Non-drowsy Sinutab Tablets

This variation is being submitted to implement the PRAC recommendations following the outcome of the ibuprofen / pseudoephedrine PSUSA (PSUSA/00001711/201707). These recommendations include updating Sections 4.4 and 4.8 of the Summary of Product Characteristics and to update Section 2 and 4 of the Package Leaflet accordingly

PSE V3 CCDS update plus incorporating paracetamol updates.

Section 4.2 removed text “Oral”

Added Text “Posology”

Replaced text “over” with “aged” added text “and over”

Removed text “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]”

Added text “Children under 12 years

This medicine is contraindicated in children under the age of 12 years (see section 4.3).”

Removed text “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.”

Removed text “to severe” and “particularly if accompanied by cardiovascular disease.” Added text “mild to”

Added text “Duration of use:

Patients should be advised not to use this product for more than 5 days and to seek medical advice if symptoms persist.

Do not exceed the stated dose.

Keep out of the sight and reach of children.

Method of administration:

For oral use.”

Section 4.3 Replaced “Non-drowsy Sinutab is contra-indicated in individuals with known hypersensitivity” with “Hypersensitivity” “the product” to “Paracetamol pseudoephedrine” and “its components (see Section 6)” to “the excipients listed in section 6.1”

Replaced “Non-drowsy Sinutab” with “This product”

Added text

·         “Cardiovascular disease including hypertension.

·         Diabetes mellitus

·         Phaeochromocytoma

·         Hyperthyroidism

·         Closed angle glaucoma

·         Severe renal impairment”

·         “Monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs. The concomitant use of pseudoephedrine and these products may cause a rise in blood pressure or hypertensive crisis.

·         Other sympathomimetic decongestants

·         Furazolidone

·         Beta-blockers”

Removed text “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.”

Added text “This medicine is contraindicated in patients at risk of developing respiratory failure.”

Removed text “Use in patients with thyrotoxicosis, glaucoma or urinary retention.

Use in patients who are currently receiving other sympathomimetic drugs”

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

Replaced “6” with “12” and added “of age”

Section 4.4 removed text “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.”

“should be exercised when using Non-drowsy Sinutab”

“(particularly if accompanied by cardiovascular disease).”

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

“Contains paracetamol. Do not take any other paracetamol containing products.”

“should be sought”

Added text “Use with” “patients with” “or difficulty in urination due to prostatic enlargement.”

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

“Although pseudoephedrine has virtually no pressor effects in normotensive patients, this medicine should be used with caution in patients taking other sympathomimetic agents (such as appetite suppressants and amphetamine-like psychostimulants).”

“(see sections 4.3 and 4.5)”

“Patients should be advised not to take other paracetamol-containing medicines concurrently”

“Patients should seek”

“(see section 4.9)”

“A variety of allergic skin reactions, with or without systemic features such as bronchospasm, angioedema have been reported following use of pseudoephedrine (see section 4.8).

Hypersensitivity reactions, including skin rashes, angioedema and anaphylaxis have been reported very rarely with paracetamol (see section 4.8).

Serious skin reactions such as acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported very rarely in patients receiving paracetamol. Patients should be informed about the signs of serious skin reactions, and use of the product should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

This product may act as a cerebral stimulant giving rise to hyperpyrexia, tremor and epileptiform convulsions.

If any of the following occur, this product should be stopped:

·         Hallucinations

·         Restlessness

·         Sleep disturbances

Use with caution in occlusive vascular disease”

Section 4.5 Added text “Pseudoephedrine” “Pseudoephedrine exerts its vasoconstricting properties by stimulating α-adrenergic receptors and displacing noradrenaline from neuronal storage sites. Since MAOIs impede the metabolism of sympathomimetic amines and increase the store of releasable noradrenaline in adrenergic nerve endings, MAOIs may potentiate the pressor effect of pseudoephedrine.

