Standardized Mite D. pteronyssinus 10000 [AU]/mL Solution, 5 mL — NDC 0268-7001-06 (Billing 00268-7001-06)

WARNINGS See warnings at the beginning of this package insert. Standardized allergenic extracts are not directly interchangeable with allergenic extracts of the same labeled potency from different manufacturers. The patient must be re-evaluated with the newly selected extract.

A reduction in starting dose is recommended in the following circumstances: Changing to a new lot of extract from the same manufacturer Using product from a different manufacturer Using non-standardized extract or any other change in formula Changing to a product bearing a later expiration date When a prolonged lapse in time has occurred since the last injection Withhold allergenic extracts temporarily or reduce the dose in patients with any one of the following conditions: - Severe rhinitis or asthma symptoms; - Infection or flu accompanied by fever; - Exposure to excessive amounts of clinically relevant allergen prior to therapy.

Allergenic extracts slowly become less potent with age. During the course of treatment, it may be necessary to continue therapy with a vial of extract bearing a later expiration date. The initial dose of the extract bearing the later expiration date should be lowered to a safe non-reaction-eliciting level.

When switching one standardized extract with another, at least 75% reduction in dose is suggested. Patients should always be observed for at least 20 to 30 minutes after any injection. In the event of a marked systemic reaction such as urticaria, angioedema, wheezing, dyspnea, respiratory obstructions, hypotension and coma, application of a tourniquet above the injection site and administration of 0.2 mL to 1.0 mL (0.01 mg/kg) of Epinephrine Injection (1:1000) is recommended.

Maximal recommended dose for children between 2 and 12 years of age is 0.3 mL. The tourniquet should not be left in place without loosening for 90 seconds every 15 minutes. Patients under treatment with beta-blockers may be refractory to the usual dose of epinephrine.

Volume expanders and vasopressor agents may be required to reverse hypotension. Inhalation bronchodilators and parenteral aminophylline may be required to reverse bronchospasm. In cases of respiratory obstruction, oxygen and intubation may be necessary.

Life-threatening reactions unresponsive to the above may require cardiopulmonary resuscitation. DO NOT GIVE INTRAVENOUSLY . Mite Extracts (D. farinae and/or D. pteronyssinus) contain small (<1%) amounts of residual media components (pork and yeast).

The physician should proceed with caution when using mite extract in mite sensitive individuals that also demonstrate sensitivity to these media components and only if clearly warranted. In the presence of active symptoms such as rhinitis, wheezing, dyspnea, etc., the indications of immunotherapy must be weighed carefully against the risk of temporarily aggravating the symptoms by the injection itself. If the protective action of allergenic extract injections is considered essential for the patient's welfare, appropriate symptomatic therapy with antihistaminic, adrenergic or other drugs might be needed either prior to or in conjunction with allergenic extract injections.

ADVERSE REACTIONS Local: Reactions at the site of injection may be immediate or delayed. Immediate wheal and erythema reactions are ordinarily of little consequence, but if very large, may be the first manifestation of systemic reaction. If large local reactions occur, the patient should be observed for systemic symptoms for which treatment is outlined below.

However, systemic reactions may occur in the absence of large local reactions. Delayed reactions start several hours after injection with local edema, erythema, itching or pain. They are usually at their peak at 24 hours and usually require no treatment.

Antihistamine drugs may be administered orally. The next therapeutic dose should be reduced to the dose which did not elicit a reaction, and subsequent doses increased more slowly, i.e., use of intermediate dilutions. Systemic: Reports from regulatory authorities in Sweden to the FDA, indicated that several deaths have been associated with the use of mite extracts.

The FDA was subsequently informed that these deaths may have been related to use by physicians untrained in the administration of potent extracts rather than a product defect. It should be noted that anaphylaxis and deaths following the injection of mite and other extracts have also been reported by The British Committee on Safety in Medicine. 9 Fatalities from immunotherapy in the United States since 1945 have been extensively reviewed by Lockey, R F, et al 10 , Reid M J et al.

11 and more recently by Bernstein, D. I. et al 23 . With careful attention to dosage and administration, such reactions occur infrequently, but it must be remembered that allergenic extracts are highly potent to sensitive individuals and OVERDOSE could result in anaphylactic symptoms.

Therefore, it is imperative that physicians administering allergenic extracts understand and be prepared for the treatment of severe reactions. Systemic reactions are characterized by one or more of the following symptoms: Sneezing, mild to severe general urticaria, itching other than at the injection site, extensive or generalized edema, wheezing, asthma, dyspnea, cyanosis, hypotension, syncope and upper airway obstruction. Symptoms may progress to shock and death.

