1. Name of the medicinal product
SANDOSTATIN® LAR® 10 mg powder and solvent for suspension for injection.
SANDOSTATIN® LAR® 20 mg powder and solvent for suspension for injection.
SANDOSTATIN® LAR® 30 mg powder and solvent for suspension for injection.
2. Qualitative and quantitative composition
The active substance is octreotide free peptide. 10 mg, 20 mg or 30 mg nominally 4.15% of fill weight equivalent to 4.65% of octreotide acetate.
For a full list of excipients, see section 6.1 List of excipients.
3. Pharmaceutical form
Powder and solvent for suspension for injection.
Powder: white to off-white powder.
Solvent for suspension for injection: clear, colourless solution.
Sandostatin® LAR® is a long-acting depot injection form of octreotide. Powder (microspheres for suspension for injection) to be suspended in a vehicle immediately prior to i.m. injection.
Sandostatin® LAR® suspension contains less than 1 mmol (23 mg) of sodium per dose, i.e.essentially 'sodium-free'.
4. Clinical particulars
4.1 Therapeutic indications
Treatment of patients with acromegaly:
- who are adequately controlled on s.c. treatment with Sandostatin®,
- in whom surgery or radiotherapy is inappropriate or ineffective, or in the interim period until radiotherapy becomes fully effective (see 4.2. Posology and method of administration).
Treatment of patients with symptoms associated with functional gastro-entero-pancreatic endocrine tumours in whom symptoms are adequately controlled on s.c. treatment with Sandostatin®:
- Carcinoid tumours with features of the carcinoid syndrome.
- VIPomas.
- Glucagonomas.
- Gastrinomas/Zollinger-Ellison syndrome.
- Insulinomas, for pre-operative control of hypoglycaemia and for maintenance therapy.
- GRFomas.
4.2 Posology and method of administration
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 (see 6.6 Instructions for use/handling).
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.
Use in patients with impaired renal function
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.
Use in patients with impaired hepatic function
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 therapeutic window of octreotide, no dose adjustment of Sandostatin® LAR® is necessary in patients with liver cirrhosis.
Use in the elderly
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®.
Use in children
There is limited experience with the use of Sandostatin® LAR® in children.
4.3 Contraindications
Known hypersensitivity to octreotide or to any of the excipients, (see section 6.1 List of excipients).
4.4 Special warnings and precautions for use
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 (see also section 4.6 Pregnancy and lactation).
Thyroid function should be monitored in patients receiving prolonged treatment with octreotide.
Cardiovascular related events
Uncommon 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-entero-pancreatic 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.
(See page 16 ‘Recommendation for the management of patients during Sandostatin® LAR® treatment with respect to the development of gallstones’). [This section to be included ONLY as an advice, NOT COMPULSORY to include (depending on s.c. Sandostatin® registration).]
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.
4.5 Interaction with other medicinal products and other forms of interaction
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 analogs might decrease the metabolic clearance of compounds known to be metabolized 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 metabolized by CYP3A4 and which have a low therapeutic index (e.g. quinidine, terfenadine) should therefore be used with caution.
4.6 Pregnancy and lactation
Pregnancy
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 to 300 micrograms/day of Sandostatin® s.c. or 20 to 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).
Sandostatin® should only be prescribed to pregnant women under compelling circumstances (see also section 4.4 Special warnings and precautions for use).
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.
4.7 Effects on ability to drive and use machines
No data exist on the effects of Sandostatin® LAR® on the ability to drive and use machines.
4.8 Undesirable effects
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, localized 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 Sandostatin® s.c. treatment and resolved on withdrawal of the drug. In addition, cholelithiasisinduced pancreatitis has been reported for patients on long-term Sandostatin® s.c. 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:
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
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.
4.9 Overdose
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 overdosage is symptomatic.
5. Pharmacological properties
Pharmacotherapeutic group: anti-growth hormone. ATC code H01CB02.
5.1 Pharmacodynamic properties
Octreotide is a synthetic octapeptide derivative of naturally occurring somatostatin with similar pharmacological effects, but with a considerably prolonged duration of action. It inhibits pathologically increased secretion of growth hormone (GH) and of peptides and serotonin produced within the gastro-entero-pancreatic (GEP) endocrine system.
