1st generation histamine

MOA

Diphynelhydramine

blocks histamine H1-receptors on

effector cells of the GI tract, blood
vessels and respiratory tract. It also
causes sedation and has some
anticholinergic action.
Absorption: Absorbed well from the
GI tract (oral); peak plasma
concentrations after 1-4 hr.
Distribution: Widely distributed,
CNS; crosses the placenta and enters
breast milk. Protein-binding:Highly
bound.
Metabolism: Extensive first-pass
metabolism.
Excretion: Via urine (as metabolites,
small amounts as unchanged drug); 14 hr (elimination half-life).

Chlorphenamine maleate

an H1-receptor antagonist which

competetively blocks H1-receptor sites
on tissues.
Duration: 4-6 hr.
Absorption: Absorbed relatively
slowly from the GI tract (oral); peak
plasma concentrations after 2.5-6 hr.
Distribution: Widely distributed;
CNS. Protein-binding: 70%.
Metabolism: Extensive; converted to
desmethyl- and
didesmethylchlorphenamine.
Excretion: Via urine (as unchanged
drug and metabolites).

Hydroxycine

Hydroxyzine blocks histamine H1receptors on effector cells of the GI

tract, blood vessels and respiratory
tract; a sedating anihistamine with
antimuscarinic and significant sedative
properties. It also possesses skeletal
muscle relaxing, bronchodilator,
antiemetic and analgesic properties.
Absorption: Absorbed rapidly from
the GI tract (oral).
Metabolism: liver, Converted to
cetirizine (has antihistaminic
properties).
Excretion: 20 hr (elimination half-life
3hr).

Pharmacody
namics
Onset\
Oral: 1560mins
IM: 30mins
IV:
immediate
Peak
Oral:1-4hrs
IM:1-4hrs
IV:unknown
Duration: 48hrs

Administration/Dose/Indication

Drug interaction

Side effect

Special precaution

Contraindication

PO As HCl: 25-50 mg 3-4

times/day. Max: 300 mg/day.
IV/IM As 1 or 5% soln: As HCl:
10-50 mg, up to 100 mg. Max:
400 mg/24 hr. May be taken
with or without food

Masks ototoxicity produced

by aminoglycosides.
Increases gastric
degradation of levodopa and
decreases its absorption by
reduction of gastric
emptying. Antagonises
therapeutic effects of
cholinergic agents e.g.
tacrine, donezepil and
neuroleptics. Valerian, St.
John's wort, Kava Kava and
gotu kola may increase CNS
depression.
Potentially Fatal:
Potentiates CNS depression
with alcohol, barbiturates,
analgesics, sedatives and
neuroleptics
Potentiates sedative effect
of psychotropic drugs e.g.
barbiturates, hypnotics,
opiod analgesics,
anxiolytics and
antipsychotics. Interaction
with alcohol could be
dangerous
(sedation/excitation).

CNS depression, dizziness,

headache, sedation;
paradoxical stimulation in
children; dryness of mouth,
thickened respiratory
secretion, blurring of vision,
urinary retention; GI
disturbances; blood dyscrasia

Epilepsy; elderly; performing tasks

which require mental alertness;
angle-closure glaucoma;
pyroduodenal obstruction; urinary
tract obstruction; hyperthyroidism;
raised intraocular pressure; CV
disease; acute asthma; pregnancy

Hypersensitivity ;
neonates, lactation.

CNS depression, sedation,

drowsiness, lassitude,
dizziness. GI upsets,
anorexia, or increased
appetite, epigastric pain,
blurring of vision, dysuria,
dryness of mouth, tightness in
chest, hypotension, muscular
weakness, tinnitus, euphoria,
headache, paradoxical CNS
stimulation.

Elderly, pylori duodenal obstruction,

angle-closure glaucoma, urinary
retention, prostatic hyperplasia,
epilepsy, renal and hepatic
impairment. May affect performance
of skilled tasks. BPH, bladder neck
obstruction, hypertension.
Pregnancy, lactation.

