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Parakol
DESCRIPTION
A pink, oblong tablet with marking 'dp500' on one side.
COMPOSITION
Each tablet contains: Paracetamol 500 mg, Pseudoephedrine HCI
60 mg, Dexchlorpheniramine Maleate 2 mg.
PHARMACODYNAMICS
Paracetamol is a para-aminophenol derivative that exhibits analgesic and
anti-pyretic activity. It does not possess anti-inflammatory activity. It is
given by mouth or rectally for mild to moderate pain and fever.
Pseudoephedrine is a direct and indirect acting sympathomimetic agent. It is
a stereoisomer of ephedrine and has a similar action but has less pressor
activity and central nervous system effects. It is administered orally for
symptomatic relief from nasal congestion.
Chloroheniramine maleate, an alkylamine derivatives, is a sedating
antihistamines that causes a moderate degree of sedation; it also has
antimuscarinic activity.
PHARMACOKINETICS
After oral administration, paracetamol is absorbed rapidly and completely
from the gastrointestinal tract; peak plasma levels occur 10 to 60 minutes
after administration. Paracetamol is uniformly distributed throughout most
body fluids; the apparent volume of distribution is 1 to 1.2 L/kg.
Paracetamol can cross the placenta and is excreted in breast milk. Plasma
protein binding is negligible at usual therapeutic concentrations but
increases with increasing concentrations. Paracetamol is metabolised by the
hepatic microsomal enzyme system. In adults at therapeutic doses,
paracetamol is mainly conjugated with glucuronide (45 to 55%) or sulfate (20
to 30%). A minor proportion (less than 20%) is metabolised to catechol
derivatives and mercapturic acid compounds via oxidation. Paracetamol is
metabolised differently by infants and children compared to adults, the
sulfate conjugate being predominant. Paracetamol is excreted in the urine
mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted
as unchanged paracetamol with 85 to 90% of the administered dose eliminated
in the urine within 24 hours of ingestion. The elimination half-life varies
from 1 to 3 hours. Food intake delays paracetamol absorption.
Pseudoephedrine is readily and completely absorbed from the gastrointestinal
tract after oral administration. Peak concentrations are reached between 0.5
and 2 hours after administration. Distribution into extravascular sites is
extensive with the apparent volume of distribution between 2.6 and 5 L/kg.
Protein binding data does not appear to be readily available.
Pseudoephedrine is not substantially metabolised and is excreted primarily
unchanged in the urine, with only a small proportion excreted as the active
metabolite norpseudoephedrine. As pseudoephedrine is a weak base with pKa
9.4, the elimination half life varies from 1.9 hours at a urine pH of 5.6 to
21 hours at urine pH of 7.4. At high urine pH (>7.0) the drug is extensively
reabsorbed in the renal tubules and the rate of excretion and is therefore
dependant on urine flow rate. This does not appear to be the case at low
urine pH.
Chlorpheniramine maleate is absorbed relatively slowly from the
gastro-intestinal tract, peak plasma concentration occurring about 2.5 to 6
hours after administration by mouth. Bioavailability is low, values of 25 to
50% having been reported. Chlorpheniramine appears to undergo considerable
first-pass metabolism. About 70% of chlorpheniramine in the circulation is
bound to plasma proteins. There is wide interindividual variation in the
pharmacokinetics of chlorpheniramine; values ranging from 2 to 43 hours have
been reported for the half-life. Chlorpheniramine is widely distributed in
the body, including passage into the CNS. Chlorpheniramine maleate is
extensively metabolized. Metabolites include desmethyl- and didesmethyl
chlorpheniramine. Unchanged drug and metabolites are excreted primarily in
the urine; excretion is dependent on urinary pH and flow rate. Only trace
amount have been found in the faeces. A duration of action of 4 to 6 hours
has been reported; this is shorter than may be predicted from
pharmacokinetics parameters. More rapid and extensive absorption, faster
clearance, and a shorter half-life have been reported in children.
INDICATIONS
For the temporary relief of nasal congestion and associated
aches, pains and general discomfort due to colds, flu or allergy.
RECOMMENDED DOSAGE
Adults: 1 or 2 tablets every six hours.
