of action of Efonidipine.

Metabolism

Efonidipine is primarily metabolized in the liver. The important metabolites are N-dephenylated Efonidipine (DPH), deaminated Efonidipine (AL) and N-debenzylated Efonidipine (DBZ). DBZ and DPH exhibit activity as calcium antagonists. The vasodilating properties of DBZ and DPH were about two-thirds and one-third respectively than that of the parent compound. Results suggest that the majority of the pharmacological effect after oral dosing of Efonidipine hydrochloride in man is due to unchanged compound and its metabolites make a small contribution to the pharmacological effect.

Elimination

Biliary route is the main pathway of excretion. No significant amount of unchanged drug is excreted in urine. In the urine collected for 24 h after an oral dosing, 1.1% of the dose was excreted as deaminated Efonidipine, and 0.5% as a pyridine analogue of deaminated Efonidipine.

6.1 Animal Toxicology or Pharmacology

The acute toxicology of efonidipine was studied in male and female mice, rats, and dogs following oral or intravenous administration. The intravenous LD, values in male mice and rats were 77 and 51 mg/kg, respectively. The oral LD, values for efonidipine in mice, rats, and dogs were higher than 1,500 mag. The signs of toxicity observed in mice and rats were depression of spontaneous movement, hypothermia, sedation, piloerection, lying, gasping, and clonic convulsion. The dogs developed mild diarrhea, soft stools, or a temporary decrease in food consumption.

A 13-week oral subacute toxicity study of efonidipine was performed in male or female rats and dogs. Increases in water consumption and urine volume were observed in male and female rats receiving efonidipine at 300 mg/kg/day. Urinalysis revealed a high concentration of Na+ and C1- in the rats receiving 100 or 300 mg/kg/day. Organ weight measurement revealed an increase in liver and heart weight in male animals receiving 10 mg/kg/day or more and in female animals receiving 30 mg/kg/day or more.

Thus, in this study, the noneffective dose level was 3 mg/kg/day in rats. The effects observed at 300 or 100 mg/kg/day in groups of male or female dogs included reversible hyperemia of the sclera. Pathological examination revealed a dose-induced increase in the absolute and relative heart weight in female dogs treated with the drug at 100 mg/kg/day or more. Thus, the maximum noneffective dose of efonidipine in dogs of either sex was estimated to be around 30 mg/kg/day.

An oral chronic toxicity study of efonidipine was carried out in rats and dogs. Efonidipine was administered to rats at a daily dose of 1.5, 7, or 30 mg/kg for one year.

Organ weight measurement revealed an increase or a tendency of increase in heart weight in male or female rats receiving 30 mg/kg/day. A decreased thyroid weight in the males and an elevated liver weight in the females were found in the 30 mg/kg/day group.

Therefore, the noneffective estimated oral dose of efonidipine in rats was 7 mg/kg/day. Efonidipine in a gelatin capsule containing 2.0, 6.5, or 20 mg/kg/day was administered to dogs once daily for one year. The estimated effective dose was ca 20 mg/kg/day and the noneffective dose was ca 6.5 mg/kg/day

Efonidipine is a novel dihydropyridine calcium channel blocker having anti-hypertensive and anti-anginal properties.

Chemical name: (±) -2 - [benzyl (phenyl) amino] ethyl 1, 4-dihydro-2 ,6-dimethyl- 5-(5,5-dimethyl-2-oxo-1 ,3,2-dioxaphosphorinan-2-yl) -4 - (3-nitrophenyl) -3-pyridinecarboxylate hydrochloride ethanol.

Molecular formula: C34H38 N3O7P • HCl •C2H6O

Molecular mass: 714.18 g/mol

8.1 Incompatibilities

Not applicable.

8.2 Shelf-life

Refer on pack

8.3 Packaging information

10 Blister strips of 10 tablets each

8.4 Storage and handing instructions

• Store below 25°C. Protected from light & moisture.
• Keep out of reach of children.

Efnocar is a type of medicine known as a calcium channel blocker (CCB). It is used to treat high blood pressure (hypertension) and a type of chest pain called angina. It can be used by itself or with other medicines to treat these conditions. Do not use Efnocar if you are allergic to efonidipine (the active ingredient in Efnocar), or to the inactive ingredients.

Tell your doctor about any prescription and non-prescription medicines you are taking, including natural or herbal remedies. Tell your doctor if you:

• ever had heart disease
• ever had liver problems
• are pregnant, or plan to become pregnant.
• are breast-feeding. Do not breast-feed while taking Efnocar.

You can stop breast-feeding or take a different medicine.

It may be easier to take your dose if you do it at the same time every day, such as with breakfast or dinner, or at bedtime.

While you are taking Efnocar do not stop taking your other prescription medicines, including any other blood pressure medicines, without talking to your doctor.

09/10/2024