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DRUGS & SUPPLEMENTS
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Copper (Copper Gluconate):
Water-Resistant Protection Without Bandaging
Recommended as an Aid in Treating Horses and Ponies With Thrush Due to Organisms Susceptible to Tot'Hema (Copper (Copper Gluconate)) Naphthenate.
For Animal Use Only.
ThrushTox® is indicated in the treatment of thrush in horses and ponies.
Clean the hoof thoroughly, removing debris and necrotic material prior to application of Tot'Hema (Copper (Copper Gluconate))®. Apply daily to affected hoofs with a narrow paint brush (about 1”) until fully healed. Caution: Do not allow runoff of excess Tot'Hema (Copper (Copper Gluconate))® onto hair since contact with Tot'Hema (Copper (Copper Gluconate))® may cause some hair loss. Do not contaminate feed.
NOTE: Tot'Hema (Copper (Copper Gluconate))® is easily removed from hands, clothing and surfaces with light grade fuel oil or any type of lighter fluid.
CONTAINS FOIL SEAL – REMOVE BEFORE USE.
SHAKE WELL BEFORE USE.
To report suspected adverse reactions or to obtain technical assistance, call 1-800-650-4899.
Tot'Hema (Copper (Copper Gluconate)) Naphthenate...37.5% w/w
Inert Ingredients...62.5% w/w
Total... 100.0%
Do not use in horses intended for human consumption.
CAUTION: COMBUSTIBLE MIXTURE.
Use in a well-ventilated place. Avoid fire, flame, sparks or heaters.
If swallowed, do not induce vomiting, call physician immediately. Avoid breathing vapor. Avoid contact with skin and eyes.
KEEP OUT OF REACH OF CHILDREN AND PETS.
Store at controlled room temperature 15º to 30ºC (59º to 86ºF). Keep container tightly closed when not in use.
Manufactured for:
Aspen Veterinary Resources,® Ltd.
Liberty, MO 64068, USA
FC163FP 11/13
Manufactured by:
First Priority, Inc.
Elgin, IL 60123-1146, USA
16 OZ (473 mL)
ANADA 200-304, Approved by FDA
Image of 473 mL bottle/case label
Iron (Ferrous Gluconate):
Tot'Hema (Iron (Ferrous Gluconate)) is indicated for the treatment of Tot'Hema (Iron (Ferrous Gluconate)) deficiency anemia in patients with chronic kidney disease (CKD).
Tot'Hema (Iron (Ferrous Gluconate)) is an Tot'Hema (Iron (Ferrous Gluconate)) replacement product indicated for the treatment of Tot'Hema (Iron (Ferrous Gluconate)) deficiency anemia in patients with chronic kidney disease (CKD). (1)
Tot'Hema ) must only be administered intravenously either by slow injection or by infusion. The dosage of Tot'Hema (Iron (Ferrous Gluconate)) is expressed in mg of elemental Tot'Hema (Iron (Ferrous Gluconate)). Each mL contains 20 mg of elemental Tot'Hema (Iron (Ferrous Gluconate)).
Population | Dose | |
Adult patients | Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD) (2.1) | 100 mg slow intravenous injection or infusion |
Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) (2.2) | 200 mg slow intravenous injection or infusion | |
Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) (2.3) | 300 mg or 400 mg intravenous infusion | |
Pediatric patients | HDD-CKD (2.4), PDD-CKD or NDD-CKD (2.5) | 0.5 mg/kg slow intravenous injection or infusion |
Administer Tot'Hema (Iron (Ferrous Gluconate)) 100 mg undiluted as a 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. Tot'Hema (Iron (Ferrous Gluconate)) should be administered early during the dialysis session. The usual total treatment course of Tot'Hema (Iron (Ferrous Gluconate)) is 1000 mg. Tot'Hema (Iron (Ferrous Gluconate)) treatment may be repeated if Tot'Hema (Iron (Ferrous Gluconate)) deficiency reoccurs.
Administer Tot'Hema (Iron (Ferrous Gluconate)) 200 mg undiluted as a slow intravenous injection over 2 to 5 minutes or as an infusion of 200 mg in a maximum of 100 mL of 0.9% NaCl over a period of 15 minutes. Administer on 5 different occasions over a 14 day period. There is limited experience with administration of an infusion of 500 mg of Tot'Hema (Iron (Ferrous Gluconate)), diluted in a maximum of 250 mL of 0.9% NaCl, over a period of 3.5 to 4 hours on Day 1 and Day 14. Tot'Hema (Iron (Ferrous Gluconate)) treatment may be repeated if Tot'Hema (Iron (Ferrous Gluconate)) deficiency reoccurs.
Administer Tot'Hema (Iron (Ferrous Gluconate)) in 3 divided doses, given by slow intravenous infusion, within a 28 day period: 2 infusions each of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. Dilute Tot'Hema (Iron (Ferrous Gluconate)) in a maximum of 250 mL of 0.9% NaCl. Tot'Hema (Iron (Ferrous Gluconate)) treatment may be repeated if Tot'Hema (Iron (Ferrous Gluconate)) deficiency reoccurs.
