Sainsburys Cold Relief Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Sainsbury’s Cold Relief Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Paracetamol 300mg
Caffeine 25mg
Phenylephrine hydrochloride 5mg
For excipients, see section 6.1.
3 PHARMACEUTI CAL FORM
Capsules
Hard gelatine white and orange capsules
4 CLI NICAL PARTICULARS
4.1 Therapeutic indications
For relief of cold and flu symptoms, more specifically:
P aracetamol: To relieve headache.
C affeine: To relieve fatigue and drowsiness.
Phenylephrine hydrochloride: To reduce nasal congestion
4.2 Posology and method of administration
ADULTS AND CHILDREN OVER 12 YEARS:
One to two capsules every four hours as required, to a maximum of 8 capsules per any 24 hours.
The dose should not be repeated more frequently than 4 hour intervals.
The capsules are to be administered orally with water, preferably with or after food.
CHILDREN UNDER 12 YEARS:
Do not give to children under 12 years unless your doctor tells you to.
4.3 Contraindications
Hypersensitivity to paracetamol, caffeine, phenylephrine and/or any other constituents of the formulation.
Caffeine:
Do not give to patients with a history of peptic ulceration.
Phenylephrine hydrochloride
Do not give to hyper susceptible patients or those with severe hyperthyroidism, aneurysm, hypertension, arteriosclerosis phaeochromocytoma and prostatic enlargement.
Concomitant use with monoamine oxidase inhibitors, including moclobemide, is contraindicated.
4.4 Special warnings and precautions for use Paracetamol
Care is advised in the administration of paracetamol to patients with renal or hepatic impairment. The hazards of paracetamol overdose are greater in those with alcoholic liver disease. Paracetamol should be given with care to patients with alcoholic dependence.
Paracetamol is well tolerated by the majority of people with asthma. However, a small percentage of aspirin sensitive asthmatics are also sensitive to paracetamol. The likelihood of a reaction to paracetamol increases with a patient’s level of sensitivity to aspirin (see also 4.8 Undesirable Effects).
Caffeine
Care is advised in the administration of caffeine to patients with cardiac disease.
Phenylephrine
Care is advised in the administration of phenylephrine in patients with cardiovascular conditions such as Prinzmetal’s angina, thromboembolic disorders, following myocardial infarction or a history of ischaemic heart disease.
Care should be taken in administration of phenylephrine in patients with hyperthyroidism (see also section 4.3 Contraindications) or diabetes mellitus.
The following warnings appear in the leaflet and on the label:
Label-
Do not take with any other paracetamol-containing products.
Immediate medical advice should be sought in the event of an overdose, even if you feel well.
L
eaflet-
Immediate medical advice should be sought in the event of an overdose even if you feel well, because of the risk of delayed, serious liver damage.
Generally:
• Do not exceed the recommended dose.
• If symptoms persist consult your doctor.
• Do not give to children under twelve years except on advice from a doctor.
• Keep out of the reach and sight of children.
• Do not take for more than three days unless your doctor agrees.
Patients should be advised not to take other paracetamol-containing products concurrently.
4.5 Interaction with other medicinal products and other forms of interaction
Paracetamol
Alcohol: Paracetamol should be given with care to patients with alcohol dependence (see Section 4.4).
Analgesics: Diflunisal increases blood concentrations of paracetamol.
Anion-exchange resins: Absorption re duced by colestyramine; administration should be separated by at least one hour.
Antibacterials: Isoniazid may incre ase the risk of he patotoxicity with therapeutic doses of paracetamol.
Anticoagulants: The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol, with increas ed risk of bleeding; occasional doses have no significant effect.
Anti epileptics: Carbamaze pine, phenobarbital, p henytoin and primidone can reduce the effects of pa racetamol and increase the risk of he patotoxicity. Paracetamol may increase lamotrigine metabolism.
