Siobion

Uses

This preparation is used for Pernicious anemia,Vitamin B12 deficiency due to low intake from food,Thyrotoxicosis, Hemorrhage, Malignancy, Liver or kidney disease,Gastric bypass surgery, Total or partial gastrectomy, Gluten enteropathy or sprue, Folic acid deficiency, Macrocytic anaemia

Ferrous Fumarate is used to prevent or treat iron deficiency anaemia. The prevention of iron deficiency during pregnancy usually requires a combination of iron and folic acid. Iron is usually found in foods and is necessary for the normal development of red blood cells. A lack of iron affects the development of the red blood cells and causes a reduction in the number of red blood cells found in the body (iron deficiency anaemia).

Sorbitol is a product that can be used as a laxative to relieve constipation, and also as a urologic irrigating fluid. May also be used as a pharmaceutical sweetener.

Used as a non-stimulant laxative via an oral suspension or enema.

Siobion is also used to associated treatment for these conditions: Anemia, Anemia, Pernicious, Combined Vitamin B1 and B12 deficiency, Convalescence, Diabetic Neuropathies, Folate deficiency, Iron Deficiency Anemia (IDA), Neuritis, Vitamin B1 deficiency, Vitamin B12 Deficiency, Vitamin B12 concentration, Vitamin B6 Deficiency, Vitamin Deficiency, Nutritional supplementation, Vitamin supplementationFolic acid antagonist overdose, Iron Deficiency (ID), Iron Deficiency Anemia (IDA), Oral ContraceptivesConstipation, Constipation caused by Pregnancy, Occasional Constipation, Bladder irrigation therapy, Bowel preparation therapy, Preparation for rectoscopic or sigmoidoscopic examination

How Siobion works

Vitamin B12 serves as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA in the degradation of propionate , an important reaction required for both fat and protein metabolism. It is a lack of vitamin B12 cofactor in the above reaction and the resulting accumulation of methylmalonyl CoA that is believed to be responsible for the neurological manifestations of B12 deficiency . Succinyl-CoA is also necessary for the synthesis of hemoglobin .

In tissues, vitamin B12 is required for the synthesis of methionine from homocysteine. Methionine is required for the formation of S-adenosylmethionine, a methyl donor for nearly 100 substrates, comprised of DNA, RNA, hormones, proteins, as well as lipids . Without vitamin B12, tetrahydrofolate cannot be regenerated from 5-methyltetrahydrofolate, and this can lead to functional folate deficiency , . This reaction is dependent on methylcobalamin (vitamin B12) as a co-factor and is also dependent on folate, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to form methionine and tetrahydrofolate. Vitamin B12 incorporates into circulating folic acid into growing red blood cells; retaining the folate in these cells . A deficiency of vitamin B12 and the interruption of this reaction leads to the development of megaloblastic anemia.

Iron is necessary for the production of hemoglobin. Iron-deficiency can lead to decreased production of hemoglobin and a microcytic, hypochromic anemia.

Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements.

Dosage

Siobion dosage

Usual Adult Dose for Pernicious Anemia

Initial dose: 1000 mcg intramuscularly or deep subcutaneous once a day for 6 to 7 daysIf clinical improvement and reticulocyte response is seen from the above dosing:

• 100 mcg every other day for 7 doses, then
• 100 mcg every 3 to 4 days for 2 to 3 weeks, then
• Maintenance dose: 100 to 1000 mcg monthly

Administer concomitant folic acid if needed. Chronic treatment should be done with an oral preparation in patients with normal intestinal absorption.

Usual Adult Dose for B12 Nutritional Deficiency: 25 to 2000 mcg orally daily

Usual Adult Dose for Schilling Test: 1000 mcg intramuscularly is the flushing dose

Usual Pediatric Dose for B12 Nutritional Deficiency: 0.5 to 3 mcg daily

Iron-deficiency anemia:

• Adult: Usual dose range: Up to 600 mg daily. May increase up to 1.2 g daily if necessary.
• Child:Preterm neonate: 0.6-2.4 ml / kg daily; up to 6 yr: 2.5-5 ml bid.

Should be taken on an empty stomach. Best taken on an empty stomach. May be taken with meals to reduce GI discomfort.

Side Effects

Arthralgia (12%), Dizziness (12%), Headache (12%), Nasopharyngitis (12%), Anaphylaxis, Angioedema, Congestive heart failure, Peripheral vascular disease,Pulmonary edema, Diarrhea, Dyspepsia, Polycythemia vera, Sore throat, Nervousness, Rhinitis, Glossitis, Hypoesthesia

Like all medicines, Ferrous Fumarate Tablets can sometimes cause side effects, although not everybody gets them. They might be:

• Heartburn
• Feeling sick or being sick
• Diarrhoea or constipation.

Also, you might find your stools are darker in color after you have taken this medicine. This is quite commonly seen with all iron preparations and is normal.

Toxicity

LD50 Oral (mouse): > 5,000 mg/kg .

General toxicity

Vitamin B12 is generally non-toxic, even at higher doses. Mild, transient diarrhea, polycythemia vera, peripheral vascular thrombosis, itching, transitory exanthema, a feeling of swelling of entire body, pulmonary edema and congestive heart failure in early treatment stages, anaphylactic shock and death have been observed after vitamin B12 administration .

Carcinogenesis and mutagenesis

Long term studies in animals examining the carcinogenic potential of any of the vitamin B12 formulations have not completed to date. There is no evidence from long-term use in patients with pernicious anemia that vitamin B12 has carcinogenic potential. Pernicious anemia is known to be associated with an increased incidence of stomach carcinoma, however, this malignancy has been attributed to the underlying cause of pernicious anemia and has not been found to be related to treatment with vitamin B12 .

