Cod-Acamol 15/325

/ Teva

The tablets should not be chewed or crushed.
The tablets may be divided.
Adults and Children above the age of 12 Years: 1-2 tablets every 4-6 hours, as needed. Dosage should not exceed 8 tablets in 24 hours.
This product should only be taken for a maximum of 3 days at a time. If needed to be taken for longer than 3 days the physician should be consulted.
If this medicine is taken for headaches for more than three days it can make them worse.

Relief of mild to moderate pain.
Relief of fever and cough associated with fever.

Known hypersensitivity to paracetamol or codeine, or to any other ingredient of the preparation.
Breastfeeding.
Diarrhoea caused by poisoning until the toxic material has been eliminated, or
diarrhoea associated with pseudomembraneous colitis.
Because of the codeine contents, this preparation must not be used:
– in children under the age of 12 years.
– in children (aged below 18 years) who undergo surgery for the removal of
the tonsils (tonsillectomy) or adenoids (adenoidectomy) to treat obstructive
sleep apnoea, as these patients are more susceptible to respiratory
problems and due to an increased risk of developing serious and
lifethreatening adverse reactions.
– in patients with moderate to severe degrees of renal or hepatic impairment.
– It is contraindicated in patients for whom opiate medications should not be
used, such as patients with acute asthma, obstructive airway disease,
respiratory depression, acute alcoholism, head injuries, raised intracranial
pressure, after biliary surgery, patients suffering from diarrhoea of any
cause, and patients who have taken MAOIs within 14 days.
– in patients for whom it is known they are CYP2D6 ultra-rapid metabolizers

WARNING: Death related to ultra-rapid metabolism of codeine to morphine respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine due to a CYP2D6 polymorphism.
This product 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 co-codamol 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, eg Addison’s Disease
• hypotension and shock
• myasthenia gravis
• phaeochromocytoma – opioids may stimulate catecholamine release by inducing the release of endogenous histamine
Where analgesics are used long-term (longer than 3 months) with administration every two days or more frequently, headache may develop or worsen. Headache induced by overuse of analgesics should not be treated by dose increase. In such cases, the use of analgesics should be discontinued in consultation with the doctor.
See prescribing information for full details.

At the recommended dosage, paracetamol may cause the following side effects:
• Allergic reactions – rare but may include skin rash, drug fever, mucosal lesions.
• Effects on CNS – drowsiness, impaired mental functions
• Effects on GI system – Chronic hepatic necrosis has been reported in a patient who took daily therapeutic doses of paracetamol for about a year, and liver damage has been reported after daily ingestion of excessive amounts for shorter periods. Acute pancreatitis has been reported. A review of a group of patients with chronic active hepatitis failed to reveal differences in the abnormalities of liver function in those who were long-term users of paracetamol, nor was the control of their disease improved after paracetamol withdrawal.
• Effects on CVS – toxic myocarditis.
• Effects on blood – There have been reports of blood dyscrasias including methaemoglobinaemia, neutropenia, pancytopenia, leukopenia, thrombocytopenic purpura, haemolytic anaemia and agranulocytosis, but these were not necessarily causality related to paracetamol.
• Effects on GU system – Nephrotoxicity following therapeutic doses of paracetamol is uncommon, but papillary necrosis has been reported after prolonged administration.
• Other effects – Most reports of adverse reactions to paracetamol relate to
overdosage with the drug. Very rare cases of skin reactions have been reported.
Adverse effects of opioid treatment which have been reported include:
• Allergic reactions (may be caused by histamine release) – including rash, urticaria, difficulty breathing, increased sweating, redness or flushed face.
• Effects on CNS – confusion, drowsiness, vertigo, dizziness, changes in mood,
hallucinations, CNS excitation (restlessness/excitement), convulsions, mental
depression, headache, trouble sleeping, or nightmares, raised intracranial pressure, tolerance or dependence.
• Effects on GI system – constipation, GI irritation, biliary spasm, nausea, vomiting, loss of appetite, dry mouth, paralytic ileius or toxic megacolon.
• Effects on CVS – bradycardia, palpitations, hypotension.
• Effects on sensory system -blurred or double vision.
• Effects on GU system – ureteral spasm, antidiuretic effect.
• Other effects – trembling, unusual tiredness or weakness, malaise, miosis,
hypothermia.
• Effects of withdrawal – abrupt withdrawal precipitates a withdrawal syndrome.
Symptoms may include tremor, insomnia, nausea, vomiting, sweating and increase in heart rate, respiratory rate and blood pressure. NOTE – tolerance diminishes rapidly after withdrawal so a previously tolerated dose may prove fatal.
• Regular prolonged use of codeine 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.

