Each 5 ml contains:

active ingredients: acetaminophen (paracetamol) – 160.0 mg, chlorpheniramine maleate- 1.0 mg, phenylpropanolamine HCl – 5.0 mg;

excipients: sodium saccharin, propylene glycol, glycerin, methylparaben, propylparaben, aroma orange, color yellow E-110, water purified.

Paracetamol

4′-Hydroxyacetanilide; 4-acetamidophenol; 103-90-2

Phenylephrine Hydrochloride

(1R)-1-(3-Hydroxyphenyl)-2-(methylamino)ethanol hydrochloride; 61-76-7

Phenylpropanolamine Hydrochloride

Benzenemethanol, α-(1-aminoethyl)-, hydrochloride, (R*S*)-, (±);
(±)-Norephedrine hydrochloride [154-41-6]

Analgesic, antipyretic, histamine H1-receptor antagonist, sympathomimetic; L05X.

Acetaminophen is a clinically proven analgesic-antipyretic. Acetaminophen produces analgesia by elevation of the pain threshold and antipyresis through action on the hypothalamic heat-regulating center. Acetaminophen is equal to aspirin in analgesic and antipyretic effectiveness and it is unlikely to produce many of the side effects associated with aspirin and aspirin-containing products.

Phenylpropanolamine hydrochloride is a sympathomimetic amine, which provides temporary relief of nasal congestion.

Chlorpheniramine maleate is an antihistamine that provides temporary relief of runny nose, sneezing and watery and itchy eyes.

Unless your doctor approves, do not use these products if you have heart disease, high blood pressure, thyroid disease, diabetes, high pressure within the eye (glaucoma), an enlarged prostate gland, or a breathing problem such as emphysema or chronic bronchitis.

– Dizziness; drowsiness; dry mouth, nose, or throat; headache; nausea; nervousness; trouble sleeping.

Seek medical attention right away if any of these SEVERE side effects occur:

-Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; dark urine or pale stools; difficulty urinating; hallucinations; high blood pressure; rapid pulse; severe nervousness; stomach pain; tremors; unusual fatigue; yellowing of the skin or eyes.

If you are taking a tranquilizer, or a sleep aid, do not take this medication without your doctor’s approval; the combination could cause extreme drowsiness. For the same reason, avoid alcohol while taking these products.

Paracetamol is the principal para-aminophenol derivative in use. Paracetamol has analgesic and antipyretic properties and weak anti-inflammatory activity. The mechanism of analgesic action remains to be fully elucidated, but may be due to inhibition of prostaglandin synthesis both centrally and peripherally. Paracetamol is used for the relief of mild to moderate pain and minor febrile conditions.

PHARMACOKINETICS

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 10 to 60 minutes after oral administration. Paracetamol is distributed into most body tissues. It crosses the placenta and is present in breast milk. Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations. The elimination half-life of Paracetamol varies from about 1 to 3 hours.

Paracetamol is metabolized predominantly in the liver and excreted in the urine mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol. A minor hydroxylated metabolite (n-acetyl-p-benzoquinoneimine), which is usually produced in very small amounts by mixed-function oxidases in the liver and kidney and which is usually detoxified by conjugation with glutathione, may accumulate following Paracetamol overdosage and cause tissue damage.

USES AND ADMINISTRATION

Paracetamol, a para-aminophenol derivative, has analgesic and antipyretic properties and weak anti-inflammatory activity. Paracetamol is given by mouth for mild to moderate pain and for fever. Paracetamol is often the analgesic or antipyretic of choice especially in patients in whom salicylates or other NSAIDs are contra-indicated. Such patients include asthmatics or those with a history of peptic ulcer, or children. Its use is also generally preferred in elderly patients.

The usual dose by mouth is 0.5 to 1 g every 4 to 6 hours up to a maximum of 4 g daily. Usual doses in children are: under 3 months, 10 mg per kg body-weight (reduced to 5 mg per kg if jaundiced); 3 months to 1 year, 60 to 120 mg; 1 to 5 years, 120 to 250 mg; 6 to 12 years, 250 to 500 mg. These doses may be given every 4 to 6 hours when necessary up to a maximum of 4 doses in 24 hours.

