CYCLADOL 20 mg Effervescent tablet, blister 14

Effervescent tablet (round, pale yellow, with flat faces and bevelled edges, with a break bar* on one face.
Box of 14, blister packs with unit pre-cut.

* The break bar only serves to facilitate taking the tablet; it does not divide it into equal doses.

For one effervescent tablet:

Piroxicam-beta-cyclodextrin complex: 191,20 mg
Quantity corresponding to piroxicam base: 20,00 mg

Excipients with known effect: aspartame (15 mg/tablet), lactose (208,08 mg/tablet), glucose, sodium (260 mg/tablet).

Excipients:

CYCLADOL 20 mg, effervescent tablet is indicated for the symptomatic treatment of osteoarthritis, rheumatoid arthritis or ankylosing spondylitis. Due to its tolerability profile (see sections Dosage and administration, Contraindications and Warnings and precautions), piroxicam should not be used as first-line treatment when treatment with an NSAID is indicated.

The decision to prescribe a medicinal product containing piroxicam should be based on the assessment of all risks specific to each patient (see sections Contraindications and Warnings and precautions).

Dosage

Prescription of medicinal products containing piroxicam should be initiated by physicians experienced in the diagnosis and treatment of patients with inflammatory or degenerative rheumatic diseases.

This medicine is reserved for adults and children over 15 years of age.

The recommended maximum daily dose is 20 mg, i.e. one administration per day.

The occurrence of adverse effects can be minimised by using the lowest effective dose needed for symptom relief for the shortest duration of treatment. The benefit and safety of the treatment should be re-evaluated within 14 days.

If continuation of treatment proves necessary, it should be accompanied by frequent re-evaluations.

Given that piroxicam has been associated with an increased risk of gastrointestinal complications, the possibility of using a gastric mucosa-protective treatment (e.g. misoprostol or proton pump inhibitors) should be seriously considered, particularly for elderly patients.

Elderly subject

In elderly patients, administration of piroxicam must be cautious (see sections Contraindications and Warnings and precautions). It is recommended to initiate treatment with half the recommended adult dose, using another more suitable form. The dose will then be adjusted according to the patient's clinical condition.

The combination with a gastric mucosa-protective treatment is strongly recommended (see above).

Paediatric population

This medicine must not be used in children aged less than 15 years (see section Contraindications).

Method of administration

Oral use.

The tablet must be dissolved in half a glass of water and taken during a meal.

If a half dose is needed, use a more suitable dosage form.

This medicine is contraindicated in the following situations:

• Hypersensitivity to the active substance or to any of the excipients listed in section Composition.
• history of asthma triggered by taking piroxicam or substances with similar activity such as other NSAIDs, aspirin,
• history of serious allergic drug reactions of any type, in particular skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome),
• history of gastrointestinal ulcer, haemorrhage or perforation,
• patients with a history of gastrointestinal disorders predisposing to bleeding disorders such as ulcerative colitis, Crohn's disease, gastrointestinal cancers or diverticulitis,
• patients with active peptic ulcer, inflammatory gastrointestinal disorder or gastrointestinal haemorrhage,
• severe hepatocellular insufficiency,
• severe heart failure,
• severe renal insufficiency,
• children under 15 years,
• phenylketonuria (due to the presence of aspartame).
• pregnancy, from the start of the 6th month (24 weeks of amenorrhoea) (see section Fertility, pregnancy and breastfeeding),

Risk of fetal death

CYCLADOL 20 mg, effervescent tablet exposes to a risk of fetal death even after a single intake due to its cardiopulmonary toxicity (constriction of the ductus arteriosus and occurrence of oligohydramnios, see section Contraindications).

Effects on the unborn child

CYCLADOL 20 mg, effervescent tablet also exposes the newborn to a risk of kidney damage (renal failure), premature closure of the ductus arteriosus and pulmonary hypertension (see section Fertility, pregnancy and breastfeeding).

CYCLADOL 20 mg, effervescent tablet is contraindicated in pregnant women from the beginning of the 6th month of pregnancy (24 weeks of amenorrhea).

In case of planned pregnancy or during the first 5 months (before 24 weeks of amenorrhea), CYCLADOL 20 mg, effervescent tablet should only be prescribed if absolutely necessary.