In animals, octreotide is a more potent inhibitor of GH, glucagon and insulin release than somatostatin, with greater selectivity for GH and glucagon suppression.
In healthy subjects octreotide, like somatostatin, has been shown to inhibit
- release of GH stimulated by arginine, exercise and insulin-induced hypoglycaemia,
- post-prandial release of insulin, glucagon, gastrin, other peptides of the GEP system, and arginine-stimulated release of insulin and glucagon,
- thyrotropin-releasing hormone (TRH)-stimulated release of thyroid-stimulating hormone (TSH).
Unlike somatostatin, octreotide inhibits GH preferentially over insulin and its administration
is not followed by rebound hypersecretion of hormones (i.e. GH in patients with acromegaly).
In patients with acromegaly, Sandostatin® LAR®, a galenical formulation of octreotide suitable for repeated administration at intervals of 4 weeks, delivers consistent and therapeutic octreotide serum concentrations thus consistently lowering GH and normalising IGF 1 serum concentrations in the majority of patients. In most patients, Sandostatin® LAR® markedly reduces the clinical symptoms of the disease, such as headache, perspiration, paraesthesia, fatigue, osteoarthralgia and carpal tunnel syndrome. In previously untreated acromegaly patients with GH-secreting pituitary adenoma, adenoma, Sandostatin® LAR® treatment resulted in a tumor volume reduction of > 20% in a significant proportion (50%) of patients.
For patients with functional tumours of the gastro-entero-pancreatic endocrine system, treatment
with Sandostatin® LAR® provides continuous control of symptoms related to the underlying disease. The effect of octreotide in different types of gastro-entero-pancreatic tumours are as follows:
Carcinoid tumours:
Administration of octreotide may result in improvement of symptoms, particularly of flushing and diarrhoea. In many cases, this is accompanied by a fall in plasma serotonin and reduced urinary excretion of 5 hydroxyindole acetic acid.
VIPomas:
The biochemical characteristic of these tumours is overproduction
of vasoactive intestinal peptide (VIP). In most cases, administration of octreotide results in
alleviation of the severe secretory diarrhoea typical of the condition, with consequent improvement
in quality of life. This is accompanied by an improvement in associated electrolyte abnormalities,
e.g. hypokalaemia, enabling enteral and parenteral fluid and electrolyte supplementation to be withdrawn.
In some patients, computer tomography scanning suggests a slowing or arrest of progression of the tumour,
or even tumour shrinkage, particularly of hepatic metastases. Clinical improvement is usually accompanied
by a reduction in plasma VIP levels, which may fall into the normal reference range.
Glucagonomas:
Administration of octreotide results in most cases in substantial
improvement of the necrolytic migratory rash which is characteristic of the condition.
The effect of octreotide on the state of mild diabetes mellitus which frequently occurs
is not marked and, in general, does not result in a reduction of requirements for insulin
or oral hypoglycaemic agents. Octreotide produces improvement of diarrhoea, and hence weight gain,
in those patients affected. Although administration of octreotide often leads to an immediate reduction
in plasma glucagon levels, this decrease is generally not maintained over a prolonged period of
administration, despite continued symptomatic improvement.
Gastrinomas/Zollinger-Ellison syndrome:
Although therapy with proton pump inhibitors
or H2-receptor blocking agents controls the recurrent peptic ulceration which results from chronic
gastrin-stimulated hypersecretion of gastric acid, such control may be incomplete. Diarrhoea may
also be a prominent symptom not alleviated in all patients by this therapy. Octreotide alone or
in conjunction with proton pump inhibitors or H2-receptor antagonists may reduce gastric acid
hypersecretion and improve symptoms, including diarrhoea. Other symptoms possibly due to
peptide production by the tumour, e.g. flushing, may also be relieved. Plasma gastrin levels
fall in some patients.
Insulinomas:
Administration of octreotide produces a fall in circulating immunoreactive insulin.
In patients with operable tumours, octreotide may help to restore and maintain normoglycaemia
pre-operatively. In patients with inoperative benign or malignant tumours, glycaemic control may
be improved even without concomitant sustained reduction in circulating insulin levels.
GRFomas:
These rare tumours are characterised by production of GH releasing factor (GRF) alone or in conjunction with other active peptides. Octreotide produces improvement in the features and symptoms of the resulting acromegaly. This is probably due to inhibition of GRF and GH secretion, and a reduction in pituitary enlargement may follow.
