HB-Orange Suspension

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HB-Orange Suspension uses

HB-Orange Suspension consists of Copper, Folic Acid, Iron (Ferric Ammonium Citrate), L-Lysine, Magnesium, Vitamin B12 (Cyanocobalamin), Zinc.

Copper:



Water-Resistant Protection Without Bandaging

Recommended as an Aid in Treating Horses and Ponies With Thrush Due to Organisms Susceptible to HB-Orange Suspension (Copper) Naphthenate.

For Animal Use Only.

INDICATIONS:

ThrushTox® is indicated in the treatment of thrush in horses and ponies.

GENERAL DIRECTIONS:

Clean the hoof thoroughly, removing debris and necrotic material prior to application of HB-Orange Suspension (Copper)®. Apply daily to affected hoofs with a narrow paint brush (about 1”) until fully healed. Caution: Do not allow runoff of excess HB-Orange Suspension (Copper)® onto hair since contact with HB-Orange Suspension (Copper)® may cause some hair loss. Do not contaminate feed.

NOTE: HB-Orange Suspension (Copper)® is easily removed from hands, clothing and surfaces with light grade fuel oil or any type of lighter fluid.

CONTAINS FOIL SEAL – REMOVE BEFORE USE.

SHAKE WELL BEFORE USE.

To report suspected adverse reactions or to obtain technical assistance, call 1-800-650-4899.

ACTIVE INGREDIENT:

HB-Orange Suspension (Copper) Naphthenate...37.5% w/w

INACTIVE INGREDIENTS:

Inert Ingredients...62.5% w/w

Total... 100.0%

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CAUTION:

Do not use in horses intended for human consumption.

CAUTION: COMBUSTIBLE MIXTURE.

Use in a well-ventilated place. Avoid fire, flame, sparks or heaters.

If swallowed, do not induce vomiting, call physician immediately. Avoid breathing vapor. Avoid contact with skin and eyes.

KEEP OUT OF REACH OF CHILDREN AND PETS.

STORAGE:

Store at controlled room temperature 15º to 30ºC (59º to 86ºF). Keep container tightly closed when not in use.

Manufactured for:

Aspen Veterinary Resources,® Ltd.

Liberty, MO 64068, USA

FC163FP 11/13

Manufactured by:

First Priority, Inc.

Elgin, IL 60123-1146, USA

NET CONTENTS:

16 OZ (473 mL)

ANADA 200-304, Approved by FDA

Image of 473 mL bottle/case label

Folic Acid:


INDICATIONS AND USAGE

HB-Orange Suspension (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

HB-Orange Suspension (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 HB-Orange Suspension (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

HB-Orange Suspension (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.

HB-Orange Suspension (Folic Acid) and the BIFERA logo are registered trademarks and the HB-Orange Suspension (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 (Ferric Ammonium Citrate):


1 INDICATIONS AND USAGE

HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) is indicated for the treatment of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) deficiency anemia in patients with chronic kidney disease (CKD).

HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) is an HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) replacement product indicated for the treatment of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) deficiency anemia in patients with chronic kidney disease (CKD). (1)

2 DOSAGE AND ADMINISTRATION

HB-Orange Suspension ) must only be administered intravenously either by slow injection or by infusion. The dosage of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) is expressed in mg of elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)). Each mL contains 20 mg of elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)).

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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) should be administered early during the dialysis session. The usual total treatment course of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) is 1000 mg. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) treatment may be repeated if HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) deficiency reoccurs.

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

Administer HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)), 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. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) treatment may be repeated if HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

Administer HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) in a maximum of 250 mL of 0.9% NaCl. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) treatment may be repeated if HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) deficiency reoccurs.

2.4 Pediatric Patients with HDD-CKD for HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) maintenance treatment

The dosing for HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) replacement treatment in pediatric patients with HDD-CKD has not been established.

For HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) maintenance treatment: Administer HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) treatment may be repeated if necessary.

2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) maintenance treatment

The dosing for HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

For HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) maintenance treatment: Administer HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) treatment may be repeated if necessary.

