Antihistamines

1.

1
2
3
4
5
6

3.4 Antihistamines
antihistamines (common cold)
Brompheniramine
tab, syr

Chlorpheniramine
cap, tab, syr,

Diphenhydramine
cap, sterile sol
Hydroxyzine
tab, syr

Cetirizine
tab, syr

Loratad7ine
tab, syr

2.

atopic dermatitis,
pruritus chronic
idiopathic urticaria

allergic rhinitis

topical) asthma (

search strategies

allergic

condition
conjunctivitis (

3.

1
WHO ATC group

R06 Antihistamines for

Systemic Use

Hydroxyzine ATC
code N05BB01
Anxiolytics
(N05B ATC group)

hydroxyzine

Chlorpheniramine[TI] AND
Hypersensitivity[MeSH] AND (Randomized
Controlled Trial[ptyp] OR Meta-Analysis[ptyp]
OR Review, Academic[ptyp]) NOT Asthma
[MeSH] NOT Conjunctivitis[MeSH]

antihistamines

1
ATC group

..2547
substituted alkylamines

brompheniramine
chlorpheniramine

syrup sterile

solution

tablet

capsule

1 ( ATC
Group)
Preparatio

ATC

Generic Name

Code

Hydroxyzine
Carbinoxamine
Diphenhydramin
Cyproheptadine
Desloratadine
Fexofenadine
Ketotifen
Loratadine ()
Mebhydrolin
Cetirizine ()
Oxatomide
Bromphenirami
Chlorphenirami
Dexchlorphenira

tab 10, 25
tab 4 mg
cap/tab 25
tab/cap 4
tab 5 mg
tab 30, 60
tab 1 mg
tab 10 mg
tab 50 mg
tab 10 mg
tab 30 mg
tab/cap 4
tab/cap 4
tab 2 mg

N05BB0
R06AA0
R06AA0
R06AX0
R06AX2
R06AX2
R06AX1
R06AX1
R06AX1
R06AE0
R06AE0
R06AB0
R06AB0
R06AB0

4. ISafE

ATC Group
Diphenylmethane
Aminoalkyl ethers
Aminoalkyl ethers
Other antihistamines for
Other antihistamines for
Other antihistamines for
Other antihistamines for
Other antihistamines for
Other antihistamines for
Piperazine derivatives
Piperazine derivatives
Substituted alkylamines
Substituted alkylamines
Substituted alkylamines

46

ISafE

42

US

FDA

ISafE
0.64
brompheniramine
0.49

fexofenadine,

desloratadine
cyproheptadine
Fexofenadine
administration restriction
0.95

Cmax AUC

Micromedex Healthcare Series Vol. 123,

2004

 2 ISafE FDA ( ISafE )

50 percentile = 0.64
Generic

IE

Fr
eq

Name

Loratadine

0.

1.

1.

0.

98 00 00

98

1.

0.

0.

00 00 95

95

0.

0.

0.

95 00 95

90

0.

1.

0.

Desloratadine 88 95 00

84

Hydroxyzine
()

0.

0.

93 00 85

79

Diphenhydra
mine ()

0.

0.

0.

85 00 90

77

Chlorphenira
mine ()

0.

0.

0.

83 00 85

71

Cyproheptadi

0.

0.

0.

ne

83 00 85

71

Dexchlorphen

0.

0.

0.

iramine

73 90 95

62

Ketotifen

0.

0.

()
Cetirizine ()
Fexofenadine

0.

1.
1.
0.
1.
1.
1.
1.
0.
0.

0.

Adult

Ped.

FDA

FDA*

FDA*

0.98

yes

yes

0.95

yes

yes

0.81

yes

yes

0.84

yes

yes

0.71

yes

yes

0.69

yes

yes

0.64

yes

yes

0.64

yes

yes

af

1. 1.

1.

00 00

00

1. 1.

1.

00 00

00

0. 0.

0.

95 95

90

1. 1.

1.

