Xefo 8 mg / 2 ml

/ CTS

This specific application form should only be used if a quick onset of pain relief is needed or if an oral application or an application via suppository is not possible. Generally the treatment should comprise one single injection for therapy initiation only.
For all patients the appropriate dosing regimen should be based upon individual response to treatment.
Pain: Recommended dose: 8 mg intravenous or intramuscular. Daily dose should not exceed 16 mg. Some patients may need a further 8 mg given during the first 24 hours.
The route of administration is intravenous (i.v.) or intramuscular (I.M) injection.
When given as i.v. injection, the time of injection should be at least 15 seconds, and for i.m. injection, at least 5 seconds.
After preparation of the solution, the needle should be changed. For IM injection a sufficiently long needle for a deep intramuscular injection.
The medicinal product is for single use only.
Additional information on special populations
Children and adolescents: Lornoxicam is not recommended for use in children and adolescents below age 18 due to a lack of data on safety and efficacy.
Elderly: No special dosage modification is required for elderly patients above age 65 unless renal or hepatic function is impaired. Lornoxicam should be administered with precaution as gastrointestinal adverse effects are less well tolerated in this group.
Patients with renal impairment: Lornoxicam is contraindicated in patients with severe renal impairment .
Hepatic impairment
Lornoxicam is contraindicated in patients with severe hepatic impairment.

Short term treatment of moderate postoperative pain.

– Hypersensitivity to lornoxicam, or any of its excipients
– hypersensitivity (symptoms like asthma, rhinitis, angioedema or urticaria) to other non steroidal anti-inflammatory drugs, including acetylic salicylic acid.
– gastro-intestinal bleeding, cerebrovascular bleeding or other bleeding disorders
– active or history of recurrent peptic ulceration/haemorrhage (two or more distinct episodes of proven ulceration or bleeding)
– severe hepatic impairment
– severe renal impairment (Serum creatinine > 700 µmol/L)
– thrombocytopenia
– History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy
– severe heart failure
– The third trimester of pregnancy

For the following disorders, lornoxicam should only be administered after careful risk-benefit assessment.
Renal impairment: Lornoxicam should be administered with precaution in patients with mild (serum creatinine 150-300 µmol/l) to moderate (serum creatinine 300 – 700 µmol/l) renal impairment due to dependency on renal prostaglandins for maintenance of renal blood flow. Treatment with lornoxicam should be discontinued if renal function deteriorates during treatment.
– Renal functions should be monitored in patients who undergo major surgery, with cardiac failure, receiving treatment with diuretics, receiving concomitant treatment with drugs that are suspected to or known to be able to cause kidney damage.
Patients with blood coagulation disorders: Careful clinical monitoring and laboratory assessment is recommended. (eg. APTT).
Hepatic impairment (e.g. liver cirrhosis): Clinical monitoring and laboratory assessments at regular intervals should be considered in patients with hepatic impairment as accumulation of lornoxicam (increase in AUC) may occur after treatment with daily doses of 12-16 mg. Apart from that, hepatic impairment does not seem to affect pharmacokinetic parameters of lornoxicam as compared to healthy subjects.
Long term treatment (longer than 3 months): Regular laboratory assessments of haematology (haemoglobin), renal functions (creatinine) and liver enzymes is recommended.
Elderly patients above 65 years: Monitoring of renal and hepatic function is recommended. Precaution is advised in elderly postoperative patients.
The use of lornoxicam with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.
Undesirable effects may be minimised by using lowest effective dose for the shortest duration necessary to control symptoms.
Gastrointestinal bleeding, ulceration and perforation: 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 serious 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, and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose acetylsalicylic acid or other active substances likely to increase gastrointestinal risk. Clinical monitoring at regular intervals is recommended.
Patients with a history of GI toxicity, particularly when 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 medicinal products 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 acetylsalicylic acid.
When GI bleeding or ulceration occurs in patients receiving lornoxicam, the treatment should be withdrawn.
NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) as their condition may be exacerbated.
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
Caution is required in patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with NSAID therapy.
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.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for lornoxicam.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with Lornoxicam after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Concomitant treatment with NSAIDs and heparin in the context of a spinal or epidural anaesthesia increases the risk of spinal/epidural haematoma.
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. Patients appear to be at highest risk of 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. Lornoxicam should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.
Lornoxicam reduces platelet aggregation and prolongs bleeding time and consequently care should be taken when administering to patients with increased bleeding tendency.
Concomitant treatment of NSAIDs and tacrolimus may increase the risk of nephrotoxicity owing to reduced synthesis of prostacyclin in the kidney. Renal function must therefore be monitored closely in patients receiving combination therapy.
As with most NSAIDs occasional increase in serum transaminases level, increase in serum bilirubin or other liver function parameters, as well as increases in serum creatinine and blood urea nitrogen as well as other laboratory abnormalities have been reported. Should any such abnormality prove significant or persist the administration of lornoxicam should be stopped and appropriate investigations prescribed.
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The use of lornoxicam, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair 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 lornoxicam should be considered.
Exceptionally, varicella can be at the origin of serious cutaneous and soft tissues infectious complications.
To date, the contributing role of NSAIDs in the worsening of these infections cannot be ruled out. Thus, it is advisable to avoid use of lornoxicam in case of varicella.
Fetal Toxicity- Premature Closure of Fetal Ductus Arteriosus:
Avoid use of NSAIDs, including lornoxicam, in pregnant women at about 30 weeks gestation and later. NSAIDs, including lornoxicam, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.
Oligohydramnios/Neonatal Renal Impairment:
Use of NSAIDs, including lornoxicam, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit lornoxicam use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if lornoxicam treatment extends beyond 48 hours. Discontinue lornoxicam if oligohydramnios occurs and follow up according to clinical practice

