McNeil Healthcare (Ireland) Ltd

Non-drowsy Sinutab Tablets

Paracetamol 500mg

Pseudoephedrine hydrochloride 30mg

Each tablet contains 30mg Pseudoephedrine Hydrochloride and 500mg Paracetamol

For a full list of excipients, see section 6.1

Tablets

White round biconvex tablets

Non-drowsy Sinutab is indicated for the short term symptomatic relief of conditions where congestion of the mucous membranes of the upper respiratory tract, especially nasal mucosa and sinuses, is accompanied by mild to moderate pain or pyrexia, eg the common cold, influenza, sinusitis and nasopharyngitis.

Adults and Children over 12 years

Oral. Two tablets to be taken every four to six hours, up to four times a day.

Maximum daily dose: 8 tablets (240 mg pseudoephedrine and 4 g paracetamol).

Children aged 6 to 12 years

One tablet every four to six hours, up to four times a day when simple measures have failed to provide adequate relief. Do not use for more than 5 days without consulting your doctor or pharmacist. Do not exceed the stated dose.

Maximum daily dose: 4 tablets

Children under 6 years

Non-drowsy Sinutab is not recommended for children under 6 years of age. [see Section 4.3]

The Elderly

Experience has indicated that normal adult dosage is appropriate. However in frail, immobile, elderly subjects, a reduction in the size or frequency of dosing may be appropriate.

Hepatic dysfunction:

Caution should be exercised when administering the product to patients with severe hepatic impairment.

Renal dysfunction:

Caution should be exercised when administering Non-drowsy Sinutab to patients with moderate to severe renal impairment, particularly if accompanied by cardiovascular disease.

Non-drowsy Sinutab is contra-indicated in individuals with known hypersensitivity to the product or any of its components.

Non-drowsy Sinutab is contra-indicated in patients with severe hypertension or severe coronary artery disease.

Non-drowsy Sinutab is contra-indicated in patients who are taking or have taken monoamine oxidase inhibitors within the previous two weeks. The concomitant use of pseudoephedrine and this type of product may cause a rise in blood pressure. The product should not be used concurrently with furazolidone.

Use in patients with thyrotoxicosis, glaucoma or urinary retention.

Use in patients who are currently receiving other sympathomimetic drugs

Not to be used in children under 6 years.

Consult a pharmacist or doctor before use in children aged 6-12 years.

Although pseudoephedrine has mild pressor effects in normotensive patients, Non-drowsy Sinutab should be used with caution in patients suffering mild to moderate hypertension.

As with other sympathomimetic agents Non-drowsy Sinutab should be used with caution in patients with heart disease, hyperthyroidism, elevated intraocular pressure or prostatic enlargement.

Caution should be exercised when using Non-drowsy Sinutab in the presence of severe hepatic impairment or moderate to severe renal impairment (particularly if accompanied by cardiovascular disease).

The physician or pharmacist should check that sympathomimetic containing oral preparations are not simultaneously administered by several routes i.e. orally and topically (nasal, aural and eye preparations)

The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.

Contains paracetamol. Do not take ant other paracetamol containing products.

The stated dose must not be exceeded. Immediate medical advice should be sought in the event of overdosage, because of the risk of irreversible liver damage.

Concomitant use of Non-drowsy Sinutab with tricyclic antidepressants, with sympathomimetic agents (such as decongestants, appetite suppressants and amphetamine-like psychostimulants) or with monoamine oxidase inhibitors, which interfere with the catabolism of sympathomimetic amines, may occasionally cause a rise in blood pressure (please refer to section 4.3).

Because of its pseudoephedrine content, Non-drowsy Sinutab may partially reverse the hypotensive action of drugs which interfere with sympathetic activity including bretylium, bethanidine, guanethidine, debrisoquine, methyldopa, alpha- and beta-adrenergic blocking agents.

Patients who have taken barbiturates, tricyclic antidepressants and alcohol may show diminished ability to metabolise large doses of paracetamol, the plasma half-life of which can be prolonged.