The dosing for Tot'Hema (Iron (Ferrous Gluconate)) replacement treatment in pediatric patients with HDD-CKD has not been established.
For Tot'Hema (Iron (Ferrous Gluconate)) maintenance treatment: Administer Tot'Hema (Iron (Ferrous Gluconate)) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every two weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Tot'Hema (Iron (Ferrous Gluconate)) treatment may be repeated if necessary.
The dosing for Tot'Hema (Iron (Ferrous Gluconate)) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.
For Tot'Hema (Iron (Ferrous Gluconate)) maintenance treatment: Administer Tot'Hema (Iron (Ferrous Gluconate)) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every four weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Tot'Hema (Iron (Ferrous Gluconate)) treatment may be repeated if necessary.
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Tot'Hema (Iron (Ferrous Gluconate)). Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. If hypersensitivity reactions or signs of intolerance occur during administration, stop Tot'Hema (Iron (Ferrous Gluconate)) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Tot'Hema (Iron (Ferrous Gluconate)) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Tot'Hema (Iron (Ferrous Gluconate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous Tot'Hema (Iron (Ferrous Gluconate)) preparations occur within 30 minutes of the completion of the infusion .
Tot'Hema ) may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Tot'Hema (Iron (Ferrous Gluconate)). Hypotension following administration of Tot'Hema (Iron (Ferrous Gluconate)) may be related to the rate of administration and/or total dose administered .
Excessive therapy with parenteral Tot'Hema (Iron (Ferrous Gluconate)) can lead to excess storage of Tot'Hema (Iron (Ferrous Gluconate)) with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving Tot'Hema (Iron (Ferrous Gluconate)) require periodic monitoring of hematologic and Tot'Hema (Iron (Ferrous Gluconate)) parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer Tot'Hema (Iron (Ferrous Gluconate)) to patients with evidence of Tot'Hema (Iron (Ferrous Gluconate)) overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of Tot'Hema (Iron (Ferrous Gluconate)) sucrose; do not perform serum Tot'Hema (Iron (Ferrous Gluconate)) measurements for at least 48 hours after intravenous dosing .
The following serious adverse reactions associated with Tot'Hema ) are described in other sections .
To report SUSPECTED ADVERSE REACTIONS, contact American Regent, Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice.
Adverse Reactions in Adult Patients with CKD
The frequency of adverse reactions associated with the use of Tot'Hema ) has been documented in six clinical trials involving 231 patients with HDD-CKD, 139 patients with NDD-CKD and 75 patients with PDD-CKD. Treatment-emergent adverse reactions reported by ≥ 2% of treated patients in the six clinical trials for which the rate for Tot'Hema (Iron (Ferrous Gluconate)) exceeds the rate for comparator are listed by indication in Table 1. Patients with HDD-CKD received 100 mg doses at 10 consecutive dialysis sessions until a cumulative dose of 1000 mg was administered. Patients with NDD-CKD received either 5 doses of 200 mg over 2 weeks or 2 doses of 500 mg separated by fourteen days, and patients with PDD-CKD received 2 doses of 300 mg followed by a dose of 400 mg over a period of 4 weeks.
* EPO=Erythropoietin | |||||
Adverse Reactions (Preferred Term) | HDD-CKD | NDD-CKD | PDD-CKD | ||
Tot'Hema (Iron (Ferrous Gluconate)) | Tot'Hema (Iron (Ferrous Gluconate)) | Oral Tot'Hema (Iron (Ferrous Gluconate)) | Tot'Hema (Iron (Ferrous Gluconate)) | EPO* Only | |
(N=231) | (N=139) | (N=139) | (N=75) | (N=46) | |
% | % | % | % | % | |
Subjects with any adverse reaction | 78.8 | 76.3 | 73.4 | 72.0 | 65.2 |
