SANOFI

Solpadol Caplets 500mg/30mg Tablets

For excipients see 6.1.

Tablet.

White to off-white capsule-shaped tablet with flat sides marked 'SOLPADOL' on one side and blank on the reverse.

For the relief of severe pain.

Adults

Two tablets not to be taken more frequently than every four hours up to a maximum of eight tablets in any 24 hour period.

Elderly

The dosage may need to be reduced and should be titrated to the individual's need and overall medical condition.

Children

Not recommended for children under 12 years of age.

Solpadol Caplets are for oral administration.

Use in patients hypersensitive to paracetamol or codeine, or hypersensitivity to any of the other constituents.

Use in patients with acute asthma, respiratory depression, acute alcoholism, head injuries, raised intra-cranial pressure and following biliary tract surgery.

Use in patients currently receiving or within 14 days of stopping monoamine oxidase inhibitor therapy.

Use of codeine containing products is contraindicated in mothers who are breastfeeding unless prescribed by a doctor.

See also Section 4.6 Pregnancy and Lactation.

This product should only be used with great care in any patient whose condition may be exacerbated by opioids, particularly the elderly, who may be sensitive to its central and gastro-intestinal effects, those who are on concurrent CNS drugs, those with prostatic hypertrophy or those with inflammatory or obstructive bowel disorders.

Care should also be observed if prolonged therapy is contemplated.

Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazards of overdose are greater in those with alcoholic liver disease.

Patients should be advised not to exceed the recommended dose and not take other paracetamol containing products concurrently.

Tolerance and dependence can occur, especially with prolonged high dosage of codeine.

The risk-benefit of continued use should be assessed regularly by the prescriber.

Prolonged regular use, except under medical supervision, may lead to physical and psychological dependence (addiction) and result in withdrawal symptoms such as restlessness and irritability, once the drug is stopped (see Section 4.8).

Paracetamol may increase the elimination half-life of chloramphenicol. Oral contraceptives may increase its rate of 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.

The effects of CNS depressants (including alcohol) may be potentiated by codeine.

This product should not be used during pregnancy and lactation.

In nursing mothers, who are ultra-rapid metabolisers of codeine, higher than expected serum and breast milk morphine levels can occur. Morphine toxicity in babies can cause excessive somnolence, hypotonia, miosis and difficulty breastfeeding or breathing. In severe cases respiratory depression and death can occur. In severe cases, naloxone may be appropriate to reverse the effects. The lowest effective dose should be used, for the shortest possible time.

Nursing mothers should be informed about carefully monitoring the infant during treatment for any signs and/or symptoms of morphine toxicity such as increased drowsiness or sedation, difficulty breastfeeding, breathing difficulties, miosis and decreased tone, and seeking immediate medical care if such symptoms or signs are noticed. The nursing mother should be informed about monitoring for signs and symptoms of maternal opioid toxicity as well. Should such signs/symptoms be noted in mother or baby, the mother should immediately stop taking all codeine-containing medicines and seek medical advice.

Codeine-containing products must not be used while breastfeeding unless prescribed by a doctor.

Patients receiving this medication should be advised not to drive or operate machinery if affected by dizziness or sedation.

Prolonged use of a painkiller for headaches can make them worse.

Codeine can produce typical opioid effects including constipation, nausea, vomiting, dizziness, light-headedness, confusion, drowsiness and urinary retention. The frequency and severity are determined by dosage, duration of treatment and individual sensitivity.

Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

There have been very rare occurrence of pancreatitis.

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, phenobarbitone, phenytoin, primidone, rifampicin, St. John's Wort or other drugs that induce liver enzymes,

Regularly consumes ethanol in excess of recommended amounts,

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, 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.

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 the 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 serious hepatic dysfunction beyond 24h from ingestion should be discussed with the NPIC or a liver unit.

Codeine

The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Symptoms:

Central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been co-ingested, including alcohol, or the overdose is very large. The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely.

Management:

This should include general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable. Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg.

Give naloxone if coma or respiratory depression is present. Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient. Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

Pharmacotherapeutic group: Anilides, Paracetamol combinations.

ATC Code: N02B E51.

Paracetamol is an analgesic which acts peripherally, probably by blocking impulse generation at the bradykinin sensitive chemo-receptors which evoke pain. Although it is a prostaglandin synthetase inhibitor, the synthetase system in the CNS rather than the periphery appears to be more sensitive to it. This may explain paracetamol's lack of appreciable anti-inflammatory activity. Paracetamol also exhibits antipyretic activity.

Codeine is a centrally acting analgesic which produces its effect by its action at opioid-binding site (µ-receptors) within the CNS. It is a full agonist.

Following oral administration of two tablets (i.e. a dose of paracetamol 1000mg and codeine 60mg), the mean maximum plasma concentrations of paracetamol and codeine were 15.96µg/ml and 212.4ng/ml respectively. The mean times to maximum plasma concentrations were 0.88 hours for paracetamol and 1.05 hours for codeine.

The mean AUC for the 9 hours following administration was 49.05µg.ml^-1.h for paracetamol and 885.0ng.ml^-1.h for codeine.

The bioavailabilities of paracetamol and codeine phosphate when given as the combination are similar to those when they are given separately.

Not applicable.

Pregelatinised starch

Maize starch

Povidone

Potassium sorbate

Microcrystalline cellulose

Stearic acid

Talc

Magnesium stearate

Croscarmellose sodium

Not applicable.

5 years.

Do not store above 25°C. Store in the original package.

1) Amber glass bottles with tinplate screw cap with steran-faced pulpboard wad.

2) PVC/aluminium foil (250 μm/20 μm) or PVC/aluminium foil (250 μm/20 μm) / PVC (15 μm) blister packs or PVC/aluminium foil (250 μm/9 μm /Glassine paper (35 gsm). Packs of 4, 10, 60 and 100 tablets.

Not all pack sizes may be marketed.

No special requirements..

sanofi-aventis Ireland Ltd.,

Citywest Business Campus,

Dublin 24,

Ireland.

PA 540/159/1

26^th June 1991 / 1^st November 2004

16 May 2012