Astyfer Liquid

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Astyfer Liquid uses

Astyfer Liquid consists of Folic Acid, Iron (Ferrous Glycine Sulfate), L-Histidine, L-Lysine, Vitamin B1, Vitamin B12, Vitamin B2, Vitamin B3 (Nicotinamide), Vitamin B5 (D-Panthenol), Vitamin B6, Vitamin C.

Folic Acid:


INDICATIONS AND USAGE

Astyfer Liquid (Folic Acid)® is a prescription iron supplement indicated for use in improving the nutritional status of iron deficiency.

CONTRAINDICATIONS

This product is contraindicated in patients with a known hypersensitivity to any of the ingredients. Hemochromatosis and hemosiderosis are contraindications to iron therapy.

WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately.

PRECAUTIONS

Astyfer Liquid (Folic Acid) acid when administered as a single agent in doses above 0.1 mg daily may obscure pernicious anemia in that hematological remission can occur while neurological manifestations remain progressive. While prescribing this nutritional supplement for pregnant women, nursing mothers, or for women prior to conception, their medical condition and other drugs, herbs, and/or supplements consumption should be considered.

ADVERSE REACTIONS

Allergic sensitization has been reported following both oral and parenteral administration of Astyfer Liquid (Folic Acid) acid.

DOSAGE AND ADMINISTRATION

One tablet daily with or without food or as prescribed by a licensed healthcare provider with prescribing authority.

HOW SUPPLIED

Astyfer Liquid (Folic Acid)® tablets are supplied in child-resistant bottles of 90 tablets (NDC 0037-6885-90)

KEEP OUT OF REACH OF CHILDREN.

STORAGE

Store at controlled room temperature 20°-25°C (68°-77°F). Excursions permitted to 15°-30°C (59°-86°F).

Dispense in a tight, light-resistant container to protect from light and moisture.

To report SUSPECTED ADVERSE REACTIONS contact Meda Pharmaceuticals Inc. at 1-888-349-5556 or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch

Distributed by:

Meda Pharmaceuticals Inc.

Somerset New Jersey 08873-4120

© 2014 Meda Pharmaceuticals Inc.

U.S. Patent Nos. 7,585,527 and 8,080,520

Proferrin® is a registered trademark of Colorado BioLabs, Inc., Cozad, NE.

Astyfer Liquid (Folic Acid) and the BIFERA logo are registered trademarks and the Astyfer Liquid (Folic Acid) logo is a trademark of Alaven Pharmaceutical LLC, used under license by Meda Pharmaceuticals Inc.

MEDA PHARMACEUTICALS mark and logo are trademarks of Meda AB.

IN-6885-02 Rev 6/2014

Iron (Ferrous Glycine Sulfate):


1 INDICATIONS AND USAGE

Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is indicated for the treatment of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) deficiency anemia in patients with chronic kidney disease (CKD).

Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is an Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) replacement product indicated for the treatment of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) deficiency anemia in patients with chronic kidney disease (CKD). (1)

2 DOSAGE AND ADMINISTRATION

Astyfer Liquid ) must only be administered intravenously either by slow injection or by infusion. The dosage of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is expressed in mg of elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)). Each mL contains 20 mg of elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)).

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

2.1 Adult Patients with Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD)

Administer Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) should be administered early during the dialysis session. The usual total treatment course of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is 1000 mg. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) treatment may be repeated if Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) deficiency reoccurs.

2.2 Adult Patients with Non-Dialysis Dependent-Chronic Kidney Disease

Administer Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), 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. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) treatment may be repeated if Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

Administer Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) in a maximum of 250 mL of 0.9% NaCl. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) treatment may be repeated if Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) deficiency reoccurs.

2.4 Pediatric Patients with HDD-CKD for Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) maintenance treatment

The dosing for Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) replacement treatment in pediatric patients with HDD-CKD has not been established.

For Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) maintenance treatment: Administer Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) treatment may be repeated if necessary.

2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) maintenance treatment

The dosing for Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

For Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) maintenance treatment: Administer Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) treatment may be repeated if necessary.

