Paracetamol with ibuprofen oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of ibuprofen with paracetamol
Drugs List
Therapeutic Indications
Uses
Pain - mild to moderate
Dosage
Adults
One tablet to be taken up to three times a day. At least six hours should be left between doses.
If one tablet does not control symptoms, a maximum of two tablets may be taken up to three times a day. At least six hours should be left between doses.
No more than six tablets should be taken in any 24 hour period.
Elderly
One tablet to be taken up to three times a day. At least six hours should be left between doses.
If one tablet does not control symptoms, a maximum of two tablets may be taken up to three times a day. At least six hours should be left between doses.
No more than six tablets should be taken in any 24 hour period.
Contraindications
Children under 18 years
Predisposition to haemorrhage
Coagulopathy
Gastrointestinal ulcer
History of gastrointestinal haemorrhage secondary to NSAID
History of gastrointestinal ulceration
Severe cardiac failure
Severe hepatic impairment
Severe renal impairment
Third trimester of pregnancy
Precautions and Warnings
Allergic disposition
Fluid retention
Patients over 65 years
Varicella
Alcoholism
Asthma
Breastfeeding
Cardiac impairment
Cerebrovascular disorder
Congestive cardiac failure
Connective tissue disorder
Crohn's disease
First trimester of pregnancy
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of asthma
History of cardiac failure
History of gastrointestinal disorder
Hypertension
Ischaemic heart disease
Lactose intolerance
Left ventricular dysfunction
Non-cirrhotic alcoholic liver disease
Porphyria
Renal impairment
Second trimester of pregnancy
Systemic lupus erythematosus
Ulcerative colitis
NSAIDs may provoke or exacerbate asthma
Advise ability to drive/operate machinery may be affected by side effects
Some formulations contain lactose
Discontinue if signs of gastro-intestinal bleeding occur
Elderly - monitor for gastro-intestinal bleeding over initial 4 weeks
If visual disturbances occur, perform ophthalmic evaluation
May inhibit platelet aggregation - observe for signs of bleeding
Monitor blood pressure in hypertensive patients
Monitor patients with cardiovascular conditions
Monitor renal function in patients with risk factors for renal impairment
Advise patients to report signs or symptoms of gastro-intestinal ulcer
Discontinue if signs of gastro-intestinal ulceration occur
May prolong bleeding time
Overdosage causes liver damage
Seek urgent medical advice in event of overdose, even if patient feels well
Discontinue treatment if skin rash or other allergic reaction occurs
Maintain treatment at the lowest effective dose
Start treatment at lowest recommended dose
Maintain treatment for the shortest possible duration
Only recommended for short term use
May cause impaired fertility
Advise patients to report skin rash
Consult doctor if symptoms persist or treatment is required for > 3 days
Pregnancy and Lactation
Pregnancy
Paracetamol with ibuprofen is contraindicated in the third trimester of pregnancy and should be used with caution in the first and second trimester.
At the time of writing there is limited published information regarding the use of paracetamol with ibuprofen in humans during pregnancy.
Schaefer (2015) states that paracetamol does cross the placenta, however due to the drugs analgesic and antipyretic properties, it is the preferred drug of choice to use in pregnancy. Briggs (2015) states teratogenic potential in humans was initially suspected, along with an association with gastroschisis, reduction in proportion of preterm birth, possible causative factor for asthma and elevated IgE levels but subsequent investigations have indicated no developmental risk. Commonly used in all stages of pregnancy therapeutic doses in short-term is deemed safe, while routine use should be avoided
NSAIDs have been associated with spontaneous abortions and congenital abnormalities, although no teratogenic effects have been demonstrated in animal experiments (Briggs et al, 2015). Schaefer (2015) states that therapeutic doses of NSAIDs within the third trimester of pregnancy are associated with a risk of premature closure of foetal ductus arteriosus with possible persistent pulmonary hypertension as well as delaying the onset of labour but increasing the duration with an increased bleeding tendency in both mother and child.
The manufacturer recommends paracetamol with ibuprofen should be avoided in the first six months of pregnancy, unless the potential benefit to the patient outweighs the potential risk to the foetus, and contraindicated in the last three months of pregnancy due to insufficient data regarding the safety of ibuprofen during pregnancy.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Use paracetamol with ibuprofen with caution in breastfeeding.