MAOIs and/or RIMAs: this medicine should not be given to patients treated with MAOIs or within 14 days of stopping treatment as there is an increased risk of hypertensive crisis.

Moclobemide: risk of hypertensive crisis

Concomitant use of this medicine with anticholinergic drugs (such as TCAs) may enhance their effects.

The antibiotic furazolidone is a monoamine oxidase inhibitor. Therefore it should not be taken with this medicine (see Section 4.3).”

“antagonise” “antihypertensive” “reserpine” “adrenergic neurone blockers” “(see sections 4.3 and 4.4)”

“Because of its pseudoephedrine content, concomitant use of this medicine with oxytocin or cardiac glycosides may cause of a risk of hypertension or an increased risk of dysrhythmias, respectively.

When used concurrently with ergot alkaloids (ergotamine & methysergide), this product can increase the risk of ergotism.

Concurrent use with halogenated anaesthetic agents such as chloroform, cyclopropane, halothane, enflurane or isoflurane may provoke or worsen ventricular arrhythmias.

Paracetamol”

“Because of its paracetamol content” “this medicine” “little or”

Removed text “Non-drowsy Sinutab” (replaced with “this medicine”) “decongestants” “or with monoamine oxidase inhibitors, which interfere with the catabolism of sympathomimetic amines” “occasionally” “(please refer to section 4.3).”

“because of its” “content, non-drowsy Sinutab” “partially reverse” “alpha-“ “adrenergic blocking agents”

Section 4.6 added text “Fertility” to title. Replaced “P” with “p” in “Pregnancy”

Added text

“There are no adequate and well controlled clinical studies in pregnant or breast feeding women for the combination of paracetamol and pseudoephedrine.”

“Pregnancy”

“This medicine should not be used during pregnancy unless the potential benefit of treatment to the mother outweighs the possible risks to the developing foetus.”

“Paracetamol”

“When given to the mother in labelled doses, paracetamol crosses the placenta into the foetal circulation as early as 30 minutes after ingestion and is effectively metabolised by foetal sulphate conjugation.”

“Pseudoephedrine”

“Breast-feeding

This medicine should not be used during lactation unless the potential benefit of treatment to the mother outweighs the possible risks to the nursing infant.

Paracetamol

Paracetamol is excreted in breast milk in low concentrations (0.1% to 1.85% of the ingested maternal dose).

Pseudoephedrine”

“Pseudoephedrine distributes into and is concentrated in breast milk”

“Fertility”

“(see section 5.3)”

Replaced “non-drowsy Sinutab” with “this medicine”

Removed text “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 - 07% 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.”

Section 4.7 Replaced “No special comment - unlikely to produce an effect.” With “This medicine has no or negligible influence on the ability to drive and use machines”

Section 4.8 Added text “The safety of pseudoephedrine and paracetamol combination from clinical trial data is based on one randomised, placebo-controlled trial in the management of symptoms attributed to the paranasal sinus associated with the common cold. In addition there were 12 randomised, placebo-controlled trials with single ingredient pseudoephedrine.

Adverse drug reactions identified during clinical trials and post-marketing experience with paracetamol, pseudoephedrine, or the combination are listed below by System Organ Class (SOC).

The frequencies are defined according to the following convention:

Very common ≥1/10

Common ≥1/100 and < 1/10

Uncommon ≥1/1,000 and <1/100

Rare ≥1/10,000 and <1/1,000

Very rare <1/10,000

Not known (cannot be estimated from the available data)

ADRs are presented by frequency category based on 1) incidence in adequately designed clinical trials or epidemiology studies, if available, or 2) when incidence cannot be estimated, frequency category is listed as ‘Not known’.”

“Low level transaminase elevations may occur in some patients taking labelled doses of paracetamol; these elevations are not accompanied with liver failure and usually resolve with continued therapy or discontinuation of paracetamol

A variety of allergic skin reactions, with or without systemic features such as bronchospasm, angioedema have been reported following use of pseudoephedrine.

