Solpadeine Max Soluble Tablets

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains Paracetamol Ph Eur 500mg, Codeine Phosphate Hemihydrate Ph Eur 12.8mg and Caffeine Ph Eur 30mg

3 PHARMACEUTICAL FORM

Effervescent tablet

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Codeine is indicated in patients older than 12 years of age for the treatment of acute moderate pain which is not considered to be relieved by other analgesics such as paracetamol or ibuprofen alone.

Solpadeine Max Soluble Tablets are recommended for the relief of headache, migraine, d ental pa in, p eriod pa in, stra ins & sp rains, ba ckache, arthritic & rheumatic pain and sciatica.

4.2 Posology and method of administration

For oral administration Adults (including the elderly)

2 tablets dissolved in at least half a tumbler of water up to four times a day if necessary.

Do not take more than 8 tablets in 24 hours.

Paediatric population

Children and adolescents aged 12 - 18 years:

2 tablets dissolved in at least half a tumbler of water up to four times a day if necessary.

Do not take more than 8 tablets in 24 hours Children aged less than 2 years:

Codeine should not be used in children below the age of 12 years because of the risk of opioid toxicity due to the variable and unpredictable metabolism of codeine to morphine (see sections 4.3 and 4.4).

The duration of treatment should be limited to 3 days and if no e ffective pain relief is achieved the p atients/carers shoul d be ad vised to seek the views of a physician.

4.3 Contraindications

Solpadeine Max Soluble Tablets are contraindicated in patients with hypersensitivity to paracetamol, caffeine, codeine, opioid analgesics or any of the other constituents.

In all paediatric patients (0-18 years of age) who undergo tonsillectomy and/or adenoidectomy for obstructive sleep apnoea syndrome due to an increased risk of developing serious and life-threatening adverse reactions (see section 4.4).

In women during breastfeeding (see section 4.6).

In patients for whom it is known they are CYP2D6 ultra-rapid metabolisers.

4.4 Special warnings and precautions for use

Solpadeine Max Soluble Tablets contai n 427 mg sodium in each tablet. This should be taken into account where the patient has been placed on a restricted sodium intake e.g . patients with h ypertension, cardiac or r enal insufficiency, oedema or pregnancy.

Care is a dvised in the administration of So lpadeine Max Soluble Tablets to patients with severe renal or seve re hep atic i mpairment. The haz ard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

• Do not exceed the stated dose.

• Patients should be advi sed not to take oth er p aracetamol-containing o r codeine-containing products concurrently.

• If symptoms persist consult your doctor

• Keep out of the reach and sight of children.

Patients with obstructive bowel disord ers or a cute abdominal conditi ons should consult a doctor before using this product.

Patients with a histor y of cholec ystectomy sho uld consult a doctor be fore using this product as it may cause acute pancreatitis in some patients.

Excessive intake of caffeine (e.g. coffee, tea and some canned drinks) should be avoided while taking this product.

CYP2D6 metabolism

Codeine is me tabolised b y the live r enzyme C YP2D6 into morphine . If a patient has a deficiency or is c ompletely l acking this e nzyme an adequate analgesic effect will not be obtained. Estimates indicate that up to 7 % of the Caucasian population may have this defici ency. However, if the patient i s an extensive or ultra -rapid metaboliser there is an increased risk of de veloping side eff ects of opi oid t oxicity ev en at com monly pr escribed dos es. T hese patients convert codein e in to morphine rapidly resulting in hig her t han expected serum morphine levels.

General symptoms of op ioid toxicity include confusion, somnolence, shal low breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe ca ses this may inc lude s ymptoms of circulator y and respir atory depression, which may be life-threatening and very rarely fatal. Estimates of prevalence of ultra-rapid metabolisers in different populations are summarized below:

Population Prevalenc	e %
African/Ethiopian 29%
African American	3.4% to 6.5%
Asian	1.2% to 2%
Caucasian	3.6% to 6.5%
Greek 6.0%
Hungarian 1.9%
Northern European	1%-2%

Post-operative use in children

There have been reports in the published literature that codeine given postoperatively in children a fter tonsill ectomy and/or adenoide ctomy f or obstructive sleep apnoe a, led to rare, but life -threatening adv erse events including death (se e also section 4.3). All children received doses of cod eine that were within the appropriate dose range; however there was evi dence that these children were either ultra-rapid or extensive metabolisers in their ability to metabolise codeine to morphine.

Children with compromised respiratory function

Codeine is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, sever e cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surg ical pro cedures. T hese fa ctors may worsen s ymptoms of morphine toxicity.

The label will state:

Front of pack

• Can cause addiction

• Use for 3 days only

Back of pack

• Solpadeine Max Soluble Tablets are for the short term treatment of acute moderate pain when other painkillers have not worked. Wait at least four hours after taking any other painkiller before you take this medicine. For: migraine, headache, dental pain, period pain, backache, arthritic & rheumatic pain, strains & sprains and sciatica.