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3 DOSAGE FORMS AND STRENGTHS

  • 10 mL single-use vial / 200 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (20 mg/mL)
  • 5 mL single-use vial / 100 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (20 mg/mL)
  • 2.5 mL single-use vial / 50 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (20 mg/mL)
  • 10 mL single-use vial / 200 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (20 mg/mL) (3)
  • 5 mL single-use vial / 100 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (20 mg/mL) (3)
  • 2.5 mL single-use vial / 50 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (20 mg/mL) (3)

4 CONTRAINDICATIONS

  • Known hypersensitivity to HB-Orange Suspension (Iron (Ferric Ammonium Citrate))
  • Known hypersensitivity to HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (4)

5 WARNINGS AND PRECAUTIONS

  • Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after HB-Orange Suspension ) administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. (5.1)
  • Hypotension: HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) may cause hypotension. Monitor for signs and symptoms of hypotension during and following each administration of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)). (5.2)
  • HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) Overload: Regularly monitor hematologic responses during HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) therapy. Do not administer HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) to patients with HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)). 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) preparations occur within 30 minutes of the completion of the infusion .

5.2 Hypotension

HB-Orange Suspension ) may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)). Hypotension following administration of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) may be related to the rate of administration and/or total dose administered .

5.3 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) Overload

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

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6 ADVERSE REACTIONS

The following serious adverse reactions associated with HB-Orange Suspension ) are described in other sections .

  • The most common adverse reactions (≥2%) following the administration of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension ) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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
HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) Oral HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) therapy and were reported to be intolerant (defined as precluding further use of that HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) product). When these patients were treated with HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) there were no occurrences of adverse reactions that precluded further use of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) .

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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) maintenance treatment with HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 0.5 mg/kg, 53% (25/47) of the patients receiving HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 1.0 mg/kg, and 55% (26/47) of the patients receiving HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 2.0 mg/kg.

A total of 5 (11%) subjects in the HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 0.5 mg/kg group, 10 (21%) patients in the HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 1.0 mg/kg group, and 10 (21%) patients in the HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)). 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) injection. Reactions have occurred following the first dose or subsequent doses of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)). 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) have not been studied. However, HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) may reduce the absorption of concomitantly administered oral HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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, HB-Orange Suspension ) sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) sucrose. Because animal reproductive studies are not always predictive of human response, HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

It is not known whether HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) sucrose is excreted in human milk. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of HB-Orange Suspension ) for HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

Safety and effectiveness of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) for HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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)]

HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) has not been studied in patients younger than 2 years of age.

In a country where HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) or any other drugs could be established.

8.5 Geriatric Use

Clinical studies of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)), 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.

10 OVERDOSAGE

No data are available regarding overdosage of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) in humans. Excessive dosages of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) may lead to accumulation of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) in storage sites potentially leading to hemosiderosis. Do not administer HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) to patients with HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) overload.

Toxicities in single-dose studies in mice and rats, at intravenous HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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

HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (iron sucrose injection, USP), an HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) replacement product, is a brown, sterile, aqueous, complex of polynuclear HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (III)-hydroxide in sucrose for intravenous use. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) polymerization and m is the number of sucrose molecules associated with the HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (III)-hydroxide.

Each mL contains 20 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) as HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) sucrose in water for injection. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) is available in 10 mL single-use vials (200 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) per 10 mL), 5 mL single-use vials (100 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) per 5 mL), and 2.5 mL single-use vials (50 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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

HB-Orange Suspension ) is an aqueous complex of poly-nuclear HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (III)-hydroxide in sucrose. Following intravenous administration, HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) is dissociated into HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) and sucrose and the HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) is transported as a complex with transferrin to target cells including erythroid precursor cells. The HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

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

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

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

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

HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) sucrose.

HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.

HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (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 HB-Orange Suspension ).

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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) treatment and 24 in the historical control group) with HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) deficiency anemia. Eligibility criteria for HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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.

HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)), who were off intravenous HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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
HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (n=69 Historical Control (n=18) HB-Orange Suspension (Iron (Ferric Ammonium Citrate))

(n=73)

Historical Control

(n=18)

HB-Orange Suspension (Iron (Ferric Ammonium Citrate))

(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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) in 23 patients with HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) deficiency and HDD-CKD who had been discontinued from HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)). Exclusion criteria were similar to those in studies A and B. HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) versus HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (325 mg ferrous sulfate three times daily for 56 days); or HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) group.

