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c n h 010270-05 Rx only Rx only Rx only Rx only nasal spray 500 mcg/spray 010270-05 0.125 mL (Cyanocobalamin, USP) nasal spray 500 mcg/spray 0.125 mL nasal spray 500 mcg/spray 010270-05 0.125 mL nasal spray 500 mcg/spray 010270-05 0.125 mL (Cyanocobalamin, USP) Mean Serum Vitamin B 12 Trough Level ± SEM (pg/mL) Rx only Mean Serum Vitamin B 12 Trough Level ± SEM (pg/mL) (Cyanocobalamin, USP) n ) e d f l n e m d l (Cyanocobalamin, USP) a a d h 500 mcg/spray 0.125 mL Mean Serum Vitamin B 12 Trough Level ± SEM (pg/mL) s s s n (Cy Mean S 010270 500 mcg/spray 0.125 mL l r e maintaining sulfhydryl (SH) groups in the reduced form required by many SH-activated enzyme megaloblastic anemia, indiscriminate use of vitamin B12 could mask the true diagnosis. that seen one month after 100 mcg intramuscular dose (Figure). supplementation. systems. Through these reactions, vitamin B12 is associated with fat and carbohydrate metabolism Hypokalemia and thrombocytosis could occur upon conversion of severe megaloblastic to normal Distribution and protein synthesis. Vitamin B12 deficiency results in megaloblastic anemia, GI lesions, and testpotassium (Schilling Test). Nascobal Nasal Spraywith is not suitable vitamin Therefore, B12 absorption serum levels and the platelet count erythropoiesis vitamin B12fortherapy. In the blood, B 12 is bound to transcobalamin II, a specific B-globulin carrier protein, and is neurologic damage that begins with an inability to produce myelin and is followed by gradual should be monitored carefully during therapy. CONTRAINDICATIONS distributed and stored primarily in the liver and bone marrow. degeneration of the axon and nerve head. B or any component of the medication is a contraindication. Sensitivity to cobalt and/or vitamin 12 Elimination Vitamin B12 deficiency may suppress the signs of polycythemia vera. Treatment with vitamin B12 Cyanocobalamin is the most stable and widely used form of vitamin B12, and has hematopoietic may unmask this condition. activity apparently identical to that of the antianemia factor in purified liver extract. The information WARNINGS About 3-8 mcg of B12 is secreted into the GI tract daily via the bile; in normal subjects with sufficient PatientsIf with early Leber’s disease (hereditary optic nerve atrophy) who were treated with below, describing the clinical pharmacology of cyanocobalamin, has been derived from studies with intrinsic factor, all but about 1 mcg is re-absorbed. When B12 is administered in doses which ® a patient is not properly maintained with Nascobal Nasal Spray, intramuscular vitamin vitamin B12 is Figure. Vitaminproteins B 12 Serum Levels After Intramuscular severe swift optic atrophy. B12 suffered injectable vitamin B12. saturate the binding capacity of plasma and Trough the liver, the unbound B12 is rapidly eliminated necessary forand adequate treatment of the patient. No single regimen fits all cases, and the status of Solution (IM) of 100 mcg and Nasal Gel (IN) Administration of in the urine. Retention of B in the body is dose-dependent. About 80-90% of an intramuscular Hypokalemia andobserved sudden death may is occur in severe anemia which is treated Vitamin B12 is quantitatively and rapidly absorbed from intramuscular and subcutaneous sites of 12 the patient in follow-up the final criterionmegaloblastic for adequacy of therapy. 500 mcg Cyanocobalamin After Weekly dose up to 50 mcg is retained in the body; this percentage dropsDoses. to 55% for a 100 mcg dose, and intensely with vitamin B12of . Folic acid is not aSpray substitute for vitamin B12 although it may improve injection. It is bound to plasma proteins and stored in the liver. Vitamin B12 is excreted in the bile effectiveness Nascobal Nasal in patients with nasal congestion, allergic rhinitis and The decreases to 15% when a 1000 mcg dose is given. B12-deficient megaloblastic anemia. Exclusive use ofTherefore, folic acid treatment in treatingwith vitamin B12- Nasal vitaminupper and undergoes some enterohepatic recycling. Absorbed vitamin B12 is transported via specific B12 respiratory infections has not been determined. Nascobal deficient megaloblastic anemia could result in progressive and irreversible neurologic damage. binding proteins, transcobalamin I and II, to the various tissues. The liver is the main organ for Spray should be deferred until symptoms have subsided. vitamin B12occurs storage. Anaphylactic shock and death have been reported after parenteral vitamin B12 administration. No Cyanocobalamin as dark red crystals or orthorhombic needles or crystalline red powder. It is 2. LABORATORY TESTS Pernicious anemia associated with antrials increased incidenceNasal of carcinoma the stomach, such reactions have beenis reported in clinical with Nascobal Spray orofNascobal Nasalbut this reverses megaloblastic Parenteral in (intramuscular) of vitamin B12 completely very the anhydrousadministration form, and sparingly to moderately soluble in waterthe (1:80). Its Rx onlyhygroscopic INDICATIONS AND USAGE and levels should be obtained Hematocrit, vitamin pathology B12, folateand is believed to reticulocyte be related tocount, the underlying notiron to treatment with vitamin B12. prior to Gel. anemia and GI symptoms of vitamin B deficiency; the degree of improvement in neurologic pharmacologic activity is destroyed by heavy metals (iron) and strong oxidizing or reducing agents 12 Nascobal Nasal Spray is indicated for the maintenance of normal hematologic status in pernicious treatment. If folate levels are low, folic acid should also be administered. All hematologic depends on the duration severity of the lesions, although progression of the lesions as infection, Blunted5.orPREGNANCY impeded therapeutic response to vitamin B12 may be due to such conditions (vitaminsymptoms C), but not by autoclaving for shortand periods of time (15-20 minutes) at 121°C. The vitamin anemia patients who are in remission following intramuscular vitamin B12 therapy and who have no ® Nasal Spray. parameters should beC:normal beginning treatment Nascobal Pregnancy Category Animalwhen reproduction studies havewith not been with vitamin B12. It is is immediately arrested. uremia, drugs having bone marrow suppressant properties such asconducted chloramphenicol, and are very unstable in light. B12 coenzymes nervous system involvement. Vitamin B blood levels and peripheral blood counts must be monitored initially atpregnant one month after also not known whether vitamin B can cause fetal harm when administered to a woman concurrent iron or folic acid deficiency. 