Noxicam 8 mg film-coated tablets

/ CTS

For all patients the appropriate dosing regimen should be based upon individual response to treatment. Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms
Pain: 8-16 mg lornoxicam daily divided into 2 or 3 doses. The maximum recommended daily dose is 16 mg.
Osteoarthritis and rheumatoid arthritis: The recommended initial dose is 12 mg lornoxicam daily divided into 2 or 3 doses. The maintenance dose should not exceed 16 mg lornoxicam daily.
Renal impairment/ Hepatic impairment: In patients with mild to moderate impairment, the maximum recommended daily dose is 12 mg divided in 2 or 3 doses. Lornoxicam is contraindicated in patients with severe impairment.

* Short-term treatment of moderate pain such as pain after dental surgery.
* Treatment of pain associated with acute lumbo-sciatica.
* Symptomatic treatment of pain and inflammation in osteoarthritis and rheumatoid arthritis.

* Hypersensitivity to lornoxicam or to any of the excipients
* Thrombocytopenia
* Hypersensitivity reactions (symptoms like asthma, rhinitis, angioedema or urticaria) to other non-steroidal anti-inflammatory drugs (NSAIDs) including acetylsalicylic acid
* Severe heart failure
* Gastrointestinal hemorrhage, cerebrovascular hemorrhage or other bleeding disorders
* History of gastrointestinal hemorrhage or perforation, associated with a prior use of NSAIDs
* Active peptic ulcer/hemorrhage or history of recurrent peptic ulcer/hemorrhage (two or more distinct episodes of established ulceration or bleeding)
* Severe hepatic impairment
* Severe renal impairment (serum creatinine >700 μmol/L)
* Third trimester of pregnancy

* Lornoxicam reduces platelet aggregation and prolongs bleeding time. For this reason, caution should be exercised when treating patients with a bleeding diathesis.
* Lornoxicam should only be used after a careful benefit-risk assessment in patients with:
− impaired renal function lornoxicam must be used with caution in patients with mild (serum creatinine 150-300 μmol/L) to moderate (serum creatinine 300-700 μmol/L) renal impairment due to the dependence on renal prostaglandins to maintain renal blood flow. Treatment with lornoxicam should be discontinued if renal function becomes compromised during treatment.
− Renal function must be monitored in the following patients:
o patients awaiting major surgery;
o patients with heart failure;
o patients receiving concomitant treatment with diuretics or medicinal products with known or suspected renal toxicity.
− In patients with bleeding disorders, close clinical and laboratory monitoring is recommended (e.g. PTT).
− Impaired liver function (e.g. liver cirrhosis): In patients with impaired liver function, clinical and laboratory monitoring should be considered given that accumulation of lornoxicam (increase in AUC) may occur following treatment with daily doses of 12-16 mg. That being said, impaired liver function is not expected to affect the pharmacokinetics of lornoxicam compared to that in healthy individuals.
− Patients receiving long-term treatment (longer than 3 months) with NSAIDs should have their liver and kidney parameters checked regularly. In addition, regular hematology laboratory tests should be performed.
− Monitoring of renal and liver function is recommended for elderly patients over 65 years of age. Caution is advised in elderly patients post surgery.
Gastrointestinal bleeding, ulceration and perforation
Gastrointestinal (GI) bleeding, ulceration, or perforation, which may be fatal, have been reported with all NSAIDs and may occur at any time during therapy, with or without prior warning signs or a history of serious gastrointestinal events.
Combination therapy with gastroprotective agents (e.g. misoprostol or proton pump inhibitors) should be considered in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly, concomitant other medicinal products that may increase the gastrointestinal risk.
Cardiovascular and cerebrovascular effects
Appropriate monitoring and counseling are required in patients with hypertension and/or mild to moderate decompensated heart failure (past or current) as fluid retention and edema have been reported in association with NSAID therapy.
The concomitant use of NSAIDs and heparin during spinal or epidural anesthesia increases the risk of spinal/epidural hematoma.
Skin disorders: Serious, sometimes fatal, skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported very rarely in association with the use of NSAIDs. The highest risk of said reactions is likely to be at the start of therapy, with the majority of these reactions occurring within the first month of treatment. Lornoxicam should be discontinued at the first appearance of a skin rash, mucosal lesions or other signs of hypersensitivity.
Respiratory disorders: Caution should be exercised when using NSAIDs in patients suffering from bronchial asthma or patients with a history of asthma, as NSAIDs have been reported to cause bronchospasm in these patients.
Systemic lupus and mixed connective tissue disease
Caution is advised in patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease, as they may be at increased risk of aseptic meningitis.
Nephrotoxicity: Concomitant treatment with NSAIDs and tacrolimus may increase the risk of nephrotoxicity due to reduced renal synthesis of prostacyclin. Renal function should therefore be closely monitored in patients receiving such combination therapy.
Fertility: The use of lornoxicam, like any medicinal product known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is therefore not recommended for use in women planning pregnancy. Discontinuation of lornoxicam should be considered in women who have difficulty conceiving or are undergoing fertility testing.
Varicella: In isolated cases, varicella can lead to serious infectious skin and soft tissue complications. As of yet, NSAIDs’ association with the exacerbation of said infections cannot be ruled out. It is therefore advisable to avoid using lornoxicam in varicella.

