Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

•   Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).

•   The use of Indovis capsules with concomitant NSAIDs including cyclooxygenase-2- selective inhibitors, should be avoided (See section 4.5).

•   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 (see section 4.8). 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 (see also section 4.3).
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 (See section 4.2).

•   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 haemorrhage or perforation (see section 4.3), 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 (see below and section 4.5).
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 (See section 4.5).
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 (See section 4.8).

•   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 (See section 4.8).

•   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 haemostatic 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 (anaemia), liver function (see section 4.8) 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-medicationoveruse 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 (see section 4.8). 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.

•   Fetal Toxicity

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.

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 [see 4.6 Fertility, pregnancy and lactation].


•   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.

Effects on Driving

4.7 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.