Indovis

/ CTS

The dosage of Indovis should be carefully adjusted to suit the needs of the individual patient.
In order to reduce the possibility of gastro-intestinal disturbances, Indovis Capsules should always be taken with food or an antacid.
In chronic conditions, starting therapy with a low dosage, increasing this gradually as necessary, and continuing a trial of therapy for an adequate period (in some cases, up to one month) will give the best results with a minimum of unwanted reactions.
The recommended oral dosage range is 50 mg to 200 mg daily in divided doses.
Paediatric dosage not established.
Use in the elderly: Indovis should be used with particular care in older patients who are more prone to adverse reactions.

Non-steroidal anti-inflammatory indicated for the active stages of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, degenerative joint disease of the hip, acute musculoskeletal disorders, low-back pain.

NSAIDs are contra-indicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other non- steroidal anti-inflammatory drugs.
Hypersensitivity to indomethacin or any of the excipients.
Severe heart failure, hepatic failure and renal failure.
Not to be used in patients who have nasal polyps.
During the last trimester of pregnancy or lactation.
Safety in children has not been established.
Active or history of recurrent peptic ulcer/ hemorrhage (two or more distinct episodes of proven ulceration or bleeding).
History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
The use of Indovis capsules with concomitant NSAIDs including cyclooxygenase-2-selective inhibitors, should be avoided.
 Cardiovascular and cerebrovascular effects:
Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for Indovis.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with Indovis after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Indovis should be used cautiously in patients with impaired renal function, bleeding disorders, psychiatric disorders, epilepsy or parkinsonism, as it may tend to aggravate these.  Gastro-intestinal disturbances may be minimised by giving Indovis orally with food, milk or an antacid. They usually disappear on reducing the dosage; if not, the risks of continuing therapy should be weighed against the possible benefits.
Indovis may mask the signs and symptoms of an infection. Indovis should be used with caution in patients with existing but controlled infection, so antibiotic therapy should be initiated promptly if an infection occurs during therapy with Indovis. It should be used with cautiously in patients with existing but controlled infection. Caution is advised with concomitant use of live vaccines
During prolonged therapy, periodic ophthalmic examinations are recommended, as corneal deposits and retinal disturbances have been reported. In patients with rheumatoid arthritis, eye changes may occur which may be related to the underlying disease or to the therapy.
Therefore, in chronic rheumatoid disease, ophthalmological examinations at periodic intervals are recommended. Therapy should be discontinued if eye changes are observed.
Patients should be carefully observed to detect any unusual manifestations of drug sensitivity.
Cardiovascular, Renal and Hepatic Impairment:
In patients with renal, hepatic, cardiac impairment, hypertension, heart failure or conditions predisposing to fluid retention caution is required since the use of NSAIDs may result in deterioration of renal function. The dose should be kept as low as possible and renal function should be monitored. NSAIDs may also cause fluid retention which may further aggravate these conditions.
In patients with reduced renal blood flow where renal prostaglandins play a major role in maintaining renal perfusion, administration of NSAID may precipitate overt renal decompensation. The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver
dysfunction, those taking diuretics, the elderly, diabetes mellitus, extracellular volume depletion, congestive heart failure, sepsis, or concomitant use of any nephrotoxic drug. Indovis should be given with caution and renal function should be monitored in patients.
Discontinuation of non-steroidal anti-inflammatory therapy is usually followed by recovery to the pre-treatment state.
Elderly:
The elderly have an increased frequency of adverse reactions to
NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal.
 Respiratory disorders:
Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
Gastrointestinal bleeding, ulceration and perforation:
Caution is advised in patients with pre-existing sigmoid lesions (such as diverticulum or carcinoma) (or the development of these conditions) as Indovis can aggravate these conditions.
GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events. When GI bleeding or ulceration occurs in patients receiving Indovis, the treatment should be withdrawn.
The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with hemorrhage or perforation., and in the elderly. These patients should commence treatment on the lowest dose available.
Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk.
Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as aspirin.
NSAIDs should only be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) as these conditions may be exacerbated.
SLE and mixed connective tissue disease:
In patients with systemic lupus erythematous (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.
Impaired female fertility:
The use of Indovis may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of Indovis should be considered.
Indovis should be used with caution in patients with coagulation defects as Indovis can inhibit platelet aggregation. This effect may be exaggerated in patients with underlying hemostatic defects.
Inhibition of platelet aggregation usually disappears within 24 hours of discontinuing Indovis.
Caution is required in post-operative patients as bleeding time is prolonged (but within normal range) in normal adults.
Patients should be periodically observed to allow early detection of any unwanted effects on peripheral blood (anemia), liver function  or gastrointestinal tract especially during prolonged therapy.
Medication Overuse Headache (MOH):
After long term treatment with analgesics, headache may develop or aggravate. Headache caused by overuse of analgesics (MOH-medication overuse headache) should be suspected in patients who have frequent or daily headache despite (or because of) regular use of analgesics. Patients with medication overuse headache should not be treated by increasing the dose. In such cases the use of analgesics should be discontinued in consultation with a doctor.
Avoid concomitant use of two or more NSAIDs.
Dermatological:
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported very rarely in association with the use of NSAIDs. Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Indovis should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Increases in plasma potassium concentration, including hyperkalaemia have been reported, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninaemic-hypoaldosteronism state.
Excipient with known effect:
Indovis Capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucosegalactose malabsorption should not take this medicine.