Hypersensitivity reactions, including skin rashes, angioedema and anaphylaxis have been reported very rarely with paracetamol.

Very rare cases of serious skin reactions have been reported.”

“Reporting of Suspected Adverse Reactions.

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail:medsafety@hpra.ie.”

Removed text “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”

“of shorter periods”

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

Section 4.9 Removed text “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.”

“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.”

Added text “Please refer to local guidance for the treatment of paracetamol overdose.

Liver damage is likely in adults and adolescents who have taken 7.5 to10 g or more of paracetamol over a period of 8 hours or less. Fatalities are infrequent (less than 3-4% of untreated cases) and have rarely been reported with overdoses of less than 15 g.  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.

Ingestion of 5 g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

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.

Or

b, Regularly consumes ethanol in excess of recommended amounts.

Or

c, Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms”

“usually occur within” “and” “hyperhidrosis” “malaise” “not” “until” “to 72” “This may include hepatomegaly, liver tenderness, jaundice, acute hepatic failure and hepatic necrosis”

“Blood bilirubin, hepatic enzymes, INR, prothrombin time, blood phosphate and blood lactate may be increased. These clinical events associated with paracetamol overdose are considered expected, including fatal events due to fulminant hepatic failure or its sequelae.

The following sequalae to acute [hepatic failure] associated with paracetamol overdose (adults and adolescents: ≥ 12 years of age :> 7.5 g within 8 hours) are considered expected and may be fatal”

“Expected Sequelae to Acute Hepatic Failure Associated with Paracetamol Overdose”

“strongly suggested by loin pain, haematuria and proteinuria”

“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.

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 8 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 24h from ingestion should be discussed with the local centres and/or experts that provide advice on poisons and overdoses or a liver unit.

Pseudoephedrine

Symptoms

Overdosage may result in:

Metabolism and nutrition disorders: hyperglycaemia, hypokalaemia

Psychiatric disorders: CNS stimulation, insomnia; irritability, restlessness, anxiety, agitation; confusion, delirium, hallucinations, psychoses

Nervous system disorders: convulsions, tremor, intracranial haemorrhage including intracerebral haemorrhage, drowsiness in children

Eye disorders: mydriasis

Cardiac disorders: palpitations, tachycardia, reflex bradycardia, supraventricular and ventricular arrhythmias, dysrhythmias, myocardial infarction

Vascular disorders: hypertension, hypertensive crisis

Gastrointestinal disorders: nausea, vomiting, ischaemic bowel infarction

Musculoskeletal and connective tissue disorders: rhabdomyolysis

Renal and urinary disorders: acute renal failure, difficulty in micturition

Management

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.”

Section 5.3 Replaced “Non-Drowsy SUDAFED Decongestant Tablets” with “this medicine”

Added text “There is insufficient information available to determine whether pseudoephedrine has mutagenic or carcinogenic potential.

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.

Systemic administration of pseudoephedrine in rats, up to 7 times the human daily dosage in females and 35 times the human daily dosage in males, did not impair fertility nor alter foetal morphological development and survival”

Section 6.6 removed text “of a used medicinal product or waste materials      derived from such medicinal product” “of the product”

Section 10 Removed “(Partial)” and replaced date with “15 March 2016”

4.6        Pregnancy and Lactation

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 – 07% of a single 60 mg dose of pseudoephedrine ingested by a mother will be excreted in the breast milk over 24 hours.

has been corrected to:

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.

Section 4.2

Statement added –

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.

Section 4.3

Statement added –

 
Not to be used in children under 6 years.

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

Section 10

Changed to June 2009

To change the MAH from Pfizer Consumer Healthcare, Pottery Road, Dun Laoghaire, Co. Dublin to McNeil Healthcare (Ireland) Limited, Airton Road, Tallaght, Dublin 24, Ireland.