General characteristics:
General physico-chemical properties:
For Larfix Tablet 4 mg Oval shape

white to yellowish

oblong film-coated tablet plain on both sides.
For Larfix Tablet 8 mg
Oval shape

white to yellowish oblong film-coated tablet with imprint “L8″on one side and plain on other side.
Composition:
Each film-coated tablet contains:
Lornoxicam………………..…………4/8 mg
Additional ingredients:
Lactose

microcrystalline cellulose

polyvinyl pyrrolidone

croscarmellose sodium

magnesium stearate

opadry white 03F58750 and purified water.

Indications:
Short term treatment of mild to moderate pain associated with extra articular inflammation. Symptomatic treatment of pain and inflammation in osteoarthritis and rheumatoid arthritis.
Dosage and administration:
Larfix film-coated tablets are supplied for oral administration with a sufficient quantity of liquid. Lornoxicam is not recommended for use in children (under 18 years). No special dosage modification is required for elderly patients

unless renal or hepatic function is impaired

in which case the daily dosage should be considered. For all patients the appropriate dosing regimen should be based upon individual response to treatment. Lornoxicam should be given in doses of 4 mg or 8 mg

and the daily dose should in general not exceed 16 mg. Renal and liver impairment Reduction of dose frequency of larfix to once daily in patients suffering from renal and hepatic impairment should be considered.

Adverse effects:
Approximately 16% of patients (in case of long term treatment 20 – 25%) can be expected to experience adverse reaction concerning the gastrointestinal tract

5% concerning the general disorders and/or central nervous system disorders

and 2% concerning the skin.
In common with other NSAIDs including oxicam the following undesirable effects may occur:
– Gastrointestinal ulcerations with intestinal perforation

which may be severe

– Duodenal ulcers

haematemesis and melaena

– Possible onset of severe skin reactions and serious life threatening hypersensitivity reactions

– In rare cases: interstitial nephritis

glomerulonephritis

renal medullary necrosis or nephrotic syndrome

– Disturbances of blood count

blood dyscrasia

leukocytopenia.
Gastrointestinal disorders
Frequent (≥1% and <10%): abdominal pain

diarrhoea

dyspepsia

nausea

vomiting.
Infrequent (<1%):
constipation

dysphagia

dry mouth

flatulence

gastritis

gastroesophageal reflux

peptic ulceration and/or gastrointestinal bleeding

stomatitis

haemorrhoidal bleeding.
General disorders
Frequent:
dizziness

headache
Infrequent:
insomnia

somnolence

malaise

weakness

flushing Skin and Subcutaneous Tissue Disorders
Infrequent:
alopecia

dermatitis

pruritus

increased sweating

rash

urticaria

purpura

ecchymoses
Haemopoietic Disorders
Infrequent:
thrombocytopenia

increased bleeding time

anaemia

decrease in erythrocytes

haemoglobin

leucocytes Cardiovascular Disorders
Infrequent:
oedema

hypertension

palpitations

tachycardia

hypotension
Neurological disorders Infrequent:

drowsiness

dizziness

vertigo

paraesthesia

tremor

taste perversion
Respiratory Disorders
Infrequent:
dyspnoea

bronchospasm

cough

rhinitis Renal and Urinary disorders
Frequent:
Increase in blood urea nitrogen and creatinine levels
Infrequent:
Micturition disorder
Psychiatric disorders
Infrequent:
Agitation

depression Hepato-biliary Disorders
Frequent:
Increase in serum transaminase levels

alkaline phosphatase level Infrequent: liver function abnormalities
Musculoskeletal

Connective Tissue and Bone Disorders
Infrequent:
Myalgia

leg cramps Disorders of the Eye
Infrequent:
Conjunctivitis

vision disorder Disorders of the Ear
Infrequent:
Tinnitus Disorders of the Immune System Infrequent:
Allergic reactions

Interactions with other medicinal products and other forms of interactions:
Concomitant administration of Lornoxicam and
– Anticoagulants or platelet aggregation inhibitors:
May prolong the bleeding time (increased risk of bleeding)
– Sulphonylureas: May increase the hypoglycaemic effect
– Other non steroidal anti-inflammatory drugs:
Increased risk of adverse reactions
– Diuretics:
Decreased efficacy of loop diuretic drugs
– ACE inhibitors:
The effect of the ACE inhibitor may decreas
– Lithium:
Might lead to an increase for the lithium peak concentration and thus to a possible increase in adverse events.
– Methotrexate and cyclosporine:
Increased serum concentration of methotrexate and cyclosporine
– Cimetidine: Higher plasma concentrations of lornoxicam. (No interaction between XEFO and ranitidine

or XEFO and antacids has been demonstrated).
– Digoxin:
Decreased renal clearance of digoxin
Lornoxicam as other NSAIDs depending on the cytochrome P4502C9 (CYP2C9 isoenzyme) has interactions with known inducers and inhibitors of CYP2C9 isoenzymes (such as tranylcypromine and rifampicin).
NSAIDs increase the risk of spinal or epidural hematoma when given concomitantly to heparin in the context of spinal or epidural anaesthesia

