Summary of medicine characteristics - PERRIGO PARACETAMOL GUAIFENESIN PHENYLEPHRINE HYDROCHLORIDE 250 MG / 100 MG / 5 MG TABLETS
1 NAME OF THE MEDICINAL PRODUCT
Perrigo Paracetamol, Guaifenesin, Phenylephrine Hydrochloride 250 mg/100 mg/5 mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
3 PHARMACEUTICAL FORM
Film-coated tablet
White capsule shaped tablet, embossed with “PGP”, free from specks and blemishes.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the relief of symptoms associated with colds and flu, including aches and pains, headache, blocked nose and sore throat, chills and chesty cough.
4.2 Posology and method of administration
Route of administration : Oral.
Take tablets with water. Swallow whole, do not chew.
For all indications:
Adults, the elderly and children aged 12 years and over:
Two tablets every 4–6 hours when necessary to a maximum of 4 doses in 24 hours.
Children under 12 years:
Not to be used unless recommended by a doctor.
Dosage should not be continued for longer than 3 days without consulting a doctor.
4.3 Contraindications
Hypersensitivity to paracetamol, guaifenesin or phenylephrine or any of the other ingredients.
Hypertension (high blood pressure), hyperthyroidism, diabetes, serious heart disease, cardiovascular disorders or those patients receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors (see Section 4.5).
Those taking tricyclic anti-depressant drugs (see Section 4.5).
Phaeochromocytoma.
Prostatic enlargement or urinary retention.
Use in patients with glaucoma, including closed angle glaucoma.
Hepatic and renal impairment.
Use in patients who are currently receiving other sympathomimetic drugs (see Section 4.5).
Pregnancy (see Section 4.6)
Porphyria.
4.4 Special warnings and precautions for use
The physician or pharmacist should check that sympathomimetic containing preparations are not simultaneously administered by several routes i.e. orally and topically (nasal, aural and eye preparations).
Care is advised in the administration of paracetamol to patients with severe renal or hepatic impairment. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.
Use with caution in patients with circulatory disorders such as Raynaud’s
Phenomenon. Patients with prostatic hypertrophy may have increased difficulty with micturition.
Sympathomimetic-containing products should be used with great care in patients suffering from angina.
Sympathomimetic-containing products may act as cerebral stimulants giving rise to insomnia, nervousness, hyperpyrexia, tremor and epileptiform convulsions.
This product should not be used by patients taking other sympathomimetics (such as decongestants, appetite suppressants and amphetamine-like psychostimulants).Patients suffering from chronic cough or asthma should consult a physician before taking this product. Patients should stop using the product and consult a health care professional if cough lasts for more than 3 days or comes back, or is accompanied by a fever, rash or persistent headache. Do not take with a cough suppressant. Concomitant use of other paracetamol containing products should be avoided. If symptoms persist consult your doctor.
Do not exceed the recommended dose.
Do not take with alcohol
If symptoms persist or worsen, consult your doctor. Keep out of the sight and reach of children.
Special label warnings
If you are taking medication or are under medical care, consult your doctor before using this medicine. Do not take with any other flu, cold or decongestant products.
Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor.
Keep out of the sight and reach of children.
Contains paracetamol. Do not take anything else containing paracetamol while taking this medicine. Talk to a doctor at once if you take too much of this medicine even if you feel well.
Special leaflet warnings
Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor.
Keep out of the sight and reach of children.
Contains paracetamol. Do not take anything else containing paracetamol while taking this medicine. Talk to a doctor at once if you take too much of this medicine even if you feel well. This is because too much paracetamol can cause delayed, serious liver damage.
If you are taking medication or are under medical care, consult your doctor before using this medicine. Do not take with any other flu, cold or decongestant products.
4.5 Interaction with other medicinal products and other forms of interaction
PARACETAMOL
The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine.
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding, occasional doses have no significant effect.
Drugs which induce hepatic microsomal enzymes, such as alcohol, barbiturates, monoamine oxidase inhibitors and tricyclic antidepressants, may increase the hepatotoxicity of paracetamol particularly after overdosage. Contraindicated in patients currently receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors because of a risk of hypertensive crisis.
PHENYLEPHRINE HYDROCHLORIDE
Phenylephrine may adversely interact with other sympathomimetics, vasodilators and beta blockers. Concomitant use of phenylephrine with other sympathomimetic amines can increase the risk of cardiovascular side effects.
Hypertensive interactions occur between sympathomimetic amines such as phenylephrine and monoamine oxidase inhibitors.
