Alk-abello, Inc.

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Alk-abello, Inc. Drugs

Advanced Acne Wash

Advanced Acne Wash

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

When diluting bulk extracts, use of either Sterile Diluent for Allergenic Extracts or Sterile Diluent for Allergenic Extracts Normal Saline with HSA is recommended. Dilutions should be made with sterile disposable syringes using aseptic technique. Commonly 10 fold dilutions are used to achieve a desired concentration for intradermal testing or initiation and continuation of immunotherapy. For example, transferring 0.5 mL of a 10,000 AU/mL extract into 4.5 mL of diluent will yield 5 mL of extract @ 1,000 AU/mL. Prepare as many additional serial dilutions as necessary to reach the appropriate concentration.

Care should be exercised to avoid cross contamination of allergens if mixing with other allergenic extracts. The use of separate syringes for each allergen and diluent when compounding patient mixes is recommended.

Diagnosis - In diagnosing the sensitive individual, the symptom history must be associated with exposure to the allergen. Skin testing is used in conjunction with a definitive history for diagnosing individual sensitivities.

An excellent method of recording results is to cover the skin reaction with transparent tape, outline the erythema first then the wheal with an indelible pen, then remove the tape and transfer it to the patient's permanent record. For preferred results, it is recommended that the actual measurement of the extent of both responses be recorded. This can be accomplished by measuring the longest erythema diameter, then selecting the mid - point of that line and measuring at a 90° angle to that line to determine the orthogonal diameter. The sum of these two measurements is the sum of erythema (ƩE); the sum of wheal diameters is determined in a similar manner.

Patient's response is graded on the basis of the size of erythema and/or wheal.

Percutaneous (prick/scratch/puncture) test:

Prick, scratch, or puncture skin tests should be performed initially using an extract specially made for this purpose. The usual dose is one drop.

In a skin test study of 10 patients who were determined to be allergic to mite (D. farinae), the mean puncture test (using a bifurcated needle) to a solution containing 10,000 AU/mL had a sum of erythema of 73 mm (range 43 - 138 mm) and a sum of wheal of 17 mm (range 7 - 31 mm).

In another skin test study of 11 patients who were determined to be allergic to mite (D. pteronyssinus), the mean puncture test (using a bifurcated needle) to a solution containing 10,000 AU/mL had a sum of erythema of 84 mm (range 56 - 112 mm) and a sum of wheal of 20 mm (range 7 - 33 mm).

What follows are general guidelines for percutaneous testing. Different devices and/or techniques influence the size of the reaction, therefore it is important to refer to the device manufacturer's or distributor's instructions when grading reactions.

0       No wheal. Erythema absent or very slight (not more than 1 mm in diameter).

+       Wheal absent or very slight erythema present (not more than 3 mm diameter).

++       Wheal not more than 3 mm diameter, or erythema not more than 5 mm diameter.

+++       Wheal between 3 mm and 5 mm in diameter with erythema. Possible pseudopodia and itching.

++++       Any larger reaction with itching and possible pain.

Intradermal test:

On the forearm or upper outer aspect of the arm, using a 26 - 27 gauge, short bevel needle, inject intradermally .05 mL of the intradermal test solution. Skin whealing responses should be observed 10 - 20 minutes after administering the test.

In a skin test study of the 10 mite puncture reactive patients (D. farinae) described above, the mean intradermal dose for ƩE = 50 mm was 0.01 AU/mL ( range = <0.0003 to 0.4 AU/mL).

In the skin test study of the 11 mite puncture reactive patients (D. pteronyssinus) described above, the mean intradermal dose for ƩE = 50 mm was 0.006 AU/mL ( range = <0.0007 to 0.05 AU/mL).

Intradermal testing should start with a dilute solution, usually in the range of 1 AU or less.

Glycerinated extracts diluted for intradermal testing may be diluted at least 25 fold to less than 2% glycerin (by volume) as glycerin above this level can cause false positive intradermal skin tests.

A negative skin test is one where the sum of erythema was 0 or equal to the sum of the wheal. As a negative control, the diluent should be tested and included in the interpretation of the skin reactions.

0       No increase in size of bleb since injection. No erythema.

+       An increase in size of bleb and a wheal not more than 5 mm diameter with associated erythema.

++       Wheal between 5 mm and 8 mm in diameter with erythema.

+++       Wheal between 8 mm and 12 mm in diameter with erythema and possible pseudopodia, itching or pain.

++++       Any larger reaction with itching and pain and possible diffuse blush of the skin surrounding the reaction area.

Immunotherapy - Starting dose for immunotherapy is related directly to a patient's sensitivity as determined by carefully executed skin testing. Degree of sensitivity can be established by determination of D50 (the intradermal dose, base three, that produces a ƩE = 50 mm).1

A general rule is to begin at 1/10 of the dose that produces sum of erythema of 50 mm (approximately a 2+ positive skin test reaction). For example, if a patient exhibits a 2+ intradermal reaction to

1 AU/mL, the first dose should be no higher than 0.05 mL of 0.1 AU/mL. Dosage may be increased by 0.05 mL each time until 0.5 mL is reached, at which time the next 10-fold more concentrated dilution can be used, beginning with 0.05 mL, if no untoward reaction is observed. (See beginning of DOSAGE AND ADMINISTRATION section for instructions in preparing dilutions of concentrates.)

If a tolerated dose of allergenic extract has been established, the initial dose from the new extract should be reduced by 75% of the previously well tolerated dose (see also Precautions).

Interval between doses in the early stages of immunotherapy is no more than once to twice a week, and may gradually be increased to once every two weeks. Generally, maintenance injections may be given as infrequently as once every two weeks to once a month. The progress of patients on immunotherapy should be closely monitored. If improvement is realized a usual course of treatment may be from 3 to 5 years. If progress is unsatisfactory for a year or more, discontinuation of immunotherapy should be considered.

Injections are given subcutaneously preferably in the arm. It is advantageous to give injections in alternate arms and routinely in the same area. In some patients, a local tolerance to the allergen may develop thus preventing a possible severe local reaction.

After inserting the needle, but before injecting the dose, pull plunger of the syringe slightly, if blood returns in the syringe, discard the syringe and contents and repeat injection at another site.

Bulk concentrated extracts must be diluted for initial therapy and intradermal skin testing. For recommended diluent, refer to the beginning of the DOSAGE AND ADMINISTRATION section.

Use standard aseptic precautions when making dilutions. The first dose of the new extract should be reduced at least 50% - 75% of the amount of the dosage from the previous extract.