The most commonly-observed adverse events are gastrointestinal in nature. Visual disturbances, optic neuritis, tinnitus, headaches, dizziness and lightheadedness are also common side effects.
See prescribing information for full details.

Other Analgesics including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects.
Antacids: the bioavailability of indomethacin may be reduced by concomitant antacid therapy
 Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin.
Anti-diabetics: The effect of sulphonylureas may be increased by NSAIDs.
Antidepressants (SSRI): increased risk of bleeding.
Antihypertensive medications: Reduced anti-hypertensive effect. Indovis may acutely reduce the antihypertensive effect of beta-blockers due partly to indomethacin’s inhibition of prostaglandin synthesis. Patients receiving dual therapy should have the antihypertensive effect of their therapy reassessed.
Therefore, caution should be exercised when considering the addition of Indovis to the regimen of a patient taking any of the following antihypertensive agents: alpha-adrenergic blocking agents, ACE inhibitors, beta-adrenergic blocking agents, angiotensin II receptor antagonists, hydralazine, or nifedipine. An increased risk of hyperkalaemia has also been reported when NSAIDs are taken with ACE inhibitors.
Diuretics: NSAIDS may reduce the effect of diuretics and antihypertensive medicinal products. The risk of acute renal insufficiency, which is usually reversible, may be increased in some patients with compromised renal function (e.g. dehydrated patients or elderly patients) when angiotensin II receptor antagonists are combined with NSAIDs. Therefore, the combination should be administrated with caution, especially.
in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.
Indovis may reduce the diuretic and antihypertensive effect of thiazides and furosemide in some patients. Indovis may cause blocking of the furosemide- induced increase in plasma rennin activity. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
 Anti-platelet agents: increased risk of gastrointestinal bleeding. Indovis can inhibit platelet aggregation, an effect which disappears within 24 hours of discontinuation; the bleeding time may be prolonged and this effect may be exaggerated in patients with an underlying haemostatic defect.
Antipsychotics: increased drowsiness with Indovis and haloperidol.
Antivirals: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
Risk of Indovis toxicity with ritonavir, avoid concomitant use.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.
Ciclosporin: Increased risk of nephrotoxicity. Administration NSAIDs concomitantly with ciclosporin has been associated with an increase in ciclosporin-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking ciclosporin, and renal function should be monitored carefully.
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding . If the patient is receiving corticosteroids concomitantly, a reduction in dosage of these may be possible but should only be effected slowly under supervision.  Cytotoxics: Indovis may decrease the tubular secretion of methotrexate thus potentiating toxicity; simultaneous use should be undertaken with caution.
Desmopressin: effect potentiated by Indovis.  Diflunisal: avoid concomitant use. Increased plasma level of Indovis by about a third with a concomitant decrease in renal clearance. Fatal gastro-intestinal haemorrhage has occurred.
Lithium: Decreased elimination of lithium.
Indovis is an inhibitor of prostaglandin synthesis and therefore the following drug reaction may occur; Indovis may raise plasma lithium levels and reduce lithium clearance in subjects with steady state plasma lithium concentration. At the onset of such combined therapy, plasma lithium concentrations should be monitored more frequently.
Methotrexate: Decreased elimination of methotrexate.  Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Muscle Relaxants: increased risk of baclofen toxicity due to reduced rate of excretion.
Pentoxifylline: possible increased risk of bleeding when taken with NSAIDs.
Probenecid: co-administration of probenecid may increase plasma levels of indomethacin. When increases in the dose of Indovis are made under these circumstances, they should be made cautiously and in small increments.
Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.
Salicylates: the use of Indovis with aspirin or other salicylates is not recommended because there is no enhancement of therapeutic effect while the incidence of gastro-intestinal side effects is increased. Moreover, coadministration of aspirin may decrease the blood concentrations of indomethacin.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Tiludronic acid: the bioavailability of tiludronic acid is increased by Indovis.
Triamterene: Indovis and triamterene should not be administered together since reversible renal failure may be induced.
Laboratory tests: false-negative results in the dexamethasone suppression test (DST) in patients being treated with Indovis have been reported. Thus, results of this test should be used with caution in these patients.
See prescribing information for full details.

Pregnancy: I
Fetal Toxicity
Oligohydramnios/Neonatal Renal Impairment:
Use of NSAIDs, including Indovis, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit Indovis use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if Indovis treatment extends beyond 48 hours. Discontinue Indovis if oligohydramnios occurs and follow up according to clinical practice.

Premature Closure of Fetal Ductus Arteriosus:
Avoid use of NSAIDs, including Indovis, in pregnant women at about 30 weeks gestation and later. NSAIDs, including Indovis, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.
See prescribing information for full details.
Lactation: an the limited studies so far available, NSAIDs can appears in the breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.

Symptoms
Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, tinnitus, fainting, occasionally convulsions, abdominal pain, anorexia, restlessness and agitation. In cases of significant poisoning acute renal failure and liver damage are possible.
 Therapeutic measures
Patients should be treated symptomatically as required .Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered .Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.
Good urine output should be ensured. Renal and liver function should be closely monitored. Patients should be observed for at least four hours after ingestion of potentially toxic amounts.
Frequent or prolonged convulsions should be treated with intravenous diazepam. Other measures may be indicated by the patient’s clinical condition.

Effects on ability to drive and use machines:
Undesirable effects such as dizziness, light-headedness, drowsiness, fatigue, visual disturbances or vertigo are possible after taking NSAIDs, if affected, patients should not drive or operate machinery.