Mybucod 10 mg/200 mg/350 mg FC tablets

MYBUCOD is indicated for the relief of mild to moderate pain or fever of inflammatory origin for a maximum treatment period of 5 days.

Posology
DO NOT EXCEED THE RECOMMENDED DOSE. Use the lowest effective dose for the shortest possible duration of treatment.
Adults (over the age of 12 years): Take 1 to 2 tablets 4 hourly. Do not take more than 6 tablets in 24 hours. Consult your healthcare professional if you require further treatment after 5 days.
Paediatric population
MYBUCOD should not be used in children 12 years of age and younger (see section 4.3).

Method of administration
For oral administration.

MYBUCOD is contraindicated in:
u2022 Patients with hypersensitivity to ibuprofen, codeine, paracetamol or to any excipients in MYBUCOD (see section 6.1).
u2022 Patients with acute respiratory depression especially in the presence of cyanosis and excessive bronchial secretion, after operations on the biliary tract, acute alcoholism, head injuries and conditions in which intracranial pressure is raised.
u2022 Patients with heart failure or cardiovascular disease.
u2022 Concurrent use with Monoamine Oxidase Inhibitors (MAOIs) or within 14 days of stopping such treatment (see section 4.5).
u2022 Patients with diarrhoea associated with pseudomembranous colitis.
u2022 Patients with impaired hepatic and renal function (see section 4.4).
u2022 Patients with history of peptic ulcer disease or gastrointestinal perforation, ulceration, or bleeding (PUBs) related to previous NSAIDs, including MYBUCOD.
u2022 Patients with an active or a history of recurrent gastrointestinal ulcer, haemorrhage or perforations.
u2022 Patients sensitive to aspirin or another nonsteroidal anti-inflammatory medicine.
u2022 Patients during an attack of bronchial asthma, uncontrolled asthma or bronchospasm or in heart failure secondary to chronic lung disease.
u2022 Patients with nasal polyps associated with aspirin-induced bronchospasm.
u2022 Patients with bleeding disorders.
u2022 Patients who are receiving coumarin anticoagulants (see section 4.5).
u2022 Women who are breastfeeding their infants and women in the third trimester of pregnancy (see section 4.6).
u2022 Women around the third trimester in pregnancy due to the risks of oligohydramnios/ foetal renal dysfunction and premature closure of the foetal ductus arteriosus (see section 4.4 and 4.6).
u2022 Patients for whom it is known they are CYP2D6 ultra-rapid metabolisers (see section 4.4).
u2022 Chronic constipation.
u2022 Children under the age of 12.
u2022 Codeine should not be used at all in children (aged below 18 years) who undergo surgery for the removal of the tonsils or adenoids to treat obstructive sleep apnoea, as these patients are more susceptible to respiratory problems.

MYBUCOD should not be administered continuously for longer than 5 days as safety has not been established.
Paracetamol as contained in MYBUCOD
MYBUCOD contains paracetamol which may be fatal in overdose. In the event of overdosage or suspected overdose and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital or Poison Centre must be contacted immediately. Dosages in excess of those recommended may cause severe liver damage. Alcohol should be avoided. Increased risk of liver toxicity, especially in alcoholics using high doses of MYBUCOD for a prolonged period of time.
Severe cutaneous adverse reactions
Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS), acute generalised exanthematous pustulosis (AGEP), Drug reaction with eosinophilia and systemic (DRESS)/Drug induced hypersensitivity syndrome (DIHS) and fixed drug eruptions (FDE) have been reported in patients treated with paracetamol containing medicines. If a patient develops SCAR, treatment with MYBUCOD must immediately be discontinued and appropriate treatment instituted.
High Anion gap metabolic acidosis (HAGMA)
Caution is advised if MYBUCOD is administered concomitantly with flucloxacillin due to increased risk of high anion gap metabolic acidosis (HAGMA), particularly in patients with severe renal impairment, sepsis, malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism), as well as those using maximum daily doses of MYBUCOD. Close monitoring, including measurement of urinary 5-oxoproline, is recommended.