12 on the presence sufficient intrinsicasfactor Gastrointestinal of vitamin B12 depends USP ® Nasal Sprayabsorption is a solution of Cyanocobalamin, (vitamin B12)offor administration a and Nascobal DESCRIPTION PHARMACOKINETICS intestinal parasites or bacteria. The fish tapeworm IV.or Competition for vitamin B 12 by12 ® Nascobal Nasal Spray is also indicated as a supplement for other vitamin B12 deficiencies, the startaffect of treatment with Nascobal Nasal Spray, then at intervals of 3have to 6 months. can reproduction capacity. Adequate andand well-controlled studies not been done in calcium ions. Intrinsic factor deficiency causes pernicious anemia, which may be associated with spray to the nasal mucosa. Each unit dose device of Nascobal Nasal Spray contains 0.125 mL of a infested patients often (Diphyllobothrium latum) absorbs huge quantities of vitamin B12 and Cyanocobalamin is a synthetic form of vitamin B12 with equivalent vitamin B12 activity. The chemical Absorption PRECAUTIONS including: pregnant women. However, vitamin B is an essential vitamin and requirements are increased Ahave decline in the serum levels of B12The after oneloop month of treatment B12 nasal sprayofmay 12blind of the spinal cord. Prompt parenteral administration of vitamin 500 mcg/0.1 mLcombined solution degeneration of cyanocobalamin withThe sodium citrate, citric acid, glycerin and associated gastric atrophy. syndrome may with produce deficiency vita-indicate name issubacute 5,6-dimethyl-benzimidazolyl cyanocobamide. cobalt content is 4.35%. The molecular 1. GENERAL during Amounts ofadjusted vitamin Bupward. that are recommended the one Food and Nutrition Board, A three way crossover study in 25 fasting healthy subjects was conducted to compare the that dose may of need to be Patients should beby seen month each progression ofwater. neurologic damage. B12 benzalkonium in purified The spray solution has a pHweight between and 5.5. or folate. minthe Bpregnancy. recommended before Nascobal Nasal after Spray is dose An intradermal dose parenteral vitamin B1212 isResearch H88CoN corresponds to a molecular of 4.5 1355.38 andEach the formula is prevents C 63chloride 12test 14O 14P, which Academy of Science -of Council for should be bioavailabilityI. ofDietary the B12deficiency nasal spray the B12 gel and evaluate the relative bioavailability adjustment; continued low levels serum Bmay indicate that thepregnant patient is women not a that candidate for 12 may of to vitamin B12nasal occurring in to strict vegetarians (Isolated vitamin B12 defispray delivers an average of 500 mcg of cyanocobalamin. The average diet supplies about 4 to 15 mcg/day of vitamin B12 in a protein-bound form that is . This occur if antimetabolites for the vitamin are V.National Inadequate utilization of vitamin BNational deficiency is administered to patients suspected of cyanocobalamin sensitivity. Vitamin B following structural formula: 12 12 consumed during pregnancy. of the nasal formulations as compared to the intramuscular injection. The peak concentrations this mode of administration. ciency is very rare). available for absorption after normal digestion. Vitamin B12 is not present in foods of plant origin, employed thelonger treatment neoplasia. allowed to progressinfor thanofthree months may produce permanent degenerative lesions of CLINICAL PHARMACOLOGY after administration of intranasal spray were reachedfrom in 1.25 +/- 1.9 hours. The average peak 6. NURSING MOTHERS structural or functional damage to the stomach, II. Malabsorption of vitamin B12 resulting Patients with pernicious anemia have about 3 times the incidence of carcinoma of the stomach as but is abundant in foods of animal origin. In people with normal absorption, deficiencies have been spinal cord. Doses of folic greaterdisease than 0.1bymg per day may result in hematologic remission GENERAL PHARMACOLOGY AND MECHANISM OF ACTION Itthe may be to treat theinacid underlying surgical of anatomic lesions leading concentration ofwhere B12 obtained correction of factor intranasal sprayvitamin Vitamin Bvitamin the so milk of nursing mothers in concentrations which approximate the intrinsicafter factorbaseline is secreted, or to following the ileum,administration where intrinsic facilitates in possible the general population, appropriate tests for correction this condition should be carried out when who consume no productsand of nucleoprotein animal origin and (including only in strict vegetarians Neurologic manifestations will not be prevented with folic in small patients with B12 deficiency. 12 appears to growth, cell reproduction, hematopoiesis, myelinno milk Vitaminreported B12 is essential to bowel bacterial overgrowth, expulsion of fish tapeworm, discontinuation of drugs leading to was 757.96 +/532.17 pg/mL. The bioavailability of the nasal spray relative to the intramuscular mother’s vitamin B blood level. Amounts of vitamin B that are recommended by the Food and B12 absorption. These conditions include HIV infection, AIDS, Crohn’s disease, tropical indicated. products eggs). acid, and if not treated (see with 12 vitamin B12, irreversible damage will 12result. synthesis. Cells or characterized by rapid division (e.g., epithelial cells, bone marrow, myeloid cells) vitamin malabsorption "Drug/Laboratory Interactions"), use of a gluten free diet in non-women injection was found to be 6.1%. The bioavailability of the steatorrhea, B12 nasal spray was found toenteropathy). be 10% less Folate Board, National Academy ofTest Science-National Research Council lactating sprue, and nontropical sprue (idiopathic gluten-induced 3. DRUG/LABORATORY TEST bound requirement to intrinsic factor duringBtransit through the stomach; separation occurs in the Doses Nutrition of vitamin B 10 mcgINTERACTIONS daily may produce hematologic response infor patients with 12 is 12 exceeding of appear Vitamin to have B the greatest for vitamin sprue. Such measures remove the need tropical sprue, or consumed administration antibiotics in tropical than the B12 nasal gel. Thein90% confidence for thesevere loge - than transformed 12. Vitamin B12 can be converted to coenzyme (0-t) and Cmax should be during lactation. deficiency. deficiency these patients isintervals usually more vitamin BAUC 12 Persons taking most antibiotics, methotrexate or pyrimethamine invalidate folic acid and vitamin B12 terminal ileum in the presence of calcium, and vitamin B enters the mucosal cell for absorption. It folate deficiency. Indiscriminate administration may mask the true diagnosis. 