• If you need to take this medicine continuously for more than 3 days you should see your doctor or pharmacist

• This medicine contains codeine which can cause addiction if you take continuously for more than 3 days. If you take this medicine for headaches for more than 3 days it can make them worse

The leaflet will state:

Headlines section (to be prominently displayed)

• This medicine is for the short term treatment of acute moderate pain when other painkillers have not worked

• You should only take this product for a maximum of 3 days at a time. If you need to take it for longer than 3 days you should see your doctor or pharmacist for advice

• This medicine contains codeine which can cause addiction if you take it continuously for more than 3 days. This can give you withdrawal symptoms from the medicine when you stop taking it

• If you take this medicine for headaches for more than 3 days it can make them worse.

Section 1: What the medicine is for:

• Solpadeine Max Soluble Tablets can be used in patients older than 12 years of the age for the short term relief of moderate pain that is not relieved by other painkillers such as paracetamol or ibuprofen alone. They can be used for migraine, dental pain, period pain, strains & sprains, backache, arthritic & rheumatic pain and sciatica.

Section 2: Before taking

• This medicine contains codeine which can cause addiction if you take it continuously for more than 3 days. This can give you withdrawal symptoms from the medicine when you stop taking it

• If you take a painkiller for headaches for more than 3 days it can make them worse.

Section 3: Dosage

• This medicine should not be taken for more than 3 days. If the pain does not improve after 3 days, talk to your doctor for advice.

• This medicine contains codeine and can cause addiction if you take it continuously for more than 3 days. When you stop taking it you may get withdrawal symptoms. You should talk to your doctor or pharmacist if you think you are suffering from withdrawal symptoms.

Section 4: Side effects

• Some people may have side-effects when taking this medicine. If you have any unwanted side-effects you should seek advice from your doctor, pharmacist or other healthcare professional. Also you can help to make sure that medicines remain as safe as possible by reporting any unwanted side-effects via the internet at www.mhra.gov.uk/yellowcard; alternatively you can call Freephone 0808 100 3352 (available between 10 am - 2 pm Monday - Friday) or fill in a paper form available from your local pharmacy.

• How do I know if I am addicted?

If you take the medicine according to the instructions on the pack it is unlikely that you will become addicted to the medicine. However, if the following apply to you it is important that you talk to your doctor:

• You need to take the medicine for longer periods of time

• You need to take more than the recommended dose

• When you stop taking the medicine you feel very unwell but you feel better if you start taking the medicine again

4.5 Interaction with other medicinal products and other forms of interaction

Paracetamol

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 us e of par acetamol wi th i ncreased ri sk of bl eeding; oc casional d oses have no significant effect.

Codeine_

Codeine may antagonize the effe cts of metoclopramide and domperidone on gastrointestinal motility.

Codeine potentiates the central depressive effects of central nervous system depressants including alcohol, anaesthetics, hypnotics, sedatives, tricyclic antidepressants and phenothiazines.

MAOIs taken with pethidine have been associated with severe CNS excitation or depression (including hypertension or hypotension). Although this has not

been documented with codeine, it is possible that a similar interaction may occur and therefore the use of codeine should be avoided while the patient is taking MAOIs and for 2 weeks after MAOI discontinuation.

Opiate analgesics may interact with monoamine oxidase inhibitors (MAOI) and result in serotonin syndrome.

4.6 Fertility, pregnancy and lactation

Pregnancy

Use during pregnancy should be avoided, unless advised by a physician. This includes maternal use during labour because of the potential for respiratory depression in the neonate.

The safety of paracetamol-caffeine-codeine during pregnancy has not been established relative to the possible adverse effects of foetal development and should be avoided during pregnancy due to the possible increased risk of lower birth weight and spontaneous abortion associated with caffeine consumption.

Lactation

Codeine should not be used during breastfeeding (see section 4.3).

At normal therapeutic doses codeine and its active metabolite may be present in breast milk at very low doses and is unlikely to adversely affect the breast fed infant.

However, if the patient is an ultra-rapid metaboliser of CYP2D6, higher levels of the active metabolite, morphine, may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant, which may be fatal.

Although significant caffeine toxicity has not been observed in breastfed infants, caffeine may have a stimulating effect on the infant.

Due to the caffeine content of this product it should not be used if you are pregnant or breastfeeding.

4.7. Effects on Ability to Drive and Use Machines

Patients sh ould be advis ed not to drive or operat e machinery i f affect ed by diz ziness or sedation.

This medicine can impair cognitive function and can affect a patient’s

ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When taking this medicine, patients should be told:

• The medicine is likely to affect your ability to drive

• Do not drive until you know how the medicine affects you

• It is an offence to drive while under the influence of this medicine

• However, you would not be committing an offence (called ‘statutory defence’) if:

o The medicine has been taken to treat a medical or dental problem and

o You have taken it according to the information provided with the medicine and

o It was not affecting your ability to drive safely

4.8 Undesirable effects

Adverse events from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive postmarketing experience at therapeutic/labelled dose and considered attributable are tabulated below by system. Due to the limited clinical trial data the frequency of these adverse events is not known (cannot be estimated from available data) but the post-marketing experience indicates that adverse drug reactions to paracetamol are rare and serious reactions are very rare.

