Sinugesic 30 mg/ 500 mg Tablets

SINUGESIC is indicated for the symptomatic relief of nasal, sinus and Eustachian tube mucal congestion and associated pain and fever due to colds and influenza.

Posology
DO NOT EXCEED THE RECOMMENDED DOSE.
Adults and children over 12 years: One to two tablets every four to six hours. Do not exceed eight tablets in 24 hours.
Children 6 to 12 years: A half to one tablet every six hours. Do not exceed four tablets in 24 hours. Do not use continuously for longer than 10 days without consulting your doctor. Not recommended for children under 6 years.
Paediatric population
SINUGESIC is not recommended for children under 6 years (see section 4.3).
Method of administration
For oral administration.

SINUGESIC is contraindicated in:
u2022 Patients with hypersensitivity to pseudoephedrine hydrochloride or paracetamol or to any excipients in SINUGESIC (see section 6.1).
u2022 Patients receiving monoamine oxidase inhibitors or within 14 days of its termination.
u2022 Hyperexcitability and phaeochromocytoma.
u2022 Patients with severe liver disease.
u2022 Pregnancy or whilst breastfeeding.
u2022 Children under 6 years.
u2022 Severe renal impairment.
u2022 Severe acute or chronic kidney disease/renal failure.
u2022 Cardiovascular disease including hypertension or uncontrolled hypertension and peripheral vascular disease.
u2022 Patients with diabetes mellitus.
u2022 Patients with hyperthyroidism.
u2022 Patients with closed-angle glaucoma or where intraocular pressure is raised.
u2022 Concomitant use of other sympathomimetic decongestants.
u2022 Concomitant use with beta-blockers (see section 4.5).

SINUGESIC contains paracetamol which may be fatal in overdose. In the event of overdosage or suspected overdose and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital or Poison Centre must be contacted immediately. Dosages in excess of those recommended may cause severe liver damage.
Pseudoephedrine hydrochloride
Hypersensitivity
Severe Skin reactions
Severe skin reactions such as acute generalized exanthematous pustulosis (AGEP) may occur with pseudoephedrine hydrochloride containing products as in SINUGESIC. This acute pustular eruption may occur within the first 2 days of treatment, with fever, and numerous, small, mostly non-follicular pustules arising on a widespread oedematous erythema and mainly localized on the skin folds, trunk, and upper extremities. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema, or many small pustules are observed, administration of this medicine should be discontinued and appropriate measures taken if needed (see section 4.8).
If any of the following occur, the product should be stopped:
u2022 Hallucinations.
u2022 Restlessness.
u2022 Sleep disturbances.
Ischaemic colitis
Some cases of ischaemic colitis have been reported with pseudoephedrine hydrochloride. Pseudoephedrine hydrochloride should be discontinued and medical advice sought if sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop (see section 4.8).
Ischaemic optic neuropathy
Cases of ischaemic optic neuropathy have been reported with pseudoephedrine. Pseudoephedrine hydrochloride should be discontinued if sudden loss of vision or decreased visual acuity such as scotoma occurs (see section 4.8).
Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS)
Cases of PRES and RCVS have been reported with the use of pseudoephedrine-containing products (see section 4.8). The risk is increased in patients with severe or uncontrolled hypertension, or with severe acute or chronic kidney disease/renal failure (see section 4.3). Pseudoephedrine hydrochloride should be discontinued, and immediate medical assistance sought if the following symptoms occur: sudden severe headache or thunderclap headache, nausea, vomiting, confusion, seizures and/or visual disturbances. Most reported cases of PRES and RCVS resolved following discontinuation and appropriate treatment.
Risks of abuse
Pseudoephedrine hydrochloride, as contained in SINUGESIC, carries the risk of abuse. Prolonged administration has no cumulative effect, but continuous use can lead to tolerance resulting in an increased risk of overdosing. The recommended maximum dose and treatment duration should not be exceeded (see section 4.2).
Glucose-6-phosphate dehydrogenase deficiency
Haemolysis may occur in patients with glucose-6-phosphate dehydrogenase deficiency.
Paracetamol
Severe cutaneous adverse reactions (SCARs)
Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS)/Drug-induced hypersensitivity syndrome (DIHS) and fixed drug eruptions (FDE) have been reported in patients treated with paracetamol containing medicines. If a patient develops SCAR, treatment with SINUGESIC must immediately be discontinued and appropriate treatment instituted (see section 4.8).