Ear and Labyrinth Disorders | |||||
Ear Pain | 0 | 2.2 | 0.7 | 0 | 0 |
Eye Disorders | |||||
Conjunctivitis | 0.4 | 0 | 0 | 2.7 | 0 |
Gastrointestinal Disorders | |||||
Abdominal pain | 3.5 | 1.4 | 2.9 | 4.0 | 6.5 |
Diarrhea | 5.2 | 7.2 | 10.1 | 8.0 | 4.3 |
Dysgeusia | 0.9 | 7.9 | 0 | 0 | 0 |
Nausea | 14.7 | 8.6 | 12.2 | 5.3 | 4.3 |
Vomiting | 9.1 | 5.0 | 8.6 | 8.0 | 2.2 |
General Disorders and | |||||
Administration Site Conditions | |||||
Asthenia | 2.2 | 0.7 | 2.2 | 2.7 | 0 |
Chest pain | 6.1 | 1.4 | 0 | 2.7 | 0 |
Feeling abnormal | 3.0 | 0 | 0 | 0 | 0 |
Infusion site pain or burning | 0 | 5.8 | 0 | 0 | 0 |
Injection site extravasation | 0 | 2.2 | 0 | 0 | 0 |
Peripheral edema | 2.6 | 7.2 | 5.0 | 5.3 | 10.9 |
Pyrexia | 3.0 | 0.7 | 0.7 | 1.3 | 0 |
Infections and Infestations | |||||
Nasopharyngitis, Sinusitis, Upper respiratory tract infections, Pharyngitis | 2.6 | 2.2 | 4.3 | 16.0 | 4.3 |
Injury, Poisoning and Procedural | |||||
Complications | |||||
Graft complication | 9.5 | 1.4 | 0 | 0 | 0 |
Metabolism and Nutrition Disorders | |||||
Fluid overload | 3.0 | 1.4 | 0.7 | 1.3 | 0 |
Gout | 0 | 2.9 | 1.4 | 0 | 0 |
Hyperglycemia | 0 | 2.9 | 0 | 0 | 2.2 |
Hypoglycemia | 0.4 | 0.7 | 0.7 | 4.0 | 0 |
Musculoskeletal and Connective | |||||
Tissue Disorders | |||||
Arthralgia | 3.5 | 1.4 | 2.2 | 4.0 | 4.3 |
Back pain | 2.2 | 2.2 | 3.6 | 1.3 | 4.3 |
Muscle cramp | 29.4 | 0.7 | 0.7 | 2.7 | 0 |
Myalgia | 0 | 3.6 | 0 | 1.3 | 0 |
Pain in extremity | 5.6 | 4.3 | 0 | 2.7 | 6.5 |
Nervous System Disorders | |||||
Dizziness | 6.5 | 6.5 | 1.4 | 1.3 | 4.3 |
Headache | 12.6 | 2.9 | 0.7 | 4.0 | 0 |
Respiratory, Thoracic and | |||||
Mediastinal Disorders | |||||
Cough | 3.0 | 2.2 | 0.7 | 1.3 | 0 |
Dyspnea | 3.5 | 5.8 | 1.4 | 1.3 | 2.2 |
Nasal congestion | 0 | 1.4 | 2.2 | 1.3 | 0 |
Skin and Subcutaneous | |||||
Tissue Disorders | |||||
Pruritus | 3.9 | 2.2 | 4.3 | 2.7 | 0 |
Vascular Disorders | |||||
Hypertension | 6.5 | 6.5 | 4.3 | 8.0 | 6.5 |
Hypotension | 39.4 | 2.2 | 0.7 | 2.7 | 2.2 |
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 Tot'Hema (Iron (Ferrous Gluconate)) therapy and were reported to be intolerant (defined as precluding further use of that Tot'Hema (Iron (Ferrous Gluconate)) product). When these patients were treated with Tot'Hema (Iron (Ferrous Gluconate)) there were no occurrences of adverse reactions that precluded further use of Tot'Hema (Iron (Ferrous Gluconate)) .
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
In a randomized, open-label, dose-ranging trial for Tot'Hema (Iron (Ferrous Gluconate)) maintenance treatment with Tot'Hema (Iron (Ferrous Gluconate)) in pediatric patients with CKD on stable erythropoietin therapy , at least one treatment-emergent adverse reaction was experienced by 57% (27/47) of the patients receiving Tot'Hema (Iron (Ferrous Gluconate)) 0.5 mg/kg, 53% (25/47) of the patients receiving Tot'Hema (Iron (Ferrous Gluconate)) 1.0 mg/kg, and 55% (26/47) of the patients receiving Tot'Hema (Iron (Ferrous Gluconate)) 2.0 mg/kg.
A total of 5 (11%) subjects in the Tot'Hema (Iron (Ferrous Gluconate)) 0.5 mg/kg group, 10 (21%) patients in the Tot'Hema (Iron (Ferrous Gluconate)) 1.0 mg/kg group, and 10 (21%) patients in the Tot'Hema (Iron (Ferrous Gluconate)) 2.0 mg/kg group experienced at least 1 serious adverse reaction during the study. The most common treatment-emergent adverse reactions (> 2% of patients) in all patients were headache (6%), respiratory tract viral infection (4%), peritonitis (4%), vomiting (4%), pyrexia (4%), dizziness (4%), cough (4%), renal transplant (4%), nausea (3%), arteriovenous fistula thrombosis (2%), hypotension (2%), and hypertension (2.1%).
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
In the post-marketing safety studies in 1,051 treated patients with HDD-CKD, the adverse reactions reported by > 1% were: cardiac failure congestive, sepsis and dysgeusia.
