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Report of committee on therapy
AMERICAN
ACADEMY
OF
“xi
ALLERG\+
Maurice M. Hillman, M.D., 31 Howe Street, New Haven, (lonn. James Holman, M.D., 1406 Medical Arts Building, Dallas, Tex. Gertrude R. Holmes, M.D., 213 East North Street, Greenville, S. C. Daniel M. Rraus, M.D., 326 Republic Building, Denver, Colo. Robert G. Lovell, M.D., University of Michigan Hospital, Ann Arbor, Mich. Kenneth P. Mathews, M.D., University of Michigan Hospital, Allergy Clinic, Ann i\rbor, Mich. Alexander McCausland, M.D., 818 S. Jefferson Street, Roanoke, Va. Ernest0 Mendes, M.D., Rua Angatuba, 308, Sao Paulo, Brazil, S. A. Robert E. Miller, M.D., 5408 Forest Blvd., East St. Louis, Ill. Meyer Monchek, M.D., 63-75 Dry Harbor Road, West Forest, L. I., N. Y. Ira R. Morrison, M.D., Suite 11, Blair Building, Atchison, k’an~as George Murgatroyd, Jr., M.D., 1114 St. Paul Street, Baltimore 2, Md. William A. Nelson, M.D., The Johns Hopkins Hospital, Baltimore, Mtl. Francis A. Pflum, M.D., 116 East 53rd Street, New York 22, N. Y. J. W. Piekarski, M.D., 27 East South Street, Wilkes-Barre, Pa. Bennette B. Pool, M.D., 410-414 Nissen Bldg., Winston-Salem, N. C. Edwin P. Preston, M.D., DuPont Building, East Flagler St. at 2nd .4venue, Miami 32, Fla. James H. Putman, M.D., 902 Huntington Bldg., Miami 32, Fla. 5. W. Schoolnic, M.D., 130 West Fifth Street, East Liverpool, Ohio, Paul M. Seebohm, M.D., University of Iowa Medical School, Iowa City, Iowa Bernard B. Siegel, M.D., 1301 Cornaga Avenue, Far RocAkaway, N. T. Nathan E. Silbert, M.D., 214 Ocean Street, Lynn, Mass. Max A. Sklar, M.D., 566 53rd Street, Brooklyn 20, N. Y. Perry Sperber, M.D., 136 Elmwood Avenue, Providence i, R. 1. Charles E. Spratt, M.D., 158 Midwood Street, Brooklyn 25, N. Y. Sarah L. C. Stevens, M.D., Professional Building, Huntington, W. Va. Henry Suesserman, M.D., 389 Lyons Avenue, Newark 8, N. J. Sames Sutton, M.D., 607 North Grand Avenue, St. Louis 3, MO. R. T. Terry, M.D., Thayer Veterans Administration Hospital, Nashville 5, Term. Irving Weirrstock, M.D., 350 Ocran Avenue, Brooklyn 26, N. Y. Avenue, Milwaukee t’, \Viac. A. C. Wilson, M.D., 208 East Wisconsin
REPORT
OE’ COMMITTEE
ON THERAPY
Two antihistaminic drugs were submitted to the Committee for study and evaluatioll. The first was Chlor-Trimeton Maleate, +Q,ch was supplied through the Schering Corporation, Bloomfield, N. J., and the other product was Chloroyclizine Hydrochloride (‘Perazil’) furnished by the Burroughs Wellcome Bi Co., Tuckahoe, N. Y. This latter drug was also tleveloped, independently, by Abbott Laboratories, Chicago, Ill., trade name Di-Paralent: (Abbott). Both of these drugs were card was prepared and used by patients were given individual placebos). At the end of the information on the IBM cards. this survey all the IBM cards and cross relationship. From
with
this
data
the following
1. The effect of the each allergic condition.
drug
studied in a similar manner. A uniform type of special lRM each of the participating physicians. In addition to this card daily symptom cards to record the effects of the drug (01: trial period with the drug the investigator would fill out the One card was used for each patient. At the termination of were collected and sent to t,he TAM Service Bureau for sorting information on each
individual
could
be tnbulatrd: symptom
and
the
tlcgree
uf
relief
obt,ainefl
256
THE
JOURNAL
2. The effects.
effect
of
variable
individual
3. The symptoms.
effect
of
duration
of
symptoms
4. The symptoms.
effect
of
the
of
the
5. The
effect
of the drug
6. The
effect
of
side
ious
age
OF
and
patient
and
daily
dosages
of the
on the
results
obtained
on the
on the incidence
variable
ALLERGY
and
individual
results
severity
doses
drug
on the
with
obtained
the
with
symptoms drug
and
on various
the
drug
severity
of
on var-
of side effects.