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3 DOSAGE FORMS AND STRENGTHS

  • 10 mL single-use vial / 200 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (20 mg/mL)
  • 5 mL single-use vial / 100 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (20 mg/mL)
  • 2.5 mL single-use vial / 50 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (20 mg/mL)
  • 10 mL single-use vial / 200 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (20 mg/mL) (3)
  • 5 mL single-use vial / 100 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (20 mg/mL) (3)
  • 2.5 mL single-use vial / 50 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (20 mg/mL) (3)

4 CONTRAINDICATIONS

  • Known hypersensitivity to Astyfer Liquid (Iron (Ferrous Glycine Sulfate))
  • Known hypersensitivity to Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (4)

5 WARNINGS AND PRECAUTIONS

  • Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after Astyfer Liquid ) administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. (5.1)
  • Hypotension: Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) may cause hypotension. Monitor for signs and symptoms of hypotension during and following each administration of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)). (5.2)
  • Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) Overload: Regularly monitor hematologic responses during Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) therapy. Do not administer Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) to patients with Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) overload. (5.3)

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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)). 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) preparations occur within 30 minutes of the completion of the infusion .

5.2 Hypotension

Astyfer Liquid ) may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)). Hypotension following administration of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) may be related to the rate of administration and/or total dose administered .

5.3 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) Overload

Excessive therapy with parenteral Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) can lead to excess storage of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) require periodic monitoring of hematologic and Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) to patients with evidence of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose; do not perform serum Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) measurements for at least 48 hours after intravenous dosing .

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6 ADVERSE REACTIONS

The following serious adverse reactions associated with Astyfer Liquid ) are described in other sections .

  • The most common adverse reactions (≥2%) following the administration of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema. (6.1)

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 Astyfer Liquid ) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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
Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) Oral Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) therapy and were reported to be intolerant (defined as precluding further use of that Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) product). When these patients were treated with Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) there were no occurrences of adverse reactions that precluded further use of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) .

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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) maintenance treatment with Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 0.5 mg/kg, 53% (25/47) of the patients receiving Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 1.0 mg/kg, and 55% (26/47) of the patients receiving Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 2.0 mg/kg.

A total of 5 (11%) subjects in the Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 0.5 mg/kg group, 10 (21%) patients in the Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 1.0 mg/kg group, and 10 (21%) patients in the Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)). 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) injection. Reactions have occurred following the first dose or subsequent doses of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)). 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.

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7 DRUG INTERACTIONS

Drug interactions involving Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) have not been studied. However, Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) may reduce the absorption of concomitantly administered oral Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) preparations.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, Astyfer Liquid ) sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose. Because animal reproductive studies are not always predictive of human response, Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

It is not known whether Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose is excreted in human milk. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Astyfer Liquid ) for Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

Safety and effectiveness of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) for Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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)]

Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) has not been studied in patients younger than 2 years of age.

In a country where Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) or any other drugs could be established.

8.5 Geriatric Use

Clinical studies of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), 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.

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10 OVERDOSAGE

No data are available regarding overdosage of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) in humans. Excessive dosages of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) may lead to accumulation of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) in storage sites potentially leading to hemosiderosis. Do not administer Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) to patients with Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) overload.

Toxicities in single-dose studies in mice and rats, at intravenous Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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.

11 DESCRIPTION

Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (iron sucrose injection, USP), an Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) replacement product, is a brown, sterile, aqueous, complex of polynuclear Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (III)-hydroxide in sucrose for intravenous use. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) polymerization and m is the number of sucrose molecules associated with the Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (III)-hydroxide.

Each mL contains 20 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) as Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose in water for injection. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is available in 10 mL single-use vials (200 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) per 10 mL), 5 mL single-use vials (100 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) per 5 mL), and 2.5 mL single-use vials (50 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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

Astyfer Liquid ) is an aqueous complex of poly-nuclear Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (III)-hydroxide in sucrose. Following intravenous administration, Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is dissociated into Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) and sucrose and the Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is transported as a complex with transferrin to target cells including erythroid precursor cells. The Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.