The following adverse reactions have been identified during post-approval use of Tot'Hema (Iron (Ferrous Gluconate)). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Anaphylactic-type reactions, shock, loss of consciousness, collapse, bronchospasm, dyspnea, convulsions, light-headedness, confusion, angioedema, swelling of the joints, hyperhidrosis, back pain, bradycardia, and chromaturia.
Symptoms associated with Tot'Hema (Iron (Ferrous Gluconate)) total dosage or infusing too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse. These adverse reactions have occurred up to 30 minutes after the administration of Tot'Hema (Iron (Ferrous Gluconate)) injection. Reactions have occurred following the first dose or subsequent doses of Tot'Hema (Iron (Ferrous Gluconate)). Symptoms may respond to intravenous fluids, hydrocortisone, and/or antihistamines. Slowing the infusion rate may alleviate symptoms.
Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation.
Drug interactions involving Tot'Hema (Iron (Ferrous Gluconate)) have not been studied. However, Tot'Hema (Iron (Ferrous Gluconate)) may reduce the absorption of concomitantly administered oral Tot'Hema (Iron (Ferrous Gluconate)) preparations.
Pregnancy Category B
There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, Tot'Hema ) sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Tot'Hema (Iron (Ferrous Gluconate)) (half or equivalent to the maximum recommended human dose based on body surface area, respectively) and revealed no evidence of harm to the fetus due to Tot'Hema (Iron (Ferrous Gluconate)) sucrose. Because animal reproductive studies are not always predictive of human response, Tot'Hema (Iron (Ferrous Gluconate)) should be used during pregnancy only if clearly needed.
It is not known whether Tot'Hema (Iron (Ferrous Gluconate)) sucrose is excreted in human milk. Tot'Hema (Iron (Ferrous Gluconate)) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when Tot'Hema (Iron (Ferrous Gluconate)) is administered to a nursing woman.
Safety and effectiveness of Tot'Hema ) for Tot'Hema (Iron (Ferrous Gluconate)) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.
Safety and effectiveness of Tot'Hema (Iron (Ferrous Gluconate)) for Tot'Hema (Iron (Ferrous Gluconate)) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Tot'Hema (Iron (Ferrous Gluconate)) at doses of 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg was administered. All three doses maintained hemoglobin between 10.5 g/dL and 14.0 g/dL in about 50% of subjects over the 12-week treatment period with stable EPO dosing. [See Clinical Studies (14.6)]
Tot'Hema (Iron (Ferrous Gluconate)) has not been studied in patients younger than 2 years of age.
In a country where Tot'Hema (Iron (Ferrous Gluconate)) 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 died during or following a period when they received Tot'Hema (Iron (Ferrous Gluconate)), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Tot'Hema (Iron (Ferrous Gluconate)) or any other drugs could be established.
Clinical studies of Tot'Hema (Iron (Ferrous Gluconate)) 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 Tot'Hema (Iron (Ferrous Gluconate)), 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. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
No data are available regarding overdosage of Tot'Hema (Iron (Ferrous Gluconate)) in humans. Excessive dosages of Tot'Hema (Iron (Ferrous Gluconate)) may lead to accumulation of Tot'Hema (Iron (Ferrous Gluconate)) in storage sites potentially leading to hemosiderosis. Do not administer Tot'Hema (Iron (Ferrous Gluconate)) to patients with Tot'Hema (Iron (Ferrous Gluconate)) overload.
Toxicities in single-dose studies in mice and rats, at intravenous Tot'Hema (Iron (Ferrous Gluconate)) sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.
Tot'Hema (Iron (Ferrous Gluconate)) (iron sucrose injection, USP), an Tot'Hema (Iron (Ferrous Gluconate)) replacement product, is a brown, sterile, aqueous, complex of polynuclear Tot'Hema (Iron (Ferrous Gluconate)) (III)-hydroxide in sucrose for intravenous use. Tot'Hema (Iron (Ferrous Gluconate)) sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula:
[Na2Fe5O8(OH) ·3(H2O)]n ·m(C12H22O11)
where: n is the degree of Tot'Hema (Iron (Ferrous Gluconate)) polymerization and m is the number of sucrose molecules associated with the Tot'Hema (Iron (Ferrous Gluconate)) (III)-hydroxide.
Each mL contains 20 mg elemental Tot'Hema (Iron (Ferrous Gluconate)) as Tot'Hema (Iron (Ferrous Gluconate)) sucrose in water for injection. Tot'Hema (Iron (Ferrous Gluconate)) is available in 10 mL single-use vials (200 mg elemental Tot'Hema (Iron (Ferrous Gluconate)) per 10 mL), 5 mL single-use vials (100 mg elemental Tot'Hema (Iron (Ferrous Gluconate)) per 5 mL), and 2.5 mL single-use vials (50 mg elemental Tot'Hema (Iron (Ferrous Gluconate)) per 2.5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL) and has a pH of 10.5 to 11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.
