Lenadol 10 mg/5 mg/400 mg/50 mg Tablets

LENADOL relieves fever and pain-tension states.

Posology
Adults and children over 12 years: Take one to two tablets every 3 to 4 hours, to a maximum of 8 tablets daily.
Method of administration
For oral administration.

LENADOL is contraindicated in:
u2022 Patients with hypersensitivity to codeine phosphate, diphenhydramine hydrochloride, paracetamol, caffeine anhydrous or to any excipients in LENADOL (see section 6.1).
u2022 Patients hypersensitive to other opioid analgesics.
u2022 Patients with severe liver or kidney complications.
u2022 Pregnancy and breastfeeding (see section 4.6).
u2022 Asthma, respiratory depression, especially in the presence of cyanosis and excessive bronchial secretion.
u2022 Head injuries and conditions in which intracranial pressure is raised.
u2022 Heart failure secondary to chronic lung disease.
u2022 A history of cardiac disease.
u2022 Epilepsy and all convulsive states.
u2022 Patients taking monoamine oxidase inhibitors or within 14 days of stopping such treatment (see section 4.5).
u2022 Acute alcoholism.
u2022 Comatose patients.
u2022 Children under 12 years of age.
u2022 In all paediatric patients who undergo tonsillectomy and/or adenoidectomy for obstructive sleep apnoea syndrome due to an increased risk of developing serious and life-threatening adverse reactions (see section 4.4)
u2022 Conditions where inhibition of peristalsis is to be avoided, where there is a risk of paralytic ileus, where abdominal distension develops, or in acute diarrhoeal conditions such as acute ulcerative colitis or antibiotic associated colitis (e.g., pseudomembranous colitis) or diarrhoea caused by poisoning.
u2022 Patients for whom it is known they are CYP2D6 ultra-rapid metabolisers.
u2022 Porphyria.

