1. Name Of The Medicinal Product
Paramol Soluble Tablets.
2. Qualitative And Quantitative Composition
Paracetamol 500 mg
Dihydrocodeine tartrate 7.46 mg
3. Pharmaceutical Form
Effervescent tablet
4. Clinical Particulars
4.1 Therapeutic Indications
For the treatment of mild to moderate pain; including headache, migraine, feverish conditions, period pain, toothache and other dental pain, back pain, muscular and joint pains, neuralgia, the aches and pains of cold and flu, and as an antipyretic.
4.2 Posology And Method Of Administration
For oral administration.
Dosage and administration
Paramol Soluble Tablets should be taken during or after meals. The tablets should be dissolved in water.
Adults and children over 12 years:
1 or 2 tablets every four to six hours. Do not exceed eight tablets in any 24-hour period. Do not take for more than 3 days continuously without medical review.
Children under 12 years:
Not recommended.
Elderly:
Caution should be observed in increasing the dose in the elderly.
4.3 Contraindications
Known hypersensitivity to paracetamol, dihydrocodeine, other opioids or other constituents of the tablets.
Respiratory depression, obstructive airways disease, convulsive disorders.
Diarrhoea caused by poisoning until the toxic material has been eliminated, or diarrhoea associated with pseudomembranous colitis.
4.4 Special Warnings And Precautions For Use
Paramol Soluble Tablets should be used with caution in patients with:
• Hepatic function impairment (avoid if severe) and those with non-cirrhotic alcoholic liver disease. The hazards of overdose are greater in those with alcoholic liver disease.
• Prolonged use of Paramol Soluble Tablets may cause hepatic necrosis.
• Renal function impairment.
• Hypothyroidism (risk of depression and prolonged CNS depression is increased)
• Inflammatory bowel disease – risk of toxic megacolon
• Opioids should not be administered during an asthma attack
• Convulsions - may be induced or exacerbated
• Drug abuse, dependence (including alcoholism), enhanced instability, suicidal ideation or attempts – predisposed to drug abuse
• Head injuries or conditions where intracranial pressure is raised
• Gall bladder disease or gall stones - opioids may cause biliary contraction
• Gastro-intestinal surgery - use with caution after recent GI surgery as opioids may alter GI motility
• Prostatic hypertrophy or recent urinary tract surgery
• Adrenocortical insufficiency, e.g. Addison's Disease
• Hypotension and shock
• Myasthenia gravis
• Phaeochromocytoma - opioids may stimulate catecholamine release by inducing the release of endogenous histamine
The label will state:
Do not exceed the recommended dose.
Do not take with any other paracetamol-containing products. Immediate medical attention should be sought in the event of an overdose, even if you feel well.
May cause dizziness, if affected do not drive or operate machinery.
If symptoms persist, consult your doctor.
Keep out of the reach and sight of children.
The label will state (to be displayed prominently on outer pack, not boxed):
If you need to use this medicine for more than three days at a time, see your doctor or pharmacist. Taking dihydrocodeine regularly for a long time can lead to addiction. Taking a painkiller for headaches too often or for too long can make them worse.
The leaflet will state:
Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage.
The leaflet will state in a prominent position in the before taking section:
If you need to use this medicine for more than three days at a time, see your doctor, pharmacist or healthcare professional. Taking codeine regularly for a long time can lead to addiction, which might cause you to feel restless and irritable when you stop taking the tablets. Taking a painkiller for headaches too often or for too long can make them worse.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.
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.
The depressant effects of opioid analgesics are enhanced by other CNS depressants such as alcohol, anaesthetics, anxiolytics, hypnotics, tricyclic antidepressants and antipsychotics.
Dihydrocodeine tartrate may interact with monoamine oxidase inhibitors (MAOI's), such that opioids should not be used in patients taking MAOI's or within 14 days of stopping such treatment. If opioid analgesics are required they should be given with extreme caution.
The effects of dihydrocodeine tartrate in reducing gastrointestinal motility may interfere with the absorption of such as mexiletine, and may counteract the stimulatory effect of metoclopramide and domperidone.
Cimetidine inhibits the metabolism of some opioids
4.6 Pregnancy And Lactation
Epidemiological studies in human pregnancy have shown no effects due to paracetamol used in the recommended dosage. However, paracetamol should be avoided in pregnancy unless considered essential by the physician.
Risk benefit must be considered because opioid analgesics cross the placenta. Studies in animals have shown opioids to cause delayed ossification in mice and increased resorption in rats.