Special warnings

The occurrence of adverse effects can be minimised by using the minimum effective dose for the shortest duration of treatment necessary to relieve symptoms (see section Dosage and administration and the paragraphs "Gastrointestinal events" and "Cardiovascular and cerebrovascular effects" below). The clinical benefit and safety of use must be periodically reassessed. Treatment should be stopped immediately at the first signs of skin reactions or symptomatic gastrointestinal events.

Patients with asthma associated with chronic rhinitis, chronic sinusitis and/or nasal polyposis have a higher risk of allergic manifestations when taking aspirin and/or non-steroidal anti-inflammatory drugs than the rest of the population.

Administration of this medicinal product may cause an asthma attack, particularly in certain subjects allergic to aspirin or to an NSAID (see section Contraindications).

Due to interactions with arachidonic acid metabolism, the medicine may induce bronchospasm attacks and possibly shock and other allergic reactions in asthmatic or predisposed patients.

Piroxicam, like other NSAIDs, reduces platelet aggregation and prolongs bleeding time; this aspect must be taken into account when taking blood samples and requires increased vigilance in case of concomitant treatment with platelet aggregation inhibitors.

Gastrointestinal (GI) events: risk of GI ulcers, bleeding and perforations.

NSAIDs, including piroxicam, may cause serious gastrointestinal adverse effects including bleeding, ulceration and perforation of the stomach, small intestine or large intestine, some of which may be fatal. These serious adverse events may occur at any time, without necessarily having warning signs, in all patients treated with NSAIDs.

Whether short or long term, any NSAID treatment leads to an increased risk of serious GI adverse effects. Observational studies have suggested that piroxicam may be associated with a higher risk of serious gastrointestinal toxicity compared with other NSAIDs.

Patients presenting with risk factors for serious GI adverse effects should only be treated with piroxicam after careful assessment of the benefit/risk ratio (see section Contraindications and below).

The possibility of using a gastric mucosa-protective treatment (e.g. misoprostol or proton pump inhibitors) should be seriously considered (see section Dosage and administration).

Serious GI complications - Identification of subjects at risk

The incidence of serious GI complications increases with age. Beyond 70 years, there is a high risk of complications. Administration to patients older than 80 years should be avoided.

Patients receiving concomitant treatments, such as oral corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or antiplatelet agents such as low-dose acetylsalicylic acid, are at increased risk of serious GI complications (see below and section Interactions). As with other NSAIDs, the use of piroxicam in combination with a gastric mucosa-protective treatment (e.g. misoprostol or proton pump inhibitors) should be considered for these patients at risk.

Vigilance is required for patients and physicians in order to detect any signs and symptoms of ulceration and/or gastrointestinal bleeding during piroxicam treatment. Patients should be asked to report any new or unusual abdominal symptoms during treatment. If a gastrointestinal complication is suspected during treatment, piroxicam must be discontinued immediately. Further clinical evaluation and a therapeutic alternative should be considered.

Cardiovascular and cerebrovascular effects

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

Clinical studies and epidemiological data suggest that the use of certain NSAIDs (especially when used at high doses and for long durations) may be associated with a slight increase in the risk of arterial thrombotic events (for example, myocardial infarction or stroke). Data are currently insufficient to rule out this increased risk for piroxicam.

Patients with uncontrolled arterial hypertension, congestive heart failure, ischaemic heart disease, peripheral arterial disease, and/or a history of stroke (including transient ischaemic attack) should only be treated with piroxicam after careful assessment of the benefit/risk ratio.

Similar attention should be paid before initiating long-term treatment in patients with risk factors for cardiovascular disease (such as hypertension, hyperlipidaemia, diabetes or smoking).

Skin reactions

Serious skin reactions, some of which have been fatal, including drug hypersensitivity syndrome with eosinophilia and systemic symptoms (DRESS syndrome), exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), have been reported during treatment with piroxicam (see section Adverse effects). Studies have suggested that piroxicam may be associated with a higher risk of serious skin reactions compared with other NSAIDs not derived from oxicams. Patients should be warned of the signs and symptoms of these syndromes and should be closely monitored for skin reactions. The incidence of these adverse effects appears to be greater at the start of treatment, with onset occurring, in the majority of cases, during the first month of treatment. Piroxicam treatment must be stopped at the first appearance of symptoms or signs of Stevens-Johnson Syndrome or Lyell's Syndrome (for example a skin rash of progressive onset often associated with a bullous reaction or mucosal lesions).

