Honey Bee Hymenoptera Venom Venomil Diagnostic: Package Insert and Label Information (Page 2 of 4)

WARNINGS

See WARNINGS box at the beginning of this Instruction Sheet. See also PRECAUTIONS.
Venom extract must be temporarily withheld from patients or the dose adjusted downward if any of the following conditions exist: (1) severe symptoms of rhinitis and/or asthma; (2) infection or flu accompanied by fever; (3) any evidence of an excessively large local or any generalized reaction during the initial stages of immunotherapy, or during maintenance therapy; and/or (4) insect sting prior to a scheduled injection. Do not administer venom injections during a period of symptoms following an insect sting or on the day the patient received an insect sting, since this could result in an allergen load that exceeds the patient’s tolerance.
THE CONCENTRATE MUST NOT BE INJECTED AT ANY TIME UNLESS TOLERANCE HAS BEEN ESTABLISHED. DILUTE CONCENTRATED EXTRACTS WITH STERILE ALBUMIN SALINE WITH PHENOL (0.4%) FOR SKIN TESTING AND IMMUNOTHERAPY.
INJECTIONS MUST NEVER BE GIVEN INTRA VENOUSLY. Subcutaneous injection is recommended. Intracutaneous or intramuscular injections may produce large local reactions or be excessively painful. AFTER INSERTING NEEDLE SUBCUTANEOUSLY, BUT BEFORE INJECTING, ALWAYS WITHDRAW THE PLUNGER SLIGHTLY. IF BLOOD APPEARS IN THE SYRINGE, CHANGE NEEDLE AND GIVE THE INJECTION IN ANOTHER SITE.
Patients with hypersensitivity to insect venom who undergo desensitization treatment while under concomitant therapy with ACE (angiotensin-converting enzyme) inhibitors, may have an increased risk of life-threatening anaphylactic reactions.(9) Patients without insect venom hypersensitivity, who take ACE inhibitors, and are stung by insects such as bee or wasp can show such reactions as well.(10)
Two patients undergoing desensitization treatment with Hymenoptera Venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.(11)

IF CHANGING TO A DIFFERENT LOT OR A FRESHLY RECONSTITUTED VIAL OF VENOM EXTRACT:
All extracts lose potency over time, and a fresh extract could have an effective potency that is substantially greater than that of the old extract. The first dose from the new vial should not exceed 50% of the previous dose.
IF THE VENOM EXTRACT PREVIOUSLY USED WAS FROM ANOTHER MANUFACTURER: Since manufacturing processes and sources of raw materials differ among manufacturers, the interchangeability of extracts from different manufacturers cannot be insured. The starting dose of the venom extract therefore should be greatly decreased even though the extract is the same formula and dilution. In general, a dose reduction to 50% of the previous product dose should be adequate, but each situation must be evaluated separately considering the patient’s history of sensitivity, tolerance of previous injections, and other factors. If the patient tolerates a 50% decrease, the next dose could be raised to the previous dose amount. If the decrease is greater than 50%, the next dose would need to be determined by the allergist, depending on the situation. Dose intervals should not exceed one week when rebuilding dose. See DOSAGE AND ADMINISTRATION.
IF A PROLONGED PERIOD OF TIME HAS ELAPSED SINCE THE LAST INJECTION: Patients may lose tolerance for allergen injections during prolonged periods between doses. The duration of tolerance is an individual characteristic and varies from patient to patient. In general, the longer the lapse in the injection schedule, the greater dose reduction required. If the interval since last dose is over four weeks, perform skin tests to determine starting dose. See DOSAGE AND ADMINISTRATION.
IF THE PREVIOUS EXTRACT WAS OUTDATED: The dating period for allergenic extracts indicates the time that they can be expected to remain potent under refrigerated storage conditions (2° — 8°C). During the storage of extracts, even under ideal conditions, some loss of potency occurs. For this reason, extracts should not be used beyond their expiration date. If a patient has been receiving injections of an outdated extract, s/he may experience excessive local or systemic reactions when changed to a new, and possibly more potent extract. In general, the longer the material has been outdated, the greater the dose reduction necessary when starting the fresh extract.

Proper selection of the dose and careful injection should prevent most systemic reactions. It must be remembered, however, that allergenic extracts are highly potent in sensitive individuals and that systemic reactions of varying degrees of severity may occur, ranging from mild to life-threatening anaphylaxis, or even death, as described under INDICATIONS AND USAGE and ADVERSE REACTIONS. Patients should be informed of this, and the warnings and precautions should be discussed prior to immunotherapy. See PRECAUTIONS below. Systemic reactions should be treated as indicated in ADVERSE REACTIONS.

