Fevadol Fast is a mild analgesic and antipyretic, and is recommended for the treatment of most painful and febrile conditions, for example, headache including migraine and tension headaches, toothache, backache, rheumatic and muscle pains, dysmenorrhoea, sore throat, and for relieving the fever, aches and pains of colds and flu.

For oral administration.

Adults, including the elderly and children 16 years and over:

Two tablets to be taken with half a tumbler of water (100 ml).

To ensure fast onset of pain relief no less than two tablets must be taken with 100 ml of water. For maximum speed of action this should be on an empty stomach.

Two tablets up to four times daily as required. The dose should not be repeated more frequently than every four hours nor should more than four doses be taken in any 24-hour period.

Children aged 12-15 years:

One tablet to be taken with half a tumbler of water (100ml), up to four times daily as required. The dose should not be repeated more frequently than every four hours nor should more than 4 doses be given in any 24-hour period.

Children under 12 years of age:

Fevadol Fast is not recommended for children under 12 years of age.

Contains paracetamol. Do not use with any other paracetamol-containing products.

Underlying liver disease increases the risk or paracetamol related liver damage. Patients who have been diagnosed with liver or kidney impairment must seek medical advice before taking this medication.

Do not exceed the stated dose.

This medicinal product contains 352mg sodium per dose, equivalent to 17.6% of the WHO recommended maximum daily intake for sodium. The maximum daily dose of this product is equivalent to 70.4% of the WHO recommended maximum daily intake for sodium.

Fevadol Fast is considered high in sodium. This should be particularly taken into account for those on a low salt diet.

Patients should be advised to consult their doctor if their headaches become persistent.

Patients should be advised to consult a doctor if they suffer from non-serious arthritis and need to take painkillers every day.

Caution should be exercised in patients with glutathione depleted states, as the use of paracetamol may increase the risk of metabolic acidosis (refer also to section 4.9).

Use with caution in patients with glutathione depletion due to metabolic deficiencies.

If symptoms persist consult your doctor.

Keep out of the sight and reach of children.

Pack Label:

Talk to a doctor at once if you take too much of this medicine even if you feel well. Do not take anything else containing paracetamol while taking this medicine.

Patient Information Leaflet:

Talk to a doctor at once if you take too much of this medicine even if you feel well. This is because too much paracetamol can cause delayed, serious liver damage.

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 daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy if clinically needed, however, as with any medicine it should be used at the lowest effective dose for the shortest possible time.

Paracetamol is excreted in breast milk but not in a clinically significant amount in recommended dosages. Available published data do not contraindicate breastfeeding.

None.

Adverse events of paracetamol from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by system class and frequency.

The following convention has been utilised for the classification of the undesirable effects: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000) and very rare (<1/10,000), not known (cannot be estimated from available data).

Adverse event frequencies have been estimated from spontaneous reports received through post-marketing data.

Post marketing data

* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.

Reporting of suspected adverse reactions

The National Pharmacovigilance and Drug Safety Centre (NPC)

o Fax: +966-11-205-7662

o Toll free phone: 19999

o E-mail: npc.drug@sfda.gov.sa

o Website: www.sfda.gov.sa/npc

Paracetamol overdose may cause liver failure which may require liver transplant or lead to death.

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

a, Is on long term treatment with carbamazepine, phenobarbitone, 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

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.

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, 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 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 NPIS or a liver unit.

High doses of sodium bicarbonate may be expected to induce gastrointestinal symptoms including belching and nausea. In addition, high doses of sodium bicarbonate may cause hypernatraemia; electrolytes should be monitored and patients managed accordingly.

ATC Code N02B E01

Paracetamol has analgesic and antipyretic actions. The mechanism of action is based on the inhibition of prostaglandin biosynthesis.

Paracetamol is poorly absorbed in the stomach but well absorbed in the small intestine due to the greater surface area and hence adsorptive capacity.

Sodium bicarbonate is an excipient in the formulation which has a role in increasing the rates of gastric emptying and of paracetamol dissolution and hence the speed of absorption of paracetamol to provide faster onset of relief.

The amount of sodium bicarbonate contained in 2 tablets of Fevadol Fast are required per dose to have such effects. Sodium bicarbonate influences the rate of gastric emptying in a concentration dependant manner with the maximal effect achieved at near isotonic concentrations (150 mmol/litre)(i.e. 150 millimolar) – equivalent to 2 Fevadol Fast tablets in 100 ml water.

Hypertonic solutions (500-1,000 mmol/litre)(i.e. 500 to 1,000 millimolar – equivalent to the amount of sodium bicarbonate in 6-12 Fevadol Fast tablets given with 100 ml water) appear to inhibit gastric emptying. The therapeutic application of enhanced gastric emptying has previously been demonstrated with significantly faster rate of absorption of paracetamol and significantly faster onset of pain relief from soluble tablets containing sodium bicarbonate compared to conventional tablets. Fevadol Fast has been formulated with 630 mg sodium bicarbonate per tablet that results in near isotonicity at a 2-tablet dose in gastric fluid.

The role of the dissolution rate of Fevadol Fast Tablets in vivo at gastric pH is unknown. Therefore the role of tablet dissolution in the speed of action of Fevadol Fast Tablets is unclear.

It is likely that no single mode of action is responsible for the pharmacokinetic profile observed with Fevadol Fast. The relative contributions of the different factors will vary depending on the circumstances under which the product is taken.

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. It is metabolised in the liver and excreted in the urine as the glucuronide and sulphate conjugates, - less than 5% is excreted unchanged in the urine as unmodified paracetamol. Binding to plasma proteins is minimal.

The mean elimination half-life of paracetamol following administration of Fevadol Fast is 2 to 3 hours and is similar to that achieved following administration of standard paracetamol tablets in fasted and fed states.

Following administration of Fevadol Fast, paracetamol has a median time to peak plasma concentrations (tmax) of 25 minutes in fasted subjects and 45 minutes in the fed subjects. Maximum plasma concentrations were reached at least twice as fast for Fevadol Fast as for standard paracetamol tablets in both the fed and fasted state (p= 0.0002). Following administration of Fevadol Fast, paracetamol is generally measurable in plasma within 10 minutes in both the fed and fasted state.

Two tablets of Fevadol Fast are required to be taken with 100 ml of water to obtain this fast rate of absorption of paracetamol. The maximum rate of absorption is obtained on an empty stomach. When one tablet is taken the rate of absorption of paracetamol for Fevadol Fast is the same as for standard paracetamol tablets. This is thought to be due to insufficient sodium bicarbonate present in the single tablet dose to increase the rate of paracetamol absorption. In addition, tablets taken with insufficient (<100 mls) water are unlikely to have increased speed of action. (See 5.1 Pharmacodynamic properties).

The extent of absorption of paracetamol from Fevadol Fast tablets is equivalent to that of standard paracetamol tablets as shown by AUC in both fed and fasted states.

Conventional studies using the currently accepted standards for the evaluation of toxicity to reproduction and development are not available.

Sodium Bicarbonate, Kollidon , Rxcipients FM , Povidone K , Sodium Stearyl Fumerate , Hydroxypropyl Cellulose Low-S

None known.

Store below 25°C.

A white to off-white, oblong, biconvex uncoated tablet, engraved with a number “197” on one side and plain surface on the other side.

Not applicable.