Clarinase Repetabs Tablets

CCDS-MK2985A-TBr-122013

Description
Clarinase Repetabs Tablets contain 5mg loratadine (Figure1.1) in the tablet coating for immediate release and 120mg
pseudoephedrine sulfate (Figure1.2) equally distributed between the tablet coating for immediate release and the barrier-coated
extended core. Loratadine is tricyclic antihistamine with selective Peripherals H1-receptor antagonistic activity, which is currently
used for the relief of symptoms associated with allergic rhinitis. Pseudoephedrine sulfate is an orally active sympathomimetic
amine that exerts a decongestant action on the nasal mucosa.
Drug Substance
Loratadine
The structure of loratadine is shown in Figure 1.1.
Its chemical name is: ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate.
The empirical formula is C22H23ClN2O2 and Molecular Weight (MW) is 382.89.
Figure 1.1 Chemical structure of Loratadine

Pseudoephedrine sulfate
Pseudoephedrine sulfate, a sympathomimetic amine, is a salt of pseudoephedrine, one of thenaturally occurring alkaloids
obtained from various species of the plant Ephedra. The structure of pseudoephedrine sulfate is shown in Figure 1.2. The
chemical name is [S-(R*, R*)]-a-[1(methylamino)ethyl] benzenemethanol sulfate (2:1)(salt).The empirical formula for
pseudoephedrine sulfate is (C10H15NO)2H2SO4 and the molecular weight of pseudoephedrine sulfate is 428.54.
Figure 1.2 Chemical structure of Pseudoephedrine Sulfate

Drug Product
Each Clarinase Repetabs Tablets contains 5mg micronized loratadine and 120mg pseudoephedrine sulfate. It also contains
acacia, calcium sulfate, carnauba wax, corn starch, lactose, magnesium stearate, microcrystalline cellulose, medicinal soap,
oleic acid, povidone, gum rosin, sucrose, talc, titanium dioxide, white beeswax and zein as the inactive ingredients.
Therapeutical Indications
Clarinase Repetabs Tablets are indicated for temporary relief the related symptoms such as nasal congestion, sneezing, runny
nose, itching and tears caused from allergic rhinitis, and cold.
Clarinase Repetabs Tablets should be administrated when both the antihistamine properties of loratadine and the nasal
decongestant activity of pseudoephedrine sulfate is desired.
Dosage and Administration
Adult and children 12 years of age and over: One Clarinase Repetabs Tablet twice daily (every 12 hours). Children under 12
years of age (not including 12 years of age) are not recommended to use it.
Clinical Pharmacology
LORATADINE
After oral administration of loratadine in the conventional tablet formulation, the drug is rapidly and well absorbed and undergoes
an extensive first pass metabolism. In normal subjects, plasma distribution half-lives of loratadine and its active metabolite are
approximately 1 and 2 hours, respectively. The mean elimination half-lives found in normal adult subjects were 8.4 hours
(range=3 to 20 hours) for loratadine and 28 hours (range= 8.8 to 92 hours) for the major active metabolite
descarboethoxyloratadine.
Approximately 40% of the dose is excreted in the urine and 42% in the feces over a 10-day period.
Loratadine and its active metabolite are excreted in the breast milk of lactating women. Forty-eight hours after dosing, only
0.029% of the loratadine dose is detected in the milk as unchanged loratadine and its active metabolite.
PSEUDOEPHEDRINE SULFATE
After oral administration, pseudoephedrine sulfate is rapidly and completely absorbed. Onset of action occurs within 30 minutes
and a dose of 60mg has a decongestive action lasting for 4 to 6 hours. It undergoes incomplete hepatic metabolism by
N-demethylation to an inactive metabolite. Its elimination half-life in humans ranges from 5 to 8 hours. The drug and its metabolite
are excreted in urine. The drug may be distributed in the breast milk of lactating women.
Safety Information
Contraindication
Clarinase Repetabs Tablets are contraindicated in patients who are hypersensitive or show idiosyncrasy to this medication, to
any of its ingredients, to adrenergic agents, or to other drugs of similar chemical structures.
This product, due to its pseudoephedrine component, is contraindicated in patients with narrow-angle glaucoma or urinary
retention, and in patients receiving monoamine oxidase (MAO) inhibitor therapy or within fourteen days of stopping such
treatment (see Drug Interactions Section). It is also contraindicated in patients with severe hypertension, severe coronary
artery disease or hyperthyroidism.
Precautions

Please keep it safely from children in order to prevent a mistake eating.

To avoid direct sunlight and please store in the shady place.

Pregnant and lactating women are not recommended to use it by their will unless the guidance by physicians and
pharmacists.

Don't excess the recommended dose. If the undesirable events occur, please discontinue it immediately and seek for
medical help.

Warnings

After taking this medicine, it may develop tiredness, dry mouth, and occasionally visual disturbance and excitement
(commonly observed in younger children and elders).

Patients with severe metabolic liver and kidney diseases should not use it unless they have physicians' prescription.

Patients who have the history of hypersensitivity should not use this kind of medicines unless the guidance by
physicians and pharmacists.

Patients with cardiac dysfunction, hypertension, diabetes mellitus, hyperthyroidism, and renal impairment
should not use it unless the guidance by the physicians and pharmacists

The elderly should use this medicine with caution.

The patients who have respiratory illness or chronic bronchitis, glaucoma, emphysema, chronic pulmonary diseases,
dyspnea, or dysuria due to prostate enlargement should not use it.

