Version May 2024
Early administration of diphtheria antitoxin (DAT) is critical for survival; administer DAT as soon as possible after assessing for hypersensitivity to horse serum and performing desensitization (as needed based on results of sensitivity testing).
Sensitivity testing: Perform prior to each course of treatment with DAT. Perform a scratch, prick, or puncture skin test; if the skin test is negative then perform an intradermal (ID) test. The patient should undergo desensitization if the skin test or ID test is positive or if the patient has a history suggesting increased risk from DAT administration (even with a negative or equivocal sensitivity test).
Skin test (scratch, prick, or puncture skin test): A positive skin test is a wheal with surrounding erythema ≥3 mm larger than the negative control test, read at 15 to 20 minutes. The histamine control must be positive (a wheal at the scratch site surrounded by an erythematous area) for valid interpretation. If the skin test is negative, perform an ID test. If the skin test is positive, the patient should undergo desensitization.
Patients with a negative history for animal allergy and no prior exposure to animal serum: Scratch, prick, or puncture: Apply 1 drop of 1:100 dilution of the serum in NS to the site. Apply positive (histamine) and negative (physiologic saline) control tests to similar scratch, prick, or puncture sites.
Patients with a positive history for animal allergy or prior exposure to animal serum: Scratch, prick, or puncture: Apply 1 drop of 1:1,000 dilution of the serum in NS to the site. If the test is negative, repeat using a 1:100 dilution. Apply positive (histamine) and negative (physiologic saline) control tests to similar scratch, prick, or puncture sites.
Intradermal test: A positive ID test is a wheal with surrounding erythema ≥3 mm larger than the negative control test, read at 15 to 20 minutes. The histamine control must be positive (a wheal at the ID site surrounded by an erythematous area) for valid interpretation. If the ID test is negative and the patient does not have a history suggesting increased risk from DAT administration, begin the treatment regimen. If the ID test is positive or the patient has a history suggesting increased risk from DAT administration (even with a negative or equivocal sensitivity test), the patient should undergo desensitization.
Patients with a negative history for animal allergy and no prior exposure to animal serum: Intradermal: Administer 0.02 mL of 1:100 dilution of the serum in NS. This quantity should raise a small ID wheal. Apply positive (histamine) and negative (physiologic saline) control tests to similar ID sites.
Patients with a positive history for animal allergy or prior exposure to animal serum: Intradermal: Administer 0.02 mL of 1:1,000 dilution of the serum in NS. This should raise a small ID wheal. If the test is negative, repeat using a 1:100 dilution. Apply positive (histamine) and negative (physiologic saline) control tests to similar ID sites.
Desensitization: Desensitization should be performed if the skin test or ID test is positive or if the patient has a history suggesting increased risk from DAT administration (even with a negative or equivocal sensitivity test). The protection from anaphylaxis requires that no interruption occur in the sequence of administration of doses; if an interruption occurs, the protection is lost. All patients undergoing desensitization require close monitoring in a setting that has ready access to medications and equipment for resuscitation.
IV (preferred): Note: The IV route is preferred as it offers better control. Administer desensitization doses at 15-minute intervals.
|
Dose number |
Dilution of DATa in NS |
Amount of injection |
|---|---|---|
|
aDAT = Diphtheria antitoxin. b1 mL (DAT) + 9 mL NS = 1:10 dilution of DAT. 1 mL (1:10 dilution of DAT) + 9 mL NS = 1:100 dilution of DAT. 0.1 mL (1:10 dilution of DAT) + 9.9 mL NS = 1:1,000 dilution of DAT. 1 mL (1:100 dilution of DAT) + 9 mL NS = 1:1,000 dilution of DAT. | ||
|
1 |
1:1,000b |
0.1 mL |
|
2 |
1:1,000 |
0.3 mL |
|
3 |
1:1,000 |
0.6 mL |
|
4 |
1:100b |
0.1 mL |
|
5 |
1:100 |
0.3 mL |
|
6 |
1:100 |
0.6 mL |
|
7 |
1:10b |
0.1 mL |
|
8 |
1:10 |
0.3 mL |
|
9 |
1:10 |
0.6 mL |
|
10 |
undiluted |
0.1 mL |
|
11 |
undiluted |
0.2 mL |
|
12 |
undiluted |
0.6 mL |
|
13 |
undiluted |
1 mL |
Intradermal, SubQ, and IM: Note: Administer doses at 15-minute intervals.