Stability studies for diluted and undiluted forms of this product are not complete. Indications are the undiluted product will retain its potency under recommended storage conditions at least until the expiration date on the vial label is reached. It is recommended that minimal amounts of the concentrate be diluted so that the diluted product is used up within a relatively short period of time, i.e., preferably not more than four weeks.
Fire Ant

Fire Ant

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

When diluting bulk extracts, use of Sterile Diluent for Allergenic Extracts or Sterile Diluent for Allergenic Extracts Normal Saline with HSA (albumin saline) is recommended. Dilutions should be made with sterile disposable syringes using aseptic technique. Commonly, 10 fold dilutions are used to achieve a desired concentration for initiation and continuation of immunotherapy. For example, transferring 0.5 mL of a 10,000 PNU/mL extract into 4.5 mL of diluent will yield 5 mL of extract at 1,000 PNU/mL. For weight volume products, a 1:100 w/v dilution may be prepared from a 1:10 w/v by transferring 0.5 mL of the 1:10 w/v to 4.5 mL of diluent. Prepare as many additional serial dilutions as necessary to reach the appropriate concentration.

Starting dose for immunotherapy is related directly to a patient’s sensitivity as determined by carefully executed skin testing. Degree of sensitivity can be established by determination of D50.11 A general rule is to begin at 1/10 of the dose that produces sum of erythema of 50 mm (approximately a 2+ positive skin test reaction).

For example, if a patient exhibits a 2+ intradermal reaction to 1 AU/mL, the first dose should be no higher than 0.05 mL of 0.1 AU/mL. Dosage may be increased by 0.05 mL each time until 0.5 mL is reached, at which time the next 10-fold more concentrated dilution can be used, beginning with 0.05 mL, if no untoward reaction is observed.

Interval between doses in the early stages of immunotherapy is no more than once to twice a week, and may gradually be increased to once every two weeks. Generally, maintenance injections may be given as infrequently as once every two weeks to once a month.

Injections are given subcutaneously, preferably in the arm. It is advantageous to give injections in alternate arms and routinely in the same area. In some patients, a local tolerance to the allergen may develop thus preventing a possible severe local reaction.

Formal stability studies for diluted and undiluted forms of unstandardized extracts have not been performed; therefore, it is recommended that minimal amounts of the concentrate be diluted so that the diluted product is used up within a relatively short period of time; i.e., preferably not more than four weeks.

PRE-SEASONAL METHOD OF TREATMENT

Treatment of hay fever by the pre-seasonal method should be started 6-10 weeks prior to the usual onset of symptoms. Therapy should be started early enough to permit a graduated series of doses at 2-7 day intervals. It is recommended that the larger doses be spaced 5-7 days apart.

Some physicians continue therapy into or through the season by repeating a reduced or MAINTENANCE dose at weekly or biweekly intervals. If during the season, hay fever symptoms develop, relief may be provided by giving supplemental treatment. If the last dose was well-tolerated and not more than 2 weeks has elapsed since it was given, this dose may be given again and repeated every 4 to 7 days.

PERENNIAL TREATMENT

The patient’s tolerance to the offending pollen or pollens is first established by the injection of a series of graduated doses as outlined in the PRE-SEASONAL METHOD, not necessarily given pre-seasonally, since perennial therapy may be begun at any time. After completion of the ascending series of injections, from 1/4 to 1/2 of the highest well-tolerated dose is continued at 2 to 3 week intervals throughout the year. Shortly before the usual onset of symptoms (4 to 5 weeks prior to the season) the interval between injections is shortened and the dosage is gradually increased, according to the Pre-Seasonal schedule, until maximum well-tolerated dose is again attained. This top dose should be reached just before the usual onset of symptoms at which time the treatment is discontinued. If patient’s symptoms persist, therapy may be continued at a reduced dosage level, usually 1/4 to 1/2 of the top dose.

DOSAGE ADJUSTMENTS

For Products Containing Short Ragweed.

In transferring patients from unstandardized to standardized product, the physician should establish the potency relationships, perhaps by comparative skin testing, prior to injecting the first standardized dose.

AgE is important in adjusting dosage of Short Ragweed extracts to accurately transfer a patient from older extracts to fresher material. In such cases, the dosage of AgE should be considered in addition to the W/V dilution or protein nitrogen units. Antigen E concentration continuously declines in Short Ragweed Pollen extracts at a rate that varies with the formulation of the product. Aqueous extracts retain Antigen E potency less effectively than glycerin 50% (v/v) extracts. These differences are reflected in the expiration date declared on the vial. The continuous decline should be considered. Also, where ragweed is a component of an allergen mixture, clinical response to the other components must be considered in adjustment of dosage based on AgE content alone. The usual course of immunotherapy is three to five years.

Caution: A small percent of individuals allergic to Short Ragweed are more sensitive to minor antigens such as Ra3 Ra5 than AgE. There is no correlation between the amount of these antigens and either AgE or PNU content.

NOTE: For extracts of Short Ragweed or equal part mixture of Short and Tall Ragweed refer to AgE dosage schedule. The AgE content for those products is indicated on the vial label. The physician may use the formula below to determine the AgE dosage for each injection.

AgE dosage can be monitored by using the following formula:W/V compounded products:Labeled AgE X Dose (mL) = dose in AgEPNU compounded products:Labeled AgE/mL X dose in PNU = dose in AgELabeled PNU/mL
Bermuda Grass

Bermuda Grass

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

When diluting bulk extracts, use of Sterile Diluent for Allergenic Extracts or Sterile Diluent for Allergenic Extracts Normal Saline with HSA are recommended. Dilutions should be made with sterile disposable syringes using aseptic technique. Commonly 10 fold dilutions are used to achieve a desired concentration for intradermal testing or initiation and continuation of immunotherapy. For example transferring 0.5 mL of a 10,000 BAU/mL extract into 4.5 mL of diluent will yield 5 mL of extract @ 1,000 BAU/mL. Prepare as many additional serial dilutions as necessary to reach the appropriate concentration.

Stock mixtures of grass pollen extracts are compounded from individual grass pollen extracts. The total potency per milliliter (mL) of these mixtures is described on the container label, where space permits. The contribution each individual component is expressed in the supplemental labeling accompanying the vial.

Diagnosis –

In diagnosing the sensitive individual, the symptom history must be associated with exposure to the allergen. Skin testing is used in conjunction with a definitive history for diagnosing individual sensitivities.

An excellent method of recording results is to cover the skin reaction with transparent tape, outline the erythema first then the wheal with an indelible pen, then remove the tape and transfer it to the patient's permanent record. For preferred results, it is recommended that the actual measurement of the extent of both responses be recorded. This can be accomplished by measuring the longest erythema diameter, then selecting the mid-point of that line and measuring at a 90o angle to that line to determine the orthogonal diameter. The sum of these two measurements is the sum of erythema (ƩE); the sum of wheal diameters is determined in a similar manner.

Patient's response is graded on the basis of the size of erythema and/or wheal.

Percutaneous (prick/scratch/puncture) test:

Prick, scratch, or puncture skin tests should be performed initially using a glycerinated extract at 10,000 BAU/mL.

