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175 μg Fe/mL
[ferumoxsil, oral suspension]
Gastromark™ (ferumoxsil, oral suspension) is an aqueous suspension of silicone-coated, superparamagnetic iron oxide, intended for oral administration as a magnetic resonance imaging contrast media. Gastromark is designated chemically as poly [N-(2-aminoethyl)-3-aminopropyl] siloxane coated non-stoichiometric magnetite (FeOx[C5H13N2SiO2]y), which has been manufactured to obtain a small uniform particle size of approximately 0.4 microns.
Gastromark is an oral aqueous suspension of a superparamagnetic magnetic resonance imaging (MRI) contrast agent. After oral administration of Gastromark, the agent fills the stomach and small intestine by 30 to 45 minutes after ingestion. The imaging agent passes distally to the large intestine by 4 to 7 hours after ingestion. Gastromark is primarily eliminated in the feces.
Generally, the extent of absorption of iron from the gastrointestinal tract is expected to depend upon the existing body stores of iron. The lower the body iron stores, the more iron may be absorbed from Gastromark.
Distribution and Metabolism – Iron absorbed from Gastromark enters the hematopoietic pathway and is incorporated into the hemoglobin of the red blood cells or into ferritin for storage. The extent to which silicone is absorbed or metabolized in humans is not known.
Elimination – Unabsorbed iron in Gastromark is eliminated in feces. Based upon literature information, iron absorbed into the blood is highly conserved. In healthy normal adult men, about 10% of the body’s iron store is lost per year (1 mg per day). Iron is excreted from the gastrointestinal tract in extravasated red cells, in bile and in exfoliated mucosal cells. Small amounts of iron are lost in the urine and in desquamated skin. Additional iron loss occurs in menstrual flow in women.
Food Effect – Gastromark is intended for administration under fasting conditions. The effect of food on the disposition of Gastromark has not been studied.
Special Populations – Studies have not been conducted to evaluate the disposition of Gastromark in special populations such as patients with hepatic and renal diseases, or patients with hemochromatosis, hemosiderosis and other blood disorders.
The amount of iron absorbed in patients with active inflammatory bowel disease has not been studied adequately.
Drug-Drug Interactions – Drug interaction studies have not been conducted with Gastromark. The effect of iron supplements or drugs that increase or decrease gastrointestinal transit time on imaging with Gastromark has not been studied.
Of the above, 186 patients were enrolled in two identical clinical studies of 93 subjects each. Patients were referred for magnetic resonance imaging (MRI) and had known or suspected abdominal masses. Gastromark was evaluated for its ability to enhance the bowel and improve the definition of anatomic markings in the MRI. Confirmation of the final diagnosis for lesions external to the bowel was not obtained.
The MRI images from the two studies were evaluated by blinded readers for bowel marking and the delineation of anatomy. The before and after Gastromark images were rated for the percent of images that were “better, same, worse, or not evaluable.” The table below lists the percentage of patients in each study with MRls in different regions of the abdomen that were “better” after Gastromark. After Gastromark, artifacts were rated as present (yes) and absent (no).
After Gastromark, depending upon the site evaluated, 11 to 70% of the patients had images rated “the same” as those without Gastromark; and 1 to 3% of the patients had images rated worse or not evaluable. After Gastromark, artifacts were seen in 1 to 3% of the MRI images.
The presence or absence of mass lesions was further evaluated in a subset of 67 of the 186 patients (36%), 32 with pancreatic/gastric masses and 35 with possible bowel obstruction. For these patients, in comparison to MRls before Gastromark and depending upon the anatomic location, the visualized abnormalities on MRI images after Gastromark increased confidence excluding the mass in 31 to 41% of the patients; increased confidence in delineating the mass in 44 to 49% of the patients; and in 16 to 26% of the patients the information was not helpful. Confirmation of findings or MRI images judged normal after Gastromark was not obtained. Gastromark was not evaluated for the contribution of the Gastromark MRI to the final diagnosis or patient management.
INDICATIONS AND USAGE
Gastromark™ is indicated in adult patients for oral use with magnetic resonance imaging to enhance the delineation of the bowel to distinguish it from organs and tissues that are adjacent to the upper regions of the gastrointestinal tract.
Like other large volume oral contrast agents, Gastromark is contraindicated in patients with known or suspected intestinal perforation or obstruction.
Gastromark is contraindicated in patients with known allergy to its active or inactive ingredients.
The ingestion of Gastromark may cause abdominal pain, diarrhea, nausea and vomiting. In 78/256 (30%) of patients and normal volunteers, gastrointestinal adverse events occurred within the first 2 hours after ingestion of Gastromark. In 30/256 (12%), gastrointestinal events had their onset within 30 minutes. In 63/256 (24%), diarrhea occurred within 24 hours.
Gastromark is associated with nausea, vomiting, diarrhea, and abdominal cramping. In patients who have these symptoms before Gastromark, the symptoms may increase in severity. This could confound the ability to distinguish adverse effects of Gastromark from the signs and symptoms of obstruction or perforation, and from the pre-existing conditions.
