Aclovate

Generic Name: Alclometasone Dipropionate
Class: Anti-inflammatory Agents
ATC Class: D07AB10
VA Class: DE200
Chemical Name: (7α,11β,16α)-7-Chloro-11-hydroxy-16-methyl-17,21-bis (1-oxopropoxy)pregna-1,4-diene-3,20-dione
Molecular Formula: C₂₈H₃₇ClO₇
CAS Number: 66734-13-2

Introduction

A synthetic corticosteroid.^{1 2 12 d}

Uses for Aclovate

Corticosteroid-responsive Dermatoses

Relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.^{1 4 5 6 7 8 9 10 11 13 14 17 18 d}

Generally most effective in acute or chronic dermatoses (e.g., seborrheic or atopic dermatitis, localized neurodermatitis, anogenital pruritus, psoriasis, late phase of allergic contact dermatitis, inflammatory phase of xerosis).^b

Topical therapy generally preferred over systemic therapy; fewer associated adverse systemic effects.^b

Topical therapy generally only controls manifestations of dermatoses; eliminate cause if possible.^b

Topical efficacy may be increased by using a higher concentration or occlusive dressing therapy. (See Administration with Occlusive Dressing under Dosage and Administration.)^b

Response may vary from one topical corticosteroid preparation to another.^b

Anti-inflammatory activity may vary considerably depending on the vehicle, drug concentration, site of application, disease, and individual patient.^b

Manufacturers state that alclometasone should not be used for the treatment of acne, rosacea, or perioral dermatitis.^{22 23}

Alclometasone dipropionate 0.05% cream and ointment are considered to have low-to-medium range potency.^{b c d}

Aclovate Dosage and Administration

General

• 
  

  Consider location of the lesion and the condition being treated when choosing a dosage form.^b

  
  


• 
  

  Creams are suitable for most dermatoses, but ointments may also provide some occlusion and are usually used for the treatment of dry, scaly lesions.^b

  
  


• 
  

  Formulation affects percutaneous penetration and subsequent activity; extemporaneous preparation or dilution of commercially available products with another vehicle may decrease effectiveness.^b

  
  


• 
  

  Patients applying a topical corticosteroid to a large surface area and/or to areas under occlusion should be evaluated periodically for evidence of hypothalamic-pituitary-adrenal (HPA)-axis suppression by appropriate endocrine testing (e.g., ACTH stimulation, plasma cortisol, urinary free cortisol).^{c d} (See Hypothalamic-Pituitary-Adrenal Axis Suppression and also Systemic Effects, under Cautions.)

  
  

Administration

Topical Administration

For dermatologic use only; avoid contact with eyes.^d

Apply creams and ointments topically to the skin or scalp.^c

The area of skin to be treated may be thoroughly cleansed before topical application to reduce the risk of infection; however, some clinicians believe that, unless an occlusive dressing is used, cleansing of the treated area is unnecessary and may be irritating.^b

Apply cream or ointment sparingly in a thin film and rub gently into the affected area.^{1 d}

After a favorable response is achieved, frequency of application or concentration (strength) may be decreased to the minimum necessary to maintain control and to avoid relapse; discontinue if possible.^b

Administration with Occlusive Dressing

Occlusive dressings may be used for severe or resistant dermatoses (e.g., psoriasis).^{1 17} (See Occlusive Dressings under Cautions.)

Soak or wash the affected area to remove scales; apply a thin film of cream or ointment; rub gently into the lesion; and apply another thin film.^b Cover affected area with a thin, pliable plastic film and seal it to adjacent normal skin with adhesive tape or hold in place with a gauze or elastic bandage.^b

If affected area is moist, incompletely seal the edges of the plastic film or puncture the film to allow excess moisture to escape.^b For added moisture in dry lesions, apply cream or ointment and cover with a dampened cloth before the plastic film is applied or briefly soak the affected area in water before application of the drug and plastic film.^b

Thin polyethylene gloves may be used on the hands and fingers, plastic garment bags may be used on the trunk or buttocks, a tight shower cap may be used for the scalp, or whole-body suits may be used instead of plastic film to provide occlusion.^b

Frequency of occlusive dressing changes depends on the condition being treated; cleansing of the skin and reapplication of the corticosteroid are essential at each dressing change.^b

Occlusive dressing is usually left in place for 12–24 hours and therapy is repeated as needed.^b Although occlusive dressing may be left in place for 3–4 days at a time in resistant conditions, most clinicians recommend intermittent use of occlusive dressings for 12 hours daily to reduce the risk of adverse effects (particularly infection) and systemic absorption and for greater convenience.^b

The drug and an occlusive dressing may be used at night, and the drug or a bland emollient may be used without an occlusive dressing during the day.^b

In patients with extensive lesions, sequential occlusion of only one portion of the body at a time may be preferable to whole-body occlusion.^b (See Occlusive Dressings under Cautions.)

Dosage

Pediatric Patients

Administer the least amount of topical preparations that provide effective therapy.^b (See Pediatric Use under Cautions.)

Corticosteroid-responsive Dermatoses

Topical

Children ≥1 year of age: Apply cream or ointment sparingly 2–3 times daily.^{1 d}

Discontinue when control is achieved; if improvement does not occur within 2 weeks, consider reassessment of the diagnosis.^{c d}

Adults

Corticosteroid-responsive Dermatoses

Topical

Apply cream or ointment sparingly 2–3 times daily.^{1 d}

May be used for 2–6 weeks^{5 6 7 8 9 10 11 13 14 18} ; however, more prolonged therapy²³ with appropriate monitoring¹⁷ may be necessary in patients with resistant or chronic conditions.^a

Discontinue when control is achieved; if improvement does not occur within 2 weeks, consider reassessment of the diagnosis.^{c d}

Prescribing Limits

Pediatric Patients

Corticosteroid-responsive Dermatoses

Topical

Children ≥1 year of age: Maximum 3 weeks.^c

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.^{c d}

Renal Impairment

No specific dosage recommendations at this time.^{c d}

Geriatric Patients

Careful dosage selection recommended.^d

Cautions for Aclovate

Contraindications

• 
  

  Known hypersensitivity to alclometasone, other corticosteroids, or any ingredient in the formulation.^{1 d}

  
  

Warnings/Precautions

Sensitivity Reactions

Allergic contact dermatitis may manifest as failure to heal rather than irritation as occurs with other topical preparations that do not contain corticosteroids; confirm with diagnostic patch testing.^{b c d}

General Precautions

Hypothalamic-Pituitary-Adrenal Axis Suppression

Topically applied corticosteroids can be absorbed in sufficient amounts to reversibly suppress the HPA axis.^{c d}

Perform periodic HPA-axis evaluation by appropriate testing (e.g., ACTH stimulation, morning plasma cortisol, urinary free cortisol), especially in patients applying a topical corticosteroid to a large surface area or to areas under occlusion.^{b c d}

If HPA-axis suppression occurs, withdraw the drug, reduce the frequency of application, and/or substitute a less potent corticosteroid.^{c d}

HPA-axis function recovery generally is prompt and complete following drug discontinuance.^{c d}

Rarely, glucocorticosteroid insufficiency may require systemic corticosteroid therapy.^{b c d}

Systemic Effects

Systemic absorption following topical administration may result in manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.^{b c d}

Adverse systemic effects may occur when corticosteroids are used on large areas of the body, for prolonged periods of time, with an occlusive dressing, and/or concurrently with other corticosteroid-containing preparations.^b

Infants and children may be more susceptible to adverse systemic effects.^{c d} (See Pediatric Use under Cautions.)