Common: Mild and transient headache, dizziness, nausea, abdominal pain, dyspepsia, diarrhea, vomiting.
See prescribing information for full details.

Cimetidine: resulted in increased plasma concentrations of lornoxicam, which could increase the risk of adverse reactions to lornoxicam (No interactions were demonstrated between lornoxicam and ranitidine or between lornoxicam and antacids);
Anticoagulants: NSAIDs may increase the effects of anticoagulants such as warfarin. Close monitoring of the INR is indicated;
Heparin: NSAIDs increase the risk of bleeding and spinal or epidural hematoma when used concomitantly with heparin in conjunction with spinal or epidural anesthesia.
Reduced antihypertensive efficacy: ACE inhibitors, Diuretics (increased risk of hyperkalemia and nephrotoxicity), Beta-blockers, Angiotensin II receptor blockers.
Digoxin: reduced renal clearance of digoxin, increasing the risk of digoxin toxicity.
Corticosteroids: increased risk of gastrointestinal ulcers or hemorrhage
Quinolone antibiotics (e.g. levofloxacin, ofloxacin): increased risk of seizures;
Antiplatelet agents (e.g. clopidogrel): increased risk of hemorrhage;
Other NSAIDs: increased risk of gastrointestinal hemorrhage or ulceration;
Methotrexate: increased serum levels of methotrexate. This may lead to increased toxicity. If concomitant therapy is necessary, careful monitoring is advised;
Selective serotonin reuptake inhibitors (SSRIs): increased risk of hemorrhage;
Lithium: NSAIDs inhibit the renal clearance of lithium, causing the serum lithium levels to possibly increase above toxicity limits. For this reason, serum lithium levels should be monitored, particularly at the start of therapy, at dose adjustments or on discontinuation of therapy;
Cyclosporine: increased serum levels of cyclosporine. The nephrotoxicity of cyclosporine may be increased due to effects mediated by renal prostaglandins. During concomitant therapy, renal function should be monitored accordingly;
Sulfonylureas (e.g. glibenclamide): increased risk of hypoglycemia;
CYP2C9 inducers/inhibitors
Tacrolimus: increases the risk of nephrotoxicity due to the reduced synthesis of prostacyclin in the kidneys. When used together, renal function should be monitored;
Pemetrexed: NSAIDs may decrease renal pemetrexed clearance, thereby increasing renal and gastrointestinal toxicity and leading to myelosuppression.
Food: One meal can reduce absorption by about 20% and increase Tmax.
See prescribing information for full details.

Pregnancy: Lornoxicam is contraindicated in the third trimester of pregnancy.
There is insufficient data regarding the use of lornoxicam in pregnant women.
From the 20th week of gestation onwards, the use of lornoxicam may cause oligohydramnios secondary to fetal renal impairment. This can occur shortly after starting treatment and is usually reversible after treatment is discontinued. In addition, there were reports of fetal ductus arteriosus constriction occurring after treatment in the second trimester of pregnancy, although it was reversible upon discontinuation of treatment in most cases.
During the third trimester of pregnancy, prostaglandin synthesis inhibitors can lead to fetal cardiopulmonary toxicity (with premature closure/constriction of the ductus arteriosus and pulmonary hypertension) and cause renal dysfunction.
Lactation: There is no data on the passage of lornoxicam into human breast milk.
Fertility: As with all active substances that inhibit cyclooxygenase/prostaglandin synthesis, the use of
lornoxicam can impair fertility and is therefore not recommended for women planning pregnancy. Discontinuation of lornoxicam should be considered in women who have difficulty conceiving or are undergoing fertility tests.

There is currently no experience with acute overdose of lornoxicam to describe the consequences of an overdose or to recommend specific measures. However, the following symptoms can be expected after an overdose with lornoxicam: nausea and vomiting, cerebral symptoms (dizziness, visual disturbances). Serious symptoms such as ataxia (including coma and convulsions), liver and kidney damage and possibly coagulation disorders can also occur.
In the event of an actual or suspected overdose, the medicinal product should be discontinued. Due to its short half-life, lornoxicam is rapidly excreted. Lornoxicam is not dialyzable. A specific antidote is currently not known. Usual emergency measures are indicated for treatment of overdose. In principle, the administration of activated charcoal can only reduce the absorption of the active substance immediately after lornoxicam is taken.
Gastrointestinal symptoms can be managed using prostaglandin analogues or ranitidine.