INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
XEFO® 8 IV/IM Injection

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

XEFO^® 8 IV/IM Injection

COMPOSITION:
Each vial contains 8 mg lornoxicam

PHARMACOLOGICAL CLASSIFICATION:
A 3.1 Antirheumatics (anti-inflammatory agents)

PHARMACOLOGICAL ACTION:
Pharmacodynamic properties:
Lornoxicam is a non-steroidal anti-inflammatory drug with analgesic properties and belongs to the class oxicams. The mode of action of lornoxicamis partly based on inhibition of prostaglandin synthesis (inhibition of the cyclo-oxygenase enzyme).
In vitro the inhibition of cyclo-oxygenase does not result in an increase in leukotriene formation.
The mechanism of the analgesic action of lornoxicam has not been fully determined.
Pharmacokinetic properties:
XEFO 8 IV/IM is intended for intravenous or intramuscular administration. After intramuscular injection maximum plasma concentrations are achieved after approximately 20-25 minutes. The absolute bio-availability (calculated on AUC) after intramuscular injection is 97%. 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 metabolised completely, and approximately 2/3 is eliminated via the liver and 1/3 via the kidneys as inactive substance.

INDICATIONS:
Short term treatment of mild to moderate pain when oral administration is inappropriate (e.g. after dental surgery).

CONTRA-INDICATIONS:
XEFO is contra-indicated in the following groups of patients:

-	those allergic to lornoxicam, or any of its excipients
-	those who have suffered hypersensitivity reactions (bronchospasm, rhinitis, angioedema or urticaria) to other non-steroidal anti-inflammatory medicines, including acetylsalicylic acid
-	those with hypovolaemia or dehydration
-	those with confirmed or suspected cerebrovascular bleeding
-	those with bleeding and coagulation disorders
-	those with active peptic ulceration or with a history of recurrent peptic ulceration
-	those with severe liver impairment
-	those with severe renal impairment (serum creatinine >700 micromol/L or creatinine clearance <30 mL/min)
-	those with thrombocytopenia
-	those with severe or uncontrolled cardiac failure
-	the elderly (>65 years)
-	those that are pregnancy or lactating
-	those under 18 years of age

WARNINGS:
In patients with the following disorders, XEFO should only be administered after careful risk-benefit assessment (see also Special precautions):
Gastro-intestinal ulceration and bleeding in medical history; previous cerebrovascular haemorrhage; SLE; ulcerative colitis; Crohn’s disease; 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.
Liver diseases (e.g. liver cirrhosis).

DOSAGE AND DIRECTIONS FOR USE:
The route of administration is intravenous (IV) or intramuscular (IM) injection.
Lornoxicam should be given in doses of 8 mg, and the daily dose should in general not exceed 16 mg. In some patients a further 8 mg given within the first 24 hours could be needed.
Instructions for use/handling:
The solution for injection is prepared by dissolving the contents of one vial in Water for Injection (2 mL) or in the accompanying ampoule immediately prior to use. The solution is intended for intramuscular or intravenous injection, administered slowly over not less than 15 seconds as an intravenous injection and over not less than 5 seconds as an intramuscular injection.
After preparation of the solution, change the needle. For IM injection use a sufficiently long needle for a deep intramuscular injection.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
General: Headache, dizziness, injection site reactions (e.g. pain, rubor, stinging, tension), somnolence, sedation, changes in appetite, sweating, loss of weight, oedema, allergic reactions, debility, weight increase.
Central nervous system (CNS): Depression, insomnia.
Eyes: Conjunctivitis, vision disorders.
Gastro-intestinal (GI): Abdominal pain, diarrhoea, dyspepsia, nausea, vomiting, flatulence, dysphagia, constipation, gastritis, dry mouth, stomatitis, pyrosis, peptic ulceration with or without bleeding, esophagitis, haemorrhoidal or rectal bleeding.
Haematological: Anemia, ecchymosis, prolonged bleeding time, thrombocytopenia.
Liver: Increased transaminases.
Musculo-skeletal: Cramps in leg, myalgia.
Neurological: Migraine, paraesthesia, taste perversion, tinnitus and tremor.
Respiratory: Dyspnoea, symptoms of irritation in upper respiratory tract.
Skin: Allergic skin reactions such as dermatitis, flushing and pruritis, loss of hair.
Urogenital: Micturition disorders.
Vascular: Palpitations, tachycardia, changes in blood pressure.
Special precautions:
Gastro-intestinal ulceration and bleeding in medical history:
Clinical monitoring at regular intervals is recommended. Patients developing peptic ulceration and/or gastro-intestinal bleeding while taking XEFO should discontinue medicine administration with appropriate therapeutic actions being taken.
Renal impairment:
Patients with mild renal impairment (serum creatinine 150 - 300 micromol/L) should be monitored quarterly, patients with moderate renal impairment (serum creatinine 300 - 700 micromol/L) should be monitored at 1 to 2 month intervals. Should renal function deteriorate during treatment, XEFO should be discontinued.
Patients with coagulation disorders:
Careful clinical monitoring and laboratory assessment is recommended (e.g. PTT).
Liver diseases (e.g. liver cirrhosis):
Clinical monitoring and laboratory assessment at regular intervals is recommended (e.g. liver enzymes).
Long term treatment (longer than 3 months):
A regular laboratory assessment of haematology (haemoglobin), renal function (creatinine) and liver enzymes is recommended.
Elderly patients (65 years or above):
There is no clinical experience with this dosage form in this patient group.
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

Interactions:

-	Concomitant administration of XEFO and anticoagulants or platelet aggregation inhibitors may prolong the bleeding time.
-	sulphonylureas: may increase the hypoglycaemic effect.
-	other non-steroidal anti-inflammatory medicines and aspirin: increased risk of adverse reactions.
-	diuretics: decreased efficacy of loop diuretic drugs; 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.
-	lithium: might lead to an increase of the lithium peak concentration and thus to a possible increase in adverse events. Avoid concomitant use if frequent analysis of lithium concentration in plasma cannot be performed.
-	methotrexate: increased serum concentration of high dose methotrexate; avoid concomitant use. Special care must be taken if both NSAID and methotrexate are administered within 24 hours.
-	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.
-	cyclosporin: increased renal toxicity.

Lornoxicam has interactions with known inducers and inhibitors of CYP2C9 isoenzymes such as phenytoin, amiodarone, miconazole, tranylcypromine and rifampicin. See Pharmacokinetics.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Overdose may cause nausea and vomiting, dizziness, ataxia, coma and cramps, liver and kidney damage, coagulation disorders.
In the case of a real or suspected overdose, the medication should be withdrawn. Treatment is symptomatic and supportive.


IDENTIFICATION:
XEFO 8 IV/IM: Yellow freeze-dried powder in an amber coloured glass vial.
XEFO Water for Injection: A clear, colourless liquid in a clear glass ampoule.
When reconstituted the product is a yellow, clear liquid free of visible particles.

PRESENTATION:
A vial containing freeze-dried powder and a 2 mL glass ampoule with Water for Injection packed as a set in one pack.
Package sizes available: 1 set, 5 sets, 6 sets and 10 sets

STORAGE INSTRUCTIONS:
Store at room temperature below 25°C.
Do not use the preparation later than 24 hours after reconstitution.
Keep out of reach of children.

REGISTRATION NUMBERS:

XEFO 8 IV/IM:	33/3.1/0249
XEFO Water for Injection:	33/34/0250

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Pharmacia South Africa (Pty) Limited
Alphen West G
George Street
Midrand
1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
29 October 1998

New addition to this site: February 2005
Source: Pharmaceutical Industry
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