Histamine Phosphate

For use as a positive control in evaluation of allergenic (immediate hypersensitivity or "Type I") skin testing.

Histamine should not be injected into individuals with hypotension, severe hypertension, severe cardiac, pulmonary, or renal disease. Not to be used for diagnosis of pheochromocytoma or to test the ability of the gastric mucosa to secrete hydrochloric acid.

Care must be taken in intracutaneous testing to avoid injection into a venule or capillary. Pull back gently on the syringe plunger and note if blood is drawn. If blood is drawn, withdraw needle and inject into another skin site. Small doses by any route of administration may precipitate asthma in patients with bronchial hyperactivity. This product is not intended for inhalation, or subcutaneous injection. The utmost caution is advised in using histamine in such patients and in those with a history of bronchial asthma.

General A separate sterile needle or other percutaneous testing device should be used for each individual patient to prevent transmission of hepatitis and other infectious agents from one person to another. Epinephrine Injection (1:1,000) and injectable antihistamines should be available for immediate use in the event the patient exhibits a severe response. A tourniquet can be applied above the test site to slow absorption if a severe response occurs. Drug Interactions Drugs can interfere with the performance of skin tests in general, and specifically with histamine 1 . Antihistamines: Response to histamine is suppressed by antihistamines. The length of suppression varies, and is dependent on individual patient, type of antihistamine and length of time the patient has been on antihistamines. The duration of this suppression may be as little as 24 hours (chlorpheniramine), and can be as long as 40 days (astemizole). Tricyclic Antidepressants: These exert a potent and sustained decrease of skin reactivity to histamine, which may last for a few weeks. Beta 2 Agonists: Oral terbutaline and parenteral ephedrine, in general, have been shown to decrease allergen induced wheal. Theoretically, this may also reduce whealing capacity to histamine. Dopamine: Intravenous infusion of dopamine has been shown to inhibit skin test responses to histamine. Beta Blocking Agents: Propranolol can significantly increase skin test reactivity, including histamine. Other Drugs: Short acting steroids, inhaled beta agonists, theophylline and cromolyn do not seem to affect skin test response. Carcinogenesis, Mutagenesis, Impairment of Fertility Animal studies have not been conducted with Histamine. Nursing Mothers It is not known if Histamine administered percutaneously or intracutaneously appears in human milk. Because many drugs are excreted in human milk, caution should be exercised when histamine is administered to a nursing woman. Pregnancy Category C It is not known whether Histamine can cause fetal harm when administered during pregnancy or whether it can affect reproduction capacity. Histamine should be given during pregnancy only if clearly needed. There are no adequate and well-controlled studies during pregnancy. However, based on histamine's known ability to contract uterine muscle, exposure or repeated doses should be avoided. HISTATROL ® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus or mother. Pediatric Use Histamine solutions for percutaneous testing have been given safely in infants and young children. 2,3,4,5 Neonates and infants have lower skin test reactivity to histamines as well as common allergens. 3,4,5,6 About 20% of infants less than six months of age have been observed to have a negative reaction to histamine hydrochloride (1 mg/mL of salt). 4 Skin test reactivity gradually increases to age six and plateaus to age sixty. 2,3 Therefore, small skin test reactions should be anticipated in children under age six.

Local: Reactions such as wheal, erythema and localized pruritus are to be expected, but if very large (i.e. greater than 4+ as described dosage and administration) may be the first manifestation of a systemic reaction. Systemic: Following the injection of large doses of histamine, systemic reactions may include flushing, dizziness, headache, bronchial constriction, urticaria, asthma, marked hypertension or hypotension, abdominal cramps, vomiting, metallic taste, and local or generalized allergic manifestations (see also OVERDOSAGE ).

Drugs can interfere with the performance of skin tests in general, and specifically with histamine 1 . Antihistamines: Response to histamine is suppressed by antihistamines. The length of suppression varies, and is dependent on individual patient, type of antihistamine and length of time the patient has been on antihistamines. The duration of this suppression may be as little as 24 hours (chlorpheniramine), and can be as long as 40 days (astemizole). Tricyclic Antidepressants: These exert a potent and sustained decrease of skin reactivity to histamine, which may last for a few weeks. Beta 2 Agonists: Oral terbutaline and parenteral ephedrine, in general, have been shown to decrease allergen induced wheal. Theoretically, this may also reduce whealing capacity to histamine. Dopamine: Intravenous infusion of dopamine has been shown to inhibit skin test responses to histamine. Beta Blocking Agents: Propranolol can significantly increase skin test reactivity, including histamine. Other Drugs: Short acting steroids, inhaled beta agonists, theophylline and cromolyn do not seem to affect skin test response.

Category C It is not known whether Histamine can cause fetal harm when administered during pregnancy or whether it can affect reproduction capacity. Histamine should be given during pregnancy only if clearly needed. There are no adequate and well-controlled studies during pregnancy. However, based on histamine's known ability to contract uterine muscle, exposure or repeated doses should be avoided. HISTATROL ® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus or mother.

It is not known if Histamine administered percutaneously or intracutaneously appears in human milk. Because many drugs are excreted in human milk, caution should be exercised when histamine is administered to a nursing woman.

Histamine solutions for percutaneous testing have been given safely in infants and young children. 2,3,4,5 Neonates and infants have lower skin test reactivity to histamines as well as common allergens. 3,4,5,6 About 20% of infants less than six months of age have been observed to have a negative reaction to histamine hydrochloride (1 mg/mL of salt). 4 Skin test reactivity gradually increases to age six and plateaus to age sixty. 2,3 Therefore, small skin test reactions should be anticipated in children under age six.