12 for long-term administration of vitamin B12. B 12 in tissues, and as such is essential for conversion of methylmalonate to succinate and was 71.71%III. - 114.19% and 71.6% - 118.66% respectively. Inadequate secretion of intrinsic factor, resulting from lesions that destroy the gastric 7. PEDIATRIC USE diagnostic blood assays. is then transported byhomocysteine, the transcobalamin binding proteins. A smallfolate. amount (approximately The validity of diagnostic vitamin B or folic acid blood assays could be compromised by synthesis of methionine from a reaction which also requires In the absence of 1% of 12 in associata In pernicious anemia patients, once weekly intranasal dosing with 500 B12 gelofresulted mucosa (ingestion of corrosives, extensive neoplasia), andmcg a number conditions Requirements of vitamin B in excess of normal (due to pregnancy, thyrotoxicosis, hemolytic aneIntake in pediatric patients should be in the amount recommended by the Food and Nutrition Board, 12 the total amount ingested) is absorbed by simple diffusion, but this mechanism is adequate only medications, and this should be considered before relying on such tests therapy. Colchicine, para-aminosalicylic acid and heavy alcohol intake for for longer than 2 weeks may produce coenzyme B12, tetrahydrofolate cannot be regenerated from its inactive storage form, 5-methyl consistent increase in pre-dose serum B12oflevels during one(such month treatment (p < 0.003) above AIDS, ed with a variable degree gastric atrophy asof multiple sclerosis, HIV infection, mia, hemorrhage, malignancy, hepatic and renal disease)Council. can usually be met with intranasal or oral National Academy of Science-National Research with very large Oral folate absorption is considered undependable to rely in patients malabsorption of vitamin B . tetrahydrofolate, and adoses. functional deficiency occurs. too Vitamin B 12 also may be on involved in with Vitamin B 12 is not a substitute 12for folic acid and since it might improve folic acid deficient that seen one month after 100 mcg intramuscular dose (Figure). certain endocrine disorders, iron deficiency, and subtotal gastrectomy). Total gastrectomy supplementation. pernicious anemia or other conditions resulting in malabsorption of vitamin B12. maintaining sulfhydryl (SH) groups in the reduced form required by many SH-activated enzyme true diagnosis. megaloblastic anemia, indiscriminate use of vitamin B12 could mask ADVERSE REACTIONS 4. CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF the FERTILITY Distribution always produces vitamin B12 deficiency. Structural lesions leading to vitamin B12 deficienColchicine, para-aminosalicylic acid, heavy alcohol for longer than 2 weeks may test (Schilling Test). Nascobal Nasal Spray of is not for vitamindescribed Bcarcinogenic systems. Through these reactions, vitamin B12 and is associated with fatintake and carbohydrate metabolism 12 absorption The incidence adverse experiences in the Table below are been based onnormal data from a Long-term in suitable animals to evaluate potential have not done. There is no regional ileitis, ileal resections, malignancies, etc.carrier protein, and is is bound to transcobalamin II, a specific B-globulin In the blood, Bcy Hypokalemia and studies thrombocytosis could occur upon conversion of severe megaloblastic to 12 include . produce malabsorption B and protein synthesis. Vitaminof Bvitamin deficiency results in megaloblastic anemia, GI lesions, and 12 short-term clinical trialB in therapy. vitamin patients in hematologic Nascobal evidence from long-term use in Bpatients withserum pernicious anemia thatremission vitamin Breceiving 12 12 deficient 12 is carcinogenic. CONTRAINDICATIONS distributed and stored primarily in the liver and bone marrow. Therefore, potassium levels and the platelet count erythropoiesis with vitamin 12 neurologic damage that begins with an inability to produce myelin and is followed by gradual (Cyanocobalamin, USP) Gel for Intranasal Administration (N=24) and intramuscular vitamin B Pernicious anemia is associated with an increased incidence of carcinoma of the stomach, but this 12 to cobalt and/or vitamin B12therapy. or any component of the medication is a contraindication. Sensitivity should be monitored carefully during Elimination degeneration of the axon and nerve head. (N=25). In the pharmacokinetic study comparing Nascobal Spray with and vitamin Nascobal Gel, is believed to be related to the underlying pathology and not Nasal to treatment B Nasal . WARNINGS About 3-8 mcg of B12 is secreted into the GI tract daily via the bile; in normal subjects with sufficient deficiency may suppress of polycythemia vera. Treatment with vitamin12B12 Vitaminthe B12 Cyanocobalamin is the most stable and widely used form of vitamin B12, and has hematopoietic incidence of adverse events the wassigns similar. 5. PREGNANCY Patients with early Leber’s disease (hereditary optic nerve atrophy) who were treated with vitamin intrinsic factor, all but about 1 mcg is re-absorbed. When B is administered in doses which may unmask this condition. 12 activity apparently identical to that of the antianemia factor in purified liver extract. The information Table Adverse Experiences by Body System, Number of Patients and Number Pregnancy Category C: Animal reproduction studies have not been conducted with vitamin B . is 12 Itof B12 suffered severe and swift optic atrophy. saturate the binding capacity of plasma proteins and the liver, the unbound B12 is rapidly eliminated below, describing the clinical pharmacology of cyanocobalamin, has been derived from studies with ®fetal Occurrences by Treatment Intramuscular and Intranasal to Administration of If a patient properly maintained with Nascobal Nasal Spray, intramuscular vitamin B12 is woman also is notnot known whether vitaminFollowing B cause harm when administered a pregnant 12 can in the urine. Retention of Vitamin B12 in the is Trough dose-dependent. About 80-90% of an intramuscular Hypokalemia and sudden death may occur in severe megaloblastic anemia which is treated Figure. B 12body Serum Levels After Intramuscular injectable vitamin B12. Cyanocobalamin. necessary for adequate treatment capacity. of the patient. No single regimen fits all cases, the status or can affect reproduction Adequate andfor well-controlled studiesand have beenofdone in dose up to 50 mcgSolution is retained this Nasal percentage drops to 55% for of a 100 mcg dose, and intensely vitamin Folic is acid isfinal notcriterion a substitute vitamin B12 although it maynotimprove (IM)inofthe 100body; mcg and Gel (IN) Administration 12.However, Vitamin B12 is quantitatively and rapidly absorbed from intramuscular and subcutaneous sites of the patientwith observed inBfollow-up the for essential adequacy of therapy. women. vitamin vitamin requirements areB increased 12 is an decreases to 15% 500 when a 1000 mcg dose is After given.Weekly Doses. megaloblastic anemia.BExclusive use of folic acidand in Patients treating vitamin vitamin pregnant B12-deficient Number of (Occurrences) mcg Cyanocobalamin 12injection. It is bound to plasma proteins and stored in the liver. Vitamin B12 is excreted in the bile during pregnancy. Amounts of vitamin B that are recommended by the Food and Nutrition allergic rhinitis The effectiveness of Nascobal Nasal