Reporting of adverse events

Susan Carson; Nancy Lee; Sujata Thakurta

This publication is provided for historical reference only and the information may be out of date.

Appendix EReporting of adverse events

Publication Details

Table

Adverse events from head-to-head and active control trials in adults (Original Report).

Table

Adverse events from studies in adults (includes only studies from update 2003–2005).

Table

Adverse events from studies in children (Original Report and Update 1).

Publication Details

Copyright

Publisher

Oregon Health & Science University, Portland (OR)

NLM Citation

Carson S, Lee N, Thakurta S. Drug Class Review: Newer Antihistamines: Final Report Update 2 [Internet]. Portland (OR): Oregon Health & Science University; 2010 May. Appendix E, Reporting of adverse events.

Adverse events from head-to-head and active control trials in adults (Original Report)^a

Author Year	Adverse events	Total withdrawals	Withdrawals from AEs
Head-to-head trials
Ciprandi 199729 L: loratadine 10 mg qd C: cetirizine 10 mg qd	No significant AEs reported	Total: 0	0
Hampel 200331 F: fexofenadine 180mg qd C: cetirizine 10mg qd	Total AEs: 16.7% AEs per group: F: 16.9% C: 16.6% F: less overall drowsiness P=0.0110, NS effect on motivation	Total: 3.2% F: 2.8% C: 3.6%	1.2% AEs 3 efficacy Safety evaluated in AE population
Howarth 199932 F1: fexofenadine 120 mg qd F2: fexofenadine 180 mg qd C: cetirizine 10 mg qd P: placebo	Treatment-related AEs: F1: 23% F2: 23% C: 25% P: 25 %	Total: 14% Similar among groups (numbers per group NR)	F: 2% C: <1% P: 2%
Prenner 200033 L: loratadine 10 mg qd F: fexofenadine 120 mg qd	F 22.1% vs. L 18.2% had ≥1 AE. Considered treatment related in F 8.3% L 5.3%	NR	NR
Van Cauwenberge 200036 L: loratadine 10 mg qd F: fexofenadine 120 mg qd P: placebo	16.4% of total F: 16.8% L: 17.5% P: 14.7%	Total: 10% F: 9% L: 12% P: 11%	F: 1% L: 2% P: 3%
Guerra 199474 L: loratadine 10mg C: cetirizine 10mg P: placebo	20.7% Total NSD. L: 15.8% C: 27.5% P: 15.8%	C: 1	C: 2.5% stomach pain
Active control trials
Frolund 199072 L: loratadine 10 mg qd C: clemastine 1 mg bid P: placebo	32.9% Total L: 15% (P<0.05) C: 58.8%, sedation significant P: 49% placebo	Total: 13.5% L: 9.4% C: 5.8% P: 25.4%	L: 0% C: 1.9%: 1 AE/2 efficacy P: 0%
Breneman 199687 C: cetirizine 10mg qd H: hydroxyzine 25 mg tid P: placebo	C: 18% H: 30% P: 6% H vs. P. P=0.001	Total: 4.8% C: 1.7% H: 6.3% P: 6.1%	Somnolence: C: 1.7% H: 6.3% P: 6.1%
Berger 200327 D: desloratadine 5 mg A1: azelastine nasal A2: azelastine nasal + loratadine P: placebo	Most common per treatment: Bitter taste A1: 11% vs. A2: 4% D: Headache 3%, pharyngitis 4% P: headache 7% Somnolence: A1: 2%; A2: 1%; D: 1%; P: 1%	A1: 2% D: 1% P: 1%	A1: 2% (moderate chest pain, lightheadedness) D: 1% (headache and nausea) P: 1% (rash)
Dockhorn 198756 L: loratadine 10 mg C: clemastine 2 mg P: placebo	More AEs (considered probably or possibly treatment-related) in C C: 37% L: 21% P: 20% (p≤0.01) More sedation in C: C: 22% L: 6% (p≤0.01)	NR	NR

a: Only fair- and good-quality studies are presented in the table. Poor-quality studies are listed in Appendix F.

: Abbreviations: bid, twice daily; mg, milligrams; NSD, no significant difference; NR, not reported; qd, once daily; tid, 3 times daily.