PRECAUTIONS

1. GENERAL

The presence of asthmatic signs and symptoms appear to be an indicator for severe reactions following allergy injections. An assessment of airway obstruction either by measurement of peak flow or an alternate procedure may provide a useful indicator as to the advisability of administering an allergy injection. (1, 12-16)
Concentrated extracts must not be injected unless tolerance has been established.
Diluting fluid should be forcibly drawn into the sealed vial when the syringe needle penetrates the seal during reconstitution. Failure of this to occur for a particular vial indicates possible loss of vacuum. Vials without vacuum should be returned to the manufacturer.
Record date of reconstitution and expiration date of reconstituted product in the space provided on the product label. Date of expiration after reconstitution must not exceed the Final Expiration Date indicated on the container label. (See table below for expiration dates, including dilutions).
Store freeze-dried and reconstituted venom product, stock solutions and venom dilutions constantly at 2 — 8 C.

Venom Concentration Diluent Recommended Expiration Date*
100 µg/mL Albumin Saline with Phenol (0.4%) 6 Months
10µg/mL Albumin Saline with Phenol (0.4%) 1 month
1 µg/mL Albumin Saline with Phenol (0.4%) 1 month
0.1 µg/mL Albumin Saline with Phenol (0.4%) 14 days
Less than 0.1 µg/mL Albumin Saline with Phenol (0.4%) Prepare fresh daily

*But not to exceed Final Expiration Date indicated on the container label.


Sterile solutions, vials, syringes, etc., should be used and aseptic precautions observed in making dilutions.
To avoid cross-contamination, do not use the same needle to withdraw materials from vials of more than one extract, or extract followed by diluent.
A sterile tuberculin syringe, with a needle at least 5/8″ long and graduated in 0.01 mL units, should be used to measure carefully each dose from the appropriate dilution. Aseptic techniques should always be employed when injections are being administered.
A separate sterile syringe should be used for each patient to prevent transmission of hepatitis and other infectious agents from one person to another.
Patient reactions to previous injections should be reviewed before each new injection so that dose can be adjusted accordingly. See ADVERSE REACTIONS and WARNINGS.
Rarely, a patient is encountered who develops systemic reactions to minute doses of allergen and does not demonstrate increasing tolerance to injections after several months of treatment. It is suggested that if systemic reactions or excessive local responses occur persistently at very small doses, efforts at immunotherapy should be stopped.
PATIENTS SHOULD BE OBSERVED IN THE OFFICE FOR AT LEAST 30 MINUTES AFTER SKIN TESTING AND AFTER EACH TREATMENT INJECTION. Most severe reactions will occur within this time period, and rapid treatment measures should be instituted. See ADVERSE REACTIONS for such treatment measures.

2. INFORMATION FOR PATIENTS

Patients should be instructed in the recognition of adverse reactions to immunotherapy, and in particular, to the symptoms of shock. (See WARNINGS box at the beginning of this Instruction Sheet). Patients should be made to understand the importance of a 30 minute observation period following skin testing or therapeutic injections, and be cautioned to return to the office promptly if symptoms occur after leaving. Patients should be instructed in the use of, and have available, an Emergency Anaphylaxis Kit for self-administration of epinephrine.
Patients must be instructed to report any insect stings that have occurred, since a venom injection should not be given on the same day as the sting, nor during a time when the patient is still experiencing symptoms from the sting.

3. DRUG INTERACTIONS

Patients with cardiovascular diseases and/or pulmonary diseases such as symptomatic, unstable, steroid-dependent asthma, and/or those who are receiving cardiovascular drugs such as beta blockers, may be at higher risk for severe adverse reactions. These patients may also be more refractory to the normal allergy treatment regimen. Patients should be treated only if the benefit of treatment outweighs the risks.(1)
Patients on beta blockers may be more reactive to allergens given for testing or treatment and may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.
See WARNINGS section regarding concurrent treatment with ACE inhibitors.
Certain medications may lessen the skin test wheal and erythema responses elicited by allergens and histamine for varying time periods. Conventional antihistamines should be discontinued at least 5 days before skin testing. Long acting antihistamines should be discontinued for at least 3 weeks prior to skin testing.(17) Topical steroids should be discontinued at the skin test site for at least 2-3 weeks before skin testing.(17, 18)
Tricyclic antidepressants such as doxepin, should be withheld for at least 7 days before skin testing.(19) Topical local anesthetics may suppress the flare responses and should be avoided on skin test sites .(20)
When using other drugs in patients receiving allergenic extracts, always consult the product labeling of the other drugs to determine any possible interaction with use of allergenic extracts, and specifically with stinging insect (Hymenoptera) venom extracts.

4. CARCINOGENESIS AND MUTAGENSIS AND IMPAIRMENT OF FERTILITY

Long-term studies in animals have not been conducted with allergenic extracts to determine their potential for carcinogenicity, mutagenicity, or impairment of fertility.

5. PREGNANCY

(12, 21)
Animal reproduction studies have not been conducted with Hymenoptera Venom Products. It is also not known whether Hymenoptera Venom Products can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Hymenoptera Venom Products should be given to a pregnant woman only if clearly needed.