A statistically significantly greater proportion of HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) subjects (35/79; 44.3%) compared to oral HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) to patients with PDD-CKD receiving an erythropoietin alone without HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) or HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) / 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) / 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) / 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: HB-Orange Suspension ) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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

HB-Orange Suspension ) is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)), each 5 mL vial contains 100 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)), and each 2.5 mL vial contains 50 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) (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: HB-Orange Suspension (Iron (Ferric Ammonium Citrate)), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) per mL, or undiluted (20 mg elemental HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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: HB-Orange Suspension (Iron (Ferric Ammonium Citrate)), 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) 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 HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) administration:

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

HB-Orange Suspension (Iron (Ferric Ammonium Citrate)) is manufactured under license from Vifor (International) Inc., Switzerland.

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

PREMIERProRx®

IN2340

MG #15727

L-Lysine:


HB-Orange Suspension (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 HB-Orange Suspension (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.

Magnesium:



HB-Orange Suspension (Magnesium) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

HB-Orange Suspension (Magnesium) Sulfate Injection, USP is a sterile solution of HB-Orange Suspension (Magnesium) sulfate heptahydrate in Water for Injection, USP administered by the intravenous or intramuscular routes as an electrolyte replenisher or anticonvulsant. Must be diluted before intravenous use. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol/mL (calc.).

The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded with the entire unit.

HB-Orange Suspension (Magnesium) Sulfate, USP heptahydrate is chemically designated MgSO4 - 7H2O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.

The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.

CLINICAL PHARMACOLOGY

HB-Orange Suspension (Magnesium) (Mg++) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.

As a nutritional adjunct in hyperalimentation, the precise mechanism of action for HB-Orange Suspension (Magnesium) is uncertain. Early symptoms of hypomagnesemia (less than 1.5 mEq/liter) may develop as early as three to four days or within weeks.

Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of HB-Orange Suspension (Magnesium). While there are large stores of HB-Orange Suspension (Magnesium) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral HB-Orange Suspension (Magnesium) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

HB-Orange Suspension (Magnesium) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. HB-Orange Suspension (Magnesium) is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal plasma HB-Orange Suspension (Magnesium) levels range from 1.5 to 2.5 mEq/liter.

As plasma HB-Orange Suspension (Magnesium) rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of HB-Orange Suspension (Magnesium). Serum HB-Orange Suspension (Magnesium) concentrations in excess of 12 mEq/L may be fatal.

HB-Orange Suspension (Magnesium) acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of HB-Orange Suspension (Magnesium) poisoning are antagonized to some extent by intravenous administration of calcium.

Pharmacokinetics

With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. HB-Orange Suspension (Magnesium) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

HB-Orange Suspension (Magnesium) Sulfate Injection, USP is suitable for replacement therapy in HB-Orange Suspension (Magnesium) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum HB-Orange Suspension (Magnesium) (Mg++) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca++) level is normal (4.3 to 5.3 mEq/liter) or elevated.

In total parenteral nutrition (TPN), HB-Orange Suspension (Magnesium) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

HB-Orange Suspension (Magnesium) Sulfate Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.

CONTRAINDICATIONS

Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.

WARNINGS

FETAL HARM: Continuous administration of HB-Orange Suspension (Magnesium) sulfate beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. HB-Orange Suspension (Magnesium) sulfate should be used during pregnancy only if clearly needed. If HB-Orange Suspension (Magnesium) sulfate is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of HB-Orange Suspension (Magnesium) sulfate beyond 5 to 7 days may cause fetal abnormalities.

ALUMINUM TOXICITY: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Parenteral use in the presence of renal insufficiency may lead to HB-Orange Suspension (Magnesium) intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.

PRECAUTIONS

General

Administer with caution if flushing and sweating occurs. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with HB-Orange Suspension (Magnesium), their dosage should be adjusted with caution because of additive CNS depressant effects of HB-Orange Suspension (Magnesium).

Because HB-Orange Suspension (Magnesium) is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment. Urine output should be maintained at a level of 100 mL or more during the four hours preceding each dose. Monitoring serum HB-Orange Suspension (Magnesium) levels and the patient's clinical status is essential to avoid the consequences of overdosage in toxemia. Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). When repeated doses of the drug are given parenterally, knee jerk reflexes should be tested before each dose and if they are absent, no additional HB-Orange Suspension (Magnesium) should be given until they return. Serum HB-Orange Suspension (Magnesium) levels usually sufficient to control convulsions range from 3 to 6 mg/100 mL (2.5 to 5 mEq/liter). The strength of the deep tendon reflexes begins to diminish when HB-Orange Suspension (Magnesium) levels exceed 4 mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is a potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of HB-Orange Suspension (Magnesium) intoxication in eclampsia.