ADVERSE EFFECTS AND TREATMENT

Side effects of Paracetamol are rare and usually mild, although haematological reactions including thrombocytopenia, leucopenia, pancytopenia, neutropenia, and agranulocytosis have been reported. Skin rashes, and other hypersensitivity reactions occur occasionally.

Overdosage with Paracetamol can result in severe liver damage and sometimes, acute renal tubular necrosis. Prompt treatment with acetylcysteine or methionine is essential.

Overdosage. Acute overdosage with Paracetamol, whether accidental or deliberate, is relatively common and can be extremely serious because of the narrow margin between therapeutic and toxic doses. Ingestions of as 10 to 15 g of Paracetamol by adults may cause sever hepatocellular necrosis and, less often, renal tubular necrosis. Indeed, any patient should be considered at risk of severe liver damage if they have ingested more than 150 mg per kg body-weight of Paracetamol or 12 g or more in total, whichever is the smaller.

Early features of overdosage such as nausea and vomiting usually settle within 24 hours; other early symptoms may include lethargy and sweating. Abdominal pain may be the first indication of liver damage, which is not usually apparent for 24 to 48 hours and sometimes may be delayed for up to 4 to 6 days after ingestion. Liver damage is generally at a maximum 72 to 96 hours after ingestion. Hepatic failure, encephalopathy, coma, and death may result. Complications of hepatic failure include acidosis, cerebral oedema, haemorrhage, hypoglycaemia, hypotension, infection, and renal failure. An increasing prothrombin time is a reliable indicator of deteriorating liver function and it is recommended by some that the prothrombin time should be measured regularly. Measurement of serum concentrations of aspartate aminotransferase and alanine aminotransferase is also considered to be of value. Patients receiving enzyme-inducing drugs or those with a history of alcohol abuse are at special risk of hepatic damage, as may be patients suffering from malnutrition such as those with anorexia or AIDS. It has also been suggested that fasting may predispose to hepatotoxicity.

Toxicity following overdosage with Paracetamol has been attributed to the production of a minor but highly reactive metabolite, N-acetyl-p-benzoquinoneimine (NABQI) by mixed function oxidaze enzymes in the liver and kidney. The amount of NABQI produced after normal doses of Paracetamol is usually completely detoxified by conjugation with glutathione and excreted as mercaptopurine and cysteine conjugates. In Paracetamol overdosage, tissue stores of glutathione become depleted, allowing NABQI to accumulate and bind to sulfhydryl groups within hepatocytes causing cell damage. Substances capable of replenishing depleted stores of glutathione, such as acetylcysteine or methionine, are thus used as antidotes in Paracetamol overdosage. Acetylcysteine may also be involved in the repair of damaged tissue.

Treatment of Paracetamol overdosage: Prompt treatment is essential, even when there are no obvious symptoms, and all patients should be admitted to hospital; full supportive measures should also be instituted. Activated charcoal may be given to reduce gastrointestinal absorption, if it can be given within 1 hour of the overdose, and if more than 150 mg per kg of Paracetamol has been ingested. However, if acetylcysteine or methionine is to be given by mouth the charcoal is best cleared from stomach to prevent it reducing the absorption of antidote.

Choice of antidote: acetylcysteine is most effective when administered during the first 8 hours following ingestion of the overdosage and the effect diminishes progressively thereafter. In the UK, an initial dose of 150 mg per kg body-weight of acetylcysteine in 200 ml of glucose 5% is given intravenously over 15 minutes, followed by an intravenous infusion of 50 mg per kg in 500 ml of glucose 5% over the next 4 hours and then 100 mg per kg in one litre over the next 16 hours. Sodium chloride 0.9% may be used where glucose 5% is unsuitable. The volume of intravenous fluids should be modified for children. In the USA, acetylcysteine is given by mouth in an initial dose of 140 mg per kg as a 5% solution followed by 70 mg per kg every 4 hours for an additional 17 doses.

Methionine is an alternative to acetylcysteine and, likewise, is most effective when given as early as possible following Paracetamol overdosage. The usual dose to methionine is 2.5 g by mouth every 4 hours for 4 doses starting less than 10 to 12 hours after ingestion of the paracetamol and provided the patient is not vomiting.

PREGNANCY AND LACTATION

The use of Paracetamol should be avoided in all trimesters of pregnancy.

Since it is not known if Paracetamol is distributed into milk, the drug should be used with caution in nursing women.

