HAPACOL FLU
HAPACOL FLU
INFORMATION FOR MEDICAL STAFF
COMPOSITION:
Paracetamol ............................ 500 mg Chlorpheniramine maleate .................... 2 mg
Phenylephrine Hcl..................... 10 mg Excipients q.s ................................. 1 tablet
(Pregelatinized starch (National 78-1551), wheat starch, colloidal silicon dioxide, sodium benzoate, PVP K30, croscarmellose sodium, magnesium stearate, talc, hypromellose 2910 (6cp), hypromellose 2910 (15cp), PEG 6000, titanium dioxide, yellow ferric oxide).
PHARMACEUTICAL FORM: Film coated tablet.
PHARMACODYNAMIC PROPERTIES:
ATC CODE: R05X
Paracetamol produces analgesia, antipyresis. The drug acts on the hypothalamus to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. Paracetamol lowers body temperature in patients with fever but rarely lowers normal body temperature.
Phenylephrine HCl is a sympathomimetic with mainly direct effects on alpha 1-adrenergic receptors to produce vasoconstriction. Phenylephrine is topically vasoconstrictive, so it relieves nasal and sinusal congestion caused by cold.
Chlorpheniramine maleate is an antihistamine. By competitive blockage of histamine H1-receptor, chlorpheniramine reduces edema, urticaria in hypersensitivity reactions such as allergies and anaphylaxis. Chlorpheniramine also has anticholinergic effect.
PHARMACOKINETIC PROPERTIES:
Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Paracetamol has a plasma half-life of 1.25 to 3 hours. The drug is metabolized by the liver into N - acetyl - benzoquinoneimine, and is excreted through the kidneys.
Phenylephrine HCl is abnormally absorbed from the gastrointestinal tract by its direct metabolism on the gastrointestinal tract. Phenylephrine HCl is metabolized in the liver and intestine by MAO enzyme.
Chlorpheniramine maleate is well absorbed by oral administration. Chlorpheniramine is rapidly and extensively metabolized. Unchanged drug and active metabolites are excreted primarily in the urine; excretion is dependent on urinary pH and flow-rate. The half-life is about 12 to 15 hours.
PRESENTATION: Box of 10 blisters x 10 tablets. Box of 1 bottle x 100 tablets.
THERAPEUTIC INDICATIONS: For the treatment of symptoms of feverish cold, headache, musculoskeletal aches and pains associated with nasal congestion, coryza, rhinitis, catarrhal mucositis, sinusitis caused by flu or seasonal allergy.
DOSAGE & ADMINISTRATION: Orally taken every 4 to 6 hours.
Adults and children aged > 12 years: 1 - 2 tablets, not exceeding 6 tablets daily.
Or as directed by the physician.
CONTRAINDICATIONS:
Paracetamol: Hypersensitivity, severe hepatic failure, glucose-6-phosphate dehydrogenase deficiency.
Chlorpheniramine: Hypersensitivity, acute course of asthma, prostatomegaly, narrow-closed glaucoma, urinary retention, pyloric obstruction, nursing mothers, full term infants and late preterm infants, children younger than 2 years of age receiving nonprescription cough and cold preparations.
Phenylephrine: Severe cardiovascular disease, myocardial infarction, coronary artery disease, severe hypertension, AV block, severe arteriosclerosis, ventricular tachycardia, severe hyperthyroidism or narrow-closed glaucoma, hypersensitivity to the drug or cross-sensitivity with pseudoephedrine or other ingredients contained in the drug, and those patients who do not take or have taken, within the last 14 days, monoamine oxidase inhibitors and women in the first trimester of pregnancy.
PRECAUTIONS:
Paracetamol:
Paracetamol is relatively nontoxic in therapeutic doses. Dermatologic reactions including pruritic maculopapular rash and urticaria have been reported and other sensitivity reactions including laryngeal oedema, angioedema, and anaphylactoid reactions may occur rarely. Thrombocytopenia, leukopenia, and pancytopenia have been associated with the use of p-aminophenol derivatives, especially with prolonged administration of large doses. Neutropenia and thrombocytopenic purpura have been reported with paracetamol use. Rarely, agranulocytosis has been reported in patients receiving paracetamol.