Use in pregnancy

No adverse effects have been reported with ingestion of normal daily requirements during pregnancy .

A note on the use of the nasal spray in pregnancy

Although vitamin B12 is an essential vitamin and requirements are increased during pregnancy, it is currently unknown whether the nasal spray form can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. The nasal spray form should be given to a pregnant woman only if clearly needed, as it is considered a pregnancy category C drug in this form. Sufficient well-controlled studies have not been done to this date in pregnant women .

Use in lactation

Vitamin B12 has been found distributed into the milk of nursing women in concentrations similar to the maternal blood vitamin B12 concentrations. No adverse effects have been reported to date with intake of normal required doses during lactation .

Acute iron overdosage can be divided into four stages. In the first stage, which occurs up to six hours after ingestion, the principal symptoms are vomiting and diarrhea. Other symptoms include hypotension, tachycardia and CNS depression ranging from lethargy to coma. The second phase may occur at 6-24 hours after ingestion and is characterized by a temporary remission. In the third phase, gastrointestinal symptoms recur accompanied by shock, metabolic acidosis, coma, hepatic necrosis and jaundice, hypoglycemia, renal failure and pulmonary edema. The fourth phase may occur several weeks after ingestion and is characterized by gastrointestinal obstruction and liver damage. In a young child, 75 milligrams per kilogram is considered extremely dangerous. A dose of 30 milligrams per kilogram can lead to symptoms of toxicity. Estimates of a lethal dosage range from 180 milligrams per kilogram and upwards. A peak serum iron concentration of five micrograms or more per ml is associated with moderate to severe poisoning in many.

Acute oral toxicity (LD50): 15900 mg/kg [Rat].

Precaution

Intensive treatment of B12-deficient megaloblastic anemia may cause hypokalemia and sudden death. Use with caution in patients with Leber optic nerve atrophy. Thrombocytosis may occur with treatment of severe vitamin B12 megaloblastic anemia

Patients with intestinal strictures and diverticular disease. May worsen diarrhoea in patients with inflammatory bowel disease. May cause constipation and faecal impaction in elderly. Avoid prolonged admin (>6 mth) except in patients with continued bleeding, menorrhagia or repeated pregnancies. Not for routine use in treatment of haemolytic anaemia unless an iron-deficient state exists. Parenteral iron should not be used concurrently with oral iron treatment. Avoid use in patients receiving repeated blood tranfusions. Pregnancy.

Interaction

Absorption reduced by antibiotics, aminosalicylic acid, anticonvulsants, biguanides, cholestyramine, cimetidine, colchicine, K salts, methyldopa.

Oral absorption of iron may be increased when taken with ascorbic acid. May reduce the absorption of quinolones and tetracyclines when taken concurrently via the oral route. Concurrent admin with antacids may reduce the absorption of ferrous fumarate from the GI tract. May reduce the absorption of penicillamine in the gut when taken concurrently.

Volume of Distribution

Cobalamin is distributed to tissues and stored mainly in the liver and bone marrow .

Elimination Route

Vitamin B12 is quickly absorbed from intramuscular (IM) and subcutaneous (SC) sites of injection; with peak plasma concentrations achieved about 1 hour after IM injection .

Orally administered vitamin B12 binds to intrinsic factor (IF) during its transport through the stomach. The separation of Vitamin B12 and IF occurs in the terminal ileum when calcium is present, and vitamin B12 is then absorbed into the gastrointestinal mucosal cells. It is then transported by transcobalamin binding proteins . Passive diffusion through the intestinal wall can occur, however, high doses of vitamin B12 are required in this case (i.e. >1 mg). After the administration of oral doses less than 3 mcg, peak plasma concentrations are not reached for 8 to 12 hours, because the vitamin is temporarily retained in the wall of the lower ileum .

The efficiency of absorption depends on the salt form, the amount administered, the dosing regimen and the size of iron stores. Subjects with normal iron stores absorb 10% to 35% of an iron dose. Those who are iron deficient may absorb up to 95% of an iron dose.

Half Life

Approximately 6 days (400 days in the liver) .

Clearance

During vitamin loading, the kidney accumulates large amounts of unbound vitamin B12. This drug is cleared partially by the kidney, however, multiligand receptor megalin promotes the reuptake and reabsorption of vitamin B12 into the body , .

Elimination Route

This drug is partially excreted in the urine . According to a clinical study, approximately 3-8 mcg of vitamin B12 is secreted into the gastrointestinal tract daily via the bile. In patients with adequate levels of intrinsic factor, all except approximately 1 mcg is reabsorbed. When vitamin B12 is administered in higher doses that saturate the binding capacity of plasma proteins and the liver, the unbound vitamin B12 is eliminated rapidly in the urine. The body storage of vitamin B12 is dose-dependent .

Sorbitol will either be excreted in the urine by the kidneys, or metabolized to carbon dioxide and dextrose.

Pregnancy & Breastfeeding use

Pregnancy Category A. Adequate and well-controlled human studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).

Lactation: Drug distributed in milk.

Pregnancy Category- Not Classified. FDA has not yet classified the drug into a specified pregnancy category

Contraindication

Leber's disease, tobacco amblyopia.

Patients with a known hypersensitivity to any of the ingredients. Hemochroma

Acute Overdose

Symptoms: Nausea, vomiting, abdominal pain, diarrhoea, haematemesis and rectal bleeding. Hypotension, coma and hepatocellular necrosis may occur later.

Treatment: Empty stomach contents by gastric lavage within 1 hr of ingestion. In severe toxicity, IV desferrioxamine may be given. Whole bowel irrigation may also be considered in severe poisoning.

Innovators Monograph

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