Paracetamol Drug Interactions
Paracetamol/Oral Anticoagulants: Regular administration of paracetamol may
enhance the activity of coumarin anticoagulants, when given concurrently.
Occasional doses have no significant effect.
Paracetamol/Drugs which Alter Gastric-Emptying Time: (eg Cimetidine, Ethyl alcohol, Oral Steroid contraceptives). These drugs reduce or delay peak paracetamol blood levels.
Paracetamol/ Drugs which interfere with the metabolism of paracetamol by competition with metabolic pathways or substrates eg anticonvulsants (phenytoin), hepatic enzyme inducers, alcohol, barbiturates, tricyclic antidepressants. A poor diet (low protein) may also have a similar effect on the risk of serious paracetamol toxicity to hepatic enzyme inducers. Patients who have taken barbiturates, tricyclic antidepressants and alcohol may show diminished ability to metabolise large doses of paracetamol, the plasma half-life of which may be prolonged.
Paracetamol/ Hepatic Enzyme-Inducing Agents (e.g., Barbiturates, Phenytoin,
Primidone)/Hepatotoxic Medications/ Alcohol: Concurrent administration of enzyme inducers and paracetamol may decrease the therapeutic effect of paracetamol, probably because of increased metabolism resulting from induction of hepatic microsomal enzyme activity.
The risk of hepatotoxicity with single toxic doses or prolonged use of high doses of paracetamol may be increased in alcoholics or in patients taking other hepatotoxic medications.
Paracetamol/ Salicylates/ Other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Chronic high-dose administration of paracetamol with salicylates and/or other nonsteroidal anti-inflammatory drugs increases the risk of analgesic nephropathy.
Paracetamol/ Zidovudine: Paracetamol may competitively inhibit the hepatic
glucuronidation and decrease the clearance of zidovudine. Zidovudine may also inhibit the hepatic glucuronidation of paracetamol. Concurrent use should be avoided, because the toxicity of either or both medications may be potentiated.
Paracetamol/Cholestyramine: Cholestyramine may reduce the absorption of paracetamol. Oral doses of cholestyramine and paracetamol should be given at least 1 hour apart.
Paracetamol/Metoclopramide/Domperidone: The speed of absorption of paracetamol may be increased by metoclopramide or domperidone.
Codeine Drug Interactions
Codeine/Centrally-acting Drugs: Codeine may potentiate the effect of drugs which depress the central nervous system and/or have hypotensive effect with alcohol, anesthetics, hypnotics, anxiolytics, antipsychotics, hydroxyzine, tricyclic antidepressants, such as, monoamine oxidase inhibitors, phenothiazines, antihistamines and barbiturates. Concurrent use requires the adjustment of dosage.
Codeine Phosphate can also interact with the following:
• CNS depressants – enhanced sedative
• Antibacterials, eg ciprofloxacin, – avoid premedication with opioids as reduced
plasma ciprofloxacin concentration
• Cyclizine
• Mexiletine – delayed absorption
• Metoclopramide and domperidone – antagonise GI effects
• Cisapride – possible antagonism of GI effects
• Dopaminergics (eg selegiline) – possible risk of hyperpyrexia and CNS toxicity. This risk is greater with pethidine but with other opioids the risk is uncertain
• Ulcer healing drugs – cimetidine inhibits the metabolism of opioid analgesics.
• Anticholinergics (eg atropine) – risk of severe constipation which may lead to
paralytic illness, and /or urinary retention
• Antidiarrhoeal drugs (eg loperamide, kaolin) – increased risk of severe constipation
• Antihypertensive drugs (eg guanethidine, diuretics) – enhanced hypotensive effect
• Opioid antagonists (eg buprenorphine, naltrexone, naloxone)
• Neuromuscular blocking agents – additive respiratory depressant effects.
Diagnostic Interference
Blood Glucose: Blood glucose determinations, when measured by the glucose oxidase/peroxidase method, may be falsely decreased; but probably not when measured by the hexokinase/glucose-6-phosphate dehydrogenase (G6PD) method.
Serum Uric Acid: Falsely increased serum uric acid values may occur when the phosphotungstate uric acid test method is used.
Urine 5-Hydroxyindoleactic Acid (5-HIAA): Qualitative screening tests using nitrosonaphthol may produce false-positive test results. The quantitative test is unaffected.
Pancreatic Function Test using Bentiromide: Administration of paracetamol prior to the bentiromide test will invalidate the test results, because paracetamol is also metabolized to an arylamine and will therefore increase the apparent quantity of para-aminobenzoic acid (PABA) recovered.
It is recommended that paracetamol be discontinued at least three days prior to
administration of bentiromide.

Pregnancy: Safety of use in pregnancy has not been established.
Breastfeeding: Paracetamol appears in very low concentration in breast milk. Codeine can pass to the baby through breast milk, therefore breastfeeding is
contraindicated.

Manifestations: The first toxic symptoms to appear upon overdosage with this preparation relate to codeine. They are nausea, vomiting, and evidence of circulatory and respiratory depression.
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia, and abdominal pain. 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.
In massive overdosage, paracetamol may cause hepatic toxicity. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48-72 hours postingestion.
Serious toxicity or fatalities are extremely infrequent in children, possibly due to
differences in the way they metabolize paracetamol. An acute overdose of less than 150 mg/kg body weight in children has not been associated with hepatic toxicity.
Treatment: Immediate treatment should first relate to codeine intoxication. It should consist of gastric lavage, artificial respiration and eventual treatment with naloxone HCl 400 mcg I.V., I.M. or S.C., to be repeated as needed every 2-3 minutes.
See prescribing information for full details.