Lornoxicam
Encyclopedia
Lornoxicam 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.
, surgery, sciatica
, and other inflammations.
, 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.
and diarrhea
) and headache
. Severe but seldom side effects include bleeding, bronchospasm
s and the extremely rare Stevens–Johnson syndrome.
ated 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. Lornoxicam 5’-hydroxylation by the variant CYP2C9*3 and CYP2C9*13 is markedly reduced compared with wild type, both in vitro and in vivo.
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.
s 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 diuretic
s, ACE inhibitor
s and angiotensin II receptor antagonist
s 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.
Non-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
(NSAID) of the oxicam
Oxicam
Oxicam are members of a class of non-steroidal anti-inflammatory drugs that bind closely to plasma proteins. Most oxicams are unselective inhibitors of the cyclooxygenase enzymes...
class with analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
(pain relieving), anti-inflammatory
Anti-inflammatory
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....
and antipyretic
Antipyretic
Antipyretics ; an-tee-pahy-ret-iks; from the Greek anti, against, and pyreticus, are drugs or herbs that reduce fever. Normally, they will not lower body temperature if one does not have a fever. Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature...
(fever reducing) properties. It is available in oral
Oral administration
Oral administration is a route of administration where a substance is taken through the mouth.-Terminology:Per os is an adverbial phrase meaning literally from Latin "by mouth" or "by way of the mouth." The expression is used in medicine to describe a treatment that is taken orally. The...
and parenteral
Parenteral
Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...
formulations.
Indications
Lornoxicam is used for the treatment of various types of pain, especially resulting from inflammatory diseases of the joints, osteoarthritisOsteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
, surgery, sciatica
Sciatica
Sciatica is a set of symptoms including pain that may be caused by general compression or irritation of one of five spinal nerve roots that give rise to each sciatic nerve, or by compression or irritation of the left or right or both sciatic nerves. The pain is felt in the lower back, buttock, or...
, and other inflammations.
Contraindications
The drug is contraindicated in patients that must not take other NSAIDs, possible reasons including salicylate sensitivitySalicylate sensitivity
Salicylate sensitivity, also known as salicylate intolerance, is any adverse effect that occurs when a normal amount of salicylate is introduced into a person's body...
, 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.
Adverse effects
Lornoxicam has side effects similar to other NSAIDs, most commonly mild ones like gastrointestinal disorders (nauseaNausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
) and headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
. Severe but seldom side effects include bleeding, bronchospasm
Bronchospasm
Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...
s and the extremely rare Stevens–Johnson syndrome.
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%.Distribution
The absolute bioavailability of Lornoxicam is 90–100%. No first-pass effect was observed.Metabolism
Lornoxicam is found in the plasma in unchanged form and as its hydroxylHydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
ated metabolite. The hydroxylated metabolite exhibits no pharmacological activity. CYP2C9
CYP2C9
Cytochrome P450 2C9 is a protein that in humans is encoded by the CYP2C9 gene.- Function :CYP2C9 is an important cytochrome P450 enzyme with a major role in the oxidation of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes...
has been shown to be the primary enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
responsible for the biotransformation of the lornoxicam to its major metabolite, 5’-hydroxylornoxicam. 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.Mechanism of action
Like other NSAIDs, lornoxicam inhibits prostaglandinProstaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
biosynthesis by blocking the enzyme cyclooxygenase
Cyclooxygenase
Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
.
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
Synovial fluid
Synovial fluid is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its yolk-like consistency , the principal role of synovial fluid is to reduce friction between the articular cartilage of synovial joints during movement.-Overview:The inner membrane of synovial joints...
. The AUC ratio of synovial fluid to blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
is 0.5 after administration of 4 mg twice daily.
Interactions
Interactions with other drugs are typical of NSAIDs. Combination with vitamin K antagonistVitamin K antagonist
Vitamin K antagonists are a class of anticoagulants. They reduce blood clotting by inhibiting the recycling of vitamin K epoxide back to the active reduced form of vitamin K. The term Vitamin K antagonists is a misnomer. These drugs do NOT antagonize the action of Vitamin K...
s like warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
increases the risk of bleeding. Combination with ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
can lead to reduced kidney function, and to acute renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
in rare cases. Lornoxicam can also increase the adverse effects of lithium
Lithium
Lithium is a soft, silver-white metal that belongs to the alkali metal group of chemical elements. It is represented by the symbol Li, and it has the atomic number 3. Under standard conditions it is the lightest metal and the least dense solid element. Like all alkali metals, lithium is highly...
, methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
and digoxin
Digoxin
Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...
and its derivatives. The effect of diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
s, ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
s and angiotensin II receptor antagonist
Angiotensin II receptor antagonist
Angiotensin II receptor antagonists, also known as angiotensin receptor blockers , AT1-receptor antagonists or sartans, are a group of pharmaceuticals which modulate the renin-angiotensin-aldosterone system...
s can be reduced, but this is only relevant in patients with special risks like heart failure. As with piroxicam
Piroxicam
Piroxicam is a non-steroidal anti-inflammatory drug of the oxicam class used to relieve the symptoms of rheumatoid and osteoarthritis, primary dysmenorrhoea, postoperative pain; and act as an analgesic, especially where there is an inflammatory component...
, cimetidine
Cimetidine
Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
can increase plasma levels but is unlikely to cause relevant interactions.