Local Effects

Possible adverse local reactions (e.g., burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria); may occur more frequently with the use of occlusive dressings, especially with prolonged therapy.^b

Prolonged use of topical corticosteroids may cause atrophy of the epidermis and subcutaneous tissue;^b these effects are most likely to occur (even with short-term use) in intertriginous (e.g., axilla, groin), flexor, and facial areas.^b

If irritation occurs, discontinue drug and institute appropriate therapy.^{c d}

Skin Infection

If concurrent skin infection is present or develops, initiate appropriate anti-infective therapy.^{c d} If infection does not respond promptly, discontinue topical corticosteroid therapy until the infection has been controlled.^{c d}

When topical corticosteroids and topical anti-infectives are used concomitantly, consider that the corticosteroid may mask clinical signs of bacterial, fungal, or viral infections; prevent recognition of ineffectiveness of the anti-infective; or suppress hypersensitivity reactions to ingredients in the formulation.^b In addition, consider the cautions, precautions, and contraindications associated with the anti-infective.^b (See Occlusive Dressings under Cautions.)

Some manufacturers state that topical corticosteroids are contraindicated in patients with tuberculosis of the skin, dermatologic fungal infections, and cutaneous or systemic viral infection (including vaccinia and varicella and herpes simplex of the eye or adjacent skin).^b However, most clinicians believe topical corticosteroids can be used with caution if the infection is treated.^b

Occlusive Dressings

Adverse systemic corticosteroid effects may occur with use of occlusive dressings on large areas of the body and for prolonged periods of time; monitor accordingly.^b (See Hypothalamic-Pituitary-Adrenal Axis Suppression and also see Systemic Effects, under Cautions.)

Adverse local reactions may occur more frequently with the use of occlusive dressings, especially with prolonged therapy.^{b c d} (See Local Effects under Cautions.)

Do not use occlusive dressings on weeping or exudative lesions.^b

Do not use occlusive dressings in patients with primary skin infection.^b

Remove occlusive dressings covering large areas if body temperature increases; thermal homeostasis may be impaired.^b

Use plastic occlusive material with care to avoid the risk of suffocation.^b

Specific Populations

Pregnancy

Category C.^{c d}

Lactation

Not known whether topical alclometasone is distributed into milk.^{c d} Caution advised if topical alclometasone is used.^{c d}

Pediatric Use

Safety and efficacy not established in children <1 year of age.^{c d}

Do not use for the treatment of diaper dermatitis; tight-fitting diapers or plastic pants should not be used on a child being treated with alclometasone in the diaper area, since such garments may constitute occlusive dressings.^{c d}

Children are more susceptible to topical corticosteroid-induced HPA-axis suppression and Cushing's syndrome than mature individuals because of a greater skin surface area-to-body weight ratio, especially when topical corticosteroids are applied to >20% of body surface area.^{c d} The risk of adrenal suppression appears to increase with decreasing age.^b (See Systemic Effects under Cautions.)

Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol concentrations, and lack of response to corticotropin (ACTH) stimulation.^{b c d}

Children also are at greater risk of glucocorticoid insufficiency during and/or after withdrawal of treatment.^{b c d}

Intracranial hypertension has occurred in children; manifestations include bulging fontanelles, headaches, and bilateral papilledema.^{b c d}

Striae have been reported in children treated inappropriately with topical corticosteroids.^{b c d}

Topical corticosteroid therapy in children should be limited to the minimum amount necessary for therapeutic efficacy; chronic topical corticosteroid therapy may interfere with growth and development.^b

Geriatric Use

Response in limited number of patients ≥65 years of age does not appear to differ from that in younger adults.^{c d}

Common Adverse Effects

Burning, itching, erythema, irritation,, dryness, papular rash, folliculitis, acneiform eruptions, hypopigmentation^c , perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, miliaria.^{c d}

Interactions for Aclovate

Specific Drugs and Laboratory Tests

Drug or Test	Interaction
Nitroblue-tetrazolium test for bacterial infection	Concurrent use of corticosteroids reportedly may result in false-negative resultsb

Aclovate Pharmacokinetics

Absorption

Bioavailability

Topically applied alclometasone can be absorbed through normal intact skin.^{4 22 b c d}

Percutaneous penetration varies among individuals¹⁴ and can be altered by using occlusive dressings,^{1 4 16 17 d} high corticosteroid concentrations, and certain vehicles.^{1 15 16 b d}

Only minimal amounts of topical corticosteroid reach the dermis and subsequently the systemic circulation after application to most normal skin areas; more absorption occurs from the scrotum, axilla, eyelid, face, and scalp than from the forearm, knee, elbow, palm, and sole.^b

Absorption is markedly increased by loss of the skin’s keratin layer and by inflammation and/or diseases of the epidermal barrier (e.g., psoriasis, eczema).^{1 16 17 b d}

Distribution

Extent

Not known whether topical alclometasone is distributed into milk.^{c d}

Elimination

Metabolism

Once absorbed through the skin, topically applied corticosteroids are metabolized primarily in the liver.^{22 b}

Elimination Route

Topical corticosteroids and metabolites are excreted by the kidneys and, to a lesser extent, in bile.^{1 22}

Stability

Storage

Topical

Cream and ointment: 2–30°C.¹ Some manufacturers state 20–25°C.^d Consult product information for specific recommendations.

ActionsActions

• 
  

  Precise mechanism of action for topical anti-inflammatory activity is unknown; therapeutic benefit in the management of corticosteroid-responsive dermatoses mediated primarily through anti-inflammatory, antipruritic, and vasoconstrictive actions.^{c d}

  
  


• 
  

  Anti-inflammatory effects may occur through induction of phospholipase A₂ inhibitory proteins (lipocortins); decreased arachidonic acid release from membrane phospholipids.^d Decreased arachidonic acid precursors may downregulate biosynthesis of potent inflammatory mediators (e.g., prostaglandins, leukotrienes).^d

  
  


• 
  

  Decreases inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown.^b

  
  

Advice to Patients

• 
  

  Importance of using only as directed, only for the disorder for which it was prescribed, and for no longer than prescribed; avoid contact with the eyes and only apply externally as directed.^{c d} (See Topical Administration under Dosage and Administration.)