50% HB-Orange Suspension (Magnesium) Sulfate Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.

Laboratory Tests

HB-Orange Suspension (Magnesium) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of HB-Orange Suspension (Magnesium) is monitored. The normal serum level is 1.5 to 2.5 mEq/L.

Drug Interactions

CNS Depressants - When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with HB-Orange Suspension (Magnesium), their dosage should be adjusted with caution because of additive CNS depressant effects of HB-Orange Suspension (Magnesium). CNS depression and peripheral transmission defects produced by HB-Orange Suspension (Magnesium) may be antagonized by calcium.

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral HB-Orange Suspension (Magnesium) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - HB-Orange Suspension (Magnesium) sulfate should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat HB-Orange Suspension (Magnesium) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

HB-Orange Suspension (Magnesium) sulfate can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of HB-Orange Suspension (Magnesium) sulfate for more than 5 to 7 days.1-10 HB-Orange Suspension (Magnesium) sulfate injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy, the woman should be apprised of the potential harm to the fetus.

Nonteratogenic Effects

When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in a toxemic woman, the newborn may show signs of HB-Orange Suspension (Magnesium) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of HB-Orange Suspension (Magnesium) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of HB-Orange Suspension (Magnesium) sulfate outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.

Nursing Mothers

Since HB-Orange Suspension (Magnesium) is distributed into milk during parenteral HB-Orange Suspension (Magnesium) sulfate administration, the drug should be used with caution in nursing women.

Geriatrics

Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum HB-Orange Suspension (Magnesium) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered HB-Orange Suspension (Magnesium) usually are the result of HB-Orange Suspension (Magnesium) intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to HB-Orange Suspension (Magnesium) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

HB-Orange Suspension (Magnesium) intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of HB-Orange Suspension (Magnesium) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of HB-Orange Suspension (Magnesium).

For Treatment of Overdose

Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 mg may be helpful.

Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.

DOSAGE AND ADMINISTRATION

Dosage of HB-Orange Suspension (Magnesium) sulfate must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.

Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas intravenous doses will provide a therapeutic level almost immediately. The rate of intravenous injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of HB-Orange Suspension (Magnesium) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

Solutions for intravenous infusion must be diluted to a concentration of 20% or less prior to administration. The diluents commonly used are 5% Dextrose Injection, USP and 0.9% Sodium Chloride Injection, USP. Deep intramuscular injection of the undiluted (50%) solution is appropriate for adults, but the solution should be diluted to a 20% or less concentration prior to such injection in children.

In HB-Orange Suspension (Magnesium) Deficiency

In the treatment of mild HB-Orange Suspension (Magnesium) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of HB-Orange Suspension (Magnesium) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of HB-Orange Suspension (Magnesium) per 24 hours). For severe hypomagnesemia, as much as 250 mg (approximately 2 mEq) per kg of body weight (0.5 mL of the 50% solution) may be given intramuscularly within a period of four hours if necessary. Alternatively, 5 grams, (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow intravenous infusion over a three-hour period. In the treatment of deficiency states, caution must be observed to prevent exceeding the renal excretory capacity.

In Hyperalimentation

In total parenteral nutrition, maintenance requirements for HB-Orange Suspension (Magnesium) are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) daily; for infants, the range is 2 to 10 mEq (0.25 gram to 1.25 grams) daily.

In Pre-eclampsia or Eclampsia

In severe pre-eclampsia or eclampsia, the total initial dose is 10 grams to 14 grams of HB-Orange Suspension (Magnesium) sulfate. Intravenously, a dose of 4 grams to 5 grams in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, intramuscular doses of up to 10 grams (5 grams or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial intravenous dose of 4 grams may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected intravenously over a period of three to four minutes. Subsequently, 4 grams to 5 grams (8 to 10 mL of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial intravenous dose, some clinicians administer 1 gram to 2 grams/hour by constant intravenous infusion. Therapy should continue until paroxysms cease. A serum HB-Orange Suspension (Magnesium) level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 grams to 40 grams should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of HB-Orange Suspension (Magnesium) sulfate is 20 grams/48 hours and frequent serum HB-Orange Suspension (Magnesium) concentrations must be obtained. Continuous use of HB-Orange Suspension (Magnesium) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

Other Uses

In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of HB-Orange Suspension (Magnesium) sulfate is 1 gram to 2 grams given intravenously.