12.2 Pharmacodynamics

Following intravenous administration, Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is dissociated into Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose containing 100 mg of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), three times weekly for three weeks, significant increases in serum Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) and serum ferritin and significant decreases in total Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) binding capacity occurred four weeks from the initiation of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose treatment.

12.3 Pharmacokinetics

In healthy adults administered intravenous doses of Astyfer Liquid ), its Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) containing 100 mg of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) labeled with 52Fe/59Fe in patients with Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) deficiency showed that a significant amount of the administered Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) trapping compartment.

Following intravenous administration of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose is dissociated into Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) containing 1,510 mg of sucrose and 100 mg of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose containing 500 to 700 mg of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) have not been studied.

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

In a single-dose PK study of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), the half-life of total serum Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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.

Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose.

Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.

Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (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 Astyfer Liquid ).

14.1 Study A: Hemodialysis Dependent-Chronic Kidney Disease (HDD–CKD)

Study A was a multicenter, open-label, historically-controlled study in 101 patients with HDD-CKD (77 patients with Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) treatment and 24 in the historical control group) with Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) deficiency anemia. Eligibility criteria for Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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.

Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), who were off intravenous Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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
Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (n=69 Historical Control (n=18) Astyfer Liquid (Iron (Ferrous Glycine Sulfate))

(n=73)

Historical Control

(n=18)

Astyfer Liquid (Iron (Ferrous Glycine Sulfate))

(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%).

14.2 Study B: Hemodialysis Dependent-Chronic Kidney Disease

Study B was a multicenter, open label study of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) in 23 patients with Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) deficiency and HDD-CKD who had been discontinued from Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)). Exclusion criteria were similar to those in studies A and B. Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) versus Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (325 mg ferrous sulfate three times daily for 56 days); or Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) group.

A statistically significantly greater proportion of Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) subjects (35/79; 44.3%) compared to oral Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) to patients with PDD-CKD receiving an erythropoietin alone without Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) or Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) / 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) / 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) / 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: Astyfer Liquid ) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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

Astyfer Liquid ) is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), each 5 mL vial contains 100 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), and each 2.5 mL vial contains 50 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) (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

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: Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) per mL, or undiluted (20 mg elemental Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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: Astyfer Liquid (Iron (Ferrous Glycine Sulfate)), 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) 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 Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) administration:

  • Question patients regarding any prior history of reactions to parenteral Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) products
  • Advise patients of the risks associated with Astyfer Liquid (Iron (Ferrous Glycine Sulfate))
  • Advise patients to report any symptoms of hypersensitivity that may develop during and following Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems [see Warnings and Precautions (5)]

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Astyfer Liquid (Iron (Ferrous Glycine Sulfate)) is manufactured under license from Vifor (International) Inc., Switzerland.

PremierProRx® is a trademark of Premier, Inc., used under license.

PREMIERProRx®

IN2340

MG #15727

L-Histidine:


An essential amino acid that is required for the production of histamine.

Indication: The actions of supplemental Astyfer Liquid (L-Histidine) are entirely unclear. It may have some immunomodulatory as well as antioxidant activity. Astyfer Liquid (L-Histidine) may be indicated for use in some with rheumatoid arthritis. It is not indicated for treatment of anemia or uremia or for lowering serum cholesterol.

Is found abundantly in hemoglobin; has been used in the treatment of rheumatoid arthritis, allergic diseases, ulcers and anemia. A deficiency can cause poor hearing.

L-Lysine:


Astyfer Liquid (L-Lysine) (abbreviated as Lys or K) is an О±-amino acid with the chemical formula HO2CCH(CH2)4NH2. This amino acid is an essential amino acid, which means that humans cannot synthesize it. Its codons are AAA and AAG.L-Lysine is a base, as are arginine and histidine. The Оµ-amino group often participates in hydrogen bonding and as a general base in catalysis. Common posttranslational modifications include methylation of the Оµ-amino group, giving methyl-, dimethyl-, and trimethyllysine. The latter occurs in calmodulin. Other posttranslational modifications include acetylation. Collagen contains hydroxylysine which is derived from lysine by lysyl hydroxylase. O-Glycosylation of lysine residues in the endoplasmic reticulum or Golgi apparatus is used to mark certain proteins for secretion from the cell.

