Lenazine Forte Cough Linctus 9 mg/7,2 mg/3,6 mg/5 ml Syrup

LENAZINE FORTE COUGH LINCTUS is indicated for the alleviation of cough.

Posology
DO NOT EXCEED THE RECOMMENDED DOSE
Adults
Take one to two medicine measuresful (5 ml to 10 ml) 2 to 3 times a day.
Children
12 years and over: Take one to one and a half medicine measuresful (5 ml to 7,5 ml) 2 to 3 times a day.
7 to 11 years: Take half to one medicine measureful (2,5 ml to 5 ml) 2 to 3 times a day.
2 to 6 years: Take quarter to half a medicine measureful (1,25 ml to 2,5 ml) 2 to 3 times a day.
Method of administration
For oral administration.

LENAZINE FORTE COUGH LINCTUS is contraindicated in:
u2022 Hypersensitivity to codeine phosphate, ephedrine hydrochloride, promethazine hydrochloride or to any of the excipients in LENAZINE FORTE COUGH LINCTUS (see section 6.1).
u2022 Respiratory depression.
u2022 Acute alcoholism.
u2022 Head injuries and conditions in which intracranial pressure is raised.
u2022 Patients receiving mono-amine oxidase inhibitors or within 14 days of its termination.
u2022 Premature infants or neonates.
u2022 During acute attacks of asthma.
u2022 Heart failure secondary to chronic lung disease.
u2022 Children under 2 years of age.
u2022 Breastfeeding mothers (see section 4.6).
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 Safety in pregnancy has not been established.
u2022 Patients for whom it is known that they are CYP2D6 ultra-rapid metabolisers.
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 The use of promethazine as contained in LENAZINE FORTE COUGH LINCTUS may be associated with the sudden infant death syndrome.

This medicine may lead to drowsiness and impaired concentration, which may be aggravated by the simultaneous intake of alcohol, or any other central nervous system depressant agents. Patients should be warned not to drive a motor vehicle, operate dangerous machinery, or climb dangerous heights, as impaired decision making could lead to accidents. Exceeding the prescribed dose, together with prolonged and continuous use of this medication, may lead to dependency and addiction.
Codeine phosphate
Codeine phosphate, as contained in LENAZINE FORTE COUGH LINCTUS, should be given with caution or in reduced doses to patients with hypothyroidism, adrenocortical insufficiency, impaired kidney or liver function, prostatic hypertrophy, or shock. Patients with obstructive bowel disorders and myasthenia gravis also need to be cautious when taking codeine phosphate.
CYP2D6 metabolism
Codeine, as contained in LENAZINE FORTE COUGH LINCTUS, 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.
Post-operative use in children
There have been reports in the published literature that codeine as contained in LENAZINE FORTE COUGH LINCTUS, 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 LENAZINE FORTE COUGH LINCTUS, 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.
Children with compromised respiratory function
Codeine is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures. These factors may worsen symptoms of morphine toxicity.
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.
Alcohol
Alcohol should be avoided whilst under treatment with codeine as contained in LENAZINE FORTE COUGH LINCTUS.
Ephedrine hydrochloride
Ephedrine hydrochloride, as contained in LENAZINE FORTE COUGH LINCTUS, should be used with care in patients with hyperthyroidism, cardiovascular disease, occlusive vascular disorders, aneurysms, diabetes mellitus or closed-angle glaucoma. Angina pain may be precipitated in patients with angina pectoris. Ephedrine hydrochloride, as contained in LENAZINE FORTE COUGH LINCTUS, should be avoided or used with caution in patients undergoing anaesthesia with halogenated anaesthetics and may cause an increased risk of dysrhythmias in patients receiving cardiac glycosides, quinidine or tricyclic antidepressants.
Promethazine hydrochloride
Promethazine hydrochloride, as contained in LENAZINE FORTE COUGH LINCTUS, should be used with care in patients with cardiovascular or hepatic diseases, narrow angle glaucoma, urinary retention and prostatic hypertrophy. Promethazine hydrochloride has anticholinergic properties and should be used with care in conditions such as glaucoma. Promethazine may potentiate the hypotensive effect of some anti-hypertensives. Elderly patients are more susceptible to the many adverse effects of promethazine. Cases of respiratory depression, including fatalities have been reported in children under two years of age. Promethazine hydrochloride may thicken or dry lung secretions and impair expectoration. It should therefore be used with caution in patients with asthma, bronchitis or bronchiectasis. Use with care in patients with severe coronary artery disease, narrow angle glaucoma, epilepsy or hepatic and renal insufficiency. Caution should be exercised in patients with bladder neck or pyloro-duodenal obstruction. The use of promethazine hydrochloride should be avoided in children and adolescents with signs and symptoms suggestive of Reye's Syndrome. Promethazine hydrochloride may mask the warning signs of ototoxicity caused by ototoxic medicines e.g. salicylates. Promethazine hydrochloride may also delay the early diagnosis of intestinal obstruction or raised intracranial pressure through the suppression of vomiting.