  
  


• 
  

  Importance of not applying on the face, underarms, or groin unless directed by clinician.^{c d}

  
  


• 
  

  Importance of informing patients that treated areas of the skin should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by a clinician.^{c d}

  
  


• 
  

  Importance of reporting any local adverse reactions, especially those occurring under occlusive bandage, to a clinician.^{b c d}

  
  


• 
  

  Importance of informing parents of children not to use in the treatment of diaper dermatitis and not to apply in the diaper area as diapers or plastic pants may constitute occlusive dressings.^{c d}

  
  


• 
  

  Importance of discontinuing use when control is achieved; importance of contacting clinician if no improvement is seen in 2 weeks.^{c d}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{c d}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{c d}

  
  


• 
  

  Importance of advising patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Alclometasone Dipropionate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Topical	Cream	0.05%*	Alclometasone Dipropionate Cream (with propylene glycol)	Fougera, Taro
			Aclovate (with propylene glycol)	GlaxoSmithKline
	Ointment	0.05%*	Alclometasone Dipropionate Ointment	Fougera, Taro
			Aclovate (with propylene glycol)	GlaxoSmithKline

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions January 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Glaxo Inc. Aclovate prescribing information. Research Triangle Park, NC; 1986 Sep.

2. Windholz M, ed. The Merck index. 10th ed. Rahway, NJ: Merck & Co, Inc; 1983:34.

3. Cornell RC, Stoughton RB. Correlation of the vasoconstriction assay and clinical activity in psoriasis. Arch Dermatol. 1985; 121:63-7. [IDIS 195066] [PubMed 3881088]

4. Thornfeldt C, Cornell RC, Stoughton RB. The effect of alclometasone dipropionate cream 0.05% on the hypothalamic-pituitary-adrenal axis of normal volunteers. J Int Med Res. 1985; 13:276-80. [PubMed 4054428]

5. Lassus A. Clinical comparison of alclometasone dipropionate cream 0.05% with hydrocortisone butyrate cream 0.1% in the treatment of atopic dermatitis in children. J Int Med Res. 1983; 11:315-9. [PubMed 6357892]

6. Bagatell FK, Barkoff JR, Cohen HJ et al. A multicenter comparison of alclometasone dipropionate cream 0.05% and hydrocortisone cream 1.0% in the treatment of atopic dermatitis. Curr Ther Res. 1983; 33:46-52.

7. Cornell RC. Atrophogenic potential of alclometasone dipropionate ointment 0.05% vs hydrocortisone ointment 1.0%. Curr Ther Res. 1986; 39:260-8.

8. Kalivas J, Kanof NB, Miller OF III et al. A controlled clinical comparison of alclometasone dipropionate cream 0.05% and hydrocortisone cream 1.0% in patients with psoriasis. Curr Ther Res. 1983; 33:408-14.

9. Aggerwal A, Maddin S. Alclometasone dipropionate in psoriasis: a clinical study. J Int Med Res. 1982; 10:414-8. [PubMed 7152079]

10. Frost P. Clinical comparison of alclometasone dipropionate and desonide ointments (0.05%) in the management of psoriasis. J Int Med Res. 1982; 10:375-8. [PubMed 6754511]

11. Lassus A. Alclometasone dipropionate cream 0.05% versus clobetasone butyrate cream 0.05%: a controlled clinical comparison in the treatment of atopic dermatitis in children. Int J Dermatol. 1984; 23:565-6. [PubMed 6389385]

12. Green MJ, Berkenkopf J, Xiomara F et al. Synthesis and structure-activity relationships in a novel series of topically active corticosteroids. J Steroid Biochem. 1979; 11:61-6. [PubMed 491605]

13. Duke EE, Maddin S, Aggerwal A. Alclometasone dipropionate in atopic dermatitis: a clinical study. Curr Ther Res. 1983; 33:769-74.

14. Crespi HG. Topical corticosteroid therapy for children: alclometasone dipropionate cream 0.05%. Clin Ther. 1986; 8:203-10. [PubMed 2938740]

15. Cornell RC, Stoughton RB. The use of topical steroids in psoriasis. Dermatol Clin. 1984; 2:397-409.

16. Cornell RC, Stoughton RB. Use of glucocorticosteroids in psoriasis. Pharmacol Ther. 1980; 2:497-508.

17. Food and Drug Administration. Topical corticosteroids class labeling guideline. (Undated.) Available from: Professional Labeling Branch, Division of Drug Advertising and Labeling, Food and Drug Administration, Rockville, MD.

18. Mobacken H, Hersle K. Alclometasone dipropionate ointment 0.05% versus hydrocortisone ointment 1.0% in children with eczema. Acta Ther. 1986; 12:269-78.

19. Green MJ, Shue HJ, Tiberi R et al. The influence of esterification on the topical antiinflammatory activity of 7 alpha-chloro- and 7 alpha-bromo-16 alpha-methylprednisolones. Arzneimittelforschung. 1980; 30:1618-20. [PubMed 7192095]

20. Lutsky BN, Berkenkopf J, Fernandez X et al. Selective effects of 7 alpha-halogeno substitution on corticosteroid activity: Sch 22219 and Sch 23409. Arzneimittelforschung. 1979; 29:992-8. [PubMed 583002]

21. Lutsky BN, Berkenkopf J, Fernandez X et al. A novel class of potent topical antiinflammatory agents: 17-benzoylated, 7 alpha-halogeno substituted corticosteroids. Arzneimittelforschung. 1979; 29:1662-7. [PubMed 543873]

22. Vonderweidt J (Glaxo, Research Triangle Park, NC): Personal communication; 1987 Apr 15.

23. Reviewers’ comments (personal observations); 1987 Apr.

24. Tokiwa T, Oyama T, Kimura S et al. [Studies on the primary dermal irritation, ocular mucosa irritation and local anaesthetic effect of alclometasone dipropionate (ADP)]. (Japanese; with English abstract.) Oyo Yakuri. 1986; 32:937-43.

25. Fujii K, Uda F, Yamamoto K. [Phototoxicity and photosensitivity tests of alclometasone dipropionate (ADP).] (Japanese; with English abstract.) Oyo Yakuri. 1986; 32:945-51.

26. Hasegawa T, Tujita K, Fujino A et al. [Immunogenicity study on alclometasone dipropionate (ADP)]. (Japanese; with English abstract.) Oyo Yakuri. 1986; 32:953-60.

27. Sills J (Schering, Kenilworth, NJ): Personal communication; 1987 May 28.

28. Lechner D (Schering, Kenilworth, NJ): Personal communication; 1987 June 3.

a. AHFS drug information 2007. McEvoy GK, ed. Alclometasone dipropionate. Bethesda, MD: American Society of Health-Systems Pharmacists; 2007: 3525–6.

b. AHFS drug information 2007 McEvoy GK, ed. Topical corticosteroids general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007:3423–5.

c. GlaxoSmithKline. Aclovate (alclometasone dipropionate) cream and ointment 0.05% prescribing information. Pittsburgh, PA; 2002 Aug.

d. Taro Pharmaceuticals. Alclometasone dipropionate ointment USP, 0.05% prescribing information. Hawthorne, NY; 2004 Jul.

More Aclovate resources

• Aclovate Side Effects (in more detail)
• Aclovate Use in Pregnancy & Breastfeeding
• Aclovate Drug Interactions
• Aclovate Support Group
• 0 Reviews for Aclovate - Add your own review/rating

• Aclovate Prescribing Information (FDA)


• Aclovate Concise Consumer Information (Cerner Multum)


• Aclovate Cream MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Aclovate with other medications

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Agenerase

Pronunciation: am-PREN-ah-veer
Generic Name: Amprenavir
Brand Name: Agenerase

Agenerase is used for:

Treating HIV infection. Agenerase is used in combination with other medicines.