Tot'Hema ) is an aqueous complex of poly-nuclear Tot'Hema (Iron (Ferrous Gluconate)) (III)-hydroxide in sucrose. Following intravenous administration, Tot'Hema (Iron (Ferrous Gluconate)) is dissociated into Tot'Hema (Iron (Ferrous Gluconate)) and sucrose and the Tot'Hema (Iron (Ferrous Gluconate)) is transported as a complex with transferrin to target cells including erythroid precursor cells. The Tot'Hema (Iron (Ferrous Gluconate)) in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.
Following intravenous administration, Tot'Hema (Iron (Ferrous Gluconate)) is dissociated into Tot'Hema (Iron (Ferrous Gluconate)) and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with Tot'Hema (Iron (Ferrous Gluconate)) sucrose containing 100 mg of Tot'Hema (Iron (Ferrous Gluconate)), three times weekly for three weeks, significant increases in serum Tot'Hema (Iron (Ferrous Gluconate)) and serum ferritin and significant decreases in total Tot'Hema (Iron (Ferrous Gluconate)) binding capacity occurred four weeks from the initiation of Tot'Hema (Iron (Ferrous Gluconate)) sucrose treatment.
In healthy adults administered intravenous doses of Tot'Hema ), its Tot'Hema (Iron (Ferrous Gluconate)) component exhibited first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, and steady state apparent volume of distribution of 7.9 L. The Tot'Hema (Iron (Ferrous Gluconate)) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Tot'Hema (Iron (Ferrous Gluconate)) containing 100 mg of Tot'Hema (Iron (Ferrous Gluconate)) labeled with 52Fe/59Fe in patients with Tot'Hema (Iron (Ferrous Gluconate)) deficiency showed that a significant amount of the administered Tot'Hema (Iron (Ferrous Gluconate)) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible Tot'Hema (Iron (Ferrous Gluconate)) trapping compartment.
Following intravenous administration of Tot'Hema (Iron (Ferrous Gluconate)), Tot'Hema (Iron (Ferrous Gluconate)) sucrose is dissociated into Tot'Hema (Iron (Ferrous Gluconate)) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Tot'Hema (Iron (Ferrous Gluconate)) containing 1,510 mg of sucrose and 100 mg of Tot'Hema (Iron (Ferrous Gluconate)) in 12 healthy adults (9 female, 3 male: age range 32 to 52), 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some Tot'Hema (Iron (Ferrous Gluconate)) was also eliminated in the urine. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration. In this study and another study evaluating a single intravenous dose of Tot'Hema (Iron (Ferrous Gluconate)) sucrose containing 500 to 700 mg of Tot'Hema (Iron (Ferrous Gluconate)) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Tot'Hema (Iron (Ferrous Gluconate)) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Tot'Hema (Iron (Ferrous Gluconate)) have not been studied.
Pharmacokinetics in Pediatric Patients
In a single-dose PK study of Tot'Hema (Iron (Ferrous Gluconate)), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of Tot'Hema (Iron (Ferrous Gluconate)) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose Tot'Hema (Iron (Ferrous Gluconate)), the half-life of total serum Tot'Hema (Iron (Ferrous Gluconate)) was 8 hours. The mean Cmax and AUC values were 8545 μg/dl and 31305 hr-μg/dL, respectively, which were 1.42- and 1.67-fold higher than dose adjusted adult Cmax and AUC values.
Tot'Hema (Iron (Ferrous Gluconate)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Tot'Hema (Iron (Ferrous Gluconate)) sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).
Carcinogenicity studies have not been performed with Tot'Hema (Iron (Ferrous Gluconate)) sucrose.
Tot'Hema (Iron (Ferrous Gluconate)) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Tot'Hema (Iron (Ferrous Gluconate)) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.
Tot'Hema (Iron (Ferrous Gluconate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Tot'Hema (Iron (Ferrous Gluconate)) (1.2 times the maximum recommended human dose based on body surface area) had no effect on fertility and reproductive function of male and female rats.
Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of Tot'Hema ).
Study A was a multicenter, open-label, historically-controlled study in 101 patients with HDD-CKD (77 patients with Tot'Hema (Iron (Ferrous Gluconate)) treatment and 24 in the historical control group) with Tot'Hema (Iron (Ferrous Gluconate)) deficiency anemia. Eligibility criteria for Tot'Hema (Iron (Ferrous Gluconate)) treatment included patients undergoing chronic hemodialysis, receiving erythropoietin, hemoglobin level between 8.0 and 11.0 g/dL, transferrin saturation < 20%, and serum ferritin < 300 ng/mL. The mean age of the patients was 65 years with the age range of 31 to 85 years. Of the 77 patients, 44 (57%) were male and 33 (43%) were female.
