Benylin Forte Syrup

Benylin Forte is indicated for the relief of cough.

A maximum of four doses per day should not be exceeded. Shake the bottle before use.

Adults 18 years and older:

• One to two 5 mL medicine measures (5 mL u2013 10 mL) every 4 hours.

Use the lowest effective dose for the shortest duration. DO NOT USE FOR LONGER THAN 3 DAYS.

Method of administration

For oral administration

Known hypersensitivity to diphenhydramine hydrochloride, codeine phosphate, ammonium chloride or to any of the other ingredients in Benylin Forte (see section 6.1). Neither diphenhydramine hydrochloride nor codeine phosphate should be used with monoamine oxidase inhibitors or within 14 days of stopping treatment with monoamine oxidase inhibitors (see section 4.5). Contraindicated during acute asthma attacks, in the presence of acute alcoholism, head injuries and raised intracranial pressure, and in patients with impaired hepatic or renal function. Benylin Forte is contraindicated during pregnancy. Benylin Forte is contraindicated in breastfeeding mothers (see section 4.6). Contraindicated in children under 18 years of age for cough. Contraindicated in CYP2D6 ultra-rapid metabolisers who convert codeine into its active metabolite more rapidly and completely than other people. These individuals may experience signs of overdose/toxicity including symptoms such as extreme sleepiness, confusion, or shallow breathing, which may be life threatening (see section 4.4 and section 5.2).

Exceeding the prescribed dose, together with prolonged and continuous use of Benylin Forte, may lead to dependency and addiction. The use of Benylin Forte may lead to drowsiness and impaired concentration which may be aggravated by the simultaneous intake of alcohol or other central nervous system depressant medicines (see section 4.5). In infants and children, it may act as a cerebral stimulant. Symptoms of stimulation include insomnia, nervousness, tachycardia, tremors and convulsions. The positive results of skin tests may be suppressed. Diphenhydramine hydrochloride: Large doses may precipitate fits in epileptics. Deepening coma, extrapyramidal effects and photosensitivity of the skin may occur. Elderly patients are more susceptible to the central nervous system depressant and hypotensive effects. Diphenhydramine hydrochloride as contained in Benylin Forte has anticholinergic properties and should be used with care in respiratory conditions such as emphysema, chronic bronchitis, or acute or chronic bronchial asthma and if the patient has glaucoma, urinary retention and prostatic hypertrophy. Diphenhydramine hydrochloride as contained in Benylin Forte should be used with caution in patients with liver impairment or cardiovascular disease. Do not use Benylin Forte with any other product containing diphenhydramine, even ones used on skin. Codeine phosphate: Codeine belongs to a class of medicines called opioids. Opioids have been associated with the following conditions:

• Adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure, which has been reported more often following greater than 1 month of use. Advise patient to seek medical attention if they experience a constellation of these symptoms.
• Androgen deficiency, which may present with non-specific symptoms and signs such as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. Advise patient to seek medical attention if they experience any of these symptoms.
• Serotonin syndrome, a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic medicines (see section 4.5). Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their health care provider if they are taking, or plan to take serotonergic medications.
• Sleep-related breathing disorders such as sleep apnoea syndromes (including central sleep apnoea (CSA)) and hypoxia (including sleep-related hypoxia). Opioid use increases the risk of CSA in a dose dependent fashion. Advise patients to inform their health care provider if they have a history of sleep-related breathing disorders or if they experience symptoms of this disorder, for instance if anyone notices that they stop breathing whilst sleeping.
• Hyperalgesia may occur with the use of opioids, particularly at high doses. An unexplained increase in pain, or increased levels of pain can occur with increasing opioid dosages. If you are on any opioid for pain, consult a physician before using Benylin Forte.