Agenerase is an HIV-protease inhibitor. It works by inhibiting the growth of HIV.

Do NOT use Agenerase if:

• you are allergic to any ingredient in Agenerase


• you are taking astemizole, cisapride, delavirdine, an ergot derivative (eg, ergotamine), eletriptan, erythromycin, certain HMG-CoA reductase inhibitors (lovastatin, simvastatin), midazolam, nevirapine, an oral contraceptive (birth control pills), pimozide, a quinazoline (eg, alfuzosin), rifampin, St. John's wort, sumatriptan, terfenadine, or triazolam

Contact your doctor or health care provider right away if any of these apply to you.

Before using Agenerase:

Some medical conditions may interact with Agenerase. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other sulfonamide medicine, such as acetazolamide, celecoxib, certain diuretics (eg, hydrochlorothiazide), glyburide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide


• if you have diabetes, hemophilia or other bleeding disorders, high cholesterol or triglyceride levels, high blood sugar, liver disease, a skin rash, or kidney problems

Some MEDICINES MAY INTERACT with Agenerase. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Carbamazepine, dexamethasone, methadone, non-nucleoside reverse transcriptase inhibitors (NNRTIs) (eg, efavirenz, nevirapine), oral contraceptives (birth control pills), phenobarbital, phenytoin, rifampin, saquinavir, or St. John's wort because the effectiveness of Agenerase may be decreased


• HIV protease inhibitors (eg, indinavir, ritonavir) because the actions and side effects of Agenerase may be increased


• Astemizole, certain HMG-CoA reductase inhibitors (eg, lovastatin, simvastatin), cisapride, eletriptan, ergot derivatives (eg, ergotamine), erythromycin, midazolam, pimozide, quinazolines (eg, alfuzosin), sumatriptan, terfenadine, or triazolam because the risk of side effects may be increased by Agenerase


• Aldosterone blockers (eg, eplerenone), antiarrhythmics (eg, amiodarone, bepridil, flecainide, lidocaine, propafenone, quinidine), azole antifungals (eg, itraconazole, ketoconazole), benzodiazepines (eg, alprazolam), calcium channel blockers (eg, diltiazem, amlodipine), fluoxetine, fluticasone, immunosuppressants (eg, cyclosporine, tacrolimus), muscarinic receptor antagonists (eg, darifenacin), narcotic analgesics (eg, fentanyl), rifabutin, sildenafil, trazodone, or tricyclic antidepressants (eg, amitriptyline) because the risk of side effects may be increased by Agenerase


• Delavirdine because effectiveness may be decreased by Agenerase


• Anticoagulants (eg, warfarin) because actions and effectiveness may be altered by Agenerase

This may not be a complete list of all interactions that may occur. Ask your health care provider if Agenerase may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Agenerase:

Use Agenerase as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Agenerase may be taken with or without food. If you take it with food, do not take it with a high fat meal.


• Agenerase comes with an additional patient leaflet. Read it carefully and reread it each time you get Agenerase refilled.


• Do not take antacids or a buffered form of didanosine within 1 hour before or 1 hour after taking Agenerase.


• Continue to use Agenerase even if you feel well. Do not miss any doses.


• Do not switch between the capsule and liquid forms of Agenerase. They are not equal milligram to milligram. Consult with your doctor or pharmacist.


• If you miss a dose of Agenerase, take it as soon as possible. If you miss a dose by more than 4 hours, skip the missed dose and go back to your regular dosing schedule. It is important not to miss doses of Agenerase. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Agenerase.

Important safety information:

• Agenerase is not a cure for HIV infection and patients may continue to acquire illnesses and infections associated with HIV. Remain under the care of your doctor.


• Agenerase may not prevent other infections. If your health changes, check with your doctor.


• When your medicine supply begins to run low, get more from your doctor or pharmacist as soon as possible. The virus may develop resistance to Agenerase and become more difficult to treat if you stop taking it, even for a short period of time.


• Agenerase offers no protection from the transmission of HIV to others through sexual contact or blood contamination. Use barrier forms of contraception (eg, condoms) if you are infected with HIV. Do not share needles, other injection equipment, or personal items such as toothbrushes or razor blades.


• Certain birth control pills may decrease the effectiveness of Agenerase. Women should not take birth control pills and should use additional or other birth control measures (eg, condoms, diaphragms) while taking Agenerase.


• Do not take vitamin E supplements while you are taking Agenerase. Agenerase already contains vitamin E.


• Agenerase may cause high blood sugar (eg, thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, fruity breath odor). If these symptoms occur, tell your doctor immediately.


• Changes in body fat may occur in some patients taking this type of medicine. These changes may include increased amount of fat in the upper back and neck, breast, and around the trunk, and loss of fat from the legs, arms, and face. The cause and long-term effects are unknown. Discuss any concerns with your doctor.


• LAB TESTS, including liver function, blood cholesterol or triglyceride levels, and white blood cell counts, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.


• Use Agenerase with caution in the ELDERLY because they may be more sensitive to its effects.


• Agenerase is not recommended for use in CHILDREN younger than 4 years of age. Safety and effectiveness in this age group have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Agenerase during pregnancy. It is unknown if Agenerase is excreted in breast milk. Do not breast-feed while taking Agenerase. HIV-infected mothers should not breast-feed their infants because of the risk of transmitting the HIV infection or Agenerase.

Possible side effects of Agenerase:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Diarrhea/loose stools; headache; nausea; numbness or tingling around the mouth and in the hands and feet; rash; shift of body fat to stomach and upper back; stomach pain; taste disorders; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); change in mood, emotions, or behavior; clumsiness; depression; excessive urination, thirst, or hunger; fever, chills, or sore throat; muscle pain or stiffness; red, swollen, or blistered skin; seizures; unusual tiredness or weakness; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Agenerase side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Agenerase:

Store Agenerase at 77 degrees F (25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Agenerase out of the reach of children and away from pets.

General information:

• If you have any questions about Agenerase, please talk with your doctor, pharmacist, or other health care provider.


• Agenerase is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Agenerase. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

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• HIV Infection

Allergenic Extracts, Grass Pollen

Standardized Grasses

ALLERGY LABORATORIES, INC.

Oklahoma City OK 73109

INSTRUCTIONS AND DOSAGE SCHEDULE FOR 

STANDARDIZED ALLERGENIC EXTRACTS

BERMUDA GRASS POLLEN (Cynodon dactylon)

KENTUCKY BLUE GRASS POLLEN (Poa pratensis)

MEADOW FESCUE POLLEN (Festuca elatior)

ORCHARD GRASS POLLEN (Dactylis glomerata)

REDTOP GRASS POLLEN (Agrostis alba)

PERENNIAL RYE GRASS POLLEN (Lolium perenne)

SWEET VERNAL GRASS POLLEN (Anthoxanthum odoratum)

TIMOTHY GRASS POLLEN (Phleum pratense)

WARNING

This product is intended for use by physicians who are experienced in the administration of allergenic extracts and the emergency care of anaphylaxis or for use under the guidance of an allergy specialist.