Regular use during pregnancy may cause physical dependence in the fetus, leading to withdrawal symptoms in the neonate. During labour opioids enter the fetal circulation and may cause respiratory depression in the neonate.
Administration should be avoided during the late stages of labour and during the delivery of a premature infant.
Paracetamol is excreted in breast milk but not in a clinically significant amount.
Available published data do not contraindicate breast feeding; however some opioids are distributed in breast milk in small amounts and it is advisable to avoid administration of opioids in a breastfeeding woman.
4.7 Effects On Ability To Drive And Use Machines
Opioid analgesics can impair mental function and can cause blurred vision and dizziness. Patients should make sure they are not affected before driving or operating machinery.
4.8 Undesirable Effects
Adverse effects of paracetamol are rare but hypersensitivity, including skin rash, may occur. There have been rare reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol. Constipation if it occurs, is readily treated with a mild laxative. Nausea, headache, vertigo, dizziness and urinary retention may occur in a few patients.
Regular prolonged use of dihydrocodeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is stopped. Prolonged use of a painkiller for headaches can make them worse.
4.9 Overdose
Paracetamol:
Symptoms: Pallor, nausea, vomiting, anorexia and abdominal pain in the first 24 hours. 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 have been reported.
Liver damage is likely in adults who have taken 10g or more of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.
Treatment: 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 and any patient who had ingested around 7.5g or more of paracetamol in the preceding 4 hours should undergo gastric lavage. Administration of oral methionine or intravenous N-acetylcysteine, which may have a beneficial effect up to at least 48 hours after the overdose, may be required.
General supportive measures must be available.
Opioids:
Symptoms: cold clammy skin, confusion, convulsions, severe drowsiness, tiredness, low blood pressure, pinpoint pupils of eyes, slow heart beat and respiratory rate coma.
Treatment: Treat respiratory depression or other life-threatening adverse effects first.
Empty the stomach via gastric lavage or induction of emesis.
The opioid antagonist naloxone (0.4-2mg subcutaneous) can be given and repeated at 2-3 minute intervals to a maximum of 10mg. Naloxone may also be given by intramuscular injection or intravenous infusion. The patient should be monitored as the duration of opioid analgesic may exceed that of the antagonist.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Paracetamol is an effective analgesic possessing a remarkably low level of side effects. Its broad clinical utility has been extensively reported, and it now largely replaces aspirin for routine use. Paracetamol is well tolerated, having a bland effect on gastric mucosa, unlike aspirin, it neither exacerbates symptoms of peptic ulcer nor precipitates bleeding. Dihydrocodeine tartrate has been widely used for a number of years as a powerful analgesic; 30 mg of dihydrocodeine has been reported to have analgesic potency equal to 60 or 120 mg codeine.
In addition the compound exhibits well-defined anti-tussive activity.
Fortifying paracetamol with 7.46 mg dihydrocodeine tartrate provides an effective combination of drugs for the treatment of severe pain.
5.2 Pharmacokinetic Properties
Dihydrocodeine is well absorbed from the gastrointestinal tract. Like other phenanthrene derivatives, dihydrocodeine is mainly metabolised in the liver with the resultant metabolites being excreted mainly in the urine. Metabolism of dihydrocodeine includes o-demethylation, n-demethylation and 6-keto reduction.
Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring 30 minutes to 2 hours after ingestion. It is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates.
5.3 Preclinical Safety Data
Not applicable.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Citric acid (anhydrous, added as citric acid monohydrate)
Sodium hydrogen carbonate
Sodium carbonate (anhydrous)
Sodium benzoate
Saccharin sodium
Povidone
6.2 Incompatibilities
None known.
6.3 Shelf Life
24 months.
6.4 Special Precautions For Storage
Store at or below 25ºC.
6.5 Nature And Contents Of Container
1. Blister packs: 43 µm soft tempered aluminium foil coated with 25 µm polyethylene on the inside.
2. Aluminium foil strip packs: 25 µm aluminium foil coated with 40g/m2 paper and 12g/m2 polyethylene on the outside and 18g/m2 surlyn on the inside.
Pack sizes: 2, 12, 24 tablets
6.6 Special Precautions For Disposal And Other Handling
None stated.
7. Marketing Authorisation Holder
Seton Products Ltd.
Tubiton House
Oldham
OL1 3HS
8. Marketing Authorisation Number(S)
PL 11314/0058.
9. Date Of First Authorisation/Renewal Of The Authorisation
20th December 1995.
10. Date Of Revision Of The Text
June 2007
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