Active Ingredients
Paracetamol 500 mg Codeine phosphate 15 mg
Excipients
Starch - maize, talc - purified, stearic acid, titanium dioxide, povidone, starch pregelatinised maize, potassium sorbate, magnesium stearate. Contains no sugar, lactose or wheat starch.
Paracetamol is a para-aminophenol derivative that exhibits analgesic and anti-pyretic activity. It does not possess anti-inflammatory activity. It is given by mouth or rectally for mild to moderate pain and fever. Codeine phosphate is an opioid analgesic which binds with stereospecific receptors at many sites within the central nervous system. It alters processes affecting both the perception of pain and the emotional response to pain. Codeine has about one- sixth of the analgesic activity of morphine.
After oral administration, paracetamol is absorbed rapidly and completely from the gastrointestinal tract; peak plasma levels occur 10 to 60 minutes after administration. Paracetamol is uniformly distributed throughout most body fluids; the apparent volume of distribution is 1 to 1.2 L/kg. Paracetamol can cross the placenta and is excreted in breast milk. Plasma protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations. Paracetamol is metabolised by the hepatic microsomal enzyme system. In adults at therapeutic doses, paracetamol is mainly conjugated with glucuronide (45 to 55%) or sulfate (20 to 30%). A minor proportion (less than 20%) is metabolised to catechol derivatives and mercapturic acid compounds via oxidation. Paracetamol is metabolised differently by infants and children compared to adults, the sulfate conjugate being predominant. Paracetamol is excreted in the urine mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol with 85 to 90% of the administered dose eliminated in the urine within 24 hours of ingestion. The elimination half-life varies from 1 to 3 hours. Food intake delays paracetamol absorption. Codeine phosphate is absorbed from the gastrointestinal tract and peak plasma concentrations are reached one hour after oral administration. Codeine is metabolised in the liver to morphine and norcodeine. Codeine and its metabolites are excreted almost entirely by the kidney within 24 hours. The metabolites are mainly conjugates with glucuronic acid. Patients who metabolise drugs poorly via CYP2D6 are likely to obtain reduced benefit from codeine due to reduced formation of the active metabolite. The plasma half-life varies between three and four hours after oral administration.
For the temporary relief of pain and discomfort associated with
| Headache | Arthritis |
| Migraine headache | Toothache |
| Tension headache | Neuralgia |
| Period pain | Cold & flu symptoms |
| Back pain | Dental procedures |
| Muscle pain | Sore throat |
| Reduces fever. |
Known sensitivity to paracetamol, codeine or any of the other ingredients. Active alcoholism. Acute respiratory depression. The use of codeine containing products is contraindicated in mothers who are breastfeeding, unless prescribed by a doctor.
Panadeine should be administered with caution to patients with hepatic or renal dysfunction. Patients with obstructive bowel disorders or acute abdominal conditions should consult a doctor before using this product. Patients with a history of cholecystectomy should consult a doctor before using this product as it may cause acute pancreatitis in some patients. Codeine should be used with caution in patients with CNS depression or decreased respiratory reserve. Prolonged use of high doses of codeine may produce dependence. Adults: Not to be taken for more than three days unless on the advice of a doctor. Children and adolescents 12-17 years: Not to be given for more than two days at a time unless on the advice of a doctor. Patients should be advised not to drive or operate machinery if affected by dizziness or drowsiness. Panadeine is for the relief of minor and temporary ailments and should be used strictly as directed. If symptoms persist or worsen, medical advice must be sought.
Category A - Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed. Use during pregnancy should be avoided unless advised by a physician. This includes maternal use during labor because of the potential of respiratory depression in the neonate. The safety of paracetamol and codeine during pregnancy has not been established relative to possible adverse effects on foetal development. Codeine-containing products must not be used while breastfeeding unless prescribed by a doctor Paracetamol is excreted in breast milk. Peak concentrations of 10 to 15 mcg/mL have been measured within 1 to 2 hours of a single 650 mg maternal dose. The half life of paracetamol in breast milk is 1.35 to 3.5 hours. Neither paracetamol or its metabolites were detected in the urine of breastfed infants following the maternal 650 mg dose. 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 and difficulty breastfeeding or breathing. In severe cases respiratory depression and death can occur. 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 sign and symptoms of morphine toxicity such as increased drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone, and should seek immediate medical care if such symptoms or signs are noticed.