Individuals with phenylketonuria and other individuals who must restrict their intake of phenylalanine should be warned that concurrent use of paracetamol and paracetamol-containing foods or drugs should not be recommended. Patients with hypersensitivity (asthma) should not use concurrently paracetamol and sulfite-containing food or drugs. Cautions should be taken in patients with previous anemia, hepatic and renal impairments. Because excessive consumption of alcohol may increase the risk of paracetamol-induced hepatotoxicity, it is advised to avoid or limit ingestion of alcohol.
Patients with liver failure, kidney failure, malnutrition, diabetes, hyperthyroidism, prostate tumors, vascular occlusive disease should be used with caution.
The physician should warn patients of serious signs of skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or Lyell's syndrome, acute generalized exanthematous pustulosis (AGEP).
Chlorpheniramine: Chlorpheniramine can increase the risk of urine retention, particularly in patients with prostatic hyperplasia, urinary obstruction, pyloro-duodenal obstruction; it causes more severity in myasthenia gravis patients. Sedative effect of chlorpheniramine has been reported to increase when taking alcohols and co-administrating with other tranquillisers. Use with caution in patients with chronic lung disease, apnee or breathing troubles, glaucoma, and in elderly patients. Risk of tooth decay occurs in patients having long-term treatment.
Phenylephrine: Phenylephrine should be used with caution in the elderly, patients with hyperthyroidism, slow heart rate, partial heart block, cardiomyopathy, severe arteriosclerosis, type 1 diabetes, bronchial asthma, intestinal obstruction, hyperthyroidism, benign prostatic hypertrophy. If symptoms, including irritation, dizziness, sleep disorders occur, the drug should be discontinued and notify the medical staff.
Pregnancy and lactation:
Pregnancy: The drug should be administered to pregnant women if really necessary. Serious reactions (including epilepsy) in newborn baby can happen if chlorpheniramine is used in the last trimester of pregnancy.
Lactation: A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Effects of the drug on works: The drug is not administered while driving a motor vehicle, operating machines, working at height, and other cases.
INTERACTIONS:
Paracetamol:
Chronic ingestion of paracetamol has been reported to potentiate the effects of coumarin- and indandione-derivative anticoagulants.
The possibility of severe hypothermia should be considered in patients receiving concomitant phenothiazine and antipyretic therapy (e.g., paracetamol).
The chronic, excessive consumption of alcohol may increase the risk of paracetamol-induced hepatotoxicity.
Anticonvulsants (including phenytoin, barbiturates, carbamazepine) that induce hepatic microsomal enzymes may increase paracetamol-induced liver toxicity.
Probenecid can reduce the elimination of paracetamol and increase the half-life of paracetamol.
Isoniazid and anti-TB drugs increase the toxicity of paracetamol to the liver.
Chlorpheniramine:
The antimuscarinic effects of antihistamines are enhanced by MAO inhibitors.
Ethanol or certain other central nervous system depressants such as hypnotics can potentiate the sedative effects of chlorphenamine.
Metabolism of phenytoin may be inhibited by chlorpheniramine with the possible development of phenytoin toxicity.
CYP3A4 inhibitors (e.g., dasatinib, pramilintid) increase the concentration or effect of chlorpheniramine. Chlorpheniramine reduces the effect of cholinesterase and betahistidin inhibitors.
Chlorphenamine is contraindicated in patients who have had treatment with MAO inhibitors within the last 14 days as the antimuscarinic properties of chlorphenamine are intensified by MAOIs.
Phenylephrine:
The vasopressor response to phenylephrine is decreased by prior administration of an alpha-adrenergic blocking agent such as phentolamine.
Phenothiazine drugs (e.g., chlorpromazine) may reduce the pressor effect and duration of action of phenylephrine.
