Paracetamol/ Pseudoephedrine/ Codeine/ Chlorphenamine

Registered South African indications:

• Symptomatic relief of severe sinus pain, including maxillary, frontal or facial pain
• Associated malaise, fever and congestion of the nasal sinus and eustachian tube mucosa
• Symptomatic relief of hay fever, influenza and the common cold

This combination product contains paracetamol, which may be fatal in overdose. In the event of overdosage or suspected overdosage and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital or poison centre must be contacted immediately.

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of the excipients in the combination product
• Persons receiving monoamine oxidase inhibitor treatment or within 14 days of ceasing such treatment
• Chronic respiratory insufficiency
• Severe renal impairment
• Severe liver function impairment
  • Codeine is not recommended in patients with severe hepatic impairment because codeine is not converted to morphine leading to poor analgesia
• Most forms of cardiovascular disease, including:
  • Angina
  • Hypertension
• Hyperthyroidism
• Hyperexcitability
• Phaeochromocytoma
• Closed angle glaucoma
• Patients undergoing anaesthesia with halothane or other halogenated anaesthetic agents (pseudoephedrine)

South African recommendations

• Pregnancy
• Breastfeeding
• Mild to moderate renal impairment
• Mild to moderate hepatic impairment

Elderly

• The dosage should be reduced in elderly and debilitated patients

Persistent pain and fever

• Patient should consult doctor if pain or fever persists or gets worse at the recommended dosage, if new symptoms occur or if redness and swelling are present, as these could be signs of a more serious condition

Treatment duration

• For pain the combination product should not be used for more than 5 days in adults and children over 12 years of age without doctor consultation
• For fever the combination product should not be used for more than 3 days without doctor consultation

Excess doses

• Dosages in excess of those recommended may provoke severe liver, kidney and cardiovascular repercussions

Drowsiness and impaired concentration

• This combination medicine may lead to drowsiness and impaired concentration which may be aggravated by the simultaneous intake of alcohol or other central nervous system depressant agents

Ability to drive and use machines

• Patients should be advised, particularly at the initiation of therapy, against taking charge of vehicles or machinery, or performing hazardous tasks where loss of concentration could lead to accidents

Coadministration of specific other medications

• This combination product should not be used in patients presently taking monoamine oxidase inhibitors or other medicines for depression, psychiatric or emotional conditions, or hypertension or other cardiovascular conditions without medical consultation and evaluation
• Should not be used concurrently with any other paracetamol- or sympathomimetic-containing medicines
• Avoid concurrent use of medicines containing the same or similar ingredients

Serious skin reactions

• Serious skin reactions such as acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported very rarely in patients receiving paracetamol
• Patients should be informed about the signs of serious skin reactions and use of this combination medicine should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity

Liver disease

• Patients suffering from hepatitis or alcoholism, or recovering from any form of liver disease, should not take excessive quantities (more than 8 tablets in 24 hours) of this combination product

Renal disease

• Use with caution in renal disease. Patients with known renal disease should consult their healthcare provider for guidance relating to their dosage

Prolonged and continuous use

• Tolerance with dependence may occur after continued use
• Exceeding the prescribed dose, together with prolonged and continuous use of this combination product may lead to dependency and addiction

Prostatic hyperplasia

• Paracetamol/ pseudoephedrine/ codeine/ chlorphenamine may cause urinary retention in patients with prostatic hyperplasia

Hypertensive patients

• Paracetamol/ pseudoephedrine/ codeine/ chlorphenamine may increase blood pressure and therefore special care is advisable in patients receiving antihypertensive therapy

Sudden abdominal pain

• Consider discontinuation if patient experiences sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop

Caution for patients with:

• Persistent respiratory conditions such as emphysema, chronic bronchitis, bronchial asthma
• Cough is accompanied by excessive secretions
• Chronic pulmonary disease
• Hypothyroidism
• Diabetes
• Adrenocortical insufficiency
• Impaired kidney or liver function
• Obesity
• Obstructive sleep apnoea
• Prostatic hyperplasia
• Shock
• Inflammatory or obstructive bowel disorders
• Myasthenia gravis

Overdose

• Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver or kidney damage

Pseudoephedrine hydrochloride

Coadministration with other medicines

• The effects of pseudoephedrine hydrochloride are lessened by medicines containing guanethidine, reserpine, methyldopa and may be diminished or enhanced by tricyclic antidepressants

Severe skin reactions

• Severe skin reactions such as acute generalised exanthematous pustulosis (AGEP) have been reported with pseudoephedrine-containing medicines
• This acute pustular eruption may occur within the first 2 days of treatment, with fever, and numerous, small, mostly non-follicular pustules arising on widespread oedematous erythema and mainly localised on the skin folds, body, and upper extremities
• If signs and symptoms such as formation of small pustules occur, with or without pyrexia or erythema, then treatment with pseudoephedrine should be discontinued and a doctor should be consulted

