Propain Plus

1. Name Of The Medicinal Product

Sedinol, Painex, Propain Plus or Feminax Plus Period Pain Caplets

2. Qualitative And Quantitative Composition

Paracetamol BP 450mg

Doxylamine Succinate USP 5mg

Caffeine Anhydrous BP 30mg

Codeine Phosphate BP 10mg

For excipients see 6.1

3. Pharmaceutical Form

Tablet (capsule shaped tablet – caplet).

4. Clinical Particulars

4.1 Therapeutic Indications

For the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone of the following conditions:

Treatment of tension headache, headache, toothache, backache, migraine, neuralgia, dysmenorrhoea, muscular and rheumatic aches and pains, post-operative analgesia following surgical and dental procedures.

4.2 Posology And Method Of Administration

Adults and children over 12 years: One to two tablets every 4-6 hours. Not suitable for children under 12 years of age.

Elderly: Dosage as for adults.

Do not exceed 8 tablets per 24 hours.

Do not take for more than 3 days continuously without medical review.

Route of Administration: Oral.

4.3 Contraindications

Sensitivity to paracetamol, doxylamine succinate, codeine phosphate, caffeine or any of the other ingredients in the product.

4.4 Special Warnings And Precautions For Use

Should be taken only with caution by asthmatics.

This medicine may lead to drowsiness and impaired concentration, which may be aggravated by simultaneous intake of alcohol or other central nervous system depressant agents. Patients should be warned against taking charge of vehicles or machinery or performing potentially hazardous tasks where loss of concentration may lead to accidents.

Dosage in excess of those recommended may cause severe liver damage.

Care is advised in the administration of paracetamol-containing product to patients with severe renal or severe hepatic impairment and in those with non-cirrhotic alcoholic liver disease. The hazards of overdose are greater in those with alcoholic liver disease. Patients suffering from liver or kidney disease should take paracetamol under medical supervision. The dosage in renal impairment must be reduced.

The elderly are more likely to metabolise or eliminate opioid analgesics more slowly than young adults.

Codeine may cause faecal impaction, producing incontinence, spurious diarrhoea, abdominal pain and rarely colonic obstruction.

Dependence can develop with repeated use of codeine and therefore withdrawal symptoms may appear if the product is withdrawn abruptly.

Caution is advised when treating patients with hypertension, hypothyroidism, adrenocortical insufficiency, prostatic hypertrophy, shock, obstructive bowel disorders, acute abdominal conditions, recent gastrointestinal surgery, gallstones, a history of cardiac arrhythmias or convulsions. Care should be taken with patients with a history of drug abuse or emotional instability.

Patients should be warned of the following via the label and leaflet:

• Do not exceed the recommended dose.

• Do not take any other paracetamol-containing products.

• Consult your doctor if no relief is obtained with the recommended dosage.

• Keep out of the reach of children.

• This product contains paracetamol.

• Immediate medical advice should be sought in the event of an overdose even if you feel well due to the risk of severe liver damage.

• Alcoholic drink should be avoided.

The leaflet will state:

Headlines section (to be prominently displayed)

• This medicine can only be used for …….(indications)

• You should only take this product for a maximum of three days at a time. If you need to take it for longer than three 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 three 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 three days it can make them worse

Section 1: What the medicine is for

• Succinct description of the indications from 4.1 of the SmPC Section 2: Before taking

• This medicine contains codeine which can cause addiction if you take it continuously for more than three 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 three days it can make them worse

Section 3: Dosage

• Do not take for more than 3 days. If you need to use this medicine for more than three days you must speak to your doctor or pharmacist

• This medicine contains codeine and can cause addiction if you take it continuously for more than three 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.yellowcard.gov.uk; alternatively you can call Freephone 0808 100 3352 (available between 10am-2pm 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

The label will state (prominently but not in a box):

Front of Pack

• Can cause addiction

• For three days use only

Back of Pack

• List of indications as agreed in 4.1 of the SmPC

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

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

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Paracetamol:

The gastro-intestinal absorption of paracetamol may be delayed by drugs such as anticholinergic agents or opioid analgesics which decrease gastric emptying. Colestyramine may reduce the absorption of paracetamol. Metoclopramide and domperidone may potentiate the speed of absorption of paracetamol.

The likelihood of toxicity may be increased by the concomitant use of enzyme-inducing agents such as alcohol, anti-epileptics, barbiturates and tricyclic antidepressants.

Repeated doses of paracetamol increase the anticoagulant response to coumarins.

Paracetamol with aspirin has been noted to increase the blood concentration of unhydrolysed aspirin.

Doxylamine Succinate:

The antihistamines can enhance the sedative effect of central nervous system depressants, including alcohol, barbiturates, hypnotics, narcotic analgesics, sedatives and tranquillisers. The effects of the anticholinergic drugs such as atropine and tricyclic antidepressants may be enhanced. MAOI's may enhance the antimuscarinic effects of antihistamines

Caffeine:

Caffeine enhances the action of the ergot alkaloids in the treatment of migraine. Small doses of caffeine (5 to 10mg/kg) also appear to reduce the ED 50 for aspirin, indometacin and phenylbutazone by more than threefold.

