Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Use in patients with renal impairment
In the absence of bone safety data in patients with severe renal impairment treated with strontium ranelate, PROTELOS is not recommended in patients with a creatinine clearance below 30 ml/min (see section 5.2). In accordance with good medical practice, periodic assessment of renal function is recommended in patients with chronic renal impairment. Continuation of treatment with PROTELOS in patients developing severe renal impairment should be considered on an individual basis.

Venous thromboembolism
In phase III placebo-controlled studies, strontium ranelate treatment was associated with an increase in the annual incidence of venous thromboembolism (VTE), including pulmonary embolism (see section 4.8). The cause of this finding is unknown. PROTELOS is contra-indicated in patients with a past history of venous thromboembolic events (see section 4.3) and should be used with caution in patients at risk of VTE.
When treating patients over 80 years at risk of VTE, the need for continued treatment with PROTELOS should be re-evaluated. PROTELOS should be discontinued as soon as possible in the event of an illness or a condition leading to immobilisation (see section 4.3) and adequate preventive measures taken. Therapy should not be restarted until the initiating condition has resolved and the patient is fully mobile. When a VTE occurs, PROTELOS should be stopped.

Cardiac ischaemic events
In pooled randomised placebo-controlled studies of post-menopausal osteoporotic patients, a significant increase in myocardial infarction has been observed in PROTELOS treated patients compared to placebo (see section 4.8).
Before starting treatment and at regular intervals, patients should be evaluated with respect to cardiovascular risk.
Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with strontium ranelate after careful consideration (see sections 4.3 and 4.8).
During PROTELOS treatment, these cardiovascular risks should be monitored on a regular basis generally every 6 to 12 months.
Treatment should be stopped if the patient develops ischaemic heart disease, peripheral arterial disease, cerebrovascular disease or if hypertension is uncontrolled (see section 4.3).

Skin reactions
Life-threatening cutaneous reactions (Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS)) have been reported with the use of PROTELOS.
Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment and usually around 3-6 weeks for DRESS
If symptoms or signs of SJS or TEN (e.g. progressive skin rash often with blisters or mucosal lesions) or DRESS (e.g. rash, fever, eosinophilia and systemic involvement (e.g. adenopathy, hepatitis, interstitial nephropathy, interstitial lung disease) are present, PROTELOS treatment should be discontinued immediately.
The best results in managing SJS, TEN or DRESS come from early diagnosis and immediate discontinuation of any suspect drug. Early withdrawal is associated with a better prognosis. The outcome of DRESS is favorable in most cases upon discontinuation of PROTELOS and after initiation of corticosteroid therapy when necessary. Recovery could be slow and recurrences of the syndrome have been reported in some cases after discontinuation of corticosteroid therapy.
If the patient has developed SJS, TEN or DRESS with the use of PROTELOS, PROTELOS must not be re-started in this patient at any time.
A higher incidence, although still rare, of hypersensitivity reactions including skin rash, SJS or TEN in patients of Asian origin has been reported.

Interaction with laboratory test
Strontium interferes with colorimetric methods for the determination of blood and urinary calcium concentrations. Therefore, in medical practice, inductively coupled plasma atomic emission spectrometry or atomic absorption spectrometry methods should be used to ensure an accurate assessment of blood and urinary calcium concentrations.

Excipient
PROTELOS contains aspartame, a source of phenylalanine, which may be harmful for people with phenylketonuria.

Effects on Driving

4.7   Effects on ability to drive and use machines

Strontium ranelate has no or negligible influence on the ability to drive and use machines.