Codeine phosphate

Children between 12-18 years

• Codeine is not recommended in adolescents 12 to under 18 years of age for pain

Ultra-rapid metabolisers of codeine

• Even at recommended dosages, 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)
• Use of paracetamol/ pseudoephedrine/ codeine/ chlorphenamine 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

Caution in patients with:

• Convulsive disorders
• Head injuries
• Conditions in which intracranial pressure is raised

High opioid doses

• 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

Prolonged use

• The prolonged use of high doses of codeine has produced dependence of the morphine type

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

South African registered indications and dosages

Symptomatic relief of severe sinus pain, including maxillary, frontal or facial pain
Associated malaise, fever and congestion of the nasal sinus and eustachian tube mucosa
Symptomatic relief of hay fever, influenza and the common cold

Paracetamol/ Pseudoephedrine/ Codeine/ Chlorphenamine
500/30/10/2 (mg)

• Oral (tab): 1-2 tab, 4-6hrly; Max: 8 tab/24hrs

---

Do not exceed recommended dose

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

South African registered indications and dosages

Symptomatic relief of severe sinus pain, including maxillary, frontal or facial pain
Associated malaise, fever and congestion of the nasal sinus and eustachian tube mucosa
Symptomatic relief of hay fever, influenza and the common cold

Paracetamol/ Pseudoephedrine/ Codeine/ Chlorphenamine
500/30/10/2 (mg)

• Younger than 12 years: Not recommended
• Older than 12 years: See adult dosage

---

Do not exceed recommended dose

---

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

Pregnancy

South African recommendations

• Caution
• Safety in pregnancy has not been established

Breastfeeding

South African recommendations

• Caution
• Safety during lactation has not been established

Fertility

South African recommendations

• No information available

South African recommendations

• Mild to moderate: Caution; no dose adjustment recommended
  Use with caution in renal disease. Patients with known renal disease should consult their healthcare provider for guidance relating to their dosage
• Severe: Contraindicated

South African recommendations

• Mild to moderate: Caution; no dose adjustment recommended
  Patients suffering from hepatitis or alcoholism, or recovering from any form of liver disease, should not take excessive quantities (more than 8 tablets in 24 hours)
• Severe: Contraindicated

South African recommendations

• Caution; dose adjustment recommended
  The dosage should be reduced in elderly and debilitated patients

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

Paracetamol

Blood and Lymphatic System Disorders

Less frequent

• Agranulocytosis
• Thrombocytopenia
• Leucopenia
• Pancytopenia
• Neutropenia
• Anaemia

Gastrointestinal Disorders

Less frequent

• Pancreatitis

Renal and Urinary Disorders

Less frequent

• Renal colic
• Renal failure
• Sterile pyuria

Hepato-biliary Disorders

Less frequent

• Hepatitis

Skin and Subcutaneous Tissue Disorders

Less frequent

• Dermatitis
• Skin rashes and other allergic reactions
  • Rash types include erythematous or urticarial, which can sometimes be serious and accompanied by fever and mucosal lesions

Pseudoephedrine Hydrochloride

Metabolism and Nutrition Disorders

Less frequent

• Decreased appetite
• Hypokalaemia
• Altered metabolism

Psychiatric Disorders

Frequent

• Fear
• Anxiety
• Insomnia
• Confusion
• Irritability
• Psychotic states

Nervous System Disorders

Frequent

• Restlessness
• Tremor
• Dizziness

Less frequent

• Cerebral haemorrhage
• Headache

Cardiac Disorders

Less frequent

• Pulmonary oedema
• Cardiac arrhythmias
• Anginal pain
• Palpitations
• Cardiac arrest

Vascular Disorders

Less frequent

• Hypertension
• Reflex bradycardia
• Tachycardia
• Hypotension
• Fainting

Respiratory, Thoracic and Mediastinal Disorders

Less frequent

• Dyspnoea

Gastrointestinal Disorders

Less frequent

• Nausea
• Vomiting
• Hypersalivation

Renal and Urinary Disorders

Less frequent

• Difficulty in micturition
• Urinary retention

General Disorders and Administration Site Conditions

Frequent

• Weakness
• Sweating
• Tolerance with dependence

Investigations

Less frequent

• Changes in blood sugar levels

Codeine Phosphate

Psychiatric Disorders

Frequency not specified

• Restlessness
• Mood changes
• Hallucinations

Nervous System Disorders

Frequency not specified

• Drowsiness
• Confusion
• Dry mouth
• Dizziness
• Sweating
• Facial flushing
• Headache
• Vertigo
• Raised intracranial pressure

Eye Disorders

Frequency not specified

• Miosis

Cardiac Disorders

Frequency not specified

• Bradycardia
• Tachycardia
• Palpitations

Vascular Disorders

Frequency not specified

• Orthostatic hypotension

Gastrointestinal Disorders

Common

• Nausea
• Vomiting
• Constipation

Skin and Subcutaneous Tissue Disorders

Frequency not specified

• Urticaria (due to histamine-releasing effect)
• Pruritus (due to histamine-releasing effect)
• Itching of the nose (due to histamine-releasing effect)