LENADOL 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.
LENADOL contains codeine and exceeding the prescribed dose, together with prolonged and continuous use, may lead to dependence and addiction. The lowest effective dose should be used, and the duration of treatment should be as short as possible. Consult your doctor if no relief is obtained with the recommended dosage. Do not use continuously for longer than 5 days without consulting your doctor.
Codeine phosphate
Codeine, as contained in LENADOL, should be given with caution or in reduced doses in patients with adrenocortical insufficiency. The dosage should be reduced in the debilitated and in the elderly. It should be used with caution or in reduced doses in patients with hypothyroidism, impaired kidney or liver function (see section 4.3), prostatic hypertrophy, urethral stricture, hypotension, shock, or myasthenia gravis.
CYP2D6 metabolism
Codeine, as contained in LENADOL, 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 therapeutic 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. These patients convert codeine into morphine rapidly resulting in higher-than-expected serum morphine levels.
General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation, and lack of appetite. In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal (see section 4.3).
Post-operative use in children
There have been reports in the published literature that codeine as contained in LENADOL, given post-operatively in children after tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, led to rare, but life-threatening adverse events including death (see section 4.3). All children received doses of codeine, as contained in LENADOL, that were within the appropriate dose range; however, there was evidence that these children were either ultra-rapid or extensive metabolisers in their ability to metabolise codeine to morphine.
Drug dependence, tolerance, and potential for abuse
For all patients, prolonged use of LENADOL may lead to drug dependence (addiction), even at therapeutic doses. The risks are increased in individuals with current or history of substance misuse disorder (including alcohol misuse) or mental health disorder (e.g., major depression). Should be used with caution in patients with personal or family history of substance abuse or mental health disorders. Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of pain control as initially experienced. Patients may also supplement their treatment with additional pain relievers. These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient.
Drug withdrawal syndrome
Discontinuation should be carried out gradually in patients who may have developed physical dependence, to avoid precipitating withdrawal symptoms. Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.
The opioid medicine withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.
Hyperalgesia
Hyperalgesia may be diagnosed if the patient on long-term opioid therapy, as contained in LENADOL, presents with increased pain. Symptoms of hyperalgesia may resolve with a reduction of opioid dose.
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 (safety switching the patient to a different opioid moiety).
Monoamine Oxidase Inhibitors (MAOIs)
Administration of pethidine and possibly other opioid analgesics to patients taking a monoamine oxidase inhibitor (MAOI) has been associated with very severe and sometimes fatal reactions (see section 4.3).
Alcohol
Alcohol should be avoided whilst under treatment with codeine as contained in LENADOL.
Sedatives
Concomitant use of LENADOL and sedative medicines such as benzodiazepines or related medicines may result in sedation, respiratory depression, coma, and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. These patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5).
Paracetamol
As LENADOL contains paracetamol, doses in excess of those recommended may cause severe liver damage to occur. Not more than 4 000 mg should be taken in 24 hours. There may be an added risk of liver damage when patients with certain pre-existing liver diseases are given paracetamol, as contained in LENADOL. It is recommended that patients suffering from hepatitis or who are recovering from any form of liver disease should not take paracetamol, as contained in LENADOL.
Sensitivity reactions resulting in reversible skin rash or blood dyscrasia may occur following paracetamol intake, as contained in LENADOL (see section 4.8). Prolonged excessive use may cause irreversible kidney damage. Patients suffering from kidney or liver disease should take paracetamol, as contained in LENADOL, under strict medical supervision. Caution should be exercised in patients with glutathione depleted states, as the use of paracetamol, as contained in LENADOL, may increase the risk of metabolic acidosis.
Severe cutaneous adverse reactions (SCARs)
Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic syndrome (DRESS)/Drug-induced hypersensitivity syndrome (DIHS) and fixed drug eruptions (FDE) have been reported in patients treated with paracetamol containing medicines, as contained in LENADOL. If a patient develops SCAR, treatment with LENADOL must immediately be discontinued and appropriate treatment instituted.
High Anion gap metabolic acidosis (HAGMA)
Caution is advised if LENADOL 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 LENADOL. Close monitoring, including measurement of urinary 5-oxoproline, is recommended.
Diphenhydramine hydrochloride
Diphenhydramine, as contained in LENADOL, should be used with care in conditions such as closed-angle glaucoma, urinary retention, prostatic hyperplasia, myasthenia gravis, hepatic impairment and mild to moderate renal impairment (see section 4.3).
Antihistamines
Avoid use of other antihistamine-containing preparations, including topical antihistamine and cough and cold medicines.
Alcohol
Avoid concurrent use with alcohol, as diphenhydramine, as contained in LENADOL, may increase the sedative effects of alcohol (see section 4.5).
Caffeine anhydrous
Caffeine, as contained in LENADOL, should be taken with care by patients with a history of peptic ulceration or hyperacidity. With prolonged use, some degree of tolerance and psychic dependence may occur. Excessive intake of caffeine (e.g., coffee, tea, and some canned drinks) should be avoided while taking LENADOL.
Paediatric population
LENADOL should not be used in children below the age of 12 years because of the risk of opioid toxicity due to the variable and unpredictable metabolism of codeine to morphine (see section 4.3).

LENADOL SHOULD NOT BE TAKEN WITH SEDATIVES AND TRANQUILISERS.
Codeine phosphate
Monoamine oxidase inhibitors (MAOIs) (e.g. moclobemide, selegiline, linezolid) due to the possible risk of excitation or depression, avoid concomitant use for 14 days after discontinuation of MOAIs (see section 4.3).
Codeine as contained in LENADOL, may affect the activity of other medicines by delaying their absorption.
Alcohol
The hypotensive, sedative and respiratory depressive effects of alcohol may be enhanced.
Anaesthetics
Concomitant administration of codeine, as contained in LENADOL and anaesthetics may cause increased CNS depression and/or respiratory depression and/or hypotension.
Antidepressants
The depressant effects of opioid analgesics, as contained in LENADOL, may be enhanced by tricyclic antidepressants.
Anti-dysrhythmics
Codeine, as contained in LENADOL, delays the absorption of mexiletine. The analgesic activity of codeine is likely to be significantly impaired by quinidine which impairs codeine metabolism.
Sedative medicines
The concomitant use of opioids such as codeine, as contained in LENADOL, with sedative medicines such as benzodiazepines or related medicines increases the risk of sedation, respiratory depression, coma, and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited (see section 4.4).
Anxiolytics and hypnotics
Enhanced sedative effect.
Antipsychotics
Enhanced sedative and hypotensive effect.
Antihistamines
Concomitant administration of codeine, as contained in LENADOL, and antihistamines with sedative properties may cause increased CNS depression and/or respiratory depression and/or hypotension.
Cisapride, domperidone and metoclopramide
Codeine as contained in LENADOL, antagonises the effect of cisapride, metoclopramide and domperidone on gastrointestinal activity.
Sodium oxybate
Concomitant administration of codeine, as contained in LENADOL and sodium oxybate may cause increased CNS depression and/or respiratory depression and/or hypotension.
Cimetidine
Cimetidine may inhibit the metabolism of codeine as contained in LENADOL resulting in increased plasma concentrations.
Laboratory tests
Opioids such as codeine as contained in LENADOL may interfere with gastric emptying studies as they delay gastric emptying and with hepatobiliary imaging using technetium Tc 99m disofenin as opioid treatment may cause constriction of the sphincter of Oddi and increase biliary tract pressure.
Paracetamol
Barbiturates
The risk of liver-cell toxicity of paracetamol as contained in LENADOL, may be somewhat greater in patients who receive concurrent medicines which induce hepatic enzymes, such as the barbiturates.
Metoclopramide, domperidone and colestyramine
The absorption of paracetamol, as contained in LENADOL, may be accelerated by metoclopramide or domperidone and absorption reduced by colestyramine.
Warfarin and other coumarins
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.
Salicylates
Prolonged concurrent use of paracetamol with salicylates increases the risk of adverse renal effects.
Isoniazid
Chronic use of isoniazid may increase the risk of liver damage when combined with paracetamol, even at recommended doses.
Probenecid
Excretion may be affected, and plasma concentrations altered when administered with probenecid.
Flucloxacillin
Caution should be taken when LENADOL is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risks factors (see section 4.4).