What follows are general guidelines for percutaneous testing14. Different devices and/or techniques influence the size of the reaction, therefore it is important to refer to the device manufacturer's or distributor's instructions when grading reactions. As a negative control the diluent should be tested and included in the interpretation in the skin test reactions. Use of a positive control such as histamine base at 1 mg/mL should be used to assess skin test reactivity.
0 No reaction or less than control + Erythema greater than control, smaller than a nickel (21 mm diameter) ++ Erythema greater than a nickel in diameter, no wheal +++ Wheal and erythema without pseudopods ++++ Wheal and erythema with pseudopods
Intradermal test:

Intradermal testing should start with a dilute solution, usually in the range of 0.1 BAU/mL or less.

Glycerinated extracts diluted for intradermal testing may be diluted at least 25-fold to less than 2% glycerin (by volume) as glycerin above this level can cause false positive intradermal skin tests. Use a negative control skin test with glycerin content equal to the glycerin content of the allergen dose used for intradermal testing. Use of a positive control such as histamine base at 0.1 mg/mL or 0.01 mg/mL should be used to test reactivity.

On the forearm or upper outer aspect of the arm, using a 26 - 27 gauge, short bevel needle, inject intradermally 0.05 mL of the intradermal test solution. Skin whealing responses should be observed 10 - 20 minutes after administering the test.

A negative skin test is one where the sum of erythema was 0 or equal to the sum of the wheal. As a negative control, the diluent should be tested and included in the interpretation of the skin reactions. What follows are general guidelines intradermal testing 14.
0 No reaction or less than negative control + 3-4 mm wheal with erythema, or erythema alone larger than a nickel (21 mm diameter) ++ 4-8 mm wheal and erythema without pseudopods +++ Over 8 mm wheal and erythema without pseudopods ++++ Wheal and erythema with pseudopods
Immunotherapy -

Starting dose for immunotherapy is related directly to a patient's sensitivity as determined by carefully executed skin testing. Degree of sensitivity can be established by determination of D50 (the intradermal dose, base three, that produces a ƩE = 50 mm).1

A general rule is to begin at 1/10 of the dose that produces sum of erythema of 50 mm (approximately a 2+ positive skin test reaction). For example, if a patient exhibits a 2+ intradermal reaction to 1 BAU/mL, the first dose should be no higher than 0.05 mL of 0.1 BAU/mL. Dosage may be increased by 0.05 mL each time until 0.5 mL is reached, at which time the next 10-fold more concentrated dilution can be used, beginning with 0.05 mL, if no untoward reaction is observed.

If a tolerated dose of allergenic extract has been established, the initial dose from the new extract should be reduced to 25% of the previously well tolerated dose (see also Precautions).

Interval between doses in the early stages of immunotherapy is no more than once to twice a week, and may gradually be increased to once every two weeks. Generally, maintenance injections may be given as infrequently as once every two weeks to once a month.

Injections are given subcutaneously preferably in the arm. It is advantageous to give injections in alternate arms and routinely in the same area. In some patients, a local tolerance to the allergen may develop thus preventing a possible severe local reaction.

After inserting the needle, but before injecting the dose, pull plunger of the syringe slightly. If blood returns in the syringe, discard the syringe and contents and repeat injection at another site.

Bulk concentrated extracts must be diluted for initial therapy and intradermal skin testing. For recommended diluent, refer to DOSAGE AND ADMINISTRATION section.

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.

Use standard aseptic precautions when making dilutions. The first dose of the new extract should be reduced at least 75% of the amount of the dosage from the previous extract.

Stability studies for diluted and undiluted forms of this product are not complete. Indications are the undiluted product will retain its potency under recommended storage conditions at least until the expiration date on the vial label is reached. It is recommended that minimal amounts of the concentrate be diluted so that the diluted product is used up within a relatively short period of time; i.e., preferably not more than four weeks.
Cat Hair

Cat Hair

Dilution

Allergenic extract concentrates must be diluted before use in intradermal skin testing or the initial stages of immunotherapy. As with any parenteral product, always use careful aseptic technique in preparing dilutions, assuring that the vials, diluents, and syringes are sterile, and that the dilutions are prepared under aseptic conditions, Sterile diluents that can be used include Normal Saline, Buffered Saline, 50% glycerin or Albumin Saline (HSA).

To obtain the concentrations required for intradermal testing or for the initial stages of immunotherapy, prepare serial 5 or 10 fold dilutions of the concentrate, to achieve the concentrations specified in Table 2 or 3, below. The relatively small 0.5 ml volume conserves the original concentrate, and is convenient because sterile diluent is readily available in prefilled 2.0 and 4.5 ml volumes.
Table 2 Examples of Ten-fold Dilution Series DilutionNumber Add ThisVolume/Dilutionof Extract To thisDiluentVolume To Obtain Extractat the FollowingConcentration (BAU/ml) 0123456 Concentrate0.5 ml concentrate0.5 ml dilution #10.5 ml dilution #20.5 ml dilution #30.5 ml dilution #40.5 ml dilution #5 __4.5 ml4.5 ml4.5 ml4.5 ml4.5 ml4.5 ml 10,0001,000100101.00.100.01 Table 3 Examples of Five-fold Dilution Series DilutionNumber Add ThisVolume/Dilutionof Extract To thisDiluentVolume To Obtain Extractat the FollowingConcentration (BAU/ml) 0123456 Concentrate0.5 ml concentrate0.5 ml dilution #10.5 ml dilution #20.5 ml dilution #30.5 ml dilution #40.5 ml dilution #5 __2.0 ml2.0 ml2.0 ml2.0 ml2.0 ml2.0 ml 5,0001,0002004081.60.32
For each vial, record the date of dilution on the label.

Skin Testing

Scratch or prick-puncture testing should be performed using the 10,000 BAU/ml concentrate, a negative control (diluent) and a positive control (histamine 1.8 mg/ml). Extract for intradermal testing can be prepared by diluting the concentrate with any appropriate aqueous sterile diluent, as described above. A 100 BAU/ml concentration is also available for intradermal testing.