Propranolol and beta-adrenergic blocking agents: The cardiostimulating effects of phenylephrine are blocked by prior administration of beta-adrenergic blocking drugs such as propranolol. Propranolol may be used to treat cardiac arrhythmias occurring during administration of phenylephrine.
Oxytocic drugs (oxytocin): When phenylephrine is used in conjunction with oxytoxic drugs, the pressor effects is potentiated.
Sympathomimetic agents: Combination products containing phenylephrine should not be used concomitantly with epinephrine or other sympathomimetic agents because tachycardia or other arrhythmias may occur.
General anesthetics: Administration of phenylephrine to patients who have received cyclopropane or halogenated hydrocarbon general anesthetics that increase cardiac irritability and seem to sensitize the myocardium to phenylephrine that result in arrhythmias. However, in usual therapeutic doses, phenylephrine is less likely to produce arrhythmias than is norepinephrine or metaraminol.
Monoamine oxidase inhibitors: The cardiac and pressor effects of phenylephrine are potentiated by prior administration of monoamine oxidase (MAO) inhibitors. Oral administration of phenylephrine to patients receiving a MAO inhibitor should be avoided.
Tricyclic antidepressants (e.g., imipramine) or guanethidine may also potentiate the vasopressor effects of phenylephrine.
Atropine sulfate and cycloplegics block the reflex bradycardia caused by phenylephrine and enhances the pressor response and mydriasis to phenylephrine.
An excessive rise in blood pressure may occur if phenylephrine is administered to patients receiving a parenteral injection of an ergot alkaloid.
The possibility that digitalis can sensitize the myocardium to the effects of sympathomimetic drugs should be considered.
Administration of furosemide or other diuretics may decrease arterial responsiveness to vasopressors such as phenylephrine.
Pilocarpine is a pupillary drug, which acts as an antagonistic and mydriatic effect of phenylephrine.
Guanethidine: Concurrent use of phenylephrine and guanethidine which was used for a long time by patients gives a response to a significantly increased mydriasis of phenylephrine and a very high blood pressure.
Levodopa: Decreased mydriasis of phenylephrine has been reported by concurent use of phenylephrine and levodopa.
Concurrent use of phenylephrine and bromocriptine should be avoided because of vasoconstriction events and hypertension.
ADVERSE EFFECTS:
Paracetamol:
Uncommon: 1/1,000 < ADR < 1/100
Skin disorders: Rash.
Gastrointestinal disorders: Nausea, vomiting.
Blood disorders: Hematopoietic dysfunction (neutropenia, thrombocytopenia and pancytopenia), anemia.
Renal disorders: Kidney disease, renal toxicity due to long-term abuse.
Rare: ADR < 1/1,000
Skin disorders: Stevens-Johnson syndrome, toxic epidermal necrotoxicosis, Lyell's syndrome, acute generalized exanthematous pustuslosis.
Other: Hypersensitivity reaction.
Chlorpheniramine:
Common: ADR > 1/100
Nervous disorders: CNS inhibition: slight to deep sleep, fatigue, dizziness, loss of coordination (sometimes paradoxical stimulation, especially in infants, high doses in the elderly or children). Headache, mental - motor disorders.
Muscarin effects: Dry mouth, sputum, blurred vision, urinary retention, constipation, gastroesophageal reflux.
Uncommon: 1/1,000 < ADR < 1/100
Gastrointestinal disorders: Nausea, vomiting, diarrhea, epigastric pain.
Cardiac disorders: Palpitations, arrhythmias.
Skin disorders: Rash, hypersensitivity reaction (bronchospasm, angioedema and anaphylaxis).
Rare: ADR < 1/1,000
Blood disorders: Agranulocytosis, leucopenia, hemolytic anemia, thrombocytopenia.
Other ADRs: Convulsions, sweating, muscle pain, paresthesia, extrapyramidal effects, sleep disorders, depression, confusion, tinnitus, hypotension, hair loss.
Phenylephrine:
Common: ADR > 1/100
CNS disorders: nervousness, restlessness, anxiety, sleep trouble, weakness, dizziness, chest pain, tremors, paresthesia.
Cardiovascular disorders: Hypertension.