Incompatibility:
Incompatible with
calcium chloride,
kanamycin sulfate,
noradrenaline acid
tartrate, pentobarbital
sodium and meglumine
adipiodone

Masks ototoxicity of
aminoglycoside antibiotics.
Potentially Fatal:
Potentiates CNS depression
by barbiturates, hypnotics,
opioid analgesics, sedatives
and neuroleptics. MAOIs,
atropine, and TCAs
potentiate antimuscarinic
effects

CNS depression, paradoxical

CNS stimulation, dry mouth,
thickened respiratory
secretions, constipation,
blurring of vision,
tachycardia, GI disturbances,
headache, hypotension,
tinnitus.

Renal and hepatic impairment;

narrow-angle glaucoma; epilepsy;
prostatic hypertrophy; bladder neck
obstruction; asthma; COPD. May
impair ability to drive or operate
machinery.

Porphyria, neonates,
pregnancy, lactation.

Oral ( May be taken with or

without food)
Allergic conditions
Adult: 4 mg every 4-6 hr. Max:
24 mg daily.

Onset
Oral/IM: 1530 mins
Peak
Oral/IM:2hr
s
Duration:
Oral?IM: 46hrs

Oral (May be taken with or

without food)
Pruritus in acute and chronic
urticaria and dermatosis
Adult: Initially, 25 mg at night
increased if required up to 25
mg 3-4 times daily.
.
Renal impairment: Moderatesevere impairment: Reduce
dose by 50%.
Hepatic impairment: Reduce
total daily dose by 33%.

overdose

Cremastine Fumarate

Clemastine fumarate is an
antihistamine with anticholinergic
(drying) and sedative side effects.
Antihistamines appear to compete
with histamine for cell receptor sites
on effector cells. The inherently long
duration of antihistaminic effects of
clemastine has been demonstrated in
wheal and flare studies. In normal
human subjects who received
histamine injections over a 24-hour
period, the antihistaminic activity of
clemastine reached a peak at 5 to 7
hours, persisted for 10 to 12 hours
and, in some cases, for as long as 24
hours. Pharmacokinetic studies in man
utilizing 3H and 14C labeled
compound demonstrates that:
clemastine is rapidly and nearly
completely absorbed from the
gastrointestinal tract, peak plasma
concentrations are attained in 2 to 4
hours, and urinary excretion is the
major mode of elimination.

are indicated for the relief of

symptoms associated with
allergic rhinitis such as
sneezing, rhinorrhea, pruritus,
and lacrimation.

Mequitazine is a phenothiazine
derivative having antihistaminic,
antimuscarinic and mild sedative
properties

Oral
Hypersensitivity reactions,
urticaria, rhinitis,
conjunctivitis, pruritic skin
disorders
Adult: 5 mg bid.

Chlorphenoxamine

Chlorphenoxamine is a congener of
diphenhydramine that has
antimuscarinic and antihistaminic
properties. It has been used in nausea,
vomiting, vertigo and hypersensitivity
reactions and was formerly used in the
sympathomimetic treatment of
parkinsonism.

Topical/Cutaneous
Allergic reactions
Adult: Apply when required
several times daily.

Doxylamine succinate

Doxylamine is an antihistamine
derived from monoethanolamine
possessing antimuscarinic and
pronounced sedative effects.
Absorption: Plasma concentrations
peak 2-3 hr after oral admin.

Oral ( Should be taken with

food. (Take w/ food or milk.))
Hypersensitivity reactions
Adult: 25 mg every 4-6 hr.
Max: 150 mg daily.

Mequitazine

MAO inhibitors prolong and

intensify the anticholinergic
(drying) effects of
antihistamines.

Transient drowsiness, the

most common adverse
reaction associated with
clemastine fumarate, occurs
relatively frequently and may
require discontinuation of
therapy in some instances.

should be used with caution in

patients with: history of bronchial
asthma, increased intraocular
pressure, hyperthyroidism,
cardiovascular disease, and
hypertension.

Enhanced effects of CNS

depressants e.g. alcohol,
barbiturates, hypnotics,
opioid analgesics, anxiolytic
sedatives and
antipsychotics. Can mask
signs of ototoxicity caused
by aminoglycosides. QT
prolongation reported with
spiramycin.

