Lornbloc 4 mg, 8 mg FC tablets

u2022 Short term treatment of mild to moderate pain associated with extra articular inflammation.

u2022 Symptomatic treatment of pain and inflammation in osteoarthritis and rheumatoid arthritis.

Posology

For all patients the appropriate dosing regimen should be based upon individual response to treatment. Use the lowest effective dose for the shortest possible duration of treatment.

Adults (> 18 years of age)

Treatment of pain

8 mg to 16 mg per day given in 2 to 3 divided doses. The total daily dose should not exceed 16 mg.

Rheumatoid Arthritis (RA) and Osteoarthritis (OA)

Initial recommended total daily dose is 12 mg, divided in two or three doses. Maintenance dose should not exceed 16 mg per day.

Special populations

Elderly population

No special dosage modification is required for elderly patients (> 65 years), unless renal or hepatic function is impaired, in which case the daily dosage should be restricted (see section 4.4).

Renal impairment and hepatic impairment

For patients with renal or hepatic impairment the maximal recommended daily dose is reduced to 12 mg (one film-coated tablet LORNBLOC 4 mg three times per day). For details see section 4.4.

Paediatric population

LORNBLOC is not recommended for use in children under 18 years (see section 4.3).

Method of administration

LORNBLOC film-coated tablets are supplied for oral administration and should be taken before meals with a sufficient quantity of liquid.

LORNBLOC is contraindicated in:

• Patients with hypersensitivity to lornoxicam or to any excipients in LORNBLOC (see section 6.1).
• Patients who have suffered hypersensitivity reactions (bronchospasm, rhinitis, angioedema or urticaria) to other non-steroidal anti-inflammatory drugs (NSAIDs), including, acetylsalicylic acid.
• Patients with a history of gastrointestinal bleeding or perforation related to previous NSAID use.
• Patients who suffer from cerebrovascular bleeding.
• Patients with bleeding and coagulation disorders.
• Patient with active peptic ulcer or history of recurrent peptic ulceration/ haemorrhage/ perforations.
• Patient with severe liver impairment.
• Patient with severe renal impairment (serum creatinine > 700 u03bcmol/L).
• Patients with thrombocytopenia.
• Patients who have heart failure.
• The elderly (> 65 years), those weighing less than 50 kg and those undergoing acute surgery.
• Patient under 18 years of age (see section 4.2).
• In pregnancy and lactation.

Hypersensitivity

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 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. LORNBLOC should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Drug reaction with eosinophilia and systemic symptoms

Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported in patients using NSAIDs such as LORNBLOC. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, haematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue LORNBLOC and evaluate the patient immediately.

Gastrointestinal (GI) ulceration and bleeding in medical history

GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events. The risk of gastrointestinal bleeding or perforation is higher with increasing doses of LORNBLOC in patients with a history of ulcers, particularly if complicated with haemorrhage or perforation (see section 4.3), and the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective medicines (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 (see below and section 4.5). 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 medicines such as acetylsalicylic acid (see section 4.5).

Clinical monitoring at regular intervals is recommended. Patients developing peptic ulceration and/or gastro-intestinal bleeding while taking LORNBLOC should discontinue medicine administration with appropriate therapeutic actions being taken.

LORNBLOC should be given with caution to patients with a history of gastrointestinal disease (e.g. ulcerative colitis, Crohnu2019s disease, hiatus hernia, gastro-oesophageal reflux disease, angiodysplasia) as the condition may be exacerbated.

LORNBLOC should only be administered after careful risk-benefit assessment in previous cerebrovascular haemorrhage, SLE, porphyria, haematopoietic disorders, patients with reduced cardiac function. When treating patients with mild to moderate cardiac failure, attention must be paid to the risk of fluid retention and decreased renal function.

Caution is required in 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 LORNBLOC therapy.

Studies 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, as contained in LORNBLOC.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with LORNBLOC 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).

Hepatic impairment (e.g. liver cirrhosis)

Clinical monitoring and laboratory assessment at regular intervals is recommended (e.g. liver enzymes) as accumulation of lornoxicam, as contained in LORNBLOC (increase in AUC) may occur after treatment with daily doses of 12 to 16 mg. Apart from that, hepatic impairment does not seem to affect pharmacokinetic parameters of lornoxicam as compared to healthy subjects (see section 4.3).