Risk of death in ultra-rapid metabolisers of codeine: These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher-than-expected serum morphine levels (see section 5.2). Even at labelled dosage regimens, ultra-rapid metabolisers of codeine may have life-threatening or fatal respiratory depression or experience signs of overdose (such as extreme sleepiness, confusion, or shallow breathing) (see section 4.9). Respiratory depression and death have occurred in children who received codeine in the postoperative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolisers of codeine (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6 or high morphine concentrations). Children who are ultra-rapid metabolisers of codeine with obstructive sleep apnoea when treated with codeine for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to the respiratory depressant effects of codeine. Codeine is contraindicated in CYP2D6 ultra-rapid metabolisers (see section 4.3). Codeine should be used with caution in patients with convulsive disorders, head injuries, and in conditions in which intracranial pressure is raised (see section 4.3). Codeine should be used with caution in patients with compromised respiratory function, such as bronchial asthma, pulmonary oedema, obstructive airways disease, acute respiratory depression, severe lung disease, obesity, obstructive sleep apnoea and in patients at risk of paralytic ileus. Codeine should be given with caution to patients with hypothyroidism, adrenocortical insufficiency, impaired liver function, prostatic hypertrophy or shock. It should be used with caution in patients with obstructive bowel disorders and in patients with myasthenia gravis. The dosage should be reduced in elderly and debilitated patients. The prolonged use of high doses of codeine has produced dependence of the morphine type. Codeine is an opioid medicine and carries the risk of misuse and abuse. The prolonged use of high doses of codeine has produced dependence of the morphine type. Benylin Forte is intended for short-term use only. It should not be used continuously without medical review. There is an increased risk of addiction in patients with a personal or family history of substance abuse or mental health disorders. Caution is advised and the benefit and risk of Benylin Forte should be carefully assessed by a health care professional based on the individual needs of each patient. The use of Benylin Forte should be discontinued and quick medical attention should be sought at the earliest sign of codeine toxicity including symptoms such as extreme sleepiness, confusion, or shallow breathing, which may be life threatening. Patients should not use Benylin Forte for persistent or chronic cough, such as occurs with asthma, or where cough is accompanied by excessive secretions, unless directed by a medical practitioner. Patients should stop use and consult a medical practitioner if a cough persists or gets worse, or if new symptoms occur. Benylin Forte should not be used with alcohol.

• Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedations, respiratory depression, coma, and death (see section 4.5).
• Diphenhydramine may enhance the sedative effects of CNS depressants including alcohol, sedatives, and tranquilisers.

Benylin Forte is intended for short-term use only. It should not be used continuously without medical review. Benylin Forte contains sugar: sucrose and glucose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take Benylin Forte. Benylin Forte contains sodium benzoate. An increase in bilirubinaemia following its displacement from albumin may increase neonatal jaundice which may develop into kernicterus (non-conjugated bilirubin deposits in the brain tissue). Benylin Forte contains 200 mg of alcohol (ethanol) in each dosage unit which is equivalent to 3.94 % w/v alcohol. The amount in 5 mL dose of this medicine is equivalent to 5 mL beer or 2 mL wine. Benylin Forte contains 5 % ethanol (alcohol). Harmful for those suffering from alcoholism. To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.

Central nervous system (CNS) depressants (alcohol, sedatives, tranquilisers) Concomitant use with central nervous system depressants (e.g. barbiturates, chloral hydrate, benzodiazepines, phenothiazines, alcohol and centrally acting muscle relaxants) may cause additive CNS depression and respiratory depression.

Diphenhydramine hydrochloride The anticholinergic effects of atropine and tricyclic antidepressants may be enhanced by diphenhydramine hydrochloride. Monoamine oxidase inhibitors (MAOIs) may enhance the anticholinergic effects (see section 4.3). Diphenhydramine hydrochloride may mask the warning symptoms of damage caused by ototoxic medicines such as aminoglycoside antibiotics, and may affect the metabolism of other medicines in the liver. Diphenhydramine hydrochloride may enhance the sedative effect of central nervous system depressants including alcohol, barbiturates, hypnotics, narcotic analgesics, sedatives and tranquilisers.

Codeine phosphate The depressant effects of codeine are enhanced by depressants of the central nervous system such as alcohol, anaesthetics, hypnotics and sedatives, phenothiazines and tricyclic antidepressants.

CYP2D6 inhibitors Codeine analgesia is believed to be dependent upon the cytochrome P450 isoenzyme CYP2D6 catalysed o-demethylation to form the active metabolite morphine although other mechanisms have been cited. An interaction with quinidine, methadone, and paroxetine (CYP2D6 inhibitors) leading to decreased plasma concentrations of morphine has been described, which may have the potential to decrease codeine analgesia.

Opioid analgesics Concurrent use with other opioid receptor agonists may cause additive CNS depression, respiratory depression and hypotensive effects.

Serotonergic medicines The concomitant use of opioids with other medicines that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, medicines that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and monoamine oxidase inhibitors (MAOIs) (used to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), may result in serotonin syndrome.

Benylin Forte should not be used in pregnancy and lactation.

Pregnancy Diphenhydramine and codeine cross the placenta. Neonates who have been exposed to codeine in utero can develop withdrawal syndrome (neonatal abstinence syndrome) after delivery. Cerebral infarction has been reported in this setting.

Lactation Ammonium chloride It is not known whether ammonium chloride or its metabolites are excreted in breast milk.

