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Sunday, June 10, 2012

Nascobal

cyanocobalamin

Dosage Form: nasal spray
Nascobal®

Nasal spray

(Cyanocobalamin, USP)

500 mcg/spray

Nascobal Description

Cyanocobalamin is a synthetic form of vitamin B12 with equivalent vitamin B12 activity. The chemical name is 5,6-dimethyl-benzimidazolyl cyanocobamide. The cobalt content is 4.35%. The molecular formula is C63H88CoN14O14P, which corresponds to a molecular weight of 1355.38 and the following structural formula:

Cyanocobalamin occurs as dark red crystals or orthorhombic needles or crystalline red powder. It is very hygroscopic in the anhydrous form, and sparingly to moderately soluble in water (1:80). Its pharmacologic activity is destroyed by heavy metals (iron) and strong oxidizing or reducing agents (vitamin C), but not by autoclaving for short periods of time (15-20 minutes) at 121°C. The vitamin B12 coenzymes are very unstable in light.

Nascobal Nasal Spray is a solution of Cyanocobalamin, USP (vitamin B12) for administration as a spray to the nasal mucosa. Each bottle of Nascobal Nasal Spray contains 1.3mL of a 500 mcg/0.1mL solution of cyanocobalamin with sodium citrate, citric acid, and glycerin and benzalkonium chloride in purified water. The spray solution has a pH between 4.5 and 5.5. The spray pump unit must be fully primed (see Dosage and Administration) prior to initial use. After initial priming, each spray delivers an average of 500 mcg of cyanocobalamin and the 1.3mL of spray solution contained in the bottle will deliver 4 doses of Nascobal Nasal Spray. The unit must be re-primed before each dose. (see Dosage and Administration).

CLINICAL PHARMACOLOGY

GENERAL PHARMACOLOGY AND MECHANISM OF ACTION

Vitamin B12 is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis. Cells characterized by rapid division (e.g., epithelial cells, bone marrow, myeloid cells) appear to have the greatest requirement for vitamin B12. Vitamin B12 can be converted to coenzyme B12 in tissues, and as such is essential for conversion of methylmalonate to succinate and synthesis of methionine from homocysteine, a reaction which also requires folate. In the absence of coenzyme B12, tetrahydrofolate cannot be regenerated from its inactive storage form, 5-methyltetrahydrofolate, and a functional folate deficiency occurs. Vitamin B12 also may be involved in maintaining sulfhydryl (SH) groups in the reduced form required by many SH-activated enzyme systems. Through these reactions, vitamin B12 is associated with fat and carbohydrate metabolism and protein synthesis. Vitamin B12 deficiency results in megaloblastic anemia, GI lesions, and neurologic damage that begins with an inability to produce myelin and is followed by gradual degeneration of the axon and nerve head.

Cyanocobalamin is the most stable and widely used form of vitamin B12, and has hematopoietic activity apparently identical to that of the antianemia factor in purified liver extract. The information below, describing the clinical pharmacology of cyanocobalamin, has been derived from studies with injectable vitamin B12.

Vitamin B12 is quantitatively and rapidly absorbed from intramuscular and subcutaneous sites of injection. It is bound to plasma proteins and stored in the liver. Vitamin B12 is excreted in the bile and undergoes some enterohepatic recycling. Absorbed vitamin B12 is transported via specific B12 binding proteins, transcobalamin I and II, to the various tissues. The liver is the main organ for vitamin B12 storage.

Parenteral (intramuscular) administration of vitamin B12 completely reverses the megaloblastic anemia and GI symptoms of vitamin B12 deficiency; the degree of improvement in neurologic symptoms depends on the duration and severity of the lesions, although progression of the lesions is immediately arrested.

Gastrointestinal absorption of vitamin B12 depends on the presence of sufficient intrinsic factor and calcium ions. Intrinsic factor deficiency causes pernicious anemia, which may be associated with subacute combined degeneration of the spinal cord. Prompt parenteral administration of vitamin B12 prevents progression of neurologic damage.

The average diet supplies about 4 to 15 mcg/day of vitamin B12 in a protein-bound form that is available for absorption after normal digestion. Vitamin B12 is not present in foods of plant origin, but is abundant in foods of animal origin. In people with normal absorption, deficiencies have been reported only in strict vegetarians who consume no products of animal origin (including no milk products or eggs).

Vitamin B12 is bound to intrinsic factor during transit through the stomach; separation occurs in the terminal ileum in the presence of calcium, and vitamin B12 enters the mucosal cell for absorption. It is then transported by the transcobalamin binding proteins. A small amount (approximately 1% of the total amount ingested) is absorbed by simple diffusion, but this mechanism is adequate only with very large doses. Oral absorption is considered too undependable to rely on in patients with pernicious anemia or other conditions resulting in malabsorption of vitamin B12.

Colchicine, para-aminosalicylic acid, and heavy alcohol intake for longer than 2 weeks may produce malabsorption of vitamin B12.

PHARMACOKINETICS

Absorption

A three way crossover study in 25 fasting healthy subjects was conducted to compare the bioavailability of the B12 nasal spray to the B12 nasal gel and to evaluate the relative bioavailability of the nasal formulations as compared to the intramuscular injection. The peak concentrations after administration of intranasal spray were reached in 1.25 +/- 1.9 hours. The average peak concentration of B12 obtained after baseline correction following administration of intranasal spray was 757.96 +/- 532.17 pg/mL. The bioavailability of the nasal spray relative to the intramuscular injection was found to be 6.1%. The bioavailability of the B12 nasal spray was found to be 10% less than the B12 nasal gel. The 90% confidence intervals for the loge-transformed AUC(0-t) and Cmax was 71.71% - 114.19% and 71.6% - 118.66% respectively.

In pernicious anemia patients, once weekly intranasal dosing with 500 mcg B12 gel resulted in a consistent increase in pre-dose serum B12 levels during one month of treatment (p < 0.003) above that seen one month after 100 mcg intramuscular dose (Figure).

Distribution

In the blood, B12 is bound to transcobalamin II, a specific B-globulin carrier protein, and is distributed and stored primarily in the liver and bone marrow.

Elimination

About 3-8 mcg of B12 is secreted into the GI tract daily via the bile; in normal subjects with sufficient intrinsic factor, all but about 1 mcg is reabsorbed. When B12 is administered in doses which saturate the binding capacity of plasma proteins and the liver, the unbound B12 is rapidly eliminated in the urine. Retention of B12 in the body is dose-dependent. About 80-90% of an intramuscular dose up to 50 mcg is retained in the body; this percentage drops to 55% for a 100 mcg dose, and decreases to 15% when a 1000 mcg dose is given.

Figure. Vitamin B12 Serum Trough Levels After Intramuscular Solution (IM) of 100 mcg and Nasal Gel (IN) Administration of 500 mcg Cyanocobalamin After Weekly Doses.

INDICATIONS AND USAGE

Nascobal Nasal Spray is indicated for the maintenance of normal hematologic status in pernicious anemia patients who are in remission following intramuscular vitamin B12 therapy and who have no nervous system involvement.

Nascobal Nasal Spray is also indicated as a supplement for other vitamin B12 deficiencies, including:

I. Dietary deficiency of vitamin B12 occurring in strict vegetarians (Isolated vitamin B12 deficiency is very rare).

II. Malabsorption of vitamin B12 resulting from structural or functional damage to the stomach, where intrinsic factor is secreted, or to the ileum, where intrinsic factor facilitates vitamin B12 absorption. These conditions include HIV infection, AIDS, Crohn's disease, tropical sprue, and nontropical sprue (idiopathic steatorrhea, gluten-induced enteropathy). Folate deficiency in these patients is usually more severe than vitamin B12 deficiency.

III. Inadequate secretion of intrinsic factor, resulting from lesions that destroy the gastric mucosa (ingestion of corrosives, extensive neoplasia), and a number of conditions associated with a variable degree of gastric atrophy (such as multiple sclerosis, HIV infection, AIDS, certain endocrine disorders, iron deficiency, and subtotal gastrectomy). Total gastrectomy always produces vitamin B12 deficiency. Structural lesions leading to vitamin B12 deficiency include regional ileitis, ileal resections, malignancies, etc.

IV. Competition for vitamin B12 by intestinal parasites or bacteria. The fish tapeworm (Diphyllobothrium latum) absorbs huge quantities of vitamin B12 and infested patients often have associated gastric atrophy. The blind loop syndrome may produce deficiency of vitamin B12 or folate.

V. Inadequate utilization of vitamin B12. This may occur if antimetabolites for the vitamin are employed in the treatment of neoplasia.

Requirements of vitamin B12 in excess of normal (due to pregnancy, thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, hepatic and renal disease) can usually be met with intranasal or oral supplementation.

Nascobal Nasal Spray is not suitable for vitamin B12 absorption test (Schilling Test).

CONTRAINDICATION

Sensitivity to cobalt and/or vitamin B12 or any component of the medication is a contraindication.

Warnings

Patients with early Leber's disease (hereditary optic nerve atrophy) who were treated with vitamin B12 suffered severe and swift optic atrophy.

Hypokalemia and sudden death may occur in severe megaloblastic anemia which is treated intensely with vitamin B12. Folic acid is not a substitute for vitamin B12 although it may improve vitamin B12-deficient megaloblastic anemia. Exclusive use of folic acid in treating vitamin B12-deficient megaloblastic anemia could result in progressive and irreversible neurologic damage.