CNS depression including

slight drowsiness to deep
sleep, lassitude, dizziness,
incoordination. Headache,
psychomotor impairment and
antimuscarinic effects.
Rarely, rashes and
hypersensitivity reactions,
blood disorders, convulsions,
sweating, myalgia,
paraesthesias, extrapyramidal
effects, tremor, confusion,
sleep and GI disturbances,
tinnitus, hypotension, hair
loss. Photosensitivity,
jaundice.

Pregnancy, lactation; severe CV

disorders; asthma; angle-closure
glaucoma, urinary retention,
prostatic hyperplasia,
pyloroduodenal obstruction; renal
and hepatic impairment; elderly,
children; epilepsy. May impair
ability to drive or operate machinery.

Severe liver disease;

Enhance effects of CNS

depressants eg alcohol,
barbiturates, hypnotics,
opioid analgesics, anxiolytic
sedatives and
antipsychotics. Atropine,
TCAs, MAOIs. Can mask
signs of ototoxicity caused
by aminoglycosides.

Acute dystonic reactions and

long-lasting impaired
consciousness in child. CNS
depression including slight
drowsiness to deep sleep,
lassitude, dizziness,
incoordination. Headache,
psychomotor impairment and
antimuscarinic effects. Rarely
rashes and hypersensitivity
reactions, blood disorders,
convulsions, sweating,
myalgia, extrapyramidal
effects, tremor, confusion,
tinnitus, hypotension, hair
loss.

May impair ability to drive and

operate machinery. Angle-closure
galucoma, urinary retention,
prostatic hypertrophy or
pyloroduodenal obstruction;
epilepsy; hepatic impairment.
Elderly. Lactation.

Severe liver disease;

avoid alcohol;
premature infants or
full-term neonates.

DOSAGE SHOULD BE
INDIVIDUALIZED
ACCORDING TO THE
NEEDS AND RESPONSE OF
THE PATIENT.The
recommended starting dose is
1.34 mg (1/2 tablet) twice daily.
Dosage may be increased as
required. Clemastine fumarate
tablets are recommended for the
dermatologic indications at the
2.68 mg dosage level only.The
maximum recommended
dosage is 2.68 mg 3X daily.
Many patients respond
favorably to a single dose
which may be repeated as
required, but not to exceed three
tablets daily.

premature infants or
full-term neonates.

Loratidine (2nd Generation

anti- histamine)

Desloratidine

Ebastine

Loratadine is a non-sedating
antihistamine. It works by selectively
binding to peripheral histamine H1
-receptors on effector cells.
Absorption: Absorbed rapidly from
the GI tract (oral); peak plasma
concentrations after 1 hr. Absorption
delayed by the presence of food.
Distribution: Enters breast milk, does
not cross the blood-brain barrier.
Protein-binding: 98%.
Metabolism: Extensively hepatic;
converted to descarboethoxyloratadine
(desloratadine).
Excretion: Via urine and faeces (as
metabolites);elimination half-life 8.4
hr (loratadine) and 28 hr
(desloratadine
Desloratadine is a long-acting,
tricyclic, non-sedating, selective
peripheral histamine H1-receptor
antagonist which inhibits the release of
pro-inflammatory mediators from
human mast cells and basophils.
Absorption: Peak plasma
concentrations after 3 hr (oral).
Distribution: Protein-binding: 8287%.
Metabolism: Hepatic; converted to 3hydroxydesloratadine.
Excretion: Via urine and faeces (as
metabolites).

Onset: 1 hr

Ebastine, a piperidine derivative, is a

long-acting, nonsedating, secondgeneration histamine receptor
antagonist that binds preferentially to
peripheral H1 receptors. It is
metabolised to active metabolite,
carebastine. It has antihistaminic,
antiallergic activity and prevents
histamine-induced
bronchoconstriction. It does
not have significant sedative or
antimuscarinic actions
Absorption: Oral:rapidly absorbed
Distribution: Highly bound,>95%

Peak: 2.64hrs

Peak
Oral: 1 hr
Duration:
24hrs

Oral
Onset:1hr
Peak:3hr
Duration:
4hrrs

Oral- May be taken with or

without food.
Oral
Allergic conditions
Adult: 10 mg once daily.
Child: 2-5 yr: 5 mg once daily.
6-12 yr: 10 mg once daily.
Renal impairment: Dosage
may need to be reduced to
alternate day admin.
Hepatic impairment: Dosage
may need to be reduced to
alternate day admin.