Antihistamines may enhance the sedative effects of central nervous system depressants including alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytics, sedatives and antipsychotics. Antihistamines have an additive antimuscarinic action with other antimuscarinic medicines such as atropine, and some antidepressants including tricyclic antidepressants and monoamine oxidase inhibitors. It has been suggested that some antihistamines could mask the warning signs of damage caused by ototoxic medicines such as aminoglycoside antibiotics.
The depressant effects of codeine are enhanced by other central nervous system depressants such as alcohol, anaesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. The actions of codeine may affect the activities of other medicines e.g. the gastrointestinal effects of codeine may delay absorption as with mexiletine or may be counteractive as with cisapride, metoclopramide or domperidone.
Interactions with laboratory tests
Promethazine hydrochloride should be discontinued at least 72 hours before the start of skin tests as it may inhibit the cutaneous histamine response thus producing false-negative results. Opioids 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.

Safety in pregnancy and lactation has not been established (see section 4.3).

LENAZINE FORTE COUGH LINCTUS may lead to drowsiness and impaired concentration, which may be aggravated by the simultaneous intake of alcohol, or any other central nervous system depressant agents. Patients should be warned not to drive a motor vehicle, operate dangerous machinery or climb dangerous heights, as impaired decision making could lead to accidents.

a) Tabulated list of adverse reactions
Codeine Phosphate
System organ class
Frequent
Less Frequent
Frequency unknown
Blood and lymphatic system disorders
Splenomegaly, lymphadenopathy
Metabolism and nutrition disorders
Hyperglycaemia, anorexia, loss of appetite
Psychiatric disorders
Euphoria
Restlessness and confusion
Mood changes, hallucinations
Nervous system disorders
Drowsiness
Deepening coma with high doses, increased intracranial pressure.
Convulsion may occur,
Headache, dizziness
System organ class
Frequent
Less Frequent
Frequency unknown
Eye disorders
Miosis
Ear and labyrinth disorders
Ringing or buzzing in the ears
Vertigo
Cardiac disorders
Bradycardia, palpitations
Tachycardia
Vascular disorders
Circulatory failure, hypotension, orthostatic hypotension
Hypothermia
Respiratory, thoracic and mediastinal disorders
Respiratory depression
Gastrointestinal disorders
Constipation
Nausea, vomiting and dry mouth
Abdominal pain, including pancreatitis
Hepato-biliary disorders
Biliary spasm
Skin and subcutaneous tissue disorders
Pruritus, urticaria, sweating
Musculoskeletal and connective tissue disorders
Muscle rigidity has been reported following high doses
Renal and urinary disorders
Difficulty in micturition, ureteric and anti-diuretic effect
Reproductive system and breast disorders
Sexual dysfunction, erectile dysfunction, decreased potency, decreased libido
General disorders and administration site conditions
Facial flushing, hypothermia
Ephedrine hydrochloride
System organ class
Frequent
Less Frequent
Frequency unknown
Metabolism and nutrition disorders
Altered metabolism including disturbances of glucose metabolism
System organ class
Frequent
Less Frequent
Frequency unknown
Psychiatric disorders
Psychotic states
Nervous system disorders
Anxiety, restlessness, insomnia, headache
Tremor, fear
Confusion, irritability, weakness
Cardiac disorders
Tachycardia, palpitations
Reflex bradycardia, cardiac dysrhythmias, angina pain, cardiac arrest
Dyspnoea
Vascular disorders
Vasoconstriction with resultant hypertension, hypotension with dizziness and fainting
Respiratory, thoracic and mediastinal disorders
Chest discomfort or pain
Gastrointestinal disorders
Nausea
Decrease in appetite and vomiting
Hypersalivation
Skin and subcutaneous tissue disorders
Sweating
Musculoskeletal and connective tissue disorders
Muscle cramps
Renal and urinary disorders
Difficulty in micturition, urinary retention
General disorders and administration site conditions
Flushing
Promethazine hydrochloride
System organ class
Frequent
Less Frequent
Frequency unknown
Blood and lymphatic system disorders
Agranulocytosis, leucopenia, haemolytic anaemia, thrombocytopenia
Immune system disorders
Allergy and anaphylaxis
Metabolism and nutrition disorders
Anorexia
Psychiatric disorders
Depression, euphoria, confusion
Nervous system disorders
Sedation, headache, dizziness, lassitude and inco-
Paradoxical central nervous system stimulation especially at high doses in children or elderly
Convulsions, extrapyramidal effects, tremor, sleep disturbances,
System organ class
Frequent
Less Frequent
Frequency unknown
Eye disorders
Blurred vision
Ear and labyrinth disorders
Tinnitus
Cardiac disorders
Tachycardia
Vascular disorders
Hypotension and dizziness
Respiratory, thoracic and mediastinal disorders
Tightness of the chest
Gastrointestinal disorders
Dryness of the mouth and constipation
Nausea, vomiting, diarrhoea, epigastric pain, anorexia or increased appetite and gastrointestinal disturbances
Hepato-biliary disorders
Jaundice
Skin and subcutaneous tissue disorders
Photosensitivity and angioedema
Sweating
Musculoskeletal and connective tissue disorders
Myalgia, muscle twitching, heaviness and weakness of hands
Renal and urinary disorders
Difficulty in micturition, dysuria
General disorders and administration site conditions
Lassitude
b) Description of selected adverse reactions
Regular prolonged use of codeine phosphate, as contained in LENAZINE FORTE COUGH LINCTUS, is known to lead to addiction and tolerance. Symptoms of restlessness and irritability may result when treatment is then stopped.
Tolerance and some of the most common side effects u2013 drowsiness, nausea, and vomiting, and confusion u2013 generally develops with long term use. Ephedrine hydrochloride, as contained in LENAZINE FORTE COUGH LINCTUS, may act as stimulant in children with nocturnal enuresis and cause sleeplessness. It may have sedative effects in some children. The elderly are more sensitive to the cardiovascular effects of ephedrine hydrochloride. Post marketing data for codeine, as contained in LENAZINE FORTE COUGH LINCTUS, has reported increased risk of abdominal pain, including pancreatitis as an undesirable effect with unknown frequency.