Spray in patients with nasal congestion, 12 deficient megaloblastic anemia could resultAdverse in progressive and irreversible neurologicIntramuscular damage. and Board, System Vitamin B and undergoes some enterohepatic recycling. Absorbed vitamin B12 is transported via specific B12 12pregnant NationalBody Academy of Science - National Research Council for women should be upper respiratory infections has not been determined. Therefore, treatment with Nascobal Nasal Anaphylactic shock and death have beenExperience reported after parenteralNasal vitamin Gel, B12 administration. Vitamin B12,No binding proteins, occurs transcobalamin I and II, toorthe various tissues. The is thered main organItfor powder. is Cyanocobalamin as dark red crystals orthorhombic needles or liver crystalline consumed during pregnancy. Spray should be deferred until symptoms have subsided. such reactions have been reported in clinical trials with Nascobal Nasal Spray or Nascobal Nasal 500 mcg 100 mcg vitamin B12 storage. very hygroscopic in the anhydrous form, and sparingly to moderately soluble in water (1:80). Its 6. NURSING MOTHERS 2. LABORATORY TESTS Gel. N=24 N=25 pharmacologic activity is destroyed by heavy and strong oxidizing reducing agents reverses or the megaloblastic Parenteral (intramuscular) administration of metals vitamin(iron) B12 completely Vitamin B12 appears in the milk Bof ,nursing mothers in concentrations which approximate the INDICATIONS AND USAGE folate and iron levels should be obtained prior to Hematocrit, reticulocyte count, vitamin Bluntedmother’s or impeded response to12vitaminofB12 may be due to1are such conditions as4by infection, (vitamin by autoclaving for short periods of time (15-20 minutes) at 121°C.inThe vitamin Body as atherapeutic Whole Asthenia (1) recommended (4)the Food anemia C), andbut GI not symptoms of vitamin B12 deficiency; the degree of improvement neurologic Nascobal Nasal Spray is indicated for the maintenance of normal hematologic status in pernicious vitamin B12 are blood level. Amounts vitamin and 12 that treatment. If folate levels low, folic acid should alsoBbe administered. All hematologic uremia, drugs having bone marrow suppressant properties such as chloramphenicol, B are very unstable in light. Back Pain 0 (0) 1lactating (1) and women symptoms depends on the duration and severity of the lesions, although progression of the lesions 12 coenzymes anemia patients who are in remission following intramuscular vitamin B12 therapy and who have no Nutrition Board, National Academy of Science-National Research Council for ® parameters should be normal when beginning treatment with Nascobal Nasal Spray. concurrent iron or folic acid deficiency.Generalized Pain ® Nasal 0 (0) 2 (3) is immediately arrested. Spray is a solution of Cyanocobalamin, USP (vitamin B12) for administration as a Nascobal nervous system involvement. should be consumed during lactation. Vitamin B12 blood levels and peripheral blood counts must be monitored initially at one month Headache 1 (2)* 5 (11) after spray to the nasal mucosa. Each unit dose device ofonNascobal NasalofSpray contains 0.125 mL of a the presence sufficient intrinsic factor and Gastrointestinal absorption of vitamin B12 depends PRECAUTIONS 7.ofPEDIATRIC USE ® Infection a Nascobal Nasal Spray is also indicated as a supplement for other vitamin B deficiencies, the start treatment with Nascobal Nasal Spray, and then at intervals of 3 to 6 months. 3 (4) 3 (3) 12 500 mcg/0.1 mL solution of cyanocobalamin with sodium citrate, citric acid, glycerin and calcium ions. Intrinsic factor deficiency causes pernicious anemia, which may be associated with 1. GENERAL Intake in pediatric patients should be in the amount recommended by the Food and Nutrition Board, including: Peripheral Vascular 0B(0) 1 Spray (1) System A decline inCardiovascular thetest serum levels of B12 after one month ofDisorder treatment spray may indicate benzalkonium chloride in purified water. spray solution a pH between 4.5 and of 5.5.vitamin Each subacute combined degeneration of the The spinal cord. Prompthas parenteral administration before Nascobal Nasal is An intradermal dose of vitamin B 12 nasal 12 is recommended National Academy ofparenteral Science-National Research Council. with Digestive System Dyspepsia 0 (0) 1 (2)that that the dose may need tosuspected be adjusted Patients should be seen one month after each dose spray deliversprogression an averageofofneurologic 500 mcg of cyanocobalamin. B12 prevents damage. Vitamin B12 deficiency is administered to patients of upward. cyanocobalamin sensitivity. Glossitis 1 (1) degenerative 0 (0) ADVERSE REACTIONS adjustment; continued levels of three serum B12 may indicate that the patient is not a candidate for allowed to progress forlow longer than months may produce permanent lesions of I. Dietary deficiency of vitamin B12 occurring in strict vegetarians (Isolated vitamin B12 defiThe average diet supplies about 4 to 15 mcg/day of vitamin B12 in a protein-bound form that is CLINICAL PHARMACOLOGY Nausea 1 (1)* (1) data from a The adverse experiences described in the Table below are based1remission on this spinal mode ofincidence administration. the cord. Doses of folic acid greater than 0.1 mg per day may result in hematologic ciency is very rare). available forPHARMACOLOGY absorption after normal digestion. Vitamin B12 is not present in foods of plant origin, GENERAL AND MECHANISM OF ACTION (1) Nausea & Vomiting 0 (0) 1 short-term clinical trial in vitamin B deficient patients in hematologic remission receiving Nascobal Neurologic willcarcinoma not be prevented with folic in patients with vitamin B II. Malabsorption of vitamin B12 resulting from structural or functional damage to the stomach, Patients with pernicious anemia have about the incidence of of the stomach as 12 3 timesmanifestations 12 deficiency. but is abundant in foodstoofgrowth, animal origin. In people with normal absorption, deficiencies and havemyelin been cell reproduction, hematopoiesis, and nucleoprotein Vitamin B12 is essential 0 (0) and 1 (1) when (Cyanocobalamin, Gel for Intranasal Administration (N=24) vitamin B12 , irreversible damage will result. acid, if not treated withUSP) vitamin B12Vomiting where intrinsic factor is secreted, or to the ileum, where intrinsic factor facilitates vitamin in theand general population, so appropriate tests for this condition should be intramuscular carried out who division consume no products animal (including nocells) milk reported only in characterized strict vegetarians synthesis. Cells by rapid (e.g., epithelial of cells, boneorigin marrow, myeloid Musculoskeletal System Arthritis 0 (0) 2 (2) (N=25). theexceeding pharmacokinetic Nascobal Nasalresponse Spray and Nasal Gel, B12 absorption. These conditions include HIV infection, AIDS, Crohn’s disease, tropical indicated. Doses of vitaminInB12 10 mcgstudy daily comparing may produce hematologic in Nascobal patients with products eggs). appear toor have the greatest requirement for vitamin B12. Vitamin B12 can be converted to coenzyme Myalgia 0 (0) 1 (1) the incidence of adverseadministration events was similar. sprue, and nontropical sprue (idiopathic steatorrhea, gluten-induced enteropathy). Folate folate deficiency. Indiscriminate may mask the true diagnosis. 