Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1510
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Venofer (Injection)
|
| dailymed-instance:dosage |
The dosage of Venofer is expressed in terms of mg of elemental iron. Each mL contains 20 mg of elemental iron. Most CKD patients will require a minimum cumulative repletion dose of 1,000 mg of elemental iron, administered over sequential sessions, to achieve a favorable hemoglobin response and to replenish iron stores (ferritin, TSAT). Hemodialysis patients may continue to require therapy with Venofer or other intravenous iron preparations at the lowest dose necessary to maintain target levels of hemoglobin, and laboratory parameters of iron storage within acceptable limits. Administration: Venofer must only be administered intravenously either by slow injection or by infusion.<br/>Recommended Adult Dosage:: Hemodialysis Dependent-Chronic Kidney Disease Patients (HDD-CKD): Venofer may be administered undiluted as a 100 mg slow intravenous injection over 2 to 5 minutes or as an infusion of 100 mg, diluted in a maximum of 100 mL of 0.9% NaCl over a period of at least 15 minutes per consecutive hemodialysis session for a total cumulative dose of 1,000 mg. Non-Dialysis Dependent-Chronic Kidney Disease Patients (NDD-CKD): Venofer is administered as a total cumulative dose of 1,000 mg over a 14 day period as a 200 mg slow IV injection undiluted over 2 to 5 minutes on 5 different occasions within the 14 day period. There is limited experience with administration of an infusion of 500 mg of Venofer, diluted in a maximum of 250 mL of 0.9% NaCl, over a period of 3.5-4 hours on day 1 and day 14; hypotension occurred in 2 of 30 patients treated. (See CLINICAL TRIALS, Study D: Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) Patients and ADVERSE REACTIONS, Adverse Events Observed in Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD) Patients sections.) Peritoneal Dialysis Dependent-Chronic Kidney Disease Patients (PDD-CKD): Venofer is administered as a total cumulative dose of 1,000 mg in 3 divided doses, given by slow intravenous infusion, within a 28 day period: 2 infusions of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. The Venofer dose should be diluted in a maximum of 250 mL of 0.9% NaCl.
|
| dailymed-instance:descripti... |
Venofer (iron sucrose injection, USP) is a brown, sterile, aqueous, complex of polynuclear iron (III)-hydroxide in sucrose for intravenous use. Iron sucrose injection has a molecular weight of approximately 34,000���60,000 daltons and a proposed structural formula: [NaFeO(OH)��3(HO)]��m(CHO) where: n is the degree of iron polymerization and m is the number of sucrose molecules associated with the iron (III)-hydroxide. Each mL contains 20 mg elemental iron as iron sucrose in water for injection. Venofer is available in 5 mL single dose vials (100 mg elemental iron per 5 mL) and 10 mL single dose vials (200 mg elemental iron per 10 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL) and has a pH of 10.5-11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L. Therapeutic class: Hematinic
|
| dailymed-instance:clinicalP... |
Pharmacodynamics: Following intravenous administration of Venofer, iron sucrose is dissociated by the reticuloendothelial system into iron and sucrose. In 22 hemodialysis patients on erythropoietin (recombinant human erythropoietin) therapy treated with iron sucrose containing 100 mg of iron, three times weekly for three weeks,significant increases in serum iron and serum ferritin and significant decreases in total iron binding capacity occurred four weeks from the initiation of iron sucrose treatment. Pharmacokinetics: In healthy adults treated with intravenous doses of Venofer', 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 volume of 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 Venofer as compared to healthy individuals. The effects of age and gender on the pharmacokinetics of Venofer have not been studied. Venofer is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of iron sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million). Distribution: In healthy adults receiving intravenous doses of Venofer', its iron component appears to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Venofer containing 100 mg of iron labeled withFe/Fe 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. Metabolism and Elimination: Following intravenous administration of Venofer, iron sucrose is dissociated into iron and sucrose by the reticuloendothelial system. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Venofer containing 1,510 mg of sucrose and 100 mg of iron in 12 healthy adults (9 female, 3 male: age range 32-52), 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some iron also is eliminated in the urine. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration[1]. In this study and another study evaluating a single intravenous dose of iron sucrose containing 500-700 mg of iron in 26 anemic patients on erythropoietin therapy (23 female, 3 male; age range 16-60), approximately 5% of the iron was eliminated in urine in 24 h at each dose level [2]. Drug-drug Interactions: Drug-drug interactions involving Venofer have not been studied. However, like other parenteral iron preparations, Venofer may be expected to reduce the absorption of concomitantly administered oral iron preparations.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
The use of Venofer is contraindicated in patients with evidence of iron overload, in patients with known hypersensitivity to Venofer or any of its inactive components, and in patients with anemia not caused by iron deficiency.