on the
incidence
and
the
side
effects. 7. The
time
8. The
duration
9. The
effect
10.
The
of action
of the drug.
of action.
number
of variable
dosage
of days
the drug
on the duration
of action.
was used.
CHLOR-TRIMETON
The following meton Maleate: Bernstein, Hampton,
members Drs. Schiller, MacQuiddy,
of
the Committee participated Chait, Sherman, Schwartz, Keeney, and Arbesman.
TABLE
I.
CHLOR-TRIMETON
(990
CONDITION
Seasonal allergic Perennial allergic Bronchial asthma Urticaria Atopic dermatitis Contact dermatitis *Only those patients
MALEATE
MALEATE
NIJMBEROF' PATIENTS
rhinitis rhinitis
PERCENTOFPATIENTS IMPROVED*
715 151 118 63 15 15 50 per
of Chlor-TriFriedlaender,
Patients)
-
having
in the survey Winkenwerder,
cent
or more
relief
of all
61.3 52.5 24.6 70.0 73.0 73.0 were classified
symptoms
as
improved. TABLE
II.
TIME
LENGTHOFTIMETOBECOME EFFECTIVE
15 to 45 to 75 to
NUMBEROFCASES
30 minutes 60 minutes 150 minutes
&,d TABLE
LENGTH
OF TIME
OF ACTION
III.
DURATION
EFFECTIVE
1
increase
in single
dosage
NUMBEROFCASES
Similar illustrated moderate
side
/
PERCENTIMPROVED
276 42 53 63 tends
to SIDE
Trimeton
75.0 21.5 3.5
OF ACTION
31 to 62 hours 7 to 8 hours 9 or more hours An
PERCENTIMPROVED
324 92 14
prolong
the
action
6:‘: 12:o 14.6 of
Chlor-Trimeton
Maleate.
EFFECTS
effects as those produced by other antihistaminics were noted from ChlorThe, chief symptom was drowsiness. The incidence of side effects is in Table IV. Of 890 treated with Chlor-Trimeton Maleate, 67 or 7.5 per cent, had to severe side reactions. Maleate.
AMERICAN TABLE
-____-
ACADEMY
IV.
INCIDENCE
OF
255
.4LLERGT
OF SIDE
EFFECTS
_....
Total number of patients Total number of side effects Total number of moderate to severe side effects Number of patients with moderate to severe side
890 240
(27
-
%)
effects
COIVCLUSIONS 1. Chlor-Trimeton Maleate is a very effective antihistaminic drug. of this type it is most effective in the relief of sneezing and rhinorrhea in the pruritus of urticaria. 2. The most effective dosage is 2 to 4 mg. given 3 to 4 times daily. dosage does not increase its efficacy, but may prolong its action. The patients had relief from 3 to 6 hours. 3. Children with bronchial asthma responded better to Chlor-Trimeton adults. However, even the younger age groups were not greatly benefited 4. The incidence of side effects of this drug was found to be less able antihistaminics. ‘ PERAZIL The following Chait, Sherman, Arbesman.
members Friedlarnder,
of
I.
(588
-
*Only improved.
those
patients
rhinitis rhinitis
50 per TABLE
cent II.
Maleate than did from this drug. than most othrr avnil-
in the survey of ‘ Peraxil’: Keenrv, Rem&in, Huher,
Drs.
anti
‘PERAZII,'
I
having
increase in this percentage of
PatirntP)
CONDITION
Seasonal allergic Perennial allergic Rronchial asthma Urticaria Atopic dermatitis Contact dermatitis
An greatest
’
t,he Committe participated Hampton, Winkenwertlrr,
TABLE
Like other substances in allergic rhinitis and
more TIME
! PER CENTOF 1 PATIENTSIMPROVED"
NlJMBER OF PATIENTS -___
329 130 111 28 17 2 relief
of
all
symptoms
55.5 38.4 12.8 68.0 47.0 No relief were classified
as
OF ACTION _--..---..
