Paracetamol/ Ibuprofen

Registered South African indications:

• Pain

Contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product  
• History of hypersensitivity reactions (e.g. bronchospasm, angioedema, asthma, rhinitis, or urticaria)
• Third trimester of pregnancy
• Severe renal impairment
• Severe hepatic impairment
• Severe heart failure (NYHA Class IV)
• Active or history of recurrent peptic ulcer/haemorrhage
• History of or an existing gastrointestinal ulceration/perforation or bleeding
• Patients with defects in coagulation
• Coadministration with other products containing paracetamol
• Coadministration with other products containing acetylsalicylic acid above 75mg daily
• Coadministration with any other non-steroidal anti-inflammatory drugs (NSAIDs), including cyclo-oxygenase-2 (COX-2) specific inhibitors

Cautions

• First and second trimester of pregnancy
• Breastfeeding
• Females of reproductive potential
• Mild to moderate renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Non-cirrhotic alcoholic liver disease
• Respiratory disorders
• Current or history of bronchial asthma or allergic disease
• Systemic lupus erythematosus and mixed connective tissue disease disorders
• Doses of ibuprofen higher than 2400 mg/day
• Risk factors for cardiovascular events
• Cardiac impairment
• Mild to moderate congestive heart failure
• Hypertension
• Hyperlipidaemia
• Diabetes mellitus
• Smoking
• Established ischaemic heart disease
• Peripheral arterial disease
• Cerebrovascular disease or other active bleeding
• History of gastrointestinal disease
• Ulcerative colitis
• Crohn's disease
• History of gastrointestinal toxicity
• Onset of skin rash or mucosal lesions
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: cap, sus, tab

Pain - mild to moderate

Paracetamol/ Ibuprofen
250/ 200 (mg/10ml)

• Oral (sus): 5-10ml, 4 hrly; Max: 30ml/24hrs

250/ 200 (mg)

• Oral (cap): 2 cap, 4hrly; Max: 6 cap/24hrs

350/ 200 (mg)

• Oral (tab): 1-2 tab, 8hrly

325/ 400 (mg)

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

For short-term use only; instruct patient to consult a doctor if the symptoms persist or worsen if the product is required for >3 days

Take with food

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

Pain - mild to moderate

Paracetamol/Ibuprofen
250/ 200 (mg/10ml)

• Younger than 2 years: Not established for use
• Between 2-5 years: Oral (sus): 2.5-5ml, 6-8hrly
• Between 6-12 years: Oral (sus): 5-10ml, 6-8hrly
• Older than 12 years: See adult dosage

250/ 200 (mg)
350/ 200 (mg)
325/ 400 (mg)

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

Pregnancy

• First and second trimester: Caution; not recommended
  Third trimester: Contraindicated  
• There is no experience of the use of paracetamol/ibuprofen combination in humans during pregnancy
• Congenital abnormalities have been reported in association with NSAID administration in humans; however these are low in frequency and do not appear to follow any discernible pattern
• In view of the known affects of NSAIDs on the foetal
  cardiovascular system (risk of closure of ductus arteriosus), use in the last trimester is contraindicated. The onset of
  labour may be delayed and duration increased with an increased bleeding tendency in both mother and child  
• NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus
• Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol use at the recommended
  dosage

Breastfeeding

• Caution
• Ibuprofen and its metabolites can pass in very small amounts into breast milk. No harmful effects to infants are known
• Paracetamol is excreted in breast milk but not in a clinically significant amount and available published data do not contraindicate breastfeeding
• Therefore, it is not necessary to interrupt breastfeeding for short-term treatment with the recommended dose of this combination product

Fertility

• There is limited evidence that drugs which inhibit cyclo-oxygenase/ prostaglandin synthesis may impair female fertility by an effect on ovulation and is not recommended in women attempting to conceive
• This is reversible on withdrawal of treatment
• In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of the product should be considered

Renal Impairment 

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Contraindicated

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Contraindicated

Elderly 

• Caution; no dose adjustment recommended
  The lowest effective dose should be used for the shortest possible duration

Porphyria Information

• Paracetamol: Probably not porphyrinogenic (PNP)
• Ibuprofen: Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Aseptic meningitis
• Paraesthesia
• Optic neuritis
• Somnolence
• Confusion
• Depression
• Hallucinations
• Malaise
• Convulsions