00 00

00

1. 0.

0.

00 90

90

1. 0.

0.

00 90

90

1. 0.

0.

00 90

90

1. 0.

0.

00 90

90

1. 0.

0.

00 90

90

0.56

yes

yes

1. 0.

0.

0.55**

no

no

1
1
2
1
3
3
3
3

ISafE

80 85 90

61

00 95

95

0.

0.

0.

1. 0.

0.

70 90 85

54

00 90

90

0.

0.

0.

1. 0.

0.

78 90 80

56

00 90

90

0.

0.

0.

1. 0.

0.

Mebhydrolin

65 80 80

42

00 90

90

Carbinoxamin

0.

0.

0.

1. 0.

0.

60 80 85

41

00 90

90

Bromphenira
mine ()
Oxatomide

0.
0.
0.
0.

3
3
3
3

0.49

yes

yes

0.48**

no

no

0.36**

n/a

n/a

0.35**

n/a

n/a

FDA approval status (

Micromedex)

ISafE US FDA ketotifen,

**

oxatomide, mebhydrolin carbinoxamine 0.58, 0.50, 0.38 0.37

50 percentile 0.64

5.

diphen-hydramine,
mebhydrolin, oxatomide

carbinoxamine

WHO/DDD
200, 200, 60 16
.

preparation ( 1),
frequency ( 2)

. .

..2547

brompheniramine
diphenhydra-mine

cyproheptadine,
ketotifen fexofenadine

0.18

4.10
tolerance 7.30
(
)

 tolerance

loratadine cetirizine

median cost

2.29

3 (
Patient Day)
D
Generic

Name

Chlorphenira
mine ()

12

Hydroxyzine
()
Cetirizine ()

30

0.2

0.

1 06

10

5,422, 875,878
420

Baht

Baht/

Day

PD

53,691, 293,767

,900

442

,107

9,947, 150,562

30,628,

53,503,

328

183

42,396, 132,162

49,291,

550

,000

62 39

670

120

,622

790

0.

22,479

98,955,

37,505,

40,478,

0 22

,500

188

791

229

27,588, 146,958

35,886,

1.

8,297,

56 85

580

606

,946

186

1.

186,50

11,814,

13,246,

6,000,3

8 00

240

560

70

7.6
Ketotifen

t O

Patient

6,895,

11.
10

Amoun Amount

1.

0.7
12

0.

6 14
10.

Loratadine
()

CO

0.9

Cyproheptadi
ne

0.18 *
0.57 *
2.68 *
0.93 *
4.10 *
2.21

12
Fexofenadine

Bromphenira
mine ()

24

6,462,

6 00

900

784

0.

968,00

18,351,

2,908,7

3,219,8

3 12

300

96

83

0.

1,457,

3,944,2

4,126,4

1,800,4

2 30

000

50

15

17

4,787,7

5,122,8

1,595,9

00

39

00

2.0
75
15

Mebhydrolin

0.

0.7

Diphenhydra
mine ()

6.9

0.0

0 07
4.3

Oxatomide

90

Dexchlorphen
iramine

2,301,

8 00

500

0.

487,00

1,779,0

7 17

36.
Desloratadine

Carbinoxamin
e

12

0.

0.1
6

1.

44,981,

0.

637,97

70 00

0.1

0.

11

3,231,4
50 13.92 *
0.90
2.29 *
3.21

10,080,
570 767,167 13.14

00 385,220 755,333

0.51

23,413,
0

499 637,970 36.70 *

402,00
0 262,000

73,040 221,333

0.33

(1) * ISafE
(2) 1.04
(3) median cost 2.29 (4)
7.30 (5) 3.54 (6)
7.30 tolerance (7) hydroxyzine fexofenadine
10 mg 60 mg

6. EMCI

6.1 .
.
6
chlorpheniramine,
hydroxyzine,
cyproheptadine, cetirizine, diphenhydramine
loratadine

..2542

1

cyproheptadine

.
.

sedative nonsedative antihistamines

6.2

ISafE

6.3

EMCI

( ?? )

fexofenadine

desloratadine

ketotifen,

dexchlorpheniramine,

..2542 fexofenadine

bromphenira-mine,

oxatomide, mebhydrolin

desloratadine

carbinoxamine

ketotifen

brom-pheniramine

..2547

4 ..2547
(47) EMCI
PP (Propose) ..2542 (42)
Generic

IE

Name

af

IS

Patient

afE CO

Day

Baht/ EM
PD

CI

4 P 4
7 P

Chlorphenira

0.