-
LENGTH OF TIME BECOMEEFFECTIVE
TO NUMBER
15 to 30 minutes 45 to 60 minutes 75 to 90 minutes TABLE 19NGTH
OF TIME
3 to 6 9 to 12 15 18 to 27
OF CASES
PER CENT IMPROVED
176
EFFECTIVE
III.
DURATION
79.0
OF ACTION -___
/
hours hours hours hours
NUMBEROFCASES
70 120 14 29
1
____ ---PER CENTlMPROVED
30.0 51.5 6.0 12.4
SIDEEFFECTS
The type of side effects produced by ‘Perazil’ are similar to those from other antihistaminics. Drowsiness was the most prevalent of all side effects. However, none of these ill effects were of severe magnitude, as removal of the drug would clear the side effect. The incidence of side effects is illustrated in Table IV. Of 588 patients who received ‘Yrrazil’ only 74, or 12.6 per rent, had moderate to severe side effects.
258
THE TABLE
JOURNAL
IV.
Ol? ALLERGY
INCIDENCE
OF SIDE EFFECTS
Total number of patients Total number of side effects Total number of moderate to severe side effects Number of uatients with moderate to severe side
588
124 (21 effects
85 74
%)
(14.4%) (12.6%)
CONCLUSIONS ‘Perazil,’ like other antihistaminies, is most effective in the symptomatic relief of sneezing and rhinorrhea of seasonal allergic rhinitis, and in the relief of pruritus and whealing in It is of little or no value in bronchial asthma, but may be of slight benefit in urticaria. atopic eczema. The most effective dosage was found to be 50 mg. 2 to 3 times daily for all conditions studied. The original claims that one 50 mg. tablet could control symptoms for 24 hours The Burroughs Wellcome & Co. now recommends 2 to 3 50 mg. tablets could not be verified. daily. This dosage is substantiated by the results obtained here, that 51 per cent of the patients had relief for from 9 to 12 hours. The side reactions from ‘Perazil’ are not fatal and of the same type as other antihistaminics. However, the incidence of moderate to severe side effects was perhaps slightly less than most antihistaminics. Although this drug is not the most potent of antihistaminics available it also is not the least potent. It is known that many patients will get relief from one antihistaminic and not there is a definite place for it on the market. another. This is true with ‘Perazil. ’ Hence, with another antiSeveral investigators have found that a combination ot ’ ‘Perazil’ histaminic often gave excellent results. DUST-SEAL
supplied laender,
Through the courtesy to the Committee Keeney, Sherman,
of the L. S. Green Associates, _ Those reporting for evaluation. and Arbesman.
New York, N. Y., Dust-Seal was on this study were: Drs. Fried-
CONCLUSIONS It is the consensus of the Committee that Dust-Seal is another useful adjunct in partial control of the house dust allergen. However, more reassurance as to this product’s harmlessness to fabrics must be supplied. Applying Dust-Seal alone is not sufficient. Treatment with dust extract should be given. Another objection to this product is the laborious nature of applying it. Respectfully submitted, CARL E. ARBESMAN, M.D., Chairman L ,&ittee on Therapy
SYNOPSES STUDIES IN
OF PAPERS
ON THE RELEASE OF HISTAMINE DURING HEMOLYTIC BLOOD AND THE EFFECTS OF CORTISONE AND ANTIHISTAMINE AGENTS IN THESE REACTIONS HADWN
M. CARRYER,
M.D.,
AND CHARLES
REACTIONS
F. CODE, M.D.
Studies have been made concerning the release of histamine from its fixed to its physiIn vitro studies employing the blood of rabbits sensiologically active position in the blood. tized to sheep erythrocytes were made. An in vitro hemolytic reaction was found to effect a substantial release of histamine The plasma histamine concentration infrom ‘its fixed to its free position in rabbit blood. creased from two t,o fifteen times in the course of this reaction.