The following skin testing protocol can be recommended:
The location for both prick and intradermal testing is usually the flexor surface of the forearm. Use aseptic technique throughout. Perform a preliminary skin prick test with the extract concentrate, by placing a drop of the extract on the skin and then using a needle to prick the skin gently through the drop. Use a normal diluent as negative control and histamine as a positive control. Read the test after 15 minutes. Patients reacting strongly to the prick test should be considered highly sensitive to the extract, and suitable precautions should be taken. A suggested grading system appears in Table 4. If the histamine control is negative, the possibility of skin non-reactivity must be considered. Begin intradermal testing, generally starting at the 100 BAU/ml dilution if the prick test was negative, or at 0.1 or 0.01 BAU/ml if the test was positive or if no prick test was done. Use a separate, sterilized syringe and needle for each extract and each patient. Introduce the needle into the superficial skin layers until the bevel is completely buried, then slowly inject approximately 0.02 - 0.05 ml. Measure the wheal and erythema after 15 minutes, and determine the degree of response to the injection, in comparison to the negative control. A suggested grading system appears in Table 5. If the intradermal reaction is negative at the initial concentration, continue intradermal testing with 10-fold increments in the concentration until a clearly positive response has been obtained or a peak concentration of 100 BAU/ml has been tested, whichever occurs first. Table 4 Skin Test Grading System12 Grade Wheal Results 0 + ++ +++ ++++ No Wheal/same size as negative<Half the Histamine DiameterHalf the Histamine DiameterSame Size as Histamine ControlSize of Histamine Control +2mm Table 5 Intradermal Skin Test Grading System13 Mean Diameters (mm) Grade Wheal Erythema 0±1+2+3+4+ <5.05.0-10.05.0-10.05.0-10.05.0-10.0 or pseudopods>15.0, many pseudopods <5.05.0-10.011.0-20.021.0-30.031.0-40.0>40.0
The interpretation of the skin response is based on the size of the wheal, the size of the erythema, and the appearance of irregular, spreading, pseudopodllike projections from the test area. The presence of the latter indicates marked hypersensitivity. A patient is considered sensitive to the test extract if there is a reaction of 1 + or greater at a concentration of 100 BAU/ml or less, providing that the 1 + reaction is in relation to the negative control.

Immunotherapy

Administer the extract solution subcutaneously, using a suitable sterile 1 ml syringe and a 25-27 gauge 1/4 to 5/8 inch needle. The injections are typically given in the lateral aspect of the upper arm.

Dosage of allergenic extracts is a highly individualized matter12, and varies according to the degree of sensitivity of the patient, the clinical response, and tolerance of the extract administered previously.

A safe starting dose for any allergic patient is that dose which on intradermal testing produces a 1 + reaction. For most patients a starting dose that is 0.1 ml of 0.01 BAU/ml dilution of the extract concentrate should be well tolerated, although in some very sensitive patients a more dilute concentration may be required.

If no untoward symptoms are observed following the initial injection, the dose can be increased gradually for each subsequent injection until the injection volume reaches 0.6 -0.8 ml. Then begin using the next more concentrated ten-fold dilution, and proceed with this dosage pattern until the maintenance dose-defined as that dose that either relieves the patient's symptoms or is the highest that the patient can tolerate is reached. Care must be taken, however, in administering a volume greater than 0.2 ml of any extract in 50% glycerin; such injections can be painful to the patient due to the glycerin content.

After each injection, evaluate the patient's skin reaction and overall response to determine whether the next scheduled dose can be given:
If a single dose results in more than a moderate local reaction (>50 mm wheal) within 1/2 hour, the same dose should be repeated at the next visit - or visits - until the patient has tolerated it. lf any systemic manifestation of sensitivity occurs during or following a visit, or if a single dose results in an excessive local reaction (> 100 mm wheal) within ½ hour, the total dosage for the next visit should be reduced to half of the dose that caused the reaction. Delayed local reactions (occurring 24-48 hours after injection) are relatively common, and do not appear to predict difficulties with future doses. As a rule, therefore, dosage adjustment is not required in most instances. However, at the physician's discretion and for the comfort of the patient, if delayed large local reactions over 10 mm are reported, the subsequent dose should be held at the same level as the one causing the reaction.
The optimal interval between doses of allergenic extract has not been definitely established. However, as is customarily practiced, injections are given 1, 2, or 3 times per week until the maintenance dose of extract is reached. At this time, the injection interval may be increased to 2 weeks, then to 3 weeks and finally to 4 weeks depending on the clinical status. lf the patient does not return for 6 to 8 weeks after the last injection, the dose should be reduced to 25% of the last dose.

If longer than 8 weeks, a dose reduction of one, two or three dilutions may be made depending on a consideration of the components and the patient’s sensitivity. The dosage and the interval between injections may need to be modified according to the clinical response of the patient. When switching patients to fresh extract, the initial dose should be reduced to one-quarter of the previous dose.

Duration of treatment: Careful selection of allergens and cautious progression to maximally tolerated doses are important elements in the success of immunotherapy. The optimal length of treatment with allergen immunotherapy is unknown. A treatment period of 3 to 5 years is common, although continuation for longer periods may be appropriate13.

Allergenic extracts, as any parenteral drug product should be inspected visually for evidence of foreign material or discoloration prior to administration. Some variation in color is normal and a minor level of extract precipitate may occur with some extracts, but do not use the extract if there is any question of its condition exists.
Histamine Positive Skin...

Histamine Positive Skin Test Control

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

For Prick, Puncture and Scratch Testing

Histamine base 1 mg/mL (Histamine Phosphate 2.75 mg/mL) should be used to give a reaction. (Refer to Interpretation Section.)

Prick, Puncture or Scratch Test Techniques
The skin in the test area should be cleansed with alcohol and air dried. The histamine control skin test solution should be placed at the same site with the other skin test antigens, either on the patient's back or on the volar surface of the forearm. The patient should be placed in a comfortable position before the testing is begun. For the prick test, a sharp needle is used to puncture the skin, but not to draw blood. If the scratch test is used, carefully break or scratch the skin with a sterile scarifier. Do not draw blood. Each scratch should be about 2 mm - 4 mm in length. A small drop of the histamine base 1 mg/mL (Histamine Phosphate 2.75 mg/mL) is placed on the abraded skin site no closer than 4 or 5 cm from an adjacent test site. Some physicians prefer to place the solution on the test area and then prick through the drop with a sharp needle. Use a separate sterile scarifier or needle for each patient. The test should be read at 15 minutes; if a large wheal reaction occurs before that time the test site should be wiped free of histamine.
Interpretation

The patient's response is based on the size of: erythema (degree of redness) and/or size of wheal (smooth, slightly elevated area) which appear after 10 minutes.

For percutaneous testing, different devices and/or techniques influence the size of the reaction. Therefore, it is important to refer to the device manufacturer's or distributor's instructions when grading reactions.

For prick, puncture and scratch testing, histamine base 1 mg/mL (Histamine Phosphate 2.75 mg/mL) should be used to give a positive reaction. In a large population, the NHANES II survey reports a mean diameter (average of length and width) wheal of 4.4 mm ± 1.65 mm (± standard deviation) and a mean erythema of 18.4 mm ± 8.55 mm (± standard deviation) when using 25 gauge B-D needle by prick puncture (Pepys) technique.7 All positive reactions should be interpreted against an appropriate negative control.

For Intradermal Skin Testing

Histamine base 0.1 mg/mL (Histamine Phosphate 0.275 mg/mL) or 0.01 mg/mL should be used to give a reaction. (Refer to Interpretation Section.)