Cardiovascular Disorders

• Cardiac failure
• Oedema
• Hypertension
• Tachycardia
• Hypotension

Respiratory Disorders

• Exacerbation of asthma
• Bronchospasm
• Dyspnoea

Gastrointestinal Disorders

• Abdominal pain
• Nausea and vomiting
• Diarrhoea
• Dyspepsia
• Abdominal discomfort
• Peptic ulcer
• Gastrointestinal perforation
• Gastrointestinal haemorrhage
• Melaena
• Haematemesis
• Mouth ulceration
• Exacerbation of ulcerative colitis  
• Exacerbation of Crohn's disease
• Gastritis
• Pancreatitis
• Flatulence
• Constipation

Hepatobiliary Disorders

• Abnormal liver function
• Hepatitis
• Jaundice

Genitourinary Disorders

• Nephrotoxicity
• Interstitial nephritis
• Nephrotic syndrome
• Renal impairment

Endocrine and Metabolic Disorders

• Increased alanine aminotransferase
• Increased gamma-glutamyltransferase
• Increased blood creatinine
• Increased blood urea
• Increased aspartate aminotransferase
• Increased blood alkaline phosphatase
• Increased blood creatinine phosphokinease

Skin and Subcutaneous Tissue Disorders

• Hyperhidrosis
• Rash
• Pruritus
• Stevens-Johnson syndrome
• Erythema multiforme
• Toxic epidermal necrolysis
• Exfoliative dermatoses
• Purpura
• Photosensitivity
• DRESS syndrome
• Angioedema

Immune, Blood and Lymphatic System Disorders

• Haematopoietic disorders
• Hypersensitivity with urticaria and pruritus
• Severe hypersensitivity reactions
• Facial, tongue and throat swelling
• Anaphylaxis
• Severe shock
• Decreased haemoglobin
• Decreased platelet count

Sensory Disorders

• Visual disturbance
• Tinnitus
• Vertigo

• Paracetamol-containing products
• Ibuprofen-containing products
• Non-steroidal anti-inflammatory drugs
• Acetylsalicylic acid
• Anticoagulants
• Antihypertensives
• Angiotensin-Converting Enzyme inhibitors
• Angiotensin II Antagonists
• Diuretics
• Beta-blockers
• Antiplatelet agents
• Selective serotonin reuptake inhibitors
• Cardiac glycosides
• Corticosteroids
• Quinolone antibiotics
• Cholestyramine
• Metoclopramide
• Domperidone
• Warfarin
• Ciclosporin
• Lithium
• Methotrexate
• Mifepristone
• Tacrolimus
• Zidovudine

None routine. Specific cases may require

• Renal function

Paracetamol
Paracetamol's exact mechanism of action is still not completely defined; however there is considerable evidence to support the hypothesis of a central antinociceptive effect and the inhibition of central cycloxygenase-2 (COX-2) activity. Paracetamol may also stimulate the activity of descending 5-hydroxytryptamine (serotonin) pathways that inhibit nociceptive signal transmission in the spinal cord. Evidence has shown that paracetamol is a very weak inhibitor of peripheral COX-1 and 2 isoenzymes.

Ibuprofen
Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that reduces inflammatory pain, swellings and fever. Ibuprofen iinhibits prostaglandin synthesis by inhibition of cycloxygenase-2 (COX-2) isoenzyme and reduces sensitisation of nociceptive nerve terminals. Ibuprofen has also been shown to inhibit induced-leucocyte migration into inflamed areas. Ibuprofen has a pronounced action within the spinal cord due, in part, to the inhibition of COX. Ibuprofen's antipyretic effects are produced by the central inhibition of prostaglandins in the hypothalamus. Ibuprofen reversibly inhibits platelet aggregation.

COMBINATION PREPARATIONS

Paracetamol/ Ibuprofen

Tablet 350mg/200mg

• Ibumol (Pharmacare) originator

Tablet 400mg/325mg

• Mypaid Forte (Adcock Ingram) originator

Capsule 200mg/250mg 

• Ibugesic Plus (Cipla Medpro)
• Ibupain (Sandoz)
• Mypaid (Adcock Ingram) 
• Panado Plus (Adcock Ingram)

Suspension (per 10ml) 250mg/200mg

• Ibumol Banana (Pharmacare)
• Ibumol Grape (Pharmacare)
• Lotem (Adcock Ingram) originator