Skin disorders: Paleness, whiteness, a feeling of coolness in the skin, bristle hairs.
Local: Local stimulation.
Uncommon: 1/1,000 < ADR < 1/100
Cardiovascular disorders: Hypertension associated with pulmonary edema, cardiac arrhythmia, slow heart rate, peripheral and visceral vasoconstriction, reduced blood flow to vital organs.
Respiratory disorders: Respiratory failure.
Nervous disorders: Excitement, hallucinations, delirium.
Skin disorders: Necrosis or exfoliation if extravasation occurs following subcutaneous administration.
Eye disorders: Release of pigments on the iris, blurring the cornea.
Rare: ADR < 1/1,000
Cardiovascular disorders: Myocarditis, pericardium hemorrhage.
OVERDOSE: Paracetamol toxicity may result from a single toxic dose, from repeated ingestion of large doses of paracetamol (e.g. 7.5 - 10 g daily for 1 - 2 days), or from chronic ingestion of the drug. Dose-dependent, hepatic necrosis is the most serious acute toxic effect associated with overdosage and potentially fatal.
Symptoms of paracetamol overdosage include nausea, vomiting, abdominal pain, cyanosis on skin, mucosa, and nails.
Management: In the event of severe paracetamol intoxication, full supportive measures should also be instituted. Gastric lavage should be carried out especially if the overdose was taken within the previous 4 hours.
The main detoxication therapy is use of sulfhydryl compound. N-acetylcysteine gives its effect followed by oral route or an intravenous infusion. N-acetylcysteine should be administered as soon as possible, preferably within 36 hours of overdosage. N-acetylcysteine is more effective if administered within 10 hours of overdosage. It can be diluted with water or alcohol-free drinks to a 5% solution and orally taken within 1 hour. Oral N-acetylcysteine is given as a 140 mg/kg body-weight initial dose followed by 70 mg/kg body-weight every four hours for 17 more doses.
Methionin, activated charcoal and/or saline cathartic are also used to treat overdose.
Symptoms of phenylephrine overdosage include hypertension, headache, seizures, cerebral hemorrhage, palpitation, extrasystole, and paresthesia. Bradycardia usually happens soon.
Management: Hypertension may be relieved by administration of alpha 1-adrenergic blocking agent (e.g., phentolamine
5 - 10 mg, IV injection).
Symptoms of chlorpheniramine overdosage include sedation, psychosis, seizures, apnea, seizures, anti-acetylcholine effect, ect.
Management: Gastric lavage or emesis with ipecacuanha syrup is given, then, administering activated charcoal and cathartic to reduce absorption. In cases of hypotension and arrhythmias, an active treatment should be applied. Seizures can be treated with diazepam or phenytoin intravenously. Blood transfusion may be required in severe cases.
Read the direction carefully before use.
Consult a physician for more information.
STORAGE CONDITIONS: Store in dry places, not exceeding 30oC, protect from light.
SHELF-LIFE: 36 months from the manufacturing date.
DATE OF REVISION OF THE TEXT: July 24, 2018.
INFORMATION FOR THE USER
Read all of this leaflet carefully before you start taking this medicine.
Keep out of reach of children.
Immediately tell your doctor or pharmacist of undesirable effects encountered during the treatment.
QUALITATIVE AND QUANTITATIVE COMPOSITION:
Paracetamol ................................ 500 mg Chlorpheniramine maleate .................. 2 mg
Phenylephrine HCl......................... 10 mg Excipients q.s.................................. 1 tablet
(Pregelatinized starch (National 78-1551), wheat starch, colloidal silicon dioxide, sodium benzoate, PVP K30, sodium croscarmellose, magnesium stearate, talc, hypromellose 2910 (6cp), hypromellose 2910 (15cp), PEG 6000, titanium dioxide, yellow ferric oxide).
PRODUCT DESCRIPTION: A yellow film coated caplet, plain on one side, a score line on the other, intact edges.
PRESENTATION: Box of 10 blisters x 10 tablets. Box of 1 bottle x 100 tablet