STANDARDIZED GRASS POLLEN EXTRACTS LABELED IN BAU/ml ARE NOT INTERCHANGEABLE WITH GRASS POLLEN EXTRACTS LABELED IN AU/ml OR WITH NON-STANDARDIZED (WEIGHT/VOLUME) GRASS POLLEN EXTRACTS. For guidance in selecting dose, refer to Table A in the Clinical Pharmacology section that describes the potency of non-standardized grass pollen extracts. Comparative skin tests can be performed to determine the relative potency before initial use of new extracts. For previously untreated patents, initial dose must be based on skin testing as described in the Dosage and Administration section of this insert. Patients being switched from other types of extracts to Allergy Laboratories should have their dose adjusted. Extracts standardized in BAU (Bioequivalent Allergy Unit) may differ in potency from non-standardized extracts. Comparative skin tests can be performed to determine relative potency of standardized versus non-standardized extracts. The dosage should be reduced 75% when switching from one lot of standardized grass pollen extract to another Iot. Patients with unstable or severe asthma, including steroid-dependent asthma, are at increased risk for more frequent and more severe reactions from allergy extract injections. Greater caution must be exerted with such patients at all phases of extract administration, but particularly during build up. For example, extract therapy might be initiated at weaker concentrations and built by smaller dosage increments than in comparably allergic rhinitis patients without asthma. Also when asthma is poorly controlled, the injection regimen might be temporarily interrupted (at the discretion of the physician) until control of asthma is re-established. Whenever a reaction occurs in such patients their asthma should be medically stabilized before injections are resumed with an appropriate dosage reduction. Patients should be instructed to recognize adverse reaction symptoms and cautioned to contact physician's office if reaction symptoms occur. As with all allergenic extracts, severe systemic reactions may occur. In certain individuals these life threatening reactions may be fatal. Patients should be observed for at least 30 minutes following treatment and emergency measures as well as personnel trained in their use should be immediately available in the event of a life threatening reaction. Serious adverse reactions can be reported to the U S Food and Drug Administration MedWatch Program. The MedWatch forms can be obtained by calling 1-800-FDA-1088. The address is MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787.

This product should not be injected intravenously. Subcutaneous injections are recommended.

Patients who are taking non-selective 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. Refer also to the warnings, precautions, adverse reactions and dosage sections below.

DESCRIPTION:

      Standardized grass pollen extracts labeled in BAU/ml are not interchangeable with grass pollen extracts labeled in AU/ml or with non-standardized grass pollen extracts. The recommended route of administration for immunotherapy is subcutaneous. The routes of administration for diagnostic purposes are intradermal or prick-puncture of the skin. Do not inject intravenously. The extract is sterile and contains 50% (v/v) glycerin as a preservative. Standardized grass pollen extracts are available in both 10,000 BAU/ml and 100,000 BAU/ml potencies, except for Bermuda which is only available in 10,000 BAU/ml. The source material of the standardized grass extracts are the grass pollens. The 100,000 BAU/ml grass pollen extracts are prepared by extracting pollen at a 1:10 w/v ratio then diluting if necessary to the appropriate range for 100,000 BAU/ml. The 10,000 BAU/ml grass pollen extracts are prepared by dilution of the 100,000 BAU/ml grass pollen extracts. The 10,000 BAU/ml Bermuda grass pollen extract is prepared by extracting Bermuda grass pollen at a 1:10 w/v ratio then diluting if necessary to the appropriate range for 10,000 BAU/ml.

      The potency (in Bioequivalent Allergy Units per ml or BAU/ml) of standardized grass pollen extracts is determined by an in-vitro ELISA Competition assay (1) against CBER reference extracts and CBER reference serum pools distributed by the Center for Biologics Evaluation and Research, U S Food and Drug Administration. Potency based on Bioequivalent Allergy Units (BAU/ml) is printed on the label. FDA reference grass pollen extracts were assigned potency designations based on quantitative skin testing (2). The FDA reference extracts which can be diluted 1:500,000 fold intradermally to produce a sum of erythema diameter response of 50mm in highly puncture reactive subjects have been assigned 10,000 BAU/ml. References which can be diluted 1:5,000,000 fold intraderrnally to produce a sum of erythema diameter response of 50mm have been assigned 100,000 BAU/ml.

INACTIVE INGREDIENTS:

Glycerinated extracts contain:

glycerin	50.0 % v/v
sodium chloride	0.166 % w/v
sodium bicarbonate	0.091 % w/v

CLINICAL PHARMACOLOGY: 

The allergic state is initiated by an immune response inducing B cells to produce IgE antibodies to specific allergens. IgE antibodies bind to surface receptors on mast cells and basophils. When antigens gain access to the immune system they react with the bound IgE. The reacting antigen to the surface bound IgE stimulates a number of chemical mediators to be released from the mast cells and basophils. These include histamine, Eosinophil Chemotactic Factor (ECF-A) and leukotrienes. These chemical mediators are pharmacologically active at low concentrations and are partially responsible for the biological manifestations of the allergic response. (3) 

The mechanism by which immunotherapy achieves hyposensitization is not completely understood. There is an increase in "blocking antibody" (lgG) titer and in some patients a decrease in specific IgE, a decrease in histamine release to specific allergen and an increase in suppressor celI population to specific allergen. These changes may occur only after prolonged therapy. (4)

TABLE A Potency of Commercially Available Allergy Laboratories, Inc. Non-standardized Grass Pollen Extracts (glycerinated 1:20 w/v) In-vitro data by ELISA Competition Assay

		Potency	in	BAU/ml	BAU/ml Range for  Equivalence to Reference
GRASS POLLEN EXTRACT		Lot #1		Lot #2
Bermuda		14,600		8,500		6,999- 14,310
Kentucky Blue		94,000		150,000		69,990-143,100
Meadow Fescue		275,000		105,000		69,990-143,100
Orchard		96,000	Not tested			69,990-143,100
Redtop		117,000		58,000		69,990-143,100
Perennial Rye		195,000		101,000		69,990-143,100
Sweel Vernal		67,000		72,000		69,990-143,100
Timothy		140,000		149,000		69,990-143,100

Clinical data from the Center for Biologics Evaluation and Research is shown in the following tables

TABLE B Puncture and Intradermal Data with CBER Grass Pollen References

1. Puncture Data with 10,000 BAU/ml Grass Pollen Extracts using bifurcated needle
Reference Pollen		FDA Lot #		N		P∑E (mm)  Mean    Range				P∑W (mm) Mean             Range
Bermuda		E4-Ber		15		90.3		43-123		15.7		7-31
June		E3-Jkb		15		77.3		47-107		15.9		6-28
Meadow Fescue		E4-MF		15		81.1		57-115		11.9		7-22
Orchard		E4 Or		15		84.3		57-111		14.1		9-19
Perennial Rye		E10-Rye		15		92.3		73-135		17.5		6.36
Redtop		E4-Rt		15		77.1		42-98		14.1		8-19
Sweel Vernal		E4-SV		15		81.2		28-123		15.7		8-30
Timothy		E6-T		15		88.3		51-109		16.9		8-40
∑E = The sum of the longest diameter of erythema and the orthogonal erythema diameter measured at one half the longest erythema diameter.
∑W = The sum of the longest diameter of wheal and the orthogonal wheal diameter measured at one half the longest wheal diameter.