3. DRUG/LABORATORY to intrinsic during throughofthe stomach; separation occurs inand the Vitamin B12 is bound B and as such is factor essential fortransit conversion methylmalonate to succinate 12 in tissues, Nervous System TEST INTERACTIONS Abnormal Gait 0 (0) 1 (1) deficiency. deficiency in these patients is usually more severe than vitamin B Table Adverse Experiences by Body System, Number of Patients and Number of 12 The validity of diagnostic vitamin B or folic acid blood assays could be compromised Persons taking most antibiotics, methotrexate or pyrimethamine invalidate terminal ileum in the presence of calcium, and vitamin B mucosal cellInfor absorption. synthesis of methionine from homocysteine, a reaction which also the requires folate. the absence ofIt 12 12 12 enters Anxiety 0 (0) folic acid and vitamin 1 (1)* Bby III. Inadequate secretion of intrinsic factor, resulting from lesions that destroy the gastric Occurrences by Treatment Following Intramuscular and of medications, and assays. this should be considered before relying on such tests forIntranasal therapy. Administration diagnostic blood is then transported by the transcobalamin proteins. A small amount (approximately 1% of coenzyme B12, tetrahydrofolate cannot bebinding regenerated from its inactive storage form, 5-methyl Dizziness 0 (0) 3 (3) mucosa (ingestion of corrosives, extensive neoplasia), and a number of conditions associatCyanocobalamin. the total amount and ingested) is absorbed simple diffusion, but this B mechanism is be adequate only tetrahydrofolate, a functional folateby deficiency occurs. Vitamin involved in Vitamin B 12para-aminosalicylic is not a substitute forand folic acidalcohol and since might improve folic acid Colchicine, acid heavy intakeit for longer than 2 weeks may1deficient produce 12 also may Hypoesthesia 0 (0) (1) ed with a variable degree of gastric atrophy (such as multiple sclerosis, HIV infection, AIDS, with very large doses. (SH) Oral absorption is considered too required undependable to rely on in patients with maintaining sulfhydryl groups in the reduced form by many SH-activated enzyme could mask the true diagnosis. megaloblastic anemia, indiscriminate use of vitamin B malabsorption of vitamin B12. 12 Incoordination 0 (0) of Patients (Occurrences) 1 (2)* Number certain endocrine disorders, iron deficiency, and subtotal gastrectomy). Total gastrectomy perniciousThrough anemia these or other conditions resulting in associated malabsorption vitamin B12. withoffat and carbohydrate metabolism systems. reactions, vitamin B12 is Nervousness 0 (0) B 1 4. CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY Hypokalemia andBody thrombocytosis could occur upon conversion of Vitamin severe megaloblastic to(3)* normal Intramuscular System Adverse always produces vitamin B12 deficiency. Structural lesions leading to vitamin B12 deficien12 and protein synthesis. Vitamin Bacid, results in megaloblastic anemia, and Colchicine, para-aminosalicylic and heavy alcohol intake for longer thanGI2 lesions, weeks may 12 deficiency Paresthesia 1 (1) 1 (1)B Long-term studies in animals to evaluate carcinogenic potential have not been done. There is12,no therapy. Therefore, serum potassium levels and the platelet count erythropoiesis with vitamin B Experience Nasal Gel, Vitamin cy include regional ileitis, ileal resections, malignancies, etc. 12 neurologic damage thatof begins produce malabsorption vitamin with B12. an inability to produce myelin and is followed by gradual Respiratory System Dyspnea 0vitamin (0) 1 (1) is carcinogenic. evidence from long-term use in patients with pernicious anemia that B should be monitored carefully during therapy. 500 mcg 100 mcg 12 PHARMACOKINETICS IV. Competition for vitamin B 12 by intestinal parasites or bacteria. The fish tapeworm degeneration of the axon and nerve head. Rhinitis 1 (1)* 2 (2) N=25 B (Diphyllobothrium latum) absorbs huge quantities of vitamin B12 and infested patients often Absorption Treatment with vitamin Vitamin B12 deficiency may suppress the signs of polycythemia vera.N=24 Cyanocobalamin is the most stable and widely used form of vitamin B12, and has hematopoietic 12 a Whole Asthenia 1 (1) 4 (4) have associated gastric atrophy. The blind loop syndrome may produce deficiency of vitamay unmask this as condition. aBody activity identical to that antianemia factor in purified extract. to The information Sore throat, common coldBack *There may be a possible relationship between these adverse A threeapparently way crossover study in of 25the fasting healthy subjects was liver conducted compare the Pain 0 (0) 1 (1) or folate. min B 12 below, describing theBclinical pharmacology of cyanocobalamin, has been derived from studies with ® experiences and the study drugs. These adverse experiences could have also been bioavailability of the nasal spray to the B nasal gel and to evaluate the relative bioavailability Nasal Spray, intramuscular vitamin B If a patient is not properly maintained with Nascobal 12 12 Generalized Pain 0 (0) 2 (3) 12 is This may occur if antimetabolites V. Inadequate utilization of vitamin B12.Trough Figure. Vitamin B 12 Serum Levels After Intramuscular for the vitamin are injectable vitamin B12. the patient’s clinical state otherregimen concomitant therapy. of the nasal formulations as compared to the intramuscular injection. The peak concentrations necessary forproduced adequatebytreatment of the patient. Noorsingle fits1 all of neoplasia. employedSolution in the treatment Headache (2)*cases, and the 5status (11) of (IM) of 100 mcg and Nasal Gel (IN) Administration of and rapidly absorbed frominintramuscular subcutaneous sites of Vitamin B12 is quantitatively after administration of intranasal spray were reached 1.25 +/- 1.9 and hours. The average peak the patient is theInfection final criterion for adequacy of therapy. The observed intensity inoffollow-up the reported adverse following the administration of Nascobal a experiences 3 (4) 3 (3) mcg the Cyanocobalamin After Weekly Doses. It may be possible500 to treat underlying disease by surgical correction of anatomic lesions leading injection. It is bound plasmaafter proteins and correction stored in the liver. Vitamin B12 is excreted in thespray bile concentration of B12 to obtained baseline following administration of intranasal (Cyanocobalamin, USP) Gel