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JECTOFERŽ
Astra
Iron-Sorbitol-Citric Acid Complex, Dextrin-Stabilized
Intramuscular Hematinic
 
Action And Clinical Pharmacology: Many of the properties of iron sorbitol result from its relatively low molecular weight. It is rapidly absorbed from the injection site and is stable in tissue fluids. Two-thirds of the injected dose is absorbed from an i.m. site within 3 hours, most of it directly into the blood circulation and, to a lesser extent, via lymphatics. Within approximately 10 days, little or no residue of iron remains at the injection site.

Absorption is followed by a rapid increase in serum iron concentration. In man, maximum plasma levels are attained in about 2 hours and return to normal values within 24 hours. This pattern of absorption is repeated in day-by-day injections and appears to be constant from patient to patient.

Clearance from the circulation is rapid. A proportion of the absorbed complex immediately gives up its iron directly to transferrin in the plasma and thus is available for marrow utilization and hemoglobin synthesis without intermediate metabolism. During this period, serum transferrin is fully saturated. The amount of iron sorbitol taken up by the liver and bone marrow is determined by iron status. A larger proportion is taken up by the liver in nonanemic patients than in the iron deficient. The main route of plasma clearance is via reticulo-endothelial uptake in the liver from which iron is released to plasma transferrin for utilization. A fraction of the iron is taken up by renal convoluted tubules, appearing there as ferritin which is mobilized and cleared from the tubules in the course of some weeks.

Iron sorbitol has no effect on blood clotting at the concentrations achieved clinically.

Indications And Clinical Uses: Treatment of iron deficiency anemia. Replenishment of storage iron.

Absolute Indications: In cases where intestinal malabsorption may occur; when oral iron produces gastrointestinal intolerance.

Practical Indications: In cases where oral iron is contraindicated because of diseases or disorders of the gastrointestinal tract e.g., peptic ulceration; failure of patient to cooperate in oral iron therapy; in late pregnancy when an assured response to iron is needed; in cases of chronic blood loss when it is desired to avoid the use of blood transfusion.

Note: Iron sorbitol can only replace iron loss. In acute hemorrhage when the amount of blood loss may be considerable, attention must be given to the replacement of blood volume in the form of blood transfusion or blood substitutes or other volume expanders, according to the clinical situation, as well as to the replacement of iron loss.

Contra-Indications: Anemias not due to iron deficiency: e.g., hemolytic anemia, aplastic or hypoplastic anemia, acute leukemia, thalassemia, untreated megaloblastic anemias; acute pyelonephritis; acute liver disease; early pregnancy (see Precautions); known sensitivity to iron sorbitol. tag_WarningWarnings

Manufacturers' Warnings In Clinical States: Iron sorbitol is for i.m. use only.

Iron sorbitol, a low molecular weight complex, contains 6% dialyzable iron. If given i.v., this fraction will rapidly saturate the transferrin and the excess can cause a toxic reaction, i.e., hypotension, flushing, dizziness and vomiting. When iron sorbitol is given i.m. the iron release proceeds at a controlled rate, greatly reducing the potential for a toxic reaction.

Iron sorbitol may form a grey precipitate when refrigerated. Do not use if precipitate forms and/or solution is unclear (see Supplied).

Precautions: Iron sorbitol should be administered only by i.m. injection in the treatment of accurately diagnosed iron deficiency anemia (see Warnings). If expected results are not obtained during or following the course of treatment, a complicating illness or an inaccurate diagnosis should be suspected. Do not continue without establishing the reason for failure to respond as it may be possible that iron sorbitol is not indicated.

The importance of using the correct recommended dose in relation to body weight is emphasized (1.5 mg iron/kg), especially in patients who are already markedly underweight (see Adverse Effects).

Iron sorbitol should not be administered concurrently with oral iron medication. Such concurrent administration has been reported to produce an increase in the incidence of side effects.

As with other iron therapy, iron sorbitol is not effective in anemia of rheumatoid arthritis and in anemias of infection unless iron deficiency is present.

Pregnancy: It is highly unlikely that iron sorbitol will cause fetal abnormalities when administered to women in late pregnancy.

There have been a few reports of abortion and congenital malformation after iron sorbitol in early pregnancy. In view of the severe conditions in the patients treated with iron sorbitol, and the use of concomitant medication, a relation between the events and the drug does not seem to be proven. However, the use of iron sorbitol in the first 3 or 4 months of pregnancy is not recommended.

Drug Interactions: The concomitant administration of chloramphenicol may delay the response to iron therapy in patients with iron deficiency anemia. Most likely this effect is due to the bone marrow depressing properties of chloramphenicol.

Adverse Reactions: Initial local discomfort, sometimes described as painful, may be experienced at the site of injection. Temporary skin discoloration at the injection site may occur. In a very small percentage of cases the injection may be followed by a localized or generalized urticaria.

A transient metallic taste is common, which may be accompanied by a temporary loss of taste. Nausea, vomiting, diarrhea, headache, dizziness, sweating and flushing of the face may occur. Hematuria has been reported.

Severe systemic reactions with cardiac involvement are seen mostly in connection with overdose. Those reported include sensations of pressure in the chest, circulatory failure, hypertension, syncope, hypotension, arrhythmia, palpitation, AV block, bradycardia, atrial fibrillation and tachycardia.