Patients should always be observed for 20 to 30 minutes after any injection. Volume expanders and vasopressor agents may be required to reverse hypotension. Inhalational bronchodilators and parenteral aminophylline may be required to reverse bronchospasm.

Severe airway obstruction, unresponsive to bronchodilator, may require tracheal intubation and use of oxygen. In the event of a marked systemic reaction, application of a tourniquet above the injection site and the administration 0.2 mL to 1.0 mL of Epinephrine Injection (1:1000) is recommended. Maximal recommended dose for children under 2 years of age is 0.3 mL.

Maximal recommended dose for children between 2 and 12 years of age is 0.5 mL. The tourniquet should not be left in place without loosening for 90 seconds every 15 minutes. The next therapeutic injection of extract should be reduced to the dose which did not elicit a reaction, and subsequent doses increased more slowly, i.e., use of intermediate dilutions.

DRUG INTERACTIONS: Drugs can interfere with the performance of skin tests. 8 Antihistamines: Response to mediator (histamine) released by allergens 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 to several days. 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.

Dopamine: Intravenous infusion of dopamine may inhibit skin test responses. Beta Blocking Agents: Propranolol can significantly increase skin test reactivity (See WARNINGS ). Other Drugs: Short acting steroids, inhaled beta 2 agonists, theophylline and cromolyn do not seem to affect skin test response.

PRECAUTIONS INFORMATION TO PATIENTS: Patients should be instructed to describe any active allergic symptoms such as rhinitis, wheezing, dyspnea, etc., prior to injection including any late reactions from previous administration. Patients should remain in doctor's office for 20-30 minutes following injections and be instructed to report any local or systemic symptoms before leaving. Also, see ADVERSE REACTIONS and WARNINGS Sections.

If the protective action of allergenic extract injections is considered essential for the patient's welfare, appropriate symptomatic therapy with antihistaminic, adrenergic or other drugs might be needed either prior to or in conjunction with the allergenic extract injections. GENERAL Store allergenic extracts between 2 o - 8 o C at all times, even during use. Use sterile precautions.

Using a sterile tuberculin syringe, injections are given subcutaneously. A separate syringe must be used for each patient to prevent transmission of hepatitis and other infectious disease. Care must be taken to avoid injecting into a blood vessel.

Pull gently on syringe plunger to determine if a blood vessel has been entered (See Warnings ). Extracts in 50% glycerin can cause discomfort at the site of the injection during the injection. Standardized concentrates of allergenic extracts must be diluted prior to initiation of immunotherapy.

Dilute allergenic extracts may be more potent when diluted with Albumin saline than those which do not contain stabilizers such as albumin. PREGNANCY - CATEGORY C: Animal reproduction studies have not been conducted with allergenic extracts. It is also not known whether allergenic extracts can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

Controlled studies of hyposensitization with moderate to high doses of allergenic extracts during conception and all trimesters of pregnancy have failed to demonstrate any risk to the fetus or to the mother. However, on the basis of histamine's known ability to contract the uterine muscle, the release of significant amounts of histamine from allergen exposure of hyposensitization overdose should be avoided on theoretical grounds. Therefore, allergenic extracts should be used cautiously in a pregnant woman, and only if the benefit outweighs the risk.

PEDIATRIC USE: Children can receive the same dose as adults, however, to minimize the discomfort associated with dose volume it may be advisable to reduce the volume of the dose by half and administer the injection at two different sites. GERIATRIC USE: Studies in geriatric patients have not been conducted. Physicians should consider risk to benefit of immunotherapy in this patient population.

NURSING MOTHERS: It is not known if allergens administered subcutaneously appear in human milk. Because many drugs are excreted in human milk, caution should be exercised when allergenic extracts are administered to a nursing woman. CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: Long term studies in animals have not been performed.

DRUG INTERACTIONS: Drugs can interfere with the performance of skin tests. 8 Antihistamines: Response to mediator (histamine) released by allergens 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 to several days. 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.

Dopamine: Intravenous infusion of dopamine may inhibit skin test responses. Beta Blocking Agents: Propranolol can significantly increase skin test reactivity (See WARNINGS ). Other Drugs: Short acting steroids, inhaled beta 2 agonists, theophylline and cromolyn do not seem to a… [Excerpted — this section continues on DailyMed.]