2. Intradermal Dose of CBER Grass Pollen References for 50mm Sum of Erythema (BAU50)
Reference Pollen		FDA Lot #			BAU50/ml Mean                   Range
Bermuda		E4-Ber			0.02		0.4 – 0.0003
June		E3-Jkb			0.02		0.1 – 0.004
Meadow Fescue		E4-MF			0.02		0.9 – 0.002
Orchard		E4 Or			0.02		1.9 – 0.002
Perennial Rye		E10-Rye			0.02		0.7 – 0.002
Redtop		E4-Rt			0.02		0.8 – 0.004
Sweel Vernal		E4-SV			0.02		1.0 – 0.002
Timothy		E6-Ti			0.02		0.6 – 0.002

INDICATIONS AND USAGE:

      Standardized grass pollen extracts are used for the diagnosis and treatment of allergic disease to grass pollen. The standardized (Bioequivalent Allergy Unit) extract in these vials is designed primarily for the physician equipped to prepare dilutions and mixtures as required. STANDARDIZED GRASS POLLEN EXTRACTS LABELED IN BAU/ml ARE NOT INTERCHANGEABLE WITH GRASS POLLEN EXTRACTS LABELED IN AU/ml OR WITH NON-STANDARDIZED (WEIGHT/VOLUME) GRASS POLLEN EXTRACTS. Patients being switched from other types of extracts to Allergy Laboratories should have their dose adjusted. Diagnosis of allergic disease to these grasses is made through a combined medical history sufficiently complete to identify allergic symptoms to grass pollen and identification of grass allergy by diagnostic skin testing. It is recommended that diagnostic skin testing (scratch or puncture) be performed with 10,000 BAU/ml grass pollen extracts before testing with 100,000 BAU/ml grass pollen extracts. 10,000 BAU/mL and 100,000 BAU/ml grass pollen extracts for immunotherapy are available for previously treated patients to facilitate dose selection for safe switching from non-standardized to standardized extracts. Patients being treated with grass pollen extracts for the first time can be initially immunized with dilutions prepared from the 10,000 BAU/ml extract (see Dosage and Administration). 100,000 BAU/ml grass pollen extract can be administered if the patient tolerates the 10,000 BAU/ml extract.

      Grass pollen immunotherapy is intended for patients whose grass allergic symptoms cannot be satisfactorily controlled by avoidance of the offending allergen or by the use of symptomatic medications. (5)

CONTRAINDICATIONS:

      There are no known absolute contraindications to hyposensitization therapy. See precautions section for pregnancy risks.

      A patient without a history of grass pollen allergy symptoms and a positive skin test reaction to grass pollen should not be treated. The physician must determine if the benefits outweigh the risks in using these products for treating patients. The benefit to risk ratio should be carefully weighed especially where risks of immunotherapy are higher than usual. This includes severe unstable asthma, highly allergic patients who have had previous severe or unusual problems with injections, pregnancy, or any fragile general medical condition. This also includes patients where potential benefits are limited due to coexisting non-allergic disease such as: non-specific vasomotor rhinitis, nasal septal deviation, nasal polyps, COPD (chronic obstructive pulmonary disease), cardiovascular or other non-allergic respiratory disease.

WARNINGS 

See WARNINGS box at the beginning of the instruction sheet.

      Extracts standardized using the Bioequivalent Allergy Unit may be more or less potent than extracts based on AU/ml, weight to volume, or PNU methods of expressing potency. See Adverse Reactions section in this insert for a description of the possible local reactions and systemic reactions. Comparative skin tests can be performed to determine the relative potency before initial use of new extracts. DO NOT GIVE ALLERGY INJECTIONS INTRAVENOUSLY. Subcutaneous injections are recommended. Injections may produce large local reactions that may be painful to the patient. DO NOT GIVE FULL-STRENGTH INJECTIONS UNTIL COMPARATIVE SKIN TESTING IS PERFORMED. After inserting the needle, but before injecting extract, withdraw the plunger slightly. If blood appears in the syringe re-insert the needle at another site. Careful selection of dose and injection should prevent most systemic reactions.

PRECAUTIONS:

GENERAL:

      The dosage should be reduced 50-75% from the previous dose when starting a patient on a new lot of standardized grass extract from the same manufacturer or from a different manufacturer. Table A in the Clinical Pharmacology section of this insert can be used for guidance when changing from a non-standardized grass extract to a standardized grass extract. The table shows the similarity in potency of two Iots of the non-standardized grass extracts with respect to the 10,000 BAU/ml standardized extracts. Comparative skin testing can be used to determine the dose.

      A separate sterile tuberculin type syringe should be used with each patient to prevent cross contamination of extracts. This will also prevent transmission of disease such as hepatitis, AIDS and other infectious diseases. Aseptic technique should always be used when injections of allergenic extracts are administered.

INFORMATION FOR PATIENTS:

      Because most serious reactions following the administration of allergenic extracts occur within 30 minutes of the injection, the patient should remain under observation for this period of time. The size of the local reaction should be recorded, because increasingly large local reaction may precede a subsequent systemic reaction with increasing dosage. The patient should be instructed to report any unusual reactions to the attention of the physician. In particular, this includes swelling and/or tenderness at the injection site or reactions such as rhinorrhea, sneezing, coughing, wheezing, shortness of breath, nausea, dizziness or faintness.

DRUG INTERACTIONS:

      Patients who are taking non-selective beta blockers may be more reactive to skin tests and may be unresponsive to the usual doses of epinephrine used to treat allergic reactions. Antihistamines can significantly inhibit the immediate skin test reactions. If long acting antihistamines have been taken recently, it is recommended that they should be stopped for the following minimum intervals before skin testing is performed: at least 1 month for astemizole; 1 week for hydroxyzine or cetirizine; 4 to 7 days for Ioratadine; 3 to 4 days for terfenadine or fexofenadine; and 24 to 48 hours for other sustained release antihistamines. (6)

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY:

      Long term studies with extracts have not been conducted in animals to determine their potential for carcinogenesis, mutagenesis, or impairment of fertility.

PREGNANCY:

      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. Allergenic extracts should be given to a pregnant woman only if clearly needed.

      Controlled studies of hyposensitization with moderate to high doses of allergenic extracts in pregnant women have failed to demonstrate any risk to the mother or fetus. (7)

      Initiation of effective immunotherapy may be beneficial if it allows a pregnant patient to forego medications during the first trimester when the fetus is more vulnerable to teratogenic agents, or if it contributes to better control of asthma so the fetus has less likelihood of being damaged by hypoxemia.