PRECAUTIONS

Paracetamol should be given with care to patients with impaired kidney or liver function. It should also be given with care to patients with alcohol dependence.

INTERACTIONS

The risk of Paracetamol toxicity may be increased in patients receiving other potentially drugs or drugs that induce liver microsomal enzymes. The absorption of Paracetamol may be accelerated by drugs such as metoclopramide. Excretion may be affected and plasma concentrations altered when administered with probenecid. Colestyramine reduces the absorption of paracetamol if given within one hour of Paracetamol administration.

PHARMACOLOGY

Chlorpheniramine maleate, an alkylamine derivative, is a sedating antihistamine that causes a moderate degree of sedation; it also has antimuscarinic activity. Chlorpheniramine maleate diminishes or abolishes the major actions of histamine in the body by competitive, reversible blockade of histamine H1-receptor sites on tissues; it does not inactivate histamine or prevent its synthesis, nor, in most cases, its release. Histamine H1 receptors are responsible for vasodilation, increased capillary permeability, flare and itch reactions in the skin, and to some extent for contraction of smooth muscle in the bronchi and gastrointestinal tract.

Chlorpheniramine is a racemic mixture; the dextrorotatory isomer, dexchlorpheniramine, has approximately twice the activity of Chlorpheniramine by weight.

PHARMACOKINETICS

Chlorpheniramine maleate is absorbed relatively slowly from the gastrointestinal tract, peak plasma concentrations 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 inter-individual 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 didesmethylchlorpheniramine. 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.
A 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.

USES AND ADMINISTRATION

Chlorpheniramine maleate is used for symptomatic relief of allergic conditions including urticaria and angioedema, rhinitis, and conjunctivitis, and in pruritic skin disorders. It is common ingredient of compound preparations for symptomatic treatment of coughs and common cold.
Chlorpheniramine maleate is given by mouth in doses of 4 mg every 4 to 6 hours up to a maximum of 24 mg daily. Doses for children are: 1 to 2 years, 1 mg twice daily; 2 to 5 years, 1 mg every 4 to 6 hours (maximum 6 mg daily); 6 to 12 years, 2 mg every 4 to 6 hours (maximum 12 mg daily).

ADVERSE EFFECTS AND TREATMENT

OVERDOSAGE

Overdosage with sedating antihistamines is associated with antimuscarinic, extrapyramidal, and CNS effects. When CNS stimulation predominates over CNS depression, which is more likely in children or the elderly, it causes ataxia, excitement, tremors, psychoses, hallucinations, and convulsions; hyperpyrexia may also occur. Deepening coma and cardiorespiratory collapse may follow. In adults, CNS depression is more common with drowsiness, coma, and convulsions, progressing to respiratory failure and cardiovascular collapse.

Treatment of overdosage: treatment is symptomatic and supportive.

PRECAUTIONS

INTERACTIONS

Phenylpropanolamine is largely indirect-acting sympathomimetic with an action similar to that of ephedrine but less active as a CNS stimulant.

PHARMACOKINETICS

Phenylpropanolamine is readily and completely absorbed from the gastrointestinal tract, peak plasma concentrations being achieved about 1 to 2 hours after oral administration. It undergoes some metabolism in the liver, to an active hydroxylated metabolite, but up to 80 to 90% of a dose is excreted unchanged in the urine within 24 hours. The half-life has been reported to be about 3 to 5 hours.

Systemic absorption follows topical application.

USES AND ADMINISTRATION

ADVERSE EFFECTS

PRECAUTIONS

DRUG INTERACTIONS

Administration of Phenylpropanolamine may cause a hypertensive crisis in patients receiving and MAOI (including an RIMA). Phenylpropanolamine should be avoided or used with care in patients undergoing anaesthesia with cyclopropane, halothane, or other volatile anaesthetics. An increased risk of arrhythmias may occur if given to patients receiving cardiac glycosides, quinidine, or trycyclic antidepressants, and there is an increased risk of vasoconstrictor or pressor effects in patients receiving ergot alkaloids or oxytocin.

To be dispensed withоut prescription.

A clear yellow colored, flavored (orange) syrup.

Amber glass bottles containing 60 ml.

3 years.

Store at a room temperature (15-25⁰C), in a dry place, out of the reach of children. Protect from light.