Ibuprofen 200mg Coated Tablets – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Ibuprofen 200mg Coated Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 200mg ibuprofen

Excipient(s) with known effect:

Sucrose

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Coated tablet

Round white sugar coated tablet.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Rheumatic or muscular pain, backache, neuralgia, migraine, headache, dental pain, dysmenorrhoea, feverishness, symptoms of cold and influenza.

4.2 Posology and method of administration

Method of administration

For oral administration

To be taken preferably with or after food.

For short-term use only.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

The patient should consult a doctor if symptoms persist or worsen, or if the product is required for more than ten days. If in adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.

Adults, the elderly and children over 12 years

200mg – 400mg, up to three times a day as required.

Leave at least four hours between doses and do not take more than 1200mg in any 24 hour period.

Do not give to children under 12 years of age, except on the advice of a doctor.

4.3. Contraindications

Ibuprofen is contraindicated during the third trimester of pregnancy (see section 4.6).

4.4. Special warnings and precautions for use

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).

As with other NSAIDs, ibuprofen may mask the signs of infection.

The use of ibuprofen product with concomitant NSAIDs including cyclo-oxygenase-2 specific inhibitors should be avoided due to the increased risk of ulceration or bleeding (See section 4.5 Interactions).

Elderly:

The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation which may be fatal (See section 4.2 Posology and administration).

Paediatric population

There is a risk of renal impairment in dehydrated children and adolescents.

NSAIDs should be given with care to patients with a history of ulcerative colitis or Crohn's disease as these conditions may be exacerbated (see section 4.8).

Respiratory disorders and hypersensitivity reactions:

Caution is required if Ibuprofen is administered to patients suffering from, or with a previous history of, bronchial asthma, chronic rhinitis or allergic disorders, since NSAIDs have been reported to precipitate bronchospasm, urticarial or angioedema in such patients.

Cardiac, Renal and Hepatic Impairment:

The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. The habitual concomitant intake of various similar painkillers further increases this risk. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. For these patients, use the lowest effective dose, for the shortest possible duration and monitor renal function especially in long-term treated patients (see also section 4.3).

Ibuprofen should be given with care to patients with as history of heart failure or hypertension since oedema has been reported in association with Ibuprofen administration

There is a risk of renal impairment in dehydrated children and adolescents.

Cardiovascular and cerebrovascular effects

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Cases of Kounis syndrome have been reported in patients treated with

Ibuprofen tablets. Kounis syndrome has been defined as cardiovascular symptoms secondary to an allergic or hypersensitive reaction associated with constriction of coronary arteries and potentially leading to myocardial infarction.

Clinical studies suggest that use of ibuprofen, particularly at a high dose

(2400mg/day) may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke. Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. ≤ 1200mg/day) is associated with an increased risk of arterial thrombotic events.

Patients with uncontrolled hypertension, congestive heart failure (NYHA II-

III), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (2400 mg/day) should be avoided.

Careful consideration should also be exercised before initiating long-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking), particularly if high doses of ibuprofen (2400 mg/day) are required.

role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependant reduction in prostaglandin formation and, secondarily, in renal blood flow, which may cause renal failure. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state.

Renal tubular acidosis and hypokalaemia may occur following acute overdose and in patients taking ibuprofen products over long periods at high doses (typically greater than 4 weeks), including doses exceeding the recommended daily dose.

SLE and mixed connective tissue disease

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see below and section 4.8).

Aseptic meningitis has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease

Impaired female fertility:

The use of ibuprofen may impair female fertility and is not

recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of ibuprofen should be considered.

Masking of symptoms of underlying infections

Ibuprofen can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella. When Ibuprofen is administered for fever or pain relief in relation to infection, monitoring of infection is advised. In non-hospital settings, the patient should consult a doctor if symptoms persist or worsen.

The label will include:

Read the package leaflet before use.

Do not take if you

• have or have ever had a stomach ulcer, perforation or bleeding
• are allergic to ibuprofen or any other ingredient of the product, aspirin or other related painkillers
• are taking other NSAID painkillers, or aspirin with a daily dose above 75mg
• are in the last three months of pregnancy

Speak to a pharmacist or your doctor before taking this product if you

• have or have had asthma, diabetes, high cholesterol, high blood pressure, a stroke, liver, heart, kidney or bowel problems
• are pregnant or trying to get pregnant
• are elderly
• are a smoker.

