Pbh Cold Relief Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Cold Relief Capsules
Paracetamol Cold Relief with Decongestant
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains:-
Paracetamol EP 300 mg
Caffeine EP 25 mg
Phenylephrine Hydrochloride EP 5 mg
For excipients, see 6.1
3 PHARMACEUTICAL FORM
Capsule, hard.
Green and yellow capsule.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the symptomatic relief of aches, pains, headache, sore throat, fever and nasal congestion associated with colds and influenza.
4.2 Posology and method of administration
Adults: 1 - 2 capsules every four hours up to a maximum of 4 doses in any 24 hours. The dosage should not be continued for more than 3 days without
consulting a doctor. Dose not to be repeated more frequently than 4 hour intervals.
The Elderly: One capsule every 4 hours.
Children under 12 years: Not recommended.
4.3 Contraindications
Paracetamol: known hypersensitivity to paracetamol.
Caffeine: should be given with care to patients with a history of peptic ulcer.
Phenylephrine hydrochloride: should be avoided or only used with great caution in hypersusceptible patients or those with hyperthyroidism, aneurism, hypertension, arteriosclerosis and cardiovascular disorders. As an alpha-adrenoceptor stimulant it may provoke uterine changes which can result in foetal asphyxia.
4.4 Special warnings and precautions for use
Do not exceed the stated dose.
If symptoms persist for more than 3 days consult your Doctor.
If you are receiving a course of medicinal treatment, consult your doctor before taking this product.
Do not take this medicine if you are taking any other product containing PARACETAMOL.
Contains PARACETAMOL
Do not give to children under 12 years.
Paracetamol should be given with care to patients with impaired liver or kidney function, and to patients taking other drugs that affects the liver. Liver function tests may be required at periodic intervals during high dose or long term therapy, especially in patients with pre-existing hepatic disease. Care should be taken in giving paracetamol to patients with alcohol dependence. Care should be taken giving paracetamol to patients with glucose-6-phosphate dehydrogenase deficiency. Caution is advised in patients with cardiovascular disease or those on a sodium restricted diet who should not use buffered paracetamol without medical advice.
4.5 Interaction with other medicinal products and other forms of interaction
Paracetamol: Alcohol and hepatotoxic medications reduce the capacity of the liver to metabolise paracetamol. Chronic use of paracetamol enhances the effects of anticoagulants. Cholestyramine reduces absorption of paracetamol. Metoclopramide and domperidone accelerate absorption of paracetamol. Plasma levels of chloramphenicol may increase with concurrent administration of paracetamol.
Concurrent use of paracetamol with NSAID may increase the risk of adverse renal effects. Prolonged concurrent use of paracetamol and aspirin or other salicylate may increase the risk of renal damage (such as analgesic nephropathy and renal papillary necrosis).
Effervescent preparations of paracetamol which contain a high sodium concentration may increase the risk of oedema and/or hypernatraemia when administered concurrently with adrenocorticoids, anabolic steroids, androgens or ACTH. Oral tetracyclines may form non-absorbable complexes with the buffering agents present in effervescent preparations; these medications should be taken 1-2 hours apart.
Interactions with laboratory tests: paracetamol may interfere with a number of test results; blood glucose, urate, bilrubin, lactate dehydrogenase and transaminase concentrations, urine 5-hydroxyindoleacetic acid determination, prothrombin time and pancreatic function using benitromide.
Caffeine: The effect of caffeine may be enhanced by izoniazid and meprobamate. It is claimed to enhance the action of ergotamine.
Phenylephrine Hydrochloride: The hypersensitive effect can be markedly enhanced by the administration of debrisoquine. Rare severe hypertension may be associated with 2, 4, beta adrenoceptor-blocking drugs.
4.6 Fertility, Pregnancy and lactation
Paracetamol : Crosses the placenta. There is no known hazard in normal dosage, but like all non-essential medications paracetamol should be avoided especially during the first trimester unless considered essential by the physician. Paracetamol is excreted in breast milk but there is no evidence that this is clinically significant.