Motility stimulants: The speed of absorption of paracetamol may be increased by metoclopramide or domperidone
Oral C ontraceptives: P aracetamol i s cleared from the body m ore qui ckly in women taking oral contraceptives and the analgesic effects may be reduced.
Uricosurics: Probenecid can reduce the loss of paracetamol from the body.
Caffeine
Antibacterials: Some q uinolone a ntibiotics c an re duce the c learance of caffeine and prolong its plasma half-life.
Antidepressants: F luvoxamine can r educe th e clear ance of ca ffeine and increase its stimulant and side effects.
Antiepileptics: Phenytoin may increase the clearance of caffeine. Benzodiazepines: Caffeine can reduce the sedative effects of diazepam. Disulfiram: may reduce the clearance of caffeine.
Lithium: Caffeine may increase the clearance of lithium.
Mexiletine: may reduce the clearance of caffeine.
Oestrogens and progestogens: Oral cont raceptives or oestro gen replacement therapy may reduce the clearance of caffeine.
Phenylpropanolamine: Concomitant a dministration may in crease b lood pressure, re sulting in h ypertensive crise s in a fe w susc eptible individua ls. Manic ps ychosis has o ccurred. Phen ylpropanolamine can inc rease ser um caffeine levels.
Theophylline: c oncomitant a dministration c an i ncrease pla sma the ophylline and plasma caffeine levels.
Phenylephrine Hydrochloride
Adrenergic neu rone bl ockers: ma y enhance the h ypertensive ef fect of phenylephrine.
Antidepressants: Concomitant use of monoamine oxidase inhibitors (MAOIs) including moclobemide, is contraindicated (see Section 4.3 Contraindications). There i s an i ncreased ri sk of h ypertension when used wi th t ricyclic antidepressants e.g. imipramine.
Atropine: There is an increased risk of hypertension when used with atropine. Ergot alkaloids: increased risk of vasoconstriction and hypertension.
Oxytocin: potential increased risk of hypertension with oxytocin.
Sympathomimetics: c oncomitant use with othe r s ympathomimetics can increase the hypertensive effect.
4.6 Pregnancy and lactation
Paracetamol:
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol use 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.
Caffeine:
Taken during pregnancy, it appears that the half-life of caffeine is prolonged. This is a possible contributing factor in hypermesis gravidarum. Caffeine crosses the placenta, and foetal blood and tissue levels similar to maternal concentrations are achieved. Caffeine intake during pregnancy should be kept to a minimum.
Caffeine is excreted in breast milk, but with moderate intake amounts are probably too low to be clinically significant. Regular intake of large amounts of caffeine can affect the nursing infant.
Phenylephrine Hydrochloride:
The safety of phenylephrine during pregnancy has not been established but there is some evidence suggesting a possible association of foetal abnormalities with first trimester exposure to phenylephrine. As an alpha-adrenoceptor stimulant, it might provoke uterine changes, which can result in foetal asphyxia. There is no information on the excretion of phenylephrine into breast milk; however no clinical problems have been documented.
In view of the above, Sainsburys Cold Relief Capsules should be avoided during pregnancy and lactation unless prescribed by a doctor.
4.7 Effects on ability to drive and use machines
Paracetamol:
None.
Caffeine:
None.
Phenylephrine Hydrochloride:
May cause dizziness, if affected, do not drive or operate machinery.
4.8 Undesirable effects
Paracetamol:
Adverse effects of paracetamol are rare.
Haematological: There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.
Immune system: Hypersensitivity including skin rash may occur. A small percentage of aspirin-sensitive asthmatics are also sensitive to paracetamol. In such cases, the deterioration in respiratory function induced by paracetamol is milder and shorter than with aspirin (see also 4.4 Special warnings and precautions for use).
Renal and urinary disorders: Nephropathy has been associated with chronic high dose use.
Caffeine:
Tremor, anxiety and insomnia may be experienced. Withdrawal may induce headache. Large doses may cause restlessness, excitement and extrasystoles.