If symptoms persist consult your doctor.

Do not exceed the stated dose. Keep out of the sight and reach of children.

Ibuprofen 200mg Coated Tablets contain sucrose and sodium Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

This medicine contains less than 1mmol sodium (23mg) per tablet, that is to say essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

Care should be taken in patients treated with any of the following drugs as interactions have been reported in some patients.

Antihypertensives, beta-blockers and diuretics: NSAIDs may reduce the effect of anti-hypertensives, such as ACE inhibitors, angiotensin-II receptor antagonists, beta-blockers and diuretics. Diuretics can also increase the risk of nephrotoxicity of NSAIDs.

Mifepristone: A decrease in the efficacy of the medicinal product can theoretically occur due to the antiprostaglandin properties of NSAIDs. Limited evidence suggests that coadministration of NSAIDs on the day of prostaglandin administration does not adversely influence the effects of mifepristone or the prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medicinal termination of pregnancy.

Other analgesics including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs, including Cox – inhibitors, as this may increase the risk of adverse effects (See section 4.4 Special Warnings and Precautions).

Aspirin (Acetylsalicylic acid): As with other products containing NSAIDs, concomitant administration of ibuprofen and aspirin (unless low-dose aspirin, not above 75mg daily, has been advised by a doctor) is not generally recommended because of the potential of increased adverse effects such as gastrointestinal side effects and toxicity including ulceration or haemorrhage (See section 4.4 Special Warnings and Precautions).

Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Although there are uncertainties regarding extrapolation of these data to the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).

Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin and heparin (See section 4.4 – Special warnings and precautions for use).

Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Sulfonylureas: NSAIDs may potentiate the effects of sulfonylurea medications. There have been rare reports of hypoglycaemia in patients on sulfonylurea medications receiving ibuprofen.

Antiplatelet agents and selective serotonin uptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding with NSAIDs (see section 4.4).

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

4.6. Fertility, pregnancy and lactation

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period.

From the 20th week of pregnancy onward, ibuprofen use may cause oligohydramnios resulting from foetal renal dysfunction. This may occur shortly after treatment initiation and is usually reversible upon discontinuation. In addition, there have been reports of ductus arteriosus constriction following treatment in the second trimester, most of which resolved after treatment cessation. Therefore, during the first and second trimester of pregnancy, ibuprofen should not be given unless clearly necessary. If ibuprofen is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible. Antenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to ibuprofen for several days from gestational week 20 onward. Ibuprofen should be discontinued if oligohydramnios or ductus arteriosus constriction are found.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

• cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction, (see above);

the mother and the neonate, at the end of pregnancy, to:

• possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses;
• inhibition of uterine contractions resulting in delayed or prolonged labour. Consequently, ibuprofen is contraindicated during the third trimester of pregnancy (see section 4.3).

There are no clinical data from the use of topical forms of ibuprofen during pregnancy. Even if systemic exposure is lower compared with oral administration, it is not known if the systemic ibuprofen exposure reached after topical administration can be harmful to an embryo/fetus. During the first and second trimester of pregnancy, Ibuprofen tablets should not be used unless clearly necessary. If used, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, systemic use of prostaglandin synthetase inhibitors including ibuprofen may induce cardiopulmonary and renal toxicity in the fetus. At the end of the pregnancy prolonged bleeding time in both mother and child may occur, and labour can be delayed. Therefore, ibuprofen is contraindicated during the last trimester of pregnancy (see Section 4.3)

Lactation

In the limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.

See section 4.4 Special warnings and precautions for use, regarding female fertility.

4.7 Effects on ability to drive and use machines

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.

4.8. Undesirable effects

Gastrointestinal disorders: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, gastrointestinal haemorrhage and exacerbation of colitis and Crohn's disease (see section 4.4) have been reported following ibuprofen administration. Less frequently, gastritis, duodenal ulcer, gastric ulcer and gastrointestinal perforation have been observed.

Immune system disorders: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reaction and anaphylaxis, (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and, very rarely, erythema multiforme, bullous dermatoses (including Stevens- Johnson syndrome and toxic epidermal necrolysis).