Effective management of Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome) is linked to early diagnosis and immediate discontinuation of any suspected drug.

Early discontinuation of the drug is associated with a better prognosis.

If a patient has developed Stevens-Johnson syndrome or toxic epidermal necrolysis (Lyell's syndrome) with the use of piroxicam, piroxicam must not be re-initiated in this patient at any time.

Cases of fixed drug eruption (FDE) have been reported with piroxicam.

Piroxicam must not be re-introduced in patients with a history of piroxicam-related FDE. Potential cross-reactivity may occur with other oxicams.

Functional renal failure

NSAIDs, by inhibiting the vasodilatory action of renal prostaglandins, may cause functional renal failure through reduced glomerular filtration (see section Contraindications).

At the start of treatment, monitoring of diuresis and renal function is recommended in patients with the following risk factors:

• elderly subjects,
• concomitant medicinal products such as: ACE inhibitors, sartans, diuretics (see section Interactions),
• hypovolaemia whatever the cause,
• heart failure,
• chronic renal failure,
• nephrotic syndrome,
• lupus nephropathy,
• decompensated hepatic cirrhosis.

Fluid and sodium retention

Hydrosodium retention with possible oedema, hypertension or worsening of hypertension, worsening of heart failure. Clinical monitoring is necessary at the start of treatment in cases of hypertension or heart failure. A decrease in the effect of antihypertensive agents is possible (see section Interactions).

Hyperkalaemia

Hyperkalaemia favoured by diabetes or treatment with hyperkalaemic medicinal products (see section Interactions).

Regular monitoring of serum potassium should be carried out in these circumstances.

   

When prescribing, the physician should take into account that cases of secondary anovulatory infertility due to non-rupture of the de Graaf follicle, reversible upon discontinuation of treatment, have been described in patients receiving long-term treatment with certain prostaglandin synthesis inhibitors.

Precautions for use

This medicine is available in other pharmaceutical forms that may be more suitable.

The occurrence of asthma attacks in some subjects may be linked to an allergy to aspirin or NSAIDs (see section Contraindications).

Particular attention should be paid to patients with a history of hypertension and/or heart failure, as cases of hydrosodium retention and oedema have been reported in association with NSAID treatment.

Excipients with known effect

This medicine contains 260 mg of sodium per tablet, which is equivalent to 13 % of the WHO-recommended maximum daily dietary intake of 2 g of sodium per adult.

Patients with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases) must not take this medicine.

Risk related to hyperkalaemia

Certain medicines or therapeutic classes may promote the occurrence of hyperkalaemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, angiotensin II inhibitors, non-steroidal anti-inflammatory drugs, heparins (low molecular weight or unfractionated), ciclosporin and tacrolimus, trimethoprim. The occurrence of hyperkalaemia may depend on the presence of associated factors. This risk is increased when the above-mentioned medicines are combined.

Simultaneous administration of piroxicam with the following products requires rigorous monitoring of the patient's clinical and biological status.

Combinations not recommended

+ Other NSAIDs

Increased risk of ulcerogenic and digestive hemorrhage.

+ Acetylsalicylic acid

At anti-inflammatory doses (≥ 1 g per intake and/or ≥ 3 g per day)

At analgesic or antipyretic doses (≥ 500 mg per intake and/or < 3 g per day).

Increased risk of ulcerogenic and digestive hemorrhage.

+ Oral anticoagulants

Increased risk of bleeding with oral anticoagulant (damage to the gastroduodenal mucosa by NSAIDs). If the combination cannot be avoided, close clinical monitoring, and possibly biological monitoring.

+ Unfractionated heparins, low molecular weight heparins and related products (at therapeutic doses or in elderly subjects)

Increased risk of bleeding (inhibition of platelet function and damage to the gastroduodenal mucosa by NSAIDs).

If the combination cannot be avoided, close clinical monitoring. Do not exceed a few days of NSAID treatment.

+ Lithium

Increase in lithium levels that may reach toxic values (decreased renal excretion of lithium).

If the combination cannot be avoided, closely monitor lithaemia and adjust the lithium dosage at initiation of treatment, during the combination and after discontinuation of the NSAID.