Pseudoephedrine hydrochloride
u2022 Pseudoephedrine hydrochloride should be avoided or used with extreme caution in patients undergoing anaesthesia with cyclopropane, halothane, or other halogenated anaesthetics, as they may induce ventricular fibrillation.
u2022 An increased risk of dysrhythmias may also occur if pseudoephedrine hydrochloride is given to patients receiving cardiac glycosides, quinidine, or tricyclic antidepressants. The effects of pseudoephedrine hydrochloride may be diminished or enhanced by tricyclic antidepressants.
u2022 There is an increased risk of vasoconstrictor or pressor effects in patients receiving ergot alkaloids or oxytocin.
u2022 Special care is advisable in patients receiving antihypertensive therapy since pseudoephedrine hydrochloride increases blood pressure. It specifically reverses the antihypertensive effects of guanethidine with the risk of severe hypertension. The effects of pseudoephedrine hydrochloride are diminished by guanethidine, reserpine, methyldopa.
u2022 Severe hypertension may also develop if pseudoephedrine hydrochloride is given with a beta blocker (see section 4.3).
u2022 A combination with alpha-adrenoceptor blockers, such as phenoxybenzamine and phentolamine, may result in both antihypertensive and cardiac-accelerating effects.
u2022 The effects of pseudoephedrine hydrochloride are enhanced by an MAOI and may result in hazardous hypertensive interactions (see section 4.3).
u2022 The hypokalaemic effects of pseudoephedrine hydrochloride may be potentiated by corticosteroids, potassium-depleting diuretics, and aminophylline or theophylline.
u2022 Appetite suppressants and amphetamine-like psychostimulants as there is a risk of hypertension.
u2022 Concomitant use of SINUGESIC with sympathomimetic medicines such as decongestants may cause a rise in blood pressure (see section 4.3).
Paracetamol
u2022 The absorption of paracetamol may be accelerated by metoclopramide.
u2022 Excretion may be affected and plasma concentrations altered when administered with probenecid.
u2022 Colestyramine reduces the absorption of paracetamol if given within one hour of paracetamol administration.
u2022 Medicines which induce hepatic microsomal enzymes, such as anticonvulsants and oral contraceptive steroids, may increase the rate at which paracetamol, as contained in SINUGESIC, is metabolised, leading to a reduced plasma concentration of the medicine.
u2022 Alcohol may reduce the capacity of the liver to metabolise paracetamol (see section 4.4).
u2022 Chronic use of paracetamol enhances the effects of anticoagulants.
u2022 Concurrent use of paracetamol, as contained in SINUGESIC, with NSAIDs may increase the risk of adverse renal effects. The prolonged combined use of these medicines may increase the risk of renal damage.
u2022 Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risk factors (see section 4.4).

The use of SINUGESIC is contraindicated in pregnancy and lactation (see section 4.3).
Fertility
No data

Since adverse reactions such as headaches, dizziness and tremors have been reported in patients taking SINUGESIC, patients should not drive, use machinery or perform any tasks that require concentration, until they are certain that SINUGESIC does not adversely affect their ability to do so (see section 4.8).

a) Tabulated list of adverse reactions
System organ class
Frequent
Less frequent
Frequency unknown (cannot be estimated from the available data)
Blood and the lymphatic system disorders
Haematological reactions including thrombocytopenia*, leucopenia*, pancytopenia*, neutropenia*, and agranulocytosis* have been reported
Immune system disorders
Other hypersensitivity reactions* including cross-sensitivity that may occur with other sympathomimetics #
Metabolism and nutrition disorders
Hyperglycaemia #
Altered metabolism including changes in blood sugar concentrations #, reduced appetite #, anorexia #
Psychiatric disorders
Hallucinations (particularly in children) #
Fear #, anxiety #, restlessness #, insomnia #, sleep disturbance #, irritability #, psychotic states #, excitability #
Nervous system disorders
Headache #
Dizziness #
Tremor #, confusion #, posterior reversible encephalopathy syndrome (PRES) # (see section 4.4). Reversible cerebral vasoconstriction syndrome (RCVS) # (see section 4.4).
Eye disorders
Ischaemic optic neuropathy #
Cardiac disorders
Reflex bradycardia #, tachycardia and cardiac dysrhythmias #, anginal pain #, palpitations #, and cardiac arrest #
Vascular disorders
Hypertension #, hypotension with dizziness, fainting, and flushing #, cerebral haemorrhage #
Respiratory, thoracic and mediastinal disorders
Dyspnoea #, pulmonary oedema #
Gastrointestinal disorders
Dry mouth #, Pancreatitis*, hypersalivation #, nausea #, vomiting #, ischaemic colitis #
Skin and subcutaneous tissue disorders
Skin rashes*
Sweating #, severe skin reactions, including acute generalized exanthematous pustulosis (AGEP)* #, fixed drug eruptions (FDE)* and Drug-induced hypersensitivity syndrome (DIHS)* (see section 4.4)
Musculoskeletal and connective tissue disorders
Weakness #
Renal and urinary disorders
Difficulty in micturition and urinary retention #
General disorders and administrative site conditions
Coldness of extremities #
*Paracetamol
#Pseudoephedrine
c. Description of selected adverse reactions
Skin rashes and other hypersensitivity reactions occur less frequently. The rash usually appears as red areas or allergic wheals and may be accompanied by fever and involvement of the mucous membranes. Effects on the cardiovascular system are complex. Stimulation of alpha-adrenergic receptors produces vasoconstriction with resultant hypertension. This vasoconstriction is sometimes sufficiently severe to produce gangrene when sympathomimetics are infiltrated into the digits. The rise in blood pressure may produce cerebral haemorrhage and pulmonary oedema. There may also be a reflex bradycardia, but stimulation of u03b21-adrenergic receptors of the heart may produce tachycardia and cardiac dysrhythmias, anginal pain, palpitations, and cardiac arrest; hypotension with dizziness, fainting, and flushing, may occur due to stimulation of the u03b22-adrenergic receptors and the resulting vasodilatation. Prolonged administration has no cumulative effect, but tolerance with dependence may occur.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