Indication: Supplemental Astyfer Liquid (L-Lysine) has putative anti-herpes simplex virus activity. There is preliminary research suggesting that it may have some anti-osteoporotic activity.

Insures the adequate absorption of calcium; helps form collagen ( which makes up bone cartilage & connective tissues); aids in the production of antibodies, hormones & enzymes. Recent studies have shown that Lysine may be effective against herpes by improving the balance of nutrients that reduce viral growth. A deficiency may result in tiredness, inability to concentrate, irritability, bloodshot eyes, retarded growth, hair loss, anemia & reproductive problems.

Vitamin B12:


Pharmacological action

Astyfer Liquid refers to a group of water-soluble vitamins. It has high biological activity. Astyfer Liquid (Vitamin B12) is necessary for normal hematopoiesis (promotes maturation of erythrocytes). Involved in the processes of transmethylation, hydrogen transport, synthesis of methionine, nucleic acids, choline, creatine. Contributes to the accumulation in erythrocytes of compounds containing sulfhydryl groups. Has a beneficial effect on liver function and the nervous system. Activates the coagulation of blood in high doses causes an increase in the activity of thromboplastin and prothrombin.

Pharmacokinetics

After oral administration Astyfer Liquid (Vitamin B12) absorbed from the gastrointestinal tract. Metabolized in the tissues, becoming a co-enzyme form - adenosylcobalamin which is the active form of cyanocobalamin. Excreted in bile and urine.

Why is Astyfer Liquid prescribed?

Anemia due to B12-deficiency conditions; in the complex therapy for iron and posthemorrhagic anemia; aplastic anemia caused by toxic substances and drugs; liver disease (hepatitis, cirrhosis); funicular myelosis; polyneuritis, radiculitis, neuralgia, amyotrophic lateral sclerosis; children cerebral palsy, Down syndrome, peripheral nerve injury; skin diseases (psoriasis, photodermatosis, herpetiformis dermatitis, neurodermatitis); to prevent and treat symptoms of deficiency of Astyfer Liquid (Vitamin B12) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.

Dosage and administration

Astyfer Liquid is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Astyfer Liquid (Vitamin B12) deficiency is introduced on 100-200 mcg in 2 days. In anemia with symptoms of funicular myelosis and megalocytic anemia with diseases of the nervous system - 400-500 micrograms in the first 7 days daily, then 1 time every 5-7 days. In the period of remission in the absence of events funicular myelosis maintenance dose - 100 mcg 2 times a month, in the presence of neurological symptoms - at 200-400 mcg 2-4 times a month. In acute post-hemorrhagic anemia and iron anemia by 30-100 mcg 2-3 times a week. When aplastic anemia (especially in children) - 100 micrograms before clinical improvement. When nutritional anemia in infants and preterm - 30 mcg / day during 15 days.

In diseases of the central and peripheral nervous system and neurological diseases with a pain syndrome is administered in increasing doses - 200-500 mcg, with the improvement in the state - 100 mcg / day. The course of treatment with Astyfer Liquid (Vitamin B12) is 2 weeks. In traumatic lesions of peripheral nervous system - at 200-400 mcg every other day for 40-45 days.

When hepatitis and cirrhosis - 30-60 mcg / day or 100 mg every other day for 25-40 days.

Dystrophy in young children, Down syndrome and cerebral palsy - by 15-30 mcg every other day.

When funicular myelosis, amyotrophic lateral sclerosis can be introduced into the spinal canal at 15-30 mcg, gradually increasing the dose of 200-250 micrograms.

In radiation sickness, diabetic neuropathy, sprue - by 60-100 mcg daily for 20-30 days.

When deficiency of Astyfer Liquid (Vitamin B12) to prevent - IV or IM for 1 mg 1 time a month; for treatment - IV or IM for 1 mg daily for 1-2 weeks, the maintenance dose is 1-2 mg IV or IM from 1 per week, up to 1 per month. Duration of treatment is determined individually.