Special warnings and precautions for use:
For the following disorders

Lornoxicam should only be administered after careful risk benefit assessment.
– Gastrointestinal ulceration and bleeding in medical history:
Clinical monitoring at regular intervals is recommended. Patients developing peptic ulceration and/or gastrointestinal bleeding while taking Lornoxicam should discontinue drug administration and with appropriate therapeutic actions being taken.
– Renal impairment
– Patients with mild renal impairment (Serum creatinine 150 – 300 µmol/L) should be monitored quarterly; patients with moderate renal impairment (Serum creatinine 300 – 700 µmol/L) should be monitored in 1 to 2 months intervals. Should renal function deteriorate during treatment Lornoxicam should be discontinued.
– Patients with blood coagulation disorders
Careful clinical monitoring and laboratory assessment is recommended. (eg. PTT).
– Liver diseases (eg. liver cirrhosis)
Clinical monitoring and laboratory assessment at regular intervals is recommended. (eg. liver enzymes).
– Long term treatment (longer than 3 months)
Regular laboratory assessments of haematology (haemoglobin)

renal functions (creatinine) and liver enzymes are recommended.
– Elderly patients (65 years or above)
Monitoring of renal and hepatic function is recommended It is important to monitor renal function in patients

– Who are to undergo major surgery?
– With stressed 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 drugs that are suspected to or known to be able to cause kidney damage.
Concomitant treatment with NSAIDs and Heparin in the context of a spinal or peridural anaesthesia increase the risk of spinal/epidural hematoma.

Overdosage:
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 and vomiting

cerebral symptoms (dizziness

ataxia ascending to coma and cramps). Change of liver and kidney function

may be 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. The usual emergency measures including gastric lavage should be considered. Lornoxicam can lead to diminished absorption of the preparation. Gastrointestinal disorders can for example be treated with a prostaglandin analogue or ranitidine.
Contraindications:
Lornoxicam must not be administered in the following groups of patients:
– Those allergic to lornoxicam

or any of its excipients
– Those who has suffered hypersensitivity reactions (symptoms like asthma

rhinitis

angioedema or urticaria) to other non steroidal anti-inflammatory drugs

including acetylic salicylic acid. – Patients with gastro-intestinal bleeding

cerebrovascular bleeding or other bleeding disorders
– Patients with active peptic ulceration or with a history of recurrent peptic ulceration
– Patients with severe liver impairment
– Patients with severe renal impairment (Serum creatinine > 700 µmol/L)
– Patients with severe thrombocytopenia
– Patients with severe heart insufficiency – Elderly patients (>65 years) and weighing less than 50kg and undergoing acute surgery.
– Pregnancy or lactation
– Patients under 18 years of age

due to lack of clinical experience

Pharmaceutical Form: Film Coated Tablets
Pharmacotherapeutic group: Non-steroidal Anti-inflammatory and Antirheumatic agent
ATC code: M 01 AC 05
Pharmacologic properties:
Pharmacodynamics:
Lornoxicam is a non steroidal anti-inflammatory drug with analgesic properties and belongs to the class of oxicams. Lornoxicam’s mode of action is partly based on inhibition of the prostaglandin synthesis (inhibition of the cyclooxygenase enzyme). The inhibition of cyclooxygenase does not result in an increase in leukotriene formation.The mechanism of the analgesic action of lornoxicam

as well as that of other NSAIDs

has not yet been fully determined.
Pharmacokinetics:
Lornoxicam is absorbed rapidly and almost completely from the gastrointestinal tract. Maximum plasma concentrations are achieved after approximately 1 to 2 hours. The absolute bioavailability (calculated on AUC) of Larfix film-coated tablets is 90-100%. No first-pass effect was observed. The mean elimination half-life is 3 to 4 hours. Lornoxicam is found in the plasma in unchanged form and as its hydroxylated metabolite. The hydroxylated metabolite exhibits no pharmacological activity.
The plasma protein binding of lornoxicam is 99% and not concentration dependent. Lornoxicam is metabolized completely

and approximately 2/3 is eliminated via the liver and 1/3 via the kidneys as inactive substance.
Lornoxicam is metabolized by cytochrome P450 2C9. Due to genetic polymorphism slow and rapid metabolisers exist for this drug

which could result in markedly increased plasma levels of lornoxicam in slow metabolisers.
Simultaneous intake of lornoxicam with meals reduced Cmax by approximately 30%. Tmax was increased from 1.5 to 2.3 hours. The absorption of lornoxicam (calculated on AUC) can be reduced up to 20%.
Simultaneous intake with antacids has no effect on the pharmacokinetics of lornoxicam. In elderly subjects the clearance is reduced by 30 to 40%. Apart from this reduced clearance there is no significant change in the kinetic profile of lornoxicam in elderly patients

or in patients with mild hepatic or kidney dysfunction.

Storage condition:
Store below 30°C.
Keep all medicines out of reach of children.
Shelf-life:
24 months
Dosage form and packing available:
For 8 mg: Opaque PVC-PVDC blister of 10 tablets

3 or 10 blisters are packed into a carton along with the pack insert. For 4 mg:
Opaque PVC-PVDC blister of 10 tablets

3 blisters are packed into a carton along with the pack insert.
Name and address of manufacturer:
Kusum Healthcare Pvt. Ltd.
SP 289(A)

RIICO Indl. Area

Chopanki

Bhiwadi (Rajasthan)

India
Larfix 4 mg – MM Reg. No.: 1812AA 7081 14073052461705
Larfix 8 mg – MM Reg. No.: 1812AA 7082