Promag Double Action

Uses

Adult: One Calcium Carbonate 500 tablet or as directed by the physician. For the prevention of osteoporosis, 1-3 Calcium Carbonate 500 tablet is recommended generally as a dietary supplement . Doses for children is half of those for adults. A large dose should not be taken without physician\'s advice.

Adolescent: One to two Calcium Carbonate tablet daily.

Children: One Calcium Carbonate tablet daily.

Famotidine is used for-

• Short term treatment of active duodenal ulcer and benign gastric ulcer
• Maintenance therapy for prevention of relapses of duodenal ulceration
• Gastro-oesophageal reflux disease
• Zollinger Ellison Syndrome

Acid regurgitation, Constipation, Gastric ulcer, Gastrointestinal hyperacidity, Heartburn, Indigestion, Non ulcer dyspepsia, Osmotic laxative

Promag Double Action is also used to associated treatment for these conditions: Acid Reflux, Acid indigestion, Bloating, Calcium Deficiency, Calcium Metabolism Disorders, Calcium and Vitamin D Deficiencies, Colic, Dyspepsia, Gastric Ulcer, Gastroesophageal Reflux, Heartburn, Hemorrhoids, Hot Flushes, Hyperacidity, Hyperphosphataemia, Hypovitaminosis D, Low Bone Density, Osteodystrophy, Osteomalacia, Osteoporosis, Postmenopausal Osteoporosis, Postoperative Gas, Proctitis, Vertebral Fractures, Calcium loss, Gastrointestinal ulceration, Dietary supplementationChronic Back Pain, Duodenal Ulcer, Erosive Esophagitis, Extra-Articular Rheumatism, Gastritis, Heartburn, Helicobacter Pylori Infection, Multiple Endocrine Neoplasia, Muscle Spasms, Nonspecific Pain Post Traumatic Injury, Osteoarthritis (OA), Postoperative pain, Stress Ulcers, Zollinger-Ellison Syndrome, Active Gastric ulcer, Acute Duodenal Ulcers, Gastrointestinal ulceration, Pathological hypersecretory conditions, Symptomatic non-erosive gastroesphageal reflux diseaseAcid indigestion, Colic, Constipation, Dyspepsia, Flatulence, Gastric Ulcer, Heartburn, Upset stomach, Antacid therapy, Gastric Acid Suppression

How Promag Double Action works

Calcium carbonate is a basic inorganic salt that acts by neutralizing hydrochloric acid in gastric secretions. It also inhibits the action of pepsin by increasing the pH and via adsorption. Cytoprotective effects may occur through increases in bicarbonate ion (HCO₃^-) and prostaglandins. Neutralization of hydrochloric acid results in the formation of calcium chloride, carbon dioxide and water. Approximately 90% of calcium chloride is converted to insoluble calcium salts (e.g. calcium carbonate and calcium phosphate).

Histamine acts as a local hormone that stimulates the acid output by parietal cells via a paracrine mechanism. Neuroendocrine cells called enterochromaffin-like (ECL) cells lie close to the parietal cells and regulate the basal secretion of histamine. Histamine release is also promoted from stimulation by acetylcholine and gastrin, a peptide hormone. Gastrin (G) cells release gastrin, which works on CCK₂ receptors on ECL cells. This action promotes the release of histamine from ECL cells. Upon release, histamine acts on H₂ receptors expressed on the basolateral membrane of parietal cells, leading to increased intracellular cAMP levels and activated proton pumps on parietal cells. Proton pump releases more protons into the stomach, thereby increasing the secretion of acid. In conditions that are associated with acid hypersecretion such as ulcers, there is a loss of regulation of acid secretion. Famotidine works on H₂ receptors and blocks the actions of histamine.

The suspension of magnesium hydroxide is ingested and enters the stomach. According to the amount ingested, the magnesium hydroxide will either act as an antacid or a laxative.

Through the ingestion of 0.5-1.5 grams (in adults) the magnesium hydroxide will act by simple acid neutralization in the stomach. The hydroxide ions from the magnesium hydroxide suspension will combine with the acidic H+ ions of the hydrochloric acid made by the stomachs parietal cells. This neutralization reaction will result in the formation of magnesium chloride and water.

Through the ingestion of 2-5 grams (in adults) the magnesium hydroxide acts as a laxative in the colon. The majority of the suspension is not absorbed in the intestinal tract and will create an osmotic effect to draw water into the gut from surrounding tissues. With this increase of water in the intestines, the feces will soften and the intraluminal volume of the feces will increase. These effects still stimulate intestinal motility and induce the urge to defecate. Magnesium hydroxide will also release cholecystokinin (CKK) in the intestines which will accumulate water and electrolytes in the lumen and furthermore increase intestinal motility.