Sympathomimetic-containing products should be used with great care in patients receiving phenothiazines or tricyclic antidepressants.
Sympathomimetic-containing products should be used in caution in patients receiving digitalis, beta-adrenergic blockers, guanethidine, reserpine, methyldopa or anti- hypertensive agents.
Concurrent use with halogenated anaesthetic agents such as chloroform, cyclopropane, halothane, enflurane or isoflurane may provoke or worsen ventricular arrhythmias.
This medicine should not be used with enzyme inducers such as alcohol.
Phenylephrine should be used with caution in combination with Ergot alkaloids (ergotamine and methylsergide), increase risk of ergotism.
GUAIFENESIN
If urine is collected within 24 hours of a dose of this product a metabolite of guaifenesin may cause a colour interference with laboratory determinations of urinary-5– hydroxyindolacetic acid (5-HIAA) and vanillylmandelic acid (VMA).
4.6 Fertility, pregnancy and lactation
PARACETAMOL
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use.
Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast-feeding.
GUAIFENESIN
The safety of guaifenesin in pregnancy and breast-feeding has not been fully established but this constituent is not thought to be hazardous. However the product should only be used in pregnancy when considered essential by the doctor.
PHENYLEPHRINE HYDROCHLORIDE
The safety of this medicine during pregnancy and breast-feeding has not been established but in view of a possible association of foetal abnormalities with first trimester exposure to phenylephrine, the use of the product during pregnancy should be avoided.
Phenylephrine should not be taken during pregnancy as it has been reported to cause foetal hypoxia.
Due to the vasconstrictive properties of phenylephrine, the product should be used with caution in patients with a history of pre-eclampsia.
Phenylephrine may reduce placental perfusion and the product should be used in pregnancy only if the benefits outweigh this risk. There is no information on use in lactation.
In view of the lack of data on the use of phenylephrine during breast-feeding, this medicine should not be used during breast-feeding. Excretion in breast milk is reported to be minimal.
This product should not be used during pregnancy without medical advice.
4.7 Effects on ability to drive and use machines
Patients should be advised not to drive or operate machinery if affected by dizziness.
4.8 Undesirable effects
The active ingredients are usually well tolerated in normal use. PARACETAMOL
Blood and lymphatic system disorders
Frequency unknown
Agranulocytosis; Blood disorders; Thrombocytopenia
Hepatobiliary disorders
Frequency unknown Hepatic function abnormal
Immune system disorders
Frequency unknown
Anaphylaxis, Cutaneous hypersensitivity reactions including skin rashes, angioedema and Stevens Johnson syndrome, toxic epidermal necrolysis
Respiratory, thoracic and mediastinal disorders
Frequency unknown Bronchospasm*
Skin and subcutaneous tissue disorders
Frequency unknown
Angioedema; Dermatitis allergic; Rash
Very rare cases of serious skin reactions have been reported
Gastrointestinal disorders:
Frequency unknown
Acute pancreatitis
*There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.
GUAIFENESIN
Gastrointestinal disorders
Frequency unknown
Abdominal discomfort, nausea and vomiting
Immune system disorders
Frequency unknown
Hypersensitivity, Allergic reactions, angioedema, anaphylactic reactions
Respiratory
Frequency unknown
Thoracic and mediastinal disorders: Dyspnoea
Skin and subcutaneous disorders
Frequency unknown
Rash, urticaria
PHENYLEPHRINE HYDROCHLORIDE
Cardiac disorders
Frequency unknown
Arrhythmia; Palpitations; Bradycardia; Tachycardia
Eye disorders
Frequency unknown
Mydriasis, acute angle closure glaucoma, most likely to occur in those with closed angle glaucoma.
Gastrointestinal disorders
Frequency unknown
Nausea; Vomiting; Diarrhoea
General disorders and administration site condition
Frequency unknown
Irritability
Immune system disorders
Frequency unknown
Hypersensitivity reactions – including that cross-sensitivity may occur with other sympathomimetics
Nervous system disorders
Frequency unknown
Dizziness; Headache; Paraesthesia; Insomnia
Psychiatric disorders
Frequency unknown
Anxiety; Hallucination; Insomnia; Nervousness; Restlessness; Irritability; Excitability
Renal and urinary disorders
Frequency unknown
Dysuria; Urinary retention, This is most likely to occur in those with bladder
outlet obstruction, such as prostatic hypertrophy.