Plasma concentrations
increased by ketoconazole,
cimetidine, nefazodone,
erythromycin and possibly
other inhibitors of CYP3A4.

Oral- May be taken with or

without food.
Allergic conditions
Adult: 5 mg once daily.
Child: 12 yr: 5 mg once daily;
6-11 yr: 2.5 mg; 1-5 yr: 1.25
mg; 6-11 mth: 1 mg. Doses to
be taken once daily.
Renal impairment: Initially, 5
mg every other day.
Hepatic impairment: Initially, 5
mg every other day.

Fatigue, giddiness, dizziness,

dry mouth, headache, nausea,
somnolence.

Severe hepatic damage, epilepsy,

renal insufficiency.

Pregnancy, lactation,
children <2 yr.

NA

Headache, fatigue,
somnolence, dizziness;
nausea, dyspepsia;
xerostomia, dysmenorrhoea;
pharyngitis

Severe renal or hepatic failure;

children <6 mth, elderly, epilepsy,
pregnancy and lactation.

Hypersensitivity.

Treatmen
t is
symptom
atic and
supportiv
e.
Standard
measures
to reduce
absorptio
n to be
adopted.
Haemodi
alysis
unlikely
to be
useful.

Oral
Allergic conditions
Adult: 10-20 mg once daily.

Concomitant use of
ketoconazole, itraconazole,
clarithromycin or
erythromycin may increase
plasma levels of ebastine
and cause QTc interval
prolongation.

Headache, dry mouth,

drowsiness, pharyngitis,
abdominal pain, dyspepsia,
asthenia, epistaxis, rhinitis,
sinusitis, nausea, insomnia

Caution is advised when used in

hepatic impairment, renal
insufficiency, QTc interval
prolongation. Pregnancy, lactatio

Oral
Seasonal allergic rhinitis
Adult: 120 mg once daily.
Child: 6-11 yr: 30 mg bid.

Co-admin with
ketoconazole or
erythromycin may increase
plasma levels of
fexofenadine. May increase
adverse effects of other
anticholinergics and CNS
depressants. May increase
arrhythmogenic effect of
antipsychotic agents
(phenothiazines); avoid
concurrent usage. May
reduce the efficacy of
betahistine. Pramlintide may
increase the anticholinergic
effect of fexofenadine.
Bioavailability may be
increased by verapamil.
Efficacy may be reduced by

Viral infection (cold/flu);

headache, dizziness,
drowsiness, fatigue; nausea,
dyspepsia, dysmenorrhoea
children <6 yr

Renal impairment. Pregnancy,

lactation; children.

Metabolism: Liver

fexofenadine

Excretion: Urine mainly as conjugated

metabolites
Halflife: between 15-19hours
Fexofenadine, an active metabolite of
terfenadine, is a competitive peripheral
histamine H1-receptor antagonist on
effector cells in the GI tract, blood
vessels and respiratory tract.
Absorption: Absorbed rapidly from
the GI tract (oral); peak plasma
concentrations after 2-3 hr.
Distribution: Enters breast milk. 6070% bound to plasma proteins.
Metabolism: Intestinal mucosa (5%
of total dose); hepatic (0.5-1.5% of
dose).
Excretion: Mainly via faeces, via
urine (10% of dose); 14 hr
(elimination half-life; may be
prolonged in renal impairment).