Alcohol can increase the hepatotoxicity of paracetamol overdosage and may have contributed to the acute pancreatitis reported in one patient who had taken an overdose of paracetamol.

Chronic ingestion of anticonvulsants or oral steroid contraceptives induce liver enzymes and may prevent attainment of therapeutic paracetamol levels by increasing first pass metabolism or clearance.

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.

Paracetamol has been in widespread use for many years without ill consequence. Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in recommended dosage, but patients should follow that advise of their doctor regarding its use.

Although pseudoephedrine has been in widespread use for many years without apparent ill consequence, there are no specific data on its use during pregnancy. Caution should therefore be exercised by balancing the potential benefit of treatment to the mother against any possible hazards to the developing foetus.

Systemic administration of pseudoephedrine, up to 50 times the human daily dosage in rats and up to 35 times the human daily dosage in rabbits, did not produce teratogenic effects.

There is insufficient information available to determine whether or not paracetamol has teratogenic potential.

Pseudoephedrine is excreted in breast milk in small amounts but the effect of this on breast-fed infants is not known. It has been estimated that 0.5 - 0.7% of a single 60 mg dose of pseudoephedrine ingested by a mother will be excreted in the breast milk over 24 hours.

A pharmacokinetic study of paracetamol in 12 nursing mothers revealed that less than 1% of a 650 mg oral dose of paracetamol appeared in the breast milk. Similar findings have been reported in other studies. Therefore, maternal ingestion of therapeutic dose of paracetamol does not appear to present a risk to the neonate/infant.

No studies have been conducted in animals to determine whether pseudoephedrine has potential to impair fertility. There is no information on the effects of Non-drowsy Sinutab on human fertility.

No special comment - unlikely to produce an effect.

Serious side effects associated with the use of pseudoephedrine are rare.

Urinary retention has occasionally been reported in men receiving pseudoephedrine; prostatic enlargement could have been an important predisposing factor.

Paracetamol has been widely used and, when taken at the usual recommended dosage, side effects are mild and infrequent and reports of adverse reactions are rare. Chronic hepatic necrosis has been reported in a patient who took daily therapeutic dosages of paracetamol for about a year and liver damage has been reported after daily ingestion of excessive amounts of shorter periods. A review of a group of patients with chronic active hepatitis failed to reveal differences in the abnormalities of liver function in those who were long-term users of paracetamol nor was the control of their disease improved after paracetamol withdrawal.

Nephrotoxic effects following therapeutic dosages of paracetamol are uncommon. Papillary necrosis has been reported after prolonged administration.

Pseudoephedrine

As with other sympathomimetic agents, symptoms and signs of pseudoephedrine overdose include irritability, restlessness, tremor, convulsions, palpitations, hypertension and difficulty with micturition.

Measures should be taken to maintain and support respiration and control convulsions. Gastric lavage should be performed if indicated. Catheterisation of the bladder may be necessary. If desired, the elimination of pseudoephedrine can be accelerated by acid diuresis or by dialysis.

Paracetamol

Symptoms of paracetamol overdose 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, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Liver damage is likely in adults who have taken 10 g or more of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.

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 and any patient who had ingested around 7.5 g or more of paracetamol in the preceding 4 hours should undergo gastric lavage. Administration of oral methionine or intravenous N-acetylcysteine which may have a beneficial effect up to at least 48 hours after the overdose, may be required. General supportive measures must be available.

ATC Code: R01BA02

Pseudoephedrine has direct and indirect sympathomimetic activity and is an effective upper respiratory tract decongestant. Pseudoephedrine is substantially less potent than ephedrine in producing both tachycardia and elevation in systolic blood pressure and considerably less potent in causing stimulation of the central nervous system.