In general, the systemic side effects mentioned above have been observed more commonly when doses higher than those recommended were given. This generally occurs in patients who are underweight or in those with anemias that are not, or only in part due to iron deficiency (see Contraindications). In such cases the transferrin saturation is often high. For this reason, iron sorbitol should not be administered concurrently with oral iron medication. Similar systemic reactions may rarely occur in severely debilitated or sensitive patients given recommended doses. In such cases the amount of the single daily dose should be reduced.

Isolated cases of anaphylactoid reactions have been reported.

Symptoms And Treatment Of Overdose: There have been 10 cases of overdoses reported to date: One case involved a 4-month-old infant who received 44 mg Fe/kg. Two children <3 years received 50 mg Fe. One of these children was on concomitant ampicillin. All 3 patients died.

Four reports describe patients with malabsorption diseases and who were underweight (43 to 49 kg). All 4 patients were given 1 to 6 injections of 100 mg Fe/injection. Two of the patients died and 2 recovered with sequelae. Another 2 patients had diarrhea of long duration, one received 5 injections of 100 mg Fe/injection, the other, 1 injection of 100 mg Fe. Both patients recovered. In 1 case the patient was inadvertently given an i.v. injection of 200 mg Fe. The patient recovered.Symptoms: The systemic reactions reported in overdosage are generally dose related. The reported symptoms are dizziness, nausea, vomiting, diarrhea, sweating, palpitations, pressure sensations in the chest and hypotension. The more severe reactions reported are circulatory collapse and cardiac arrhythmias (in 1 case ventricular tachycardia).

Treatment: Close clinical observation and laboratory monitoring are essential. Treatment should be adapted to the severity of overdose with reference to serum iron and total iron-binding capacity.

When the patient exhibits symptoms of systemic iron poisoning, chelation therapy with parenterally administered deferoxamine is indicated. The recommended dosing regimen for deferoxamine is 15 mg/kg/h by continuous i.v. infusion. The infusion is continued until the patient is symptom-free and the corrected serum iron concentration is normal or low. For severely ill patients, higher infusion rates might be needed.

Rehydration, acidosis- and electrolyte correction should be initiated as soon as possible. If a vasopressor is needed, dopamine has been suggested. Liver and kidney function should be monitored.

Dosage And Administration: For i.m. injection only (see Warnings).

Adults: The recommended single daily dose for injection is calculated on the basis of 1.5 mg iron/kg body weight. The calculated dose may be administered daily or every other day until hemoglobin values reach the normal range. The single daily injection of more than 2 mL of iron sorbitol is not recommended. Two mL iron sorbitol contains the recommended single daily dose (100 mg) for an adult of 70 kg body weight.

The total course of single daily doses should be adjusted according to the severity of the anemia. To increase the Hb value by 10 g/L it is necessary to administer, by the parenteral route, approximately 200 mg of elemental iron for women and 250 mg for men. Corresponding amounts to achieve an increase of 1% Hb are approximately 35 mg of iron for women and 45 mg for men. In addition, about 250 to 1 000 mg elemental iron are required for the replenishment of iron stores.

Dosage Guide: Adults: Table I may be used as a practical guide to dosage.

Note: In addition to the number suggested above, another 5 to 10 additional doses should be given to adults to replenish stores.

Children: The recommended single daily dose for injection is similarly calculated on the basis of 1.5 mg iron/kg body weight. The calculated daily dose should be administered daily or every other day until hemoglobin values reach the normal range.

Dosage Guide: Children: Table II may be used as a practical guide to dosage.

I.M. Injection Technique: 1. After loading the syringe with the appropriate dose of iron sorbitol, change to a new, dry needle.

2. Use a fine needle to ensure a deep i.m. injection even in an obese patient. A needle 50 mm in length with an outside diameter of 0.7 mm (22 gauge) is suitable in most cases. As a rule, the needle should not be shorter than 40 mm and not longer than 80 mm.

3. The injection is given into the upper outer quadrant of the buttock to avoid accidental injection into a large nerve or blood vessel. Alternate sides should be used for subsequent injections.

4. A Z-track technique should be used to prevent leakage along the needle track. The skin over the injection site is moved firmly to one side and held in this position until the needle has been inserted.

5. Insert the needle for deep i.m. injection.

6. Check that the needle point is not in a blood vessel. Exert a gentle pull on the plunger as if to withdraw it. There should be firm resistance to movement of the plunger. If the needle is in a blood vessel, the plunger will yield to the pull and blood will enter the syringe, although this may escape observation because of the dark colored solution.

7. Inject slowly without any force. Withdraw the needle quickly after about 10 seconds. As the skin and s.c. tissue resumes a normal position, this completes the Z-track procedure. Do not massage the site of injection. The patient should rest lying down for 5 minutes after the injection.

Note: When using iron sorbitol only freshly opened ampuls should be used. On no account should an opened ampul be retained for later use.

Availability And Storage: Each mL of clear, dark brown, sterile colloidal solution contains: iron 50 mg (as a complex of ferric iron, sorbitol and citric acid, stabilized with dextrin). Sorbitol for injection is added to strengthen the complex. Sodium hydroxide and/or hydrochloric acid to adjust pH to 7.2 to 7.9. Single-use ampuls of 2 mL, boxes of 10. Store at room temperature (15 to 30°C). Do not refrigerate. Lower temperatures may disturb the colloid resulting in the formation of a grey precipitate. If a precipitate forms and/or solution is unclear, discard and do not use.