|
| dailymed-instance:supply |
Venofer is supplied in 5 mL and 10 mL single dose vials. Each 5 mL vial contains 100 mg elemental iron (20 mg/mL) and each 10 mL vial contains 200 mg elemental iron (20 mg/mL). Contains no preservatives. Store in original carton at 25��C (77��F). Excursions permitted to 15��-30��C (59��-86��F). [See the USP controlled room temperature]. Do not freeze. Sterile Rx Only
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:precautio... |
General:: Because body iron excretion is limited and excess tissue iron can be hazardous, caution should be exercised to withhold iron administration in the presence of evidence of tissue iron overload. Patients receiving Venofer require periodic monitoring of hematologic and hematinic parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). 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. .<br/>Hypersensitivity Reactions:: Serious hypersensitivity reactions have been reported in patients receiving Venofer. No life-threatening hypersensitivity reactions were observed in the clinical studies. Several cases of mild or moderate hypersensitivity reactions were observed in these studies. There are post-marketing spontaneous reports of life-threatening hypersensitivity reactions in patients receiving Venofer. See ADVERSE REACTIONS.<br/>Hypotension:: Hypotension has been reported frequently in hemodialysis dependent chronic kidney disease patients receiving intravenous iron. Hypotension also has been reported in non-dialysis dependent and peritoneal dialysis dependent-chronic kidney disease patients receiving intravenous iron. Hypotension following administration of Venofer may be related to rate of administration and total dose administered. Caution should be taken to administer Venofer according to recommended guidelines. See DOSAGE AND ADMINISTRATION<br/>Carcinogenesis, Mutagenesis, and Impairment of Fertility:: No long-term studies in animals have been performed to evaluate the carcinogenic potential of Venofer. Venofer was not genotoxic in the Ames test, the mouse lymphoma cell (L5178Y/TK+/-) forward mutation test, the human lymphocyte chromosome aberration test, or the mouse micronucleus test. Venofer at IV doses up to 15 mg iron/kg/day (about 1.2 times the recommended maximum human dose on a body surface area basis) was found to have no effect on fertility and reproductive performance of male and female rats.<br/>Pregnancy Category B:: Teratology studies have been performed in rats at IV doses up to 13 mg iron/kg/day (about 0.5 times the recommended maximum human dose on a body surface area basis) and rabbits at IV doses up to 13 mg iron/kg/day (about 1 times the recommended maximum human dose on a body surface area basis) and have revealed no evidence of impaired fertility or harm to the fetus due to Venofer. There are, however, no adequate and well controlled studies 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.<br/>Nursing Mothers:: Venofer is excreted in milk of rats. 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 Venofer is administered to a nursing woman.<br/>Pediatric Use:: Safety and effectiveness of Venofer in pediatric patients have not been established. In a country where Venofer is available for use in children, at a single site, five premature infants (weight less than 1,250 g) developed necrotizing enterocolitis and two of the five expired during or following a period when they received Venofer, several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Venofer or any other drugs could be established.<br/>Geriatric Use:: Studies A through E did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Of the 1,051 patients in two post-marketing safety studies of Venofer, 40% were 65 years and older. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
|
| dailymed-instance:overdosag... |
Dosages of Venofer (iron sucrose injection, USP) in excess of iron needs may lead to accumulation of iron in storage sites leading to hemosiderosis. Periodic monitoring of iron parameters such as serum ferritin and transferrin saturation may assist in recognizing iron accumulation. Venofer should not be administered to patients with iron overload and should be discontinued when serum ferritin levels equal or exceed established guidelines [5]. 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 Venofer too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, 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.<br/>Preclinical Data:: Single IV doses of Venofer at 150 mg iron/kg in mice (about 3 times the recommended maximum human dose on a body surface area basis) and 100 mg iron/kg in rats (about 8 times the recommended maximum human dose on a body surface area basis) were lethal. The symptoms of acute toxicity were sedation, hypoactivity, pale eyes, and bleeding in the gastrointestinal tract and lungs.
