Lornoxicam

Lornoxicam

Systematic (IUPAC) name
(3E)-6-chloro-3-[hydroxy(pyridin-2-ylamino)methylene]-2-methyl-2,3-dihydro-4H-thieno[2,3-e][1,2]thiazin-4-one 1,1-dioxide
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	Not recommended; contraindicated in months 7–9
Legal status	℞ Prescription only
Routes	Oral, parenteral
Pharmacokinetic data
Bioavailability	90–100%
Protein binding	99%
Metabolism	CYP2C9
Half-life	3–4 hours
Excretion	2/3 hepatic, 1/3 renal
Identifiers
ATC code	M01AC05
PubChem	CID 5282204
DrugBank	DB06725
ChemSpider	4445392 N
UNII	ER09126G7A Y
KEGG	D01866 Y
Chemical data
Formula	C13H10ClN3O4S2
Mol. mass	371.8192 g/mol
SMILES	eMolecules & PubChem
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Lornoxicam (INN, or chlortenoxicam; trade name Xefo, among others) is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic (pain relieving), anti-inflammatory and antipyretic (fever reducing) properties. It is available in oral and parenteral formulations.

Indications

Lornoxicam is used for the treatment of various types of pain, especially resulting from inflammatory diseases of the joints, osteoarthritis, surgery, sciatica, and other inflammations.^[1]

Contraindications

The drug is contraindicated in patients that must not take other NSAIDs, possible reasons including salicylate sensitivity, gastrointestinal bleeding and bleeding disorders, and severe impairment of heart, liver or kidney function. Lornoxicam is not recommended during pregnancy and breastfeeding and is contraindicated during the last third of pregnancy.^[1]

Adverse effects

Lornoxicam has side effects similar to other NSAIDs, most commonly mild ones like gastrointestinal disorders (nausea and diarrhea) and headache. Severe but seldom side effects include bleeding, bronchospasms and the extremely rare Stevens–Johnson syndrome.^[1]

Pharmacokinetics

Absorption

Lornoxicam is absorbed rapidly and almost completely from the gastro-intestinal tract. Maximum plasma concentrations are achieved after approximately 1 to 2 hours. Food protracts the average time to maximum concentration from 1.5 to about 2.3 hours and can reduce the area under the curve (AUC) by up to 20%.^[1]

Distribution

The absolute bioavailability of Lornoxicam is 90–100%. No first-pass effect was observed.^[1]

Metabolism

5’-Hydroxylornoxicam, the main metabolite. The additional hydroxyl group is shown in green.

Lornoxicam is found in the plasma in unchanged form and as its hydroxylated metabolite. The hydroxylated metabolite exhibits no pharmacological activity. CYP2C9 has been shown to be the primary enzyme responsible for the biotransformation of the lornoxicam to its major metabolite, 5’-hydroxylornoxicam.^[1] Lornoxicam 5’-hydroxylation by the variant CYP2C9*3 and CYP2C9*13 is markedly reduced compared with wild type, both in vitro and in vivo.

Elimination

Approximately 1/2 to 2/3 is eliminated via the liver and 1/3 to 42% (data are inconsistent) via the kidneys as 5’-hydroxylornoxicam.^[1]

Mechanism of action

Like other NSAIDs, lornoxicam inhibits prostaglandin biosynthesis by blocking the enzyme cyclooxygenase.

Lornoxicam inhibits both isoforms in the same concentration range, that is, the ratio of COX-1 inhibition to COX-2 inhibition is 1:1. It readily penetrates into the synovial fluid. The AUC ratio of synovial fluid to blood plasma is 0.5 after administration of 4 mg twice daily.

Interactions

Interactions with other drugs are typical of NSAIDs. Combination with vitamin K antagonists like warfarin increases the risk of bleeding. Combination with ciclosporin can lead to reduced kidney function, and to acute renal failure in rare cases. Lornoxicam can also increase the adverse effects of lithium, methotrexate and digoxin and its derivatives. The effect of diuretics, ACE inhibitors and angiotensin II receptor antagonists can be reduced, but this is only relevant in patients with special risks like heart failure. As with piroxicam, cimetidine can increase plasma levels but is unlikely to cause relevant interactions.^[2]

References

1. ^ ^{a b c d e f g} Haberfeld, H, ed (2009) (in German). Austria-Codex (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 3-85200-196-X. 
2. ^ Klopp, T, ed (2010) (in German). Arzneimittel-Interaktionen (2010/2011 ed.). Arbeitsgemeinschaft für Pharmazeutische Information. ISBN 978-3-85200-207-1.