Anaphylactic shock and death have been reported after parenteral vitamin B12 administration. No such reactions have been reported in clinical trials with Nascobal Nasal Spray or Nascobal Nasal Gel.

Blunted or impeded therapeutic response to vitamin B12 may be due to such conditions as infection, uremia, drugs having bone marrow suppressant properties such as chloramphenicol, and concurrent iron or folic acid deficiency.

Precautions

1. GENERAL

An intradermal test dose of parenteral vitamin B12 is recommended before Nascobal Nasal Spray is administered to patients suspected of cyanocobalamin sensitivity. Vitamin B12 deficiency that is allowed to progress for longer than three months may produce permanent degenerative lesions of the spinal cord. Doses of folic acid greater than 0.1 mg per day may result in hematologic remission in patients with vitamin B12 deficiency. Neurologic manifestations will not be prevented with folic acid, and if not treated with vitamin B12, irreversible damage will result.

Doses of vitamin B12 exceeding 10 mcg daily may produce hematologic response in patients with folate deficiency. Indiscriminate administration may mask the true diagnosis.

The validity of diagnostic vitamin B12 or folic acid blood assays could be compromised by medications, and this should be considered before relying on such tests for therapy.

Vitamin B12 is not a substitute for folic acid and since it might improve folic acid deficient megaloblastic anemia, indiscriminate use of vitamin B12 could mask the true diagnosis.

Hypokalemia and thrombocytosis could occur upon conversion of severe megaloblastic to normal erythropoiesis with vitamin B12 therapy. Therefore, serum potassium levels and the platelet count should be monitored carefully during therapy.

Vitamin B12 deficiency may suppress the signs of polycythemia vera. Treatment with vitamin B12 may unmask this condition.

If a patient is not properly maintained with Nascobal® Nasal Spray, intramuscular vitamin B12 is necessary for adequate treatment of the patient. No single regimen fits all cases, and the status of the patient observed in follow-up is the final criterion for adequacy of therapy.

The effectiveness of Nascobal Nasal Spray in patients with nasal congestion, allergic rhinitis and upper respiratory infections has not been determined. Therefore, treatment with Nascobal Nasal Spray should be deferred until symptoms have subsided.

2. INFORMATION FOR PATIENTS

Patients with pernicious anemia should be instructed that they will require weekly intranasal administration of Nascobal Nasal Spray for the remainder of their lives. Failure to do so will result in return of the anemia and in development of incapacitating and irreversible damage to the nerves of the spinal cord. Also, patients should be warned about the danger of taking folic acid in place of vitamin B12, because the former may prevent anemia but allow progression of subacute combined degeneration of the spinal cord.

(Hot foods may cause nasal secretions and a resulting loss of medication; therefore, patients should be told to administer Nascobal Nasal Spray at least one hour before or one hour after ingestion of hot foods or liquids.)

A vegetarian diet which contains no animal products (including milk products or eggs) does not supply any vitamin B12. Therefore, patients following such a diet should be advised to take Nascobal Nasal Spray weekly. The need for vitamin B12 is increased by pregnancy and lactation. Deficiency has been recognized in infants of vegetarian mothers who were breast fed, even though the mothers had no symptoms of deficiency at the time.

Because the nasal dosage forms of vitamin B12 have a lower absorption than intramuscular dosage, nasal dosage forms are administered weekly, rather than the monthly intramuscular dosage. As shown in the Figure above, at the end of a month, weekly nasal administration results in significantly higher serum vitamin B12 levels than after intramuscular administration. The patient should also understand the importance of returning for follow-up blood tests every 3 to 6 months to confirm adequacy of the therapy.

Careful instructions on the actuator assembly, removal of the safety clip, priming of the actuator and nasal administration of Nascobal Nasal Spray should be given to the patient. Although instructions for patients are supplied with individual bottles, procedures for use should be demonstrated to each patient.

3. LABORATORY TESTS

Hematocrit, reticulocyte count, vitamin B12, folate and iron levels should be obtained prior to treatment. If folate levels are low, folic acid should also be administered. All hematologic parameters should be normal when beginning treatment with Nascobal® Nasal Spray.

Vitamin B12 blood levels and peripheral blood counts must be monitored initially at one month after the start of treatment with Nascobal® Nasal Spray, and then at intervals of 3 to 6 months.

A decline in the serum levels of B12 after one month of treatment with B12 nasal spray may indicate that the dose may need to be adjusted upward. Patients should be seen one month after each dose adjustment; continued low levels of serum B12 may indicate that the patient is not a candidate for this mode of administration.

Patients with pernicious anemia have about 3 times the incidence of carcinoma of the stomach as in the general population, so appropriate tests for this condition should be carried out when indicated.

4. DRUG/LABORATORY TEST INTERACTIONS

Persons taking most antibiotics, methotrexate or pyrimethamine invalidate folic acid and vitamin B12 diagnostic blood assays.

Colchicine, para-aminosalicylic acid and heavy alcohol intake for longer than 2 weeks may produce malabsorption of vitamin B12.

5. CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

Long-term studies in animals to evaluate carcinogenic potential have not been done. There is no evidence from long-term use in patients with pernicious anemia that vitamin B12 is carcinogenic. Pernicious anemia is associated with an increased incidence of carcinoma of the stomach, but this is believed to be related to the underlying pathology and not to treatment with vitamin B12.

6. PREGNANCY

Pregnancy Category C: Animal reproduction studies have not been conducted with vitamin B12. It is also not known whether vitamin B12 can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Adequate and well-controlled studies have not been done in pregnant women. However, vitamin B12 is an essential vitamin and requirements are increased during pregnancy. Amounts of vitamin B12 that are recommended by the Food and Nutrition Board, National Academy of Science - National Research Council for pregnant women should be consumed during pregnancy.

7. NURSING MOTHERS

Vitamin B12 appears in the milk of nursing mothers in concentrations which approximate the mother's vitamin B12 blood level. Amounts of vitamin B12 that are recommended by the Food and Nutrition Board, National Academy of Science-National Research Council for lactating women should be consumed during lactation.

8. PEDIATRIC USE

Intake in pediatric patients should be in the amount recommended by the Food and Nutrition Board, National Academy of Science-National Research Council.

Adverse Reactions

The incidence of adverse experiences described in the Table below are based on data from a short-term clinical trial in vitamin B12 deficient patients in hematologic remission receiving Nascobal (Cyanocobalamin, USP) Gel for Intranasal Administration (N=24) and intramuscular vitamin B12 (N=25). In the pharmacokinetic study comparing Nascobal Nasal Spray and Nascobal Nasal Gel, the incidence of adverse events was similar.

Table Adverse Experiences by Body System, Number of Patients and Number of Occurrences by Treatment Following Intramuscular and Intranasal Administration of Cyanocobalamin.
* There may be a possible relationship between these adverse experiences and the study drugs. These adverse experiences could have also been produced by the patient’s clinical state or other concomitant therapy. ± Sore throat, Common cold
		Number of Patients (Occurrences)
Body System	Adverse Experience	Vitamin B12Nasal Gel,500mcgN=24	IntramuscularVitamin B12, 100 mcgN=25
Body as a Whole	Asthenia	1 (1)	4 (4)
	Back Pain	0 (0)	1 (1)
	Generalized Pain	0 (0)	2 (3)
	Headache	1 (2)*	5 (11)
	Infection±	3 (4)	3 (3)
Cardiovascular System	Peripheral Vascular Disorder	0 (0)	1 (1)
Digestive System	Dyspepsia	0 (0)	1 (2)
	Glossitis	1 (1)	0 (0)
	Nausea	1 (1)*	1 (1)
	Nausea and Vomiting	0 (0)	1 (1)
	Vomiting	0 (0)	1 (1)
Musculoskeletal System	Arthritis	0 (0)	2 (2)
Musculoskeletal System	Myalgia	0 (0)	1 (1)
Nervous System	Abnormal Gait	0 (0)	1 (1)
	Anxiety	0 (0)	1 (1)*
	Dizziness	0 (0)	3 (3)
	Hypoesthesia	0 (0)	1 (1)
	Incoordination	0 (0)	1 (2)*
	Nervousness	0 (0)	1 (3)*
	Paresthesia	1 (1)	1 (1)
Respiratory System	Dyspnea	0 (0)	1 (1)
Respiratory System	Rhinitis	1 (1)	2 (2)

The intensity of the reported adverse experiences following the administration of Nascobal (Cyanocobalamin, USP) Gel for Intranasal Administration and intramuscular vitamin B12 were generally mild. One patient reported severe headache following intramuscular dosing. Similarly, a few adverse experiences of moderate intensity were reported following intramuscular dosing (two headaches and rhinitis; one dyspepsia, arthritis, and dizziness), and dosing with Nascobal (Cyanocobalamin, USP) Gel for Intranasal Administration (one headache, infection, and paresthesia).

The majority of the reported adverse experiences following dosing with Nascobal (Cyanocobalamin, USP) Gel for Intranasal Administration and intramuscular vitamin B12 were judged to be intercurrent events. For the other reported adverse experiences, the relationship to study drug was judged as "possible" or "remote". Of the adverse experiences judged to be of "possible" relationship to the study drug, anxiety, incoordination, and nervousness were reported following intramuscular vitamin B12 and headache, nausea, and rhinitis were reported following dosing with Nascobal (Cyanocobalamin, USP) Gel for Intranasal Administration.

The following adverse reactions have been reported with parenteral vitamin B12:

Cardiovascular: Pulmonary edema and congestive heart failure early in treatment; peripheral vascular thrombosis.