Intracutaneously (Intradermal) Test Techniques
The skin should be cleansed with alcohol and air dried. A sterile one milliliter tuberculin syringe with 26 or 27 gauge needle should be used. A single sterile syringe should be used for each solution to assure sterility. Only the histamine base 0.1 mg/mL (Histamine Phosphate, 0.275 mg/mL) or greater dilution solution should be used. The histamine base skin test solution should be injected at the same site with the other skin test allergens, either on the patient's back or on the arm. The patient should be placed in a comfortable position before the testing is begun. The skin is held tense and the needle is inserted almost parallel to the skin, bevel side up, far enough to cover the beveled portion. Slowly inject 0.01 mL or 0.02 mL, making a small bleb approximately 3 mm - 5 mm in diameter. The test should be read in 15 minutes.
Interpretation

The patient's response is based on the size of: erythema (degree of redness) and/or size of wheal (smooth, slightly elevated area) which appear after 10 minutes.

For intradermal skin testing, histamine base 0.1 mg/mL (Histamine Phosphate 0.275 mg/mL) or 0.01 mg/mL should be used to give a positive reaction. The available 0.1 mg/mL concentration must be diluted ten-fold to achieve this dose. All positive reactions should be interpreted against an appropriate negative control. In two successive years of testing, the Committee on Standardization of the American College of Allergy reported positive reactions at histamine base doses of 0.01 mg/mL and higher. Mean sum of wheal diameters was approximately 14 mm ± 4.8 mm and sum of erythema diameter was approximately 52 mm ± 21.6 mm following 0.01 mL intradermal doses of 0.01 mg/mL histamine base. When 0.01 mL of 0.1 mg/mL histamine base was injected, the sum of cross-diameters of wheal ranged from 15-20 mm and the sum of cross-diameters of erythema ranged from 60-80 mm.8
Cat Pelt

Cat Pelt

Parenteral drug products should be inspected visually for particular matter and discoloration prior to administration whenever solution and container permit.

When diluting bulk extracts, use of Sterile Diluent for Allergenic Extracts or Sterile Diluent for Allergenic Extracts Normal Saline with Human Serum Albumin (HSA) are recommended. Dilutions should be made with sterile disposable syringes using aseptic technique. Commonly 10 fold dilutions are used to achieve a desired concentration for intradermal testing or initiation and continuation of immunotherapy. For example, transferring 0.5 mL of a 10,000 AU/mL extract into 4.5 mL of diluent will yield 5 mL of extract @ 1,000 AU/mL. Prepare as many additional serial dilutions as necessary to reach the appropriate concentration.

Care should be exercised to avoid cross contamination with other allergens if mixing with other allergenic extracts. The use of separate syringes for each allergen and diluent is mandated when compounding patient mixes.

Diagnosis - In diagnosing the sensitive individual, the symptom history must be associated with exposure to the allergen. Skin testing is used in conjunction with a definitive history for diagnosing individual sensitivities.

An excellent method of recording results is to cover the skin reaction with transparent tape, outline the erythema first then the wheal with an indelible pen, then remove the tape and transfer it to the patient's permanent record. For preferred results, it is recommended that the actual measurement of the extent of both responses be recorded. This can be accomplished by measuring the longest erythema diameter, then selecting the mid-point of that line and measuring at a 90o angle to that line to determine the orthogonal diameter. The sum of these two measurements is the sum of erythema (∑E); the sum of wheal diameters is determined in a similar manner.

Patient's response is graded on the basis of the size of erythema and/or wheal.

Percutaneous (prick/scratch/puncture) test:

Prick, scratch, or puncture skin tests should be performed initially using an extract specially made for this purpose.

In a skin test study of 12 patients who were determined to be allergic to cat, the mean puncture test (using a bifurcated needle) to a Cat Pelt extract containing 10,000 BAU/mL had a sum of erythema of 71 mm (range 52 - 90 mm) and a sum of wheal of 15 mm (range 4 - 25 mm).

What follows are general guidelines for percutaneous testing13. Different devices and/or techniques influence the size of the reaction; therefore it is important to refer to the device manufacturer’s or distributor’s instructions when grading reactions. As a negative control, the diluent should be tested and included in the interpretation in the skin test reactions. Use of a positive control such as histamine base at 1 mg/mL should be used to assess skin test reactivity.
0 No reaction or less than control + Erythema greater than control, smaller than a nickel (21 mm diameter) ++ Erythema greater than a nickel in diameter, no wheal +++ Wheal and erythema without pseudopods ++++ Wheal and erythema with pseudopods
Intradermal test:

On the forearm or upper outer aspect of the arm, using a 26 - 27 gauge, short bevel needle, inject intradermally 0.05 mL of the intradermal test solution. Skin whealing responses should be observed 10 - 20 minutes after administering the test.

In a skin test study of the 12 cat puncture reactive patients described previously, the mean intradermal dose for ∑E = 50 mm was 0.03 BAU/mL (range = 1.5 to <0.002 BAU/mL).

Intradermal testing should start with a dilute solution, usually in the range of 0.1 BAU/mL or less.

Glycerinated extracts diluted for intradermal testing may be diluted at least 25 fold to less than 2% glycerin (by volume) as glycerin above this level can cause false positive intradermal skin tests.

A negative skin test is one where the sum of erythema was 0 or equal to the sum of the wheal. As a negative control, the diluent should be tested and included in the interpretation of the skin reactions. What follows are general guidelines for intradermal tests13.
0 No reaction or less than negative control + 3-4 mm wheal with erythema, or erythema alone larger than a nickel (21 mm diameter) ++ 4-8 mm wheal and erythema without pseudopods +++ Over 8 mm wheal and erythema without pseudopods ++++ Wheal and erythema with pseudopods


Immunotherapy - Starting dose for immunotherapy is related directly to a patient's sensitivity as determined by carefully executed skin testing. Degree of sensitivity can be established by determination of D50 (the intradermal dose, base three, that produces a SE = 50 mm).1

A general rule is to begin at 1/10 of the dose that produces sum of erythema of 50 mm (approximately a 2+ positive skin test reaction). For example, if a patient exhibits a 2+ intradermal reaction to 1 BAU/mL, the first dose should be no higher than 0.05 mL of 0.1 BAU/mL. Dosage may be increased by 0.05 mL each time until 0.5 mL is reached, at which time the next 10-fold more concentrated dilution can be used, beginning with 0.05 mL, if no untoward reaction is observed. (See beginning of DOSAGE AND ADMINISTRATION section for instructions in preparing dilutions of concentrates).

If a tolerated dose of allergenic extract has been established, the initial dose from the new extract should be reduced by 75% of the previously well tolerated dose (see also Precautions).

