SANDOSTATIN LAR

) injection every 8 or 12 hours. 5 ng/mL; IGF-1 within normal range) and clinical symptoms, and on tolerability. 3 mg. 5 mg per day should not be exceeded. For patients on a stable dose of Sandostatin, assessment of GH and IGF-1 should be made every 6 months.

If no relevant reduction in GH levels and no improvement in clinical symptoms have been achieved within 3 months of starting treatment with Sandostatin, therapy should be discontinued. c. injection. 2 mg 3 times daily. Under exceptional circumstances, higher doses may be required.

Maintenance doses have to be adjusted individually. In carcinoid tumours, if there is no beneficial response within 1 week of treatment with Sandostatin at the maximum tolerated dose, therapy should not be continued. c. injection for 7 consecutive days, starting on the day of surgery at least 1 hour before laparotomy.

) infusion. Sandostatin can be used in dilution with physiological saline. v. doses of up to 50 micrograms/hour for 5 days. c. injection. The dose can be adjusted according to the responses of TSH and thyroid hormones. At least 5 days of treatment will be needed to judge the efficacy.

Use in the elderly There is no evidence of reduced tolerability or altered dosage requirements in elderly patients treated with Sandostatin. Use in children Experience with Sandostatin in children is limited. Use in patients with impaired liver function In patients with liver cirrhosis, the half-life of the drug may be increased, necessitating adjustment of the maintenance dosage.

c. injection, therefore no dose adjustment of Sandostatin is necessary. ) infusion after dilution. 6.

Summary of the safety profile 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.

, decreased thyroid stimulating hormone [TSH], decreased total T4, and decreased free T4), loose stools, impaired glucose tolerance, vomiting, asthenia, and hypoglycaemia. Tabulated list of adverse reactions The following adverse drug reactions, listed in Table 1, have been accumulated from clinical studies with octreotide: Adverse drug reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000) very rare (<1/10,000), including isolated reports.

Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness. Table 1 Adverse drug reactions reported in clinical studies Gastrointestinal disorders Very common: Diarrhoea, abdominal pain, nausea, constipation, flatulence.

Common:

Dyspepsia, vomiting, abdominal bloating, steatorrhoea, loose stools, discolouration of faeces.

Nervous system disorders Very common:

Headache.

Common:

Dizziness. , decreased TSH, decreased total T4, and decreased free T4).

Hepatobiliary disorders Very common:

Cholelithiasis.

Common:

Cholecystitis, biliary sludge, hyperbilirubinaemia.

Metabolism and nutrition disorders Very common:

Hyperglycaemia.

Common:

Hypoglycaemia, impaired glucose tolerance, anorexia.

Uncommon:

Dehydration.

General disorders and administration site conditions Very common:

Injection site reactions.

Common:

Asthenia.

Investigations Common:

Elevated transaminase levels.

Skin and subcutaneous tissue disorders Common:

Pruritus, rash, alopecia.

Respiratory disorders Common:

Dyspnoea.

Cardiac disorders Common:

Bradycardia.

Uncommon:

Tachycardia. Post-marketing Spontaneously reported adverse reactions, presented in Table 2, are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure. Table 2 Adverse drug reactions derived from spontaneous reports Blood and lymphatic system disorders Thrombocytopenia Immune system disorders Anaphylaxis, allergy/hypersensitivity reactions.

Skin and subcutaneous tissue disorders Urticaria Hepatobiliary disorders Acute pancreatitis, acute hepatitis without cholestasis, cholestatic hepatitis, cholestasis, jaundice, cholestatic jaundice. Cardiac disorders Arrhythmias. Investigations Increased alkaline phosphatase levels, increased gamma glutamyl transferase levels.

Description of selected adverse reactions Gallbladder and related reactions Somatostatin analogues have been shown to inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder abnormalities or sludge.

c. Sandostatin. The incidence in the general population (aged 40 to 60 years) is about 5 to 20%. c. treatment. If gallstones do occur, they are usually asymptomatic; symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery.

Gastrointestinal disorders In rare instances, gastrointestinal side effects may resemble acute intestinal obstruction, with progressive abdominal distension, severe epigastric pain, abdominal tenderness and guarding. The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment.

Hypersensitivity and anaphylactic reactions Hypersensitivity and allergic reactions have been reported during post- marketing. When these occur, they mostly affect the skin, rarely the mouth and airways. Isolated cases of anaphylactic shock have been reported.

Injection site reactions Injection site related reactions including pain, redness, haemorrhage, pruritus, swelling or induration were commonly reported in patients receiving Sandostatin LAR; however, these events did not require any clinical intervention in the majority of the cases.

Metabolism and nutrition disorders Although measured faecal fat excretion may increase, there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption. c. treatment and resolved on withdrawal of the drug.

c. treatment. Cardiac disorders Bradycardia is a common adverse reaction with somatostatin analogues. In both acromegalic and carcinoid syndrome patients, ECG changes were observed such as QT prolongation, axis shifts, early repolarisation, low voltage, R/S transition, early R wave progression, and non-specific ST-T wave changes.

4). ) in patients with cirrhosis of the liver, and during treatment with Sandostatin LAR. This is reversible after discontinuation of treatment. Reporting of […]

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.

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.

5). 8). Additionally, cases of cholangitis have been reported as a complication of cholelithiasis in patients taking Sandostatin LAR in the post-marketing setting. Ultrasonic examination of the gallbladder before and at about 6-monthly intervals during Sandostatin LAR therapy is recommended.

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. c. Sandostatin, 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 concomitant Type I diabetes mellitus, Sandostatin LAR is likely to affect glucose regulation, and insulin requirements may be reduced. 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. Sodium content Sandostatin LAR contains less than 1 mmol (23 mg) sodium per vial, that is to say essentially ‘sodium-free’.

1.