I-KEYTM Iron Sucrose Injection USP

PHARMACOKINETICS
Following intravenous doses of Iron Sucrose, its Iron component exhibits first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h. non-steady state apparent volume of distribution of 10.0 L and steady state apparent distribution of 7.9 L. Since Iron disappearance from serum depends on the need for Iron in the Iron stores and Iron utilizing tissues of the body, serum clearance of Iron is expected to be more rapid in Iron deficient patients treated with I-Key as compared to healthy individuals. Following intravenous doses of Iron Sucrose, its Iron component appears to distribute mainly in blood and to some extent in extra vascular fluid.

A study evaluating I-Key containing 100 mg Iron labeled with 52Fe/59Fe in patients with Iron deficiency shows that a significant amount of the administered Iron distributes in the liver, spleen, and bone marrow and that the bone marrow is an Iron trapping compartment and not a reversible volume of distribution. Following intravenous doses of Iron Sucrose, its Iron component dissociated into Iron and Sucrose by the reticuloendothelial system. The Sucrose component is eliminated mainly by urinary excretion.

INDICATIONS
I-Key is indicated for the treatment of Iron deficiency anemia in cases where rapid and reliable substitution of Iron is required.

CONTRAINDICATIONS
The use of I-Key is contraindicated in patients with evidence of Iron overload, in patients with known hypersensitivity to Iron preparations or any of its inactive components, and in patients with anemia not caused by Iron deficiency.


PRECAUTIONS & WARNINGS
Hypersensitivity reactions have been reported with injectable Iron products. Serious hypersensitivity reactions have been rarely reported in patients receiving Iron Sucrose. In the event of an allergic or anaphylactoid reactions administered of Iron Sucrose must be stopped, intramuscular adrenaline should be administered immediately and other supportive measures initiated in line with the established cardio-pulmonary resuscitation procedures of the clinic or hospital. Hypotension has been reported in patients receiving intravenous Iron. Hypotension following administration of Iron Sucrose may be related to rate of administration and the total dose administered. Caution should be taken to administer Iron Sucrose according to recommended guidelines. Because body Iron excretion is limited and excess tissues Iron can be hazardous, caution should be exercised to withhold Iron administration in the presence of evidence of tissue Iron overload. Patients receiving Iron Sucrose require periodic monitoring of hematologic and hematinic parameters, Iron therapy should be withheld in patients with evidence of Iron overload. Transferrin saturation values increase rapidly after IV administration of Iron Sucrose, thus, serum Iron values may be reliably obtained 48 hours after IV dosing.

USAGE IN PREGNANCY, LACTATION & CHILDREN
No adequate and well controlled studies with Iron Sucrose Injections in pregnant women have been reported. This drug should therefore not be used in pregnant women. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Iron Sucrose is administered to a nursing woman. Safety and effectiveness of Iron Sucrose in pediatric patients have not been established.
Each white tablet contains 0.15 mg desogestrel and 0.03 mg ethinyl estradiol. The pink tablets do not contain any hormones and are included to help remember to start the new strip on time.

DRUG INTERACTIONS
Iron Sucrose should not be administered concomitantly with oral Iron preparation since the absorption of oral Iron is reduced.

DOSAGE AND ADMINISTRATION
The dosage of I-Key is expressed in terms of mg of elemental Iron. Each ml contains 20 mg elemental Iron.


DOSAGE IN HEMODIALYSIS PATIENTS
The recommended dosage of I-Key for the repletion of Iron deficiency in hemodialysis patients is 5 ml of Iron sucrose (100 mg of elemental Iron) delivered intravenously during the dialysis sessions. Most patients require a minimum cumulative dose of 1,000 mg elemental Iron, administered over 10 sequential dialysis sessions, to achieve a favorable hemoglobin or hematocrit response. Frequency of dosing should not be more than three times weekly. Patients may continue to require therapy with Iron Sucrose or other intravenous Iron preparations at the lowest dose necessary to maintain target levels of hemoglobin, hematocrit and laboratory parameters of Iron storage within acceptable limits.

Calculation of doses in other patients with Iron deficiency anemia
The total cumulative dose of I-Key equivalent to the total Iron deficit (mg), is determined by the hemoglobin level and body weight. The dose and the dosage schedule has to be individually adapted according to the total Iron deficit calculated with the following formula:
Total Iron deficit (mg) = body weight (kg) x (target Hb-actual Hb) (g/l) x 0.24* + depot Iron (mg).
Up to 35 kg body weight. Target Hb = 130 g/l & depot Iron = 15 mg/kg body weight
Above 35 kg body weight. Target Hb = 150 g/l & depot Iron = 500 mg
*Factor 0.24 = 0.0034 x 0.07 x 1000 (Iron content of hemoglobin = 0.34%
Blood volume = 7% of the body weight: Factor 1000 = conversion from g to mg). Total amount of I-Key to be administered (in ml) = Total Iron deficit (mg)
                                     20 mg/ml
If the total necessary dose exceeds the maximum allowed single dose, then the administration has to be split. If no response in the hematological parameters is observed after 1 to 2 weeks, the original diagnosis should be reconsidered.


ADMINISTRATION
I-Key must only be administered intravenously either by slow injection or by infusion. However administration by intravenous drip infusion is the preferred route of administration as this may help reduce the risk of hypotensive episodes and paravenous leakage.
I-Key is a strongly alkaline solution and must never be administered by the subcutaneous or Intramuscular route.


SLOW INTRAVENOUS INJECTION
I-Key may be administered undiluted by slow intravenous Injection at rate of 1 ml (20 mg Iron) solution per minute (i.e. 5 minutes per ampoule) not exceeding one ampoule I-Key ( 100 mg Iron) per Injection. Discard any unused portion.


INFUSION
I-Key may also be administered by infusion. The contents of each ampoule must be diluted exclusively in a maximum of 100 ml of 0.9% NaCl, immediately prior to infusion. The solution should be infused at rate of 100 mg of Iron over a period of at least 15 minutes. Unused diluted solution should be discarded.


INJECTION INTO DIALYSER
I-Key may be administered during the middle of a haemodialysis session directly into the venous limb of the dialyses under the same procedures as those outlined for Intravenous administration.

NOTE
Do not mix I-Key with other medications or add to parenteral nutrition solutions for intravenous solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit.


SIDE EFFECTS
Side effects of I-Key (Iron Sucrose injection, USP) in excess of Iron needs may lead to accumulation of Iron storage sites leading to hemosiderosis. Periodic monitoring of Iron parameters such as serum ferritin and transferring saturation may assist in recognizing Iron accumulation. Iron Sucrose should not be administered to patients with Iron overload and should be discontinued when serum ferritin levels equals or exceeds established guidelines. Particular caution should be exercised to avoid Iron overload where anemia unresponsive to treatment has been incorrectly diagnosed as Iron deficiency anemia. Symptoms associated with overdosage or infusing Iron Sucrose too rapidly included hypotension, headache, vomiting, nausea, dizziness, joint aches, parenthesis, abdominal and muscle pain, edema and cardiovascular collapse. Most symptoms have been successfully treated with IV fluids, hydrocortisone and/or antihistamines. Infusing the solution as recommended or at a slower rate may also alleviate symptoms.


STORAGE: Store at controlled room temperature. Protect from light. Do not freeze.
Keep medicine out of reach of children.


PRESENTATION
Pack of 2.5 ml Ampoule & Pack of 5 ml Ampoule.