Presentation and Status in Health Basket
1 X 10 mg powder and solvent for suspension for injection
1 X 20 mg powder and solvent for suspension for injection
1 X 30 mg powder and solvent for suspension for injection
Sandostatin LAR may only be administered by deep intragluteal injection. The site of repeat intragluteal injections should be alternated between the left and right gluteal muscle.
Acromegaly: For patients who are adequately controlled with s.c. Sandostatin, it is recommended to start treatment with the administration of 20 mg Sandostatin LAR at 4-week intervals for 3 months. Treatment with Sandostatin LAR can be started the day after the last dose of s.c. Sandostatin. Subsequent dosage adjustment should be based on serum growth hormone (GH) and insulin-like growth factor 1/somatomedin C (IGF 1) concentrations and clinical symptoms. For patients in whom, within this 3 month period, clinical symptoms and biochemical parameters (GH; IGF 1) are not fully controlled (GH concentrations still above 2.5 microgram/L), the dose may be increased to 30 mg every 4 weeks. For patients whose GH concentrations are consistently below 1 microgram/L, whose IGF 1 serum concentrations normalised, and in whom most reversible signs/symptoms of acromegaly have disappeared after 3 months of treatment with 20 mg, 10 mg Sandostatin LAR may be administered every 4 weeks. However, particularly in this group of patients, it is recommended to closely monitor adequate control of serum GH and IGF 1 concentrations, and clinical signs/symptoms at this low dose of Sandostatin LAR. For patients on a stable dose of Sandostatin LAR, assessment of GH and IGF 1 should be made every 6 months. For patients in whom surgery or radiotherapy is inappropriate or ineffective, or in the interim period until radiotherapy becomes fully effective, a short test dosing period of s.c. administration of Sandostatin is recommended to assess the response and systemic tolerability of octreotide prior to initiating treatment with Sandostatin LAR as described above.
Gastro-entero-pancreatic endocrine tumours: For patients in whom symptoms are adequately controlled with s.c. Sandostatin, it is recommended to start treatment with the administration of 20 mg Sandostatin LAR at 4-week intervals. The treatment with s.c. Sandostatin should be continued at the previously effective dosage for 2 weeks after the first injection of Sandostatin LAR. For patients who were not previously treated with s.c. Sandostatin, it is recommended to start with the administration of s.c. Sandostatin at a dosage of 0.1 mg three times daily for a short period (approximately 2 weeks) to assess the response and systemic tolerability of octreotide before initiating the treatment with Sandostatin LAR as described above. For patients in whom symptoms and biological markers are well controlled after 3 months of treatment, the dose may be reduced to 10 mg Sandostatin LAR every 4 weeks. For patients in whom symptoms are only partially controlled after 3 months of treatment, the dose may be increased to 30 mg Sandostatin every 4 weeks. For days when symptoms associated with gastro-entero-pancreatic tumours may increase during treatment with Sandostatin LAR, additional administration of s.c. Sandostatin is recommended at the dose used prior to the Sandostatin LAR treatment. This may occur mainly in the first 2 months of treatment until therapeutic concentrations of octreotide are reached.
Renal Impairment: Impaired renal function did not affect the total exposure (AUC) to octreotide when administered s.c. as Sandostatin. Therefore, no dose adjustment of Sandostatin LAR is necessary.
Hepatic Impairment: In a study with Sandostatin administered s.c. and i.v. it was shown that the elimination capacity may be reduced in patients with liver cirrhosis, but not in patients with fatty liver disease. Due to the wide theraputic window of octreotide, no dose adjustment of Sandostatin LAR is necessary in
patients with liver cirrhosis.
Geriatric Population: In a study with Sandostatin administered s.c., no dose adjustment was necessary in subjects ≥ 65 years of age. Therefore, no dose adjustment is necessary in this group of patients with Sandostatin LAR.
Pediatric Population: There is limited experience with the use of Sandostatin LAR in children.
Treatment of acromegaly in: Patients already adequately controlled on standard doses of sandostatin s.c. Patients in whom surgery or radiotherapy are inappropriate or ineffective, or who are in the latency period before radiotherapy becomes fully effective.
Endocrine Gastro-Entero-Pancreatic (GEP) tumors, carcinoid tumors.
Known hypersensitivity to octreotide or to any of the excipients.
