Acemetacin

Brands of Acemetacin in Kenya

Rantudil, Bayer

MODE OF ACTION

Acemetacin acts as an inhibitor of cyclooxygenase (COX), producing the anti-inflammatory and analgetic (pain relieving) effects. In the body, it is partly metabolized to indometacin, which also acts as a COX inhibitor. The same mechanism is responsible for the antipyretic and antiplatelet effects, which are however not clinically used, as well as for the typical NSAID adverse effects.

An advantage of acemetacin is that it reduces gastric damage as compared to indometacin, possibly because acemetacin has less effect on the increase of leukotriene B4 synthesis and tumor necrosis factor (TNF) expression, leading to less induction of leukocyte-endothelial adherence

INDICATIONS

Rheumatoid arthritis, osteoarthritis, low back pain, and post-operative pain and inflammation.

DOSAGE AND ADMINISTRATION

For oral administration.

To be taken preferably with or after food.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms

Posology:

The recommended starting dose is 120mg/day in divided doses, increasing to 180mg/day in divided doses, depending on patient response.

Special populations:

Elderly:

The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.

Paediatric population:

The safety in children and adolescents is not established

CONTRAINDICATIONS

• Hypersensitivity to the active substance, indomethacin or to any of the excipients .
• Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
• NSAIDS are contra-indicated in patients who have previously shown hypersensitivity reactions (e.g., asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs.
• Severe heart failure, hepatic failure and renal failure .
• During the last trimester of pregnancy .
• History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
• Nasal polyps associated with angioneurotic oedema.
• Blood formation disorder of unclear aetiology
• Children and adolescents

DRUG INTERACTIONS

Other analgesics including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin, other salicylates, diflusinal) as this may increase the risk of adverse effects .

Anti-hypertensives: reduced anti-hypertensive effect.

Diuretics: Reduced diuretic effect should be considered when treating patients with compromised cardiac function or hypertension. Diuretics can increase the risk of nephrotoxicity of NSAIDs. Furosemide accelerates the excretion of acemetacin.

Diuretics and antihypertensives: NSAIDS may weaken the effect of diuretic agents and hypertensive agents. In patients with impaired renal function (such as dehydrated patients or elderly patients), concomitant use of an ACE inhibitor and/or angiotensin-II receptor antagonist and a medicinal product inhibiting cyclooxygenase may lead to further exacerbation of renal function (including the possibility of acute renal failure) which is normally reversible. Therefore, such a combination should be used with caution only, in particular in the elderly. These patients should be encouraged to drink adequate liquids, and regular control of renal laboratory values should be considered after such combination therapy has been initiated.

Hyperkalaemia has been reported with use of indomethacin and this should be considered when administration with potassium-sparing diuretics is proposed. Potassium concentration must be monitored frequently.

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

Phenytoin: decreased elimination of phenytoin.

Lithium: decreased elimination of lithium.

Methotrexate: decreased elimination 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.

Corticosteroids: increased risk of gastrointestinal ulceration or bleeding .

Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin .In case of concomitant treatment, it is therefore recommended to monitor the patient’s blood clotting status.

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.

Penicillin antibiotics:

May delay the elimination of penicillin

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastro-intestinal bleeding . NSAIDS may reduce the effect of SSRIs.

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.

Probenecid, Sulphinpyrazone : Decreased elimination of acemetacin.

Anti-psychotics: increased drowsiness with haloperidol.

Alcohol: Under treatment with NSAIDs, concomitant consumption of alcohol may intensify substance-related adverse effects, in particular the occult blood loss from the gastrointestinal tract.

Antacids:

Antacids can reduce the resorption rate of acemetacin

ADVERSE EFFECTS

Hypersensitivity:

Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions 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, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Cardiovascular and cerebrovascular:

Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.

Clinical trials and epidemiological data suggest that use of some NSAIDs (especially when used at high doses and in long-term treatment) may be associated with a small increase in the risk for arterial thrombotic events (for example myocardial infarction or stroke).

Infections and infestations

In very rare cases, exacerbation of inflammation caused by infection (e.g. development of necrotising fasciitis) has been described in a temporal relationship with the systemic use of non-steroidal anti-inflammatory agents. This may be associated with the mechanism of action of NSAIDs.

Therefore, the patient should contact a doctor if any symptoms of the infection recur or become worse under treatment with Acemetacin. The doctor shall check whether an anti-infectious /antibiotic therapy should be indicated.

Blood and the lymphatic system disorders

Very rare: anaemia caused by occult blood loss from the gastrointestinal tract, haemolytic anaemia, pancytopenia (anaemia including aplastic anaemia, leucopenia, agranulocytosis, thrombocytopenia). The initial symptoms may include: fever, sore throat, superficial lesions in the mouth, flu-like symptoms, severe tiredness, epistaxis and subcutaneous haemorrhage.

In these cases, use of the medicinal product must be discontinued immediately and a doctor must be consulted. Any self-medication with analgesic agents and/or antipyretics shall not happen.

In case of long-term treatment, the blood count should be checked at regular intervals.

An influence on thrombocytes aggregation as well as increased haemorrhagic diathesis is possible.