Hematological: Polycythemia vera.

Gastrointestinal: Mild transient diarrhea.

Dermatological: Itching; transitory exanthema.

Miscellaneous: Feeling of swelling of the entire body.

Overdosage

No overdosage has been reported with Nascobal Nasal Spray, Nascobal (Cyanocobalamin, USP) Gel for Intranasal Administration or parenteral vitamin B12.

Nascobal Dosage and Administration

The recommended initial dose of Nascobal Nasal Spray is one spray (500 mcg) administered in ONE nostril once weekly. Nascobal Nasal Spray should be administered at least one hour before or one hour after ingestion of hot foods or liquids. Periodic monitoring of serum B12 levels should be obtained to establish adequacy of therapy.

Priming (Activation) of Pump

Before the first dose and administration, the pump must be primed. Remove the clear plastic safety clip from the pump. To prime the pump, place nozzle between the first and second finger with the thumb on the bottom of the bottle. Pump the unit firmly and quickly until the first appearance of spray. Then prime the pump an additional 2 times. Now the nasal spray is ready for use. The unit must be re-primed before each dose. Prime the pump once immediately before each administration of dose 2 through 4.

See LABORATORY TESTS for monitoring B12 levels and adjustment of dosage.

How is Nascobal Supplied

Nascobal Nasal Spray is available as a spray in 3 mL glass bottles containing 1.3 mL of solution. It is available in a dosage strength of 500 mcg per actuation (0.1 mL/actuation). A screw-on actuator is provided. This actuator, following priming, will deliver 0.1 mL of the spray. Nascobal Nasal Spray is provided in a carton containing a nasal spray actuator with dust cover, a bottle of nasal spray solution, and a package insert. One bottle will deliver 4 doses (NDC 49884-270-86).

PHARMACIST ASSEMBLY INSTRUCTIONS FOR Nascobal NASAL SPRAY

The pharmacist should assemble the Nascobal Nasal Spray unit prior to dispensing to the patient, according to the following instructions:

Open the carton and remove the spray actuator and spray solution bottle.

Assemble Nascobal Nasal Spray by first unscrewing the white cap from the spray solution bottle and screwing the actuator unit tightly onto the bottle. Make sure the clear dust cover is on the pump unit.

Return the Nascobal Nasal Spray bottle to the carton for dispensing to the patient.

INFORMATION FOR PATIENTS

Because the nasal dosage forms of Vitamin B12 have a lower absorption than intramuscular dosage, nasal dosage forms are administered weekly, rather than the monthly intramuscular dosage. As shown in the Figure above, at the end of a month, weekly nasal administration results in significantly higher serum Vitamin B12 levels than after intramuscular administration. The patient should also understand the importance of returning for follow-up blood tests every 3 to 6 months to confirm adequacy of the therapy.

Careful instructions on the actuator assembly, removal of safety clip, priming of the actuator and nasal administration of Nascobal Nasal Spray should be given to the patient. Although instructions for patients are supplied with individual bottles, procedures for use should be demonstrated to each patient.

STORAGE CONDITIONS

Protect from light. Keep covered in carton until ready to use. Store upright at controlled room temperature 15°C to 30°C (59°F to 86°F). Protect from freezing.

To report suspected adverse reactions, contact Par Pharmaceutical Companies, Inc. at 1-800-828-9393.

Distributed by:

Par Pharmaceutical Companies, Inc

Spring Valley, NY 10977

OS270-01-03

Rev. 07/2011

FOR NASAL USE ONLY

KEEP OUT OF REACH OF CHILDREN

Each 0.1 mL contains 500mcg Cyancobalamin USP and the following inactive ingredients: Citric Acid USP, Sodium Citrate USP, Glycerin USP, Benzalkonium Chloride NF and Purified Water USP.

One bottle will deliver four doses.

Read instructions carefully before using.

See package insert for complete prescribing information.

Store upright at controlled room temperature 15°-30° C (59°-86° F).

PACKAGE LABEL-PRINICIPAL DISPLAY PANEL: Nascobal NASAL SPRAY 500MCG/SPRAY

NDC 49884-270-14

Nascobal® Nasal Spray

(Cyanocobalamin, USP)

500mcg/spray

2.3mL (8 sprays)

PACKAGE LABEL-PRINICIPAL DISPLAY PANEL: Nascobal NASAL SPRAY 500MCG/SPRAY

NDC 49884-270-86

Nascobal® Nasal Spray

(Cyanocobalamin, USP)

500mcg/spray

1.3mL (4 sprays)

Nascobal
cyanocobalamin spray

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	49884-270
Route of Administration	NASAL	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
CYANOCOBALAMIN (CYANOCOBALAMIN)	CYANOCOBALAMIN	500 ug

Inactive Ingredients
Ingredient Name	Strength
SODIUM CITRATE
CITRIC ACID
GLYCERIN
BENZALKONIUM CHLORIDE

Product Characteristics
Color		Score
Shape		Size
Flavor		Imprint Code
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	49884-270-86	4 SPRAY In 1 BOTTLE	None
2	49884-270-14	8 SPRAY In 1 BOTTLE	None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA021642	08/13/2009

Labeler - Par Pharmaceutical , Inc (092733690)

Registrant - Par Pharmaceutical , Inc (092733690)

Establishment
Name	Address	ID/FEI	Operations
Par Pharmaceutical , Inc		092733690	manufacture

Revised: 08/2011Par Pharmaceutical , Inc

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Nascobal Use in Pregnancy & Breastfeeding
Nascobal Drug Interactions
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Saturday, June 9, 2012

Hemocyte-F

Pronunciation: FER-uhs FYOO-mar-rate/FOE-lik AS-id
Generic Name: Ferrous Fumarate/Folic Acid
Brand Name: Examples include Ferrocite F and Hemocyte-F

Hemocyte-F is used for:

Treating anemia caused by low levels of iron or folate in the blood. It may also be used to treat other conditions as determined by your doctor, which may not be listed in the professional package insert.

Hemocyte-F is an iron and folic acid combination. It works by replacing or adding iron and folic acid when the body does not produce enough of its own.

Do NOT use Hemocyte-F if:

you are allergic to any ingredient in Hemocyte-F

you have pernicious anemia or you have high levels of iron in your blood

Contact your doctor or health care provider right away if any of these apply to you.

Before using Hemocyte-F:

Some medical conditions may interact with Hemocyte-F. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, plan to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have stomach or bowel problems (eg, ulcer, bowel irritation or inflammation, Crohn disease)

if you have had multiple blood transfusions, anemia, or a blood disorder (eg, thalassemia, porphyria)

Some MEDICINES MAY INTERACT with Hemocyte-F. Tell your health care provider if you are taking any other medicines, especially any of the following:

Bisphosphonates (eg, alendronate, risedronate), cephalosporins (eg, cephalexin), hydantoins (eg, phenytoin), levodopa, methyldopa, mycophenolate, penicillamine, quinolones (eg, ciprofloxacin, levofloxacin), tetracyclines (eg, doxycycline), or thyroid hormones (eg, levothyroxine) because the effectiveness of these medicines may be decreased

Doxycycline, hydantoins (eg, phenytoin), mycophenolate, tetracyclines, or thyroid hormones (eg, levothyroxine) because the effectiveness of these medicines may be decreased

Fluorouracil because side effects of Hemocyte-Fs may be increased

This may not be a complete list of all interactions that may occur. Ask your health care provider if Hemocyte-F may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Hemocyte-F:

Use Hemocyte-F as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Hemocyte-F is absorbed better on an empty stomach but may be taken with food if it upsets your stomach.

Hemocyte-F may reduce the effectiveness of certain other medicines when taken together. Ask your doctor or pharmacist if you should separate Hemocyte-F from any other medicines that you are taking.

Do not take Hemocyte-F within 1 hour before or 2 hours after antacids, eggs, whole grain breads or cereal, milk, milk products, coffee, or tea.

Take Hemocyte-F with a full glass (8 oz/240 mL) of water.

Do not lie down for 30 minutes after taking Hemocyte-F.

If you miss a dose of Hemocyte-F, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Hemocyte-F.

Important safety information:

Accidental overdose of iron-containing products is a leading cause of fatal poisoning in CHILDREN younger than 6 years of age. Keep Hemocyte-F out of the reach of children.

Do not take large doses of vitamins (megadoses or megavitamin therapy) unless otherwise directed by your doctor.

Do not take Hemocyte-F for longer than 6 months without checking with your doctor.

While you are taking Hemocyte-F, you may notice a darkening of stools. This is normal.

Hemocyte-F may cause false test results with kits used to check for blood in the stool or blood cholesterol. Check with your doctor if you are using either kind of test kit.

LAB TESTS, including blood counts, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.

Possible side effects of Hemocyte-F:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Bitter taste; constipation; diarrhea; nausea; stomach discomfort; throat irritation.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black or green bowel movements; vomiting with continuing stomach pain.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Hemocyte-F side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center ( http://www.aapcc.org), or emergency room immediately. Symptoms may include abdominal pain; coma; fast or irregular heartbeat; fever; tiredness. Accidental overdose of iron-containing products is a leading cause of fatal poisoning in CHILDREN younger than 6 years of age. Keep Hemocyte-F out of the reach of children.

Proper storage of Hemocyte-F:

Store Hemocyte-F at room temperature between 68 and 77 degrees F (20 and 25 degrees C) away from heat, moisture, and light. Do not store in the bathroom. Keep Hemocyte-F out of the reach of children and away from pets.

