Included as part of the PRECAUTIONS section.
Obtain hematocrit, reticulocyte count, vitamin B12, folate, and iron levels prior to treatment. All hematologic parameters, including vitamin B12 concentrations, should be normal before initiating treatment with CaloMist. Monitor serum vitamin B12 concentrations periodically to confirm adequacy of therapy. Monitor Vitamin B12 concentrations and complete blood counts one month after starting CaloMist and then at 3 to 6 month intervals thereafter. Monitor methylmalonic acid and homocysteine concentrations in patients with borderline-low vitamin B12 concentrations (<300 ng/L) as these are more sensitive measures of vitamin B12 deficiency in this setting. Switch back to intramuscular route of administration for patients with declining or abnormally low vitamin B 12 concentrations despite maximal doses of CaloMist. Vitamin B12 deficiency that is inadequately treated for longer than three months may produce irreversible neurological damage.
Use In Patients With Nasal Pathology
CaloMist has not been evaluated in patients with nasal pathology. In patients with nasal pathology, defer treatment with CaloMist until nasal symptoms have subsided. Patients with chronic nasal symptoms or significant nasal pathology are not ideal candidates for intranasal vitamin B12 therapy. If CaloMist therapy is attempted in these patients, monitor vitamin B12 concentrations more frequently than in patients without nasal pathology because of the potential for erratic or blunted absorption.
Use In Patients With Leberâ€™s Disease
Patients with early Leberâ€™s disease (hereditary optic nerve atrophy) who were treated with cyanocobalamin suffered severe and swift optic atrophy. Cyanocobalamin is not recommended for use in these patients.
Anaphylaxis And Angioedema
Anaphylactic shock, death, and angioedema were not reported in the CaloMist clinical trial but have been reported with parenteral vitamin B12 administration.
Megaloblastic anemia has many causes, including vitamin B12 deficiency and folate deficiency. Folic acid may result in a hematological response in patients with vitamin B12 deficiency but will not prevent irreversible neurological manifestations. Vitamin B12 is not an appropriate treatment for folate deficiency.
Hypokalemia, thrombocytosis, and sudden death may occur when severe megaloblastic anemia is treated intensely with vitamin B12. Monitor serum potassium and platelet counts more frequently in this setting.
Blunted Response To Vitamin B12 Therapy Infections, uremia, concurrent iron or folic acid deficiency, and drugs with bone marrow suppressant properties (e.g., chloramphenicol) may blunt the therapeutic response to vitamin B12 products, including CaloMist.
Patient Counseling Information
- Advise the patient to read the FDA-approved patient labeling (Instructions for Use)
- Important Information For Patients
- Advise patients with a chronic underlying cause of vitamin B12 deficiency that they will require indefinite administration of a vitamin B12 product, such as CaloMist. Noncompliance or inadequate treatment with vitamin B12 therapy may result in recurrence of anemia and the development or worsening of irreversible neurological damage.
- Advise patients to separate the dosing of CaloMist and other intranasal medications by several hours.
- Advise patients that Vitamin B12 levels will be monitored one month after CaloMist initiation or dose change and every 3-6 months thereafter.
- Instruct patients on how to prime the actuator and administer the dose of CaloMist. Have the patient demonstrate the administration procedure.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
There are no long-term studies in animals that have evaluated the carcinogenic potential of any of the vitamin B12 products, including CaloMist. 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 malignancy has been attributed to the underlying pathology of pernicious anemia and not to treatment with vitamin B12.
No studies have been performed to evaluate the potential of CaloMist for genotoxicity.
Animal reproduction studies assessing the effects of CaloMist on male and female fertility have not been conducted.
Use In Specific Populations
Administration of the approved recommended dose of CaloMist is not expected to cause major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with CaloMist nasal spray. There are risks associated with vitamin B12 deficiency during pregnancy (see Clinical Considerations).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Disease-Associated Maternal And/Or Embryo/Fetal Risk
Severe maternal vitamin B12 deficiency during pregnancy may result in adverse pregnancy outcomes such as low birth weight, preterm birth and megaloblastic anemia.
Vitamin B12 is present in human milk. Administration of the approved recommended dose of CaloMist is not expected to cause harm to a breastfed child. There is no information on the effects of CaloMist on the breastfed child or on milk production. The developmental and health benefits of breastfeeding should be considered along with the motherâ€™s clinical need for CaloMist and any potential adverse effects on the breastfed infant from the underlying maternal condition.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of CaloMist did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Patients with vitamin B12 deficiency and concurrent renal or hepatic disease may require increased doses or more frequent administration of vitamin B12 therapy.