ATC Code: N02BE01

Paracetamol has analgesic and antipyretic actions but only weak anti-inflammatory properties. This may be explained by the presence of cellular peroxides at sites of inflammation which prevent inhibition of cyclo-oxygenase by paracetamol at other sites associated with low levels of cellular peroxides, eg pain, fever, paracetamol and successfully inhibit prostaglandin biosynthesis.

Pseudoephedrine

Pseudoephedrine is partly metabolised in the liver by N-demethylation to norpseudoephedrine, an active metabolite. Pseudoephedrine and its metabolite are excreted in the urine: 55% to 75% of a dose is excreted unchanged. The rate of urinary excretion of pseudoephedrine is accelerated when the urine is acidified. Conversely as the urine pH increases, the rate of urinary excretion is slowed.

Paracetamol

Peak plasma paracetamol concentration usually occurs between 30 and 90 minutes after oral ingestion. Paracetamol is distributed uniformly throughout most body fluids and is only 15 to 25 per cent bound to plasma proteins. The plasma half life of paracetamol after therapeutic doses is in the range of 1 to 3 hours.

Mutagenicity

Paracetamol

In vivo mutagenicity tests of paracetamol in mammals are limited and show conflicting results. Therefore, there is insufficient information to determine whether paracetamol poses a mutagenic risk to man.

Paracetamol has been found to be non-mutagenic in bacterial mutagenicity assays, although a clear clastogenic effect has been observed in mammalian cells in vitro following exposure to paracetamol (3 and 10 mM for 2 hr).

Pseudoephedrine

The results of a wide range of tests indicate that pseudoephedrine does not post a mutagenic risk to man.

Carcinogenicity

Paracetamol

There is inadequate evidence to determine the carcinogenic potential of paracetamol in humans. A positive association between the use of paracetamol and cancer of the ureter (but not of other sites of the urinary tract) was observed in a case-control study in which approximate lifetime consumption of paracetamol (whether acute or chronic) was estimated. However, other similar studies have failed to demonstrate statistically significant association between paracetamol and cancer of the urinary tract, or paracetamol and renal cell carcinoma.

There is limited evidence for the carcinogenicity of paracetamol in experimental animals. Liver cell tumours can be detected in mice and liver and bladder carcinomas can be detected in rats, following chronic feeding 500 mg/kg/day paracetamol.

Pseudoephedrine

There is insufficient information available to determine whether pseudoephedrine has carcinogenic potential.

Teratogenicity

Paracetamol

There is no information relating to the teratogenic potential paracetamol. In humans, paracetamol crosses the placenta and attains concentrations in the foetal circulation similar to those in the maternal circulation. Intermittent maternal ingestion of therapeutic doses of paracetamol is not associated with teratogenic effects in humans. Paracetamol has been found to be fetotixic to cultured rat embryos.

Pseudoephedrine

Systemic administration of pseudoephedrine, up to 50 times the human daily dosage in rats and up to 35 times the human daily dosage in rabbits did not produce teratogenic effects.

Fertility

Paracetamol

There is no information relating to the effects of paracetamol on human fertility. A significant decrease in testicular weight was observed when male Sprague-Dawley rats were given daily high doses of paracetamol (500 mg/kg body weight/day) orally for 70 days.

Pseudoephedrine

Systemic administration of pseudoephedrine to rats, up to 7 times the human daily dosage in females and 35 times the human daily dosage in males, did not impair fertility or alter foetal morphological development and survival.

Microcrystalline cellulose

Pregelatinised maize starch

Crospovidone

Sodium starch glycolate (Type A)

Povidone

Stearic acid

Magnesium stearate

Not applicable

3 years

Do not store above 25°C. Store in original pack.

Opaque white PVC and PVPC/Aluminium foil blister packs

Packs of 4, 12, 15 and 24 tablets

Not all pack sizes may be marketed.

No special requirements

McNeil Healthcare (Ireland) Limited

Airton Road

Tallaght

Dublin 24

Ireland

PA 823/5/1

Date of first authorisation: 06 February 1998

Date of last renewal: 06 February 2008

April 2011