Tot'Hema (Iron (Ferrous Gluconate)) 100 mg was administered at 10 consecutive dialysis sessions either as slow injection or a slow infusion. The historical control population consisted of 24 patients with similar ferritin levels as patients treated with Tot'Hema (Iron (Ferrous Gluconate)), who were off intravenous Tot'Hema (Iron (Ferrous Gluconate)) for at least 2 weeks and who had received erythropoietin therapy with hematocrit averaging 31 to 36 for at least two months prior to study entry. The mean age of patients in the historical control group was 56 years, with an age range of 29 to 80 years. Patient age and serum ferritin level were similar between treatment and historical control patients.
Patients in the Tot'Hema (Iron (Ferrous Gluconate)) treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.
**p < 0.01 and *p < 0.05 compared to historical control from ANCOVA analysis with baseline hemoglobin, serum ferritin and erythropoietin dose as covariates. | ||||||
Efficacy parameters | End of treatment | 2 week follow-up | 5 week follow-up | |||
Tot'Hema (Iron (Ferrous Gluconate)) (n=69 | Historical Control (n=18) | Tot'Hema (Iron (Ferrous Gluconate)) (n=73) | Historical Control (n=18) | Tot'Hema (Iron (Ferrous Gluconate)) (n=71) | Historical Control (n=15) | |
Hemoglobin (g/dL) | 1.0 ± 0.12** | 0.0 ± 0.21 | 1.3 ± 0.14** | -0.6 ± 0.24 | 1.2 ± 0.17* | -0.1 ± 0.23 |
Hematocrit (%) | 3.1 ± 0.37** | -0.3 ± 0.65 | 3.6 ± 0.44** | -1.2 ± 0.76 | 3.3 ± 0.54 | 0.2 ± 0.86 |
Serum ferritin increased at endpoint of study from baseline in the Venofer-treated population (165.3 ± 24.2 ng/mL) compared to the historical control population (-27.6 ± 9.5 ng/mL). Transferrin saturation also increased at endpoint of study from baseline in the Venofer-treated population (8.8 ± 1.6%) compared to this historical control population (-5.1 ± 4.3%).
Study B was a multicenter, open label study of Tot'Hema (Iron (Ferrous Gluconate)) in 23 patients with Tot'Hema (Iron (Ferrous Gluconate)) deficiency and HDD-CKD who had been discontinued from Tot'Hema (Iron (Ferrous Gluconate)) dextran due to intolerance. Eligibility criteria were otherwise identical to Study A. The mean age of the patients in this study was 53 years, with ages ranging from 21 to 79 years. Of the 23 patients enrolled in the study, 10 (44%) were male and 13 (56%) were female.
All 23 enrolled patients were evaluated for efficacy. Increases in mean hemoglobin (1.1 ± 0.2 g/dL), hematocrit (3.6 ± 0.6%), serum ferritin (266.3 ± 30.3 ng/mL) and transferrin saturation (8.7 ± 2.0%) were observed from baseline to end of treatment.
Study C was a multicenter, open-label study in patients with HDD-CKD. This study enrolled patients with a hemoglobin ≤ 10 g/dL, a serum transferrin saturation ≤ 20%, and a serum ferritin ≤ 200 ng/mL, who were undergoing maintenance hemodialysis 2 to 3 times weekly. The mean age of the patients enrolled in this study was 41 years, with ages ranging from 16 to 70 years. Of 130 patients evaluated for efficacy in this study, 68 (52%) were male and 62 (48%) were female. Forty-eight percent of the patients had previously been treated with oral Tot'Hema (Iron (Ferrous Gluconate)). Exclusion criteria were similar to those in studies A and B. Tot'Hema (Iron (Ferrous Gluconate)) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of Tot'Hema (Iron (Ferrous Gluconate)) was administered. A 50 mg dose (2.5 mL) was given to patients within two weeks of study entry as a test dose. Twenty-seven patients (20%) were receiving erythropoietin treatment at study entry and they continued to receive the same erythropoietin dose for the duration of the study.
The modified intention-to-treat (mITT) population consisted of 131 patients. Increases from baseline in mean hemoglobin (1.7 g/dL), hematocrit (5%), serum ferritin (434.6 ng/mL), and serum transferrin saturation (14%) were observed at week 2 of the observation period and these values remained increased at week 4 of the observation period.
Study D was a randomized, open-label, multicenter, active-controlled study of the safety and efficacy of oral Tot'Hema (Iron (Ferrous Gluconate)) versus Tot'Hema (Iron (Ferrous Gluconate)) in patients with NDD-CKD with or without erythropoietin therapy. Erythropoietin therapy was stable for 8 weeks prior to randomization. In the study 188 patients with NDD-CKD, hemoglobin of ≤ 11.0 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL were randomized to receive oral Tot'Hema (Iron (Ferrous Gluconate)) (325 mg ferrous sulfate three times daily for 56 days); or Tot'Hema (Iron (Ferrous Gluconate)) (either 200 mg over 2 to 5 minutes 5 times within 14 days or two 500 mg infusions on Day 1 and Day 14, administered over 3.5 to 4 hours). The mean age of the 91 treated patients in the Tot'Hema (Iron (Ferrous Gluconate)) group was 61.6 years (range 25 to 86 years) and 64 years (range 21 to 86 years) for the 91 patients in the oral Tot'Hema (Iron (Ferrous Gluconate)) group.