On the basis of histamine’s known ability to contract uterine muscle, theoretically, a systemic reaction, whether occurring from insect sting or from venom skin testing or treatment dose, should be avoided. Therefore, the physician must carefully consider the benefit-to-risk ratio, to both patient and fetus, of continuing venom immunotherapy during pregnancy, or performing venom skin testing, and especially of initiating a venom immunotherapy program where there is a possibility that the patient may not be able to reach the recommended maintenance dose without significant risk of a systemic reaction.

6. NURSING MOTHERS

There are no current studies on secretion of the allergenic extract components in human milk or effect on the nursing infant. Because many drugs are excreted in human milk, caution should be exercised when allergenic extracts are administered to a nursing woman.

7. PEDIATRIC USE

Since dosage for the pediatric population is the same as for adults, the larger volumes of solution may produce excessive discomfort. Therefore, in order to achieve the total dose required, the volume of the dose may need to be divided into more than one injection per visit. A study done in children ages 4 to 17 showed no special problems with venom immunotherapy in this population.(22)

8. GERIATRIC USE

The reactions from immunotherapy can be expected to be the same in elderly patients as in younger ones. Elderly patients may be more likely to be on medication that could block the effect of epinephrine which could be used to treat serious reactions, or they could be more sensitive to the cardiovascular side effect of epinephrine because of pre-existing cardiovascular disease.(23)

ADVERSE REACTIONS

Physicians administering Hymenoptera Venom testing or treatment materials should be experienced in the treatment of severe systemic reactions (see WARNINGS box at the beginning of this Instruction Sheet).
(1) Local Reactions
Some erythema, swelling or pruritis at the site of injection are common, the extent varying with the patient. Excessively large, painful or persistent local reactions can occur from skin tests or immunotherapy. Frequent application of cold, wet dressings to the area and/or the use of oral antihistamines will ameliorate the discomfort. Reactions usually subside in 24-36 hours. Large local reactions occurred in approximately 60% of the patients given immunotherapy in a clinical study. None of the local reactions required specific treatment; however, subsequent injections in many instances were held to the previous dose or a reduced dose. Some patients had repeated large local reactions that slowed the increase in the immunotherapy dose.4
See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION Sections.
A mild burning immediately after the injection is to be expected. This usually leaves in 10 to 20 seconds. See also WARNINGS and PRECAUTIONS regarding proper method and route of injection.
(2) Systemic Reactions
Most severe systemic reactions will begin within a 30 minute time period, but systemic reactions may occur at any time after skin tests or immunotherapy. Symptoms may range from mild to life threatening from anaphylaxis as described under INDICATIONS AND USAGE.
With careful attention to dosage and administration, severe systemic reactions occur infrequently, but it cannot be overemphasized that in sensitive individuals, any injection could result in anaphylactic shock. Therefore, it is imperative that physicians administering allergenic extracts understand and be prepared for the treatment of severe reactions. See CLINICAL PHARMACOLOGY for clinical incidence of systemic reactions and course of action following these reactions.
If a systemic or anaphylactic reaction does occur, inject 1:1000 epinephrine-hydrochloride intramuscularly or subcutaneously.
EPINEPHRINE DOSAGE
ADULT: 0.3 to 0.5 mL should be injected. Repeat in 5 to 10 minutes if necessary.
PEDIATRIC: The usual initial dose is 0.01 mg (mL) per kg body weight or 0.3 mg (mL) per square meter of body surface area. Suggested dosage for infants to 2 years of age is 0.05 mL to 0.1 mL; for children 2 to 6 years, 0.15 mL; and children 6 to 12 years, 0.2 mL. Single pediatric doses should not exceed 0.3 mg (mL). Doses may be repeated as frequently as every 20 minutes, depending on the severity of the condition and the response of the patient.
After administration of epinephrine, profound shock or vasomotor collapse should be treated with intravenous fluids, and possibly vasoactive drugs. Airway patency should be insured. Oxygen should be given by mask. Intravenous antihistamines, inhaled bronchodilators, theophylline and/or corticosteroids may be used if necessary after adequate epinephrine and circulatory support have been given.
Emergency resuscitation measures and personnel trained in their use must be available immediately in the event of a serious systemic or anaphylactic reaction not responsive to the above measures [Ref. J. Allergy and Clinical Immunology, 77(2): p.271-273, 1986]. Rarely are all of the above measures necessary; epinephrine usually produces a prompt response. However, the physician should be prepared in advance for all contingencies. Promptness in beginning emergency treatment measures is of utmost importance. For recommendations regarding how to proceed with venom extract dose following systemic reactions, see WARNINGS, PRECAUTIONS and DOSAGE AND ADMINISTRATION.
3. Adverse Event Reporting
Report all adverse events to Jubilant HollisterStier LLC Customer Technical Services Department at 1(800) 992-1120. A voluntary adverse event reporting system for health professionals is available through the FDA MEDWATCH program. Preprinted forms (FDA Form 3500) are available from the FDA by calling 1(800) FDA-1088. Completed forms should be mailed to MEDWATCH, 5600 Fisher Lane, Rockville, MD 20852-9787 or Fax to: 1(800) FDA-0178.

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2020. All Rights Reserved.