0. 0.6

mine ()

71 90

Hydroxyzine

0.

0. 0.7

()

79 90

Cyproheptadi

0.

ne

71 90
0.

Diphenhydra

0.

77 90

Loratadine

0.

0. 0.8

90 90

1. 0.8

Desloratadine

84 00

Dexchlorphen

0.

iramine

62 90
0.

1. 0.9

98 00

0.

0. 0.6

mine ()

Fexofenadine

1. 0.9

95 00

0.

0. 0.6

Cetirizine ()

()

0. 0.5
6

0. 0.5

Ketotifen

61 95

Bromphenira

0.

0. 0.4

mine ()

54 90

Oxatomide

0.

0. 0.4

0.2

0. 293,767

1 06
0.9

,107

0.

53,503,

6 14

183

0.7

0.

40,478,

0 22

229

10.

0.18 1.0 *
0.57 1.0 *
0.93 1.5 * X *

1.

49,291,

62 39

790

2.68 2.8 *

0.

1,800,4

2 30

17

2.0
11.

1.

35,886,

56 85

186

6.9

0.

3,231,4

6 00

50

36.

0.

1.

6,000,3

8 00

70

0.7

X ?

?
*

X ?

0.

7 17 755,333
7.6

4.10 4.2 *
13.9 17.
?
36.7 43.

70 00 637,970
0.1

2.29 3.3 *

0.51 1.0

X X X

2.21 4.0

X X

0.

3,219,8

3 12

83

0.90 1.8

X X

0. 767,167

13.1 27.

X X

4.3

56 90
0.

0. 0.3

Mebhydrolin

42 90

Carbinoxamin

0.

41 90

8 00
0.0

0. 0.3

1.

1,595,9

0 07

00

3.21 8.9

X X X

11 221,333

0.33 1.0

X X X

0.1

0.

Cyproheptadine ..2542 7.4.2 Prophylactic

drugs for migraine

Diphenhydramine ..2542 1 Antidotes 7.6

Anti-parkinson drugs 7.10 Antidystonia

dystonia 20.4 Antitussives syrup

Ketotifen ..2542 20.3.2 Non-steroidal

respiratory anti-inflammatory drugs

7.

cyproheptadine

7.1

cyproheptadine

antihistamines

serotonin

receptor

allergy

allergic rhinitis

vascular

headache

urticaria

Clinical Pharmacology 2004 CD ROM


..2547
4.7.3.2 Drugs

7.2 fexofenadine

fexofenadine active

used in the prophylaxis

metabolite

of migraine

terfenadine

ISafE

.
..2542

DUE
.

prolong QT interval

fexofenadine

28

cetirizine

(symptom free)

51.9% 4.4%

fexofenadine

(partial

improvement) 36.5%

42.2%

(no

improvement) 11.5%

53.3%

seasonal allergic
5

rhinitis cetirizine

chronic idiopathic

fexofenadine 33

urticaria cetirizine

Day JH, Briscoe MP, Rafeiro E, Hewlett

D Jr, Chapman D, Kramer B.Randomized

4

Handa

S,

Dogra

S,

Kumar

double-blind comparison of cetirizine and

fexofenadine after pollen challenge in the

B.,Comparative efficacy of cetirizine and

Environmental Exposure Unit: duration of

idiopathic urticaria. J Dermatolog Treat.

rhinitis.Allergy Asthma Proc. 2004 Jan-

fexofenadine in the treatment of chronic

2004 Jan;15(1):55-7.

effect in subjects with seasonal allergic

Feb;25(1):59-68.

fexofenadine

fexofenadine

12,107,166

seasonal allergic rhinitis

fexofenadine
adverse effect
loratadine

fexofenadine ( 3)

cetirizine
BMJ Clinical Evidence. Seasonal allergic

rhinitis.