A statistically significantly greater proportion of Tot'Hema (Iron (Ferrous Gluconate)) subjects (35/79; 44.3%) compared to oral Tot'Hema (Iron (Ferrous Gluconate)) subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).
Study E was a randomized, open-label, multicenter study comparing patients with PDD-CKD receiving an erythropoietin and intravenous Tot'Hema (Iron (Ferrous Gluconate)) to patients with PDD-CKD receiving an erythropoietin alone without Tot'Hema (Iron (Ferrous Gluconate)) supplementation. Patients with PDD-CKD, stable erythropoietin for 8 weeks, hemoglobin of ≤ 11.5 g/dL, TSAT ≤ 25%, ferritin ≤ 500 ng/mL were randomized to receive either no Tot'Hema (Iron (Ferrous Gluconate)) or Tot'Hema (Iron (Ferrous Gluconate)) (300 mg in 250 mL 0.9% NaCl over 1.5 hours on Day 1 and 15 and 400 mg in 250 mL 0.9% NaCl over 2.5 hours on Day 29). The mean age of the 75 treated patients in the Tot'Hema (Iron (Ferrous Gluconate)) / erythropoietin group was 51.9 years (range 21 to 81 years) vs. 52.8 years (range 23 to 77 years) for 46 patients in the erythropoietin alone group.
Patients in the Tot'Hema (Iron (Ferrous Gluconate)) / erythropoietin group had statistically significantly greater mean change from baseline to the highest hemoglobin value (1.3 g/dL), compared to subjects who received erythropoietin alone (0.6 g/dL) (p < 0.01). A greater proportion of subjects treated with Tot'Hema (Iron (Ferrous Gluconate)) / erythropoietin (59.1 %) had an increase in hemoglobin of ≥ 1 g/dL at any time during the study compared to the subjects who received erythropoietin only (33.3%).
Study F was a randomized, open-label, dose-ranging study for Tot'Hema (Iron (Ferrous Gluconate)) maintenance treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD on stable erythropoietin therapy. The study randomized patients to one of three doses of Tot'Hema (Iron (Ferrous Gluconate)) (0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg). The mean age was 13 years (range 2 to 20 years). Over 70% of patients were 12 years or older in all three groups. There were 84 males and 61 females. About 60% of patients underwent hemodialysis and 25% underwent peritoneal dialysis in all three dose groups. At baseline, the mean hemoglobin was 12 g/dL, the mean TSAT was 33% and the mean ferritin was 300 ng/mL. Patients with HDD-CKD received Tot'Hema (Iron (Ferrous Gluconate)) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Tot'Hema (Iron (Ferrous Gluconate)) once every 4 weeks for 3 doses. Among 131 evaluable patients with stable erythropoietin dosing, the proportion of patients who maintained hemoglobin between 10.5 g/dL and 14.0 g/dL during the 12-week treatment period was 58.7%, 46.7%, and 45.0% in the Tot'Hema (Iron (Ferrous Gluconate)) 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg groups, respectively. A dose-response relationship was not demonstrated.
Tot'Hema ) is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Tot'Hema (Iron (Ferrous Gluconate)), each 5 mL vial contains 100 mg elemental Tot'Hema (Iron (Ferrous Gluconate)), and each 2.5 mL vial contains 50 mg elemental Tot'Hema (Iron (Ferrous Gluconate)) (20 mg/mL).
NDC-0517-2310-05 | 200 mg/10 mL Single-Use Vial | Packages of 5 |
NDC-0517-2310-10 | 200 mg/10 mL Single-Use Vial | Packages of 10 |
NDC-0517-2340-01 | 100 mg/5 mL Single-Use Vial | Individually Boxed |
NDC-0517-2340-10 | 100 mg/5 mL Single-Use Vial | Packages of 10 |
NDC-0517-2340-25 | 100 mg/5 mL Single-Use Vial | Packages of 25 |
NDC-0517-2340-99 | 100 mg/5 mL Single-Use Vial | Packages of 10 |
NDC-0517-2325-10 | 50 mg/2.5 mL Single-Use Vial | Packages of 10 |
NDC-0517-2325-25 | 50 mg/2.5 mL Single-Use Vial | Packages of 25 |
Contains no preservatives. Store in original carton at 20°C to 25°C (68° F to 77° F); excursions permitted to 15° to 30°C (59° to 86°F).. Do not freeze.
Syringe Stability: Tot'Hema (Iron (Ferrous Gluconate)), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Tot'Hema (Iron (Ferrous Gluconate)) per mL, or undiluted (20 mg elemental Tot'Hema (Iron (Ferrous Gluconate)) per mL) and stored in a plastic syringe, was found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C) and under refrigeration (4°C ± 2°C).