Information For Patients
Patients receiving Gastromark should be instructed to inform the physician and technologist if they are pregnant or nursing. Patients should be informed that:
Gastromark is prescribed for gastrointestinal tract enhancement during MRI.
Gastromark can cause significant nausea, vomiting, diarrhea or abdominal pain, and other intestinal discomfort. In patients who have these symptoms before ingesting Gastromark, the symptoms might increase in severity.
Patients should be asked if they are able to rapidly drink approximately 20 to 30 ounces (1/2 to 1 quart of fluid, or 600 to 900 mL) over a 15 to 30 minute period. They should be asked if they have hiatal hernias or problems with regurgitation when they lie on their backs after eating.
Laboratory Test Findings
Gastromark contains iron oxide. Although iron absorption from Gastromark is low, the extent of gastrointestinal absorption of any available elemental iron from Gastromark is expected to depend upon the patient’s existing iron stores. The lower the body iron stores, the more iron will be absorbed from the GI tract. The iron may change serum measurements of iron, iron binding,
Carcinogenesis, Mutagenesis and Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic potential of Gastromark. Gastromark was not found to cause genetic toxicity in the Ames test, in a chromosome aberration assay in CHO cells, in the CHO/HGPRT forward mutation assay, or in an unscheduled DNA synthesis assay in isolated rat hepatocytes. Gastromark has not been evaluated for potential to impair fertility.
Pregnancy Category B
Reproduction studies have been performed with Gastromark dosed by iron content. During gestation in rats and rabbits respectively, doses were up to 52.5 mg Fe/kg and 26.25 mg Fe/kg (respectively about 17 and 8 times the dose for a 50 kg human on a mg/kg basis, and 8 and 2.5 times on a mg/m2 basis). Maternal toxicity was not observed and these doses were not associated with evidence of harm to the fetus. Adequate and well-controlled studies have not been conducted in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Iron is excreted in human milk; it is not known whether other ingredients of Gastromark are excreted in human milk. Caution should be exercised when Gastromark is administered to nursing women.
Gastromark was evaluated in 256 patients and normal volunteers in clinical trials. Of these, 147 (57%) had at least one adverse event. Deaths did not occur during the study period of 7 days. In 15/256 (6%) patients, the ingestion of Gastromark was either interrupted or stopped because of vomiting or because they could not ingest any more fluid. One normal volunteer had prolonged abdominal cramping for 4 hours. One patient had post-operative ileus 2 days after ingesting Gastromark.
There is a suggestion of differences in rates of adverse experiences in patients who have or do not have pancreatic or gastric masses. In patients with gastric or pancreatic masses, vomiting was reported in 4/35 (11%); in patients without gastric or pancreatic masses, vomiting was reported in 10/221 (5%) (p = 0.07). Abdominal pain was reported in 1/35 (3%) of patients with pancreatic or gastric masses and in 22/221 (10%) of patients without these lesions. The clinical relevance of these findings is not known.
The following table of adverse events is based upon clinical trials with Gastromark in 256 subjects.
In the safety database of 256 people, the type of events was similar in people of each gender and in patients and healthy volunteers. The sample size was too small to determine whether there is any association of adverse events to body weight. However, for nausea and diarrhea, as shown in the following table, the rate of adverse events was much higher in women, both in patients and in volunteers.
Other events reported in less than 0.5% of 256 healthy volunteers and patients who received Gastromark are: chills, fever, post-operative ileus, eructation, itching, urticarial rash, pustular rash, stomatitis, taste alteration, and edema of extremities. One healthy volunteer had prolonged abdominal cramping for 4 hours.
Overdose has not been reported with Gastromark. If overdose occurs, it is likely that the toxicity would be related to iron, volume intolerance, or allergic-hypersensitivity reactions.
DOSAGE AND ADMINISTRATION
The recommended dosage of Gastromark is 600 mL (105 mg Fe) administered orally at a rate of about 300 mL over 15 minutes. The maximum oral dose is 900 mL (157.5 mg Fe).
Gastromark™ is packaged in white polyethylene bottles sealed with tamper-evident screw closures. Each bottle contains 300 mL of Gastromark.
Printed in U.S.A.
PACKAGE LABEL - PRINCIPAL DISPLAY PANEL - 300 mL Bottle
(ferumoxsil oral suspension)
Before use, shake vigorously for at least one full minute.
Store between: 2° to 25°C (36° to 77°F)
Ingredients: Each mL contains 175 μg inorganic iron from silicone-coated superparamagnetic iron oxide; sodium hydroxide to adjust pH; sodium chloride to adjust osmolality.
Inactive ingredients: Carboxymethylcellulose sodium, methylparaben, orange color, orange flavor, propylparaben, saccharin sodium, sorbitol solution.
Usual Dosage: The recommended dosage is 600 mL.
Under License from:
Revised: 10/2010 Mallinckrodt Inc.
Reproduced with permission of U.S. National Library of Medicine
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