Caffeine: During pregnancy the half-life of caffeine is prolonged. This is a possible contributory factor in hyperemesis gravidarum. It is recommended that no medicines should be taken during pregnancy unless recommended by a doctor.
Phenylephrine Hydrochloride: As an alpha-adrenoceptor stimulant it may provoke uterine changes which can result in foetal asphyxia.
4.7 Effects on ability to drive and use machines
Phenylephrine Hydrochloride: May cause drowsiness. If affected, do not drive or operate machinery. Avoid alcoholic drinks
4.8 Undesirable effects
(Frequency and Seriousness)
Paracetamol: Side effects are usually mild, though haematological reactions, blood dyscrasias and anaemia have been reported. Rashes and other allergic reactions occur occasionally. There are isolated reports of thrombocytopenic purpura, methaemoglobinaemia, and agranulocytosis. Rarely renal colic, sterile pyuria, uraemia, azotaemia, acute pancreatitis and hepatitis have occurred.
Caffeine: Nausea, insomnia, headache may be experienced. Excessive consumption of beverages containing caffeine may cause headaches, irritability and signs of anxiety neurosis. Large doses may cause restlessness, excitement, muscle tremor, tinnitus, scintillating scotoma, tachycardia and extrasystoles. Caffeine increases gastric secretions and may cause gastric ulceration.
Phenylephrine hydrochloride: High blood pressure with headache, vomiting and rarely palpitations, perforation of the nasal septum and possible cardiovascular effect on a diabetic patient. Also rare reports of allergic reactions.
4.9 Overdose
(Symptoms, Emergency Procedures, Antidotes)
Paracetamol: Potentially fatal liver damage is likely in adults who have taken 15 g or more of paracetamol. As little as 10 g may lead to liver necrosis. Patients taking enzyme-inducing drugs or with a history of alcoholism may have an increased susceptibility. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are employed), become irreversibly bound to liver tissue.
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, diarrhoea, anorexia, abdominal pain and increased sweating. 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, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias have been reported.
Prompt treatment is essential in the management of paracetamol overdosage. Any patient who has ingested about 7.5 g or more of paracetamol in the preceding 4 hours should undergo gastric lavage or induced emesis. Specific therapy with an antidote such as acetylcysteine or methionine may be necessary. Acetylcysteine may be given either intravenously or by mouth or methionine may be given by mouth within 10-12 hours of ingestion of the overdose. Generally treatment is required if the blood-paracetamol concentration is higher than a line (the '200' line) drawn on a semi-log/linear paper joining the points 200 mg per litre (1.32 mmol per litre) at 4 hours and 30 mg per litre (0.20 mmol per litre) at 15 hours following ingestion.
Determination of the concentration before 4 hours is not considered to give a reliable measurement. Administration of acetylcysteine or methionine more than 15 hours after the overdose is generally ineffective and may be associated with an exacerbation of any liver abnormality and may precipitate hepatic encephalopathy. Liver function tests should be performed at 24 hour intervals for at least 96 hours post ingestion if the plasma paracetamol concentration indicates a potential for hepatotoxicity. Renal and cardiac function should be monitored and supportive treatment should be directed at maintaining fluid and electrolyte balance and correcting hypoglycaemia. Haemodialysis and haemoperfusion have been used with some success by peritoneal dialysis in ineffective.
Caffeine: symptoms - emesis and convulsions may occur. No specific antidote. However, treatment is usually fluid therapy. Fatal poisoning is rare. If symptoms become apparent or overdose is suspected, consult a doctor immediately.
Phenylephrine hydrochloride: not known - if overdose is suspected consult a doctor immediately.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Paracetamol is an effective analgesic and antipyretic agent but has only weak anti-inflammatory properties. Its mechanism of action is not fully understood. It has been suggested that it may act predominantly by inhibiting prostaglandin synthesis in the CNS and to a lesser extent through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitise pain receptors to mechanical or chemical stimulation. Paracetamol probably produces an antipyretic action by a central effect on the hypothalamic heat-regulating centre to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus. The drug has no effect on the cardiovascular and respiratory systems, and unlike salicylates it does not cause gastric irritation or bleeding.