Concomitantly use with alcoholic beverage is contraindicated.

Concomitant administration with the tranquilizers or hypnotics is contraindicated unless the guidance by physicians and
pharmacists.

After taking this medicine, it may cause drowsiness, do not drive or operate dangerous equipment

If the symptoms are not alleviated after initiating this medicine for a few days, the medicine should be
discontinued immediately and seeking for medical help is needed.

Concomitant administration with other drugs containing antihistamine or decongestant (such as common cold
remedies, antitussive expectorants, motion sickness pills, decongestants or anti-allergic medicines) is
contraindicated.

The medication containing pseudoephedrine sulfate should be used with caution as following:
1.
Patients with cardiac diseases, hypertension, thyroid illness, diabetes mellitus, dysuria due to prostate
enlargement should not use this medicine unless the guidance by physicians and pharmacists.
2.
This medicine should not be used during the treatment period of MAOI or within two weeks after MAOI
treatment. Please consult your doctor or pharmacist if you do not know the medicine you take containing
MAOI or not.
3.
As sympathomimetic drugs may be easier cause the adverse effect such as confusion, hallucinations,
spasms, central nervous system depression and even death on the patients older than 60 years of age, the
elderly should be used with care
Adverse Reactions
In the controlled trial performed by the recommended dose, in the comparison of the product and placebo, in addition to insomnia
and dry mouth, and the remaining side effects are almost equally. Side effects which related to this product or placebo is including
headache and somnolence.
Less common adverse reactions according to the frequency of occurrence as follows: tension, dizziness, fatigue, nausea,
abdominal pain, anorexia, thirst, tachycardia, pharyngitis, rhinitis, acne, itching, rashes, hives, joint pain, confusion, dysarthria,
movement is too strong, sensation, reduced libido, paresthesia, tremor, ear dizziness, flushing, postural hypotension, increased
sweating, eye irritation, earache, tinnitus, taste perversion, spirit excitement, apathy, depression, euphoria, nightmares, increased
appetite, change in bowel habits, dyspepsia, eructation, hemorrhoids, tongue decolorization and tongue discomfort, vomiting,
transient liver function abnormalities, dehydration, weight gain, hypertension, palpitations, migraine headache, bronchospasm,
cough, dyspnea, epistaxis, nasal congestion, sneezing, nasal irritation, difficulty urinating, urinary discomfort, nocturia, polyuria,
urinary retention, weakness, back pain, leg cramps, malaise, and chills.
According to Loratadine post-marketing experience, very few bald, allergic reactions, tachycardia, palpitations, abnormal liver
function and convulsion case are reported.
Drug Abuse and Dependence
There is no information to indicate that abuse or dependency occurs with loratadine. Pseudoephedrine, like other central nervous
system stimulants, has been abused. Continued use can result in tolerance and therefore, increase the risk of overdosage.
Overdosage
In the event of dosage, general symptomatic and supportive treatment should be started immediately and maintained for as long
as necessary
Manifestations: Tachycardia, headache and somnolence have been reported with overdoses of loratadine. In large doses,
sympathomimetics may give rise to giddiness, headache, nausea, vomiting, sweating, thirst, tachycardia, precordial pain,
palpitation, difficulty in micturition, muscular weakness and tenseness, anxiety, restlessness, and insomnia. Many patients can
present a toxic psychosis with delusions and hallucinations. Some may develop cardiac arrhythmias, circulatory collapse,
convulsions, coma, and respiratory failure.
Treatment: Consider the standard procedure to remove any of the insoluble drugs in the stomach, such as activated charcoal
mixed with water into slurry, taking to the adsorption of drugs; or consider performing gastric lavage. Saline cathartics may also
be of value for rapid dilution of bowel contents.
Loratadine is not eliminated by hemodialysis. It is not known if loratadine is eliminated by peritoneal dialysis.
Drug Interactions
Loratatine
Increase in plasma concentrations of loratadine has been reported with concomitant use with ketaconazole, erythromycin or
cimetidine in controlled clinical trails, but without clinically significant changes (including electrocardiographic).
Pseudoephedrine sulfate
Concomitant use of sympathomimetic drugs with monoamine oxidase (MAO) inhibitors can cause high blood pressure reaction
including hypertensive crisis. The antihypertensive effects of drugs influencing the sympathetic system such as methyldopa,
mecamylamine, reserpine and veratrum alkaloids may be reduced by sympathomimetics. Beta-adrenergic blocking agents may
also interact with sympathomimetics by reducing their activity. Increased ectopic pacemaker activity can occur when
pseudoephedrine is used concomitantly with digitalis.
Other Relevant Safety Information
Pregnancy and Lactation
There was no evidence of teratogenicity in animal studies (see Preclinical Safety Data). However, the safe use of Clarinase
Repetabs Tablets during pregnancy and lactation has not been established. Clarinase Repetabs Tablets should not be used in
pregnancy only if received the guidance by physicians and pharmacists. For nursing mothers, a decision should be made
whether to discontinue nursing or discontinue the drug.
Packaging
Boxes of 4-14 tablets in PTP blister.
Storage
Store below 25. Tablets in blister pack should beware of excessive moisture. Placed in the place where children can not be
achieved.
Version: December 2013
Manufactured by
Schering-Plough Labo N.V., Industriepark 30, B-2220 Heist-op-den-Berg, Belgium