Chemical formula: C₄₉H₆₆N₁₀O₁₀S₂ Molecular mass: 1,019.25 g/mol PubChem compound: 448601
Octreotide interacts in the following cases:
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 should therefore be used with caution (e.g. quinidine, terfenadine).
Dose adjustments of insulin and antidiabetic medicinal products may be required when octreotide is administered concomitantly.
Because of its inhibitory action on growth hormone, glucagon, and insulin, octreotide 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 octreotide 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 octreotide. In non-diabetics and type II diabetics with partially intact insulin reserves, octreotide administration can result in post-prandial increases in glycaemia. It is therefore recommended to monitor glucose tolerance and antidiabetic treatment.
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine.
Octreotide has been found to reduce the intestinal absorption of ciclosporin.
Octreotide has been found to delay the intestinal absorption of cimetidine.
In patients with liver cirrhosis, the half-life of the drug may be increased, necessitating adjustment of the maintenance dosage.
Cholelithiasis is a very common event during octreotide treatment and may be associated with cholecystitis and biliary duct dilatation. Ultrasonic examination of the gallbladder before, and at about 6- to 12-month intervals during octreotide therapy is therefore recommended.
Common cases of bradycardia have been reported. Dose adjustments of medicinal products such as beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balance, may be necessary.
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 octreotide s.c. or 10-40 mg/month of octreotide. Congenital anomalies were reported 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 octreotide during pregnancy.
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 octreotide treatment.
It is not known whether octreotide has an effect on human fertility. Late descent of the testes was found for male offsprings of dam treated during pregnancy and lactation. Octreotide, however, did not impair fertility in male and female rats at doses of up to 1 mg/kg body weight per day.
Octreotide has no or negligible influence on the ability to drive and use machines. Patients should be advised to be cautious when driving or using machines if they experience dizziness, asthenia/fatigue, or headache during treatment with octreotide.
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.
The following adverse drug reactions have been accumulated from clinical studies with octreotide. Adverse drug reactions 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.
Adverse drug reactions reported in clinical studies:
Very common: Diarrhoea, abdominal pain, nausea, constipation, flatulence.
Common: Dyspepsia, vomiting, abdominal bloating, steatorrhoea, loose stools, discolouration of faeces.
Very common: Headache.
Common: Dizziness.
Common: Hypothyroidism, thyroid disorder (e.g. decreased TSH, decreased total T4, and decreased free T4).
Very common: Cholelithiasis.
Common: Cholecystitis, biliary sludge, hyperbilirubinaemia.
Very common: Hyperglycaemia.
Common: Hypoglycaemia, impaired glucose tolerance, anorexia.
Uncommon: Dehydration.
Very common: Injection site reactions.
Common: Asthenia.
Common: Elevated transaminase levels.
Common: Pruritus, rash, alopecia.
Common: Dyspnoea.
Common: Bradycardia
Uncommon: Tachycardia.
Spontaneously reported adverse reactions presented in the list below, are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure.
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.
Somatostatin analogues have been shown to inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder abnormalities or sludge. Development of gallstones has been reported in 15 to 30% of long-term recipients of s.c. octreotide. 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.
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.
Occurrence of gastrointestinal side-effects may be reduced by avoiding meals around the time of octreotide s.c. administration, that is, by injecting between meals or on retiring to bed.
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.
Pain or a sensation of stinging, tingling or burning at the site of s.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.
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 octreotide s.c. treatment and resolved on withdrawal of the drug. In addition, cholelithiasis induced pancreatitis has been reported for patients on long-term octreotide s.c. treatment.
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. The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases.
Thrombocytopenia has been reported during post-marketing experience, particularly during treatment with octreotide (i.v.) in patients with cirrhosis of the liver. This is reversible after discontinuation of treatment.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