Skin and subcutaneous tissue disorders
Frequency unknown
Dermatitis allergic; Rash; Urticaria, Hypersensitivity reactions including crosssensitivity with other sympathomimetic may occur.
Vascular disorders
Frequency unknown
Peripheral coldness; Hypertension
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
PARACETAMOL
There is a risk of poisoning, particularly in elderly subjects, in young children, in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition. Overdosing may be fatal in these cases.
Symptoms generally appear within the first 24 hours and comprise: nausea, vomiting, anorexia, pallor, and abdominal pain.
Overdose of paracetamol in a single administration in adults or in children causes liver cell necrosis likely to induce complete and irreversible necrosis, resulting in hepatocellular insufficiency, metabolic acidosis and encephalopathy which may lead to coma and death. Simultaneously, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with increased prothrombin levels that may appear 12 to 48 hours after administration.
Liver damage is likely in adults who have taken more than the recommended amounts of paracetamol. It is considered that excess quantities of toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.
Some patients may be at increased risk of liver damage from paracetamol toxicity.
Risk Factors
If the patient
a) is on long term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.
b) Regularly consumes ethanol in excess of recommended amounts.
c) Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
Symptoms
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Management
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, see British National Formulary (BNF) overdose section.
Treatment with activated charcoal should be considered if the overdose has been taken within one hour. Plasma paracetamol concentration should be measured at four hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine, may be used up to 24 hours after ingestion of paracetamol, however, the maximum protective effect is obtained up to eight hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24 hours from ingestion should be discussed with the National Poisons Information Service (NPIS) or a liver unit.
GUAIFENESIN
Gastrointestinal discomfort has occasionally been reported with Guaifenesin.
Very large doses of guaifenesin can cause nausea and vomiting. Vomiting should be treated by fluid replacement and monitoring of electrolytes.
PHENYLEPHRINE HYDROCHLORIDE
Phenylephrine Hydrochloride may elevate blood pressure with headache, vomiting and rarely palpitations, tachycardia or reflex bradycardia, tingling and coolness of the skin. There have been rare reports of allergic reactions.
Symptoms of overdosage include irritability, palpitations, hypertension, difficulty in micturition, nausea, vomiting, thirst and convulsions.
Severe overdosage of phenylephrine may produce hypertension and associated reflex bradycardia, haemodynamic changes and cardiovascular collapse with respiratory depression.
Treatment measures include early gastric lavage and symptomatic and supportive measures. The hypertensive effects may be treated with an alphareceptor blocking agent (such as phentolamine mesylate 6 – 10 mg) given intravenously, and the bradycardia treated with atropine, preferably only after the pressure has been controlled. In severe overdosage gastric lavage and aspiration should be performed. Symptomatic and supportive measures should be undertaken, particularly with regard to cardiovascular and respiratory systems. Convulsions should be controlled with intravenous diazepam.
Chlorpromazine may be used to control marked excitement and hallucinations. Severe hypertension may need to be treated with an alpha-adrenoreceptor blocking drug, such as phentolamine. A beta blocker may be required to control cardiac arrhythmias.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic Group: Other analgesics and antipyretics & Other cold combination preparations
ATC code:N02B E51
Paracetamol is an analgesic and antipyretic.
Guaifenesin is an expectorant.
Phenylephrine Hydrochloride is a sympathomimetic decongestant.
The active ingredients are not known to cause sedation.
5.2 Pharmacokinetic properties
Paracetamol is rapidly absorbed from the gastrointestinal tract. It is metabolised in the liver and excreted in the urine, mainly as the glucuronide and sulphate conjugates.
Guaifenesin is rapidly absorbed after oral administration. It is rapidly metabolised by oxidation to ß-(2 methyoxy-phenoxy) lactic acid, which is excreted in the urine.
Phenylephrine hydrochloride is irregularly absorbed from the gastrointestinal tract and undergoes first-pass metabolism by monoamine oxidase in the gut and liver; orally administered phenylephrine thus has reduced bioavailability. It is excreted in the urine almost entirely as the sulphate conjugate.
5.3 Preclinical safety data
5.3 Preclinical safety dataPreclinical safety data on these active ingredients in the literature have not revealed any pertinent and conclusive findings which are of relevance to the recommended dosage and use in the product and which have not already been mentioned elsewhere in this Summary.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Core:
Microcrystalline cellulose
Stearic acid
Povidone
Film Coat:
Hypromellose
Polyethylene glycol
6.2 Incompatibilities
None known.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Do not store above 25°C.