Immune system disorders

Common: hypersensitivity reactions, such as skin rashes and pruritus.

Uncommon: urticaria

Very rare: severe general hypersensitivity reactions. These may manifest in the form of: oedema of the face and the eyelids, swollen tongue, internal laryngeal oedema with stenosis of the airways (angioneurotic oedema), respiratory distress that may lead to an asthma attack, aggravated asthma, tachycardia, blood pressure decrease leading to life-threatening shock.

Should the patient experience any of these phenomena (which may occur as early as upon the first use of this medicinal product), medical assistance will be required.

Very rare: allergy-related vasculitis and pneumonitis.

Endocrine disorders

Very rare: hyperglycaemia and glucosuria.

Metabolism and nutrition disorders:

Rare: hyperkalaemia

Psychiatric disorders

Common: agitation.

Rare: irritability, confusion.

Very rare: mental disorders, disorientation, anxiety, nightmares, tremor, psychosis, hallucination, depression and transitory loss of consciousness that may lead to coma.

Treatment with Acemetacin may intensify the symptoms of preexisting psychiatric diseases.

Nervous system disorders

Common: central nervous disorders such as headache, sleepiness/fatigue, dizziness, malaise and drowsiness.

Very rare: sensibility disorders, muscular asthenia, hyperhidrosis, dysgeusia, impaired memory, sleep disorders, seizures, reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease) with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation .

Administration of Acemetacin may intensify the symptoms of epilepsy and Parkinson’s disease.

Frequency not known: optic neuritis, paraesthesia

Eye disorders

Uncommon: In the course of long-term treatment with indometacin, the main metabolite of acemetacin, pigment degeneration of the retina and corneal opacity have been reported.

Blurred or double vision may be a typical symptom .

Ear and labyrinth disorders

Very rare: Tinnitus and transitory hearing impairment.

Cardiac disorders

Very rare: palpitations, angina pectoris, cardiac failure

Vascular disorders

Very rare: hypertension

Frequency not known: circulatory collapse

Gastrointestinal disorders

Very common: gastrointestinal disorders such as nausea, vomiting, abdominal pain, diarrhoea and minor haemorrhage from the gastrointestinal tract which, in exceptional cases, can cause anaemia.

Common: dyspepsia, flatulence, abdominal cramps, loss of appetite and gastrointestinal ulcers (sometimes accompanied by bleeding and perforation)

Uncommon: blood can appear in vomit, faeces or diarrhoea.

Very rare:stomatitis, inflammation of the tongue, lesions on the oesophagus, complaints in the lower abdomen (e.g. non-specific, bleeding inflammation of the colon) exacerbation of Crohn’s disease or ulcerative colitis and constipation have been reported. Formation of intestinal diaphragm-like strictures; pancreatitis.

The patient shall be instructed to discontinue the medicinal product and to consult a doctor immediately in case of any severe abdominal pain and/or the occurrence of meleana or haematemesis.

Hepatobiliary disorders

Common: hepatic enzyme increased

Uncommon: hepatic damage (toxic hepatitis with or without icterus, cholestasis

Very rare: taking a fulminant course in cases and at times without prodromal symptoms).

The patient’s liver values should therefore be monitored at regular intervals.

Skin and subcutaneous tissue disorders

Uncommon: alopecia

Very rare: eczema, enanthema, erythema, photosensitivity reaction, minor and extensive cutaneous bleeding, exfoliative dermatitis and rash with bullous eruption, which may also take a grave course such as Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome).

Renal and urinary disorders

Uncommon: development of oedema (e.g. peripheral oedema), in particular in patients with hypertension and/or impaired renal function.

Very rare: micturition disorders, increase in blood urea, acute renal insufficiency, proteinuria, haematuria or renal damage (interstitial nephritis, nephrotic syndrome, papillary necrosis).

Therefore, the patient’s renal function should be checked at regular intervals.

Reproductive system and breast disorders

Very rare: vaginal haemorrhage.

High doses of caffeine can cause tremor and palpitations.

Reporting of suspected adverse reactions:

The PPB Department of Pharmacovigilance was set up with a vision to develop, implement and continuously upgrade an appropriate system for detecting, reporting, and monitoring adverse drug reactions (ADRs) and other relevant problems with medicines in Kenya. The department strives to ensure the safety and efficacy of pharmaceutical products in Kenya.
Reporting suspected adverse reactions after authorization of the medicinal product are important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals/ Patients are encouraged to report any suspected adverse reactions via Pharmacovigilance Yellow Form, pv@pharmacyboardkenya.org or clicking below button:

Acemetacin in Kenya
Acemetacin in Kenya
Acemetacin in Kenya
Acemetacin in Kenya
Acemetacin in Kenya
Acemetacin in Kenya

Clinical | Pharmacokinetic data

Legal Status | Dosage forms & Strengths

Drug Indentifiers:

References/ Citation:

• Jacobi, H., and H. D. Dell. “On the pharmacodynamics of acemetacin (author’s transl).” Arzneimittel-Forschung 30.8A (1980): 1348.