Pregnancy
Experience with octreotide in pregnant or nursing women is not available and they should therefore be given the drug Sandostatin should only be prescribed to pregnant women under compelling circumstances (see also section 4.4 Special warnings and precautions for use).
There are no adequate and well-controlled studies in pregnant women. In the post-marketing experience, data on a limited number of exposed pregnancies have been reported in patients with acromegaly, however, in half of the cases the pregnancy outcomes are unknown. Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-300 micrograms/day of Sandostatin s.c. or 20-30 mg/month of Sandostatin LAR. In approximately two-thirds of the cases with known outcome, the women elected to continue octreotide therapy during their pregnancies. In most of the cases with known outcome, normal newborns were reported, but also several spontaneous abortions during the first trimester, and a few induced abortions.
There were no cases of congenital anomalies or malformations due to octreotide usage in the cases that reported pregnancy outcomes.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development apart from some transient retardation of physiological growth (see section 5.3 Preclinical safety data).
Lactation
Patients should not breastfeed during Sandostatin treatment. It is unknown whether octreotide is excreted in human breast milk. Animal studies have shown excretion of octreotide in breast milk.
Section 4.8
The most frequent adverse reactions reported during octreotide therapy includeThe main side effects encountered with Sandostatin LAR administration are local injection site reactions and gastrointestinal disorders, nervous system disorders, hepatobiliary disorders and metabolism and nutritional disorders reactions.
The most commonly reported adverse reactions in clinical trials with octreotide Sandostatin LAR administration were diarrhoea, abdominal pain, nausea, flatulence, headache, and local site pain or irritation 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.
In rare instances, gastrointestinal side-effects may resemble acute intestinal obstruction, with progressive abdominal distension, severe epigastric pain, abdominal tenderness and guarding.
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.
In very rare instances, acute pancreatitis has been reported within the first hours or days of s.c. Sandostatin treatment and resolved on withdrawal of the drug. In addition, cholelithiasis-induced pancreatitis has been reported for patients on long-term s.c. Sandostatin treatment.
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. The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see section 4.4 Special warnings and precautions for use).
The following adverse drug reactions, listed in Table 1, have been accumulated from clinical studies with octreotide and spontaneously reported adverse reactions:
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 trials
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Endocrine Immune system disorders
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CommonRare:
Very rare:
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Hypothyroidism, thyroid dysfunction (e.g., decreased TSH, decreased Total T4, and decreased Free T4).Hypersensitivity, rash
Anaphylaxis
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Metabolism and nutrition Endocrine disorders
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|
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Very common:
Common:
Uncommonrare:
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Hypoglycaemia, Hhyperglycaemia.
Hypoglycaemia, impaired glucose tolerance, anorexia.
Dehydration.
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Cardiac disorders
Common:
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Bradycardia.
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Uncommon:
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Bradycardia, Ttachycardia.
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Respiratory disorders
Very rareCommon:
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Dyspnoea.
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Gastrointestinal disorders
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|
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Very cCommon:
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Diarrhoea, crampy abdominal pain, nausea, constipation, flatulence.
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RareCommon:
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Steatorrhoea, nausea,Dyspepsia, vomiting, abdominal bloating, steatorrhoea, loose stools, discolouration of faeces.
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Very rare:
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Acute pancreatitis, anorexia, loose stools.
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Nervous system disorders
Very common:
Common:
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Headache.
Dizziness.
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Hepatobiliary disorders
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|
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Very Uncommon:
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CholecystitisCholelithiasis.
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RareCommon:
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GallstonesCholecystitis, biliary sludge, hyperbilirubinaemia.
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Very rare:
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Acute hepatitis without cholestasis, hyperbilirubinaemia, elevated alkaline phosphatase, gamma glutamyl transferase and transaminases.
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Skin and subcutaneous tissue disorders
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UncCommon:
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Pruritus, rash, alopecia.Transient hair loss
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General disorders and administration site
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Very cCommon:
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Local iInjection site localised pain, swelling and irritation.
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Investigations
Common:
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Elevated transaminase levels.
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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.
In very rare instances, acute pancreatitis has been reported within the first hours or days of s.c. Sandostatin treatment and resolved on withdrawal of the drug. In addition, cholelithiasis-induced pancreatitis has been reported for patients on long-term s.c. Sandostatin treatment.
Post-marketing
Spontaneously reported The following adverse drug 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. have been observed during post-marketing experience. On rare occasions thyroid dysfunction has been reported both under and over activity. In some cases dyspepsic signs have been reported in patients receiving octreotide acetate.
Table 2 Adverse drug reactions derived from spontaneous reports
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Immune disorders
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Anaphylaxis, allergy/hypersensitivity reactions.
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Skin and subcutaneous tissue disorders
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Urticaria.
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Hepatobiliary disorders
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Acute pancreatitits, acute hepatitis without cholestasis, cholestatic hepatitis, cholestasis, jaundice, cholestatic jaundice.
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Cardiac disorders
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Arrhythmias.
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Investigations
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Increased alkaline phosphatase levels, increased gamma glutamyl transferase levels.
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Symptoms and episodes of arrhythmias have been reported in patients receiving octreotide acetate. Other ECG changes such as QT prolongation, axis shifts, early repolarisation, low voltage, R/S transition, early R wave progression, and non-specific ST-T wave changes, have been reported during octreotide acetate therapy. The relationship of these events to octreotide acetate is however not established because many acromegalic and carcinoid patients have underlying cardiac diseases (see section 4.4 Special warnings and precautions for use).