Dosage

Promag Double Action dosage

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 therecommended 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.

Duodenal ulcer: 40 mg at night for 4 to 8 weeks

Benign gastric ulcer: 40 mg at night for 4 to 8 weeks; Maintenance therapy: 20 mg at night for preventing the recurrences of duodenal ulceration

Gastro-oesophageal reflux disease: 20 mg twice daily for 6 to 12 weeks

Zollinger Ellison syndrome: The recommended starting dose is 20 mg every six hours. Dosage should then be adjusted to individual response. Doses up to 160 mg every six hours have been administered to some patients without the development of significant adverse effects.

Dosage can be administered irrespective of meals. Antacids may be given concomitantly if needed.

Gastrointestinal hyperacidity:

• Adult: Up to 1 g daily, usually given in conjunction with an aluminium-containing antacid eg, aluminium hydroxide.

Osmotic laxative:

• Adult: 2.4-4.8 g daily as a single dose or in divided doses.
• Child: 6-11 yr: 1.2-2.4 g daily; 2-5 yr: 0.4-1.2 g daily. Doses may be given as a single dose or in divided doses.

Side Effects

In rare cases, flatulence, diarrhoea or constipation.

Famotidine is generally well tolerated and side effects are uncommon. Dizziness, headache, constipation and diarrhoea have been reported rarely. Other side effects reported less frequently include dry mouth, nausea and/or vomiting, rash, abdominal discomfort, anorexia and fatigue.

GI irritation, diarrhoea, abdominal cramps; hypermagnesaemia (in patients with renal impairment). Paralytic ileus.

Toxicity

The oral LD₅₀ is 4049 mg/kg in rats and 4686 mg/kg in mice. The subcutaneous LD₅₀ is 800 mg/kg in rats and mice. The lowest published toxic dose (TDLo) in man following oral administration is 4 mg/kg/7D.

Symptoms of overdose resemble the adverse events seen with the use of recommended doses, and they should be responded with supportive and symptomatic treatment. Any unabsorbed drug should be removed from the gastrointestinal tract, and the patient should be monitored accordingly. The use of hemodialysis to eliminate the drug from the systemic circulation is effective, but the experience of using hemodialysis in response to famotidine overdose is limited in clinical settings.

LD50=8500 mg/kg (rat, oral)

Common side effects include drowsiness or flushing (warmth, redness or tingly feeling).

Daily use of magnesium hydroxide can result in fluid and electrolyte disturbances.

Excessive use of the laxative effects of magnesium hydroxide may result in abdominal cramping, nausea and/or diarrhea.

In overdose, symptoms of gastrointestinal irritation and/or watery diarrhea may occur.

Magnesium hydroxide poisoning can result in hypermagnesemia which includes symptoms of: nausea, vomiting, flushing, thirst, hypotension, drowsiness, confusion, loss of tendon reflexes, muscle weakness, respiratory depression, cardiac arrhythmias, coma and cardiac arrest.

Not to be used in individuals with any form of kidney disease or renal failure, a magnesium restricted diet or with any sudden changes in bowel movement lasting over two weeks. Also not to be used in those individuals with abdominal pain, nausea, vomiting, symptoms of appendicitis or myocardial damage, heart block, fecal impaction, rectal fissures, intestinal obstruction or perforation or renal disease. Not to be used in women who are about to deliver as magnesium crosses the placenta and is excreted in small amounts in breast milk.

Using magnesium hydroxide with aluminum hydroxide can decrease the absorption rate of these drugs.

Magnesium hydroxide can react with digoxin, dicoumerol and cimetidine.

Use of ibuprofen with magnesium hydroxide can increase the absorption of the ibuprofen.

Use of magnesium hydroxide with penicallamine, bisphosphates, ketoconazole, quinolones or tetracycline can decrease the absorption of these drugs.

Enteric-coated tablets can be prematurely released when taken with magnesium hydroxide.

It is important to routinely monitor levels of serum magnesium and potassium in patients using magnesium hydroxide. Serum magnesium levels are necessary to determine how much magnesium is being absorbed and how much is being excreted by the kidneys. Excessive diarrhea can occur from use of magnesium hydroxide and thus it is important to also monitor serum potassium levels to ensure hypokalemia does not occur.

Precaution

In the presence of mild hypercalciuria, excretion levels must be carefully monitored and where necessary the dose of calcium carbonate should be reduced or treatment should be stopped. Patients with a history of stone formation should also be recommended to increase their fluid intake. High dosage of vitamin D should be avoided during Calcium therapy unless specifically indicated.