ACADEMY
OF
“xi
ALLERG\+
Maurice M. Hillman, M.D., 31 Howe Street, New Haven, (lonn. James Holman, M.D., 1406 Medical Arts Building, Dallas, Tex. Gertrude R. Holmes, M.D., 213 East North Street, Greenville, S. C. Daniel M. Rraus, M.D., 326 Republic Building, Denver, Colo. Robert G. Lovell, M.D., University of Michigan Hospital, Ann Arbor, Mich. Kenneth P. Mathews, M.D., University of Michigan Hospital, Allergy Clinic, Ann i\rbor, Mich. Alexander McCausland, M.D., 818 S. Jefferson Street, Roanoke, Va. Ernest0 Mendes, M.D., Rua Angatuba, 308, Sao Paulo, Brazil, S. A. Robert E. Miller, M.D., 5408 Forest Blvd., East St. Louis, Ill. Meyer Monchek, M.D., 63-75 Dry Harbor Road, West Forest, L. I., N. Y. Ira R. Morrison, M.D., Suite 11, Blair Building, Atchison, k’an~as George Murgatroyd, Jr., M.D., 1114 St. Paul Street, Baltimore 2, Md. William A. Nelson, M.D., The Johns Hopkins Hospital, Baltimore, Mtl. Francis A. Pflum, M.D., 116 East 53rd Street, New York 22, N. Y. J. W. Piekarski, M.D., 27 East South Street, Wilkes-Barre, Pa. Bennette B. Pool, M.D., 410-414 Nissen Bldg., Winston-Salem, N. C. Edwin P. Preston, M.D., DuPont Building, East Flagler St. at 2nd .4venue, Miami 32, Fla. James H. Putman, M.D., 902 Huntington Bldg., Miami 32, Fla. 5. W. Schoolnic, M.D., 130 West Fifth Street, East Liverpool, Ohio, Paul M. Seebohm, M.D., University of Iowa Medical School, Iowa City, Iowa Bernard B. Siegel, M.D., 1301 Cornaga Avenue, Far RocAkaway, N. T. Nathan E. Silbert, M.D., 214 Ocean Street, Lynn, Mass. Max A. Sklar, M.D., 566 53rd Street, Brooklyn 20, N. Y. Perry Sperber, M.D., 136 Elmwood Avenue, Providence i, R. 1. Charles E. Spratt, M.D., 158 Midwood Street, Brooklyn 25, N. Y. Sarah L. C. Stevens, M.D., Professional Building, Huntington, W. Va. Henry Suesserman, M.D., 389 Lyons Avenue, Newark 8, N. J. Sames Sutton, M.D., 607 North Grand Avenue, St. Louis 3, MO. R. T. Terry, M.D., Thayer Veterans Administration Hospital, Nashville 5, Term. Irving Weirrstock, M.D., 350 Ocran Avenue, Brooklyn 26, N. Y. Avenue, Milwaukee t’, \Viac. A. C. Wilson, M.D., 208 East Wisconsin
REPORT
OE’ COMMITTEE
ON THERAPY
Two antihistaminic drugs were submitted to the Committee for study and evaluatioll. The first was Chlor-Trimeton Maleate, +Q,ch was supplied through the Schering Corporation, Bloomfield, N. J., and the other product was Chloroyclizine Hydrochloride (‘Perazil’) furnished by the Burroughs Wellcome Bi Co., Tuckahoe, N. Y. This latter drug was also tleveloped, independently, by Abbott Laboratories, Chicago, Ill., trade name Di-Paralent: (Abbott). Both of these drugs were card was prepared and used by patients were given individual placebos). At the end of the information on the IBM cards. this survey all the IBM cards and cross relationship. From
with
this
data
the following
1. The effect of the each allergic condition.
drug
studied in a similar manner. A uniform type of special lRM each of the participating physicians. In addition to this card daily symptom cards to record the effects of the drug (01: trial period with the drug the investigator would fill out the One card was used for each patient. At the termination of were collected and sent to t,he TAM Service Bureau for sorting information on each
individual
could
be tnbulatrd: symptom
and
the
tlcgree
uf
relief
obt,ainefl
256
THE
JOURNAL
2. The effects.
effect
of
variable
individual
3. The symptoms.
effect
of
duration
of
symptoms
4. The symptoms.
effect
of
the
of
the
5. The
effect
of the drug
6. The
effect
of
side
ious
age
OF
and
patient
and
daily
dosages
of the
on the
results
obtained
on the
on the incidence
variable
ALLERGY
and
individual
results
severity
doses
drug
on the
with
obtained
the
with
symptoms drug
and
on various
the
drug
severity
of
on var-
of side effects.
