Pharmacokinetic properties
Absorption: Bioavailability of Gesicox is 89% following oral administration. Plasma concentrations are proportional to the dose.
Distribution: Meloxicam is very strongly bound to plasma proteins, essentially albumin (99%). Meloxicam penetrates into joints and inflamed sites, its analgesic action occur rapidly, only half an hour after oral administration. In particular, the drug is less permeable to nerve tissue and other tissues; so its side effects are reduced.
Biotransformation and elimination: The drug is strongly metabolized, especially oxidized at the methylthiazole. The proportion of unchanged excreted products is 3% compared with the dose. Meloxicam is excreted predominantly and occurs to equal extents in urine and faeces. The elimination half-life of meloxicam is 15 to 20 hours; so the patient should take only one dose per day. Balancing is achieved after 3-5 days. Mean plasma clearance amounts on average 8 ml/min and was slightly lower in elderly subjects.
Indications:
Gesicox is indicated in:
- Treatment of rheumatoid arthritis.
- Short-term symptomatic treatment of exacerbations of osteoarthritis.
- Treatment of ankylosing spondylitis.
Contraindications
- Hypersensitivity to meloxicam.
- Hypersensitivity to aspirin or other NSAIDs.
- Meloxicam should not be given to patients who have developed signs of asthma, nasal polyps, angioedema or Quincke’s oedema, urticaria following the administration of aspirin or other NSAIDs.
- Active gastro-intestinal ulceration, gastric bleeding, cerebral hemorrhage.
- Do not use rectal medicine for patients with a history of rectal inflammation or rectal bleeding.
- Severe hepatic insufficiency and non-dialysed severe renal insufficiency.
- Pregnancy or breastfeeding.
Precautions:
As with other NSAIDs, meloxicam should be used with caution in patients with known gastrointestinal diseases or with anticoagulant therapy. Meloxicam should be discontinued immediately in those with peptic ulcer disease and gastrointestinal bleeding. Dicontinuation of meloxicam should be considered at the first appearance of mucosal lesions.
NSAIDs inhibit the synthesis of renal prostaglandins that support renal perfusion. In patients whose blood volume and renal blood flow are decreased, administration of an NSAID may precipitate overt renal decompensation which typically followed by recovery to the pretreatment state upon discontinuation of NSAID therapy. Patients at greatest risk of such a reaction are:
- dehydrated patients,
- those with congestive heart failure,
- those with liver cirrhosis,
- those with nephrotic syndrome and overt renal disease,
- those receiving a concomitant treatments with a diuretic.
- or those having undergone major surgical procedures, which led to hypovolaemia.
In such patients, the volume of diuresis and the renal function should be carefully monitored at the beginning of therapy.
In rare instance NSAIDs may be the cause of interstitial nephritis, glomerulonephritis, renal medullary necrosis or nephrotic syndrome.
The dose of meloxicam in patients with end-stage renal failure on haemodialysis should not be higher than 7.5 mg. No dose reduction is required in patients with mild or moderate renal impairment (i.e. patients with a creatinine clearance of greater than 25 ml/min).
As with most NSAIDs, occasional increases in serum transaminases or other parameters of liver function have been reported. The majority of these instances involved transitory and slight abnormalities. Should any such abnormality prove significant or persistent, the administration of meloxicam should be stopped and appropriate investigations undertaken. No dose reduction is needed in patients with clinically stable cirrhosis. Frail and debilitated patients may tolerate side effects less well and such patients should be carefully supervised. As with other NSAIDs, caution should be used in the treatment of elderly patients who are more likely to be suffering from impaired renal, heaptic, or cardiac function. There are no specific studies on the effects of medication on driving and operating machinery. However, if side effects occur, such as dizziness and drowsiness, avoid such activities.
Interactions
Combination not required.
- Other NSAIDs (including high doses of salicylate): Co-administration of NSAIDs may increase the risk of gastrointestinal ulcers and bleeding, via a synergistic effect.
- Oral anticoagulant, ticlopidine, or systemically administered heparin, thrombolytics: Increased risk of bleeding. Careful monitoring of the effects of anticoagulants is required if it proves impossible to avoid such combination.
- Lithium: NSAIDs have been reported to increase blood lithium levels. If this combination appears necessary, lithium plasma concentrations should be monitored carefully during the initiation, adjustment and withdrawal of meloxicam treatment.
- Methotrexate: It should be considered that the haematological toxicity of methotrexate can be amplified by treatment with NSAID drugs. In case combination treatment is necessary blood cell count should be monitored.
- Intrauterine devices: NSAIDs have been reported to decrease the efficacy of intrauterine devices.