|
| dailymed-instance:genericMe... |
Iron Sucrose
|
| dailymed-instance:fullName |
Venofer (Injection)
|
| dailymed-instance:adverseRe... |
Adverse Events observed in all treated populations: The frequency of adverse events associated with the use of Venofer has been documented in six randomized clinical trials involving 231 hemodialysis dependent, 139 non-dialysis dependent and 75 peritoneal dialysis dependent-CKD patients; and in two post-marketing safety studies involving 1,051 hemodialysis dependent-CKD patients for a total of 1,496 patients. In addition, over 2,000 patients treated with Venofer have been reported in the medical literature. Treatment-emergent adverse events reported by���2% of treated patients in the randomized clinical trials, whether or not related to Venofer administration, are listed by indication in Table 2. Treatment-emergent adverse events reported in���2% of patients by dose group are shown in Table 3. Drug related adverse events reported by���2% of Venofer treated patients are shown by dose group in Table 4.<br/>Adverse Events Observed in Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD) Patients: Adverse reactions, whether or not related to Venofer (iron sucrose injection, USP) administration, reported by>5% of treated patients from a total of 231 patients in HDD-CKD Studies A, B, and C were as follows: hypotension (39.4%), muscle cramps (29.4%), nausea (14.7%), headache (12.6%), graft complications (9.5%), vomiting (9.1%), dizziness (6.5%), hypertension (6.5%), chest pain (6.1%), and diarrhea (5.2%). In the first post-marketing safety study, 665 chronic hemodialysis patients were treated with Venofer doses of 100 mg at each dialysis session for up to 10 consecutive dialysis sessions for their iron deficiency or on a weekly basis for 10 weeks for maintenance of iron stores. In this study, 72% of the patients received up to 10 doses, 27% received between 11-30 doses, and 1% received 40 to 50 doses of Venofer. Serious adverse events and drug-related non-serious adverse events were collected. In the second post-marketing safety study, 386 hemodialysis patients were exposed to a single dose of Venofer (100 mg IV by slow injection over 2 minutes or 200 mg IV by slow injection over 5 minutes). The mean age of patients enrolled into the two post-marketing safety studies was 59 years, with a range of 20-93 years. Males made up 60% of the population. The ethnicity of the patients enrolled in the two studies included Blacks (44%), Caucasians (41%), Hispanics (11%), Asians (3%), and others (1%). Adverse events reported by>1% of 1,051 treated patients were: cardiac failure congestive, sepsis NOS and dysgeusia.<br/>Adverse Events Observed in Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) Patients: In Study D of 182 treated NDD-CKD patients, 91 were exposed to Venofer. Adverse events, whether or not related to Venofer , reported by���5% of the Venofer exposed patients were as follows: dysgeusia (7.7%), peripheral edema (7.7%), diarrhea (5.5%), constipation (5.5%), nausea (5.5%), dizziness (5.5%), and hypertension (5.5%). One serious related adverse reaction was reported (hypotension and shortness of breath not requiring hospitalization in a Venofer patient). Two patients experienced possible hypersensitivity/allergic reactions (local edema/hypotension) during the study. Of the 5 patients who prematurely discontinued the treatment phase ofthe study due to adverse events (2 oral iron group and 3 Venofer group), three Venofer patients had events that were considered drug-related (hypotension, dyspnea and nausea). In an additional study of Venofer with varying erythropoietin doses in 96 treated NDD-CKD patients, adverse events, whether or not related to Venofer reported by���5% of Venofer exposed patients are as follows: diarrhea (16.5%), edema (16.5%), nausea (13.2%), vomiting (12.1%), arthralgia (7.7%), back pain (7.7%), headache (7.7%), hypertension (7.7%), dysgeusia (7.7%), dizziness (6.6%), extremity pain (5.5%), and injection site burning (5.5%). No patient experienced a hypersensitivity/allergic reaction during the study. Of the patients who prematurely discontinued the treatment phase of the study due to adverse events (2.1% oral iron group and 12.5% Venofer group), only one patient (Venofer group) had events that were considered drug-related (anxiety, headache, and nausea). Ninety-one (91) patients in thisstudy were exposed to Venofer either during the treatment or extended follow-up phase.<br/>Adverse Events Observed in Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) Patients: In Study E of 121 treated PDD-CKD patients, 75 patients were exposed to Venofer. Adverse events, whether or not related to Venofer reported by���5% of these patients are as follows: diarrhea, peritoneal infection, vomiting, hypertension, pharyngitis, peripheral edema and nausea. In these 75 patients exposed to Venofer, 9 patients experienced serious adverse events as follows: peritoneal infection (2 patients) and 1 patient each with cardiopulmonary arrest, myocardial infarction, upper respiratory infection NOS, anemia, gangrene, hypovolemia and tuberculosis. None of these events were considered drug-related. Two Venofer patients experienced a moderate hypersensitivity/allergic reaction (rash or swelling/itching) during the study. The only drug related adverse reaction to Venofer administration reported by���2% of patients was diarrhea. Three patients in the Venofer study group discontinued study treatment due to adverse events (cardiopulmonary arrest, peritonitis and myocardial infarction, hypertension) which were considered to be not drug-related.<br/>Hypersensitivity Reactions:: See WARNINGS and PRECAUTIONS. In clinical studies, several patients experienced hypersensitivity reactions presenting with wheezing, dyspnea, hypotension, rashes, or pruritus. Serious episodes of hypotension occurred in 2 patients treated with Venofer at a dose of 500 mg. The post-marketing spontaneous reporting system includes reports of patients who experienced serious or life-threatening reactions (anaphylactic shock, loss of consciousness or collapse, bronchospasm with dyspnea, or convulsion) associated with Venofer administration. One hundred thirty (11%) of the 1,151 patients evaluated in the 4 U.S. trials in HDD-CKD patients (studies A, B and the two post marketing studies) had prior other intravenous iron therapy and were reported to be intolerant (defined as precluding further use of that iron product). When these patients were treated with Venofer there were no occurrences of adverse events that precluded further use of Venofer
|
| dailymed-instance:warning |
Hypersensitivity reactions have been reported with injectable iron products. See PRECAUTIONS and ADVERSE REACTIONS.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Venofer
|