Phenylephrine Hydrochloride:
Hypertension with headache, vomiting, dizziness, reflex bradycardia, difficulty in micturition and urinary retention. Rare reports of palpitations, and allergic reactions.
4.9 Overdose
Paracetamol
Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).
Risk Factors If the patient
Is on long term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.
Or
Regularly consumes ethanol in excess of recommended amounts.
Or
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.
Treatment
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 BNF overdose section.
Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 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 NPIS or a liver unit.
Caffeine
Symptoms: Large doses may cause restlessness, excitement, muscle tremor, tinnitus, scintillating scotoma, tachycardia and extrasystoles. 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
Severe hypertension is possible. If overdose is suspected, consult your doctor immediately.
5 PHARMACOLOGI CAL PROPERTIES
5.1 P harmacodynamic properties
Paracetamol
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 simulation. Paracetamol probably produces an antipyretic action by a central effect on the hypothalamic heat-regulating centre to produce peripheral vasodilatation 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 central nervous system 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 work that can be performed by a muscle. It may stimulate the respiratory centre, increasing the rate and depths of respiration. Its stimulant action on the medullary vasomotor centre is usually compensated by its peripheral vasodilator effect on the arterioles, so that the 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. It is less effective as a diuretic than theobromine, which has less central stimulating effect and does not cause insomnia. The xanthines are rarely of great value in promoting increased renal function when this is depressed. Caffeine is claimed to enhance the action of ergotamine and is frequently given with ergotamine in the treatment of migraine.
Phenylephrine Hydrochloride
It is a sympathomimetic with many direct effects on adrenergic receptors. It has predominantly alpha-adrenergic activity and is without stimulating effects on the central nervous system. Its pressor activity is weaker than that of noradrenaline but of longer duration. After injection it produces peripheral vasoconstriction and increased arterial pressure; it also causes reflex bradycardia. It reduces blood flow to the skin and to the kidney. It has been used in the treatment of hypotensive states e.g. circulatory failure, spinal anaesthesia; or hypertension following the use of chlorpromazine and other
phenothiazines. Phenylephrine hydrochloride may be given in preparations for the relief of nasal congestion. Locally it is used as a nasal decongestant in rhinitis and sinusitis. In ophthalmology, phenylephrine hydrochloride is employed as a mydriatic and conjunctival decongestant. In open angle glaucoma, it is sometimes used to lower intra-ocular pressure temporarily.
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 drugs.
5.2 P harmacokinetic properties
Paracetamol
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 1-4 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 concentration 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
It is absorbed readily after oral, rectal, or parenteral administration but absorption from the gastro-intestinal 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. It is metabolised almost completely and is excreted in the urine as 1-methyluric acid, 1-methylxanthine and other metabolites with only about 1% unchanged.
Phenylephrine Hydrochloride
It has reduced bioavailability from the gastro-intestinal tract owing to first pass metabolism by monoamine oxidase in the gut and liver. When injected intramuscularly, it takes 10-15 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
Not applicable
6 PHARMACEUTI CAL PARTICULARS
6.1 List of excipients
Starch
Colloidal anhydrous silica Magnesium stearate
Capsule contains:
Gdatin
Colours: erythrosine (E127), titanium dioxide (E171) and quinoline yellow (E104)
6.2 Incom patibilities
None.
6.3 Shelf life
3 years from the date of manufacture.
6.4 Special precautions for storage
Store below 25°C in a dry place.
Protect from light
6.5 Nature and contents of container
Blister packs:
12(GSL)
Blister strips consist of a 35gsm paper/9g soft tempered aluminium foil lid and 250g PVC film base in cartons
6.6 Special precautions for disposal
Return any leftover capsules to the pharmacist
7 MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd Ash Road North Wisxham LU3 9UF
8 MARKETI NG AUTHORISATION NUMBER(S)
PL 29831/0171
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
1st March 2008
10 DATE OF REVISION OF THE TEXT
1st March 2008