on the
incidence
and
the
side
effects. 7. The
time
8. The
duration
9. The
effect
10.
The
of action
of the drug.
of action.
number
of variable
dosage
of days
the drug
on the duration
of action.
was used.
CHLOR-TRIMETON
The following meton Maleate: Bernstein, Hampton,
members Drs. Schiller, MacQuiddy,
of
the Committee participated Chait, Sherman, Schwartz, Keeney, and Arbesman.
TABLE
I.
CHLOR-TRIMETON
(990
CONDITION
Seasonal allergic Perennial allergic Bronchial asthma Urticaria Atopic dermatitis Contact dermatitis *Only those patients
MALEATE
MALEATE
NIJMBEROF' PATIENTS
rhinitis rhinitis
PERCENTOFPATIENTS IMPROVED*
715 151 118 63 15 15 50 per
of Chlor-TriFriedlaender,
Patients)
-
having
in the survey Winkenwerder,
cent
or more
relief
of all
61.3 52.5 24.6 70.0 73.0 73.0 were classified
symptoms
as
improved. TABLE
II.
TIME
LENGTHOFTIMETOBECOME EFFECTIVE
15 to 45 to 75 to
NUMBEROFCASES
30 minutes 60 minutes 150 minutes
&,d TABLE
LENGTH
OF TIME
OF ACTION
III.
DURATION
EFFECTIVE
1
increase
in single
dosage
NUMBEROFCASES
Similar illustrated moderate
side
/
PERCENTIMPROVED
276 42 53 63 tends
to SIDE
Trimeton
75.0 21.5 3.5
OF ACTION
31 to 62 hours 7 to 8 hours 9 or more hours An
PERCENTIMPROVED
324 92 14
prolong
the
action
6:‘: 12:o 14.6 of
Chlor-Trimeton
Maleate.
EFFECTS
effects as those produced by other antihistaminics were noted from ChlorThe, chief symptom was drowsiness. The incidence of side effects is in Table IV. Of 890 treated with Chlor-Trimeton Maleate, 67 or 7.5 per cent, had to severe side reactions. Maleate.
AMERICAN TABLE
-____-
ACADEMY
IV.
INCIDENCE
OF
255
.4LLERGT
OF SIDE
EFFECTS
_....
Total number of patients Total number of side effects Total number of moderate to severe side effects Number of patients with moderate to severe side
890 240
(27
-
%)
effects
COIVCLUSIONS 1. Chlor-Trimeton Maleate is a very effective antihistaminic drug. of this type it is most effective in the relief of sneezing and rhinorrhea in the pruritus of urticaria. 2. The most effective dosage is 2 to 4 mg. given 3 to 4 times daily. dosage does not increase its efficacy, but may prolong its action. The patients had relief from 3 to 6 hours. 3. Children with bronchial asthma responded better to Chlor-Trimeton adults. However, even the younger age groups were not greatly benefited 4. The incidence of side effects of this drug was found to be less able antihistaminics. ‘ PERAZIL The following Chait, Sherman, Arbesman.
members Friedlarnder,
of
I.
(588
-
*Only improved.
those
patients
rhinitis rhinitis
50 per TABLE
cent II.
Maleate than did from this drug. than most othrr avnil-
in the survey of ‘ Peraxil’: Keenrv, Rem&in, Huher,
Drs.
anti
‘PERAZII,'
I
having
increase in this percentage of
PatirntP)
CONDITION
Seasonal allergic Perennial allergic Rronchial asthma Urticaria Atopic dermatitis Contact dermatitis
An greatest
’
t,he Committe participated Hampton, Winkenwertlrr,
TABLE
Like other substances in allergic rhinitis and
more TIME
! PER CENTOF 1 PATIENTSIMPROVED"
NlJMBER OF PATIENTS -___
329 130 111 28 17 2 relief
of
all
symptoms
55.5 38.4 12.8 68.0 47.0 No relief were classified
as
OF ACTION _--..---..