General information:

If you have any questions about Hemocyte-F, please talk with your doctor, pharmacist, or other health care provider.

Hemocyte-F is to be used only by the patient for whom it is prescribed. Do not share it with other people.

If your symptoms do not improve or if they become worse, check with your doctor.

Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Hemocyte-F. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Hemocyte-F resources

Hemocyte-F Side Effects (in more detail)
Hemocyte-F Use in Pregnancy & Breastfeeding
Hemocyte-F Drug Interactions
Hemocyte-F Support Group
0 Reviews for Hemocyte-F - Add your own review/rating

Hemocyte-F Concise Consumer Information (Cerner Multum)

Compare Hemocyte-F with other medications

Anemia Associated with Iron Deficiency
Iron Deficiency Anemia

Friday, June 8, 2012

Hyoscyamine Controlled-Release Tablets

Pronunciation: HYE-oh-SYE-a-meen
Generic Name: Hyoscyamine
Brand Name: Symax Duotab

Hyoscyamine Controlled-Release Tablets are used for:

Treating certain stomach, intestinal, and bladder conditions, including spasms. It is used to control stomach secretions and cramps. It is used to relieve the symptoms of colic or runny nose. It may also be used for other conditions as determined by your doctor.

Hyoscyamine Controlled-Release Tablets are an anticholinergic agent. It works by decreasing the motion of muscles in the stomach, intestines, and bladder. It also decreases the production of stomach acid.

Do NOT use Hyoscyamine Controlled-Release Tablets if:

you are allergic to any ingredient in Hyoscyamine Controlled-Release Tablets

you have severe esophagus problems (eg, irritation, narrowing); a blockage of the stomach, bowel, or bladder; bowel motility problems; or severe bowel problems (eg, severe ulcerative colitis, toxic megacolon)

you have glaucoma, myasthenia gravis, or heart problems caused by severe bleeding

Contact your doctor or health care provider right away if any of these apply to you.

Before using Hyoscyamine Controlled-Release Tablets:

Some medical conditions may interact with Hyoscyamine Controlled-Release Tablets. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have nerve problems, prostate problems, esophagus problems (eg, reflux), stomach or bowel problems, heart or blood vessel problems (eg, fast or irregular heartbeat, heart failure, coronary heart disease), hiatal hernia, kidney problems, an overactive thyroid, high blood pressure, urinary problems, paralysis, or brain damage, or if you are at risk for glaucoma

if you have diarrhea or fever, have been very ill, or are in poor health

Some MEDICINES MAY INTERACT with Hyoscyamine Controlled-Release Tablets. Tell your health care provider if you are taking any other medicines, especially any of the following:

Amantadine, antihistamines (eg, diphenhydramine), haloperidol, monoamine oxidase inhibitors (MAOIs) (eg, phenelzine), other anticholinergics (eg, scopolamine), phenothiazines (eg, thioridazine), or tricyclic antidepressants (eg, amitriptyline) because they may increase the risk of Hyoscyamine Controlled-Release Tablets's side effects

Narcotic pain medicines (eg, codeine) or potassium chloride because the risk of their side effects may be increased by Hyoscyamine Controlled-Release Tablets

Ketoconazole or metoclopramide because their effectiveness may be decreased by Hyoscyamine Controlled-Release Tablets

This may not be a complete list of all interactions that may occur. Ask your health care provider if Hyoscyamine Controlled-Release Tablets may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Hyoscyamine Controlled-Release Tablets:

Use Hyoscyamine Controlled-Release Tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Hyoscyamine Controlled-Release Tablets are usually taken 30 to 60 minutes before a meal. Follow your doctor's instructions for taking Hyoscyamine Controlled-Release Tablets.

Swallow Hyoscyamine Controlled-Release Tablets whole. Do not break, crush, or chew before swallowing.

If you also take antacids, ask your doctor or pharmacist how to take them with Hyoscyamine Controlled-Release Tablets.

If you miss a dose of Hyoscyamine Controlled-Release Tablets, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Hyoscyamine Controlled-Release Tablets.

Important safety information:

Hyoscyamine Controlled-Release Tablets may cause drowsiness, dizziness, blurred vision, or lightheadedness. These effects may be worse if you take it with alcohol or certain medicines. Use Hyoscyamine Controlled-Release Tablets with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.

Do not drink alcohol or use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Hyoscyamine Controlled-Release Tablets; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.

Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.

Do not become overheated or dehydrated in hot weather or while you are being active; heatstroke may occur.

Drink plenty of fluids, maintain good oral hygiene, and suck on sugarless hard candy to relieve dry mouth.

Proper dental care is important while you are taking Hyoscyamine Controlled-Release Tablets. Brush and floss your teeth and visit the dentist regularly.

Hyoscyamine Controlled-Release Tablets may make your eyes more sensitive to sunlight. It may help to wear sunglasses.

Tell your doctor or dentist that you take Hyoscyamine Controlled-Release Tablets before you receive any medical or dental care, emergency care, or surgery.

Use Hyoscyamine Controlled-Release Tablets with caution in the ELDERLY; they may be more sensitive to its effects, especially constipation, trouble urinating, dry mouth, drowsiness, agitation, confusion, excitability, or memory problems.

Caution is advised when using Hyoscyamine Controlled-Release Tablets in CHILDREN; they may be more sensitive to its effects, including excitability.

Hyoscyamine Controlled-Release Tablets should be used with extreme caution in CHILDREN younger than 2 years old; safety and effectiveness in these children have not been confirmed.

PREGNANCY and BREAST-FEEDING: It is not known if Hyoscyamine Controlled-Release Tablets can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Hyoscyamine Controlled-Release Tablets while you are pregnant. Hyoscyamine Controlled-Release Tablets are found in breast milk. If you are or will be breast-feeding while taking Hyoscyamine Controlled-Release Tablets, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Hyoscyamine Controlled-Release Tablets:

All medicines may cause side effects, but many people have no, or minor side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Bloated feeling; blurred vision; constipation; decreased sweating; dizziness; drowsiness; dry mouth; enlarged pupils; excitability; headache; nausea; nervousness; trouble sleeping; weakness.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); agitation; behavior changes; confusion; decreased sexual ability; diarrhea; difficulty focusing eyes; disorientation; exaggerated sense of well-being; fast or irregular heartbeat; hallucinations; loss of consciousness; loss of coordination; memory loss; mental or mood changes; severe or persistent trouble sleeping; speech changes; taste changes or loss; trouble urinating; unusual tiredness or weakness; vision changes; vomiting.

See also: Hyoscyamine side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include disorientation; excessive thirst or excitability; fever; hot, dry skin; seizures; severe dry mouth; severe or persistent blurred vision, dizziness, headache, nausea, or vomiting; trouble breathing or swallowing.

Proper storage of Hyoscyamine Controlled-Release Tablets:

Store Hyoscyamine Controlled-Release Tablets at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Hyoscyamine Controlled-Release Tablets out of the reach of children and away from pets.

General information:

If you have any questions about Hyoscyamine Controlled-Release Tablets, please talk with your doctor, pharmacist, or other health care provider.

Hyoscyamine Controlled-Release Tablets are to be used only by the patient for whom it is prescribed. Do not share it with other people.

If your symptoms do not improve or if they become worse, check with your doctor.

Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Hyoscyamine Controlled-Release Tablets. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Hyoscyamine resources

Hyoscyamine Side Effects (in more detail)
Hyoscyamine Use in Pregnancy & Breastfeeding
Drug Images
Hyoscyamine Drug Interactions
Hyoscyamine Support Group
20 Reviews for Hyoscyamine - Add your own review/rating

Compare Hyoscyamine with other medications

Anesthesia
Crohn's Disease
Endoscopy or Radiology Premedication
Irritable Bowel Syndrome
Urinary Incontinence

Wednesday, June 6, 2012

Nasex-G

Generic Name: guaifenesin and phenylephrine (gwye FEN e sin and FEN il EFF rin)

Brand Names: Aldex G, Aquatab D, Crantex, D-Phen 1000, D-Tab, Deconex, Deconsal II, Deconsal Pediatric, Despec, Donatussin Drops, Duomax, Duraphen 1000, Duraphen II, Duratuss, Dynex LA, ExeTuss, Extendryl G, Fenesin PE IR, Genexa LA, Gentex LA, Gilphex TR, Guaiphen-D 1200, Guaiphen-D 600, Guaiphen-PD, Guiadex PD, Guiatex PE, J-Max, Liquibid D-R, Liquibid-D, Liquibid-PD, Lusonex, Maxiphen, Medent-PE, MontePhen, Mucinex Children's Cold, Mucus Relief Sinus, Mydex, Nariz, Nasex, Nescon-PD, Nexphen PD, Norel EX, PE-Guai, Pendex, Prolex D, Refenesen PE, Reluri, Rescon-GG, Respa-PE, Robitussin Head & Chest Congestion, Simuc, Simuc-GP, Sina-12X, Sinupan, SINUvent PE, Sitrex PD, Sudafed PE Non-Drying Sinus, Sudex, Triaminic Chest & Nasal Congestion, Visonex, Wellbid-D, Xedec, Xedec II, Xpect-PE, Zotex GPX

What is Nasex-G (guaifenesin and phenylephrine)?

There are many brands and forms of guaifenesin and phenylephrine available and not all brands are listed on this leaflet.

Guaifenesin is an expectorant. It helps loosen congestion in your chest and throat, making it easier to cough out through your mouth.

Phenylephrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of guaifenesin and phenylephrine is used to treat stuffy nose and sinus congestion, and to reduce chest congestion caused by the common cold or flu.

Guaifenesin and phenylephrine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Nasex-G (guaifenesin and phenylephrine)?

There are many brands and forms of guaifenesin and phenylephrine available and not all brands are listed on this leaflet.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Ask a doctor or pharmacist before using any other cough, cold, or allergy medicine. Guaifenesin and phenylephrine are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains guaifenesin or phenylephrine.

What should I discuss with my healthcare provider before taking Nasex-G (guaifenesin and phenylephrine)?

You should not use this medication if you are allergic to guaifenesin or phenylephrine, or to other decongestants, diet pills, stimulants, or ADHD medications. Do not use guaifenesin and phenylephrine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. Serious, life threatening side effects can occur if you use guaifenesin and phenylephrine before the MAO inhibitor has cleared from your body.

Ask a doctor or pharmacist if it is safe for you to take this medication if you have:

heart disease or high blood pressure;

diabetes;

circulation problems;

glaucoma;

overactive thyroid; or

enlarged prostate or problems with urination.

It is not known if this medication may be harmful to an unborn baby. Do not use this medication without your doctor's advice if you are pregnant. This medication passes into breast milk and could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Artificially-sweetened liquid forms of cold medicine may contain phenylalanine. This would be important to know if you have phenylketonuria (PKU). Check the ingredients and warnings on the medication label if you are concerned about phenylalanine.

How should I take Nasex-G (guaifenesin and phenylephrine)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving cough or cold medicine to a child. Death can occur from the misuse of cough or cold medicine in very young children.

Measure the liquid form of this medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not crush, chew, break, or open an extended-release tablet or capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time. Take guaifenesin and phenylephrine with food if it upsets your stomach. Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash. Drink extra fluids to help loosen the congestion and lubricate your throat while you are taking this medication. Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Since cough or cold medicine is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include nausea, vomiting, numbness or tingly feeling, dizziness, and feeling restless or nervous.

What should I avoid while taking Nasex-G (guaifenesin and phenylephrine)?

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of guaifenesin and phenylephrine. Ask a doctor or pharmacist before using any other cough, cold, or allergy medicine. Guaifenesin and phenylephrine are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains guaifenesin or phenylephrine.

Avoid taking this medication with diet pills, caffeine pills, or other stimulants (such as ADHD medications) without your doctor's advice. Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

Nasex-G (guaifenesin and phenylephrine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have any of these serious side effects:

fast, pounding, or uneven heartbeat;

severe dizziness, anxiety, restless feeling, or nervousness;

easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms;

dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure); or

nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

vomiting, upset stomach;

warmth, tingling, or redness under your skin;

feeling excited or restless (especially in children);

sleep problems (insomnia);

skin rash or itching;

headache; or

dizziness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Nasex-G (guaifenesin and phenylephrine)?

Ask a doctor or pharmacist if it is safe for you to take guaifenesin and phenylephrine if you are also using any of the following drugs:

medicines to treat high blood pressure;

a beta-blocker such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Dutoprol, Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others; or

an antidepressant such as amitriptyline (Elavil, Vanatrip, Limbitrol), doxepin (Sinequan, Silenor), desipramine (Norpramin), imipramine (Janimine, Tofranil), nortriptyline (Pamelor), and others.

This list is not complete and other drugs may interact with guaifenesin and phenylephrine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Nasex-G resources

Nasex-G Side Effects (in more detail)
Nasex-G Use in Pregnancy & Breastfeeding
Nasex-G Drug Interactions
Nasex-G Support Group
0 Reviews for Nasex-G - Add your own review/rating

Crantex Prescribing Information (FDA)

Despec Drops MedFacts Consumer Leaflet (Wolters Kluwer)

Entex LA Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Gentex LA Sustained-Release Tablets (12 Hour) MedFacts Consumer Leaflet (Wolters Kluwer)

Guiatex PE Prescribing Information (FDA)

Lusonex Controlled-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Rescon-GG Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

Sina-12X Suspension MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Nasex-G with other medications

Cough and Nasal Congestion
Sinus Symptoms

Where can I get more information?

Your pharmacist can provide more information about guaifenesin and phenylephrine.

See also: Nasex-G side effects (in more detail)

Saturday, June 2, 2012

Pyrantel Chewable Tablets

Pronunciation: pi-RAN-tel
Generic Name: Pyrantel
Brand Name: Pin-X

Pyrantel Chewable Tablets are used for:

Treating pinworm infections.

Pyrantel Chewable Tablets are an anthelmintic agent. It works by paralyzing the nervous system of intestinal parasites (worms). The parasite is then passed in the stool.

Do NOT use Pyrantel Chewable Tablets if:

you are allergic to any ingredient in Pyrantel Chewable Tablets

Contact your doctor or health care provider right away if any of these apply to you.

Before using Pyrantel Chewable Tablets:

Some medical conditions may interact with Pyrantel Chewable Tablets. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have worms other than pinworms

if others in your home also have pinworms

if you have liver problems or phenylketonuria

if you weigh less than 24 lbs (11 kg)

Some MEDICINES MAY INTERACT with Pyrantel Chewable Tablets. However, no specific interactions with Pyrantel Chewable Tablets are known at this time.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Pyrantel Chewable Tablets may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Pyrantel Chewable Tablets:

Use Pyrantel Chewable Tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Pyrantel Chewable Tablets may be taken alone, with milk or juice, or with a meal.

Chew thoroughly before swallowing.

Wear tight underwear both during the day and night while taking Pyrantel Chewable Tablets.

Only one dose of Pyrantel Chewable Tablets are required. If you forget to take it, take it as soon as you remember.

Ask your health care provider any questions you may have about how to use Pyrantel Chewable Tablets.

Important safety information:

Pyrantel Chewable Tablets may cause dizziness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Pyrantel Chewable Tablets. Using Pyrantel Chewable Tablets alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.

This infection spreads easily to family members and close contacts. To prevent reinfection: Disinfect toilets and change and wash underwear, bed linens, towels, clothes, and pajamas daily. Wash your hands with soap often during the day, especially before eating and after using the toilet. Do not scratch the infected area or place your fingers in your mouth.

The entire household should be treated with Pyrantel Chewable Tablets if one individual in the household has pinworms.

After treatment with Pyrantel Chewable Tablets, clean the bedroom floor by vacuuming or damp mopping.

If any worms other than pinworms are present or if symptoms persist after treatment with Pyrantel Chewable Tablets, contact your doctor.

Phenylketonuria patients - Pyrantel Chewable Tablets contains phenylalanine.

Use Pyrantel Chewable Tablets with extreme caution in CHILDREN younger than 2 years of age. Safety and effectiveness in this age group have not been confirmed.

PREGNANCY and BREAST-FEEDING: If you become pregnant while taking Pyrantel Chewable Tablets, discuss with your doctor the benefits and risks of using Pyrantel Chewable Tablets during pregnancy. It is unknown if Pyrantel Chewable Tablets are excreted in breast milk. If you are or will be breast-feeding while you are using Pyrantel Chewable Tablets, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Pyrantel Chewable Tablets:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Diarrhea; dizziness; headache; nausea; stomach cramps; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue).

See also: Pyrantel side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Pyrantel Chewable Tablets:

Store Pyrantel Chewable Tablets at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Pyrantel Chewable Tablets out of the reach of children and away from pets.

General information:

If you have any questions about Pyrantel Chewable Tablets, please talk with your doctor, pharmacist, or other health care provider.

Pyrantel Chewable Tablets are to be used only by the patient for whom it is prescribed. Do not share it with other people.

If your symptoms do not improve or if they become worse, check with your doctor.

Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Pyrantel Chewable Tablets. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Pyrantel resources

Pyrantel Side Effects (in more detail)
Pyrantel Use in Pregnancy & Breastfeeding
Pyrantel Drug Interactions
Pyrantel Support Group
0 Reviews for Pyrantel - Add your own review/rating

Compare Pyrantel with other medications

Ascariasis
Enterobiasis
Hookworm Infection, Necator or Ancylostoma
Moniliformis Infection
Pinworm Infection, Enterobius vermicularis
Trichostrongylosis

Friday, June 1, 2012

Neorecormon Solution for Injection in Pre-Filled Syringe

1. Name Of The Medicinal Product

NeoRecormon solution for injection in pre-filled syringe

2. Qualitative And Quantitative Composition

One pre-filled syringe with 0.3 ml solution for injection contains 500 international units (IU) corresponding to 4.15 micrograms epoetin beta* (recombinant human erythropoietin).

One ml solution for injection contains 1667 IU epoetin beta.

One pre-filled syringe with 0.3 ml solution for injection contains 3000 international units (IU) corresponding to 24.9 micrograms epoetin beta* (recombinant human erythropoietin).

One ml solution for injection contains 10,000 IU epoetin beta.

One pre-filled syringe with 0.3 ml solution for injection contains 4000 international units (IU) corresponding to 33.2 micrograms epoetin beta* (recombinant human erythropoietin).

One ml solution for injection contains 13,333 IU epoetin beta.

One pre-filled syringe with 0.3 ml solution for injection contains 5000 international units (IU) corresponding to 41.5 micrograms epoetin beta* (recombinant human erythropoietin).

One ml solution for injection contains 16,667 IU epoetin beta.

One pre-filled syringe with 0.3 ml solution for injection contains 6000 international units (IU) corresponding to 49.8 micrograms epoetin beta* (recombinant human erythropoietin).