Cardiac disorders and vascular disorders: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. Clinical studies suggest that use of ibuprofen, particularly at high dose (2400 mg/day) may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke (see section 4.4).

Infections and infestations: Rhinitis and aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4).

Exacerbation of infection-related inflammations coinciding with the use of NSAIDs has been described. If signs of an infection occur or get worse during use of Ibuprofen the patient is therefore recommended to go to a doctor without delay.

Skin and subcutaneous tissue disorders: In exceptional cases, severe skin infections and soft-tissue complications may occur during a varicella infection (see also "Infections and infestations")

The following adverse reactions possibly related to ibuprofen and displayed by MedDRA frequency convention and system organ classification. Frequency groupings are classified according to the subsequent conventions: very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000) and Not known (cannot be estimated from the available data).

*Renal tubular acidosis and hypokalaemia have been reported in the post-marketing setting typically following prolonged use of the ibuprofen component at higher recommended doses.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

In serious poisoning metabolic acidosis may occur and the prothrombin time/INR may be prolonged, probably due to interference with the actions of circulating clotting factors. Acute renal failure and liver damage may occur.

Prolonged use at higher than recommended doses may result in severe hypokalaemia and renal tubular acidosis. Symptoms may include reduced level of consciousness and generalised weakness (see section 4.4 and section 4.8).

Good urine output should be ensured.

Renal and liver function should be closely monitored.

Patients should be observed for at least four hours after ingestion of potentially toxic amounts. Frequent or prolonged convulsions should be treated with intravenous diazepam.

Other measures may be indicated by the patient’s clinical condition.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Ibuprofen is a propionic acid derivative with analgesic anti-inflammatory and antipyretic activity. The drug's therapeutic effects as an NSAID is thought to result from its inhibitory effect on the enzyme cyclo-oxygenase, which results in a marked reduction in prostaglandin synthesis.

Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Some pharmacodynamic studies show that when single doses of ibuprofen 400mg were taken within 8 h before or within 30 min after immediate release acetylsalicylic acid dosing (81mg), a decreased effect of acetylsalicylic acid on the formation of thromboxane or platelet aggregation occurred. Although there are uncertainties regarding extrapolation of these data to the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 4.5).

5.2 Pharmacokinetic properties

Ibuprofen is rapidly absorbed from the gastrointestinal tract, peak serum concentrations occurring 1-2 hours after administration. The elimination half-life is approximately 2 hours.

Ibuprofen is metabolised in the liver to two inactive metabolites and these, together with unchanged ibuprofen, are excreted by the kidney either as such or as conjugates. Excretion by the kidney is both rapid and complete.

Ibuprofen is extensively bound to plasma proteins.

5.3 Preclinical safety data

Not applicable

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Colloidal anhydrous silica

Starch (potato)

Povidone

Microcrystalline cellulose

Alginic acid

Magnesium stearate

Sodium lauryl sulfate

Sodium starch glycollate

Croscarmellose sodium

Coating Materials

PVAP sealcote (contains polyvinyl acetate phthalate & stearic acid) Purified talc

Sucrose

Calcium carbonate

Acacia

Titanium dioxide (E171)

Carnauba wax

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

Three years.

6.4 Special precautions for storage

Do not store above 25°C. Store the blister/bottle in the outer carton in order to protect from light and moisture.

6.5 Nature and contents of container

1. 1. Blister Packs.

Tablets are packed individually in pre-moulded PVC film and sealed with aluminium foil.

Pack sizes: 8, 12, 16.

1. 2. Bottles

Tablets are packed into-

Securitainers (polypropylene body & HDPE cap). Pack sizes: 100, 250, 500, 560, 1000.

Tamper evident bottles (polypropylene body & HDPE child resistant cap). Pack sizes: 25, 50, 250, 500, 560, 1000.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Return any left over tablets to the Pharmacist.

7 MARKETING AUTHORISATION HOLDER

Wockhardt UK Ltd,

Ash Road North,

Wrexham,

LL13 9UF,

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 29831/0116

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

Date of latest renewal: 23 May 2008

10 DATE OF REVISION OF THE TEXT

22/04/2024