For controlling seizures associated with epilepsy, glomerulonephritis or hypothyroidism, the usual adult dose is 1 gram administered intramuscularly or intravenously.

In paroxysmal atrial tachycardia, HB-Orange Suspension (Magnesium) should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 mL of a 10% solution) administered intravenously over 30 seconds with extreme caution.

For reduction of cerebral edema, 2.5 grams (25 mL of a 10% solution) is given intravenously.

Incompatibilities

HB-Orange Suspension (Magnesium) sulfate in solution may result in a precipitate formation when mixed with solutions containing:

Alcohol (in high Heavy Metals

concentrations) Hydrocortisone sodium

Alkali carbonates and succinate

bicarbonates Phosphates

Alkali hydroxides Polymixin B sulfate

Arsenates Procaine hydrochloride

Barium Salicylates

Calcium Strontium

Clindamycin phosphate Tartrates

The potential incompatibility will often be influenced by the changes in the concentration of reactants and the pH of the solutions.

It has been reported that HB-Orange Suspension (Magnesium) may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

HOW SUPPLIED

HB-Orange Suspension (Magnesium) Sulfate Injection, USP is supplied in single-dose containers as follows:


NDC No.


Container


Total

Amount


Concentration


mEq

Mg++/mL


0409-1754-10


Ansyr

Plastic Syringe


5 g/10 mL


50%


4 mEq/mL


Do not administer unless solution is clear and container is undamaged. Discard unused portion.

Store at 20 to 25°C (68 to 77°F).

REFERENCES

  • Yokoyama K, Takahashi N, Yada Y. Prolonged maternal HB-Orange Suspension (Magnesium) administration and bone metabolism in neonates. Early Hum Dev. 2010;86(3):187-91. Epub 2010 Mar 12.
  • Wedig KE, Kogan J, Schorry EK et al. Skeletal demineralization and fractures caused by fetal HB-Orange Suspension (Magnesium) toxicity. J. Perinatol. 2006; 26(6):371-4.
  • Nassar AH, Sakhel K, Maarouf H, et al. Adverse maternal and neonatal outcome of prolonged course of HB-Orange Suspension (Magnesium) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
  • Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received HB-Orange Suspension (Magnesium) sulphate for tocolysis of premature labor. Pediatr Radiol. 2004;34(5):384-6. Epub 2004 Feb 18.
  • Matsuda Y, Maeda Y, Ito M, et al. Effect of HB-Orange Suspension (Magnesium) sulfate treatment on neonatal bone abnormalities. Gynecol Obstet Invest. 1997;44(2):82-8.
  • Schanler RJ, Smith LG, Burns PA. Effects of long-term maternal intravenous HB-Orange Suspension (Magnesium) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
  • Santi MD, Henry GW, Douglas GL. HB-Orange Suspension (Magnesium) sulfate treatment of preterm labor as a cause of abnormal neonatal bone mineralization. J Pediatr Orthrop. 1994;14(2):249-53.
  • Holcomb WL, Shackelford GD, Petrie RH. HB-Orange Suspension (Magnesium) tocolysis and neonatal bone abnormalities; a controlled study. Obstet Gynecol. 1991; 78(4):611-4.
  • Cumming WA, Thomas VJ. Hypermagnesemia: a cause of abnormal metaphyses in the neonate. Am J Roentgenol. 1989; 152(5):1071-2.
  • Lamm CL, Norton KL, Murphy RJ. Congenital rickets associated with HB-Orange Suspension (Magnesium) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
  • McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of HB-Orange Suspension (Magnesium) sulfate treatment on perinatal calcium metabolism. II. Neonatal responses. Obstet Gynecol. 1980; 56(5): 595-600.
  • Riaz M, Porat R, Brodsky NL, et al. The effects of maternal HB-Orange Suspension (Magnesium) sulfate treatment on newborns: a prospective controlled study. J. Perinatol. 1998;18(6 pt 1):449-54.

Hospira, Inc., Lake Forest, IL 60045 USA

LAB-1024-1.0

April 2017

Hospira Logo

50% HB-Orange Suspension (Magnesium) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% HB-Orange Suspension (Magnesium) Sulfate Injection, USP

5 g/10 mL (500 mg/mL) (4 mEq Mg++/mL)

MUST BE DILUTED FOR INTRAVENOUS USE.