One ml solution for injection contains 20,000 IU epoetin beta.

One pre-filled syringe with 0.6 ml solution for injection contains 10,000 international units (IU) corresponding to 83 micrograms epoetin beta* (recombinant human erythropoietin).

One ml solution for injection contains 16,667 IU epoetin beta.

One pre-filled syringe with 0.6 ml solution for injection contains 20,000 international units (IU) corresponding to 166 micrograms epoetin beta* (recombinant human erythropoietin).

One ml solution for injection contains 33,333 IU epoetin beta.

One pre-filled syringe with 0.6 ml solution for injection contains 30,000 international units (IU) corresponding to 250 micrograms epoetin beta* (recombinant human erythropoietin).

One ml solution for injection contains 50,000 IU epoetin beta.

* produced in Chinese Hamster Ovary cells (CHO) by recombinant DNA technology

Excipients:

Phenylalanine (up to 0.3 mg/syringe)

Sodium (less than 1 mmol/syringe)

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Solution for injection.

Colourless, clear to slightly opalescent solution.

4. Clinical Particulars

4.1 Therapeutic Indications

- Treatment of symptomatic anaemia associated with chronic renal failure (CRF) in adult and paediatric patients.

- Prevention of anaemia of prematurity in infants with a birth weight of 750 to 1500 g and a gestational age of less than 34 weeks.

- Treatment of symptomatic anaemia in adult patients with non-myeloid malignancies receiving chemotherapy.

- Increasing the yield of autologous blood from patients in a pre-donation programme.

Its use in this indication must be balanced against the reported increased risk of thromboembolic events. Treatment should only be given to patients with moderate anaemia (Hb 10 - 13 g/dl [6.21 - 8.07 mmol/l], no iron deficiency) if blood conserving procedures are not available or insufficient when the scheduled major elective surgery requires a large volume of blood (4 or more units of blood for females or 5 or more units for males).

4.2 Posology And Method Of Administration

Therapy with NeoRecormon should be initiated by physicians experienced in the above mentioned indications. As anaphylactoid reactions were observed in isolated cases, it is recommended that the first dose be administered under medical supervision.

The NeoRecormon pre-filled syringe is ready for use. Only solutions which are clear or slightly opalescent, colourless and practically free of visible particles may be injected.

NeoRecormon in pre-filled syringe is a sterile but unpreserved product. Under no circumstances should more than one dose be administered per syringe; the medicinal product is for single use only.

Treatment of symptomatic anaemia in adult and paediatric chronic renal failure patients:

Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician's evaluation of the individual patient's clinical course and condition is necessary. NeoRecormon should be administered either subcutaneously or intravenously in order to increase haemoglobin to not greater than 12 g/dl (7.5 mmol/l). Subcutaneous use is preferable in patients who are not receiving haemodialysis to avoid puncture of peripheral veins. In case of intravenous administration, the solution should be injected over approx. 2 minutes, e.g. in haemodialysis patients via the arterio-venous fistula at the end of dialysis.

Due to intra-patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/dl (6.2 mmol/l) to 12 g/dl (7.5 mmol/l). A sustained haemoglobin level of greater than 12 g/dl (7.5 mmol/l) should be avoided; guidance for appropriate dose adjustment for when haemoglobin values exceeding 12 g/dl (7.5 mmol/l) are observed are described below.

A rise in haemoglobin of greater than 2 g/dl (1.25 mmol/l) over a four week period should be avoided. If it occurs, appropriate dose adjustment should be made as provided. If the rate of rise in haemoglobin is greater than 2 g/dl (1.25 mmol/l) in one month or if the haemoglobin level is increasing and approaching 12 g/dl (7.45 mmol/l), the dose is to be reduced by approximately 25%. If the haemoglobin level continues to increase, therapy should be interrupted until the haemoglobin level begins to decrease, at which point therapy should be restarted at a dose approximately 25% below the previously administered dose.

Patients should be monitored closely to ensure that the lowest approved dose of NeoRecormon is used to provide adequate control of the symptoms of anaemia.

In the presence of hypertension or existing cardiovascular, cerebrovascular or peripheral vascular diseases, the weekly increase in Hb and the target Hb should be determined individually taking into account the clinical picture.

Treatment with NeoRecormon is divided into two stages.

1. Correction phase

- Subcutaneous administration:

The initial dosage is 3 x 20 IU/kg body weight per week. The dosage may be increased every 4 weeks by 3 x 20 IU/kg and week if the increase of Hb is not adequate (< 0.25 g/dl per week).

The weekly dose can also be divided into daily doses.

- Intravenous administration:

The initial dosage is 3 x 40 IU/kg per week. The dosage may be raised after 4 weeks to 80 IU/kg - three times per week - and by further increments of 20 IU/kg if needed, three times per week, at monthly intervals.

For both routes of administration, the maximum dose should not exceed 720 IU/kg per week.

2. Maintenance phase

To maintain an Hb of between 10 and 12 g/dl, the dosage is initially reduced to half of the previously administered amount. Subsequently, the dose is adjusted at intervals of one or two weeks individually for the patient (maintenance dose).

In the case of subcutaneous administration, the weekly dose can be given as one injection per week or in divided doses three or seven times per week. Patients who are stable on a once weekly dosing regimen may be switched to once every two weeks administration. In this case dose increases may be necessary.

Results of clinical studies in children have shown that, on average, the younger the patients, the higher the NeoRecormon doses required. Nevertheless, the recommended dosing schedule should be followed as the individual response cannot be predicted.

Treatment with NeoRecormon is normally a long-term therapy. It can, however, be interrupted, if necessary, at any time. Data on the once weekly dosing schedule are based on clinical studies with a treatment duration of 24 weeks.

Prevention of anaemia of prematurity:

The solution is administered subcutaneously at a dose of 3 x 250 IU/kg b.w. per week. Treatment with NeoRecormon should start as early as possible, preferably by day 3 of life. Premature infants who have already been transfused by the start of treatment with NeoRecormon are not likely to benefit as much as untransfused infants. The treatment should last for 6 weeks.

Treatment of symptomatic chemotherapy-induced anaemia in cancer patients:

NeoRecormon should be administered by the subcutaneous route to patients with anaemia (e.g. haemoglobin concentration

The weekly dose can be given as one injection per week or in divided doses 3 to 7 times per week.

The recommended initial dose is 30,000 IU per week (corresponding to approximately 450 IU/kg body weight per week, based on an average weighted patient).

If, after 4 weeks of therapy, the haemoglobin value has increased by at least 1 g/dl (0.62 mmol/l), the current dose should be continued. If the haemoglobin value has not increased by at least 1 g/dl (0.62 mmol/l), a doubling of the weekly dose should be considered. If, after 8 weeks of therapy, the haemoglobin value has not increased by at least 1 g/dl (0.62 mmol/l), response is unlikely and treatment should be discontinued.

The therapy should be continued up to 4 weeks after the end of chemotherapy.

The maximum dose should not exceed 60,000 IU per week.

Once the therapeutic objective for an individual patient has been achieved, the dose should be reduced by 25 to 50 % in order to maintain haemoglobin at that level. Appropriate dose titration should be considered.

If the haemoglobin exceeds 12 g/dl (7.5 mmol/l), the dose should be reduced by approximately 25 to 50 %. Treatment with NeoRecormon should be temporarily discontinued if haemoglobin levels exceed 13 g/dl (8.1 mmol/l). Therapy should be reinitiated at approximately 25 % lower than the previous dose after haemoglobin levels fall to 12 g/dl (7.5 mmol/l) or below.

If the rise in haemoglobin is greater than 2 g/dl (1.3 mmol/l) in 4 weeks, the dose should be reduced by 25 to 50 %.

Patients should be monitored closely to ensure that the lowest approved dose of NeoRecormon is used to provide adequate control of the symptoms of anaemia.

Treatment for increasing the amount of autologous blood:

The solution is administered intravenously over approx. 2 minutes or subcutaneously.

NeoRecormon is administered twice weekly over 4 weeks. On those occasions where the patient's PCV allows blood donation, i.e. PCV

During the entire treatment period, a PCV of 48 % should not be exceeded.

The dosage must be determined by the surgical team individually for each patient as a function of the required amount of pre-donated blood and the endogenous red cell reserve:

1. The required amount of pre-donated blood depends on the anticipated blood loss, use of blood conserving procedures and the physical condition of the patient.

This amount should be that quantity which is expected to be sufficient to avoid homologous blood transfusions.

The required amount of pre-donated blood is expressed in units whereby one unit in the nomogram is equivalent to 180 ml red cells.

2. The ability to donate blood depends predominantly on the patient's blood volume and baseline PCV. Both variables determine the endogenous red cell reserve, which can be calculated according to the following formula.

Endogenous red cell reserve = blood volume [ml] x (PCV - 33) ÷ 100

Women: blood volume [ml] = 41 [ml/kg] x body weight [kg] + 1200 [ml]

Men: blood volume [ml] = 44 [ml/kg] x body weight [kg] + 1600 [ml] (body weight

The indication for treatment with NeoRecormon and, if given, the single dose should be determined from the required amount of pre-donated blood and the endogenous red cell reserve according to the following graphs.

The single dose thus determined is administered twice weekly over 4 weeks. The maximum dose should not exceed 1600 IU/kg body weight per week for intravenous or 1200 IU/kg per week for subcutaneous administration.

4.3 Contraindications

Hypersensitivity to the active substance or any of the excipients.

Poorly controlled hypertension.