-
LENGTH OF TIME BECOMEEFFECTIVE
TO NUMBER
15 to 30 minutes 45 to 60 minutes 75 to 90 minutes TABLE 19NGTH
OF TIME
3 to 6 9 to 12 15 18 to 27
OF CASES
PER CENT IMPROVED
176
EFFECTIVE
III.
DURATION
79.0
OF ACTION -___
/
hours hours hours hours
NUMBEROFCASES
70 120 14 29
1
____ ---PER CENTlMPROVED
30.0 51.5 6.0 12.4
SIDEEFFECTS
The type of side effects produced by ‘Perazil’ are similar to those from other antihistaminics. Drowsiness was the most prevalent of all side effects. However, none of these ill effects were of severe magnitude, as removal of the drug would clear the side effect. The incidence of side effects is illustrated in Table IV. Of 588 patients who received ‘Yrrazil’ only 74, or 12.6 per rent, had moderate to severe side effects.
258
THE TABLE
JOURNAL
IV.
Ol? ALLERGY
INCIDENCE
OF SIDE EFFECTS
Total number of patients Total number of side effects Total number of moderate to severe side effects Number of uatients with moderate to severe side
588
124 (21 effects
85 74
%)
(14.4%) (12.6%)
CONCLUSIONS ‘Perazil,’ like other antihistaminies, is most effective in the symptomatic relief of sneezing and rhinorrhea of seasonal allergic rhinitis, and in the relief of pruritus and whealing in It is of little or no value in bronchial asthma, but may be of slight benefit in urticaria. atopic eczema. The most effective dosage was found to be 50 mg. 2 to 3 times daily for all conditions studied. The original claims that one 50 mg. tablet could control symptoms for 24 hours The Burroughs Wellcome & Co. now recommends 2 to 3 50 mg. tablets could not be verified. daily. This dosage is substantiated by the results obtained here, that 51 per cent of the patients had relief for from 9 to 12 hours. The side reactions from ‘Perazil’ are not fatal and of the same type as other antihistaminics. However, the incidence of moderate to severe side effects was perhaps slightly less than most antihistaminics. Although this drug is not the most potent of antihistaminics available it also is not the least potent. It is known that many patients will get relief from one antihistaminic and not there is a definite place for it on the market. another. This is true with ‘Perazil. ’ Hence, with another antiSeveral investigators have found that a combination ot ’ ‘Perazil’ histaminic often gave excellent results. DUST-SEAL
supplied laender,
Through the courtesy to the Committee Keeney, Sherman,
of the L. S. Green Associates, _ Those reporting for evaluation. and Arbesman.
New York, N. Y., Dust-Seal was on this study were: Drs. Fried-
CONCLUSIONS It is the consensus of the Committee that Dust-Seal is another useful adjunct in partial control of the house dust allergen. However, more reassurance as to this product’s harmlessness to fabrics must be supplied. Applying Dust-Seal alone is not sufficient. Treatment with dust extract should be given. Another objection to this product is the laborious nature of applying it. Respectfully submitted, CARL E. ARBESMAN, M.D., Chairman L ,&ittee on Therapy
SYNOPSES STUDIES IN
OF PAPERS
ON THE RELEASE OF HISTAMINE DURING HEMOLYTIC BLOOD AND THE EFFECTS OF CORTISONE AND ANTIHISTAMINE AGENTS IN THESE REACTIONS HADWN
M. CARRYER,
M.D.,
AND CHARLES
REACTIONS
F. CODE, M.D.
Studies have been made concerning the release of histamine from its fixed to its physiIn vitro studies employing the blood of rabbits sensiologically active position in the blood. tized to sheep erythrocytes were made. An in vitro hemolytic reaction was found to effect a substantial release of histamine The plasma histamine concentration infrom ‘its fixed to its free position in rabbit blood. creased from two t,o fifteen times in the course of this reaction.