The most commonly observed adverse events of NSAIDs are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease have been reported following administration of NSAIDs. Less frequently, gastritis has been observed.
Approximately 20% of patients treated with lornoxicam can be expected to experience adverse reactions.
The most frequent adverse effects of lornoxicam include nausea, dyspepsia, indigestion, abdominal pain, vomiting, and diarrhea. These symptoms have generally occurred in less than 10% of patients in available studies.
Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke).
See prescribing information for full details.

Cimetidine: Increased plasma concentrations of lornoxicam. (No interaction between lornoxicam and ranitidine, or lornoxicam and antacids has been demonstrated).
Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin. Careful monitoring of INR should be undertaken
Phenprocoumon: Decreased effect of phenprocoumon treatment.
Heparin: NSAIDs increase the risk of spinal or epidural haematoma when given concomitantly to heparin in the context of spinal or epidural anaesthesia.
ACE inhibitors: The antihypertensive effect of the ACE inhibitor may decrease.
Diuretics: Decreased diuretic and antihypertensive effect of loop diuretics, thiazide diuretics and potassium sparing diuretics
Beta-adrenergic blockers: Decreased antihypertensive efficacy.
Digoxin: Decreased renal clearance of digoxin.
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding.
Quinolone antibiotics: Increased risk of seizures.
Anti-platelet agents: Increased risk of gastrointestinal bleeding.
Other NSAIDs: Increased risk of gastrointestinal bleeding or ulceration. .
Methotrexate: Increased serum concentration of methotrexate. Increased toxicity may result. When concomitant therapy has to be used careful monitoring should be undertaken.
Selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding.
Lithium: NSAIDs inhibit renal clearance of lithium, thus the serum concentration of lithium may increase above toxicity limits. Therefore serum lithium levels require monitoring, especially during initiation, adjustment and withdrawal of treatment.
Cyclosporine: Increased serum concentration of cyclosporine. Nephrotoxicity of cyclosporine may be enhanced via renal prostaglandin mediated effects. During combined treatment renal function should be monitored.
Sulphonylureas: Increased risk of hypoglycaemia.
Known inducers and inhibitors of CYP2C9 isoenzymes: Lornoxicam (as other NSAIDs depending on the cytochrome P450 2C9 (CYP2C9 isoenzyme)) has interactions with known inducers and inhibitors of CYP2C9 isoenzymes.
Tacrolimus: Increase the risk of nephrotoxicity owing to reduced synthesis of prostacyclin in the kidney. During combined treatment renal function should be monitored.
Pemetrexed: NSAIDs may reduce renal clearance of pemetrexed resulting in increased renal and gastrointestinal toxicity, and myelosuppression.
Food: Xefo film-coated tablets show a delayed absorption of lornoxicam when given with food. Therefore, Xefo film-coated tablets should not be taken with food when a quick onset of efficacy (relief of pain) is required.
Food may decrease the absorption with about 20% and increase Tmax.

Pregnancy : If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If lornoxicam treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue lornoxicam and follow up according to clinical practice.

Use of NSAIDs, including lornoxicam, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of lornoxicam use between about 20 and 30 weeks of gestation, and avoid lornoxicam use at about 30 weeks of gestation and later in pregnancy (see Labor and Delivery – Clinical Considerations, Data).
Premature Closure of Fetal Ductus Arteriosus
Use of NSAIDs, including lornoxicam, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.
Oligohydramnios/Neonatal Renal Impairment
Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.
Lactation: 
There are no data on the excretion of lornoxicam in human breast milk. Lornoxicam is excreted in milk of lactating rats in relatively high concentrations. Therefore lornoxicam should not be used in breastfeeding women.
See prescribing information for full details.

At this time, there is no experience of overdose to permit definition of the consequence of an overdose, or to suggest specific managements. However, it can be expected that after an overdose with lornoxicam, the following symptoms can be seen: Nausea, vomiting, cerebral symptoms (dizziness, disturbances in vision). Severe symptoms are ataxia ascending to coma and cramps, liver and kidney damages and maybe coagulation disorders.
In the case of a real or suspected overdose, the medication should be withdrawn. Due to its short half-life, lornoxicam is rapidly excreted. Lornoxicam is not dialysable. No specific antidote is known to date. Gastrointestinal disorders can for example be treated with a prostaglandin analogue or ranitidine.

Shelf life: 3 years. Single use only. Reconstituted solution can be stored up to 24 hours at +2°C to +8°C.
Storage: Do not store above 25°C. Keep vial in the outer carton. Protect from light.