Revision Year: 2013 Publisher: Takeda Pharma A/S Denmark, Langebjerg 1, DK-4000, Roskilde, Denmark
Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, non- steroidal, oxicams
ATC code: M01AC05
Lornoxicam is a non-steroidal anti-inflammatory drug(NSAID) with analgesic properties and belongs to the class of oxicams. Lornoxicams mode of action is Lornoxicams mode of action is mainly related to the inhibition of the prostaglandin synthesis (inhibition of the cyclooxygenase enzyme) leading to desensitisation of peripheral nociceptors and consequently inhibition of inflammation. A central effect on nociception which seems to be independent of anti-inflammatory effects has also been suggested.
Lornoxicam has no effect on vital signs (e.g. body temperature, respiratory rate, heart rate, blood pressure, ECG, spirometry).
The analgesic properties of lornoxicam have been demonstrated successfully in several clinical trials during development of the drug.
Due to a local gastrointestinal irritation and a systemic ulcerogenic effect related to the inhibition of prostaglandin (PG)-synthesis, gastrointestinal sequela are common side effects after treatment with lornoxicam as seen with other NSAIDs.
Lornoxicam 8 mg powder for injection is intended for intravenous (IV) as well as intramuscular (IM) administration. After IM injection, maximum plasma concentrations are achieved after approximately 0.4 hours. The absolute bioavailability (calculated on AUC) after IM administration is 97%
Lornoxicam is found in the plasma in unchanged form and as its hydroxylated metabolite. The plasma protein binding of lornoxicam is 99% and not concentration dependent.
Lornoxicam is extensively metabolised in the liver, primarily to the inactive 5–hydroxylornoxicam by hydroxylation. CYP2C9 is involved in this biotransformation of lornoxicam. Due to genetic polymorphism, slow and extensive metabolisers exist for this enzyme which could result in markedly increased plasma levels of lornoxicam in slow metabolisers. The hydroxylated metabolite exhibits no pharmacological activity. Lornoxicam is metabolised completely, and approximately ⅔ is eliminated via the liver and ⅓ via the kidneys as inactive substance.
When tested in animal models, lornoxicam did not induce liver enzymes. From clinical trial data there is no evidence of accumulation of lornoxicam after repeated administrations, when given according to recommended dosage. This finding was supported by drug monitoring data from one year studies.
The mean elimination half-life of the parent compound is 3 to 4 hours. After oral administration about 50% is excreted in the faeces and 42% through the kidneys, mainly as 5-hydroxylornoxicam. The elimination half-life of 5-hydroxylornoxicam is about 9 hours after a parenteral single or twice daily dose.
In elderly patients above age 65, the clearance is reduced with 30-40%. Apart from reduced clearance, there is no significant change in the kinetic profile of lornoxicam in elderly patients.
There is no significant change in the kinetic profile of lornoxicam in patients with renal or hepatic failure, except for accumulation in patients with chronic liver disease after 7 days of treatment with daily doses of 12 and 16 mg.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential.
Lornoxicam caused renal toxicity and gastrointestinal ulceration single- and repeat-dose toxicity studies in several species.
In animals, administration of 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.
In rat, lornoxicam impaired fertility (effects on ovulation and implantation), and affected the pregnancy and delivery. In rabbit and rat, lornoxicam caused premature closure of the ductus arteriosus due to inhibition of cyclooxygenase.
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