Renal impairment

Patients with mild renal impairment (serum creatinine 150 to 300 u03bcmol/L) should be monitored quarterly, patients with moderate renal impairment (serum creatinine 300 to 700 u03bcmol/L) should be monitored at 1 to 2 -month intervals due to dependency on renal prostaglandins for maintenance of renal blood flow. Should renal function deteriorate during treatment, LORNBLOC should be discontinued (see section 4.3).

It is important to monitor renal function in patients:

• who are to undergo major surgery;
• with compromised renal function e.g. as a result of significant blood loss or severe dehydration;
• with cardiac failure;
• receiving concomitant treatment with diuretics;
• receiving concomitant treatment with medicines that are nephrotoxic.

Patients with coagulation disorders

Lornoxicam, as contained in LORNBLOC reduces platelet aggregation and prolongs bleeding time and consequently care should be taken when administering to patients with increased bleeding tendency. Patients with blood coagulation disorders, careful clinical monitoring and laboratory assessment is recommended (e.g. PTT).

Systemic lupus erythematosus (SLE)

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.

Asthma

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.

Long term treatment (longer than 3 months)

Regular laboratory assessments of haematology (haemoglobin), renal functions (creatinine) and liver enzymes is recommended.

Elderly patients (65 years or above)

The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation which may be fatal. There is no clinical experience with this dosage form in this patient group. Monitoring of renal and hepatic function is recommended. Precaution is advised in elderly postoperative patients.

NSAIDs

The use of lornoxicam, as contained in LORNBLOC 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 (see section 4.2, and GI and cardiovascular risks above).

Heparin

Concomitant treatment with NSAIDs and heparin in the context of a spinal or epidural anaesthesia increases the risk of spinal/epidural haematoma (see section 4.5).

Tacrolimus

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 (see section 4.5).

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.

Infections

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.

Excipients

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption should not take this medicine.

Known inducers and inhibitors of CYP2C9 isoenzymes lornoxicam, as contained in LORNBLOC has interactions with known inducers and inhibitors of CYP2C9 isoenzymes such as phenytoin, amiodarone, miconazole, tranylcypromine and rifampicin (see section 5.2).

Anticoagulants or platelet aggregation:

Concomitant administration of LORNBLOC and anticoagulants or platelet aggregation inhibitors may prolong the bleeding time. LORNBLOC may enhance the effects of anti-coagulants such as warfarin (see section 4.4). Careful monitoring of INR should be undertaken.

Methotrexate:

Increased serum concentration of high dose methotrexate; avoid concomitant use.

Special care must be taken if both NSAIDs and methotrexate are administered within 24 hours.

Lithium:

Might lead to an increase of the lithium peak concentration above toxicity limits and thus to a possible increase in adverse events. Therefore, serum lithium levels require monitoring, especially during initiation, adjustment and withdrawal of treatment. Avoid concomitant use if frequent analysis of lithium concentration in plasma cannot be performed.

Sulphonylureas (e.g. glibenclamide):

May increase the hypoglycaemic effect.

Other NSAIDs and aspirin:

Increased risk of adverse reactions and increase the risk of gastrointestinal bleeding (see section 4.4).

Diuretics:

Decreased efficacy of loop diuretic medicines, thiazide diuretics, and potassium sparing diuretics. NSAIDs counteract the diuretic effect of furosemide.

ACE inhibitors:

The effect of the ACE inhibitor may decrease and there is a risk of acute renal insufficiency.

Cimetidine:

Higher plasma concentrations of lornoxicam. No interaction between lornoxicam and ranitidine, or lornoxicam and antacids has been demonstrated (see section 5.2).

Digoxin:

Decreased renal clearance of digoxin.

Ciclosporin:

Increased renal toxicity (nephrotoxicity) of ciclosporin may be enhanced via renal prostaglandin mediated effects. During combined treatment renal function should be monitored.

Corticosteroids:

Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

Antiplatelet medicines and selective serotonin reuptake inhibitors (SSRIs):

Increased risk of gastrointestinal bleeding (see section 4.4).

Heparin:

NSAIDs increase the risk of spinal or epidural haematoma when given concomitantly to heparin in the context of spinal or epidural anaesthesia (see section 4.4).

Beta-adrenergic blockers:

Decreased antihypertensive efficacy.

Angiotensin II receptor blocker:

Decreased antihypertensive efficacy.

Quinolone antibiotics:

Increased risk of seizures.

Tacrolimus:

Increase the risk of nephrotoxicity owing to reduced synthesis of prostacyclin in the kidney. During combined treatment renal function should be monitored (see section 4.4).