LENADOL is contraindicated in pregnancy and lactation as LENADOL crosses the placenta and passes into breastmilk (see section 4.3). The administration of codeine, as contained in LENADOL, during labour may cause respiratory depression in the newborn infant.
Pregnancy
Caffeine and paracetamol
Paracetamol-caffeine, as contained in LENADOL, is not recommended for use during pregnancy due to the possible increased risk of lower birth weight and spontaneous abortion associated with caffeine consumption.
Diphenhydramine hydrochloride
There are no adequate data from the use of diphenhydramine in pregnant women. Animal studies are insufficient with respect to pregnancy. The potential risk for humans is unknown. Use of sedating antihistamines such as diphenhydramine, as contained in LENADOL, during the third trimester may result in reactions in the newborn or premature neonates.
Codeine phosphate
A possible association with respiratory and cardiac malformations has been reported following first trimester exposure to codeine as contained in LENADOL. Regular use during pregnancy may cause drug dependence in the foetus, leading to withdrawal symptoms in the neonate. Administration during labour may depress respiration in the neonate. Opioid analgesics such as codeine, as contained in LENADOL, may cause gastric stasis during labour, increasing the risk of inhalation pneumonia in the mother. (see section 4.3)
Breastfeeding
Caffeine anhydrous
Caffeine as contained in LENADOL, in breast milk may potentially have a stimulating effect on breast fed infants.
Diphenhydramine hydrochloride
Diphenhydramine as contained in LENADOL has been detected in breast milk, but the effects of this on breast-fed infants are unknown.
Codeine phosphate
Administration to nursing women is not recommended as codeine phosphate may be secreted in breast milk and may cause respiratory depression in the infant (see section 4.3).
Fertility
No data available.

LENADOL has major influence on the ability to drive or operate machinery. LENADOL may lead to drowsiness and impaired concentration, which may be aggravated by the simultaneous intake of alcohol or other central nervous system depressants medicines. Patients should be warned not to drive a motor vehicle or operate dangerous machinery.