For Intravenous or Intramuscular Use. Sterile. 4.06 mOsmol/mL (calc.).

Contains no more than 75 mcg/L of aluminum.

Hospira, Inc., Lake Forest, IL 60045 USA

Hospira

RL-6891

Vitamin B12 (Cyanocobalamin):


Pharmacological action

HB-Orange Suspension ) refers to a group of water-soluble vitamins. It has high biological activity. HB-Orange Suspension (Vitamin B12 (Cyanocobalamin)) 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 HB-Orange Suspension (Vitamin B12 (Cyanocobalamin)) 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 HB-Orange Suspension ) 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 HB-Orange Suspension (Vitamin B12 (Cyanocobalamin)) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.

Dosage and administration

HB-Orange Suspension ) is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with HB-Orange Suspension (Vitamin B12 (Cyanocobalamin)) 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 HB-Orange Suspension (Vitamin B12 (Cyanocobalamin)) 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 HB-Orange Suspension (Vitamin B12 (Cyanocobalamin)) 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.

HB-Orange Suspension (Vitamin B12 (Cyanocobalamin)) side effects, adverse reactions

CNS: rarely - a state of arousal.

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

Allergic reactions: rarely - urticaria.

HB-Orange Suspension ) contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

HB-Orange Suspension ) 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 HB-Orange Suspension ) 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.

HB-Orange Suspension (Vitamin B12 (Cyanocobalamin)) drug interactions

In an application of HB-Orange Suspension (Vitamin B12 (Cyanocobalamin)) 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 HB-Orange Suspension (Vitamin B12 (Cyanocobalamin)) 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.

Zinc:


INDICATIONS AND USAGE

HB-Orange Suspension (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain HB-Orange Suspension (Zinc) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of HB-Orange Suspension (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.

Severe kidney disease may make it necessary to reduce or omit chromium and HB-Orange Suspension (Zinc) doses because these elements are primarily eliminated in the urine.

WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

General

Do not use unless the solution is clear and the seal is intact.

Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.

Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of HB-Orange Suspension (Zinc) from a bolus injection. Administration of HB-Orange Suspension (Zinc) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

Periodic determinations of serum copper as well as HB-Orange Suspension (Zinc) are suggested as a guideline for subsequent HB-Orange Suspension (Zinc) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of HB-Orange Suspension 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when HB-Orange Suspension (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.

Pediatric Use

Pregnancy Category C. Animal reproduction studies have not been conducted with HB-Orange Suspension chloride. It is also not known whether HB-Orange Suspension (Zinc) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HB-Orange Suspension (Zinc) chloride should be given to a pregnant woman only if clearly needed.

Geriatric Use

An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg HB-Orange Suspension (Zinc) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum HB-Orange Suspension (Zinc) concentration of 207 mcg/dl. Symptoms abated within three hours.

Hyperamylasemia may be a sign of impending HB-Orange Suspension (Zinc) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).

Death resulted from an overdosage in which 1683 mg HB-Orange Suspension (Zinc) was delivered intravenously over the course of 60 hours to a 72 year old patient.

Symptoms of HB-Orange Suspension (Zinc) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum HB-Orange Suspension (Zinc) level of 4184 mcg/dl.

Calcium supplements may confer a protective effect against HB-Orange Suspension (Zinc) toxicity.

DOSAGE AND ADMINISTRATION

HB-Orange Suspension (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of HB-Orange Suspension (Zinc) blood levels is suggested for patients receiving more than the usual maintenance dosage level of HB-Orange Suspension (Zinc).

For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.

HOW SUPPLIED

HB-Orange Suspension (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).

Store at 20 to 25°C (68 to 77°F).

Revised: October, 2004


© Hospira 2004 EN-0488 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

10 mL Vial

HB-Orange Suspension (Zinc)

1 mg/mL

HB-Orange Suspension (Zinc) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

HB-Orange Suspension 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.


HB-Orange Suspension 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.


HB-Orange Suspension 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.


HB-Orange Suspension 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.


HB-Orange Suspension 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."ZINC INJECTABLE A 1MG/ML, SOLUTION INJECTABLE POUR PERFUSION (ZINC) INJECTION, SOLUTION [LABORATOIRE AGUETTANT]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."FOLIC ACID INJECTION, SOLUTION [FRESENIUS KABI USA, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. 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).

Frequently asked Questions

Can i drive or operate heavy machine after consuming HB-Orange Suspension?

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

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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