Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use

General

As GH-secreting pituitary tumours may sometimes expand, causing serious complications (e.g. visual field defects), it is essential that all patients be carefully monitored. If evidence of tumour expansion appears, alternative procedures may be advisable.

The therapeutic benefits of a reduction in growth hormone (GH) levels and normalisation of insulin-like growth factor 1 (IGF-1) concentration in female acromegalic patients could potentially restore fertility. Female patients of childbearing potential should be advised to use adequate contraception if necessary during treatment with octreotide (see section 4.6).

Thyroid function should be monitored in patients receiving prolonged treatment with octreotide.

Hepatic function should be monitored during octreotide therapy.
Cardiovascular related events

Common cases of bradycardia have been reported. Dose adjustments of medicinal products such as beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balance, may be necessary (see section 4.5).

Atrioventricular blocks (including complete atrioventricular block) were reported in patients receiving high doses of continuous infusion (100 micrograms/hour) and in patients receiving bolus octreotide intravenously (50 micrograms bolus followed by 50 micrograms/hour continuous infusion). The maximum dose of 50 microgram/hour should therefore not be exceeded (see section 4.2). Patients who receive high doses of intravenous octreotide should be kept under appropriate cardiac monitoring.

Gallbladder and related events

Cholelithiasis is a very common event during Octreostat treatment and may be associated with cholecystitis and biliary duct dilatation (see section 4.8). Additionally, cases of cholangitis have been reported as a complication of cholelithiasis in patients taking Octreostat in the post-marketing setting. Ultrasonic examination of the gallbladder before, and at about 6- to 12-month intervals during Octreostat therapy is therefore recommended.

GEP endocrine tumours
During the treatment of GEP endocrine tumours, there may be rare instances of sudden escape from symptomatic control by Octreostat, with rapid recurrence of severe symptoms. If the treatment is stopped, symptoms may worsen or recur.

Glucose metabolism

Because of its inhibitory action on growth hormone, glucagon, and insulin, Octreostat may affect glucose regulation. Post-prandial glucose tolerance may be impaired and, in some instances, the state of persistent hyperglycaemia may be induced as a result of chronic administration. Hypoglycaemia has also been reported.

In patients with insulinomas, octreotide, because of its greater relative potency in inhibiting the secretion of GH and glucagon than that of insulin, and because of the shorter duration of its inhibitory action on insulin, may increase the depth and prolong the duration of hypoglycaemia. These patients should be closely monitored during initiation of Octreostat therapy and at each change of dosage. Marked fluctuations in blood glucose concentration may possibly be reduced by smaller, more frequently administered doses.

Insulin requirements of patients with type I diabetes mellitus therapy may be reduced by administration of Octreostat. In non-diabetics and type II diabetics with partially intact insulin reserves, Octreostat administration can result in post-prandial increases in glycaemia. It is therefore recommended to monitor glucose tolerance and antidiabetic treatment.

Oesophageal varices

Since, following bleeding episodes from oesophageal varices, there is an increased risk for the development of insulin-dependent diabetes or for changes in insulin requirement in patients with pre-existing diabetes, an appropriate monitoring of blood glucose levels is mandatory.

Local Site Reactions

In a 52-week toxicity study in rats, predominantly in males, sarcomas were noted at the s.c.
injection site only at the highest dose (about 8 times the maximum human dose based on body surface area). No hyperplastic or neoplastic lesions occurred at the s.c. injection site in a 52- week dog toxicity study. There have been no reports of tumour formation at the injection sites in patients treated with Octreostat for up to 15 years. All the information available at present indicates that the findings in rats are species specific and have no significance for the use of the drug in humans (see section 5.3).

Nutrition

Octreotide may alter absorption of dietary fats in some patients.
Depressed vitamin B12 levels and abnormal Schilling’s tests have been observed in some patients receiving octreotide therapy. Monitoring of vitamin B12 levels is recommended during therapy with Octreostat in patients who have a history of vitamin B12 deprivation.

Sodium content

Octreostat contains less than 1 mmol (23 mg) sodium per dose, that is to say essentially “sodium- free”.

Effects on Driving