Do not use in children under 12 years of age.
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. Paracetamol absorption is increased by drugs which increase gastric emptying, e.g. metoclopramide, and decreased by drugs which decrease gastric emptying, e.g. propantheline, antidepressants with anticholinergic properties, narcotic analgesics. Paracetamol may increase chloramphenicol concentrations. The likelihood of paracetamol toxicity may be increased by the concomitant use of enzyme inducing agents such as alcohol or anticonvulsant drugs. It is possible that interactions could occur between drugs that can inhibit CYP2D6 (such as quinidine, phenothiazines and antipsychotic agents) and codeine. Codeine enhances the central depressive effects of central nervous system depressants including alcohol, anaesthetics, hypnotics, sedatives, tricyclic antidepressants and phenothiazines. Opiate analgesics may interact with MOAI's and result in serotonin syndrome. Codeine may antagonise the effects of metoclopramide and domperidone on gastrointestinal motility.
Undesirable effects depend on dose and individual patient metabolism. Some patients are more like to experience undesirable effects because they rapidly convert codeine to morphine.
Adverse event data from clinical trials of codeine are sparse and are based on higher
doses of codeine than that contained in this product. These data are unreliable for
determining the nature and frequency of adverse reactions at dose of codeine contained in this product.
Post Marketing Data Paracetamol
Adverse events 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 Organ Class and frequency.
The following convention has been utilised for the classification of undesirable effects: very common (>=1/10), common (>=1/100, <1/10), uncommon (>=1/1,000, <1/100), rare (>=1/10,000, <1/1000), 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 and are considered to be very rare.
| Body System | Undesirable Effect |
| Blood and lymphatic system disorders | Thrombocytopaenia |
| Immune System disorders | Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angiodema, and Stevens Johnson syndrome |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm in patients sensitive to aspirin and other NSAIDs. |
| Hepatobiliary disorders | Hepatic dysfunction |
Reports of adverse reactions to paracetamol are rare. Although the following adverse reactions have been reported, a causal relationship to the administration of paracetamol has been neither confirmed nor refuted: dyspepsia and nausea.
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. |
Very rarely, skin rashes may occur in patients hypersensitive to codeine.
Adults and children 12 years and over: 2 tablets to be taken with water every four to six hours if necessary. Maximum 8 tablets in 24 hours. Do not use in children aged below 12 years. Adults: Do not exceed the stated dose or take for more than three days without a doctor's advice. Children and adolescents 12-17 years: Do not exceed the stated dose or take for more than two days at a time without a doctor's advice. If symptoms persist or worsen medical advice should be sought. Should not be used with other paracetamol or codeine products.
Effects of overdose due to codeine would be subsumed by the serious liver toxicity caused by paracetamol overdose. Immediate medical management is required in the event of overdose, even if symptoms of overdose are not present.
Paracetamol overdose may cause liver failure. Treatment Immediate medical management is required in the event of overdose, even if symptoms of overdose are not present. Administration of N-acetylcysteine or methionine may be required.
An overdose of codeine is characterized, in the first phase, by nausea and vomiting. An acute depression of the respiratory centre can cause cyanosis, slower breathing, drowsiness, ataxia and more rarely, pulmonary oedema. Respiratory pauses, miosis, convulsion, collapse and urine retention. Signs of histamine release have been observed as well.
Treatment
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 an hour of ingestion of more than 350 mg of codeine or a child more than 5 mg/kg of codeine. Give naloxone if coma or respiratory depression is present. Observe for at least four hours after ingestion or eight hours for a sustained release formulation. If an overdose is taken or suspected, phone the Poisons Information Centre should be contacted immediately for advice (131 126), or the patient should go to the hospital straight away, even if they feel well, because of the risk of delayed, serious liver damage.
Capsule-shaped tablets (white, marked PAN 15): 12s, 24s and 40s (retail pack) and 6s (health professional sample pack). Store below 30 degrees Celsius. Keep out of reach of children.
GlaxoSmithKline Consumer Healthcare 82 Hughes Avenue ERMINGTON NSW 2115
S3 - PHARMACIST ONLY MEDICINE
13.05.2004
06.08.2013
PANADEINE and The Panadeine Vibration are trade marks of the GlaxoSmithKline group of companies.