Antihistamines firstgeneration H1 antagonists and H2 antagonists

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Four studies compared the use of H1 and H2 antagonists or a combination. None of these studies had a placebo arm. Two studies compared diphenhydramine with an H2 antagonist (famotidine or cimetidine).

Moscati et al. investigated the efficacy of a single-dose intramuscular cimetidine 300 mg with

Table 21.1

Summary of data from randomised controlled trials of the treatment of acute urticaria



Outcome measures

No. of patients



Moscatl et ai.'J

Single-dose clmetidlne 300 mg IM

Itching, wheal intensity, sedation, wheal


No difference for clinical response

OR diphenhydramine 50 mg IM

extent, overall Improvement on a 3-A point

No dropouts

Diphenhydramine significantly more sedating

numerical scale; validity and reliability not


Watson et al.6

Single-dose H2-receptor antagonist

Pruritus (patient, VAS)


Only withln-group comparison (before/after

famotidine 20 mg I.m. v H1-receptor

Intensity of urticaria (physician, VAS)

No dropouts


antagonist diphenhydramine 50 mg

Surface area (physician, rule of nine)

IM in the treatment of acute urticaria

Sedation (patient, VAS)

Diphenhydramine 50 mg + ranitidine

Lin et al.7

50 mg v diphenhydramine

Presence of urticaria at baseline and after


Presence of urticaria after 2 hours: 16.2% v8-3%

50 mg + placebo

1 and 2 hours

(+ ranitidine) P= 0.02

Single-dose diphenhydramine

Extent (number of Involved areas)

Runge et al.3

50 mg + placebo IV OR

VAS (110 mm) to assess:


More urticaria patients receiving diphenhydramine +

clmetidlne 300 mg + placebo IV OR

Pruritus - throat tightness, and facial

clmetidlne (11/12) experienced relief compared

diphenhydramine 50 mg +

swelling (patient)

with those receiving diphenhydramine (5/11,

cimetldine 300 mg IV

Urticaria - pharyngeal tissue swelling, and

P= 0.027) or clmetidlne (8/10, ns) alone

facial swelling (physician)

Change of 25 mm considered clincally significant

Adverse effects

Table 21.1 (Continued)



Outcome measures

No. of patients enrolled


Simons et al.14

Oral cetirlzine 025 mg/kg twice dally v placebo over 18 months in children with atopic eczema

Incidence of diary-reported symptoms typical for acute urticaria


Cumulative Incidence of urticaria 16-2% 1/5-8% during 18-month treatment (P<0.001)

4-6% 1/3-0% during 6-month follow up (ns)

Pollack and Romano10

Single-dose diphenhydramine 50 mg IM. followed by oral hydroxyzine 25 mg every 4-8 hours plus oral prednisone 20 mg twice dally for 4 days or placebo

Pruritus (VAS 10 cm) Adverse effects


Significantly more Improvement with the addition of steroid

Zuberbier et al.2

Loratadine 10 mg/day until remission v prednisolone 50 mg/day for 3 days followed by loratadine 10 mg/day until remission

Cessation of whealing


Percentage cessation at 5 time points Significant differences only after 3 days (when the intervention arm had received prednisolone only so far) (93-8% 1/65-9%)

ns, not significant; IV, intravenous; IM, Intramuscular ns, not significant; IV, intravenous; IM, Intramuscular intramuscular diphenhydramine 50 mg intramuscular in 93 young adults.5 Both treatments yielded significant reductions in itching, wheal intensity and extent after 30 minutes, with no differences between treatments. A significant increase in sedation was reported by patients in both groups, but was significantly higher in patients treated with diphenhydramine. Absolute changes in the three-and four-point scoring scales appeared to be clinically important. The study is limited by flaws in the process of randomisation and blinding.

Watson et al. compared single-dose intramuscular diphen-hydramine 50 mg with intramuscular famotidine 20 mg in 25 adults.6 After 30 minutes pruritus was reduced significantly by both treatments, with diphenhydramine appearing more effective. Famotidine also significantly reduced the affected body surface area. Physician-rated intensity of urticaria was reduced equally and significantly by both drugs. A non-significant increase in sedation was reported by patients receiving diphenhydramine. The small sample size and unbalanced group size (diphenhydramine n = 10, famotidine n = 15; no block randomisation) does not allow for a meaningful comparison of the groups.

Lin et al. compared the efficacy of single-dose intravenous diphenhydramine 50 mg alone or in combination with intravenous ranitidine 50 mg in 91 adults.7 Significantly more patients receiving the combination therapy (91-7%) were free of symptoms after 2 hours compared with those who received diphenhydramine alone (73-8%). After control for baseline extent, the combination therapy was able to reduce the number of involved areas significantly within 2 hours. Significantly more additional antihistamines were administered in the diphenhydramine group, however, which may have shifted the effect towards the zero-effect level.

Runge et al. studied 39 adults with acute allergic reactions, including urticaria.8 Fourteen patients received a single dose of intravenous diphenhydramine 50 mg, 12 received intravenous cimetidine 300 mg) and 13 received both preparations. After 30 minutes the combination therapy led to significantly higher reduction of urticaria (evaluated using a VAS) compared with diphenhydramine alone. The latter, however, achieved the best results in reduction of pruritus, differences being significant compared with cimetidine. The study is limited by the small sample size and significant differences in mean treatment scores for urticaria between study groups, which were not adjusted for in later analyses.

Pontasch et al. compared three oral medication in the treatment of acute urticaria in adults.9 Seven patients received diphenhydramine, six received famotidine, and another seven received cromolyn sodium. Patient satisfaction was highest with diphenhydramine (6/7), followed by famotidine (3/6) and cromolyn sodium (3/7). Adverse effects were reported in 3/7 treated with diphenhydramine, in 3/6 of the famotidine group and in one patient who received cromolyn sodium.

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If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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