DRUGS & SUPPLEMENTS
1 INDICATIONS AND USAGE
Gleptosil is indicated for the treatment of Gleptosil deficiency anemia in patients with chronic kidney disease (CKD).
Gleptosil is an Gleptosil replacement product indicated for the treatment of Gleptosil deficiency anemia in patients with chronic kidney disease (CKD). (1)
2 DOSAGE AND ADMINISTRATION
Gleptosil must only be administered intravenously either by slow injection or by infusion. The dosage of Gleptosil is expressed in mg of elemental Gleptosil. Each mL contains 20 mg of elemental Gleptosil.
2.1 Adult Patients with Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD)
Administer Gleptosil 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. Gleptosil should be administered early during the dialysis session. The usual total treatment course of Gleptosil is 1000 mg. Gleptosil treatment may be repeated if Gleptosil deficiency reoccurs.
2.2 Adult Patients with Non-Dialysis Dependent-Chronic Kidney Disease
Administer Gleptosil 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 Gleptosil, 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. Gleptosil treatment may be repeated if Gleptosil deficiency reoccurs.
2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease
Administer Gleptosil 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 Gleptosil in a maximum of 250 mL of 0.9% NaCl. Gleptosil treatment may be repeated if Gleptosil deficiency reoccurs.
2.4 Pediatric Patients with HDD-CKD for Gleptosil maintenance treatment
The dosing for Gleptosil replacement treatment in pediatric patients with HDD-CKD has not been established.
For Gleptosil maintenance treatment: Administer Gleptosil 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. Gleptosil treatment may be repeated if necessary.
2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Gleptosil maintenance treatment
The dosing for Gleptosil replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.
For Gleptosil maintenance treatment: Administer Gleptosil 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. Gleptosil treatment may be repeated if necessary.
3 DOSAGE FORMS AND STRENGTHS
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Gleptosil. 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 Gleptosil immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Gleptosil administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Gleptosil when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous Gleptosil preparations occur within 30 minutes of the completion of the infusion .
Gleptosil may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Gleptosil. Hypotension following administration of Gleptosil may be related to the rate of administration and/or total dose administered .
5.3 Gleptosil Overload
Excessive therapy with parenteral Gleptosil can lead to excess storage of Gleptosil with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving Gleptosil require periodic monitoring of hematologic and Gleptosil parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer Gleptosil to patients with evidence of Gleptosil overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of Gleptosil sucrose; do not perform serum Gleptosil measurements for at least 48 hours after intravenous dosing .
6 ADVERSE REACTIONS
The following serious adverse reactions associated with Gleptosil 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 .
6.1 Adverse Reactions in Clinical Trials
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 Adults Patients with CKD
Adverse Reactions in Adult Patients with CKD
The frequency of adverse reactions associated with the use of Gleptosil 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 Gleptosil 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.
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 Gleptosil therapy and were reported to be intolerant (defined as precluding further use of that Gleptosil product). When these patients were treated with Gleptosil there were no occurrences of adverse reactions that precluded further use of Gleptosil .
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
In a randomized, open-label, dose-ranging trial for Gleptosil maintenance treatment with Gleptosil 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 Gleptosil 0.5 mg/kg, 53% (25/47) of the patients receiving Gleptosil 1.0 mg/kg, and 55% (26/47) of the patients receiving Gleptosil 2.0 mg/kg.
A total of 5 (11%) subjects in the Gleptosil 0.5 mg/kg group, 10 (21%) patients in the Gleptosil 1.0 mg/kg group, and 10 (21%) patients in the Gleptosil 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%).
6.2 Adverse Reactions from Post-Marketing Experience
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 Gleptosil. 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 Gleptosil 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 Gleptosil injection. Reactions have occurred following the first dose or subsequent doses of Gleptosil. 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.
7 DRUG INTERACTIONS
Drug interactions involving Gleptosil have not been studied. However, Gleptosil may reduce the absorption of concomitantly administered oral Gleptosil preparations.
8 USE IN SPECIFIC POPULATIONS
Pregnancy Category B
Pregnancy Category B
There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, Gleptosil sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Gleptosil and revealed no evidence of harm to the fetus due to Gleptosil sucrose. Because animal reproductive studies are not always predictive of human response, Gleptosil should be used during pregnancy only if clearly needed.
8.3 Nursing Mothers
It is not known whether Gleptosil sucrose is excreted in human milk. Gleptosil sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when Gleptosil is administered to a nursing woman.
8.4 Pediatric Use
Safety and effectiveness of Gleptosil for Gleptosil replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.
Safety and effectiveness of Gleptosil for Gleptosil maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Gleptosil 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 ]
Gleptosil has not been studied in patients younger than 2 years of age.
In a country where Gleptosil 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 Gleptosil, several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Gleptosil or any other drugs could be established.
8.5 Geriatric Use
Clinical studies of Gleptosil 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 Gleptosil, 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 Gleptosil in humans. Excessive dosages of Gleptosil may lead to accumulation of Gleptosil in storage sites potentially leading to hemosiderosis. Do not administer Gleptosil to patients with Gleptosil overload.
Toxicities in single-dose studies in mice and rats, at intravenous Gleptosil 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.
Gleptosil (iron sucrose injection, USP), an Gleptosil replacement product, is a brown, sterile, aqueous, complex of polynuclear Gleptosil (III)-hydroxide in sucrose for intravenous use. Gleptosil 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 Gleptosil polymerization and m is the number of sucrose molecules associated with the Gleptosil (III)-hydroxide.