Renal and Urinary Disorders

Frequency not specified

• Difficulty in micturition
• Ureteric or biliary spasm

Reproductive System and Breast Disorders

Frequency not specified

• Decreased libido
• Impotence

General Disorders and Administration Site Conditions

Frequency not specified

• Hypothermia

Chlorphenamine Maleate

Blood and Lymphatic System Disorders

Less frequent

• Agranulocytosis
• Leucopenia
• Haemolytic anaemia
• Thrombocytopenia

Immune System Disorders

Less frequent

• Hypersensitivity reactions such as pruritus or rash

Psychiatric Disorders

Less frequent

• Nervousness
• Euphoria
• Irritability
• Nightmares
• Hallucinations

Nervous System Disorders

Frequent

• Sedation– ranging from slight drowsiness to deep sleep
• Lassitude
• Dizziness
• Incoordination

Less frequent

• Insomnia
• Tremors
• Convulsions
• Headache
• Blurred vision
• Paraesthesias
• Extrapyramidal effects

Ear and Labyrinth Disorders

Less frequent

• Tinnitus

Vascular Disorders

Less frequent

• Hypertension
• Hypotension

Respiratory, Thoracic and Mediastinal Disorders

Less frequent

• Thickened respiratory-tract secretions
• Tightness of the chest

Gastrointestinal Disorders

Less frequent

• Nausea
• Vomiting
• Dry mouth
• Constipation
• Gastric reflux
• Diarrhoea
• Epigastric pain

Musculoskeletal and Connective Tissue Disorders

Less frequent

• Myalgia

Renal and Urinary Disorders

Less frequent

• Urinary difficulty
• Urinary retention

General Disorders and Administration Site Conditions

Less frequent

• Sweating
• Hair loss

Paracetamol/ Pseudoephedrine/ Codeine/ Chlorphenamine (post-marketing experience)

Immune System Disorders

Frequency unknown

• Anaphylactic reaction
• Hypersensitivity

Psychiatric Disorders

Frequency unknown

• Anxiety
• Euphoric mood
• Hallucination
• Visual hallucination
• Restlessness

Nervous System Disorders

Frequency unknown

• Cerebrovascular accident
• Headache
• Paraesthesia
• Psychomotor hyperactivity
• Tremor

Cardiac Disorders

Frequency unknown

• Dysrhythmia
• Myocardial infarction
• Palpitations
• Tachycardia

Respiratory, Thoracic and Mediastinal Disorders

Frequency unknown

• Respiratory depression

Gastrointestinal Disorders

Frequency unknown

• Abdominal pain
• Ischaemic colitis
• Diarrhoea
• Vomiting

Skin and Subcutaneous Tissue Disorders

Frequency unknown

• Acute generalised exanthematous pustulosis
• Angioedema
• Dermatitis
• Fixed eruption
• Pruritus
• Rash
• Pruritic rash
• Urticaria

Renal and Urinary Disorders

Frequency unknown

• Dysuria
• Urinary retention

Investigations

Frequency unknown

• Increased blood pressure
• Increased transaminases

• Agents that induce liver enzymes
• Hepatotoxic agents
• Enzyme-inducing agents
• Metoclopramide
• Cholestyramine
• Salicylates
• Central nervous system depressants
• Barbiturates
• Hypnotics
• Opioid analgesics
• Anxiolytic sedatives
• Antipsychotics
• Agents with anticholinergic properties
• Cardiovascular medications
• Sympathomimetic agents
• Decongestants
• Tricyclic antidepressants
• Appetite suppressants
• Monoamine oxidase inhibitors
• Cardiac glycosides
• Quinidine
• Ergot alkaloids
• Oxytocin or other vasoconstrictors
• Guanethidine
• Reserpine
• Digoxin
• Alpha-methyldopa
• Anaesthetic agents
• Halothane or other halogenated anaesthetics
• Aluminium hydroxide-containing preparations
• Sedatives
• Phenothiazines
• Warfarin and other coumarin derivatives

Other interactions

• Alcohol

Observations

• Skin reactions (see Warnings and Precautions)

Paracetamol
Paracetamol has analgesic and antipyretic properties. It acts predominantly by inhibiting prostaglandin synthesis in the central nervous system.

Pseudoephedrine hydrochloride
Pseudoephedrine hydrochloride acts as a decongestant. It is a direct- and indirect-acting sympathomimetic.

Chlorphenamine meleate
Chlorphenamine maleate, an alkylamine derivative, has antihistaminic properties.

Codeine phosphate
Codeine phosphate is an opioid analgesic.

COMBINATION PREPARATIONS

Paracetamol/ Pseudoephedrine/ Codeine/ Chlorphenamine

Tablet 500mg/30mg/10mg/2mg

• Sinutab Sinus Pain Extra Strength (Johnson & Johnson)