At the time of writing there is limited published information regarding the use of ibuprofen during breast feeding. Ibuprofen appears in breast milk in very low concentrations and unlikely to affect the breast fed infant adversely. Because of its extremely low levels in breast milk and short half life ibuprofen is a preferred choice as an analgesic or anti-inflammatory agent in nursing mothers.
Paracetamol is excreted into human breast milk in low concentrations that it is not considered harmful, it belongs to the group of analgesic drugs of choice during breastfeeding.
Hale (2014) and Schaefer (2015) state that paracetamol and ibuprofen are the drugs of choice when treating pain and requires no limitation of breastfeeding, but continuous treatment should be avoided. Adverse effects in breastfed infants appear to be rare (Briggs et al, 2015). The manufacturer recommends that it is not necessary to interrupt breastfeeding for short term treatment at the recommended dose.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Abdominal pain
Abnormal liver function
Agranulocytosis
Allergic reaction
Altered liver function tests
Alveolitis
Anaemia
Anaphylaxis
Angioedema
Aplastic anaemia
Aseptic meningitis
Asthma
Bronchospasm
Cardiac failure
Confusion
Constipation
Depression
Diarrhoea
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Erythema multiforme
Exacerbation of colitis
Exacerbation of Crohn's disease
Exfoliative dermatitis
Facial swelling
Fatigue
Flatulence
Fluid retention
Gamma glutamyl transferase (GGT) increased
Gastric discomfort
Gastritis
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Haematemesis
Haematuria
Haemolytic anaemia
Hallucinations
Headache
Hepatitis
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Increase in alkaline phosphatase
Increase in blood urea or creatinine
Increased platelet count
Insomnia
Interstitial nephritis
Jaundice
Leucopenia
Malaise
Myocardial infarction
Nausea
Nephrotic syndrome
Nervousness
Neutropenia
Oedema
Optic neuritis
Pancreatitis
Pancytopenia
Paraesthesia
Peptic ulceration
Photosensitivity
Pruritus
Pulmonary eosinophilia
Purpura
Rash
Renal failure
Somnolence
Stevens-Johnson syndrome
Stroke
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Ulcerative stomatitis
Urticaria
Vertigo
Visual disturbances
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
The MHRA have produced 'generic' overdose sections for the top ten drugs for which the NPIS received the greatest number of queries about management of overdose in 2002. This information is represented below:
Liver damage is possible in patients who have taken 75mg/kg or more of paracetamol in less than an hour, and these patients should be referred to hospital. To avoid underestimating the potentially toxic paracetamol dose ingested by obese patients who weigh more than 110kg, a bodyweight of 110kg (rather than the actual bodyweight) should be used to calculate the total dose of paracetamol ingested in mg/kg.
Signs and Symptoms
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Treatment
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines.
Treatment with activated charcoal should be considered if the overdose in excess of 150mg/kg has been taken within 1 hour. Treatment with acetylcysteine is used up to, and possibly beyond, 24 hours of ingesting paracetamol. It is most effective if given within 8 hours of ingestion, after which effectiveness declines. If required, the patient should be given intravenous acetylcysteine, in line with the established dosage schedule. Giving acetylcysteine by mouth (unlicensed route) is an alternative if intravenous access is not possible. Acetylcysteine can be given irrespective of the plasma paracetamol concentration:
in circumstances where the overdose is staggered or there is doubt over the time of paracetamol ingestion; or
in overdose with a timed plasma paracetamol concentration on or above a single treatment line joining points of 100mg/L at 4 hours and 15mg/L at 15 hours nomogram (https://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con184396.pdf), regardless of risk factors of hepatotoxicity.
Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentration are unreliable). If vomiting is not a problem, and overdose has been taken within 10-12 hours, oral methionine may be a suitable alternative for remote areas outside hospital. Management of patients who present beyond 24 hours from ingestion or with serious hepatic dysfunction should be discussed with the NPIS (https://www.npis.org/) or a liver unit.
Further Information
Last Full Review Date: November 2016
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 10 November 2016.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Nuromol 200 mg/500 mg tablets. Reckitt Benckiser Healthcare (UK) Ltd. Revised November 2011.
Summary of Product Characteristics: Combogesic 500 mg/125 mg film coated tablets. Thornton & Ross Ltd. Revised November 2014.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last accessed: 10 November 2016
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last accessed: 10 November 2016
MHRA 10th September 2012
https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/Paracetamol/index.htm
Last accessed: September 20, 2012
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