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Hypersensitivity to lanreotide or related peptides or any of the excipients"

Section 4.4 - deletion of the following warnings "Fat concentrations in stools may increase to levels high enough to result in steatorrhoea, requiring the use of appropriate corrective therapy" and "In patients with hepatic/renal dysfunction, kidney and liver function should be regularly monitored and the dose interval adjusted if necessary".  Addition of the following "Slight decrease in thyroid function have been seen during treatment with Somatuline LA in acromegalic patients, though clinical hypothyroidism is rare. Thyroid function tests are recommended where clinically indicated" and "In patients without underlying cardiac problems Somatuline LA may lead to a decrease of heart rate without necessarily reaching the threshold of bradycardia. In patients suffering from cardiac disorders prior to Somatuline LA treatment, sinus bradycardia may occur.  care should be taken when initiating treatment with Somatuline in patients with  bradycardia (see section 4.5)" and "In patients with carcinoid tumours, Somatuline LA must not be prescribed before excluding the presence of an obstructive intestinal tumour".

Section 4.5 - minor rewording of some data, and addition of "Limited published data indicate that concomitant administration of somatostatin analogues and bromocriptine may increase the availability of bromocriptine. Concomitant administration of bradycardia-inducing drugs (e.g. beta blockers) may have an additive effect on the slight reduction of heart rate associated with Somatuline LA.  Dose adjustments of such concomitant medications may be necessary. The limited published data available indicate that somatostatin analogues may decrease the metabolic clearance of compounds known to be metabolised by Cytochrome P450 enzymes, which may be due to the suppression of growth hormone. Since it cannot be excluded that Somatuline may have this effect, other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (e.g. quinidine, terfenadine) should therefore be used with caution".

Section 4.6 - updated from "Studies in animals showed transitory growth retardation of offspring prior to weaning. Although no teratogenic effects have been observed in animals, in the absence of clinical experience, lanreotide must not be administered to pregnant or lactating women" to "Pregnancy:  Non-clinical data: Studies in animals showed no evidence of teratogenic effects associated with Somatuline LA during organogenesis. Reduced fertility was observed in female rats due to the inhibition of GH secretion at doses in excess of those achieved in humans at therapeutic doses.  Clinical data: Data on a limited number of exposed pregnancies indicate no adverse effects of Somatuline on pregnancy or on the health of the foetus/new born child. To date, no other relevant epidemiological data are available. Because animal studies are not always predictive of human responses, Somatuline LA should be administered to pregnant women only if clearly needed. Breast-feeding: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Somatuline is administered during lactation".

Section 4.7 - updated from "Therapy with Somatuline LA is unlikely to impair a patient's ability to drive or use machinery" to "While no effect on the ability to drive and use machines has been established, dizziness has been reported with Somatuline LA.  If a patient is affected, he/she should not drive or operate machinery"

Section 4.8 - in line with regulatory requirements which have changed since the last SPC was approved in 2003, section 4.8 has been updated extensively to list undesirable effects according to frequency. Please refer to the updated SPC for full details.

Section 4.9 - the following is deleted "There is no human experience of overdosage. Animal data do not predict any effects other than those on insulin and glucagon secretion and the gastrointestinal system"

Section 5.1 - reworded, no major changes

Section 5.2 - update of section. Notably, addition of the following "Renal/Hepatic impairment - Subjects with severe renal impairment show an approximately 2-fold decrease in total serum clearance of Somatuline LA, with a consequent increase in half-life and AUC.  In subjects with moderate to severe hepatic impairment, a reduction in clearance was observed (30%). Volume of distribution and mean residence time increased in subjects with all degrees of hepatic insufficiency. It is not necessary to alter the starting dose in patients with renal or hepatic impairment, as Somatuline LA serum concentrations in these populations are expected to be well within the range of serum concentrations safely tolerated in healthy subjects.  Elderly patients - Elderly subjects show an increase in half-life and mean residence time compared with healthy young subjects. It is not necessary to alter the starting dose in elderly patients, as Somatuline LA serum concentrations in this population are expected to be well within the range of serum concentrations safely tolerated in healthy subjects".

Section 5.3 - updated from "In vitro and animal toxicology studies have not shown any specific toxic potential for lanreotide. The observed effects are related to the pharmacological properties of lanreotide on the endocrine system. The resorption of Somatuline LA is complete in 45-60 days" to "In carcinogenic bioassays studies conducted in rats and mice, no systemic neoplastic changes were observed at doses in excess of those achieved in humans at therapeutic doses. Increased incidence of subcutaneous tumours were observed at the injection sites likely due to the increased dose frequency in animals (daily) compared to monthly dosing in humans and therefore may not be clinically relevant.  In in vitro and in vivo standard battery tests, Somatuline LA did not show any genotoxic potential. Resorption of micropheres is completed in 45 – 60 days".

Section 6.1 - no change in excipients themselves, only how listed

Sections 6.2, 6.3, 6.4 - minor updates only

Section 10 - date of revision updated from 4 August 2003 to 20 July 2010