Dosage and administration

Administration Chorpheniramine maleat, chlorpheniramin tanate, and dexchlorpheniramine

maleat are administered orally.
Chlorpheniramine maleat 16 mg extended realese core tablets containing the drug in
an immediate-realese outer shell and an extended-realese core tablets should not be devided,
crushed, chewed, or dissolved. The extended realese core tablets should be taken with fluid.
Patients should be advised that the matrix core of the tablets does not completely dissolve and
may be passed in the stool.
Dosage dosage of chlorpheniramin and dexchlorpheniramine should be individualized
according to patiens response and tolerance. Dosage of dexchlorpheniramine maleat is
approximately 50% that of chlorpheniramine maleat.
Chlorpheniramine maleat for self medication in adult and children 12 years of age
and older, the usual oral dosage of chlorpeniramine maleate alone or in fixed combination
preparations is 4 mg every 4-6 hours, not to exceed 24 mg in 24 hours. Alternatively, for self
mediacation, adult and children 12 years of age and older may receive and extended realease
formulation containing 8 or 12 mg of the drug twice daily in the morning and evening, not to
exceed 24 mg in 24 hours. The usual oral dosage of chlorpheniramine maleat alone or in
fixed combinations preparations for self medications in children 6 to younger than 12 years of
age is 2 mg every 4-6 hours, not exceed 12 mg in 24 hours. Under the directions of a
clinician, children 2 to younger than 6 years of age may receive 1mg 4-6 hours, not to exceed
6 mg in 24 hours. Under the directionof a clinician,children 6 to younger than 12 years of age
may be given an extended release formulation containing 8 mg of the drug once daily at
bedtime or during the day as indicated. For fixed combimation preparations, lower maximum
daily chorpheniramine maleate dosage may be necessary because of other ingredients (e.g.,
acetaminophen, pseudoephedrine hydrochloride) included in the formulations.
The usual dosage of chlorampheniramine maleate as the 16 mg extended release core
tablets containing the drug in an immediate-release outer shell (4 mg) and in an extended-
release matrix core (12 mg) for adult and children 12 years of age and older is 1 tablets
(16mg total) once daily at 24 hours intervals. The manucfacturer recommends that this
dosage not be exceed. The extended release core tablets should not be used in children youger
than 12 years of age.
Dexchorpheniramine maleat for self mediaction in adults and children 12 years of age
and older, the usual oral dosage of dexchlorapheniramine maleate is 2 mg every 4-6 hours not
to exeed 12 mg in 24 hours. The usual oral dosage of the drug for self mediaction in children
6 to younger than 12 years of age is 1mg every 4-6 hours, not to exceed 6 mg in 24 hours.
Under the direction of clinician, children 2 to youger than 6 years of age may receive 0,5 mg
every 4-6 hours, not to exceed 3 mg in 24 hours.
The usual dosage of dexchorpheniramine maleat as extended release tablets is 4 or
6mg at bedtime or every 8-10 hours while awake in adults and children 12 years of age and
older. The usual dosage as extended release tablets for children 6 to younger than 12 years of
age is 4 mg once daily, preferably at bedtime.
Cautions
Chlorpheniramine and dexchlorpheniramine share the toxic potentials of other
antihisthamines, and the usual precautions of antihistamine therapy should be observed ( see
cautions in the antihisthamines general statement 4:00)
Individual with phenylketonuria(i.e, homozygous genetic deficiency of phenylalanine
hydroxylase) and other individuals who must restrict their intake of phenylalanine should be
warned that Triaminic cold and Allergy Softchews* chewable tablets and Tylenol* Cold
Multi-Symtomp Childrens chewable tablets containe aspartame (Nutrasweet*) which is
metabolized in the GI tract to phenylalanine following oral administration.
Pediatric precaution like other antihisthamins, chlorpheniramin and dexchlorpheniramine
should not be used in premature or full-term neonates. Conventional chlorpheniramin
preparations and extended release preparations of the drug should be used in children
younger than 6 years of age and in those younger than 12 years of age, respectively, only
under the direction and supervision of a physician. Safety and efficacy of chlorpheniramine
maleate extended release core tablets in children younger than 12 years of age have not been.
Established. Safety and efficacy of extended release tablets containing 4 or 6 mg of
dexchlorpheniramine maleate have not been established in children younger than 6 years of
age or in those younger than 12 years of age, respectively.
Mutagenic and carcinogenicity the mutagenic and carcinogenic potentials of
dexchlorpheniramine have not been determined. No evidence of chlorphrniramine induced
mutagenesis was seen in the Ames microbial mutagen test or mouse lymphoma cells, with or
without metabolic activation, nor in chinese hamster ovary cells with metabolic activation.
No evidence of carcinogenesis was seen in a 24 month study in mice or rats receiving oral
chlorpheniramine maleate dosages up to 200 orr 60 mg/kg daily, respectively, although a
proliferative effect, evidenced by an increased incidence of thyroid gland follicular cell
hyperplasia, cysts, and adenomas, was observed in female mice.
Pregnancy, Fertility, and lactation reproduction studies in animal using
dexchlorpheniramin have not been performed to date, but reproduction studies in rabbits and
rats using chlorpheniramine maleate dosage up to 50 and 85 times the usual human dosage,
respectively, have not revcaled evidence of harm to the fetus. Decreased postnatal survival in