Codeine as contained in MYBUCOD
EXCEEDING THE PRESCRIBED DOSE, TOGETHER WITH PROLONGED AND CONTINUOUS USE OF THIS MEDICATION MAY LEAD TO DEPENDENCY AND ADDICTION.
Opioid use disorder (abuse and dependence)
Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids such as codeine, as contained in MYBUCOD. Abuse or intentional misuse of MYBUCOD may result in overdose and/or death. Tolerance is the need for increasing doses to maintain analgesia. Tolerance may occur to both the desired and undesired effects of the opioid. Serious clinical outcomes, including fatalities, have been reported in association with abuse and dependence with codeine/ibuprofen combinations, as contained in MYBUCOD, particularly when taken for prolonged periods at higher than recommended doses. These have included reports of gastrointestinal perforations, gastrointestinal haemorrhages, severe anaemia, renal failure, renal tubular acidosis, and severe hypokalaemia associated with the ibuprofen component. Patients should be informed about the risks and signs of OUD as well as serious clinical outcomes. If these signs occur, patients should be advised to contact their doctor.
Withdrawal symptoms, such as restlessness and irritability may occur once the medicine is stopped.
MYBUCOD should be used with caution in patients with personal or family history of substance abuse or mental health disorders.
CYP2D6 metabolism
Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained. Estimates indicate that up to 7 % of the Caucasian population may have this deficiency. However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses (see section 4.3). These patients convert codeine into morphine rapidly resulting in higher-than-expected serum morphine levels (see section 4.3).
Opioid-Induced Hyperalgesia or Allodynia
Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain (hyperalgesia), or an increase in sensitivity to pain (allodynia). This condition differs from tolerance, which is the need for increasing doses of opioids to maintain a defined effect. Symptoms of OIH include increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia). The pain experienced may be at the same location of the underlying pain or can be more generalised or widespread in nature. These symptoms may suggest the occurrence of OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behaviour.
If a patient is suspected to be experiencing OIH, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation (safely switching the patient to a different opioid moiety).
MYBUCOD should be used with caution in the following:
u2022 Acute abdominal conditions: Diagnosis or clinical course may be obscured (see section 4.3).
u2022 Cardiac dysrhythmias: May be induced or exacerbated (see section 4.3).
u2022 Convulsions or history thereof: May be induced or exacerbated.
u2022 Alcoholism, drug abuse or dependence: Patient is predisposed to drug abuse. Avoid alcohol - Increased risk of liver toxicity, especially in alcoholics with high doses and prolonged use (see sections 4.3 and 4.5).
u2022 Gallbladder disease or gallstones: May cause biliary tract spasm (see section 4.3).
u2022 Recent gastrointestinal tract surgery.
u2022 Hypothyroidism: Increase risk of respiratory depression and prolonged central nervous system depression.
u2022 Adrenocortical insufficiency.
u2022 Inflammatory or obstructive bowel disorders: Risk of toxic megacolon may be increased (see section 4.3).
u2022 Prostatic hypertrophy, obstruction, urethral stricture, or recent urinary tract surgery: As urinary retention may be precipitated by MYBUCOD.
u2022 Risk of severe constipation if used with antidiarrhoeal medicines such as diphenoxylate (see sections 4.3 and 4.5).
u2022 Myasthenia gravis.

Ibuprofen as contained in MYBUCOD
Anticoagulants (e.g warfarin and heparin)
Enhancement of anticoagulant effect and the possibility of gastrointestinal ulceration or bleeding (see section 4.3 and 4.4).
Acetylsalicylic acid (aspirin)
Unless low-dose aspirin (not above 75 mg daily) has been advised by a doctor, concomitant administration of ibuprofen, as in MYBUCOD, and acetylsalicylic acid is not generally recommended because of the potential of increased adverse effects. Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Although there are uncertainties regarding extrapolation of data to the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded.