+ Methotrexate used at doses above 20 mg/week

Increased toxicity, particularly haematological, of methotrexate (decreased renal clearance of methotrexate by anti-inflammatory drugs).

+ Pemetrexed (patients with mild to moderate renal impairment, creatinine clearance between 45 ml/min and 80 ml/min)

Risk of increased toxicity of pemetrexed (decreased renal clearance by NSAIDs).

Associations requiring precautions for use

+ Ciclosporin, tacrolimus

Risk of additive nephrotoxic effects, particularly in elderly subjects. Monitor renal function at the start of NSAID treatment.

+ Diuretics

Acute renal failure in at-risk patients (elderly and/or dehydrated subjects) due to decreased glomerular filtration (inhibition of vasodilatory prostaglandins due to NSAIDs).

Furthermore, reduction of the antihypertensive effect.

+ Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor antagonists

Acute renal failure in at-risk patients (elderly and/or dehydrated subjects, combined treatment with diuretics, impaired renal function) due to decreased glomerular filtration (inhibition of vasodilatory prostaglandins due to NSAIDs). These effects are generally reversible. Furthermore, reduction of the antihypertensive effect. Hydrate the patient. Monitor renal function at the start of treatment and regularly during the combination.

+ Methotrexate used at doses less than or equal to 20 mg/week

Increased toxicity, particularly haematological, of methotrexate (decreased renal clearance of methotrexate by anti-inflammatory drugs).

Weekly monitoring of the blood count during the first weeks of the combination. Increased monitoring in case of impairment (even slight) of renal function, as well as in elderly subjects.

+ Pemetrexed (patients with normal renal function)

Risk of increased toxicity of pemetrexed (decreased renal clearance by NSAIDs).

Biological monitoring of renal function.

+ Tenofovir Disoproxil

Risk of increased nephrotoxicity of tenofovir, particularly with high doses of NSAIDs or in the presence of risk factors for renal failure.

In case of combination, monitor renal function.

Associations to be taken into account

+ Acetylsalicylic acid at antiplatelet doses (from 50 mg to 375 mg per day in 1 or several intakes)

Increased risk of ulcerogenic and digestive hemorrhage.

+ Glucocorticoids administered orally (except hydrocortisone used as replacement therapy)

Increased risk of ulceration and gastrointestinal bleeding (see section Warnings and precautions).

+ Antiplatelet agents

Increased risk of gastrointestinal haemorrhage.

+ Selective serotonin reuptake inhibitors (SSRIs)

Increased risk of gastrointestinal haemorrhage (see section Warnings and precautions).

+ Unfractionated heparins, low molecular weight heparins and related drugs (prophylactic doses)

Increased risk of bleeding.

+ Beta-blockers (except esmolol)

Reduction of antihypertensive effect (inhibition of vasodilatory prostaglandins by NSAIDs and sodium and water retention with pyrazolone NSAIDs).

+ Deferasirox

Increased risk of ulcerogenic and digestive hemorrhage.

+ Pentoxifylline

Increased bleeding risk.

Pregnancy

From the beginning of the 6th month of pregnancy (24 weeks of amenorrhea): any intake of CYCLADOL 20 mg, effervescent tablet, even a single one, is contraindicated. Even a single intake from 24 weeks of amenorrhoea justifies cardiac and renal ultrasound monitoring of the fetus and/or newborn.

Except in cases of absolute necessity, CYCLADOL 20 mg, effervescent tablet must not be prescribed in a woman planning pregnancy or during the first 5 months of pregnancy (before 24 weeks of amenorrhoea). Where applicable, the dose should be as low as possible and the duration of treatment as short as possible. Prolonged intake is strongly discouraged.

In case of intake from the 20th week of amenorrhoea, cardiac and renal monitoring of the foetus may prove necessary.

In case of oligohydramnios or constriction of the ductus arteriosus, treatment with CYCLADOL 20 mg, effervescent tablet must be discontinued.

Inhibition of prostaglandin synthesis by NSAIDs may affect the course of pregnancy and/or the development of the embryo or foetus.

Risks associated with use during the 1st trimester

Epidemiological studies suggest that treatment with a prostaglandin synthesis inhibitor during the 1st trimester of pregnancy is associated with an increased risk of miscarriage.

