Bromhexine Hydrochloride/ Orciprenaline Sulphate

Registered South African indications: 

• Cough associated with wheeziness (bronchospasm) and tenacious phlegm (sputum)

Registered South African contraindications

Liquid formulation

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Hypersensitivity to sympathomimetic amines
• Thyrotoxicosis
• Hypertrophic obstructive cardiomyopathy
• Tachyarrhythmia

Syrup formulation

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Hypersensitivity to sympathomimetic amines
• Hypertrophic obstructive cardiomyopathy
• Tachyarrhythmia
• Should not be given to those receiving monoamine oxidase inhibitors (MAOIs), or within 14 days of MAOI treatment termination
• Safety in pregnancy and lactation has not been established

South African recommendations

Liquid formulation

Pregnancy

• Safety not established

Breastfeeding

• Safety not established

Renal and hepatic impairment

• Clearance of bromhexine or its metabolites may be reduced in patients with severe hepatic or renal impairment

Elderly

• Use cautiously

Seizure disorders

• Use cautiously in patients with seizure disorders

Bromhexine Hydrochloride

Peptic ulceration history

• Use carefully, as mucolytics may disrupt the gastric mucosal barrier

Asthmatic patients

• Exercise caution in asthmatic patients

Impaired hepatic or renal function

• Reduced clearance in severe hepatic or renal impairment

Orciprenaline Sulphate

Combination with other bronchodilators

• Use other sympathomimetics only under strict medical supervision. Anticholinergic bronchodilators can be inhaled simultaneously

Risk/Benefit assessment

• Necessary in elderly, uncontrolled diabetes, cardiovascular disease such as ischaemic heart disease, arrhythmia or tachycardia, occlusive vascular disorders including arteriosclerosis, hypertension and aneurysms, hyperthyroidism, phaeochromocytoma, closed angle glaucoma, prostatism, angina pectoris and in patients who are unusually responsive to sympathomimetic amines

Acute dyspnoea

• Immediate doctor consultation required if acute, rapidly worsening dyspnoea occurs

Prolonged use considerations

• Prefer symptom-orientated treatment to regular use
• Evaluate need for increased anti-inflammatory therapy
• Review patient therapy plan in case of deteriorating bronchial obstruction

Risks of beta-agonist therapy

• Potentially serious hypokalaemia, especially in severe asthma or high doses
• Overdosage may cause cardiac effects
• Increased risk of serious side effects, including cardiac dysrhythmias
• Particular caution is advised in severe asthma or if high doses are used, as hypokalaemia may be potentiated by concomitant treatment with xanthine derivatives, glucocorticosteroids and diuretics
• Monitor serum potassium levels in situations of hypoxia and acidosis

Syrup formulation

Anaesthesia with halogenated agents

• Avoid or use with caution in patients undergoing anaesthesia with cyclopropane, halothane, or other halogenated anaesthetics due to risk of ventricular fibrillation

Arrhythmia risk with certain medications

• Increased risk of arrhythmias with concurrent use of cardiac glycosides, quinidine, or tricyclic antidepressants

Hypokalaemia

• Higher than recommended doses of beta-agonists may induce hypokalaemia, especially in patients on digitalis glycosides, diuretics, or those prone to cardiac dysrhythmias

Hyperthyroidism

• Exercise caution due to the sympathomimetic effects of orciprenaline sulphate

Gastric ulcer

• Caution due to bromhexine hydrochloride's mucolytic action

Cardiovascular diseases

• Use carefully in patients with ischaemic heart disease, arrhythmias or tachycardia, occlusive vascular disorders (arteriosclerosis, hypertension, aneurysms), and in those suffering from angina pectoris

Diabetes mellitus and glaucoma

• Exercise caution in patients with diabetes mellitus or closed angle glaucoma

Convulsive disorders

• Caution needed in patients with a history of convulsive disorders

Forms avail. in SA and covered in this monograph: liq, syr

South African registered indications and dosages

Cough associated with wheeziness (bronchospasm) and tenacious phlegm (sputum)

Bromhexine Hydrochloride/ Orciprenaline Sulphate
4/5 (mg/5ml)

• Oral (liq, syr): 10-20ml, 3 times daily

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Do not exceed the recommended dose

Paed. forms avail. in SA and covered in this monograph: liq, syr

South African registered indications and dosages

Cough associated with wheeziness (bronchospasm) and tenacious phlegm (sputum)

Bromhexine Hydrochloride/ Orciprenaline Sulphate
4/5 (mg/5ml)

• Younger than 1 year: Oral (syr): 2.5ml, 3 times daily
• Between 1-3 years: Oral (liq, syr): 2.5-5ml, 3 times daily
• Between 3-12 years: Oral (liq, syr): 5-10ml, 3 times daily
• Older than 12 years: See adult dosage

---

Do not exceed the recommended dose

Pregnancy 

South African recommendations

Liquid formulation

• Caution
• Safety of use in pregnancy has not been established
• Bromhexine hydrochloride/ orciprenaline sulphate may inhibit uterine contractions in pregnancy

Syrup formulation

• Contraindicated
• Safety in pregnancy has not been established

Breastfeeding

South African recommendations

Liquid formulation

• Caution
• Safety of use in lactation has not been established

Syrup formulation

• Contraindicated
• Safety in lactation has not been established

Fertility

South African recommendations

• No information available

South African recommendations

• Caution; no dose adjustment recommended
  Clearance of bromhexine or its metabolites may be reduced in patients with severe renal impairment

South African recommendations

• Caution; no dose adjustment recommended
  Clearance of bromhexine or its metabolites may be reduced in patients with severe hepatic impairment

South African recommendations

• Caution; no dose adjustment recommended

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Bromhexine Hydrochloride

Gastrointestinal Disorders

Common

• Mild gastrointestinal side effects

Uncommon

• Nausea
• Vomiting
• Diarrhoea

Endocrine Disorders

Frequency not specified

• Transient rise in serum aminotransferase values

Nervous System Disorders

Frequency not specified

• Headache
• Dizziness
• Sweating

Skin and Subcutaneous Tissue Disorders

Rare

• Skin rashes
• Angioedema
• Urticaria

Respiratory, Thoracic and Mediastinal Disorders

Rare

• Bronchospasm

Immune System

Rare

• Allergic reactions
• Anaphylaxis

Orciprenaline Sulphate

Cardiovascular Disorders

Common

• Tachycardia
• Arrhythmia
• Palpitations

Uncommon

• Decrease in diastolic blood pressure
• Increase in systolic blood pressure (particularly after higher doses)

Frequency not specified

• Hypertension
• Anginal pain
• Cardiac arrest
• Hypotension with dizziness
• Fainting
• Flushing

Skin and Subcutaneous Tissue Disorders

Common

• Skin reactions

Uncommon

• Sweating

Gastrointestinal Disorders

Common

• Nausea and vomiting

Frequency not specified

• Hypersalivation

Immune System Disorders

Common

• Allergic reactions (especially in hypersensitive patients)

Rare

• Anaphylactic or anaphylactoid reactions

Metabolism and Nutritional Disorders

Uncommon

• Potentially serious hypokalaemia
• Altered glucose metabolism

Frequency not specified

• Lactic acidosis

Musculoskeletal and Connective Tissue Disorders

Common

• Myalgia/muscle cramps

Nervous System Disorders

Common

• Fine tremor of skeletal muscles
• Headache
• Dizziness

Uncommon

• Weakness

Psychiatric Disorders

Common

• Nervousness

Rare

• Psychological alterations
  • Fear
  • Anxiety
  • Excitement
  • Restlessness
  • Insomnia
  • Confusion
  • Irritability
  • Psychotic states

Respiratory, Thoracic and Mediastinal Disorders

Frequency not specified

• Tightness in the chest
• Dyspnoea
• Asthma exacerbation

Renal and Urinary Disorders

Frequency not specified

• Difficulty in micturition
• Urinary retention

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Orciprenaline Sulphate

• Beta-adrenergics
• Anticholinergics
• Xanthine derivatives
• Theophylline
• Beta-blockers
• Halogenated hydrocarbon anaesthetics
• Cyclopropane
• Halothane
• Trichloroethylene
• Enflurane
• Cardiac glycosides
• Diuretics
• Quinidine
• Tricyclic antidepressants
• Monoamine oxidase inhibitors
• Corticosteroids

Bromhexine Hydrochloride

• No information available  

None routine. Specific cases may require

• Serum potassium

Bromhexine Hydrochloride/ Orciprenaline Sulphate combines the properties of the mucolytic agent bromhexine hydrochloride with that of the bronchodilator orciprenaline sulphate.

Bromhexine Hydrochloride
Is a mucolytic agent.

Orciprenaline Sulphate
Orciprenaline sulphate is a direct-acting sympathomimetic agent with predominantly beta-adrenergic stimulation activity and has little effect on alpha-receptors. It is considered to be relatively beta2-selective because it also has beta1-adrenergic receptor action, producing positive inotropic and chronotropic action on the heart. It has bronchodilatory properties.

COMBINATION PREPARATIONS

Bromhexine Hydrochloride/ Orciprenaline Sulphate

Syrup (per 5ml) 4mg/5mg

• Adco-Linctopent (Adcock)
• Benylin chesty (Johnson & Johnson) originator
• Bisolvon Linctus DA (Sanofi Aventis) originator
• Bronkese Compound Linctus (Pharmacare)
• Flemeze Bronchodilatory Syrup (Johnson & Johnson) originator