offspring of rats receiving 33 and 67 items the usual human dosage of chlorpheniramine
maleat has been reported. There are no adequate and controlled studies to date using
chlorpheniramine or dexchlorpheniramine in pregnant women, and the drug should be used
during the first 2 trimesters only when clearly needed. In one epiderniologic study, use of
chlorpheniramine was not associated with an in creased risk of teratogenic effects; however,
only a limited numberof pregnant women received the during in this study. Because of the
risk of severe reactions (e.g.,seizures) to antihistamines in neonates, chlorpheniramine or
dexchlorpheniramin should not be used during the third trimester.
Impaired fertility has been reported in female rats receiving chlorpheniramin maleate
dosage approximately 67 times yhe usual human dosage; however, more recent studies in
rabbits and rats testing more appopriote methodology and dosage up to 50 and 85 times the
usual human dosage, respectively, have not revealed evidence of impaired fertility.
It is not known wheter chlorampheniramine or dexchlorpheniramin is distributed into
milk, bit other antihisthamin (e.g.,diphenyldramine) have been detected in milk. Because of
the potential for serious adverse reactions to antihistamines in nurshing infants, a dicision
should be made whether to discontinue nurshing or chlorpheniramine or
dexchlorpheniramine, taking into account the importance of the drug to the woman.
Pharmacokinetics
Absorptions Chlorpheniramine maleate appears to be well absorbed following oral
administration;however, the drug undergoes substantial metabolism in the GI mucosa during
absorption and on the first pas the through the liver. Limited data indicated that about 25-45
% and 35-60% of a single oral dose of Chlorpheniramine maleate as conventional tablets or a
solution, respectively, reaches the systemic circulation as unchanged drug. Limited data also
indicate that the bioavailability of extended release preparations of the drug is a redaced
compared with that of conventional tablets or oral solutions.
Following oral administration as conventional tablets or a solution of the maleate,
chlorpheniramine appears in plasma within 30-60 minutes and peak plasma concentrations of
the drug generally occur within 2-6 hours. Following oral administration of a single 4 mg
dose of the drug as conventional tablets or a solution in fasting, healty adults, mean peak
plasma chlorpheniramine concentrations of 11 and 5,9 ng/ml, respectively, have been
reported. Following oral administration of a single 0,12mg/kg dose as a solution in fasting
children with allergic rhinitis, peak plasma drug concentrations ranged from 8-18,5 ng/ml. the
antihistamine effect, as determined by suppression of the wheal and flare responses induced
by intradermal administration of histamine, is apparent within 6 hours after a single oral dose
of the drug and may period for up to at least 24 hours.
Distribution distribution of Chlorpheniramine into human body tisues and fluids has not
beebn characterizzed fully. Following IV administration in rabbits, highest concentrations of
the drug are aftained in the lungs, heart, kidneys, brain, small intestine, nd spleen, with lower
concentration in the large intestine, muscle, stomach, adrenals, fat, liver, and mesentery.
Following IV administration in humans, chlorpheniramine undergues rapid and
extensive distribution. The apparent steady state volume of distribution of the drug following
IV administration reportedly averages 2.5-3.2 L/kg in adults and 3.8 L/kg in children.
Chlorpeniramine is distributed into saliva, and the drug and/or its metabolites appear to be
distributed in small amounts into bde.
In vitro, chlorpeniramine is a approximately 69-72% bound to plasma proteins.
Elimination Following IV administration chlorpheniramine maleate, plasma concentration
of the drug have generally been reported to decline in a biphasic manner; however, one report
indicates the drug that the drug may exhibit normal renal and hepatic function, the terminal
elemenation half-life of chlorpheniramin reportedly ranges from 12-43 hours; although early
studies suggested a half-life of 2-4 hours, these values may have resulted from short sampling
times and differences in the assays employed. In children with normal renal and hepatic
function, the terminal elimination half-life reportedly aver ages 9.6-13.1 hours (range5.2-23.1
hours). In some patients with chronic renal failure undergoing hemodialysis, the elimination
half-lifeof chlorpheniramine reportedly ranged from 280-330 hours..
Chorpheniramine is rapidly and extensively metabolized, and undergoes substantial
metabolism in the GI mucosa during absorption and on first pass N-dealkytion to from
monodesmethychlorpheniramine and didesmethylchlorpheniramine, but is principally
metabolized to other (at least 2) unidentified metabolites. Chlorpheniramine and its
metabolites are apparently excresed almost compietely in urine. Urinary excretion of
chlorpheniramine and its N-dealkylated metabolites varies with urinary pH and urine flow,
decreasing oral or IV dose of chlorpheniramine maleate in healthy individuals with normal
renal and hepatic function in one study, about 20% of the dose was excreted in urine within
24 hours and 35% within 48 hours, and less than 1% was excreted in feces within 48 hours,
2-4% as monodesmethylchlorpheniramine, 1-2% as didesmethylchlorpheniramine, and the
remainder as unidentified metabolites. In other studies in healthy individuals with normal
renal andhepatic function, about 20% of a single oral dose was excreted in urine as
unchanged drug, 20% as monodesmethylchlorpheniramine, and 5% as
didesmethylchlorpheniramine.

