Piroxicam - referral

Current status

European Commission final decision

Overview

The European Medicines Agency (EMEA) has recently completed a review of the safety of the non-steroidal anti-inflammatory drug (NSAID) piroxicam. The Agency's Committee for Medicinal Products for Human Use (CHMP) has concluded that piroxicam's benefits still outweigh its risks, but, based on safety grounds, only in certain, limited indications. In addition, the CHMP has concluded that piroxicam-containing medicines should no longer be used for the treatment of acute (short-term) pain and inflammation. The review was carried out under an 'Article 31' referral¹.

As for all NSAIDs, piroxicam should always be used at the lowest dose for the shortest possible duration to control symptoms.

¹ Article 31 of Directive 2001/83/EC as amended, referral under Community interest.

What is piroxicam?

Piroxicam is a NSAID, a medicine used to treat inflammation. It has been available on the market for many years and has been used in the treatment of many painful conditions. Piroxicam is known as a non-selective NSAID because it acts on all types of the cyclo-oxygenase enzyme, including one type that is involved in the inflammatory process.

Why was piroxicam reviewed?

The EMEA reviewed the safety of non-selective NSAIDs in 2005 and 2006. It looked at the gastro-intestinal (stomach and bowel) and skin safety of the products, and then at their cardiovascular safety. During this process, piroxicam was singled out for special review because piroxicam-containing medicines are associated with more gastro-intestinal side effects and more serious skin reactions than other non-selective NSAIDs. Consequently, the European Commission asked the CHMP to carry out a full assessment of the benefit-risk balance of piroxicam.

Which data has the CHMP reviewed?

In this review the CHMP has assessed information from previous reviews of safety data, as well as new data from clinical trials and epidemiological studies (studies of the causes and distribution of diseases in the population). It also looked at information published in scientific journals.

What are the conclusions of the CHMP?

Based on the information available, the CHMP has concluded that:

• its use in the treatment of acute painful and inflammatory conditions should be abandoned,
• the use of piroxicam should be limited only to the symptomatic relief of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis,
• it should not be used as a first-line treatment,
• the dose of piroxicam should be limited to a maximum of 20 mg a day,
• its use should only be initiated by doctors who are experienced in treating chronic (long term) painful and inflammatory conditions.

In addition, the CHMP added some contraindications and strengthened warnings for piroxicam, to ensure that it is not used in patients who are at a higher risk of developing side effects.

What are the recommendations for patients?

Patients who have been using piroxicam-containing medicines for the short-term treatment of acute pain or inflammation should not use it again. These patients will need to discuss with their doctor or pharmacist which medicine they can use in place of piroxicam. The choice of an alternative medicine is likely to be based on the type of pain being treated.

Patients who are using piroxicam on a long-term basis to relieve the pain associated with chronic conditions should arrange to see the doctor who prescribed it to them, so that their treatment can be reviewed. This review will allow the doctor to check that piroxicam is still the appropriate treatment for the patient's condition, and, if necessary, to determine which medicine should be used in place of piroxicam. It will also give the doctor the opportunity to consider prescribing another medicine to be taken along with piroxicam, to control the gastro-intestinal side effects. This only applies to patients who are not yet receiving such a medicine. If the doctor decides to continue to prescribe piroxicam, patients should not take it with any other medicine of the same type. This includes acetylsalicylic acid (aspirin) when used for pain relief, as well as other NSAIDs that can be bought without a prescription ('over-the-counter').

These changes only apply to patients who are using piroxicam 'systemically' (when it is given as a treatment throughout the body) as tablets, capsules, injections or suppositories. Patients who use piroxicam 'topically' onto the skin can continue to use the medicine in the same way as before.

What are the recommendations for prescribers?

Doctors should no longer prescribe piroxicam for the treatment of acute pain. This means that piroxicam can no longer be used for some conditions for which it was previously authorised².

Doctors can still prescribe piroxicam for the symptomatic relief of pain and inflammation in patients suffering from:

• osteoarthritis,
• rheumatoid arthritis, or,
• ankylosing spondylitis, but not as a first-line treatment.
• Only doctors who have experience in treating patients with inflammatory or degenerative rheumatic diseases will be able to initiate treatment with piroxicam. The first prescription should be for two weeks only, before treatment is reviewed.
• In any case, doctors should frequently review all patients receiving piroxicam.
• They should limit the prescription of piroxicam to a maximum of 20 mg a day.
• They should always consider prescribing piroxicam with a gastroprotective agent, such as misoprostol or a proton-pump inhibitor.
• They should not prescribe piroxicam to patients who are more likely to develop side effects, such as those with a history of gastro-intestinal disorders associated with bleeding, or those who have had skin reactions to other medicines.
• They should not prescribe piroxicam in association with any other NSAID or an anticoagulant.

² Previously-authorised indications in the European Union vary from country to country and include: acute gout; primary dysmenorrhoea (period pain); post-operative pain; dental treatment and in the course of dental infection; the relief of fever and pain associated with acute upper respiratory tract inflammation; acute musculoskeletal disorders (such as bursitis and tendonitis); acute post-traumatic disorders; and radiculalgia (pain due to nerve damage in the spine).

Questions and answers on the review of Piroxicam

Adopted Reference Number: EMEA/264578/2007

Key facts

About this medicine

• Approved name:
  Piroxicam
• International non-proprietary name (INN) or common name:
  piroxicam

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  CHMP/380917/07
• Type:
  Article 31 referrals

  This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

Key dates and outcomes

• CHMP opinion date:
  21/06/2007
• EC decision date:
  07/09/2007

All documents

Piroxicam - Article 31 referral - Annex I, II, III, IV

Adopted

Questions and answers on the review of Piroxicam

Adopted Reference Number: EMEA/264578/2007

Opinion provided by Committee for Medicinal Products for human Use

Committee for medicinal products for human use (CHMP) opinion following an Article 31(2) referral for Piroxicam containing medicinal products International Non-Proprietary Name (INN): piroxicam: Background information

Adopted Reference Number: EMEA/380917/2007

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

• Overview - lay-language summary of the stage of the procedure
• Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
• Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
• List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
• Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
• List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
• List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
• Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
• Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
• Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
• Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
• Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
• Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.