Ibuprofen 400 mg film-coated tablets

Each film-coated tablet contains 400 mg of ibuprofen.

Excipient with known effect:

Each film-coated tablet contains lactose monohydrate.

For a full list of excipients, see section 6.1.

Film-coated tablet

White coloured round shaped biconvex film-coated tablet debossed '4' on one side and break line on other side. Dimension of the tablet in diameter- 12.80 mm±0.20 mm.

The score line is to facilitate breaking for ease of swallowing and not to divide into equal doses.

For the relief of migraine-headaches, backache, dental pain, neuralgia and period pains as well as rheumatic and muscular pains.

Ibuprofen relieves pain and reduces inflammation and temperature as well as relieving headaches and other types of pain. It also relieves cold and flu symptoms.

Method of administration

For oral administration. For short-term use only.

Posology

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

Adults and adolescents weighing from 40 kg (12 years of age and above). Take one tablet with water, up to 3 times a day.

Leave at least 4 hours between doses and do not take more than 3 tablets in any 24 hour period.

If in children and adolescents between 12 and 18 years this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.

Adults should consult a doctor if symptoms persist or worsen, or if the product is required for more than 10 days.

Not for use by children under 12 years of age.

Hypersensitivity to ibuprofen or any of the excipients in the product.

Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, or urticaria) in response to aspirin or other non-steroidal anti- inflammatory drugs.

Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

Severe heart failure (NYHA ClassIV), renal failure or hepatic failure (see section 4.4).

Last trimester of pregnancy (see section 4.6)

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).

The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.

Respiratory:

Bronchospasm may be precipitated in patients suffering from, or with a previous history of, bronchial asthma or allergic disease.

Other NSAIDs:

The use of Ibuprofen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).

SLE and mixed connective tissue disease:

Systemic lupus erythematosus as well as those with mixed connective tissue disease – increased risk of aseptic meningitis (see section 4.8)

Renal:

Renal impairment as renal function may further deteriorate (see sections 4.3 and 4.8). There is a risk of renal impairment in dehydrated children and adolescents.

Hepatic:

Hepatic dysfunction (see sections 4.3 and 4.8)

Cardiovascular and cerebrovascular effects:

Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.

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 (for example 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.

Gastrointestinal:

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

GI bleeding, ulceration or perforation, which can be fatal has been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of GI events.

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available.

Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).

When GI bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn.

Masking of symptoms of underlying infections

Ibuprofen 200 mg film-coated tablets 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 200 mg film-coated tablets is administered for fever or pain relief in relation to infection, monitoring of infection is advised. In nonhospital settings, the patient should consult a doctor if symptoms persist or worsen.

Dermatological:

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens- Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Information related to excipients

This medicinal product contains lactose monohydrate and should not be given to patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.

Ibuprofen should be avoided in combination with:

Aspirin unless low-dose aspirin (not above 75mg daily) has been advised by a doctor as this may increase the risk of adverse reactions (see Section 4.4).

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).

Other NSAIDs including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs as this may increase the risk of adverse effects (see section 4.4)

Ibuprofen should be used with caution in combination with:

Corticosteroids: as these may increase the risk of gastrointestinal ulceration or bleeding (see Section 4.4)

Antihypertensives and diuretics: since NSAIDs may diminish the effects of these drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. These interactions should be considered in patients taking a coxib concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in the elderly.

Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (See section 4.4).

Ant-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).

Cardiac glycosides:NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Lithium: There is evidence for potential increase in plasma levels of lithium.

Methotrexate: There is evidence for the potential increase in plasma levels of methotrexate.

Ciclosporin: Increased risk of nephrotoxicity.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

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 haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

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.

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 embryfoetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. 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.

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

- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

- renal dysfunction, which may progress to renal failure with oligohydroamniosis; the mother and the neonate, at the end of the 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.

Lactation/Breastfeeding:

In limited studies, ibuprofen appears in the breast milk in very low concentration and is unlikely to affect the breast-fed infant adversely.

Fertility

There is limited evidence that drugs which inhibit cyclo-oxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible upon withdrawal of treatment.

Ibuprofen has no influence on the ability to drive and use machines.

Adverse events which have been associated with Ibuprofen are given below, listed by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness.

The list of the following adverse events relates to those experienced with ibuprofen at OTC doses for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse events may occur.