      However, with histamines known ability to contract uterine muscles any reaction which would release significant amounts of histamine such as hyposensitization overdose should be avoided. The physician must weigh the benefits of immunotherapy against the risk of anaphylactic reactions that could result in harm to the mother and/or fetus.

      Hyposensitization should be used during pregnancy only if clearly necessary and administered cautiously. If a woman is on maintenance dose the occurrence of pregnancy is not an indication to stop injection therapy.

NURSING MOTHERS:

      It is not known if allergenic extracts are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when extracts are administered to nursing women.

PEDIATRIC USE

      Standardized grass pollen extract has not been studied in children, so the safety in children has not been established. The extracts may cause some pain or discomfort when injected, as well as systemic, adverse reactions (see Warnings and Adverse Reactions). The maximum tolerated dose may be less than the adult dose due to the smaller size of the child. Therefore, the volume of the dose may need to be adjusted from the adult schedules provided.

ADVERSE REACTIONS:

(1) Local Reactions:

      Some swelling and redness at the site of injection is not unusual. Mild burning that occurs immediately after the injection is normal; this usually subsides in 10 to 20 seconds. If the swelling and redness persist for a period of 24 hours or longer this should be a sign to proceed with caution in increasing the dosage. With the next injection the dosage should remain the same or be decreased. Large local reactions may indicate that a systemic reaction could occur with the next injection if the dosage was increased. If a patient continues to have reactions at the maintenance dose, the patient is considered to have exceeded the maximum tolerated dosage.

(2) Systemic Reactions:

      Systemic reactions occur infrequently but must be looked for in all patients, especially highly sensitive patients. Anaphylactic shock and death are always possible, therefore, physicians must be prepared for the treatment of these reactions. Systemic reactions can also be characterized by one or more of the following symptoms: angioedema, tachycardia, conjunctivitis, cough, fainting, hypotension, pallor, rhinitis, urticaria and wheezing.

      Systemic reaction can be treated by the immediate application of a tourniquet above the site of injection and the administration of 0.3 to 0.5ml of 1:1000 Epinephrine-Hydrochloride subcutaneously or intramuscularly in the opposite arm. The dosage may be repeated two times at 15 minute intervals. Loosen the tourniquet at least every 10 minutes.

      The pediatric dosage for 1:1000 Epinephrine-Hydrochloride is 0.05 to 0.1 ml for infants to 2 years of age; 0.15ml, for children 2 to 6 years; and 0.2ml, for children 6 to 12 years.

      Patients should always be observed for at least 30 minutes after any injection. Hypotension can be reversed by using vasopressor agents and volume expanders. Parenteral aminophylline and inhalation bronchodilators may be required for bronchospasm. Oxygen may also be needed. Maintenance of an open airway is critical if upper airway obstruction is present. Adrenal corticosteroids and intravenous antihistamine can be given after adequate epinephrine and circulatory support has been administered. Physicians must be familiar with these systemic reactions and have all the equipment and drugs necessary for proper treatment. (8)

      Serious adverse reactions can be reported to the US Food and Drug Administration MedWatch Program. The MedWatch forms can be obtained by calling 1-800-FDA-1088. The address is: MedWatch, 5600 Fishers Lane, Rockville, MD, 20852-9787.

OVERDOSAGE:

Refer to Adverse Reactions section above.

DOSAGE AND ADMINISTRATION:

DIAGNOSTIC SKIN TESTING: These products are used to determine a patient's sensitivity to specific antigens and aid in the diagnosis and treatment of atopic diseases. After a thorough history, a decision can be made as to which allergens will be appropriate to use for testing. The recommended procedure is to initially perform puncture tests, then follow with intradermal tests. For enhanced safety, scratch or puncture test with 10,000 BAU/ml before testing with 100,000 BAU/ml. See recommended dosage below:

*  See Table B for information regarding range of BAU/ml that elicits a 50mm response for highly reactive patients. The negative intradermal control used for the 100 BAU/ml concentration should contain 0.5% (v/v) glycerin.
SCRATCH OR PUNCTURE TEST:		Concentration BAU/ml		Dosage
		Bermuda Grass		1 drop
		10,000
		Other Grasses
		10,000		1 drop
		100,000		1 drop
INTRADERMAL TEST:		Concentration BAU/ml		Dosage ml
When scratch or puncture test is negative:		100		0.02
When scratch or puncture test is positive:		*		0.02

FREQUENCY OF ADMINISTRATION:

      The number of skin tests applied at one time will depend on the particular patient and their allergic history. These tests should be performed and observed in 15 to 20 minutes. Additional tests may be applied in sequence. Perform tests on the anterolateral aspect of the upper arm on an area that permits the effective application of a tourniquet proximal to the site of the test. The skin at the site of injection should be disinfected with rubbing alcohol before testing.

      Puncture testing: Apply one drop of extract to the skin. Pierce the drop of extract and skin using a sterile hypodermic needle or vaccinating needle. Maintain the needle perpendicular to the skin surface and rock the needle back and forth to produce a small hole without bleeding. Do not rotate or gouge the needle. Remove needle from skin and wipe excess extract from skin surface.

      Scratch testing: Using a scarifier or needle, make a scratch 1/16 inch long on the epidermis penetrating the outer cornified area but being careful not to draw blood. Apply one drop of extract to the scratch.

      Intradermal testing: Use a separate sterile syringe (tuberculin type equipped with a 27 gauge by 3/8 inch needle with intradermal bevel) for each antigen. The tests are made by injecting 0.02ml of allergen into the epidermis. If the test has been performed properly, the solution should raise a bleb 2 to 3mm in diameter. If the bleb does not appear, the injection was made too deeply.

      A negative control consisting of the same solution that the extract was prepared in, should be applied to one of the sites in the same manner as the tests being performed. For example, the negative intradermal control should contain 0.5% (v/v) glycerin, if a 100 BAU/ml concentration grass is used for intradermal testing. Histamine phosphate should be used as a positive control for evaluation of skin testing. Histamine phosphate is available from other manufacturers. See their directions for use, for recommended dosage and interpretation of results.

      A positive reaction usually develops in 15 to 20 minutes. The positive response is a wheal and flare reaction that is larger than the negative control and judged on the size of the reaction. Scratch or puncture tests may not elicit as large and well defined reaction as the intradermal. (5)

The following grading system for intradermal testing is recommended (9):

	Reaction	Erythema	Wheal
	0	<5mm	<5mm
	+/-	5-10mm	5-10mm
	1+	11-20mm	5-10mm
	2+	21-30mm	5-10mm
	3+	31-40mm	10-15mm or with pseudopods
	4+	>40mm	>15mm or with many pseudopods

IMMUNOTHERAPY:

The following are two methods of injection therapy:

      1. Pre-seasonal in which treatment is begun three months before seasonal difficulty begins and brought to maintenance dose by injections 4 to 7 days apart and discontinued after that season ends.

      2. Perennial treatment is the recommended mode of therapy in which the patient is, by injection therapy, brought up to tolerated maintenance dose and remains at that dose until amelioration of allergic symptoms occurs. Injections may be given at intervals of 4 to 7 days.