Search

date

September

2003.

Aziz Sheikh, Sukhmeet Singh Panesar,

and Sangeeta Dhami.
7

Aziz Sheikh, et al. Seasonal allergic

rhinitis. Clin Evid 2003; 10:621-633

..2547

7.3

1 3

desloratadine
desloratadine active
metabolite
loratadine relative
potency 10-20
loratadine

ISafE

urticaria

SMP

US FDA

2546

approval

probably effective

good

..2547

allergic rhinitis
10

cetirizine

7.4 ketotifen

ketotifen

antihistamines

ISafE

allergy

asthma

allergic
rhinitis

..2547
9

Micromedex Drugdex Drugevaluation

2004
10

Lai DS, Lue KH, Hsieh JC, Lin KL,

Lee HS. The comparison of the efficacy

8

Safety Monitoring Period

and

safety

of

cetirizine,

oxatomide,

ketotifen, and a placebo for the treatment

of childhood perennial allergic rhinitis.Ann
Allergy

Asthma

Dec;89(6):589-98.

Immunol.

2002

 ketotifen

brompheniramine

prophylaxis therapy

maleate extended

asthma

release formulation

7.5
brompheniramine

..2542

brompheniramine

chlorpheniramine

chlorpheniramine
drowsiness

11

ISafE

11

Clinical Pharmacology 2004 CD ROM

ISafE

..2547

Micromedex

8. antihistamines

8.1 antihistamines

antihistamines

(common cold)
anticholinergic
effect sedative
effect

12

second
generation
antihistamines
cetirizine

severity
score 0 (no
symptoms) 3 4
(severe symptoms)
antihistamines

0.25

loratadine
anticholinergic activity
sedative effect

chlorpheniramine

11

(95% CI 0.10
to 0.40)

0.15
(95% CI 0
to 0.30)

12

Textbook of Therapeutics, Drugs and

Disease Management, 6th Edition, Eric

T.Herfindal, Dick R.Gourley Editor. 1996,
P.1253-54

0.30 (95% CI

0.15 to 0.45)

1-10

13

many

14

systematic reviews
(search
8228 adults and children
with naturally acquired

54 (RR 0.99, 95%

colds)

CI 0.93 to 1.05; at 35

days)

antihistamines

overall
symptoms

Sr,

Weintraub

M,

Russell HK, et al. The effectiveness of

antihistamines in reducing the severity of

runny

nose

analysis.

and

Clin

sneezing:

Pharmacol

meta-

Ther

1998;64:579596.
14

De

Sutter

AIM,

Lemiengre

M,

Campbell H, et al. Antihistamines for the

common cold. In: The Cochrane Library,
Issue 2, 2004.

55
892/1667

experimentally induced

RB

998/1825

colds, 702 with

D'Agostino

antihistamines

date 2003, 32 RCTs,

13

BMJ
Clinical Evidence
Common cold (new),
Search date May 2004
Bruce Arroll
decongestant

Actifed (triprolidine

+ pseudoephedrine)

Clarinase (loratadine +

pseudoephe-drine)

common

cold

Piriton

54

(chlorpheniramine)

Clarityne

(loratadine)

antihistamines

common cold

antihistamines

antihistamines

sedative non-

sedative

antihistamines

.
antihistamines

routine

non-sedating

50

antihistamines

sedating antihistamines

8.2 antihistamines
asthma
BNF (British National

Formulary) 48

September 2004

respiratory system

Antihistamines are

of no value in the

treatment of bronchial

asthma.

