OCTREOTIDE AMPOULES

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.

g. 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. g. 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 5 to 20%. If gallstones do occur, they 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.

c. administration, that is, by injecting between meals or on retiring to bed. Hypersensitivity and anaphylactic reactions Hypersensitivity and allergic reactions have been reported during post- marketing experience. When these occur, they mostly affect the skin, rarely the mouth and airways.

Isolated cases of anaphylactic shock have been reported. c. injection, with redness and swelling, rarely lasting more than 15 minutes. Local discomfort may be reduced by allowing the solution to reach room temperature before injection, or by injecting a smaller volume using a more concentrated solution.

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. This is reversible after discontinuation of treatment. Reporting of suspected adverse […]

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). 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).

2). Patients who receive high doses of intravenous octreotide should be kept under appropriate cardiac monitoring. 8). Additionally, cases of cholangitis have been reported as a complication of cholelithiasis in patients taking Sandostatin in the post-marketing setting.

Ultrasonic examination of the gallbladder before, and at about 6- to 12-month intervals during Sandostatin 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 Sandostatin, 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, Sandostatin 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 Sandostatin 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 Sandostatin. In non-diabetics and type II diabetics with partially intact insulin reserves, Sandostatin 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.

c. injection site only at the highest dose (about 8 times the maximum human dose based on body surface area). 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 Sandostatin for up to 15 years.

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 Sandostatin in patients who have a history of vitamin B12 deprivation.

Sodium content Sandostatin contains less than 1 mmol (23 mg) sodium per ampoule/vial, that is to say essentially ‘sodium-free’.

1.