Symptoms
Codeine phosphate
Poisoning with codeine phosphate, as contained in LENAZINE FORTE COUGH LINCTUS produces central nervous system depression with exhilaration, excitation, miosis and slow breathing, and in children, convulsions followed by, respiratory depression, vomiting, drowsiness, reduced levels of consciousness, somnolence, cyanosis, hypotension, and deepening coma, lack of appetite, constipation, nausea, pinpoint pupils, dry mouth, sweating and facial flushing are symptoms of overdose. High doses of codeine may produce hypotension, circulatory failure, sedation, or excitement and, in children, convulsions may occur.
Promethazine hydrochloride
Overdosage may be fatal, especially in infants and children. It is associated with antimuscarinic, extrapyramidal, gastrointestinal and central nervous system (CNS) effects. In infants and children central nervous system (CNS) stimulation predominates over central nervous system (CNS) depression, causing ataxia, excitement, tremors, psychoses, hallucinations, and convulsions; hyperpyrexia may also occur. Deepening coma and cardiorespiratory collapse may follow. In adults, central nervous system (CNS) depression is more common with drowsiness, coma and convulsions, progressing to respiratory failure or possibly cardiovascular collapse.
Ephedrine hydrochloride
The effects of ephedrine hydrochloride, as contained in LENAZINE FORTE COUGH LINCTUS in overdose include nausea, vomiting, fever, palpitations, tachycardia, hypertension, paranoid psychosis, respiratory depression, convulsions and coma.
Treatment
In the event of overdosage the stomach should be emptied by aspiration and lavage. Activated charcoal and laxatives may also be used. Intensive supportive therapy may be required to treat respiratory failure and shock. Treatment should be symptomatic and supportive.
Codeine Phosphate
In acute overdosage with respiratory depression or coma, naloxone is indicated using one of the following dose regimens: Naloxone hydrochloride is used as an antagonist to codeine phosphate in dosages of 0,4 mg to 2 mg intravenously which may be repeated at intervals of 2 to 3 minutes, if necessary, up to 10 mg. Child: 10 u03bcg/kg and, if no response, subsequent doses of 100 u03bcg/kg. Subcutaneous or intramuscular injection: As intravenous injection but only if the intravenous route is not feasible. The onset of action is slower with subcutaneous or intramuscular injection. Continuous intravenous infusion: 2 mg diluted in 500 ml of intravenous infusion solution at a rate adjusted according to the patient's response.
Ephedrine hydrochloride
The treatment of ephedrine overdose with LENAZINE FORTE COUGH LINCTUS may require intensive supportive treatment. Slow intravenous injection of labetalol 50 to 200 mg may be given with electrocardiograph monitoring for the treatment of supraventricular tachycardia. Marked hypokalaemia (< 2,8 mmol / L - 1) due to compartmental shift of potassium predisposes to cardiac dysrhythmias and may be corrected by infusing potassium chloride in addition to propranolol and correcting respiratory alkalosis, when present.