NSAIDs including cyclooxygenase-2 selective inhibitors
Use of two or more NSAIDs concomitantly could result in an increase in side effects.
Methotrexate
Increased and prolonged methotrexate plasma concentration and an increased risk of methotrexate toxicity. NSAIDs, such as ibuprofen, as contained in MYBUCOD, inhibit the tubular secretion of methotrexate and certain metabolic interactions can occur resulting in decreased clearance of methotrexate. The administration of ibuprofen within 24 hours before or after the administration of methotrexate can lead to an elevated concentration of methotrexate and an increase in its toxic effects. Therefore, concomitant use of MYBUCOD and high doses of methotrexate should be avoided. Also, the potential risk of interactions in low dose treatment with methotrexate should be considered, especially in patients with impaired renal function. In combined treatment, renal function should be monitored.
Corticosteroids
Increased risk of gastrointestinal perforation, ulceration, or bleeding (PUBs) (see section 4.4).
Cardiac glycosides
NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.
Anti-platelet medicines (e.g clopidogrel and ticlopidine) and selective serotonin reuptake inhibitors (SSRIs)
Increased risk of gastrointestinal bleeding (see section 4.4).

MYBUCOD is not recommended for use by pregnant or breastfeeding women (see section 4.3 and 4.4).
Pregnancy
Ibuprofen as contained in MYBUCOD
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1 %, up to approximately 1,5 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post- implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period.
Second and third trimester
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors, such as MYBUCOD may expose the foetus to:
u2022 cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
u2022 renal dysfunction, leading to oligohydramnios and, in some cases, neonatal renal impairment (see section 4.4).
At the end of pregnancy the mother and the neonate may be exposed to:
u2022 possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses;
u2022 inhibition of uterine contractions resulting in delayed or prolonged labour.
Because of these risks, the use of MYBUCOD dose and duration between 20 and 30 weeks of gestation should be limited and avoided at around 30 weeks of gestation and later in pregnancy (see section 4.3 and 4.4).
Codeine phosphate as contained in MYBUCOD
MYBUCOD contains codeine phosphate, a narcotic analgesic. Use of narcotic analgesics during pregnancy is associated with foetal adverse effects, which include physical dependence and withdrawal, retardation of growth, and neonatal respiratory depression with high doses. An association between abnormalities of the respiratory tract and the use of codeine during the first three months of pregnancy was found in humans. Evidence for other malformations was also found in epidemiological studies with narcotic analgesics, including codeine. Codeine, as contained in MYBUCOD, may therefore only be used during pregnancy, especially during the first three months, if clearly indicated and after a careful benefit-risk assessment. In case of imminent birth or preterm birth, the use of codeine is contraindicated since codeine crosses the placental barrier and can cause neonatal respiratory depression.
Paracetamol as contained in MYBUCOD
A large amount of data on pregnant women indicates neither malformative, nor foeto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy, however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.
Breastfeeding
Codeine as contained in MYBUCOD
Codeine should not be used during breastfeeding (see section 4.3). At normal therapeutic doses codeine, as in MYBUCOD, and its active metabolite may be present in breast milk at very low doses and is unlikely to adversely affect the breastfed 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.
Ibuprofen as contained in MYBUCOD
In limited studies, ibuprofen as contained in MYBUCOD, appears in the breast milk in very low concentration and is unlikely to affect the breastfed infant adversely. With therapeutic doses during short term treatment the risk for influence on infant seems unlikely. If, however, longer treatment is prescribed, early weaning should be considered.
Fertility
Ibuprofen as contained in MYBUCOD
There is some evidence that medicines which inhibit cyclo-oxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.

MYBUCOD has minor influence on the ability to drive or operate machinery. Since adverse events such as drowsiness have been reported in patients receiving MYBUCOD, patients should not drive, use machinery, or perform any tasks that require concentration, until they are certain that MYBUCOD does not adversely affect their ability to do so (see section 4.8).