for Intranasal Administration and intramuscular vitamin B12 were patients with nasal congestion, allergic rhinitis The effectiveness of Nascobal Nasal Spray in Cardiovascular System Peripheral Vascular Disorder 0 (0) 1 (1) and to small bowel bacterial overgrowth, expulsion of fish tapeworm, discontinuation of drugs leading to transported specific B12 and Absorbed B12 is relative was undergoes 757.96 +/- some 532.17enterohepatic pg/mL. Therecycling. bioavailability of thevitamin nasal spray to theviaintramuscular generally mild. One patient reported severe headache following dosing. Similarly, a upper respiratory infections has not been determined. Therefore, treatment with Nascobal Digestive System Dyspepsia 0 intramuscular (0) 1 (2)Nasal vitamin malabsorption (see "Drug/Laboratory Test Interactions"), use of a gluten free diet in nonbinding transcobalamin I and II, to the various The liver is the main organ for nasal spray was found to be 10% less injectionproteins, was found to be 6.1%. The bioavailability of the Btissues. experiences of moderate intensity were reported following intramuscular dosing (two few adverse 12 Spray should be deferred until symptoms have subsided. Glossitis 1 (1) 0 (0) tropical sprue, or administration of antibiotics in tropical sprue. Such measures remove the need vitamin than theBB nasal gel. The 90% confidence intervals for the loge - transformed AUC(0-t) and Cmax headaches and rhinitis; one dyspepsia, arthritis, and dizziness), 1212storage. Nausea 1 (1)* and dosing 1with (1) Nascobal 2. LABORATORY TESTS . for long-term administration of vitamin B 71.6% 118.66% respectively. was 71.71% 114.19% and 12 (Cyanocobalamin, USP) GelNausea for Intranasal Administration0 (0) (one headache, 1infection, and Parenteral (intramuscular) administration of vitamin B12 completely reverses the megaloblastic Vomiting (1) INDICATIONS AND USAGE and iron levels should be obtained prior to Hematocrit, reticulocyte count, vitamin B12,&folate paresthesia). anemia and GI symptoms of vitamin B12 deficiency; degree improvement neurologic in a In pernicious anemia patients, once weekly intranasal the dosing with of 500 mcg B12 gelinresulted Requirements vitamin of normal (due toofpregnancy, thyrotoxicosis, ane0 (0) 1 (1) Nascobal NasalofSpray is B indicated for the maintenance normal hematologic statushemolytic in pernicious 12 in excess treatment. If folate levels are low, Vomiting folic acid should also be administered. All hematologic symptoms the duration andBseverity the lesions, although progression the lesions consistent depends increase on in pre-dose serum during one month of treatment (p < of 0.003) above mia, hemorrhage, malignancy, hepaticfollowing and renalintramuscular disease) canvitamin usually Bbe met with intranasal or oral The majority of the reported adverse experiences following dosing with Nascobal 12 levelsof Musculoskeletal System Arthritis 0 (0) 2 (2) therapy and who have no anemia patients who are in remission ® 12 parameters should be normal when beginning treatment with Nascobal Nasal Spray. is immediately arrested. that seen one month after 100 mcg intramuscular dose (Figure). supplementation. intramuscular vitamin (Cyanocobalamin, USP) Gel for Intranasal Administration and Myalgia 0 (0) 1 (1) B12 were nervous system involvement. Vitaminjudged B12 blood levels and peripheral blood counts must be monitored initially at one the month to be intercurrent events. For the other reported adverse experiences, to Gastrointestinal absorption of vitamin B12 depends on the presence of sufficient intrinsic factor and Distribution Nervous System Abnormal Gait 0 (0) 1 relationship (1) after ® Nasal absorptionfor testother (Schilling Test). Nascobal Nasal Spray is is notalso suitable for vitamin Bsupplement Nascobal Nasal Spray indicated as a vitamin B deficiencies, the start of treatment with Nascobal and thenOf at intervals 6 months. judged 12 12 study drug was judged as “possible” or “remote”. the adverse experiences calcium ions. Intrinsic factor deficiency causes pernicious anemia, which may be associated with to transcobalamin II, a specific B-globulin carrier protein, and is In the blood, B 12 is bound AnxietySpray, 0 of (0)3 to 1 (1)* to be of including: A decline in the serum levels of B after one month of treatment with B nasal spray may indicate CONTRAINDICATIONS “possible” relationship to the study drug, anxiety, incoordination, and nervousness were reported subacute of the cord. Prompt parenteral administration of vitamin distributedcombined and storeddegeneration primarily in the liverspinal and bone marrow. Dizziness 012 (0) 3 (3) 12 that thefollowing dose mayintramuscular need to be adjusted upward. should be seen month afterreported each Sensitivity to cobalt and/or vitamin B12 or any component of the medication is a contraindication. vitaminHypoesthesia B12 andPatients headache, nausea, and were following B 0 one (0)rhinitis 1 (1) dose 12 prevents progression of neurologic damage. Elimination adjustment; low levels of serum B12 USP) may indicate that the patient dosingcontinued with Nascobal (Cyanocobalamin, Gel for Intranasal Incoordination 0Administration. (0) is not a candidate 1 (2)* for I. Dietary deficiency of vitamin B12 occurring in strict vegetarians (Isolated vitamin B12 defiin a protein-bound form that is The average supplies about 4 to 15 mcg/day of vitamin B 12 WARNINGS is secreted into the GI tract daily via the bile; in normal subjects with sufficient About 3-8 mcgdiet of B 12 this mode of administration. Nervousness 0 (0) 1 (3)* ciency is very rare). The following adverse reactions have been reported with parenteral vitamin B12: present in foods of plant origin, available for absorption after normal VitaminWhen B12 isBnot Patients with early Leber’s disease (hereditary optic nerve atrophy) who were treated with vitamin intrinsic factor, all but about 1 mcg digestion. is re-absorbed. 12 is administered in doses which 1 (1)and Precautions). 1 (1) as II. Malabsorption vitamin PatientsGeneralized: with pernicious anemia have Paresthesia about 3 times the incidence of carcinoma of the stomach but is abundant in foods of animal origin.proteins In people absorption, deficiencies have been 12 resulting from structural or functional damage to the stomach, Anaphylactic shock and death (See Warnings severe andofswift opticBatrophy. B12 suffered saturate the binding capacity of plasma andwith the normal liver, the unbound B 12 is rapidly eliminated Respiratory Systemso Dyspnea 0 (0) early 1 (1)when where and intrinsic factor is secreted, or tointhe ileum,megaloblastic where intrinsicanemia factor facilitates in the general population, appropriate tests this condition be carried out reported onlyRetention in strict vegetarians who consume no products of animal originof(including no milk Cardiovascular: Pulmonary edema andfor congestive heart should failure in treatment; peripheral in the urine. of B12 in the body is dose-dependent. About 80-90% an intramuscular Hypokalemia sudden death may occur severe which is vitamin treated Rhinitis 1 (1)* 2 (2) B absorption. These conditions include HIV infection, AIDS, Crohn’s disease, tropical indicated. products or eggs). 