Codeine Phosphate:

The depressant effects of some of the opioids may be exaggerated and prolonged by phenothiazines, monoamine oxidase inhibitors and tricyclic antidepressants. Codeine may cause a hypotensive or hypertensive effect if used with MAOI's. Concomitant use should be avoided and codeine should not be administered until 2 weeks after MAOI's are discontinued.

Alcohol, antipsychotics, anxiolytics and hypnotics may enhance the sedative and hypotensive effects of codeine.

When codeine is given with cisapride, metoclopramide or domperidone, the gut motility properties of these drugs may be lessened due to the constipating effect of codeine.

Cimetidine may inhibit the metabolism of opiates.

The absorption of mexiletine may be delayed by codeine and as such the anti-arrhythmic effect may be lessened.

Naltrexone and naloxone antagonise the analgesic, CNS and respiratory depressant effect of opioids.

The hypotensive action of diuretics and antihypertensives may be potentiated by codeine.

Use of antidiarrhoeals and antiperistaltic drugs such as loperamide may induce severe constipation. Concurrent use of antimuscarinics may lead to a greater risk of severe constipation which subsequently causes paralytic ileus and/or urinary retention.

4.6 Pregnancy And Lactation

No data is available on the use of these tablets in human pregnancy or on the excretion of it or its metabolites in human milk. Therefore this product is not recommended for use during pregnancy and lactation.

4.7 Effects On Ability To Drive And Use Machines

Caution is advised as this medicine may lead to drowsiness and impaired concentration aggravated by simultaneous intake of alcohol or other central nervous system depressant agents.

4.8 Undesirable Effects

In recommended therapeutic dosage, paracetamol is actually well tolerated. Skin rash and other allergic reactions occur occasionally. The rash is usually erythematous or urticarial, but sometimes more serious and may be accompanied by drug fever and mucosal lesions. In a few cases the use of paracetamol has been associated with the occurrence of thrombocytopenia, neutropenia, pancytopenia and leucopenia.

Acute pancreatitis has been reported after prolonged use of paracetamol.

Side effects of the antihistamines vary in incidence and severity with each patient as much as with each drug. The most common effect is sedation. Other side-effects include gastro-intestinal disturbances, headache, blurred vision, tinnitus, elation or depression, irritability, nightmares, anorexia, difficulty in micturition, dryness of the mouth, tightness of the chest, and tingling, heaviness and weakness of the hands.

Side effects of caffeine include nausea, headache and insomnia. Large doses may cause restlessness, excitement, muscle tremor, tinnitus, scintillating scotoma, tachycardia and extrasystoles. Caffeine increases gastric secretion and may cause gastric ulceration.

The commonest side effects of therapeutic doses of codeine are constipation, nausea and vomiting, dizziness, drowsiness, respiratory depression and hypotension, but these are less common than with morphine. Very rarely skin rashes may occur in patients hypersensitive to codeine. Regular prolonged use of codeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is then stopped. Prolonged use of a painkiller for headaches can make them worse.

4.9 Overdose

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

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

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.

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.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC Code: N02B E51

The tablets have analgesic, antipyretic and antihistaminic action.

5.2 Pharmacokinetic Properties

Paracetamol, doxylamine succinate, caffeine anhydrous and codeine phosphate, the active ingredients in these tablets, are well known and documented, and have been used in therapeutics for many years.

Paracetamol is absorbed via the gastrointestinal tract with peak plasma levels occurring within 10 to 60 minutes. Paracetamol is distributed throughout the body into the majority of body tissues. Metabolism occurs mainly in the liver and is excreted via the urine as glucuronide and sulphate conjugates. Excretion of unchanged paracetamol is less than 5%. The elimination half life is between 1 – 3 hours.

Doxylamine Succinate is absorbed with peak plasma concentrations occurring within 2 to 3 hours. The elimination half life is about 10 hours.

Caffeine is rapidly absorbed with peak plasma concentrations occurring between 5 and 60 minutes following oral administration. It is widely distributed throughout the body. Caffeine is metabolised by the liver and excreted as metabolites in the urine with only 1% as unchanged caffeine. In adults the elimination half life is about 3 – 7 hours.

Codeine is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring at about 60 minutes. Codeine is metabolised hepatically and excreted via the urine mainly as conjugates and glucuronic acid. The elimination half life is between 3 and 4 hours.

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

6.1 List Of Excipients

Maize starch

Povidone K25

Maize starch (dried)

Magnesium Stearate

Colloidal Silicon Dioxide

Microcrystalline Cellulose

Hypromellose

Hydroxypropyl Cellulose

Glycerol

Carnauba Wax

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

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

6.5 Nature And Contents Of Container

PVC (250μm) and foil (20μm) 'Blister Pack'. Pack sizes: 8, 10, 16, 20, 32.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Sandoz Ltd

Woolmer Way

Bordon

Hampshire GU35 9QE

8. Marketing Authorisation Number(S)

PL 04416/0363

9. Date Of First Authorisation/Renewal Of The Authorisation

05 January 2000 / 06 March 2009

10. Date Of Revision Of The Text

23/12/2009