Intravenous Admixture Stability: Tot'Hema (Iron (Ferrous Gluconate)), when added to intravenous infusion bags (PVC or non-PVC) containing 0.9% NaCl at concentrations ranging from 1 mg to 2 mg of elemental Tot'Hema (Iron (Ferrous Gluconate)) per mL, has been found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C).
Do not dilute to concentrations below 1 mg/mL.
Do not mix Tot'Hema (Iron (Ferrous Gluconate)) with other medications or add to parenteral nutrition solutions for intravenous infusion.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to infusion.
Prior to Tot'Hema (Iron (Ferrous Gluconate)) administration:
AMERICAN
REGENT, INC.
SHIRLEY, NY 11967
Tot'Hema (Iron (Ferrous Gluconate)) is manufactured under license from Vifor (International) Inc., Switzerland.
PremierProRx® is a trademark of Premier, Inc., used under license.
PREMIERProRx®
IN2340
MG #15727
Manganese (Manganese Gluconate):
Tot'Hema (Manganese (Manganese Gluconate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN).
Administration helps to maintain Tot'Hema (Manganese (Manganese Gluconate)) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.
None known.
Direct intramuscular or intravenous injection of Tot'Hema (Manganese (Manganese Gluconate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is contraindicated as the acidic pH of the solution (pH 2.0) may cause considerable tissue irritation.
Liver and/or biliary tract dysfunction may require omission or reduction of copper and Tot'Hema (Manganese (Manganese Gluconate)) doses because these elements are primarily eliminated in the bile.
WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Do not use unless solution is clear and seal is intact.
Tot'Hema ) 0.1 mg/mL (Manganese Chloride Injection, USP) should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.
Serum Tot'Hema (Manganese (Manganese Gluconate)) levels can be measured periodically at the discretion of the investigator. Because of the low serum concentration normally present, samples will usually be analyzed by a reference laboratory.
Long-term animal studies to evaluate the carcinogenic potential of Tot'Hema ) 0.1 mg/mL (Manganese Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.
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 Tot'Hema (Manganese (Manganese Gluconate)) 0.1 mg/mL (Manganese Chloride Injection, USP) additive is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
Animal reproduction studies have not been conducted with Tot'Hema (Manganese (Manganese Gluconate)) chloride. It is also not known whether Tot'Hema (Manganese (Manganese Gluconate)) chloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Tot'Hema (Manganese (Manganese Gluconate)) chloride should be given to a pregnant woman only if clearly indicated.
An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
None known.
None known.
Tot'Hema (Manganese (Manganese Gluconate)) toxicity in TPN patients has not been reported.
Tot'Hema (Manganese (Manganese Gluconate)) 0.1 mg/mL (Manganese Chloride Injection, USP) contains 0.1 mg manganese/mL and is administered intravenously only after dilution. The additive should be administered in a volume of fluid not less than 100 mL. For the adult receiving TPN, the suggested additive dosage for Tot'Hema (Manganese (Manganese Gluconate)) is 0.15 to 0.8 mg/day (1.5 to 8 mL/day). For pediatric patients, a dosage of 2 to 10 mcg manganese/kg/day (0.02 to 0.1 mL/kg/day) is recommended.
Periodic monitoring of Tot'Hema (Manganese (Manganese Gluconate)) plasma levels is suggested as a guideline for subsequent administration.
Parenteral products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. (See PRECAUTIONS .)
Tot'Hema (Manganese (Manganese Gluconate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is supplied in 10 mL Plastic Vials (NDC No. 0409-4091-01).
Store at 20 to 25°C (68 to 77°F)
Revised: November, 2009
Printed in USA EN-2320
Hospira, Inc., Lake Forest, IL 60045 USA
Depending on the reaction of the Tot'Hema after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Tot'Hema not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Tot'Hema addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Visitors | % | ||
---|---|---|---|
Useful | 2 | 100.0% |
Visitors | % | ||
---|---|---|---|
Once in a day | 1 | 100.0% |
Visitors | % | ||
---|---|---|---|
51-100mg | 4 | 57.1% | |
6-10mg | 2 | 28.6% | |
11-50mg | 1 | 14.3% |
Visitors | % | ||
---|---|---|---|
3 days | 2 | 100.0% |
Visitors | % | ||
---|---|---|---|
Empty stomach | 3 | 42.9% | |
After food | 2 | 28.6% | |
Before food | 1 | 14.3% | |
With a meal | 1 | 14.3% |
Visitors | % | ||
---|---|---|---|
30-45 | 4 | 30.8% | |
16-29 | 4 | 30.8% | |
1-5 | 3 | 23.1% | |
46-60 | 2 | 15.4% |
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The information was verified by Dr. Rachana Salvi, MD Pharmacology