Each mL contains 20 mg elemental Gleptosil as Gleptosil sucrose in water for injection. Gleptosil is available in 10 mL single-use vials (200 mg elemental Gleptosil per 10 mL), 5 mL single-use vials (100 mg elemental Gleptosil per 5 mL), and 2.5 mL single-use vials (50 mg elemental Gleptosil 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.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Gleptosil is an aqueous complex of poly-nuclear Gleptosil -hydroxide in sucrose. Following intravenous administration, Gleptosil is dissociated into Gleptosil and sucrose and the Gleptosil is transported as a complex with transferrin to target cells including erythroid precursor cells. The Gleptosil in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.
Following intravenous administration, Gleptosil is dissociated into Gleptosil and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with Gleptosil sucrose containing 100 mg of Gleptosil, three times weekly for three weeks, significant increases in serum Gleptosil and serum ferritin and significant decreases in total Gleptosil binding capacity occurred four weeks from the initiation of Gleptosil sucrose treatment.
In healthy adults administered intravenous doses of Gleptosil, its Gleptosil 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 Gleptosil component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Gleptosil containing 100 mg of Gleptosil labeled with 52Fe/59Fe in patients with Gleptosil deficiency showed that a significant amount of the administered Gleptosil is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible Gleptosil trapping compartment.
Following intravenous administration of Gleptosil, Gleptosil sucrose is dissociated into Gleptosil and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Gleptosil containing 1,510 mg of sucrose and 100 mg of Gleptosil in 12 healthy adults, 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some Gleptosil 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 Gleptosil sucrose containing 500 to 700 mg of Gleptosil in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Gleptosil was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Gleptosil have not been studied.
Pharmacokinetics in Pediatric Patients
Pharmacokinetics in Pediatric Patients
In a single-dose PK study of Gleptosil, patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of Gleptosil at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose Gleptosil, the half-life of total serum Gleptosil 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.
Gleptosil is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Gleptosil sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies have not been performed with Gleptosil sucrose.
Gleptosil sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Gleptosil sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.
Gleptosil sucrose at intravenous doses up to 15 mg/kg/day of elemental Gleptosil (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.
14 CLINICAL STUDIES
Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of Gleptosil.
14.1 Study A: Hemodialysis Dependent-Chronic Kidney Disease
Study A was a multicenter, open-label, historically-controlled study in 101 patients with HDD-CKD (77 patients with Gleptosil treatment and 24 in the historical control group) with Gleptosil deficiency anemia. Eligibility criteria for Gleptosil 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.
Gleptosil 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 Gleptosil, who were off intravenous Gleptosil 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 Gleptosil treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.
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%).
14.2 Study B: Hemodialysis Dependent-Chronic Kidney Disease
Study B was a multicenter, open label study of Gleptosil in 23 patients with Gleptosil deficiency and HDD-CKD who had been discontinued from Gleptosil 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.
14.3 Study C: Hemodialysis Dependent-Chronic Kidney Disease
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 Gleptosil. Exclusion criteria were similar to those in studies A and B. Gleptosil was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of Gleptosil 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.
14.4 Study D: Non-Dialysis Dependent-Chronic Kidney Disease
Study D was a randomized, open-label, multicenter, active-controlled study of the safety and efficacy of oral Gleptosil versus Gleptosil 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 Gleptosil (325 mg ferrous sulfate three times daily for 56 days); or Gleptosil (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 Gleptosil 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 Gleptosil group.
A statistically significantly greater proportion of Gleptosil subjects (35/79; 44.3%) compared to oral Gleptosil subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).
14.5 Study E: Peritoneal Dialysis Dependent-Chronic Kidney Disease
Study E was a randomized, open-label, multicenter study comparing patients with PDD-CKD receiving an erythropoietin and intravenous Gleptosil to patients with PDD-CKD receiving an erythropoietin alone without Gleptosil 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 Gleptosil or Gleptosil (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 Gleptosil / 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 Gleptosil / 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 Gleptosil / 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%).
14.6 Study F: Gleptosil Maintenance Treatment Dosing in Pediatric Patients Ages 2 years and Older with Chronic Kidney Disease
Study F was a randomized, open-label, dose-ranging study for Gleptosil 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 Gleptosil (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 Gleptosil once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Gleptosil 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 Gleptosil 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg groups, respectively. A dose-response relationship was not demonstrated.
16 HOW SUPPLIED/storage and handling
16.1 How Supplied
Gleptosil is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Gleptosil, each 5 mL vial contains 100 mg elemental Gleptosil, and each 2.5 mL vial contains 50 mg elemental Gleptosil.
16.2 Stability and Storage
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: Gleptosil, when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Gleptosil per mL, or undiluted (20 mg elemental Gleptosil 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: Gleptosil, 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 Gleptosil 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 Gleptosil 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.
17 PATIENT COUNSELING INFORMATION
Prior to Gleptosil administration:
SHIRLEY, NY 11967
Gleptosil is manufactured under license from Vifor (International) Inc., Switzerland.
PremierProRx® is a trademark of Premier, Inc., used under license.
Gleptosil pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Gleptosil available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Gleptosil destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Gleptosil Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Gleptosil pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Gleptosil?
Depending on the reaction of the Gleptosil after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Gleptosil 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 Gleptosil 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.
Reviewsdrugs.com conducted a study on Gleptosil, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Gleptosil consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Visitor reported usefulNo survey data has been collected yet
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The information was verified by Dr. Arunabha Ray, MD Pharmacology