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 are advisable. The therapeutic benefits of a reduction in growth hormone (GH) levels and normalization 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. 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 drugs such as beta-blockers, calcium channel blockers, or agents to control fluid and electrolyte balance, may be necessary.
Gallbladder and related events: Development of gallstones has been reported in 15 to 30% of long-term recipients of s.c. Sandostatin. The prevalence in the general population (aged 40 to 60 years) is about 5 to 20%. Long-term exposure to Sandostatin LAR of patients with acromegaly or gastro-enteropancreatic tumours suggests that treatment with Sandostatin LAR does not increase the incidence of gallstone formation, compared with s.c. treatment. Ultrasonic examination of the gallbladder before and at about 6 monthly intervals during Sandostatin LAR therapy is however recommended. If gallstones do occur, they are usually asymptomatic; symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery.
Glucose metabolism: Because of its inhibitory action on growth hormone, glucagon and insulin release, Sandostatin LAR may affect glucose regulation. Post-prandial glucose tolerance may be impaired. As reported for patients treated with s.c. Sandostatin, in some instances, a state of persistent hyperglycaemia may be induced as a result of chronic administration. In patients with concomitant Type I diabetes mellitus, Sandostatin LAR is likely to affect glucose regulation, and insulin requirements may be reduced. In non-diabetics and type II diabetics with partially intact insulin reserves, Sandostatin s.c. administration may result in increases in post-prandial glycaemia. It is therefore recommended to monitor glucose tolerance and antidiabetic treatment. 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.
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 Sandostatin LAR in patients who have a history of vitamin B12 deprivation.
The most frequent adverse reactions reported during octreotide therapy include gastrointestinal disorders, nervous system disorders, hepatobiliary disorders, and metabolism and nutritional disorders.
The most commonly reported adverse reactions in clinical trials with octreotide administration were diarrhoea, abdominal pain, nausea, flatulence, headache, cholelithiasis, hyperglycaemia and constipation. Other commonly reported adverse reactions were dizziness, localised pain, biliary sludge, thyroid dysfunction (e.g., decreased thyroid stimulating hormone [TSH], decreased total T4, and decreased free T4), loose stools, impaired glucose tolerance, vomiting, asthenia, and hypoglycaemia.
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Dose adjustment of medicinal products such as beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balance may be necessary when Sandostatin LAR is administered concomitantly.
Dose adjustments of insulin and antidiabetic medicinal products may be required when Sandostatin LAR is administered concomitantly.
Octreotide has been found to reduce the intestinal absorption of ciclosporin and to delay that of cimetidine.
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine.
Limited published data indicate that somatostatin analogues might 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 octreotide may have this effect, other drugs mainly metabolised by CYP3A4 and which have a low therapeutic index (e.g. quinidine,
terfenadine) should therefore be used with caution.
Pregnancy and Lactation
Pregnancy: There is a limited amount of data (less than 300 pregnancy outcomes) from the use of octreotide in pregnant women, and in approximately one third of the cases the pregnancy outcomes are unknown.
The majority of reports were received after post-marketing use of octreotide and more than 50% of exposed pregnancies were reported in patients with acromegaly. Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-1200 micrograms/day of Sandostatin s.c. or 10-40 mg/month of Sandostatin LAR. Congenital anomalies were eported in about 4% of pregnancy cases for which the outcome is known. No causal relationship to octreotide is suspected for these cases.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
As a precautionary measure, it is preferable to avoid the use of Sandostatin LAR during pregnancy.
Lactation: It is unknown whether octreotide is excreted in human breast milk. Animal studies have shown excretion of octreotide in breast milk. Patients should not breast-feed during Sandostatin treatment.
A limited number of accidental overdoses of Sandostatin LAR have been reported. The doses ranged from 100 mg to 163 mg/month of Sandostatin LAR. The only adverse event reported was hot flushes. Cancer patients receiving doses of Sandostatin LAR up to 60 mg/month and up to 90 mg/2 weeks have been reported. These doses were in general well tolerated; however, the following adverse events have been reported: frequent urination, fatigue, depression, anxiety, and lack of concentration. The management of overdose is symptomatic.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage: Store at 2°C to 8°C (in a refrigerator). Keep vial in the outer carton in order to protect it from light. Sandostatin LAR can remain below 25°C on the day of injection. However, the suspension must only be prepared immediately prior to i.m. injection.