Astyfer Liquid (Vitamin B12) side effects, adverse reactions

CNS: rarely - a state of arousal.

Cardiovascular system: rarely - pain in the heart, tachycardia.

Allergic reactions: rarely - urticaria.

Astyfer Liquid contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Astyfer Liquid using during pregnancy and breastfeeding

Cyanocobalamin can be used in pregnancy according to prescriptions.

Special instructions

When stenocardia should be used with caution in a single dose of Astyfer Liquid 100 mcg. During treatment should regularly monitor the blood picture and coagulation. It is unacceptable to enter in the same syringe with cyanocobalamin solutions of thiamine and pyridoxine.

Astyfer Liquid (Vitamin B12) drug interactions

In an application of Astyfer Liquid (Vitamin B12) with hormonal contraceptives for oral administration may decrease the concentration of cyanocobalamin in plasma.

In an application with anticonvulsant drugs decreased cyanocobalamin absorption from the gut.

In an Astyfer Liquid (Vitamin B12) application with neomycin, aminosalicylic acid, colchicine, cimetidine, ranitidine, drugs potassium decreased cyanocobalamin absorption from the gut.

Cyanocobalamin may exacerbate allergic reactions caused by thiamine.

When parenteral application of chloramphenicol may decrease the hematopoietic effects of cyanocobalamin with anemia.

Pharmaceutical incompatibility

Contained in the molecule of cyanocobalamin cobalt ion contributes to the destruction of ascorbic acid, thiamine bromide, riboflavin in one solution.

Vitamin C:


Pharmacological action

Ascorbic acid is essential for the formation of intracellular collagen, is required to strengthen the structure of teeth, bones, and the capillary walls. Astyfer Liquid (Vitamin C) participates in redox reactions, the metabolism of tyrosine, converting folic acid into folinic acid, metabolism of carbohydrates, the synthesis of lipids and proteins, iron metabolism, processes of cellular respiration. Reduces the need for vitamins B1, B2, A, E, folic acid, pantothenic acid, enhances the body's resistance to infections; enhances iron absorption, contributing to its sequestration in reduced form. Astyfer Liquid (Vitamin C) has antioxidant properties.

With intravaginal application of ascorbic acid lowers the vaginal pH, inhibiting the growth of bacteria and helps to restore and maintain normal pH and vaginal flora (Lactobacillus acidophilus, Lactobacillus gasseri).

Pharmacokinetics

After oral administration ascorbic acid is completely absorbed from the gastrointestinal tract. Widely distributed in body tissues.

The concentration of ascorbic acid in blood plasma in normal amounts to approximately 10-20 mg / ml.

The concentration of ascorbic acid in white blood cells and platelets is higher than in erythrocytes and plasma. When deficient state of concentration in leucocytes is reduced later and more slowly and is regarded as the best criterion for evaluating the deficit than the concentration in plasma.

Plasma protein binding is about 25%.

Ascorbic acid is reversibly oxidized to form dehydroascorbic acid, is metabolized with the formation of ascorbate-2-sulphate which is inactive and oxalic acid which is excreted in the urine.

Ascorbic acid taken in excessive quantities is rapidly excreted unchanged in urine, it usually happens when exceeding a daily dose is 200 mg.

Why is Astyfer Liquid prescribed?

For systemic use of Astyfer Liquid (Vitamin C) Kimia Farma: prevention and treatment of hypo- and avitaminosis of Astyfer Liquid (Vitamin C); providing increased need for Astyfer Liquid (Vitamin C) during growth, pregnancy, lactation, with heavy loads, fatigue and during recovery after prolonged severe illness; in winter with an increased risk of infectious diseases.

For intravaginal use: chronic or recurrent vaginitis (bacterial vaginosis, nonspecific vaginitis) caused by the anaerobic flora (due to changes in pH of the vagina) in order to normalize disturbed vaginal microflora.

Dosage and administration

This medication administered orally, IM, IV, intravaginally.