For certain NSAIDs, an increased risk of cardiac and abdominal wall malformations (gastroschisis) has also been described. The absolute risk of fetal cardiovascular malformation increased from less than 1% to approximately 1,5% with exposure to 1^er trimester. The risk appears to increase with dose and duration of treatment.

In animals, administration of a prostaglandin synthesis inhibitor during the organogenesis phase causes increased pre- and post-implantation loss, an increase in embryo-fetal lethality, and a higher incidence of certain malformations, including cardiovascular ones.

Risks associated with use during the 2rd and 3th trimester

• From the 12th week of amenorrhoea

Maternal intake of an NSAID exposes the fetus to a risk of renal functional impairment:

• • In utero (initiation of fetal diuresis): oligohydramnios may occur shortly after the start of treatment. This is generally reversible upon discontinuation of treatment. It may progress to anhydramnios, particularly with prolonged exposure to an NSAID.
  • At birth: renal insufficiency (reversible or not) may be observed or even persist, especially in cases of late and prolonged exposure, with a risk of delayed severe hyperkalemia.   

• From the 20th week of amenorrhea:

In addition to the renal functional impairment (see above), maternal intake of an NSAID exposes the fetus to a risk of constriction of the ductus arteriosus (most often reversible on discontinuation of treatment).

• From the 24th week of amenorrhea:

The risk of cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary arterial hypertension) becomes greater and may lead to foetal or neonatal right heart failure or even foetal death in utero. This risk is all the greater and less reversible the closer the intake is to term. This effect exists even with a single intake

In late pregnancy (close to term), NSAID intake also exposes the mother and the newborn to:

• prolongation of bleeding time due to an anti-aggregant action, which may occur even after administration of very low doses of the medicinal product;
• inhibition of uterine contractions resulting in delayed labour or prolonged delivery.

Breast-feeding

As NSAIDs pass into breast milk, this medicine is not recommended for women who are breastfeeding.

Fertility

As with all NSAIDs, use of this medicine may impair female fertility; it is therefore not recommended in women wishing to conceive a child. In women having difficulty conceiving or undergoing fertility investigations, discontinuation of treatment should be considered.

Cycladol 20 mg, effervescent tablet has a minor to moderate influence on the ability to drive vehicles and use machines. Advise patients of the possible occurrence of dizziness, drowsiness and blurred vision.

Summary of the safety profile

The most frequently observed adverse effects are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforations or haemorrhages, sometimes fatal, may occur, particularly in elderly subjects, (see section Warnings and precautions). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, ulcerative stomatitis, abdominal pain, melaena, haematemesis, exacerbation of colitis or Crohn's disease (see section Warnings and precautions) have been reported following administration of NSAIDs. Less frequently, gastritis has been observed.

Tabulated summary of adverse reactions

Adverse effects are classified by organ system and by frequency of occurrence.

Frequencies are defined as follows:

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 frequency not known (cannot be estimated from the available data). Within each frequency category, adverse effects are presented in order of decreasing seriousness.

System organ class	Adverse reaction	Frequency
Blood and lymphatic system disorders	Anaemia	Common
	Haemolytic anaemia, thrombocytopenia, leucopenia, eosinophilia, bone marrow aplasia	Rare
Immune system disorders	Serum sickness, anaphylaxis	Rare
Psychiatric disorders	Confusional state, mood disorders	Not known
Nervous system disorders	Headache	Common
	Somnolence	Uncommon
	Aseptic meningitis	Not known
Eye disorders	Blurred vision	Uncommon
Ear and labyrinth disorders	Vertigo, tinnitus	Common
	Hearing disorder	Not known
Vascular disorders	Arterial hypertension, vasculitis	Not known
Respiratory, thoracic and mediastinal disorders	Bronchospasm, epistaxis	Not known
Gastrointestinal disorders	Abdominal pain, constipation, diarrhoea, epigastric discomfort or pain, flatulence, nausea, vomiting, dyspepsia	Common
	Stomatitis	Uncommon
	Gastrointestinal haemorrhage, gastrointestinal perforation, melaena, haematemesis, peptic ulcer, pancreatitis	Not known
Hepatobiliary disorders	Jaundice, hepatitis*	Not known
Skin and subcutaneous tissue disorders	Skin rash, pruritus	Common
	Photosensitivity reaction, urticaria, angioedema, non-thrombocytopenic purpura.	Rare
	Severe cutaneous adverse reactions: Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome) (see section Warnings and precautions)	Very rare
	Alopecia, exfoliative dermatitis, erythema multiforme, fixed pigmented erythema, DRESS syndrome (see section Warnings and precautions)	Not known
Renal and urinary disorders	Interstitial nephritis, renal papillary necrosis, nephrotic syndrome, renal failure, oedema	Rare
	Hydrosodium retention, hyperkalaemia	Not known
Investigations	Increased transaminases, increased bilirubin, positive antinuclear antibodies, decreased haemoglobin, decreased haematocrit, reversible increase in blood urea, increased serum creatinine, prolonged bleeding time, decreased platelet aggregability	Not known