Dosage reduction should be considered or interval between doses should be prolonged if creatinine clearance falls to or below 30 ml/min.

Colostomy, ileostomy; electrolyte imbalance. Monitor for toxicity in patients with impaired renal function. Pregnancy.

Interaction

Oral calcium can reduce internal absorption of tetracycline and fluoride prepa-rations and an interval of at least 3 hours should therefore be allowed between ingestion of these medications. Vitamin D increases internal absorption of calcium. The intestinal uptake of calcium may be reduced by concomitant ingestion of certain foods (e.g. spinach, milk and milk products).

Famotidine does not interact with the cytochrome P450 linked drug metabolising enzyme system. So, no interactions have been found in man with Warfarin, Theophylline, Phenytoin, Diazepam, Propranolol, Aminopyrine or antipyrine.

Decreases absorption of tetracyclines and biphosphonates. Separate administration of these and other drugs by around 2 hr.

Volume of Distribution

Calcium is rapidly distributed taken up by skeletal tissues following absorption and distribution into extracellular fluids. Bone contains 99% of the body's calcium and the remaining 1% is approximately equally distributed between intracellular and extracellular fluids.

The steady-state volume of distribution ranges from 1.0 to 1.3 L/kg. Famotidine is found in breast milk; however, it is found in breast milk at the lowest concentrations compared to other H₂ receptor antagonists.

The peak action and distribution of magnesium hydroxide are variable.

Elimination Route

Maximal absorption occurs at doses of 500 mg or less taken with food. Oral bioavailability depends on intestinal pH, the presence of food and dosage.

Following oral administration, the absorption of famotidine is dose-dependent and incomplete. The oral bioavailability ranges from 40-50%, and the Cmax is reached in 1-4 hours post-dosing. While the bioavailability can be slightly increased with the intake of food and decreased by antacids, there is no clinical significance.

About 15%-50% of magnesium hydroxide is absorbed very slowly through the small intestine.

Half Life

The elimination half-life is about 2 to 4 hours. The half-life is expected to increase nonlinearly in patients with decreased renal function.

N/A

Clearance

Renal clearance is 250-450 mL/min, indicating some tubular excretion. Because the renal clearance rate exceeds the glomerular filtration rate, famotidine is thought to be mainly eliminated via both glomerular filtration and renal tubular secretion.

Magnesium hydroxide is mainly excreted in the urine by the kidneys. Since the kidneys play a major role in its clearance, individuals with renal failure are at risk of hypermagnesemia with long term consumption as the appropriate amounts of magnesium may not be excreted.

Elimination Route

Excreted mainly in the feces. The majority of renally filtered calcium is reabsorbed in the ascending limb of the loop of Henle and the proximal and distal convoluted tubules. Also secreted by sweat glands.

About 65-70% of the total administered dose of famotidine undergoes renal elimination, and 30-35% of the dose is cleared by metabolism. Following intravenous administration, about 70% of the drug is eliminated in the urine as an unchanged drug.

After oral administration, up to 50% of the magnesium hydroxide suspension may be absorbed as magnesium ions through the small intestines and then rapidly excreted in the urine through the kidneys. The unabsorbed drug is mainly excreted in the feces and saliva.

Pregnancy & Breastfeeding use

Pregnant women : Calcium containing drugs are used widely in pregnancy by way of calcium supplement or antacid therapy. No relationship between malformation in general and calcium exposure has been noted.

Lactating mother : There is no contraindication to the use of calcium carbonate in lactating mother.

Pregnancy: There are no adequate, well controlled studies on Famotidine in pregnancy, but it is known to cross the placenta and should be prescribed only if clearly needed.

Lactation: It is not known whether Famotidine is secreted into human milk, nursing mothers should either stop nursing or stop taking the drug.

Pregnancy category- A.

Contraindication

Hypersensitivity to the Calcium Carbonate or any inactive ingredient of the medication. Hypercalcemia (e.g. in hyperparathyroidism, overdosage of vitamin D, demineralizing tumours such as plasmacytomas and bone metastases), severe hypercalcuria, several renal insufficiency.

There are no known contraindication to Famotidine. If any evidence of hypersensitivity appear, the therapy should be discontinued and consultation with physician is required.

Intestinal obstruction, faecal impaction; renal failure; appendicitis.

Special Warning

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.

Storage Condition

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

Tablet: Store between 15-30° C. Concentrate for injection: Store between 2-8° C.

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