In the indication "increasing the yield of autologous blood": myocardial infarction or stroke in the month preceding treatment, unstable angina pectoris, increased risk of deep venous thrombosis such as history of venous thromboembolic disease.

4.4 Special Warnings And Precautions For Use

NeoRecormon should be used with caution in the presence of refractory anaemia with excess blasts in transformation, epilepsy, thrombocytosis, and chronic liver failure. Folic acid and vitamin B₁₂ deficiencies should be ruled out as they reduce the effectiveness of NeoRecormon.

In order to ensure effective erythropoiesis, iron status should be evaluated for all patients prior to and during treatment and supplementary iron therapy may be necessary and conducted in accordance with therapeutic guidelines.

Severe aluminium overload due to treatment of renal failure may compromise the effectiveness of NeoRecormon.

The indication for treatment with NeoRecormon of nephrosclerotic patients not yet undergoing dialysis should be defined individually, as a possible acceleration of progression of renal failure cannot be ruled out with certainty.

Pure red cell aplasia caused by neutralising anti-erythropoietin antibodies has been reported in association with erythropoietin therapy, including NeoRecormon. These antibodies have been shown to cross-react with all erythropoietic proteins, and patients suspected or confirmed to have neutralising antibodies to erythropoietin should not be switched to NeoRecormon (see section 4.8).

A paradoxical decrease in haemoglobin and development of severe anaemia associated with low reticulocyte counts should prompt to discontinue treatment with epoetin and perform anti-erythropoietin antibody testing. Cases have been reported in patients with hepatitis C treated with interferon and ribavirin, when epoetins are used concomitantly. Epoetins are not approved in the management of anaemia associated with hepatitis C.

In chronic renal failure patients an increase in blood pressure or aggravation of existing hypertension, especially in cases of rapid PCV increase can occur. These increases in blood pressure can be treated with medicinal products. If blood pressure rises cannot be controlled by drug therapy, a transient interruption of NeoRecormon therapy is recommended. Particularly at beginning of therapy, regular monitoring of the blood pressure is recommended, including between dialyses. Hypertensive crisis with encephalopathy-like symptoms may occur and require the immediate attention of a physician and intensive medical care. Particular attention should be paid to sudden stabbing migraine like headaches as a possible warning sign.

In chronic renal failure patients there may be a moderate dose-dependent rise in the platelet count within the normal range during treatment with NeoRecormon, especially after intravenous administration. This regresses during the course of continued therapy. It is recommended that the platelet count be monitored regularly during the first 8 weeks of therapy.

Haemoglobin concentration

In patients with chronic renal failure, maintenance haemoglobin concentration should not exceed the upper limit of the target haemoglobin concentration recommended in section 4.2. In clinical trials, an increased risk of death and serious cardiovascular events or cerebrovascular events including stroke was observed when erythropoiesis stimulating agents (ESAs) were administered to target a haemoglobin of greater than 12 g/dl (7.5 mmol/l).

Controlled clinical trials have not shown significant benefits attributable to the administration of epoetins when haemoglobin concentration is increased beyond the level necessary to control symptoms of anaemia and to avoid blood transfusion.

In premature infants there may be a slight rise in platelet counts, particularly up to day 12 - 14 of life, therefore platelets should be monitored regularly.

Effect on tumour growth

Epoetins are growth factors that primarily stimulate red blood cell production. Erythropoietin receptors may be expressed on the surface of a variety of tumour cells. As with all growth factors, there is a concern that epoetins could stimulate the growth of tumours. In several controlled studies, epoetins have not been shown to improve overall survival or decrease the risk of tumour progression in patients with anaemia associated with cancer.

In controlled clinical studies, use of NeoRecormon and other erythropoiesis-stimulating agents (ESAs) have shown:

- shortened time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target a haemoglobin of greater than 14 g/dl (8.7 mmol/l),

- shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target a haemoglobin of 12-14 g/dl (7.5-8.7 mmol/l),

- increased risk of death when administered to target a haemoglobin of 12 g/dl (7.5 mmol/l) in patients with active malignant disease receiving neither chemotherapy nor radiation therapy. ESAs are not indicated for use in this patient population.

In view of the above, in some clinical situations blood transfusion should be the preferred treatment for the management of anaemia in patients with cancer. The decision to administer recombinant erythropoietins should be based on a benefit-risk assessment with the participation of the individual patient, which should take into account the specific clinical context. Factors that should be considered in this assessment should include the type of tumour and its stage; the degree of anaemia; life-expectancy; the environment in which the patient is being treated; and patient preference (see section 5.1)

There may be an increase in blood pressure which can be treated with drugs. It is therefore recommended to monitor blood pressure, in particular in the initial treatment phase in cancer patients.

Platelet counts and haemoglobin level should also be monitored at regular intervals in cancer patients.

In patients in an autologous blood predonation programme there may be an increase in platelet count, mostly within the normal range. Therefore, it is recommended that the platelet count be determined at least once a week in these patients. If there is an increase in platelets of more than 150 x 10⁹/l or if platelets rise above the normal range, treatment with NeoRecormon should be discontinued.

In chronic renal failure patients an increase in heparin dose during haemodialysis is frequently required during the course of therapy with NeoRecormon as a result of the increased packed cell volume. Occlusion of the dialysis system is possible if heparinisation is not optimum.

Early shunt revision and thrombosis prophylaxis by administration of acetylsalicylic acid, for example, should be considered in chronic renal failure patients at risk of shunt thrombosis.

Serum potassium and phosphate levels should be monitored regularly during therapy with NeoRecormon. Potassium elevation has been reported in a few uraemic patients receiving NeoRecormon, though causality has not been established. If an elevated or rising potassium level is observed then consideration should be given to ceasing administration of NeoRecormon until the level has been corrected.

For use of NeoRecormon in an autologous predonation programme, the official guidelines on principles of blood donation must be considered, in particular:

- only patients with a PCV

- special care should be taken with patients below 50 kg weight;

- the single volume drawn should not exceed approx. 12 % of the patient's estimated blood volume.

Treatment should be reserved for patients in whom it is considered of particular importance to avoid homologous blood transfusion taking into consideration the risk/benefit assessment for homologous transfusions.

Misuse by healthy persons may lead to an excessive increase in packed cell volume. This may be associated with life-threatening complications of the cardiovascular system.

NeoRecormon in pre-filled syringe contains up to 0.3 mg phenylalanine/syringe as an excipient. Therefore this should be taken into consideration in patients affected with severe forms of phenylketonuria.

This medicinal product contains less than 1 mmol sodium (23 mg) per syringe, i.e. essentially “sodium-free”.

In order to improve the traceability of ESAs, the name of the prescribed ESA should be clearly recorded (or: stated) in the patient file.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The clinical results obtained so far do not indicate any interaction of NeoRecormon with other medicinal products.

Animal experiments revealed that epoetin beta does not increase the myelotoxicity of cytostatic medicinal products like etoposide, cisplatin, cyclophosphamide, and fluorouracil.

4.6 Pregnancy And Lactation

For epoetin beta no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see 5.3).

Caution should be exercised when prescribing to pregnant women.

4.7 Effects On Ability To Drive And Use Machines

NeoRecormon has no influence on the ability to drive and use machines.

4.8 Undesirable Effects

Based on results from clinical trials including 1725 patients approximately 8 % of patients treated with NeoRecormon are expected to experience adverse reactions.

- Anaemic patients with chronic renal failure

The most frequent adverse reaction during treatment with NeoRecormon is an increase in blood pressure or aggravation of existing hypertension, especially in cases of rapid PCV increase (see section 4.4). Hypertensive crisis with encephalopathy-like symptoms (e.g. headaches and confused state, sensorimotor disorders - such as speech disturbance or impaired gait - up to tonoclonic seizures) may also occur in individual patients with otherwise normal or low blood pressure (see section 4.4).

Shunt thromboses may occur, especially in patients who have a tendency to hypotension or whose arteriovenous fistulae exhibit complications (e.g. stenoses, aneurisms), see section 4.4. In most cases, a fall in serum ferritin values simultaneous with a rise in packed cell volume is observed (see section 4.4). In addition, transient increases in serum potassium and phosphate levels have been observed in isolated cases (see section 4.4).

In isolated cases, neutralising anti erythropoietin antibody-mediated pure red cell aplasia (PRCA) associated with NeoRecormon therapy has been reported. In case anti-erythropoietin antibody-mediated PRCA is diagnosed, therapy with NeoRecormon must be discontinued and patients should not be switched to another erythropoietic protein (see section 4.4).

The incidences of undesirable effects in clinical trials, considered related to treatment with NeoRecoromon are shown in the table below. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System Organ Class	Adverse Drug Reaction	Incidence
Vascular disorders	Hypertensive crisis Hypertension	Uncommon (>0.1%, <1%) Common (>1%, <10%)
Nervous system disorders	Headache	Common (>1%, <10%)
Blood and the lymphatic system disorders	Shunt thrombosis Thrombocytosis	Rare (>0.01%, <0.1%) Very rare (<0.01%)

- Patients with cancer

Epoetin beta treatment-related headache and hypertension which can be treated with drugs are common (>1%, <10%) (see section 4.4).

In some patients, a fall in serum iron parameters is observed (see section 4.4).

Clinical studies have shown a higher frequency of thromboembolic events in cancer patients treated with NeoRecormon compared to untreated controls or placebo. In patients treated with NeoRecormon, this incidence is 7 % compared to 4 % in controls; this is not associated with any increase in thromboembolic mortality compared with controls.