a) Tabulated list of adverse reactions
Paracetamol
System organ class Frequent Less frequent Frequency unknown (cannot be estimated from the available data)
Blood and the lymphatic system disorders Haematological reactions e.g. thrombocytopenia, neutropenia, pancytopenia, leucopenia, anaemia
Metabolism and nutrition disorders Pyroglutamic aciduria (5-oxoprolinuria), high-anion gap metabolic acidosis
Gastrointestinal disorders Pancreatitis
Hepatobiliary disorders Hepatitis
Skin and subcutaneous tissue disorders Skin eruptions, rash, erythematous or urticarial*
Renal and urinary disorders Renal colic, nephropathy, renal failure, and sterile pyuria
* Skin eruptions have occurred. Sensitivity reactions including skin rash may occur. This is usually erythematous or urticarial but sometimes may be more serious and may be accompanied by drug fever and mucosal lesions.
Post marketing data
System organ class Frequent Less frequent Frequency unknown (cannot be estimated from the available data)
Blood and the lymphatic system disorders Agranulocytosis, thrombocytopenia
Immune system disorders Anaphylaxis, cutaneous hypersensitivity reactions including, among others, skin rashes and angioedema. Very rare cases of serious skin reactions have been reported
Respiratory, thoracic and mediastinal disorders Bronchospasm**
Hepatobiliary disorders Hepatic dysfunction
Skin and subcutaneous tissue disorders Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic syndrome (DRESS)/Drug-induced hypersensitivity syndrome (DIHS) and fixed drug eruptions (FDE)
** There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.
Codeine phosphate
System organ class Frequent Less frequent Frequency unknown (cannot be estimated from the available data)
Immune system disorders Dose-related histamine-releasing effect, allergic reactions such as urticarial and pruritus as well as hypotension and flushing hypersensitivity syndrome as part of a maculopapular rash, fever, splenomegaly, and lymphadenopathy
Endocrine disorders Hyperglycaemia
Metabolism and nutrition disorders Anorexia
Psychiatric disorders Confusion Restlessnessu00b1, mood changesu00b1, Excitement, euphoria, mental depression, hallucinations and nightmares, and dysphoria
Nervous system disorders Dizziness, drowsiness, Faintnessu00b1, sedationu00b1, vertigou00b1 Headache, raised intracranial pressure, convulsions
Eye disorders Miosisu00b1 Blurred or double vision or other changes in vision
Cardiac disorders Bradycardia, palpitationsu00b1 Tachycardia
Vascular disorders Postural hypotension
Respiratory, thoracic and mediastinal disorders Dyspnoea
Gastrointestinal disorders Constipation, nausea, vomiting, Dry mouthu00b1 Stomach cramps, pancreatitis
Hepatobiliary disorders Biliary spasm
Skin and subcutaneous tissue disorders Facial flushingu00b1, Sweating Allergic reactions such as skin rashes, urticaria, pruritus
Musculoskeletal and connective tissue disorders Muscle rigidity, uncontrolled muscle movements
Renal and urinary disorders Urinary retention, ureteric spasm, antidiuretic effect difficulty with micturition, dysuria
Reproductive system and breast disorders Sexual dysfunction, erectile dysfunction, decreased potency, decreased libido
General disorders and administrative site conditions Drug withdrawal syndrome Hypothermia malaise, tiredness, and facial oedema
u00b1 These effects occur more commonly in ambulant patients than in those at rest in bed and in those without severe pain. These are less common than with morphine. Codeine may cause respiratory depression, circulatory failure, hypotension, orthostatic hypotension, deepening coma with larger doses.
Diphenhydramine hydrochloride
System organ class Frequent Less frequent Frequency unknown (cannot be estimated from the available data)
Blood and the lymphatic system disorders Agranulocytosis, eosinophilia, leucopenia, thrombocytopenia, aplastic anaemia
Immune system disorders Skin rashes, urticaria, purpura, angioedema, bronchospasm
Metabolism and nutrition disorders Symptoms of porphyria may be exacerbated
Psychiatric disorders Elation or depression, irritability, nightmares confusion*, paradoxical excitation* (eg increased energy, restlessness, nervousness) *the elderly are more prone to confusion and paradoxical excitation
Nervous system disorders Sedation varying from slight drowsiness to deep sleep including inability to concentrate, dizziness, unsteadiness Headache, tingling, paraesthesia, convulsions, dyskinesias
Eye disorders Blurred vision
Ear and labyrinth disorders Tinnitus
Cardiac disorders Tachycardia, cardiac dysrhythmias, palpitations
Vascular disorders Hypotension
Respiratory, thoracic and mediastinal disorders Thickened respiratory-tract secretions, tightness of the chest
Gastrointestinal disorders Dry mouth Nausea, vomiting, diarrhoea, constipation, colic, epigastric pain, anorexia
Skin and subcutaneous tissue disorders Erythema multiforme, exfoliative or bullous dermatitis
Musculoskeletal and connective tissue disorders Muscular weakness, incoordination, muscle twitching
Renal and urinary disorders Difficulty in micturition, urinary retention, anuria
General disorders and administrative site conditions Fatigue Lassitude
Post marketing Data
Caffeine anhydrous
System organ class Frequent Less frequent Frequency unknown (cannot be estimated from the available data)
Psychiatric disorders Restlessness, excitement anxiety and irritability
Nervous system disorders Headache, insomnia, dizziness
Eye disorders Scintillating scotoma
Ear and labyrinth disorders Tinnitus
Cardiac disorders Tachycardia, extrasystoles, palpitations
Gastrointestinal disorders Nausea, increased gastric secretion which may cause gastric ulceration
Musculoskeletal and connective tissue disorders Muscle tremor
b) Description of selected adverse reactions
Severe cutaneous adverse reactions (SCARs)
Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic syndrome (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 LENADOL must immediately be discontinued and appropriate treatment instituted. There is a risk of serious heart problems, seizures, coma and death associated with the use of high doses of diphenhydramine containing medicines.
c) Other special populations
Elderly
Dosage should be reduced in elderly patients. Sedating antihistamines such as diphenhydramine as contained in LENADOL, may cause confusion and paradoxical excitation in the elderly.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. Aspen Pharmacare: E-mail: [email protected] Tel: 0800 118 088/ +27 (0)11 239-6200