Combination with cautions:
- Diuretics: In dehydrated patients, the co-administration of an diuretic and a NSAID may result in possible acute renal failure. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.
- Ciclosporin: Nephrotoxicity of ciclosporin may be enhanced by NSAIDs. During combined treatment renal function is to be measured.
- Other antihypertensive drugs (e.g. beta-blockers, ACE-inhibitors, vasodilators, diuretics): A reduced effect of the antihypertensive drug by inhibition of vasodilating prostaglandins has been reported during treatment with NSAIDs.
- Cholestyramine: Cholestyramine bind meloxicam in the gastrointestinal tract leading to a faster elimination of meloxicam.
The possibility of interactions with oral anti-diabetic drugs cannot be excluded.
No relevant pharmacokinetic drug-drug interactions were detected with respect to the concomitant administration of antacids, cimetidine, digoxin and, furosemide.
Since there is no information on possible interactions, meloxicam should not be mixed with other drugs in the same syringe.
Pregnancy and lactation
- Pregnancy: Experimental studies regarding potential monster risks of meloxicam are not stated. However, meloxicam is not recommended for pregnant women, especially in the last 3 months of pregnancy because of premature closure of the ductus arteriosus or other fetal complications.
- Lactation: Meloxicam should not be used during breastfeeding.
Effects on ability to drive and use machines
There are no specific studies on the ability to drive and use machinery. However, when drowsiness, vertigo occur, it is advisable to refrain from driving and operating machinery.
Dosage
- Adults:
+ Rheumatoid arthritis, ankylosing Spondylitis: 15 mg/day. The recommended dose for long term treatment of rheumatoid arthritis and ankylosing spondylitis in the elderly or patients with increased risk of adverse reactions is 7.5 mg. Do not exceed the dose of 15 mg/day.
+ Exacerbations of osteoarthritis: 7.5 mg/day; if necessary, in the absence of improvement, the dose may be increased to 15 mg/day. Do not exceed the dose of 15 mg/day. Patients with increased risks for adverse reactions should start treatment with 7.5 mg per day. Duration of treatment is 2-3 days (this duration, if necessary, switches to oral or rectal).
- Elderly patients: The recommended dose is 7.5 mg daily.
- Mild to moderate renal, hepatic impairment: No dose reduction is required. For patients with severely impaired liver, kidney function: No use.
- In dialysis patients with severe renal failure, the dose should not exceed 7.5 mg per day.
- Children aged under 18 years: Safety and effectiveness have not been determined.
Method of administration
- Gesicox is taken orally.
- Gesicox can be taken with or without food or with antacids which do not affect the effect of the drug.
- In order to achieve the highest effective treatment, the tablet should be swallowed whole with water and should not be chewed and grinded before oral administration.
Undesirable effects
Gastrointestinal disorders:
> 1%: dyspepsia, nausea, vomiting, constipation, flatulence, diarrhea.
0.1-1%: liver function test abnomal (e.g. raised transaminases or bilirubin), eructation, esophagitis, peptic ulcer, occult or macroscopic gastrointestinal haemorrhage.
< 0.1%: gastrointestinal perforation, proctitis.
Blood disorders:
> 1%: anaemia
0.1-1%: blood count abnormal (including differential white cell count), leukopenia, thrombocytopenia. Concomitant administration of a potentially myelotoxic drug, in particular methotrexate, appears to be a predisposing factor to the onset of a cytopenia.
Skin disorders:
> 1%: pruritus, rash
0.1-1%: stomatitis, urticaria
< 0.1%: photosensitivity reaction
Respiratory disorders:
< 1%: asthma in individuals allergic to aspirin or other NSAIDs, including Gesicox which can trigger acute asthma.
Nervous system disorders:
> 1%: headache, dizziness.
0.1-1%: vertigo, tinnitus, somnolence.
Cardiac disorders:
> 1%: oedema.
0.1-1%: blood pressure increased, palpitations, flushing.
Renal and urinary disorders:
0.1-1%: increased serum creatinine and/or serum urea.
Sensitization: mucosal oedema and hypersensitivity reactions including anaphylaxis.
Administration site conditions:
> 1%: swelling at the injection site.
0.1-1%: pain at the injection site.
Inform your doctor about any side effects that may occur during the treatment.
Overdose
There is limited experience with meloxicam overdose. In case of acute overdose the standard measures of gastric evacuation and activated charcoal administration should be used.
Shelf-life: 36 months from the manufacturing date.
Storage: Store in cool dry places, below 30oC, protect from direct light.
Specifications: Manufacturer’s.