System Organ Class	Adverse Drug Reaction	Incidence
Vascular disorders	Hypertension	Common (>1%, <10%)
Blood and the lymphatic system disorders	Thromboembolic event	Common (>1%, <10%)
Nervous system disorders	Headache	Common (>1%, <10%)

- Patients in an autologous blood predonation programme

Patients in an autologous blood predonation programme have been reported to show a slightly higher frequency of thromboembolic events. However, a causal relationship with treatment with NeoRecormon could not be established.

In placebo controlled trials temporary iron deficiency was more pronounced in patients treated with NeoRecormon than in controls (see section 4.4).

System Organ Class	Adverse Drug Reaction	Incidence
Nervous system disorders	Headache	Common (>1%, <10%)

- Premature infants

A fall in serum ferritin values is very common (>10%) (see section 4.4).

- All indications

Rarely (

In very rare cases (

Data from a controlled clinical trial with epoetin alfa or darbepoetin alfa, reported an incidence of stroke as common (

4.9 Overdose

The therapeutic margin of NeoRecormon is very wide. Even at very high serum levels no symptoms of poisoning have been observed.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: antianaemic, ATC code: B03XA

Epoetin beta is identical in its amino acid and carbohydrate composition to erythropoietin that has been isolated from the urine of anaemic patients.

Erythropoietin is a glycoprotein that stimulates the formation of erythrocytes from its committed progenitors. It acts as a mitosis stimulating factor and differentiation hormone.

The biological efficacy of epoetin beta has been demonstrated after intravenous and subcutaneous administration in various animal models in vivo (normal and uraemic rats, polycythaemic mice, dogs). After administration of epoetin beta, the number of erythrocytes, the Hb values and reticulocyte counts increase as well as the ⁵⁹Fe-incorporation rate.

An increased ³H-thymidine incorporation in the erythroid nucleated spleen cells has been found in vitro (mouse spleen cell culture) after incubation with epoetin beta.

Investigations in cell cultures of human bone marrow cells showed that epoetin beta stimulates erythropoiesis specifically and does not affect leucopoiesis. Cytotoxic actions of epoetin beta on bone marrow or on human skin cells were not detected.

After single dose administration of epoetin beta no effects on behaviour or locomotor activity of mice and circulatory or respiratory function of dogs were observed.

In a randomised, double-blind, placebo-controlled study of 4,038 CRF patients not on dialysis with type 2 diabetes and haemoglobin levels

Erythropoietin is a growth factor that primarily stimulates red cell production. Erythropoietin receptors may be expressed on the surface of a variety of tumour cells.

Survival and tumour progression have been examined in five large controlled studies involving a total of 2833 patients, of which four were double-blind placebo-controlled studies and one was an open-label study. Two of the studies recruited patients who were being treated with chemotherapy. The target haemoglobin concentration in two studies was >13 g/dl; in the remaining three studies it was 12-14 g/dl. In the open-label study there was no difference in overall survival between patients treated with recombinant human erythropoietin and controls. In the four placebo-controlled studies the hazard ratios for overall survival ranged between 1.25 and 2.47 in favour of controls. These studies have shown a consistent unexplained statistically significant excess mortality in patients who have anaemia associated with various common cancers who received recombinant human erythropoietin compared to controls. Overall survival outcome in the trials could not be satisfactorily explained by differences in the incidence of thrombosis and related complications between those given recombinant human erythropoietin and those in the control group.

An individual patient data based meta-analysis, which included data from all 12 controlled clinical studies in anaemic cancer patients conducted with NeoRecormon (n=2301), showed an overall hazard ratio point estimate for survival of 1.13 in favour of controls (95 % CI 0.87, 1.46). In patients with baseline haemoglobin

A patient-level data analysis has also been performed on more than 13,900 cancer patients (chemo-, radio-, chemoradio- or no therapy) participating in 53 controlled clinical trials involving several epoetins. Meta-analysis of overall survival data produced a hazard ratio point estimate of 1.06 in favour of controls (95% CI: 1.00, 1.12; 53 trials and 13,933 patients) and for cancer patients receiving chemotherapy, the overall survival hazard ratio was 1.04 (95% CI: 0.97, 1.11; 38 trials and 10, 441 patients). Meta-analyses also indicate consistently a significantly increased relative risk of thromboembolic events in cancer patients receiving recombinant human erythropoietin (see Section 4.4).

In very rare cases, neutralising anti-erythropoietin antibodies with or without pure red cell aplasia (PRCA) occurred during rHuEPO therapy.

5.2 Pharmacokinetic Properties

Pharmacokinetic investigations in healthy volunteers and uraemic patients show that the half-life of intravenously administered epoetin beta is between 4 and 12 hours and that the distribution volume corresponds to one to two times the plasma volume. Analogous results have been found in animal experiments in uraemic and normal rats.

After subcutaneous administration of epoetin beta to uraemic patients, the protracted absorption results in a serum concentration plateau, whereby the maximum concentration is reached after an average of 12 - 28 hours. The terminal half-life is higher than after intravenous administration, with an average of 13 - 28 hours.

Bioavailability of epoetin beta after subcutaneous administration is between 23 and 42 % as compared with intravenous administration.

5.3 Preclinical Safety Data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and toxicity to reproduction.

A carcinogenicity study with homologous erythropoietin in mice did not reveal any signs of proliferative or tumourigenic potential.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Urea,

Sodium chloride,

Polysorbate 20,

Sodium dihydrogen phosphate dihydrate,

Disodium phosphate dodecahydrate,

Calcium chloride dihydrate,

Glycine,

L-Leucine,

L-Isoleucine,

L-Threonine,

L-Glutamic acid,

L-Phenylalanine,

Water for injections.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product should not be mixed with other medicinal products.

6.3 Shelf Life

2 years.

6.4 Special Precautions For Storage

Store in a refrigerator (2°C – 8°C).

Keep the pre-filled syringe in the outer carton, in order to protect from light.

For the purpose of ambulatory use, the patient may remove the product from the refrigerator and store it at room temperature (not above 25°C) for one single period of up to 3 days.

6.5 Nature And Contents Of Container

500 IU:

0.3 ml of solution in pre-filled syringe (Type I glass) with a tip cap and a plunger stopper (teflonised rubber) with a needle 30G1/2.

Pack sizes of 1 or 6

2000 IU, 3000 IU, 4000 IU, 5000 IU, 6000 IU:

0.3 ml of solution in pre-filled syringe (Type 1 glass) with a tip cap and a plunger stopper (teflonised rubber) with a needle of 27G1/2.

Pack sizes of 1 or 6

10,000 IU, 20,000IU:

0.6 ml of solution in pre-filled syringe (Type I glass) with a tip cap and a plunger stopper (teflonised rubber) with a needle 27G1/2.

Pack sizes of 1 or 6

30,000IU:

0.6 ml of solution in pre-filled syringe (Type I glass) with a tip cap and a plunger stopper (teflonised rubber) with a needle 27G1/2.

Pack sizes of 1 or 4

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

First wash your hands!

1. Remove one syringe from the pack and check that the solution is clear, colourless and practically free from visible particles. Remove the cap from the syringe.

2. Remove one needle from the pack, fix it on the syringe and remove the protective cap from the needle.

3. Expel air from the syringe and needle by holding the syringe vertically and gently pressing the plunger upwards. Keep pressing the plunger until the amount of NeoRecormon in the syringe is as prescribed.

4. Clean the skin at the site of injection using an alcohol wipe. Form a skin fold by pinching the skin between thumb and forefinger. Hold the syringe barrel near to the needle, and insert the needle into the skin fold with a quick, firm action. Inject the NeoRecormon solution. Withdraw the needle quickly and apply pressure over the injection site with a dry, sterile pad.

This medicinal product is for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.

7. Marketing Authorisation Holder

Roche Registration Limited

6 Falcon Way

Shire Park

Welwyn Garden City

AL7 1TW

United Kingdom

8. Marketing Authorisation Number(S)

NeoRecormon 500 IU solution for injection in pre-filled syringe:

EU/1/97/031/025 - 026

NeoRecormon 2000 IU solution for injection in pre-filled syringe:

EU/1/97/031/029 - 030

NeoRecormon 3000 IU solution for injection in pre-filled syringe:

EU/1/97/031/031 - 032

NeoRecormon 4000 IU solution for injection in pre-filled syringe:

EU/1/97/031/041 - 042

NeoRecormon 5000 IU solution for injection in pre-filled syringe:

EU/1/97/031/033 - 034

NeoRecormon 6000 IU solution for injection in pre-filled syringe:

EU/1/97/031/043 - 044

NeoRecormon 10,000 IU solution for injection in pre-filled syringe:

EU/1/97/031/035 - 036

NeoRecormon 20,000 IU solution for injection in pre-filled syringe:

EU/1/97/031/037 - 038

NeoRecormon 30,000 IU solution for injection in pre-filled syringe:

EU/1/97/031/045 - 046

9. Date Of First Authorisation/Renewal Of The Authorisation

500, 2000, 3000, 5000, 10,000, 20,000 IU:

Date of the first authorisation: 2 April 1998

Date of the last renewal: 16 July 2007

4000, 6000 IU:

Date of the first authorisation: 10 February 2000

Date of the last renewal: 16 July 2007

30,000 IU:

Date of the first authorisation: 23 February 2004

Date of the last renewal: 16 July 2007

10. Date Of Revision Of The Text

6^th October 2011

LEGAL STATUS

POM

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/