In the event of overdosage consult your doctor or take the patient to the nearest hospital immediately. Specialised treatment is essential as soon as possible.
Codeine phosphate
Symptoms
Symptoms of overdosage are constipation, nausea, vomiting, anorexia, dizziness, drowsiness, abdominal pain, gastrointestinal haemorrhage, potentially fatal liver damage, cerebral oedema and renal tubular necrosis, hyperglycaemia and hypoglycaemia. Central stimulation and exhilaration, followed by cardiovascular collapse, respiratory depression, and coma.
Treatment
Naloxone hydrochloride 400 u03bcg is given subcutaneously, intramuscularly, or intravenously, repeated at intervals of 2 to 3 minutes if necessary. Respiration may be assisted.
Paracetamol
Symptoms
Prompt treatment is essential. In the event of an overdosage, consult a doctor immediately, or take the person directly to a hospital. A delay in starting treatment may mean that 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 to10 g/day) of paracetamol for several days, in chronic alcoholism, chronic liver disease, AIDS, malnutrition, and with the use of drugs that induce liver microsomal oxidation such as barbiturates, isoniazid, rifampicin, phenytoin and carbamazepine. Symptoms of paracetamol overdosage in the first 24 hours 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, initially by elevation of the serum transaminase and lactic dehydrogenase activity, increased serum bilirubin concentration 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 in the absence of severe liver damage. Abnormalities of glucose metabolism and metabolic acidosis may occur. Cardiac arrhythmias have been reported.
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 formulation is not the treatment of choice, 140 mg/kg dissolved in water may be administered initially, followed by 70 mg/kg every four hours for seventeen doses. A plasma paracetamol level should be determined four hours after ingestion in all cases of suspected overdosage. Levels done before four hours may be misleading. Patients at risk of liver damage, and hence requiring continued treatment with N-acetylcysteine, can be identified according to their 4-hour plasma paracetamol level. The plasma paracetamol level can be plotted against time since ingestion in the nomogram below. The nomogram should be used only in relation to a single acute ingestion. 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. A semi-logarithmic plot of plasma-paracetamol concentration against hours after ingestion. 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. For overdose with an extended/modified release preparation the value of the nomogram is unknown. As there is no information on the plasma levels of paracetamol after an overdose of extended/modified release paracetamol preparations, all patients with suspected or known overdose with such preparations should receive N-acetylcysteine. Because of lack of data for extended/modified release formulations, a level below the u201ctreatment lineu201d of the nomogram may not exclude the possibility of toxicity. Monitor all patients with significant ingestions for at least ninety-six hours.
Diphenhydramine hydrochloride
Symptoms
Diphenhydramine overdose is likely to result in effects in effects similar to those listed under adverse reactions. Additional symptoms may include mydriasis, fever, flushing, agitation, tremor, dystonic reactions, hallucinations and ECG changes including QT prolongation. Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, dysrhythmias, coma and cardiovascular collapse.
Treatment
Treatment should be supportive and directed towards specific symptoms. Convulsions and marked CNS stimulation should be treated with parenteral diazepam. Further management should be as clinically indicated or as recommended by the national poisons centres where applicable.