|
Dose number |
Route of administration |
Dilution of DATa in NS |
Amount of injection |
|---|---|---|---|
|
aDAT = Diphtheria antitoxin. b1 mL (DAT) + 9 mL NS = 1:10 dilution of DAT. 1 mL (1:10 dilution of DAT) + 9 mL NS = 1:100 dilution of DAT. 0.1 mL (1:10 dilution of DAT) + 9.9 mL NS = 1:1,000 dilution of DAT. 1 mL (1:100 dilution of DAT) + 9 mL NS = 1:1,000 dilution of DAT. | |||
|
1 |
Intradermal |
1:1,000b |
0.1 mL |
|
2 |
Intradermal |
1:1,000 |
0.3 mL |
|
3 |
SubQ |
1:1,000 |
0.6 mL |
|
4 |
SubQ |
1:100b |
0.1 mL |
|
5 |
SubQ |
1:100 |
0.3 mL |
|
6 |
SubQ |
1:100 |
0.6 mL |
|
7 |
SubQ |
1:10b |
0.1 mL |
|
8 |
SubQ |
1:10 |
0.3 mL |
|
9 |
SubQ |
1:10 |
0.6 mL |
|
10 |
SubQ |
undiluted |
0.1 mL |
|
11 |
SubQ |
undiluted |
0.2 mL |
|
12 |
IM |
undiluted |
0.6 mL |
|
13 |
IM |
undiluted |
1 mL |
Diphtheria (confirmed or suspected), treatment: Note: Bacteriologic confirmation is not required prior to DAT administration; continue supportive treatment until all local and general symptoms are controlled. Appropriate antimicrobial agents should be initiated immediately upon suspicion of respiratory diphtheria (ideally after specimen collection). All patients require close monitoring in a setting that has ready access to medications and equipment for resuscitation. The IV route is preferred, especially in severe cases; IM administration may be considered in mild or moderate cases.
IV (preferred), IM:
Pharyngeal or laryngeal disease of 2 days duration: 20,000 to 40,000 units (2 to 4 ampules) as a single dose.
Nasopharyngeal disease: 40,000 to 60,000 units (4 to 6 ampules) as a single dose.
Extensive disease of ≥3 days duration, or any patient with diffuse swelling of neck: 80,000 to 100,000 units (8 to 10 ampules) as a single dose.
Skin lesions only (rare case where treatment is indicated): 20,000 to 40,000 units (2 to 4 ampules) as a single dose. Note: DAT is rarely required; treatment focused on wound hygiene and antimicrobial therapy.
Diphtheria, prophylaxis: Note: DAT prophylaxis is recommended only in exceptional circumstances in consultation with Centers for Disease Control and Prevention diphtheria duty officer; administer with appropriate antimicrobial prophylaxis (if needed) and immunization with diphtheria toxoid. Prior to administration of prophylactic DAT, perform appropriate sensitivity tests. If sensitivity testing is negative, administer the prophylactic regimen. If sensitivity testing is positive, patient should undergo desensitization prior to administration of prophylactic regimen. All patients require close monitoring in a setting that has ready access to medications and equipment for resuscitation.
IM: 10,000 units (1 ampule) as a single dose.
There are no dosage adjustments provided in the Food and Drug Administration's Expanded Access Investigational New Drug Application Protocol.
There are no dosage adjustments provided in the Food and Drug Administration's Expanded Access Investigational New Drug Application Protocol.
Refer to adult dosing.
Refer to adult dosing.
The following adverse drug reactions are derived from Expanded Access Investigational New Drug Application Protocol: Use of diphtheria antitoxin for suspected diphtheria cases.
Frequency not defined:
Hypersensitivity: Anaphylaxis, angioedema, serum sickness
Miscellaneous: Febrile reaction
There are no contraindications listed in the Food and Drug Administration's Expanded Access Investigational New Drug Application Protocol.
Only available in the United States under an investigational new drug (IND) protocol through the Centers for Disease Control and Prevention (CDC). Clinicians may contact the CDC Drug Service at 1-404-639-3670 (Monday to Friday 8:00 am to 4:30 pm Eastern Standard Time) or by contacting the CDC Emergency Operations Center at 1-770-488-7100. Additional information from the CDC may be found at https://www.cdc.gov/diphtheria/dat.html or https://www.cdc.gov/laboratory/drugservice/formulary.html.