The adverse events observed most often are gastrointestinal in nature. Adverse events are mostly dose-dependent, in particular the risk of occurrence of gastrointestinal bleeding is dependent on the dosage range and duration of treatment.

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 (for example myocardial infarction or stroke), (see section 4.4).

Description of Selected Adverse Reactions

¹ Examples include anaemia, leucopenia, thrombocytopenia, pancytopenia and agranulocytosis. First signs are fever, sore throat, superficial mouth ulcers, flu- like symptoms, severe exhaustion, unexplained bleeding and bruising.

² Hypersensitivity reactions: These may consist of (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract reactivity, including asthma, aggravated asthma, bronchospasm, and dyspnoea, or (c) various skin reactions, including pruritus, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatoses, including toxic epidermal necrolysis, Stevens- Johnson Syndrome and erythema multiforme.

³ The pathogenic mechanism of drug-Induced aseptic meningitis is not fully understood. However, the available data on NSAID-related aseptic meningitis points to a hypersensitivity reaction (due to a temporal relationship with drug intake, and disappearance of symptoms after drug discontinuation). Of note, single cases of symptoms of aseptic meningitis (such as stiff neck, headache, nausea, vomiting, fever or disorientation) have been observed during treatment with Ibuprofen in patients with existing auto-immune disorders (such as systemic lupus erythematosus and mixed connective tissue disease).

⁴ Clinical trial and epidemiological data suggest that use of Ibuprofen (particularly at high doses 2400 mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke), (see section 4.4).

⁵ The adverse events observed most often are gastrointestinal in nature

⁶ Sometimes fatal.

⁷ See section 4.4.

⁸ Especially in long-term use, associated with increased serum urea and oedema. Also includes papillary necrosis.

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.

In children ingestion of more than 400 mg/kg may cause symptoms. In adults the dose response effect is less clear cut. The half-life in overdose is 1.5-3 hours.

Symptoms

Most patients who have ingested clinically important amounts of NSAIDs will develop no more than nausea, vomiting, epigastric pain, or more rarely diarrhoea. Tinnitus, headache and gastrointestinal bleeding are also possible. In more serious poisoning, toxicity is seen in the central nervous system, manifesting as drowsiness, occasionally excitation and disorientation or coma. Occasionally patients develop convulsions. 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.

Exacerbation of asthma is possible in asthmatics.

Management

Management should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable. Consider oral administration of activated charcoal if the patient presents within 1 hour of ingestion of a potentially toxic amount. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.

ATC Code: M01AE01

Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In humans, ibuprofen reduces inflammatory pain, swellings and fever. Furthermore, ibuprofen reversibly inhibits platelet aggregation.

Experimental data suggests that ibuprofen may competitively inhibit the effect of low dose aspirin (acetylsalicylic acid) on platelet aggregation when they are dosed concomitantly. Some pharmacodynamics studies show that when single doses of ibuprofen 400mg were taken within 8 h before or within 30 min after immediate release aspirin (acetylsalicylic acid) dosing (81mg), a decreased effect of ASA (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).

Ibuprofen is rabidly absorbed following administration and is rapidly distributed throughout the whole body. The excretion is rapid and complete via the kidneys.

Maximum plasma concentrations are reached 45 minutes after ingestion if taken on an empty stomach. When taken with food, peak levels are observed after 1 to 2 hours. These times may vary with different dosage forms.

Elimination half-life is approximately 2 hours

In limited studies, ibuprofen appears in the breast milk in very low concentrations.

No relevant information, additional to that contained elsewhere in the SPC.

Tablet core

Silica, colloidal anhydrous

Microcrystalline cellulose

Pregelatinized starch (maize)

Sodium starch glycolate

Talc

Magnesium stearate

Film-coating

Opadry II White contains;

Hypromellose

Titanium dioxide

Lactose monohydrate

Macrogol 4000

Sodium citrate

Not applicable

2 years

This medicinal product does not require any special storage conditions.

400 mg: PVC-Aluminium Blister containing 12, 16, 24, 48, 96 tablets.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Strides Pharma UK Ltd.

Unit 4, The Metro Centre,

Dwight Road, Watford,

WD18 9SS

United Kingdom

PL 13606/0266

30/09/2022

30/09/2022