Adverse events from studies in adults (includes only studies from update 2003–2005)^a

Type of AE	Adverse event	Cetirizine	Fexofenadine	Loratadine
NEUROLOGICAL
MAJOR
MINOR	Fatigue/Asthenia	6.8% vs. rupatadine 10.5%, NSD52		6.0%; vs. rupatadine 10 mg 10.7%; vs. rupatadine 20 mg 11.7%: NSD55
	Headache	19.7% vs. 15.3% rupatadine, NSD52	2.2% vs. cetirizine 0%, NSD75 5% vs. placebo 3%79	18%; vs. fluticasone 17%168 12.1%; vs. rupatadine 10 mg 23.4%; vs. rupatadine 20 mg 14.3%, NSD55 5.8%; vs. ebastine 10 mg 4.3%; vs. ebastine 20 mg 3.2%; vs. placebo 4.3%53
	Somnolence	2.6% vs. azelastine 1.3%30 8.5% vs. rupatadine 9.6%, NSD52 Drowsiness: 7.7% vs. fexofenadine 4.5%, NSD75	Drowsiness: 4.5% vs. cetirizine 7.7%, NSD75	7.8%; vs. rupatadine 10 mg 12.5%; vs. rupatadine 20 mg 25%, significant but P value not given55 0%; vs. ebastine 10 mg 1.6%; vs. ebastine 20mg 2.7%; vs. NR placebo53
	Unspecified			0% vs. ebastine 4.6% vs. placebo 0%113
GASTROINTESTINAL
MAJOR
MINOR	Abdominal pain	0% vs. fexofenadine 2.2%, NSD75	2.2% vs. cetirizine 0%, NSD75
	Constipation	5.8% vs. fexofenadine 0 %, NSD75	0% vs. 5.8% cetirizine, NSD75
	Dry mouth			1.7% vs. rupatadine 10 mg 1.8% vs. rupatadine 20 mg 3.6%, NSD55
	Epigastric pain	3.8% vs. fexofenadine 0%, NSD75	0% vs. 3.8% cetirizine, NSD75
	Unspecified			0% vs. ebastine 3.2% vs. placebo 3.5%113
HEMATOLOGICAL
MAJOR
MINOR	Abnormalities in complete blood count
RESPIRATORY
MAJOR			1 patient had asthma requiring hospitalization79
MINOR	Cough	3.8% vs. fexofenadine 0%, NSD75	0% vs. 3.8% fexofenadine, NSD75	4.3% vs. rupatadine 10 mg 8.0% vs. rupatadine 20 mg 5.4%55
	Epistaxis	<1% vs. azelastine 2.0%30
	Nasal discomfort	<1% vs. azelastine 1.3%30
	Pharyngitis			1.7% vs. rupatadine 10 mg 7.1% vs. rupatadine 20 mg 4.5%, NSD55
	Unspecified			12.2% vs. ebastine 10 mg 8.5% vs. ebastine 20 mg 7.5% vs. placebo 10.2%53
CARDIAC
MAJOR	QT interval		No clinically relevant ECG changes vs. placebo79	Prolonged QTc: 1.6%; vs. ebastine 10 mg 3.2%; vs. ebastine 20 mg 2.2%; vs. placebo 0.5%53 Prolonged QTc: 3.6%; vs. ebastine 20 mg 3.9%; vs. placebo 5.6%113
MINOR	Unspecified			2.5%; vs. ebastine 2.8%; vs. placebo 4.2%113
OTHER
MAJOR	Back pain			4.3%; vs. rupatadine 10 mg 3.6%; vs. rupatadine 20 mg 4.5%, NSD55
MINOR	Bitter taste	<1% vs. azelastine 3.3%30
	Feet swelling	0% vs. 2.2% fexofenadine, NSD75	2.2% vs. cetirizine 0%, NSD75
	Hypospadias			OR of hypospadias with loratadine exposure: 1.29 (0.62–2.68)167 Use of nonsedating antihistamines, including loratadine, OR: 1.33 (0.73–2.40)167

a: Only fair- and good-quality studies are presented in the table. Poor-quality studies are listed in Appendix F.

: Abbreviations: mg, milligrams; NR, not reported; NSD, no significant difference; OR, odds ratio QT, cardiac output; QTc, corrected QT interval for heart rate.

: There were no data on desloratadine identified in update 1.