For the prevention of deficiency conditions Astyfer Liquid dose is 25-75 mg / day, for the treatment - 250 mg / day or more in divided doses.

For intravaginal used ascorbic acid drugs in appropriate dosage forms.

Astyfer Liquid (Vitamin C) side effects, adverse reactions

CNS: headache, fatigue, insomnia.

Digestive system: stomach cramps, nausea and vomiting.

Allergic reaction: describes a few cases of skin reactions and manifestations of the respiratory system.

Urinary system: when used in high doses - hyperoxaluria and the formation of kidney stones of calcium oxalate.

Local reactions: with intravaginal application - a burning or itching in the vagina, increased mucous discharge, redness, swelling of the vulva. Other: sensation of heat.

Astyfer Liquid contraindications

Increased sensitivity to ascorbic acid.

Using during pregnancy and breastfeeding

The minimum daily requirement of ascorbic acid in the II and III trimester of pregnancy is about 60 mg.

Ascorbic acid crosses the placental barrier. It should be borne in mind that the fetus can adapt to high doses of ascorbic acid, which takes a pregnant woman, and then a newborn baby may develop the ascorbic disease as the reaction of cancel. Therefore, during pregnancy should not to take ascorbic acid in high doses, except in cases where the expected benefit outweighs the potential risk.

The minimum daily requirement during lactation is 80 mg. Ascorbic acid is excreted in breast milk. A mother's diet that contains adequate amounts of ascorbic acid, is sufficient to prevent deficiency in an infant. It is unknown whether dangerous to the child's mother use of ascorbic acid in high doses. Theoretically it is possible. Therefore, it is recommended not to exceed the maximum daily nursing mother needs to ascorbic acid, except when the expected benefit outweighs the potential risk.

Special instructions

Astyfer Liquid (Vitamin C) is used with caution in patients with hyperoxaluria, renal impairment, a history of instructions on urolithiasis. Because ascorbic acid increases iron absorption, its use in high doses can be dangerous in patients with hemochromatosis, thalassemia, polycythemia, leukemia, and sideroblastic anemia.

Patients with high content body iron should apply ascorbic acid in minimal doses.

Astyfer Liquid (Vitamin C) is used with caution in patients with deficiency of glucose-6-phosphate dehydrogenase.

The use of ascorbic acid in high doses can cause exacerbation of sickle cell anemia.

Data on the diabetogenic action of ascorbic acid are contradictory. However, prolonged use of ascorbic acid should periodically monitor your blood glucose levels.

It is believed that the use of ascorbic acid in patients with rapidly proliferating and widely disseminated tumors may worsen during the process. It should therefore be used with caution in ascorbic acid in patients with advanced cancer.

Absorption of ascorbic acid decreased while use of fresh fruit or vegetable juices, alkaline drinking.

Astyfer Liquid drug interactions

In an application with barbiturates, primidone increases the excretion of ascorbic acid in the urine.

With the simultaneous use of oral contraceptives reduces the concentration of ascorbic acid in blood plasma.

In an application of Astyfer Liquid (Vitamin C) with iron preparations ascorbic acid, due to its regenerative properties, transforms ferric iron in the bivalent, which improves its absorption.

Ascorbic acid in high doses can decrease urine pH that while the application reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.

With the simultaneous use of aspirin reduces the absorption of ascorbic acid by about a third.

Astyfer Liquid (Vitamin C) in an application with warfarin may decrease effects of warfarin.

With the simultaneous application of ascorbic acid increases the excretion of iron in patients receiving deferoxamine. In the application of ascorbic acid at a dose of 500 mg / day possibly left ventricular dysfunction.

In an application with tetracycline is increased excretion of ascorbic acid in the urine.

There is a described case of reducing the concentration of fluphenazine in plasma in patients treated with ascorbic acid 500 mg 2 times / day.

May increase the concentration of ethinyl estradiol in the blood plasma in its simultaneous application in the oral contraceptives.