Paracetamol

Body System	Undesirable effect
Blood and lymphatic system disorders	Thrombocytopenia Agranulocytosis
Immune system disorders	Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angiodema and Stevens Johnson syndrome/toxic epidermal necrolysis
Respiratory, thoracic and mediastinal disorders	Bronchospasm*
Hepatobiliary disorders	Hepatic dysfunction

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

Caffeine

Central nervous system Nerv

ousness

Dizziness

When the recommended paracetamol-caffeine-codeine dosing regimen is combined with dietary caffeine intake, the resulting higher dose of caffeine may increase the potential for caffeine-related adverse effects such as insomnia, restlessness, anxiety, irritability, headaches, gastrointestinal disturbances and palpitations.

Codeine

Adverse reactions identified during post-marketing use are listed below by MedDRA system organ class. The frequency of these reactions is not known.

Body System	Undesirable effect
Psychiatric disorders	Drug dependency can occur after prolonged use of codeine at higher doses
Gastrointestinal disorder	Constipation, nausea, vomiting, dyspepsia, dry mouth, acute pancreatitis in patients with a history of cholecystectomy
Nervous system disorder	Dizziness, worsening of headache with prolonged use, drowsiness
Renal and urinary disorders	Difficulty with micturition
Skin and subcutaneous tissue disorder	Pruritus, sweating

4.9 Overdose

Overuse of this product, defined as consumption of quantities in excess of the recommended dose, or consumption for a prolonged period of time may lead to physical or psychological dependency. Symptons of restlessness and irritability may result when treatment is stopped.

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 coingested, 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.

Paracetamol

Liver damage is possible in adults who have taken 10 g or more of paracetamol. 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

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 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, 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.

Caffeine

Symptoms and signs

Overdose of caffeine may result in epigastric pain, vomiting, diuresis, tachycardia or cardiac arrhythmia, CNS stimulation (insomnia, restlessness, excitement, agitation, jitteriness, tremors and convulsions).

It must be noted that for clinically significant symptoms of caffeine overdose to occur with this product, the amount ingested would be associated with serious paracetamol-related liver toxicity.

Management

Patients should receive general supportive care (e.g. hydration and maintenance of vital signs). The administration of activated charcoal may be beneficial when performed within one hour of the overdose. The CNS effects of overdose may be treated with intravenous sedatives.

Summary

Treatment of overdose with So lpadeine Max Soluble Tablets requi res assessment of plasma paracetamol levels for antidote treatment, with signs and symptoms of codeine and caffeine toxicity being managed symptomatically. Sodium bicarbonate

High doses of sodium bicarbonate would 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.

5.1 Pharmacodynamic properties

Paracetamol is a well established analgesic.

Caffeine has a stimulatory effect on the central nervous system and possesses a weak diuretic action.

Codeine is a centrally acting weak analgesic. Codeine exerts its effect through p opioid receptors, although codeine has a low affinity for these receptors, and its analgesic effect is due to its convers ion to morphine. Codeine, particularly in combination with other analgesics such as paracetamol, has been shown to be effective in acute nociceptive pain.

5.2 Pharmacokinetic properties

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Concentration of the drug in plasma reaches a peak in 30 -60 minutes and the plasma half-life is 1-4 hours. Paracetamol is relatively uniformly distributed throughout most body fluid s and e xhibits variable pro tein binding. Excre tion is almost exc lusively renal, in the form of conjugated metabolites.

Codeine pho sphate is we ll absorbed af ter adm inistration an d di stributes wi dely throughout the body. 86% of an oral dose is excreted in the urine within 24 hours, 4070% of this being free or conjugated codeine, 5-15% free or conjugated morphine, 10-20% free or conjugated norcodeine.

Caffeine is rapidly but irregularly absorbed after oral administration, absorption is pH-related. After an oral dose of 100mg, peak plasma concentrations of 1.5-2pg/ml are attained within 1-2 hours. Plasma half-life is between 4-10 hours. Caffeine rapidly distributes throughout the body water, and is approximately 15% bo und to plasma proteins. In 48 hours, 45% of a dose is excreted in the urine as l-methylxanthine and l-methyluric acid.

5.3 Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6 PHARMACEUTICAL PARTICULARS

List of excipients

6.1

Sorbitol

Sodium saccharin Sodium bicarbonate Sodium lauryl Sulphate Citric acid Sodium carbonate Polyvidone Dimeticone

6.2 Incompatibilities

None known

6.3 Shelf life

48 months

6.4 Special precautions for storage

The product should be protected from light and moisture

6.5 Nature and contents of container

Laminate strips packed into cardboard cartons containing 8, 16, 20, 24 or 32 tablets. Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Not applicable

7 MARKETING AUTHORISATION HOLDER

Omega Pharma Ltd.

1^st Floor

32 Vauxhall Bridge Road LONDON, SW1V 2SA United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 02855/0078

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

19/01/84 / 28/02/2003

10. DATE OF REVISION OF THE TEXT

17/04/2015