a) Summary of the safety profile
In view of MYBUCODu2019s inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients. The most commonly observed adverse events are gastro-intestinal in nature.
b) Tabulated list of adverse reactions
Ibuprofen
System organ class Frequent Less frequent Frequency unknown (cannot be estimated from the available data)
Infections and Infestations Aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of stiff neck, nausea, vomiting, fever or disorientation.
Blood and the lymphatic system disorders Haematopoietic disorders (leucopoenia, pancytopenia, agranulocytosis, thrombocytopenia with or without purpura, aplastic anaemia, haemolytic anaemia, anaemia, neutropenia). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.
Immune system disorders Hypersensitivity reactions with urticaria and pruritus, symptoms Respiratory tract reactivity comprising asthma.
Psychiatric disorders Confusional state, nervousness, insomnia, depression, anxiety, hallucination.
Nervous system disorders Dizziness. Drowsiness, headache, somnolence, fatigue, agitation, irritability, optic neuritis, paraesthesia.
Eye disorders Blurred vision and other ocular reactions. Visual impairment and toxic optic neuropathy.
Ear and labyrinth disorders Tinnitus, hearing impairment and vertigo.
Cardiac disorders Angina pectoris, cardiac dysrhythmias, oedema, hypertension, and cardiac failure.
Respiratory, thoracic and mediastinal disorders Bronchospasm, rhinitis. Alveolitis, pulmonary eosinophilia.
Metabolism and nutrition disorders Hypokalaemia, decreased appetite.
Gastrointestinal disorders Heartburn, dyspepsia, abdominal cramps and pain, nausea, vomiting, flatulence, diarrhoea, bloating, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohnu2019s disease, gastritis, constipation. Peptic ulceration, perforation or gastrointestinal bleeding, sometimes fatal. Gastrointestinal ulcers, sometimes with bleeding and perforation, occult blood loss which may lead to anaemia, inflammatory bowel disease, complications of colonic diverticula (perforation, fistula), oesophagitis, pancreatitis, intestinal strictures.
Hepatobiliary disorders Abnormalities of liver function tests, hepatitis, jaundice, liver dysfunction, liver damage, especially in long-term use, hepatic failure. Hepatotoxicity.
Skin and subcutaneous tissue disorders Skin rash, pruritus. Severe forms of skin reactions such as bullous reactions, including Stevens-Johnson Syndrome, erythema multiforme and toxic epidermal necrolysis. Photosensitivity reactions. Severe cutaneous adverse reactions (SCARs) such as Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), Acute generalised exanthematous pustulosis (AGEP).
Renal and urinary disorders Impairment of renal function, acute reversible renal failure, oedema, papillary necrosis, nephritic syndrome, interstitial nephritis which can be associated with renal failure. Renal tubular acidosis (reported in the post- marketing setting typically following prolonged use at higher than recommended doses due to dependence on the codeine component), ureteric colic, dysuria.
Investigations Increase of blood urea nitrogen, serum transaminases and alkaline phosphatase, decrease in haemoglobin and haematocrit values, inhibition of platelet aggregation, prolonged bleeding time, decrease of serum calcium, increase in serum uric acid.
General disorders and administration site conditions Malaise, fatigue. Hyperhidrosis, irritability.
Paracetamol
System organ class Frequent Less frequent Frequency unknown (Cannot be estimated from the available data)
Blood and the lymphatic system disorders Haematological reaction (including thrombocytopenia, anaemia, leukopenia, pancytopenia, neutropenia and agranulocytosis).
Immune system disorders Anaphylactic reaction, hypersensitivity reactions characterised by urticaria, dyspnoea and hypotension.
Metabolism and nutrition disorders Pyroglutamic aciduria (5- oxoprolinuria) and high-anion gap metabolic acidosis.
Ear and labyrinth disorders Hearing loss.