12 vascular thrombosis. dose up to 50 mcg is retained in the body; this percentage drops to 55% for a 100 mcg dose, and intensely with vitamin B12. Folic acid is not a substitute for vitamin B12 although it may improve sprue, and nontropical sprue (idiopathic steatorrhea, gluten-induced enteropathy). Folate Hematological: Polycythemia vera. 3. DRUG/LABORATORY TEST INTERACTIONS bound to intrinsic factordose during transit through the stomach; separation occurs in the Vitamin B12tois15% decreases when a 1000 mcg is given. vitamin B12-deficient megaloblastic anemia. Exclusive use of folic acid in treating vitamin B12a Sore throat, common cold *There may be a possible relationship between these adverse in these patients usually severeand thanirreversible vitamin B12neurologic deficiency.damage. Mildmethotrexate transient diarrhea. Gastrointestinal: Persons taking most antibiotics, or pyrimethamine invalidate folic acid and vitamin B12 terminal ileum in the presence of calcium, and vitamin B12 enters the mucosal cell for absorption. It deficientdeficiency megaloblastic anemia couldisresult in more progressive experiences the study drugs.exanthema. These adverse experiences could have also been III. Inadequate secretion of intrinsic factor, resulting from lesions that destroy the gastric Dermatological: Itching; transitory is then transported by the transcobalamin binding proteins. A small amount (approximately 1% of diagnostic blood assays. and Anaphylactic shock and death have been reported after parenteral vitamin B administration. No 12 produced by the patient’s clinical state other body. concomitant therapy. mucosa (ingestion of corrosives, extensive neoplasia), and a number of conditions associatMiscellaneous: Feeling of swelling of theorentire the total amount ingested) is absorbed by simple diffusion, but this mechanism is adequate only Colchicine, para-aminosalicylic acid and heavy alcohol intake for longer than 2 weeks may produce such reactions have been degree reported in clinical trials with Nascobal Nasal SprayHIV or Nascobal Nasal ed with a variable of gastric atrophy (such as multiple sclerosis, infection, AIDS, The intensity of Bthe. reported adverse experiences following the administration of Nascobal with very large doses. Oral absorption is considered too undependable to rely on in patients with malabsorption of vitamin Gel. certain endocrine disorders, iron deficiency, and subtotal gastrectomy). Total gastrectomy (Cyanocobalamin, 12USP) Gel for Intranasal Administration and intramuscular vitamin B12 were pernicious anemia or other conditions resulting in malabsorption of vitamin B12. 4. CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY response to vitamin B12 maylesions be due leading to such to conditions infection, Blunted or impeded therapeutic always produces vitamin B12 deficiency. Structural vitamin Bas generally mild. One patient reported severe headache following intramuscular dosing. Similarly, a 12 deficienColchicine, para-aminosalicylic acid, and heavy alcohol intake for longer than 2 weeks may Long-term animals to evaluate carcinogenic have following not been intramuscular done. There isdosing no (two uremia, cy drugs having bone marrow suppressant propertiesetc. such as chloramphenicol, and malignancies, include regional ileitis, ileal resections, fewstudies adverseinexperiences of moderate intensity potential were reported produce malabsorption of vitamin B12. concurrent iron or folic acid deficiency. evidence from long-term use in patients with pernicious anemia that vitamin and B12 is carcinogenic. and dizziness), dosing with Nascobal headaches and rhinitis; one dyspepsia, arthritis, PHARMACOKINETICS by intestinal parasites or bacteria. The fish tapeworm IV. Competition for vitamin B (Cyanocobalamin, USP) Gel for Intranasal Administration (one headache, infection, and PRECAUTIONS 12 (Diphyllobothrium latum) absorbs huge quantities of vitamin B12 and infested patients often Absorption paresthesia). 1. GENERAL have associated atrophy. The B blind syndrome may produce deficiency of vita-is recommended before Nascobal Nasal Spray An intradermal test dose gastric of parenteral vitamin The majority of the reported adverse experiences following dosing with Nascobal 12 isloop A three way crossover study in 25 fasting healthy subjects was conducted to compare the folate. suspected of cyanocobalamin sensitivity. Vitamin B12 deficiency that is min B12 administered to or patients (Cyanocobalamin, USP) Gel for Intranasal Administration and intramuscular vitamin B12 were bioavailability of the B12 nasal spray to the B12 nasal gel and to evaluate the relative bioavailability mayproduce occur if permanent antimetabolites for the vitamin are V. Inadequate vitamin allowed to progress utilization for longerofthan threeBmonths degenerative lesions of 12. Thismay judged to be intercurrent events. For the other reported adverse experiences, the relationship to of the nasal formulations as compared to the intramuscular injection. The peak concentrations employed in theoftreatment neoplasia. the spinal cord. Doses folic acid of greater than 0.1 mg per day may result in hematologic remission study drug was judged as “possible” or “remote”. Of the adverse experiences judged to be of after administration of intranasal spray were reached in 1.25 +/- 1.9 hours. The average peak deficiency. Neurologic manifestations will not be prevented with folic in patients with vitamin B 12 “possible” relationship to the study drug, anxiety, incoordination, and nervousness were reported It may be possible to treat the underlying disease by surgical correction of anatomic lesions leading concentration of B12 obtained after baseline correction following administration of intranasal spray will result. acid, and if notbacterial treated with vitamin Bexpulsion 12, irreversible following intramuscular vitamin B12 and headache, nausea, and rhinitis were reported following to small bowel overgrowth, of fishdamage tapeworm, discontinuation of drugs leading to was 757.96 +/- 532.17 pg/mL. The bioavailability of the nasal spray relative to the intramuscular Doses of vitamin B12 exceeding 10 mcg dailyTest mayInteractions"), produce hematologic in patients with dosing with Nascobal (Cyanocobalamin, USP) Gel for Intranasal Administration. vitamin malabsorption (see "Drug/Laboratory use of aresponse gluten free diet in noninjection was found to be 6.1%. The bioavailability of the B12 nasal spray was found to be 10% less folate deficiency. Indiscriminate administration may mask the true diagnosis. tropical sprue, or administration of antibiotics in tropical sprue. Such measures remove the need The following adverse reactions have been reported with parenteral vitamin B12: than the B12 nasal gel. The 90% confidence intervals for the loge - transformed AUC(0-t) and Cmax The validity administration of diagnosticofvitamin vitamin BB12 for long-term was 71.71% - 114.19% and 71.6% - 118.66% respectively. 