CONTRAINDICATIONS
Hypersensitivity to antihistamines contraindicates the use of PARAKOL.
Pharmaceutical products containing Dexchlorpheniramine Maleate may cause
severe reactions such as convulsions in newborn or premature infants.
PARAKOL is also contraindicated for use in conjunction with monoamine
oxidase inhibitor therapy.
WARNING & PRECAUTIONS
This preparation contains Paracetamol. Do not take any other
Paracetamol containing medicines at the same time. |
Paracetamol: Should be used with caution in patients with: a history of
bronchial asthma, increased intraocular pressure, hyperthyroidism,
cardiovascular disease, hypertension, hyperthyroidism, hyperexcitability and
closed angle glaucoma.
PARAKOL contains Paracetamol which should be avoided in patients with
analgesic nephropathy.
Pseudoephedrine: Should be used with caution in patients taking other sympathomimetic agents such as decongestants, appetite suppressants and
amphetamine-like psychostimulants or antihypertensive agents. The effects of
a single dose on the blood pressure of these patients should be observed
before recommending repeated or unsupervised treatment. As with other
sympathomimetic agents and decongestants Pseudoephedrine should be used with
caution in patients with hypertension, heart disease, diabetes,
hyperthyroidism, elevated intraocular pressure, prostatic enlargement or
bladder dysfunction. An extremely rare example of pseudoephedrine
intolerance in a normotensive individual has been reported, following the
ingestion of one Pseudoephedrine tablet, which resulted in hypertension and
unconsciousness. In severe hepatic or renal dysfunction a single dose of
Pseudoephedrine should be given and the patient's response used as a guide
to the dosage requirement for further administration.
Dexchlorpheniramine: As with all antihistamines, should be used with caution
in patients with narrow angle glaucoma, stenosing peptic ulcer,
pyloroduodenal obstruction, symptomatic prostatic hypertrophy and bladder
neck obstruction.
Antihistamines are more likely to cause dizziness, sedation, and hypotension
in elderly patients (approximately 60 years or older).
General: Dexchlorpheniramine Maleate has an atropic-like action and
therefore products containing it should be used with caution in patients
with: a history of bronchial asthma; increased intraocular pressure;
hyperthyroidism; cardiovascular disease; hypertension.
Information for patients:
1. Dexchlorpheniramine may cause slight to moderate drowsiness.
2. Patients should not engage in activities requiring mental alertness, such
as driving or operating machinery.
3. Alcohol or other sedative drugs may enhance the drowsiness caused by
antihistamines.
INTERACTION WITH OTHER MEDICATIONS
Paracetamol: Anticoagulant dosage may require reduction if Paracetamol
medication is prolonged. Paracetamol absorption is increased by drugs which
increase gastric emptying, eg. metoclopramide, and decreased by drugs which
decrease gastric emptying, eg. propantheline, antidepressants with
anticholinergic properties, narcotic analgesics. Paracetamol may increase
chloramphenicol concentrations. The likelihood of paracetamol toxicity may
be increased by the concomitant use of enzyme inducing agents such as
alcohol or anticonvulsant drugs.
Pseudoephedrine: The absorption of pseudoephedrine hydrochloride has
been increased by concomitant administration of aluminium hydroxide.
Coadministration of pseudoephedrine and MAOI's may lead to hypertensive
crisis. An early warning symptom may be a throbbing headache. the danger of
this interaction persists for two weeks after MAOI therapy is discontinued.
Pseudoepedrine may cause hypertension and arrhythmia in patients taking
tricyclic antidepressants and may antagonise the effects of hypertensive
therapy which interferes with sympathetic activity (i.e. alpha and beta
blockers).
Dexchlorpheniramine:
Concomitant use with alcohol and CNS depressants (hypnotics, sedatives,
tranquillisers, etc.) may potentiate the sedative effect of
dexchlorpheniramine. Monoamine oxidase (MAO) inhibitors prolong and
intensify the effects of antihistamines. The action of oral anticoagulants
may be inhibited by antihistamines. Laboratory Tests: Antihistamines
should be discontinued approximately 48 hours prior to skin testing
procedures since these drugs may prevent or diminish otherwise positive
reactions to dermal reactivity indicators.
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