Cardiac disorders Possible increase in the risk of hypertension.
Respiratory, thoracic and mediastinal disorders Bronchospasm (There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs).
Gastrointestinal disorders Pancreatitis. Nausea and vomiting.
Hepatobiliary disorders Hepatitis, hepatic enzyme increase, hepatic dysfunction.
Skin and subcutaneous tissue disorders Dermatitis, skin rash and other allergic reactions such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalised exanthematous pustulosis (AGEP), drug rash with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) and fixed drug eruptions (FDE) (see section 4.4). The rash is usually erythematous or urticarial but sometimes more serious and accompanied by fever and mucosal lesion. More mild rashes and other hypersensitivity reactions also occur occasionally.
Renal and urinary disorders Renal colic, renal failure, sterile pyuria. Nephropathy.
General disorders Sensitivity reactions resulting in reversible skin rash (which may be accompanied by fever and mucosal lesions) or blood disorders.
Investigations Increased transaminases. Low level transaminase elevations may occur in some patients taking therapeutic doses of paracetamol, as in MYBUCOD. These elevations are not accompanied with liver failure and usually resolve with continued therapy or discontinuation of paracetamol, as in MYBUCOD.
Codeine Phosphate
System organ class Frequent Less frequent Frequency unknown (Cannot be estimated from the available data)
Psychiatric disorders Euphoria, hallucinations, dysphoria, mood changes, restlessness. Nightmares.
Nervous system disorders Confusion, vertigo, restlessness, changes in mood, raised intracranial pressure, drowsiness, dizziness, seizures, addiction, tolerance, dependence, headache vertigo, malaise, sleep disturbances. Convulsion, dyskinesia.
Eye disorders Changes in miosis, blurred or double vision. Diplopia.
Cardiac disorders Bradycardia, tachycardia, palpitations, orthostatic hypotension.
Vascular disorders Facial flushing, postural hypotension, hypothermia.
Respiratory, thoracic and mediastinal disorders Respiratory depression, cough suppression.
Gastrointestinal disorders Nausea, vomiting, constipation, dry mouth, pancreatitis.
Hepatobiliary disorders Biliary spasm, liver disorder. Biliary colic.
Skin and subcutaneous tissue disorders Urticaria, pruritus, rashes.
Musculoskeletal and connective tissue disorders Muscle rigidity.
Renal and urinary disorders Micturition difficulties, ureteric spasm or retention, dysuria (Increased frequency, decrease in amount).
General disorders and administrative site conditions Sweating.
Investigations Decreased haemoglobin.

Paracetamol
Symptoms
In the first 24 hours, symptoms include pallor, nausea, vomiting, anorexia, and possibly abdominal pain. Mild symptoms during the first two days of acute poisoning do not reflect the potential seriousness of the overdosage. Liver damage may become apparent 12 to 48 hours, or later after ingestion of paracetamol, initially by elevation of the serum transaminase and lactic dehydrogenase activity, increased serum bilirubin concentrations and prolongation of the prothrombin time. Liver damage may lead to encephalopathy, coma, and death. Acute renal failure with acute tubular necrosis may develop even the absence of severe liver damage. Abnormalities of glucose metabolism and acidosis may occur. Cardiac dysrhythmias have been reported. Cerebral oedema and non-specific myocardial depression have occurred.
Figure 1: A semi-logarithmic plot of plasma-paracetamol concentration against hours after ingestion.
Prompt treatment is essential. In the event of overdosage, consult a doctor immediately, or take the person to a hospital directly. A delay in starting treatment may mean that the antidote is given too late to be effective. Evidence of liver damage is often delayed until after the time for effective treatment has lapsed. Susceptibility to paracetamol toxicity is increased in patients who have taken repeated high doses (greater than 5 g to 10 g/day) of paracetamol for several days, in chronic alcoholism, chronic liver disease, AIDS, malnutrition, and with the use of medicines that induce liver microsomal oxidation such as barbiturates, isoniazid, rifampicin, phenytoin and carbamazepine.