Pemetrexed:

NSAIDs may reduce renal clearance of pemetrexed resulting in increased renal and gastrointestinal toxicity, and myelosuppression.

The use of LORNBLOC is contraindicated in pregnancy and lactation (see section 4.3).

Pregnancy

First trimester

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies raise concern about 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 %. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period.

Second and Third trimester.

During the third trimester of pregnancy, 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 oligo-hydramnios. At the end of pregnancy, the mother and the neonate may be exposed 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.

Breastfeeding

There are no data on the excretion of lornoxicam in human breast milk. Lornoxicam, as contained in LORNBLOC, is excreted in milk of lactating rats in relatively high concentrations. Therefore lornoxicam should not be used in breastfeeding women.

Fertility

The use of lornoxicam, as with any medicine 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.

Adverse reactions such as dizziness or sleepiness have been reported in patients receiving LORNBLOC, patients should not drive, use machinery or perform any tasks that require concentration, until they are certain that LORNBLOC does not adversely affect their ability to do so (see section 4.8).

a) Summary of the safety profile

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 (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohnu2019s disease (see section 4.4) 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 diarrhoea. 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.

Studies 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 section 4.4).

Exceptionally, occurrence of serious cutaneous and soft tissues infectious complications during varicella.

b) Tabulated list of adverse reactions

System organ class Frequent Less frequent Frequency unknown (cannot be estimated from the available data)

Infections and infestations Pharyngitis

Blood and the lymphatic system disorders Anaemia, thrombocytopenia, leucopoenia, prolonged bleeding time, ecchymosis

Immune system disorders Hypersensitivity, anaphylactoid reaction and anaphylaxis

Metabolism and nutrition disorders Anorexia, weight changes

Psychiatric disorders Insomnia, depression, confusion, nervousness, agitation

Nervous system disorders Mild and transient headache, dizziness

Somnolence, paraesthesia, dysgeusia, tremor, migraine, aseptic meningitis in patients with SLE and mixed connective tissue disorder (see section 4.4).

Eye disorders Conjunctivitis, visual disturbances

Ear and labyrinth disorders Vertigo, tinnitus

Cardiac disorders Palpitations, tachycardia, cardiac failure

Vascular disorders Flushing, oedema, hypertension, hot flush, haemorrhage, haematoma

Respiratory, thoracic and mediastinal disorders Rhinitis, dyspnoea, cough, bronchospasm

Symptoms of irritation in upper respiratory tract

Gastrointestinal disorders Nausea, abdominal pain, dyspepsia, diarrhoea, vomiting

Constipation, flatulence, eructation, dry mouth, gastritis, gastric ulcer, abdominal pain upper, duodenal ulcer, mouth ulceration, stomatitis, oesophagitis, gastroesophageal reflux, dysphagia, aphthous stomatitis, glossitis, perforated peptic ulcer, gastrointestinal haemorrhage

Haemorrhoidal or rectal bleeding

Hepatobiliary disorders Increase in liver function tests, SGPT (ALT) or SGOT (AST), hepatotoxicity resulting in e.g. hepatic failure, hepatitis, jaundice and cholestasis

Skin and subcutaneous tissue disorders Rash, pruritus, hyperhidrosis, rash erythematous, urticaria and angioedema, alopecia, dermatitis and eczema, purpura, oedema and bullous reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis

Drug Reaction with Eosinophillia and Systemic Symptoms (DRESS) (see section 4.4).

Musculoskeletal and connective tissue disorders Arthralgia, bone pain, muscle spasms, myalgia

Cramps in legs

Renal and urinary disorders Nocturia, micturition disorders, increase in blood urea nitrogen and creatinine levels

General disorders and administrative site conditions Malaise, face oedema, asthenia

Debility, changes in appetite, increased sweating

Investigations Increased transaminases

c) Description of selected adverse reactions

NSAIDs have been reported to cause potentially severe haematological disorders like neutropenia, agranulocytosis, aplastic anaemia, and haemolytic anaemia as class effects.

d) Other special populations

Renal impairment

Lornoxicam may precipitate acute renal failure in patients with pre-existing renal impairment, who are dependent on renal prostaglandins for maintenance of renal blood flow (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Aspen Pharmacare: E-mail: [email protected] Tel: 0800 118 088

Symptoms

Overdose may cause nausea and vomiting, dizziness, ataxia, coma and cramps, liver and kidney damage, coagulation disorders.

Treatment

In the case of a real or suspected overdose, the medication should be withdrawn. Treatment is symptomatic and supportive.