Symptoms
See section 4.4 and 4.8.
Pseudoephedrine overdosage: Symptoms of pseudoephedrine hydrochloride overdosage include paranoid psychosis, delusions and hallucinations.
Paracetamol overdosage: Prompt treatment is essential. In the event of an overdosage, consult a doctor immediately, or take the person directly to a hospital. A delay in starting treatment may mean that antidote is given too late to be effective. Evidence of liver damage is often delayed until after the time for effective treatment has lapsed. Susceptibility to paracetamol toxicity is increased in patients who have taken repeated high doses (greater than 5 to 10 g/day) of paracetamol for several days, in chronic alcoholism, chronic liver disease, AIDS, malnutrition, and with the use of drugs that induce liver microsomal oxidation such as barbiturates, isoniazid, rifampicin, phenytoin and carbamazepine.
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia, lethargy, sweating and abdominal pain. Liver damage may become apparent 12 to 48 hours, or later after ingestion, initially by elevation of the serum transaminase and lactic dehydrogenase activity, increased serum bilirubin concentration and prolongation of the prothrombin time. Liver damage may lead to encephalopathy, coma and death. Abnormalities of glucose metabolism and metabolic acidosis may occur.
Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac dysrhythmias have been reported.
Treatment
Specialised treatment is essential as soon as possible. N-acetylcysteine should be administered to all cases of suspected overdose as soon as possible preferably within eight hours of overdosage, although treatment up to 36 hours after ingestion may still be of benefit, especially if more than 150 mg/kg of paracetamol was taken. An initial dose of 150 mg/kg N-acetylcysteine in 200 ml dextrose injection given intravenously over 15 minutes, followed by an infusion of 50 mg/kg in 500 ml dextrose injection over the next four hours, and then 100 mg/kg in 1 000 ml dextrose injection over the next sixteen hours. The volume of intravenous fluid should be modified for children. Although the oral formulation is not the treatment of choice, 140 mg/kg dissolved in water may be administered initially, followed by 70 mg/kg every four hours for seventeen doses. A plasma paracetamol level should be determined four hours after ingestion in all cases of suspected overdosage. Levels done before four hours may be misleading. Patients at risk of liver damage, and hence requiring continued treatment with N-acetylcysteine, can be identified according to their 4-hour plasma paracetamol level. The plasma paracetamol level can be plotted against time since ingestion in the nomogram below. The nomogram should be used only in relation to a single acute ingestion. Those whose plasma paracetamol levels are above the u201cnormal treatment lineu201d, should continue N-acetylcysteine treatment with 100 mg/kg IV over sixteen hours repeatedly until recovery. Patients with increased susceptibility to liver damage as identified above, should continue treatment if concentrations are above the u201chigh risk treatment lineu201d. Prothrombin index correlates best with survival. For overdose with an extended/modified release preparation the value of the nomogram is unknown. As there is no information on the plasma levels of paracetamol after an overdose of extended/modified release paracetamol preparations, all patients with suspected or known overdose with such preparations should receive N-acetylcysteine. Because of lack of data for extended/modified release formulations, a level below the u201ctreatment lineu201d of the nomogram may not exclude the possibility of toxicity. Monitor all patients with significant ingestions for at least ninety-six hours.