* More severe hepatic involvement (jaundice, severe or fatal hepatitis) has exceptionally been reported with piroxicam. If abnormalities of liver function persist or worsen, or if clinical signs of hepatic insufficiency or general manifestations (eosinophilia, rash) occur, piroxicam must be discontinued.

Hypersensitivity reactions of the Quincke's edema type have also been reported in association with piroxicam treatment.

Clinical studies and epidemiological data suggest that the use of certain NSAIDs (especially when used at high doses and over a long duration) may be associated with a slight increase in the risk of arterial thrombotic events (for example, myocardial infarction or stroke) (see section Warnings and precautions).

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 national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/

In case of piroxicam overdose, supportive and symptomatic treatment is necessary.

• Immediate transfer to a hospital setting.
• Rapid evacuation of the ingested product by gastric lavage.
• Activated charcoal to reduce the reabsorption of piroxicam and thus reduce serum levels.
• Symptomatic treatment.

Pharmacotherapeutic class: Non-steroidal anti-inflammatory drug, Antirheumatic (M: musculoskeletal system), ATC code: M01AC01.

Mechanism of action

CYCLADOL is a piroxicam-beta-cyclodextrin complex. Piroxicam is a non-steroidal anti-inflammatory drug of the oxicam group.

It has the following properties:

• analgesic,
• antipyretic,
• anti-inflammatory,
• inhibition of platelet functions.

All of these properties are linked to inhibition of prostaglandin synthesis.

CYCLADOL is a piroxicam-beta-cyclodextrin complex. This complex dissociates rapidly. The released piroxicam is immediately absorbed. The beta-cyclodextrin remains in the digestive tract, and the glucose resulting from its degradation in the intestine is absorbed by the colon.

The effervescent tablet form and the scored tablet form are bioequivalent.

The pharmacokinetics of piroxicam are linear. Various studies have shown no change in the pharmacokinetics of piroxicam according to age.

Absorption

After oral administration, the piroxicam beta-cyclodextrin complex dissociates rapidly:

• the dissolution rate of the piroxicam beta-cyclodextrin complex is higher than that of piroxicam,
• the piroxicam released from the piroxicam beta-cyclodextrin complex is rapidly absorbed (absorption half-life = 15 minutes).

The overall bioavailability and extent of absorption are not modified by food, which only slightly delays the rate of absorption.

Distribution

Elimination half-life: approximately 50 hours.

Binding to plasma proteins is high: of the order of 99 percent.

Piroxicam crosses the synovial membrane rapidly; synovial levels are, on average, 45 to 50 percent of blood levels.

Protein binding in synovial fluid is the same as plasma protein binding.

A preliminary study showed that piroxicam is present in breast milk (approximately 1 to 3 % of plasma levels).

Biotransformation/Elimination

Piroxicam is eliminated slowly. It is almost completely metabolised.

Less than 5 percent of the ingested dose is eliminated unchanged in the urine and faeces.

One of the important metabolic pathways is hydroxylation of the pyridine ring of the piroxicam side chain, followed by glucuronide conjugation and urinary elimination.

Serum levels monitored after one year of continuous oral administration of 20 mg/day of piroxicam are equivalent to those of the steady state initially reached.

2 years.

Store at a temperature not exceeding 25 °C.

No special requirements for disposal.

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

List I

Marketing authorisation (AMM)

CIP 3400934877353 (Plq/14).

Price:

5,12 euros (Plq/14).

Social security reimbursement at 30%. Collect.