      Allergenic extracts must be diluted before use. Normally immunotherapy can be started with a 1 BAU/ml dilution. If a patient appears to be extremely sensitive, based on skin testing results, dilutions of the extract can further be made before injections are started. See Table B for additional information. The following are suggested procedures for making a proper dilution series. Recommended diluents contain 0.9% sodium chloride and 0.4% phenol as a preservative. Dlluents with HSA (Human Serum Albumin) as a stabilizer can also be used. Allergenic extracts should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

TEN FOLD DILUTION SERIES:

EXTRACT VOLUME	EXTRACT CONCENTRATION BAU/ml	DILUENT VOLUME	DILUTION CONCENTRATION BAU/ml
1 part	100,000 +	9 parts =	10,000
1 part	10,000 +	9 parts =	1,000
1 part	1,000 +	9 parts =	100
1 part	100 +	9 parts =	10
1 part	10 +	9 parts =	1

     

      Perennial treatment may be started using the following dosage and dilution schedule. (Modified from Reference 10) This schedule is only illustrative and may not be applicable to all patients, since the degree of sensitivity to grass allergens differs among individuals. The dose administered must be adjusted based on the patient's sensitivity and tolerance. Initial dose can be based on end point titration using a dose that elicits a 1-2+ reaction. Maintenance dose is based on patient tolerance.

Dose #	Dose Volume (ml)	Concentration
1	0.05	1 BAU/ml
2	0.10
3	0.20
4	0.30
5	0.40
6	0.50
7	0.05	10 BAU/ml
8	0.10
9	0.20
10	0.30
11	0.40
12	0.50
13	0.05	100 BAU/ml
14	0.10
15	0.20
16	0.30
17	0.40
18	0.50
19	0.05	1,000 BAU/ml
20	0.10
21	0.20
22	0.30
23	0.40
24	0.50
25	0.05	10,000 BAU/ml
26	0.10
27	0.20
28	0.30
29	0.40
30	0.50
31	0.05	100,000 BAU/ml
32	0.10
33	0.20
34	0.30
35	0.40

Gradually increase the dose as outlined in the schedule. If you give a dose that causes a mild local reaction (manifested by warmth or redness) repeat the same dose. If the reaction is severe or systemic (manifested as hives, asthma, or hay fever) drop back a dose in schedule and build again. If a severe local reaction or a systemic reaction is again encountered, this should be considered more than the maximum tolerance for this patient. The maintenance dose is the largest dose that relieves symptoms without producing local reactions. The size and interval of doses will vary and can be adjusted as necessary. The normal interval between doses is 4 to 7 days. The usual duration of treatment has not been established. A period of two or three years of injection therapy constitutes an average minimum course of treatment.

HOW SUPPLIED:

      Bulk extract (stock concentrate) in 50% (v/v) glycerin containing 10,000 BAU/ml or 100,000 BAU/ml is supplied in 10ml, 30ml, and 50ml vials. Bermuda Grass bulk extract is available in 10,000 BAU/ml only. Scratch testing for Bermuda Grass in 50% (v/v) glycerin containing 10,000 BAU/ml is supplied in 2ml dropper vials. Scratch testing for the other grasses in 50% (v/v) glycerin containing 10,000 BAU/ml or 100,000 BAU/ml is supplied in 2ml dropper vials. Intradermal testing (aqueous) for all standardized grasses containing 100 BAU/ml is supplied in 5ml vials.

STORAGE:

      These extracts should be stored at 2 to 8 degrees Celsius. Excessive heating (above room temperature) and repeated freeze-thawing should be avoided. The dating period (expiration date) is shown on the vial label. Once extracts are diluted the shelf life decreases. Extracts should be reordered when out of date. Please allow a minimum of three (3) weeks for delivery due to the holding period for sterility testing.

REFERENCES:

1. ELISA Competition Assay, October 1993. In Methods of the Allergenics Products Testing Laboratory, Food and Drug Administration.
   


2. Turkeltaub, P. Rastogi, S.C.: Quantitative Intradermal Procedure for Evaluation of Subject Sensitivity to Standardized Allergenic Extracts and for Assignment of Bioequivalent Allergy Units to Reference Preparations Using the ID5oEAL Method, November 1994. In Methods of the Allergenic Products Testing Laboratory Center for Biologics Evaluation and Research, Food and Drug Administration.
   


3. Wasserman, S.I.: Biochemical Mediators of Allergic Reactions. In Patterson, R (ed): Allergic Diseases: Diagnosis and Management, p. 86, Philadelphia, J.B. Lippincott Co., 1985.
   


4. Grammer, L.C.: Principle of Immunologic Management of Allergic Diseases Due to Extrinsic Antigens. In Patterson, R. (ed) Allergic Diseases: Diagnosis and Management, p. 358, Philadelphia, J.B. Lippincoit Co., 1985.
   


5. Booth, B.H., Diagnosis of Immediate Hypersensitivity, In Patterson, R. (ed): Allergic Diseases: Diagnosis and Management, p. 102, Philadelphia, J.B. Lippincott Co., 1985.
   


6. Bousquet, J., Michel F.: In vivo Methods for Study of Allergy: Skin Tests, Techniques, and Interpretation. In Middleton, E. Jr., Reed, C.E. and Ellis, E.F. (ed): Allergy Principles and Practice, (Vol. 1) p. 583, St Louis. The C.V. Mosby Co., 1993.
   


7. Metzger, W.J. et. al.: The Safety of Immunotherapy During Pregnancy. J. Allergy Clin. Immunol., 64 (4): 268-272, 1978.
   


8. Patterson, R. et. al.: Immunotherapy. In Middleton, E. Jr., Reed, C.E. and Ellis, E.F. (ed): Allergy; Principles and Practice, (Vol. 2) p. 1119, St Louis, The C.V. Mosby Co., 1983.
   


9. Norman, P.S., In vivo Methods of Study of Allergy: Skin and Mucosal Tests, Techniques and Interpretation. In Middleton, E. Jr. Reed, C.E. and Ellis, E.F. (ed): Allergy Principles and Practice, (Vol. 1) p. 258, St Louis, The C.V. Mosby Co., 1978.
   


10. Van Metre, T.E. Jr, Adkinson, N.F. Jr.: Immunotherapy for Aeroallergen Disease. In Middleton, E. Jr., Reed, C.E. and Ellis, E.F. (ed): Allergy Principles and Practice, (Vol. 2) p. 1499, St Louis, The C.V. Mosby Co. 1993.

Revised 5/20/97

ALLERGY LABORATORIES, INC. 

U.S. License #103 

Oklahoma City, OK 73109 • (405) 235-1451 • (800) 654-3971

PRINCIPAL DISPLAY PANEL

ALLERGENIC EXTRACT

STANDARDIZED POLLEN

Preservative 50% Glycerin (v/v)

Dose/Route: See Enclosure

Store at 2-8°C, NON RETURNABLE

ALLERGY

LABORATORIES, INC

Oklahoma City, OK 73109

U.S Govt. License No. 103

STANDARDIZED BERMUDA GRASS POLLEN  cynodon dactylon pollen  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 54575-084 Route of Administration PERCUTANEOUS, SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength