Paracetamol/ Phenylpropanolamine/ Phenyltoloxamine/ Codeine

Registered South African indications:

• Colds and flu 

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

Contraindications

• Hypersensitivity to active ingredient or any of the excipients in this combination product
• Pregnancy
• Lactation
• Coronary artery disease
• Hypertension
• Hyperthyroidism
• Cardiovascular disease
• Respiratory depression
• Acute alcoholism
• Head injuries
• Conditions in which intracranial pressure is raised
• Current or recent (within 14 days) use of monoamine oxidase inhibitors (e.g., tranylcypromine)
• Should not be given during an attack of bronchial asthma or in heart failure secondary to chronic lung disease

Cautions

Caution in the following patient groups

• Renal impairment
• Hepatic impairment
• Phaeochromocytoma
• Occlusive vascular disease
• Arteriosclerosis
• Aneurysms

Severe hypertensive episodes

• Severe hypertensive episodes, leading to intracranial haemorrhage, have been reported following phenylpropanolamine ingestion. Patients should be warned about the risks of exceeding the recommended dose, particularly the increased risk of hypertensive crisis and haemorrhagic stroke

Aggravation of pre-existing conditions

• May worsen conditions such as diabetes, glaucoma, or prostatic enlargement

Duration of use

• Do not use continuously for more than 7 days without consulting a doctor. Tachyphylaxis may occur after 5-7 days, causing the product to lose effectiveness. Patient should consult a doctor if symptoms persist or are accompanied by fever

Excess dosage risks

• Doses exceeding recommendations may cause severe liver damage, nervousness, dizziness, sleeplessness, tremulousness, or cardiac arrhythmias. This may also occur in sensitive individuals even at small doses

Drowsiness and impaired concentration

• May cause drowsiness and impaired concentration, which may be worsened by alcohol or other central nervous system depressants

Advice on driving and operating machinery

• Patients, particularly at the start of therapy, should avoid driving, climbing dangerous heights, or operating dangerous machinery, as impaired decision-making could lead to accidents

Dependency and addiction

• Exceeding the prescribed dose, along with prolonged and continuous use, may lead to dependency and addiction

Additional warnings for individual active ingredients

Phenylpropanolamine hydrochloride

• Should be used in caution in patients with hyperthyroidism; cardiovascular diseases such as ischaemic heart disease, arrythmia or tachycardia; occlusive vascular disorders, including arteriosclerosis, hypertension or aneurysms; diabetes mellitus and closed angle glaucoma
• Anginal pain may be precipitated in patients with angina pectoris

Phenyltoloxamine citrate

• Paradoxical central nervous stimulation may occur, especially in children, with insomnia, nervousness, tachycardia, tremors and convulsions
• May precipitate seizures in epileptics
• Caution in patients with narrow angle glaucoma, urinary retention or prostatic hypertrophy
• May lead to drowsiness, patients so affected should not drive or operate machinery. Patients should abstain from alcohol

Codeine phosphate

• Caution in patients with hypothyroidism, adrenocortical insufficiency, impaired kidney or liver function, prostatic hypertrophy, shock, patients with obstructive bowel disorders and myasthenia gravis

Forms avail. in SA and covered in this monograph: tab

Symptomatic relief of colds and flu
Paracetamol/ Phenylpropanolamine/ Phenyltoloxamine/ Codeine
300/25/22/15 (mg)

• Oral (tab): 1 tab, 4hrly; Max: 4 doses/24hrs

Paed. forms avail. in SA and covered in this monograph: tab

Symptomatic relief of colds and flu
Paracetamol/ Phenylpropanolamine/ Phenyltoloxamine/ Codeine
300/25/22/15 (mg)

• Younger than 12 years: Not established for use 
• Older than 12 years: See adult dosage

Recommendations for this combination product as per highest risk category when comparing individual active ingredients

Pregnancy

• Contraindicated

Breastfeeding

• Contraindicated

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; no information available

Drugs in Sport

• Permitted - No warnings 

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

Paracetamol
Respiratory Disorders

• Bronchospasm

Hepatobiliary Disorders

• Hepatic dysfunction

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis
• Cutaneous hypersensitivity reactions 
• Angioedema
• Stevens-Johnson syndrome
• Thrombocytopenia 
• Agranulocytosis
• Methaemoglobinaemia

Phenylpropanolamine
Central Nervous System Disorders

• Haemorrhagic stroke
• Headache
• Dystonia
• Aphasia
• Confusion
• Psychosis
• Dependance

Cardiovascular Disorders

• Hypertension
• Arrhythmias

Hepatobiliary Disorders

• Hepatotoxicity

Genitourinary Disorders

• Renal impairment

Musculoskeletal Disorders

• Rhabdomyolysis

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions

Sensory Disorders

• Blurred vision

Phenyltoloxamine
Central Nervous System Disorders

• Drowsiness
• Dizziness
• Euphoria
• Faintness
• Tiredness

Cardiovascular Disorders

• Tachycardia 
• High degree heart block

Immune, Blood and Lymphatic System Disorders

• Haemolytic anemia 
• Thrombocytopenia 
• Agranulocytosis  

Skin and Subcutaneous Tissue Disorders

• Diaphoresis

Sensory Disorders

• Blurred vision

Codeine
Central Nervous System Disorders

• Dizziness
• Drowsiness
• Mood changes
• Euphoria 
• Dysphoria
• Mental depression
• Restlessness
• Confusion
• Headache
• Raised intracranial pressure
• Hallucinations
• Nightmares
• Vertigo

Cardiovascular Disorders

• Tachycardia
• Palpitations
• Bradycardia 
• Postural hypotension
• Facial flushing 
• Hypotension

Respiratory Disorders

• Dyspnoea
• Respiratory depression

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation
• Dry mouth
• Stomach cramps
• Pancreatitis
• Biliary spasm

Genitourinary System Disorders

• Sexual dysfunction
• Erectile dysfunction
• Decreased potency
• Decreased libido
• Difficulty with micturation
• Urinary retention
• Ureteric spasm
• Dysuria

Endocrine and Metabolic Disorders

• Hyperglycaemia
• Anorexia

Musculoskeletal Disorders

• Uncontrolled muscle movements
• Muscle rigidity 

Skin and Subcutaneous Tissue Disorders 

• Skin rashes
• Urticaria
• Pruritus
• Sweating 
• Facial oedema

Immune, Blood and Lymphatic System Disorders

• Maculopapular rash
• Fever
• Splenomegaly 
• Lymphadenopathy 

Sensory Disorders

• Visual disturbance
• Double vision 
• Miosis

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

Paracetamol/ Phenylpropanolamine/ Phenyltoloxamine/ Codeine

• Monoamine oxidase inhibitor
• Tranylcypromine

Paracetamol

• Metoclopramide 
• Domperidone
• Cholestyramine
• Oral anticoagulants
• Chloramphenicol

Phenylpropanolamine

• Monoamine oxidase inhibitors
• Agomelatine
• Bromocriptine
• Dihydroergotamine
• Donepezil
• Indomethacin
• Methyldopa
• Midodrine
• Sibutramine
• Propranolol
• Fentanyl

Phenyltoloxamine

• No information available 

Codeine

• Alcohol
• Anaesthetics
• Antiarrhythmic agents
• Central nervous system depressants
• Antihistamines
• Domperidone 
• Metoclopramide
• Cimetidine

None routine. Specific cases may require

• Hepatic function  
• Respiratory function 

Paracetamol
Paracetamol increases the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin synthesis. It does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects

Phenylpropanolamine
Phenylpropanolamine is a sympathomimetic amine which acts directly on alpha-receptors in the mucosa of the respiratory tract. Stimulation of alpha-adrenergic receptors produces vasoconstriction, which reduces tissue hyperemia, oedema, and nasal congestion, and increases nasal airway patency

Phenyltoloxamine
Phenyltoloxamine is an ethanolamine-type antihistamine which possesses typical H1-histamine antagonist properties. It available only in combination preparations for the treatment of coughs, cold, allergies. In addition to antihistaminic activity, it is considered to have analgesic properties. It has been suggested that the analgesic effects of antihistamines are related to modulation serotonergic and histaminergic pathways that may be involved in nociception

Codeine
Codeine is a centrally acting weak analgesic. It exerts its effect through mu opioid receptors. It resembles morphine in its pharmacodynamic actions although much weaker in its effects

COMBINATION PREPARATIONS

Paracetamol/ Phenylpropanolamine/ Phenyltoloxamine/ Codeine

Tablet 300mg/25mg/22mg/15mg

• Adco-sinal Co (Adcock)
• Sinutab with Codeine (Johnson & Johnson) originator