12. or folic acid blood assays could be compromised by Generalized: Anaphylactic shock and death (See Warnings and Precautions). medications, and this should be considered before relying on such tests for therapy. Cardiovascular: Pulmonary edema and congestive heart failure early in treatment; peripheral In pernicious anemia patients, once weekly intranasal dosing with 500 mcg B12 gel resulted in a Requirements of vitamin B12 in excess of normal (due to pregnancy, thyrotoxicosis, hemolytic aneVitamin B is not a substitute for folic acid and since it might improve folic acid deficient vascular thrombosis. consistent increase in pre-dose serum B12 levels during one month of treatment (p < 0.003) above 12 mia, hemorrhage, malignancy, hepatic and renal disease) can usually be met with intranasal or oral megaloblastic anemia, indiscriminate use of vitamin B12 could mask the true diagnosis. Hematological: Polycythemia vera. that seen one month after 100 mcg intramuscular dose (Figure). supplementation. Gastrointestinal: Mild transient diarrhea. Distribution Hypokalemia and thrombocytosis could occur upon conversion of severe megaloblastic to normal Nascobal Nasal Spray is not suitable for vitamin B12 absorption test (Schilling Test). Dermatological: Itching; transitory exanthema. In the blood, B 12 is bound to transcobalamin II, a specific B-globulin carrier protein, and is erythropoiesis with vitamin B12 therapy. Therefore, serum potassium levels and the platelet count Miscellaneous: Feeling of swelling of the entire body. CONTRAINDICATIONS distributed and stored primarily in the liver and bone marrow. should be monitored carefully during therapy. Sensitivity to cobalt and/or vitamin B12 or any component of the medication is a contraindication. Elimination Vitamin B12 deficiency may suppress the signs of polycythemia vera. Treatment with vitamin B12 WARNINGS About 3-8 mcg of B12 is secreted into the GI tract daily via the bile; in normal subjects with sufficient may unmask this condition. Patients with early Leber’s disease (hereditary optic nerve atrophy) who were treated with vitamin intrinsic factor, all but about 1 mcg is re-absorbed. When B12 is administered in doses which patient severe is not properly with Nascobal® Nasal Spray, intramuscular vitamin B12 is and swiftmaintained optic atrophy. BIf asuffered saturate the binding capacity of plasma proteins and the liver, the unbound B is rapidly eliminated 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: Generalized: Anaphylactic shock and death (See Warnings and Precautions). 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. 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. See LABORATORY TESTS for monitoring B12 levels and adjustment of dosage. HOW SUPPLIED Nascobal Nasal Spray, 500 mcg is supplied in boxes of 4 unit dose nasal spray devices and a package insert (NDC 49884-270-82). Each unit dose spray delivers 500 mcg of cyanocobalamin, USP. 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 OVERDOSAGE should be told tohas administer Nascobal Spray at least hour before or one hour USP) after No overdosage been reported with Nasal Nascobal Nasal Spray,one Nascobal (Cyanocobalamin, ingestion of hot foods or liquids). or parenteral vitamin B12. Gel for Intranasal Administration milk products or eggs) does not ADOSAGE vegetarian diet which contains no animal products (including AND ADMINISTRATION supply any vitamin initial B 12. Therefore, patientsNasal following a diet be advised to takein The recommended dose of Nascobal Spraysuch is one sprayshould (500 mcg) administered Nascobal Nasal Spray weekly. The need for vitamin B is increased by pregnancy and lactation. 12 be administered at least one hour before ONE nostril once weekly. Nascobal Nasal Spray should Deficiency has been recognized in foods infantsorofliquids. vegetarian mothers who were even though or one hour after ingestion of hot Periodic monitoring of breast serum fed, B12 levels should the no symptoms of deficiency at the time. be mothers obtained had to establish adequacy of therapy. Because the nasal dosage forms of Vitamin B12 have a lower absorption than intramuscular See LABORATORY TESTS monitoring B12 levels and adjustment dosage. dosage, nasal dosage formsforare administered weekly, rather thanofthe monthly intramuscular dosage. As shown in the Figure above, at the end of a month, weekly nasal administration results HOW SUPPLIED inNascobal significantly higher serum Vitamin B levels than after intramuscular administration. The patient 12 Nasal Spray, 500 mcg is supplied in boxes of 4 unit dose nasal spray devices and a should also understand the importance of returning for follow-up blood 500 testsmcg every to 6 months to package insert (NDC 49884-270-82). Each unit dose spray delivers of 3cyanocobalamin, confirm USP. adequacy of the therapy. STORAGE CONDITIONS INFORMATION PATIENTS Protect from light.FOR Keep covered in carton until ready to use. Store at controlled room temperature Patients with(59°F pernicious anemia be instructed that they will require weekly intranasal 15°C to 30°C to 86°F). Protectshould from freezing. administration of Nascobal Nasal Spray for the remainder of their lives. Failure to do so will result in To report reactions, contact Par Pharmaceutical Companies, Inc.toatthe 1-800-828return of suspected the anemiaadverse and in development of incapacitating and irreversible damage nerves of 9393. 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. Distributed by: (Hot foods may cause nasalPar secretions and a resulting loss of medication; therefore, patients Pharmaceutical Companies, Inc. should be told to administer Nascobal Nasal Spray least one hour before or one hour after Valley, NY,at 10977 Spring ingestion of hot foods or liquids). Rev. 04/14 OS270-01-1-05 A vegetarian diet which contains no animal products (including milk products or eggs) does not supply any vitamin B 12. 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 B 12 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. STORAGE CONDITIONS Protect from light. Keep covered in carton until ready to use. Store 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 1-800-8289393. Rev. 04/14 Distributed by: Par Pharmaceutical Companies, Inc. Spring Valley, NY, 10977 OS270-01-1-05