Note: Current lots of diphtheria antitoxin provided under the Expanded Access IND Application Protocol have passed the manufacturer’s original labeled expiration date (Instituto Butantan lot #0710214 with original expiry of October 2010 and lot #0412178/B with original expiry of November 2007); however, both lots may continue to be used based on tests for potency/stability conducted in March 2020.
No
Diphtheria antitoxin is not currently licensed by the Food and Drug Administration and is only available in the United States under an investigational new drug protocol through the Centers for Disease Control and Prevention (CDC). Clinicians may contact the CDC Drug Service at 1-404-639-3670 (Monday to Friday 8:00 am to 4:30 pm Eastern Standard Time) or by contacting the CDC Emergency Operations Center at 1-770-488-7100. Additional information from the CDC may be found at https://www.cdc.gov/diphtheria/dat.html or https://www.cdc.gov/laboratory/drugservice/formulary.html.
Sensitivity testing:
Skin test (scratch, prick, or puncture skin test):
Diphtheria antitoxin test site: Scratch, prick, or puncture: Make 1 small scratch (2 to 4 mm in length) in the skin on the volar surface of the right forearm with a 27-gauge needle without drawing blood. Place a small drop of the diphtheria antitoxin (DAT) dilution (appropriate for the patient-specific situation) on the site of the scratch on the right forearm.
Control test sites: Scratch, prick, or puncture: Make 2 small scratches (2 to 4 mm in length and 5 cm apart from each other) in the skin on the volar surface of the left forearm with a 27-gauge needle without drawing blood. Place a small drop of NS on 1 scratch site (negative control) and one drop of histamine solution (positive control) on the other scratch site on the left forearm.
Intradermal test:
DAT test site: Administer the DAT dilution (appropriate for the patient-specific situation) intradermally using a 26- to 28-gauge needle on the volar surface of the right forearm ≥5 cm away from any other test site.
Control test sites: Administer NS (negative control) and histamine (positive control) intradermally at 2 separate sites (≥5 cm away from each other and any other test site) using a 26- to 28-gauge needle on the volar surface of the left forearm.
Desensitization: May be administered IV (preferred), intradermal, SubQ, or IM (route is based on dose sequence, refer to table for Alternate Routes of Injection).
DAT, treatment: Administer IV (preferred; especially in severe cases) slowly over 2 to 4 hours. May consider IM administration in mild or moderate cases. Warm to 32°C to 34°C (90°F to 95°F) before administration; warming above the recommended temperature may denature proteins contained in the DAT solution.
DAT, prophylaxis: Administer IM. Warm to 32°C to 34°C (90°F to 95°F) before administration; warming above the recommended temperature may denature proteins contained in the DAT solution.
Note: All patients should undergo sensitivity testing to determine if desensitization is needed prior to drug administration; see CDC DAT protocol for detailed instructions which may be found at https://www.cdc.gov/diphtheria/downloads/protocol.pdf.
IV: Preferred route especially for severe cases. Administer slowly over 2 to 4 hours.
IM: Administer IM for mild to moderate cases only.
Diphtheria (confirmed or suspected), treatment: Treatment of confirmed or suspected diphtheria with eligibility determined by Centers for Disease Control and Prevention diphtheria duty officer and the treating clinician.
Diphtheria, prevention: Prevention of diphtheria limited to the following situations:
An individual who:
Has had known exposure to toxigenic Corynebacteria diphtheriae (or possibly other toxigenic Corynebacteria) and
Is not up to date for vaccination against diphtheria and
Cannot be kept under surveillance for the development of clinical symptoms or is not available for follow-up of results of culturing for the diphtheria organism.
An individual who has suspected or known injection of diphtheria toxin (eg, laboratory workers). Note: Needle sticks do not qualify as injections.
None known.
There are no known significant interactions.
Vital signs; hypersensitivity reactions. Note: Clinicians treating a patient with diphtheria antitoxin (DAT) must follow patient's monitoring and reporting of adverse reaction parameters as described in the Centers for Disease Control and Prevention DAT protocol, which may be found at https://www.cdc.gov/diphtheria/downloads/protocol.pdf.
Equine-based diphtheria antitoxin neutralizes circulating toxin produced by C. diphtheriae and some strains of Corynebacterium ulcerans. Toxin already fixed to tissue is not neutralized by the antitoxin.
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