Interval between doses in the early stages of immunotherapy is no more than once to twice a week, and may gradually be increased to once every two weeks. Generally, maintenance injections may be given as infrequently as once every two weeks to once a month. The progress of patients on immunotherapy should be closely monitored. If improvement is realized a usual course of treatment may be from 3 to 5 yeas. If progress is unsatisfactory for a year or more discontinuation of immunotherapy should be considered.

Injections are given subcutaneously preferably in the arm. It is advantageous to give injections in alternate arms and routinely in the same area. In some patients, a local tolerance to the allergen may develop thus preventing a possible severe local reaction.

After inserting the needle, but before injecting the dose, pull plunger of the syringe slightly, if blood returns in the syringe, discard the syringe and contents and repeat injection at another site.

Bulk concentrated extracts must be diluted for initial therapy and intradermal skin testing. For recommended diluent, refer to DOSAGE AND ADMINISTRATION section.

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.

Use standard aseptic precautions when making dilutions. The first dose of the new extract should be reduced at least 50% - 75% of the amount of the dosage from the previous extract.

Stability studies for diluted and undiluted forms of this product are not complete. Indications are the undiluted product will retain its potency under recommended storage conditions at least until the expiration date on the vial label is reached. It is recommended that minimal amounts of the concentrate be diluted so that the diluted product is used up within a relatively short period of time, i.e. preferably not more than four weeks.
Standardized Mite D. Fa...

Standardized Mite D. Farinae

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

When diluting bulk extracts, use of either Sterile Diluent for Allergenic Extracts or Sterile Diluent for Allergenic Extracts Normal Saline with HSA is recommended. Dilutions should be made with sterile disposable syringes using aseptic technique. Commonly 10 fold dilutions are used to achieve a desired concentration for intradermal testing or initiation and continuation of immunotherapy. For example, transferring 0.5 mL of a 10,000 AU/mL extract into 4.5 mL of diluent will yield 5 mL of extract @ 1,000 AU/mL. Prepare as many additional serial dilutions as necessary to reach the appropriate concentration.

Care should be exercised to avoid cross contamination of allergens if mixing with other allergenic extracts. The use of separate syringes for each allergen and diluent when compounding patient mixes is recommended.

Diagnosis - In diagnosing the sensitive individual, the symptom history must be associated with exposure to the allergen. Skin testing is used in conjunction with a definitive history for diagnosing individual sensitivities.

An excellent method of recording results is to cover the skin reaction with transparent tape, outline the erythema first then the wheal with an indelible pen, then remove the tape and transfer it to the patient's permanent record. For preferred results, it is recommended that the actual measurement of the extent of both responses be recorded. This can be accomplished by measuring the longest erythema diameter, then selecting the mid - point of that line and measuring at a 90o angle to that line to determine the orthogonal diameter. The sum of these two measurements is the sum of erythema (∑E); the sum of wheal diameters is determined in a similar manner.

Patient's response is graded on the basis of the size of erythema and/or wheal.

Percutaneous (prick/scratch/puncture) test:

Prick, scratch, or puncture skin tests should be performed initially using an extract specially made for this purpose. The usual dose is one drop.

In a skin test study of 10 patients who were determined to be allergic to mite (D. farinae), the mean puncture test (using a bifurcated needle) to a solution containing 10,000 AU/mL had a sum of erythema of 73 mm (range 43 - 138 mm) and a sum of wheal of 17 mm (range 7 - 31 mm).

In another skin test study of 11 patients who were determined to be allergic to mite (D. pteronyssinus), the mean puncture test (using a bifurcated needle) to a solution containing 10,000 AU/mL had a sum of erythema of 84 mm (range 56 - 112 mm) and a sum of wheal of 20 mm (range 7 - 33 mm).

What follows are general guidelines for percutaneous testing. Different devices and/or techniques influence the size of the reaction, therefore it is important to refer to the device manufacturer's or distributor's instructions when grading reactions.
0 No wheal. Erythema absent or very slight (not more than 1 mm in diameter). + Wheal absent or very slight erythema present (not more than 3 mm diameter). ++ Wheal not more than 3 mm diameter, or erythema not more than 5 mm diameter. +++ Wheal between 3 mm and 5 mm in diameter with erythema. Possible pseudopodia and itching. ++++ Any larger reaction with itching and possible pain.
Intradermal test:

On the forearm or upper outer aspect of the arm, using a 26 - 27 gauge, short bevel needle, inject intradermally .05 mL of the intradermal test solution. Skin whealing responses should be observed 10 - 20 minutes after administering the test.

In a skin test study of the 10 mite puncture reactive patients (D. farinae) described above, the mean intradermal dose for ∑E = 50 mm was 0.01 AU/mL ( range = <0.0003 to 0.4 AU/mL).

In the skin test study of the 11 mite puncture reactive patients (D. pteronyssinus) described above, the mean intradermal dose for ∑E = 50 mm was 0.006 AU/mL ( range = <0.0007 to 0.05 AU/mL).

Intradermal testing should start with a dilute solution, usually in the range of 1 AU or less.

Glycerinated extracts diluted for intradermal testing may be diluted at least 25 fold to less than 2% glycerin (by volume) as glycerin above this level can cause false positive intradermal skin tests.

A negative skin test is one where the sum of erythema was 0 or equal to the sum of the wheal. As a negative control, the diluent should be tested and included in the interpretation of the skin reactions.
0 No increase in size of bleb since injection. No erythema. + An increase in size of bleb and a wheal not more than 5 mm diameter with associated erythema. ++ Wheal between 5 mm and 8 mm in diameter with erythema. +++ Wheal between 8 mm and 12 mm in diameter with erythema and possible pseudopodia, itching or pain. ++++ Any larger reaction with itching and pain and possible diffuse blush of the skin surrounding the reaction area.
Immunotherapy - Starting dose for immunotherapy is related directly to a patient's sensitivity as determined by carefully executed skin testing. Degree of sensitivity can be established by determination of D50 (the intradermal dose, base three, that produces a ∑E = 50 mm).1

A general rule is to begin at 1/10 of the dose that produces sum of erythema of 50 mm (approximately a 2+ positive skin test reaction). For example, if a patient exhibits a 2+ intradermal reaction to

1 AU/mL, the first dose should be no higher than 0.05 mL of 0.1 AU/mL. Dosage may be increased by 0.05 mL each time until 0.5 mL is reached, at which time the next 10-fold more concentrated dilution can be used, beginning with 0.05 mL, if no untoward reaction is observed. (See beginning of DOSAGE AND ADMINISTRATION section for instructions in preparing dilutions of concentrates.)

If a tolerated dose of allergenic extract has been established, the initial dose from the new extract should be reduced by 75% of the previously well tolerated dose (see also Precautions).

Interval between doses in the early stages of immunotherapy is no more than once to twice a week, and may gradually be increased to once every two weeks. Generally, maintenance injections may be given as infrequently as once every two weeks to once a month. The progress of patients on immunotherapy should be closely monitored. If improvement is realized a usual course of treatment may be from 3 to 5 years. If progress is unsatisfactory for a year or more, discontinuation of immunotherapy should be considered.

Injections are given subcutaneously preferably in the arm. It is advantageous to give injections in alternate arms and routinely in the same area. In some patients, a local tolerance to the allergen may develop thus preventing a possible severe local reaction.

After inserting the needle, but before injecting the dose, pull plunger of the syringe slightly, if blood returns in the syringe, discard the syringe and contents and repeat injection at another site.

Bulk concentrated extracts must be diluted for initial therapy and intradermal skin testing. For recommended diluent, refer to the beginning of the DOSAGE AND ADMINISTRATION section.

Use standard aseptic precautions when making dilutions. The first dose of the new extract should be reduced at least 50% - 75% of the amount of the dosage from the previous extract.

Stability studies for diluted and undiluted forms of this product are not complete. Indications are the undiluted product will retain its potency under recommended storage conditions at least until the expiration date on the vial label is reached. It is recommended that minimal amounts of the concentrate be diluted so that the diluted product is used up within a relatively short period of time, i.e., preferably not more than four weeks.

HOW SUPPLIED

For percutaneous testing, 5 mL vial, 10,000 AU/mL in glycerin 50% (V/V).

For immunotherapy, 10 mL, 30 mL and 50 mL vials of bulk concentrate, 10,000 AU/mL in glycerin 50% (V/V).

STORAGE:

To maintain stability of allergenic extracts, proper storage conditions are essential. Bulk concentrates and diluted extracts are to be stored at 2o to 8o C even during use. Bulk or diluted extracts are not to be frozen. Do not use after the expiration date shown on the vial label.
Alum Precipitated Extra...

Alum Precipitated Extracts

The starting dose for immunotherapy is related directly to a patient's sensitivity as determined by carefully executed percutaneous (prick/puncture) and intracutaneous (intradermal) skin testing with non-alum adsorbed allergenic extract. A general rule is to begin at 1/10 of the intradermal dose that produces sum of erythema of 50 mm (approximately a 2+ positive skin test reaction). Patient's response to skin testing is graded on the basis of the size of the erythema and wheal. Refer to the diagnostic allergenic extract package enclosure for specific information.

TRANSFER OF PATIENTS FROM OTHER

AQUEOUS EXTRACTS TO

CENTER-AL EXTRACTS

Patients may be transferred from other aqueous allergens to Center-Al Alum Precipitated Extracts during treatment. To avoid untoward reactions, it may be necessary to initiate treatment as though the patient were previously untreated. In transferring from standardized extracts, the more rapid rate of decline in activity of aqueous extract relative to alum precipitated extract must be considered in cautiously transferring patients to alum precipitated extract.

Caution should be observed since the Center-Al preparation may be more potent than the aqueous product.

TRANSFER OF PATIENTS FROM OTHER

ALUM-COMPLEXED EXTRACTS TO

CENTER-AL EXTRACTS

Patients may be transferred from other alum-complexed allergenic extracts to Center-Al Alum Precipitated extracts. In order to avoid untoward reactions, it is recommended that previous therapy be disregarded and therapy with Center-Al be initiated as though the patient were previously untreated. The first dose of Center-Al should be related to the patient's sensitivity, determined by history and confirmed by skin testing. CAUTION: Center-Al Alum Precipitated extracts should not be mixed with other alum precipitated or aqueous extracts.

PRE-SEASONAL AND PERENNIAL METHOD OF TREATMENT

The use of Center-Al Allergenic extract, Alum Precipitated, in the treatment of patients by the pre-seasonal method should be started 10 to 12 weeks prior to the usual onset of symptoms. Therapy should be initiated early enough to permit a graduated series of doses at weekly intervals. It is recommended that the larger doses be spaced 2 to 3 weeks apart and that the top dose be reached prior to the season.

Increased tolerance acquired through hyposensitization can vary from a few to several months. To assure prolongation of this acquired tolerance, perennial or year-round treatment is recommended.

Some physicians continue therapy into or through the season by repeating a reduced MAINTENANCE dose at 4 to 6 week intervals.

SUGGESTED DOSAGE SCHEDULE

A treatment schedule is related directly to the patient's degree of sensitivity, determined initially by clinical history and skin testing, and continuously by response to therapeutic doses. Thus, an individual treatment schedule for each patient must be established during the course of therapy. Maximum protection can be obtained with a dosage kept constantly below the patient's limit of tolerance. Every precaution should be taken to avoid a systemic or generalized reaction which in addition to being dangerous, may depress rather than increase the patient's tolerance.

FOR ALL PREPARATIONS (EXCEPT SHORT RAGWEED

AND MIXED SHORT AND TALL RAGWEED)

Labeled Antigen E content of extracts containing Short Ragweed at a weight/volume concentration more dilute than 1:10 may have been obtained by calculation from the Antigen E assay value of a more concentrated extract that was analyzed, officially released by the Office of Biologics, and subsequently diluted.

Below is listed a suggested dosage schedule for Pre-Seasonal Treatment. A column has been left blank for AgE dosage of short ragweed containing extracts.

Note: For extracts of short ragweed or equal part mixture of Short and Tall Ragweed refer to AgE dosage schedule. The AgE content for those products is indicated on the vial label. The physician may use the formula below to determine the AgE dosage for each injection.

AgE dosage can be monitored by using the formula:

Note: Suggested dosage schedules which follow have not been subjected to adequate and well controlled trials to establish their safety and efficacy.
Dose No. Vial Strength Volume Injected PNU Per Dose AgE Dose 1 100 PNU/mL 0.1 mL 10 2 100 PNU/mL 0.2 mL 20 3 100 PNU/mL 0.5 mL 50 4 1,000 PNU/mL 0.1 mL 100 5 1,000 PNU/mL 0.25 mL 250 6 1,000 PNU/mL 0.5 mL 500 7 10,000 PNU/mL 0.1 mL 1,000 8 10,000 PNU/mL 0.2 mL 2,000 9 10,000 PNU/mL 0.3 mL 3,000 10 10,000 PNU/mL 0.4 mL 4,000 11 10,000 PNU/mL 0.5 mL 5,000 MAINTENANCE DOSE: 10,000 PNU/mL 0.5 mL 5,000
NO SINGLE DOSE SHOULD EXCEED 5,000 PNU. For continuing therapy with extracts containing Short Ragweed, see following section on Dosage Adjustments.

SHORT RAGWEED EQUAL PARTS

MIXES OF SHORT AND TALL RAGWEED

(DOSAGE BASED ON ANTIGEN CONTENT)

Suggested dosage schedule for Short Ragweed and Equal Part Mixture of Short and Tall Ragweed:
Dose No AgE Units/mL Volume Injected AgE Per Dose 1 0.4 0.1 0.04 2 0.4 0.2 0.08 3 0.4 0.5 0.2 4 4 0.1 0.4 5 4 0.25 1 6 4 0.5 2 7 40 0.1 4 8 40 0.2 8 9 40 0.3 12 10 40 0.4 16 11 40 0.5 20 MAINTENANCE DOSE: 40 0.5 20 80 0.25 20
NO SINGLE DOSE SHOULD EXCEED 20 UNITS

DOSAGE ADJUSTMENTS

(FOR PRODUCTS CONTAINING SHORT RAGWEED)

AgE is important in adjusting dosage of Short Ragweed extracts to accurately transfer a patient from older extracts to fresher material. In such cases, the dosage of AgE should be considered in addition to the protein nitrogen units. Antigen E concentration continuously declines in Short Ragweed Pollen extracts at a rate that varies with the formulation of the product. Aqueous extracts retain Antigen E potency less effectively than 50% glycinerated or Alum Precipitated extracts. Antigen E is most stable in freeze-dried extracts. These differences are reflected in the expiration date declared on the vial label. The continuous decline should be considered. Also, where Ragweed is a component of an allergen mixture, clinical response to the other components must be considered in adjustment of dosage based on AgE content alone.

CAUTION: A small percent of individuals allergic to Short Ragweed are more sensitive to minor antigens such as Ra3 and Ra5 than AgE. There is no correlation between the amount of these antigens and either AgE or PNU content.
Rizatriptan Benzoate

Rizatriptan Benzoate

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Skin test techniques for immediate (Type I) hypersensitivity testing fall into two major categories: percutaneous, and intracutaneous.

Percutaneous techniques: For percutaneous testing, in general, skin is scratched, punctured or pricked just before the allergen is applied or through a drop of test allergen. There are several devices available for this technique. Refer to the manufacturer or distributor’s circular for specific directions for their use.

In General:

It is recommended that the test areas should be placed no closer than 4 - 5 cm apart to avoid interference of reactions when several tests are applied.

Skin test areas should be cleansed with alcohol and air dried.

Preferably, the allergen should be placed on the volar surface of the forearm, upper arm, or the patient’s back. The patient should be placed in a comfortable position prior to testing.

For scratch testing, a sharp, clean, sterile instrument is used to abrade the skin, but not to draw blood. Each scratch should be about 2 - 4 mm in length. A small drop of extract is placed on the surface of the skin.

Prick testing: For prick testing, a sharp, sterile instrument is used to puncture the skin slightly, applying it at a 15 - 20° angle to the skin. The instrument is gently raised, “tenting” the skin until it pops out, generally pricking through the drop of allergen. Do not draw blood.

For puncture testing, a sharp, clean, sterile instrument must be used. Puncture the skin, through the drop of allergen, perpendicular to the skin. Do not draw blood.

For all of the above techniques, a separate instrument must be used for each patient; if the instrument is to be used to pass through the allergen, to avoid cross-contamination, a separate instrument is to be used for each allergen. The test should be read in 15 minutes, measuring both wheal size and erythema.

Intracutaneous (intradermal) testing: General: Intradermal testing is more sensitive than percutaneous testing and its specificity is dependent on dose. Intradermal testing is not intended as an initial screen unless used in highly dilute solutions. Intradermal testing is usually reserved for allergens that have demonstrated either negative or equivocal percutaneous skin test response in the face of positive or unclear history.

Intradermal testing of one allergen in several serial dilutions (beginning with the weakest to the more concentrated dilutions) may also be useful in assessing degree of patient sensitivity for the establishment of a safe starting dose for immunotherapy.

Bulk extracts must be diluted for intradermal testing. Use of Sterile Diluent for Allergenic Extracts or Sterile Diluent for Allergenic Extracts Normal Saline with HSA (albumin saline) is recommended. Dilutions should be made with sterile disposable syringes using aseptic technique. Commonly 10 fold dilutions are used to achieve a desired concentration for intradermal testing and continuation of immunotherapy. For example, transferring 0.5 mL of a 10,000 PNU/mL extract into 4.5 mL of diluent will yield 5 mL of extract at 1,000 PNU/mL. For weight volume products, a 1:100 w/v dilution may be prepared from a 1:10 w/v by transferring 0.5 mL of the 1:10 w/v to 4.5 mL of dilutent. Prepare as many additional serial dilutions as necessary to reach the appropriate concentration. As a general rule intradermal strength should begin at no higher than 1/100 to 1/1000 of the percutaneous strength that resulted in a negative skin test reaction.

It is recommended that the test areas should be spaced no less than 5 cm apart to avoid interference with adjacent allergen or control.

Skin should be cleansed with alcohol and air dried.

A sterile 1 mL or 1/2 mL syringe with a 26 - 30 gauge needle should be used. A separate sterile syringe should be used for each extract and each patient.

Care should be taken to eliminate air bubbles from the syringe prior to injecting the test dose. It is suggested that not more than 6 - 10 allergens of each different type be used at any one time. Very sensitive patients may show rapid response.

The skin is held tensely, and the needle is inserted almost parallel to the skin, beveled side up far enough to cover the beveled portion. Slowly inject sufficient extract to make a small bleb of approximately 5 mm in diameter (0.01 - 0.02 mL).

Read the test results in 15 minutes.

Selection of the proper strength for intracutaneous testing: A general rule for the prevention of untoward reactions, particularly in extremely sensitive patients, is to screen by percutaneous methods initially, and begin intradermal testing at a strength not more than 1/100 of a negative or equivocal percutaneous reaction.

Controls: In both percutaneous and intracutaneous tests, a negative control test with diluent alone should be performed because some patients exhibit dermographia, and/or other non-specific irritant responses.

As a positive control in the evaluation of allergenic skin testing, histamine 1 mg/mL (histamine base) should be used for percutaneous testing, and histamine 0.1 mg/mL (histamine base) should be used for intradermal testing.

Interpretation of results: Patient’s response is graded on the basis of the size of erythema or wheal.6 General guidelines follow for percutaneous testing, different devices and/or techniques influence the size of the reaction, therefore it is important to refer to the device manufacturer’s or distributor’s instructions when grading reactions.

Percutaneous (prick or scratch) test:

0 No reaction or less than control.+ Erythema greater than control, smaller than a nickel (21 mm diameter).++ Erythema greater than a nickel in diameter, no wheal.+++ Wheal and erythema without pseudopods.++++ Wheal and erythema with pseudopods.

Intradermal test:

0 No reaction or less than negative control.+ 3-4 mm wheal with erythema, or erythema alone larger than a nickel (21 mm diameter).++ 4-8 mm wheal and erythema, without pseudopods.+++ Over 8 mm wheal and erythema without pseudopods.++++ Wheal and erythema with pseudopods.

Alk-abello, Inc.

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