GINA (Global Initiatives

paradoxical excitability

for Asthma) guidelines

2004

antihistamines (

ketotifen)

15

asthma
15

chlorpheniramine cetirizine

controlled trials involving

review

larger samples are

needed.

antihistamines
cetirizine
asthma

8.3 antihistamines

16

asthma

atopic dermatitis

BNF

17

Further well16

Nelson

HS.

Prospects

Chlorpheniramine
maleate
Indications: symptomatic
relief of allergy such as
hay fever, urticaria;
emergency treatment of
anaphylactic reactions

J Allergy Clin Immunol. 2003 Oct;112(4

Suppl):S96-100.

Wilson AM. Are antihistamines useful in

managing asthma? Curr Opin Allergy Clin

18

Warner JO; ETAC Study Group. Early

Treatment of the Atopic Child. A doubleblinded,

randomized,

placebo-controlled

trial of cetirizine in preventing the onset

of

asthma

in

children

with

atopic

dermatitis: 18 months' treatment and 18

months' posttreatment follow-up.J Allergy
Clin Immunol. 2001 Dec;108(6):929-37.

for

Immunol. 2002 Feb;2(1):53-9.

19

antihistamines in the treatment of asthma.

17

18

Fumagalli F, Baiardini I, Pasquali M,

Compalati E, Guerra L, Massacane P,

Canonica GW.
work?

involving

Further
larger

Antihistamines: do they
well-controlled

samples

are

trials

needed.

Allergy. 2004 Aug;59 Suppl 78:74-7.

19

BNF (British National Formulary) 48

September 2004, with permission.

Dose: by mouth, 4 mg
every 46 hours, max.
24 mg daily; CHILD under 1
year not recommended, 1
2 years 1 mg twice daily;
25 years 1 mg every 46
hours, max. 6 mg daily; 6
12 years 2 mg every 46
hours, max. 12 mg daily
By subcutaneous or
intramuscular injection or
by intravenous injection
over 1 minute, 1020 mg;
max. 40 mg in 24 hours;
INFANT 1 month1 year
250 micrograms/kg; CHILD
112 years
200 micrograms/kg or 15
years 2.55 mg, 612
years 510 mg
Brompheniramine
maleate
Indications: symptomatic
relief of allergy such as
hay fever, urticaria
Dose: 4-8 mg 3-4 times
daily; CHILD up to 3 years
0.4-1 mg/kg daily in 4
divided doses, 3-6 years 2
mg 3-4 times daily, 6-12
years 2-4 mg 3-4 times
daily
Diphenhydramine
hydrochloride
Indications: to aid relief of
temporary sleep
disturbance in adults

Note Sedating
antihistamines, such as
diphenhydramine, are used
as the cough suppressant
component of many
compound cough
preparations on sale to the
public; all tend to cause
drowsiness which may
reflect their main mode of
action.
Diphenhydramine
16
Antidotes .
cap, sterile sol.
dystonia

Hydroxyzine
Indications: pruritus,
anxiety (short-term) Dose:
pruritus, initially 25 mg at
night increased if
necessary to 25 mg 3-4
times daily; CHILD 6
months-6 years initially 515 mg daily increased if
necessary to 50 mg daily
in divided doses; over 6
years initially 15-25 mg
daily increased if
necessary to 50-100 mg
daily in divided doses
Anxiety (adults only), 50100 mg 4 times daily
Cetirizine hydrochloride
Indications: symptomatic
relief of allergy such as
hay fever, urticaria

Dose: adult and child over

6 years, 10 mg daily or 5
mg twice daily; child 26
years, hayfever, 5 mg daily
or 2.5 mg twice daily

Loratadine
Indications: symptomatic
relief of allergy such as
hay fever, urticaria
Dose: ADULT and CHILD
over 6 years 10 mg daily;
CHILD 25 years 5 mg
daily

9.

antihistamines

25442545
antihistamines

/

Cetirizine

Loratadine/Fexofenadine