Caffeine acts on the central nervous system on muscle including cardiac muscle and the kidneys. Its action on the CNS is mainly on the higher centres and produces a condition of wakefulness and increased mental activity. It facilitates the performance of muscular work and increases the total amount of work that can be performed by a muscle. It may stimulate the respiratory centre, increasing the rate and depth of respiration. Its stimulant action on the medullary vasomotor centre is usually compensated by its peripheral vasodilator effect on the arterioles, so that blood pressure usually remains unchanged. The diuretic action of caffeine has been accounted for in many ways. It may increase renal blood flow and glomerular filtration rate, but its main action may be due to the regulation of the normal tubular absorption.
The xanthines are rarely of great value in promoting increased renal function when this is depressed. Caffeine is claimed to enhance the action of ergotamines and is frequently given with ergotamine in the treatment of migraine.
Phenylephrine hydrochloride is a sympathomimetic with many direct effects on adrenergic receptors. It has predominantly alpha-adrenergic activity and is without stimulating effects on the CNS. Its pressor activity is weaker than that of noradrenaline but of longer duration. After injection it has produced peripheral vasoconstriction and increased arterial pressure; it also causes reflex bradycardia. It increases blood flow to the skin and to the kidneys. It has been used in the treatment of hypotensive states eg. circulatory failure, spinal anaesthesia or hypertension following the use of chlorpromazine and other phenothiazines. Phenylephrine hydrochloride may be given for the relief of nasal congestion. Locally it is used as a nasal decongestant in rhinitis and sinusitis. In ophthalmology it is employed as a mydriatic and conjunctival decongestant in open angle glaucoma. It is sometimes used to temporarily lower intra-ocular pressure.
There is no pharmacological information with regard to the compound preparation. However, there is no evidence to suggest that any of the actions described above are in any way impinged upon by the other active ingredients.
Pharmacokinetic properties
5.2
Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion.
It is metabolised in the liver (90-95 %) and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5 % is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 4 hours. Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.
A minor hydroxylated metabolite (n-acetyl-p-benzoquinoneimine) which is usually produced in very small amounts by mixed-function oxidases in the liver and which is usually detoxified by conjugation with liver glutathione may accumulate following paracetamol overdosage and cause liver damage. The time to peak concentrations of paracetamol is 0.5 to 2 hours, the time to peak effect 1 to 3 hours and the duration of action 3 to 4 hours.
Caffeine: is readily absorbed after oral, rectal or parenteral administration, but absorption from the gastrointestinal tract may be erratic. There is little evidence of accumulation in any particular tissue. Caffeine passes readily into the central nervous system and into saliva. Concentrations have also been detected in breast milk. Caffeine is metabolised almost completely and is excreted in the urine as 1-methyluric acid, 1-methylxanthine and other metabolises with only about 1 % unchanged.
Phenylephrine hydrochloride: has reduced bioavailability from the gastrointestinal tract owing to first pass metabolism by monoamine oxidase in the gut and liver. When injected intramuscularly it takes 10 to 15 minutes to act and subcutaneous and intramuscular injections are effective for about an hour. Intravenous injections are effective for about 20 minutes.
5.3 Preclinical safety data
No additional preclinical data.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Maize Starch
Colloidal Anhydrous Silica Magnesium Stearate
Capsule contains;
Gelatin
Patent Blue V (E13l)
Iron Oxide(E172) Quinoline Yellow (E104) Titanium Dioxide (E171)
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 Years from the date of manufacture.
6.4 Special precautions for storage
Do not store above 25°C.
Blister Packs: Keep the container in the outer carton in order to protect from light.
Tablet bottles: Store in the original container in order to protect from light.
6.5 Nature and contents of container
Blister Pack
Capsules are packed individually in pre-moulded PVC film and sealed with aluminium foil. Pack sizes of 16, 20, 24 capsules
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Max Remedies Limited
William Nadin Way Swadlincote DE11 0BB United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 31308/0041
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25/02/2009
10 DATE OF REVISION OF THE TEXT
04/11/2014