Chemistry and Stability

Chemistry chlorpheniramine is an alkylamin (propylamine) derivative anthihistamine.
Chlorpheniramin differs from brompheniramin in the substitution of a chlorine atom for the
bromine atom of the latter compound. Dexchlorpheniramine, the dextro isomer, is
apporoximately twice as active as racemic chlorpheniramine on a weight basis.
Chlorpheniramine maleate and dexchlorpheniramine maleate occur as white, odorless,
crystalline powders. Chlorpheniramine maleate has solubilities of approximately 250 mg/mL
in water and 100 mg/mL in alcohol at 25 C. Dexchlorpheniramine maleate has solubilities
of approximately 0,9 g/mL in water and 0,5 mg/mL in alcohol at 25 C. chlorpheniramine
tannate occurs as a light tan to buff or yellowish-tan,amorphoust, fine powder having not
more than a slight characteristic odor; the tannaste is slightly solube in water 25 C. the pK ,
of chlorpheniramine is aproximately 9.2.
Stability chlorpheniramine maleate and dexchlorpheniramin maleate preparations generally
ahould be stored at a temperature: less than 40%, preferably at 15-30 C. Chlorpheniramine
maleate oral solution and dexchlorampheniramine maleate oral solution be stored in tight,
light resistant containers and chlorpheniramine maleate injection should be stored in light-
resistent containers; freezing should be avoided. Chlorpheniramin maleate extended release
tablet and dxchlorpheniramin maleate extended release tablets should be stored in well-closed
containers. Chlorpheniramine maleate tablets, chewable tablets, and extended release
capsules and dexchlorpheniramine maleate tablets should be stored in tight containers.
Chlorpheniramin maleate extended release core tablets should be stored in a dry place at 4-30
C.
Chlorpheniramine Maleat
Powder *
Oral 8 mg*

Capsule ,extended release 12 mg* Teledrin*Allergy(with benzyl alcohol), hagil

Solutions 2mg/5mL* Aller-chlor*syrup(with alcohol 7%),rugby

Chlor-Trimeton*Allergy syrup (with alcohol 7%
parabens and propylene glycol), schering plough
Tablets 4mg* After-Chlor*,Rugby
Chlor-Trimeton*4 hour allergy (secored), schering-
plough

Tablets,chewable 2mg Chlo-Amine*, Bayer

Tablets extended release 8mg* Chlor-Trimeton* 8 hour allergy (with
butylparaben), schering-plough
12 mg* Chlor-Trimeton* 12 hour allergy (with
butylparaben), schering-plough

Tablets extended release 16 mg Efidac 24* chlorpheniramine (with povidone),

core (core 12 Hogil
mg with 4
mg
immediate
release)