Treatment of overdose
N-acetylcysteine should be administered to all cases of suspected overdose as soon as possible, preferably within eight hours of overdosage, although treatment up to 36 hours after ingestion may still be of benefit, especially if more than 150 mg/kg of paracetamol was taken. An initial dose of 150 mg/kg N-acetylcysteine in 200 ml dextrose injection given intravenously over 15 minutes, followed by an infusion of 50 mg/kg in 500 ml dextrose injection over the next four hours, and then 100 mg/kg in 1 000 ml dextrose injection over the next sixteen hours. The volume of intravenous fluid should be modified for children.
Although the oral formula is not the treatment of choice, 140 mg/kg dissolved in water as a 5 % solution may be administered initially, followed by 70 mg/kg every four hours for seventeen doses. If activated charcoal is used, then it should be removed by gastric lavage as it may interfere with absorption of orally administered acetylcysteine and decrease its efficacy.
A plasma paracetamol level should be determined four hours after ingestion in all cases of suspected overdose. Levels done before four hours, unless high, may be misleading. Patients at risk of liver damage and hence requiring continued treatment with N-acetylcysteine, can be identified according to their plasma paracetamol level. The plasma paracetamol level can be plotted against time since ingestion in the treatment nomogram (refer figure 1 above). Those, whose plasma paracetamol levels are above the u201cnormal treatment lineu201d, should continue N-acetylcysteine treatment with 100 mg/kg IV over sixteen hours repeatedly until recovery. Patients with increased susceptibility to liver damage as identified above, should continue treatment if concentrations are above the u201chigh risk treatment lineu201d. Prothrombin index correlates best with survival. Monitor all patients with significant ingestion for at least ninety-six hours.
Ibuprofen
Symptoms
Gastrointestinal symptoms (e.g. abdominal pain, nausea, vomiting, epigastric pain, or more rarely diarrhoea), central nervous system symptoms (e.g. lethargy, drowsiness, occasionally excitation and disorientation), gastrointestinal haemorrhage, acute renal failure, convulsions, and coma. In serious poisoning metabolic acidosis may occur and the prothrombin time/ INR may be prolonged, probably due to interference with the actions of circulating clotting factors. Prolonged use at higher than recommended doses may result in severe hypokalaemia and renal tubular acidosis. Symptoms may include reduced level of consciousness and generalized weakness (see section 4.4 and section 4.8).
Treatment
Treatment should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable. Consider oral administration of activated charcoal if the patient presents within 1 hour of ingestion of a potentially toxic amount. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.
Codeine phosphate
Symptoms
Codeine overdose may result in central nervous system and respiratory depression with hypoxia, hypotension, shock, gastric hypomotility with ileus, excitement and convulsions (especially in children) and non-cardiogenic pulmonary oedema. The opiate intoxication syndrome is described as a triad of depressed level of consciousness, miotic pupils, and decreased respiration.
Treatment
Treatment is based more on clinical presentation than on specific laboratory data, except when complications have occurred. Plasma codeine levels are not clinically useful. Support the respiratory and cardiovascular function. Monitor arterial blood gases and/or pulse oximetry, pulmonary function tests, and chest x- rays in patients with significant exposure.
Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures. Consider pre-hospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Use a minimum of 240 ml of water per 30 g charcoal. The optimum dose has not been established, but the usual dose is 25 g to 100 g in adults and adolescents; 25 g to 50 g in children aged 1 to 12 years (or 0,5 g to 1 g/kg body weight); and 1 g/kg in infants up to 1 year old. Consider naloxone as an antidote in patients with a decreased level of consciousness. The most frequently recommended initial naloxone dose for codeine overdose is 0,4 mg to 2 mg given as an intravenous bolus in both children and adults. This dose can also be given subcutaneously in the absence of intravenous access or intratracheally.