Astyfer Liquid in case of emergency / overdose

Symptoms: long-term use of large doses (more than 1 g) - headache, increased CNS excitability, insomnia, nausea, vomiting, diarrhea, gastritis giperatsidnyh, ultseratsiya gastrointestinal mucosa, inhibition of the function insular apparatus of the pancreas (hyperglycemia, glycosuria), hyperoxaluria, nephrolithiasis (calcium oxalate), damage to the glomerular apparatus of the kidneys, moderate thamuria (when receiving a dose of 600 mg / day).

Decrease capillary permeability (possibly deteriorating trophic tissues, increased blood pressure, hypercoagulability, the development of microangiopathy).

When IV administration in high doses - the threat of termination of pregnancy (due to estrogenemia), hemolysis of red blood cells.

Astyfer Liquid 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.


Astyfer Liquid 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.


Astyfer Liquid 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.


Astyfer Liquid 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.


Astyfer Liquid 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.


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References

  1. Dailymed."FOLIC ACID INJECTION, SOLUTION [FRESENIUS KABI USA, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."ASCORBIC ACID; BIOTIN; CYANOCOBALAMIN; DEXPANTHENOL; ERGOCALCIFEROL; FOLIC ACID; NIACINAMIDE; PHYTONADIONE; PYRIDOXINE HYDROCHLORIDE; RIBOFLAVIN 5'-PHOSPHATE SODIUM; THIAMINE HYDROCHLORIDE; VITAMIN A; VITAMIN E: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "L-histidine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Astyfer Liquid?

Depending on the reaction of the Astyfer Liquid after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Astyfer Liquid 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 Astyfer Liquid 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.

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Review

sdrugs.com conducted a study on Astyfer Liquid, 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 Astyfer Liquid 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 reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

Two visitors reported price estimates

What is your opinion about drug cost? Did you feel the cost is apt, or did you feel it is expensive?
The report given by the sdrugs.com website users shows the following figures about several people who felt the medicine Astyfer Liquid is expensive, and the medicine is not expensive. The results are mixed. The perception of the cost of the medicine to be expensive or not depends on the brand name of the medicine, country, and place where it is sold, and the affordability of the patient. You can choose a generic drug in the place of the branded drug to save the cost. The efficiency of the medicine will not vary if it is generic or a branded one.
Visitors%
Not expensive1
50.0%
Expensive1
50.0%

Three visitors reported frequency of use

How often in a day do you take the medicine?
Are you taking the Astyfer Liquid drug as prescribed by the doctor?

Few medications can be taken 3 times in a day more than prescribed when the doctor's advice mentions the medicine can be taken according to frequency or severity of symptoms. Most times, be very careful and clear about the number of times you are taking the medication. The report of sdrugs.com website users about the frequency of taking the drug Astyfer Liquid is mentioned below.
Visitors%
3 times in a day2
66.7%
Twice in a day1
33.3%

Three visitors reported doses

What is the dose of Astyfer Liquid drug you are taking?
According to the survey conducted among sdrugs.com website users, the maximum number of people are using the following dose 1-5mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
Visitors%
1-5mg1
33.3%
6-10mg1
33.3%
201-500mg1
33.3%

Four visitors reported time for results

What is the time duration Astyfer Liquid drug must be taken for it to be effective or for it to reduce the symptoms?
Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sdrugs.com website users needed 1 day to notice the result from using Astyfer Liquid drug. The time needed to show improvement in health condition after using the medicine Astyfer Liquid need not be same for all the users. It varies based on other factors.
Visitors%
1 day2
50.0%
1 month2
50.0%

Two visitors reported administration

The drugs are administered in various routes, like oral or injection form. They are administered before food or after food. How are you taking Astyfer Liquid drug, before food or after food?
Click here to find out how other users of our website are taking it. For any doubts or queries on how and when the medicine is administered, contact your health care provider immediately.
Visitors%
Empty stomach1
50.0%
After food1
50.0%

33 visitors reported age

Visitors%
1-510
30.3%
30-459
27.3%
16-297
21.2%
6-154
12.1%
< 12
6.1%
46-601
3.0%

Visitor reviews


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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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