Diphenhydramine Diphenhydramine crosses the placenta and is excreted into breast milk, but levels have not been reported.

Codeine Codeine is contraindicated in breastfeeding women (see section 4.3). At labelled doses codeine and its active metabolites are present in breast milk at very low concentrations.

In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose dependent. Despite the common use of codeine products to manage postpartum pain, reports of adverse events in infants are rare. However, some women are ultra-rapid metabolisers of codeine. These women achieve higher-than expected serum levels of codeineu2019s active metabolite, morphine, leading to higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants. Deaths have occurred in nursing infants who were exposed to high levels of morphine in breast milk because their mothers were ultra-rapid metabolisers of codeine. Maternal use of codeine can lead to serious adverse reactions, including death, in nursing infants. Benylin Forte is contraindicated in breastfeeding, and should not be used during pregnancy.

Benylin Forte can cause side effects, such as drowsiness, dizziness, incoordination and blurred vision and may affect the ability to drive and use machinery. 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.

Blood and the lymphatic system disorders Less frequent: thrombocytopenia Frequency unknown: agranulocytosis, leucopenia and haemolytic anaemia

Immune system disorders Less frequent: hypersensitivity Frequency unknown: allergic reactions, anaphylaxis

Endocrine disorders Less frequent: epigastric pain

Metabolism and nutrition disorders Less frequent: anorexia, increased appetite

Psychiatric disorders Less frequent: euphoria, confusion, changes of mood, agitation, hallucination, insomnia, irritability, nervousness

Nervous system disorders Frequent: sedation, drowsiness Less frequent: headache, restlessness, seizure, abnormal coordination, dizziness, paraesthesia, tremor

Eye disorders Less frequent: blurred vision, miosis

Ear and labyrinth disorders Less frequent: tinnitus, vertigo

Cardiac disorders Less frequent: bradycardia, palpitations, tachycardia

Vascular disorders Less frequent: hypotension, facial flushing, orthostatic hypotension

Respiratory, thoracic and mediastinal disorders Less frequent: tightness of the chest, dry throat, nasal dryness, respiratory depression

Gastrointestinal disorders Frequent: nausea, vomiting, constipation Less frequent: dry mouth, diarrhoea, dyspepsia

Skin and subcutaneous tissue disorders Less frequent: urticaria, pruritus and itching of the nose, sweating, rash, dermatitis

Musculoskeletal, connective tissue and bone disorders Less frequent: muscular weakness

Renal and urinary disorders Less frequent: difficulty in micturition, dysuria, antidiuretic effect, ureteric or biliary spasm, urinary retention

General disorders and administration site conditions Less frequent: hypothermia, asthenia, chest discomfort

Injury, poisoning and procedural complications Less frequent: increased intracranial pressure

Post-marketing experience Gastrointestinal disorders Less frequent: increased risk of abdominal pain, including pancreatitis Codeine is an opioid medicine. Opioids have been associated with the following: u2022 Sedation; u2022 Vertigo; u2022 Bronchospasm; u2022 Gastrointestinal disorder, such as dyspepsia, nausea, vomiting, constipation; u2022 Euphoric mood; u2022 Medicine dependence can develop following long-term use of high doses.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of Benylin Forte is important. It allows continued monitoring of the benefit/risk balance of Benylin Forte. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. For further information, please contact the Consumer Care Contact Centre: www.kenvuecontact.eu.

Ammonium chloride Large doses of ammonium chloride may cause nausea, vomiting, drowsiness, thirst, headache, hyperventilation, profound acidosis and hypokalaemia. Excessive doses may give rise to hepatic encephalopathy.

Diphenhydramine hydrochloride Overdosage may be fatal especially in infants and children. In infants & children CNS stimulations predominates over CNS depression causing ataxia, excitement, tremors, psychoses, hallucinations and convulsions; hyperpyrexia may also occur. Deepening coma and cardiorespiratory collapse may follow. In adults, CNS depression with drowsiness, coma and convulsions, progressing to respiratory failure or possibly cardiovascular collapse.

Codeine phosphate Produces central stimulation with exhilaration and, in children, convulsions, followed by vomiting, drowsiness, respiratory depression and cyanosis, and coma.

Treatment Naloxone hydrochloride is used to counteract the respiratory depression and coma produced by excessive doses of codeine. A dose of 0,4 to 2 mg is given intravenously, repeated at intervals of 2 to 3 minutes if necessary, up to 10 mg. In children, an initial dose of 10 u03bcg per kg body weight may be given intravenously followed, if necessary, by a larger dose of 100 u03bcg per kg. Further treatment is symptomatic and supportive.