fexofenadine

Azelastine

Levocetirizine

cetirizine + pseudoephedrine

Azelastine blocks histamine H1receptor activity and inhibits release of

inflammatory mediators from mast
cells. Antagonizes action of
acetylcholine, histamine, serotonin,
inhibits the synthesis and release of
leukotrienes.
Absorption: 40% absorbed
sytemically through the nasal mucosa
(intranasal).
Metabolism: Hepatic.
Excretion: Via faeces
Levocetirizine, an active isomer of
cetirizine, selectively inhibits
peripheral histamine H1-receptors.
Absorption: Rapidly and extensively
absorbed from the GI tract (oral); peak
plasma concentration in 0.9 hr.
Distribution: Protein-binding: 9192%.
Metabolism: Via aromatic oxidation,
N- and O-dealkylation and taurine
conjugation.
Excretion: Via urine (85.4%), via
faeces (12.9%), as metabolites and
unchanged drug; 8 hr (plasma halflife).
Cetirizine is an antihistamine that
works mainly via selective inhibition
of H1 receptors. Pseudoephedrine
hydrochloride is an orally active
sympathomimetic amine that exerts a
decongestant action on the nasal
mucosa. It is used for the relief of
nasal congestion due to allergic
rhinitis.
Absorption: Cetirizine: Rapidly
absorbed from the GI tract after oral
admin. Pseudoephedrine: Readily
absorbed after oral admin.
Distribution: Cetirizine: About 93%
bound to plasma proteins.
Metabolism: Cetirizine: Limited
metabolism by oxidative Odealkylation to a metabolite with little
or no antihistaminic activity.
Pseudoephedrine: About 1-7% of a
dose is metabolised to norpseudoephedrine by N-demethylation.
Excretion: Mean elimination half-life:
7.9 hr (cetirizine) and 6 hr
(pseudoephedrine)

Onset:
unknown
Peak: 4-5hrs
Duration:
Unknown

Ophthalmic
conjunctivitis
Adult: Instill 1-2 drops of
0.05% solution into the affected
eye/s bid, may increase to four
times daily in severe cases.

rifampin.
Additive effects with CNS
depressants and ethanol.

Irritation, stinging and itching

of the nasal mucosa.
Sneezing, nosebleeds,
headache; nausea, taste
disturbances, somnolence, dry
mouth.

Pregnancy, lactation. Tip of the

bottle should be dipped in boiling
water, dried and capped
appropriately after every use.

Hypersensitivity.

Nasal
rhinitis
Adult: 140 mcg by nasal spray
into each nostril bid.
Oral
Allergic conditions e.g.
rhinitis and chronic urticaria
Adult: As hydrochloride: 5 mg
daily in the evening; 2.5 mg
may be adequate in some
patients. Max dose: 5 mg daily.

Additive sedation with

alcohol and other CNS
depressants

Fatigue, somnolence, dry

mouth, nasopharyngitis,
pyrexia, cough, epistaxis.

Renal impairment. May impair

ability to drive or operate machinery

Lactation. End-stage
renal disease (CrCl
<10 ml/min) or
haemodialysis patients.
Child 6-11 yr with
renal impairment

Extended-release: May be taken

with or without food. (Swallow
whole, do not chew/ crush.)
PO Extended release Per tab
contains cetirizine 5 mg and
pseudoephedrine

Concurrent use with

digitalis may increase
ectopic pacemaker activity.
Additive effects on the CV
system may occur when
used with sympathomimetic
amines.
Potentially Fatal: Not to be
used concurrently with
MAOIs or within 14 days of
stopping MAOI treatment.

Insomnia, dry mouth,

somnolence, fatigue.

Caution when used in patients with

Patients with narrowangle glaucoma or

urinary retentionMAOI
treatment or within 14
days of stopping such
treatment. Patients
with severe
hypertension or severe
coronary artery
disease.

hypertension, DM, ischaemic heart

disease, increased intraocular
pressure, hyperthyroidism, renal
impairment or prostatic hypertrophy.
May cause CNS stimulation with
convulsions or CV collapse with
accompanying hypotension. Elderly
are more prone to developing the
adverse reactions. Pregnancy.

Antihistaminic Compounds
It should be noted that the following reactions have occurred with one or more antihistamines and, therefore, should be kept in mind when prescribing drugs belonging to this class.
The most frequent adverse reactions are underlined.
1.
2.
3.
4.
5.
6.
7.

General: Urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspiration, chills, dryness of mouth, nose, and throat.
Cardiovascular System: Hypotension, headache, palpitations, tachycardia, extrasystoles.
Hematologic System: Hemolytic anemia, thrombocytopenia, agranulocytosis.
Nervous System: Sedation, sleepiness, dizziness, disturbed coordination, fatigue, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, euphoria, paresthesias, blurred vision, diplopia, vertigo, tinnitus, acute labyrinthitis, hysteria, neuritis,
convulsions.
GI System: Epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation.
GU System: Urinary frequency, difficult urination, urinary retention, early menses.
Respiratory System: Thickening of bronchial secretions, tightness of chest and wheezing, nasal stuffiness.