Adverse events from studies in children (Original Report and Update 1)^a

Type of AE	Adverse event	Cetirizine	Desloratadine	Fexofenadine	Loratadine
NEUROLOGICAL
MAJOR		Somnolence and irritability (1 patient, led to withdrawal)110
MINOR	Behavioral screening	NSD vs. placebo117, 147
	Fatigue	4.0% vs. chlorpheniramine 6.3% 101 5.3% vs. placebo 0%, NSD109 5.9% vs. placebo 7.5%104
	Headache	6.3% vs. chlorpheniramine 0%101 0% vs. placebo 6.3%, NSD109 15.1% vs. placebo 19.7%99 3.2% vs. placebo 1.6%98 15% vs. placebo 18.8%149	1.8 vs. placebo 5.4% (2–5 years)156 1.7 vs. placebo 6.7% (6–11 years)156	1–2% in treatment and placebo groups144	25% vs. fluticasone 42%103
	Somnolence	5.5% vs. placebo 0%95 NSD vs. placebo117, 147 21.4% vs. placebo 30.2%148 1/38 patients withdrew due to somnolence vs. 0 in loratadine group110			0% vs. dexchlorpheniramine 4.3%102 3% vs. placebo 5%, NSD169 0.5 vs. placebo 1.0%, NSD155
	Insomnia	23.8% vs. placebo 44.2%148			0 vs. placebo 1.0%, NSD155
	Irritability				0 vs. placebo 0.5%, NSD155
	Nervousness	28.6% vs. placebo 44.2%148
	Vertigo	1.6% vs. placebo 0%98
GASTROINTESTINAL
MAJOR
MINOR	Abdominal pain	9.6% vs. chlorpheniramine 4.8%101 9.4% vs. placebo 4.5%99 9.3% vs. placebo 4.3%149
	Abnormal liver function	9.4% vs. placebo 0%104 NSD vs. placebo in blood chemistry117, 147
	Dry mouth	1.6% vs. placebo 0%98
	Increased appetite	1.6% vs. placebo 0%98
	Nausea	1.6% vs. chlorpheniramine 0%101
HEMATOLOGICAL
MAJOR				Neutropenia (asymptomatic) in 1 child100
MINOR	Abnormalities in complete blood count	NSD vs. placebo107 Leucocytosis: 5% vs. placebo 7%104 NSD vs. placebo117, 147
CARDIAC
MAJOR	QT interval	NSD vs. placebo (2 week follow-up)99 NSD vs. placebo117, 147 NSD QT cetirizine vs. placebo148 NSD QTc vs. placebo149	NSD rate, PR, QRS or QT vs. placebo156	NSD QTc vs. placebo92
RESPIRATORY
MAJOR
MINOR	Coughing				3% vs. placebo 5%, NSD169
	Epistaxis	7.1% vs. placebo 4.3%99 7.1% vs. placebo 4.3%149			4.8% (moderate) vs. dexchlorpheniramine 0%102 4% vs. fluticasone 7%103
	Pharyngitis	10.1% vs. placebo 13.6%99 1.6% vs. placebo 4.9%98 10.0% vs. placebo 13.0%149			10% vs. fluticasone 16%103 18.8% vs. 18.1%, NSD155
OTHER
MAJOR	Accidental overdose	2 children vs. 8 placebo117, 147
MINOR	Rash	3.2% vs. placebo 0%98 1/40 patients withdrew due to rash110
	Mean increase height and weight	NSD vs. placebo117, 147
	Fever		5.5 vs. placebo 5.4% (2–5 years)156 5.5 vs. placebo 5.4% (6–11 years)156		3% vs. placebo 5%, NSD169

a: Only fair- and good-quality studies are presented in the table. Poor-quality studies are listed in Appendix F.

: Abbreviations: NSD, no significant difference; QT, cardiac output; QTc, corrected QT interval for heart rate.

Appendix EReporting of adverse events

Table

Table

Table

Publication Details

Copyright

Publisher

NLM Citation

Adverse events from head-to-head and active control trials in adults (Original Report)a

Adverse events from studies in adults (includes only studies from update 2003–2005)a

Adverse events from studies in children (Original Report and Update 1)a

Adverse events from head-to-head and active control trials in adults (Original Report)^a

Adverse events from studies in adults (includes only studies from update 2003–2005)^a

Adverse events from studies in children (Original Report and Update 1)^a