1.
Composition
Phenylephrine 2.5 mg
Chlorpheniramine maleate 1mg
2. Dosage form and strength
Sinarest AF Oral Drops is available in 15 ml bottle.
3. Clinical particulars
3.1 Therapeutic indication
Sinarest AF Oral Drops is indicated for:
• Relief of nasal and sinus congestion.
• Relief of allergic symptoms of the nose or throat due to upper respiratory
tract allergies.
• Relief of sinus pain and headache.
• Adjunct with antibacterials in sinusitis, tonsillitis and otitis media.
3.2 Posology and method of administration
The usual recommended oral dose of Sinarest AF Oral Drops is:
1-6 months =0.2 ml thrice or four times a day
7-12 months= 0.2-0.4 ml thrice or four times a day
1-2 years =0.4-0.8 ml thrice or four times a day
3.3 Contraindication
The use of Sinarest AF Oral Drops is contraindicated in patients with:
• Hypersensitivity to any of the ingredients of the formulation.
• Severe hypertension.
3.4 Special warnings and precautions for use
• In case a hypersensitivity reaction occurs which is rare, Sinarest AF Oral Drops
should be discontinued.
• Sinarest AF Oral Drops contains Paracetamol and therefore should not be
used in conjunction with other Paracetamol containing products.
• Sinarest AF Oral Drops should be used with caution in patients with renal or
hepatic dysfunction, diabetes mellitus, hyperthyroidism, cardiovascular
problems, epilepsy and closed angle glaucoma.
3.5 Drug interactions
Clinically significant drug interactions may occur on concomitant administration of Sinarest
AF Oral Drops with monoamine oxidase inhibitors, tricyclic antidepressants, beta-adrenergic
agents, and methyldopa, reserpine and veratrum alkaloids.
3.6 Use in special population
Pediatric: Safe.
Geriatric: Elderly population may be at greater risk for the side-effects.
Liver impairment: Use with caution.
Renal failure: Use with caution.
Pregnancy and lactation: US Food and Drug Administration (FDA) has
specified Chlorphenamine maleate as a pregnancy category B drug which
indicates that animal and human studies have failed to demonstrate a risk to
the fetus in any trimester. Paracetamol has been specified as a pregnancy
category C drug which indicates that animal studies show an adverse effect
on the fetus but there are no teratogenic studies of Paracetamol in pregnant
women. Sinarest is recommended to be taken during pregnancy only under
doctor's recommendation.
3.7 Effects on ability to drive and use machine
Chlorpheniramine in Sinarest AF Oral Drops may cause sedation. It is advisable not to drive
or operate machinery when on treatment with Sinarest AF Oral Drops.
3.8 Undesirable effects
Sinarest AF Oral Drops is generally well tolerated and adverse events are rare.
Hypersensitive individuals may display ephedrine-like reactions such as tachycardia,
palpitations, headache, dizziness and nausea. Use of sympathomimetics has been associated
with fear, anxiety, restlessness, tremor, weakness, dysuria, insomnia, hallucinations and
convulsions. Chlorpheniramine in Sinarest AF Oral Drops may cause sedation.
3.9 Overdose
There is limited experience of overdose with Sinarest AF Oral Drops. Initiate general
symptomatic and supportive measures in all cases of overdosages where necessary.
4. Pharmacological properties
4.1 Mechanism of action
Phenylephrine decreases nasal congestion by acting on α1-adrenergic receptors in the
arterioles of the nasal mucosa to produce constriction; this leads to decreased edema and
increased drainage of the sinus cavities.
In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast
cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex
series of events occurs that eventually leads to cell-degranulation and the release of
histamine (and other chemical mediators) from the mast cell or basophil. Once released,
histamine can react with local or widespread tissues through histamine receptors.
Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing,
headache, tachycardia, and bronchoconstriction. Histamine also increases vascular
permeability and potentiates pain. Chlorpheniramine maleate binds to the histamine H1
receptor. This block the action of endogenous histamine, which subsequently leads to
temporary relief of the negative symptoms brought on by histamine.
4.2 Pharmacodynamic properties
Phenylephrine is a powerful vasoconstrictor. It is used as a nasal decongestant and
cardiotonic agent. Phenylephrine is a postsynaptic α1-receptor agonist with little effect on
β-receptors of the heart. Parenteral administration of phenylephrine causes a rise in systolic
and diastolic pressures, a slight decrease in cardiac output, and a considerable increase in
peripheral resistance; most vascular beds are constricted, and renal, splanchnic, cutaneous,
and limb blood flows are reduced while coronary blood flow is increased. Phenylephrine
also causes pulmonary vessel constriction and subsequent increase in pulmonary arterial
pressure. Vasoconstriction in the mucosa of the respiratory tract leads to decreased edema
and increased drainage of sinus cavities.
Chlorpheniramine maleate is a histamine H1 antagonist of the alkylamine class. It competes
with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal
tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing,
watery and itchy eyes, and runny nose due to hay fever and other upper respiratory
allergies.
4.3 Pharmacokinetic properties
Phenylephrine has low oral bioavailability owing to irregular absorption and first-pass
metabolism by monoamine oxidase in the gut and liver. When injected subcutaneously or
intramuscularly it takes 10 to 15 minutes to act; subcutaneous and intramuscular injections
are effective for up to about 1 hour and up to about 2 hours, respectively. Intravenous
injections are effective for about 20 minutes. Systemic absorption follows topical
application.
Chlorphenamine maleate is absorbed relatively slowly from the gastrointestinal tract, peak
plasma concentrations occurring about 2.5 to 6 hours after oral doses. Bioavailability is low,
values of 25 to 50% having been reported. Chlorphenamine appears to undergo
considerable first-pass metabolism. About 70% of chlorphenamine in the circulation is
bound to plasma proteins. There is wide inter individual variation in the pharmacokinetics of
chlorphenamine; values ranging from 2 to 43 hours have been reported for the half-life.
Chlorphenamine is widely distributed in the body, and enters the CNS. Chlorphenamine
maleate is extensively metabolised. Metabolites include desmethyl- and
didesmethylchlorphenamine. Unchanged drug and metabolites are excreted primarily in the
urine; excretion is dependent on urinary pH and flow rate. Only trace amounts have been
found in the faeces. Duration of action of 4 to 6 hours has been reported; this is shorter
than may be predicted from pharmacokinetic parameters. More rapid and extensive
absorption, faster clearance, and a shorter half-life have been reported in children.
5. Nonclinical properties
5.1 Animal Toxicology or Pharmacology
Not required.
6. Description
Already mentioned and covered in the above points.
7. Pharmaceutical particulars
7.1 Incompatibilities
There are no known incompatibilities.
7.2 Shelf-life
36 months.
7.3 Storage and handling instructions
Store below 30 ⁰C in a dark and dry place.