5.2 Pharmacokinetic properties
After single i.m. injections of Sandostatin® LAR®, the serum octreotide concentration
reaches a transient initial peak within 1 hour after administration, followed by a progressive
decrease to a low undetectable octreotide level within 24 hours. After this initial peak
on day 1, octreotide remains at sub-therapeutic levels in the majority of the patients for
the following 7 days. Thereafter, octreotide concentrations increase again, and reach plateau
concentrations around day 14 and remain relatively constant during the following 3 to 4 weeks.
The peak level during day 1 is lower than levels during the plateau phase and no more than 0.5% of
the total drug release occurs during day 1. After about day 42, the octreotide concentration
decreases slowly, concomitant with the terminal degradation phase of the polymer matrix of the
dosage form.
In patients with acromegaly, plateau octreotide concentrations after single doses of 10 mg, 20 mg and 30 mg Sandostatin® LAR® amount to 358 ng/L, 926 ng/L, and 1,710 ng/L, respectively. Steady-state octreotide serum concentrations, reached after 3 injections at 4 week intervals,
are higher by a factor of approximately 1.6 to 1.8 and amount to 1,557 ng/L and 2,384 ng/L after
multiple injections of 20 mg and 30 mg Sandostatin® LAR®, respectively.
In patients with carcinoid tumours, the mean (and median) steady-state serum concentrations of octreotide after multiple injections of 10 mg, 20 mg and 30 mg of Sandostatin® LAR® given at 4 week intervals also increased linearly with dose and were 1,231 (894) ng/L, 2,620 (2,270) ng/L and 3,928 (3,010) ng/L, respectively.
No accumulation of octreotide beyond that expected from overlapping release profiles
occurred over a duration of up to 28 monthly injections of Sandostatin® LAR®.
The pharmacokinetic profile of octreotide after injection of Sandostatin® LAR® reflects the release profile from the polymer matrix and its biodegradation.
Once released into the systemic circulation, octreotide distributes according to
its known pharmacokinetic properties, as described for s.c. administration.
The volume of distribution of octreotide at steady-state is 0.27 L/kg and the total body clearance is 160 mL/min. Plasma protein binding amounts to 65% and essentially no drug is bound to blood cells.
5.3 Preclinical safety data
Acute toxicity
Acute toxicity studies of octreotide in mice revealed LD50 values of 72 mg/kg by the
i.v. route and of 470 mg/kg by the s.c. route. The acute i.v. LD50 value of octreotide
in rats was determined at 18 mg/kg. Octreotide acetate was well tolerated by dogs
receiving up to 1 mg/kg body weight by i.v. bolus injection.
Repeat dose toxicity
In a repeat dose study performed in rats by i.m. injection of 2.5 mg Sandostatin® LAR®
in 50 mg microspheres every 4 weeks for 21 weeks, with necropsy at 26 weeks, no drug-related
necropsy findings were observed. The only histopathological findings considered to be of
significance were at the injection site in treated and control animals, where the microspheres
had provoked a reversible granulomatous myositis. After a single i.m. injection of Sandostatin® LAR®
in rats and rabbits, biodegradation of microspheres was complete by day 75 after injection in both species.
Mutagenicity
Octreotide and/or its metabolites were devoid of mutagenic potential when
investigated in vitro in validated bacterial and mammalian cell test systems.
Increased frequencies of chromosomal changes were observed in V79 Chinese hamster
cells in vitro, albeit at high and cytotoxic concentrations only. Chromosomal aberrations
were however not increased in human lymphocytes incubated with octreotide acetate in vitro.
In vivo, no clastogenic activity was observed in the bone marrow of mice treated with octreotide
i.v. (micronucleus test) and no evidence of genotoxicity was obtained in male mice using a DNA
repair assay on sperm heads. The microspheres were devoid of mutagenic potential when tested
in a validated in vitro bacterial assay.
Carcinogenicity/chronic toxicity
In studies in rats in which s.c. Sandostatin® at daily doses up to
1.25 mg/kg body weight were administered, fibrosarcomas were observed,
predominantly in a number of male animals, at the s.c. injection site after
52, 104 and 113/116 weeks. Local tumours occurred also in the control rats,
however development of these tumours was attributed to disordered fibroplasia
produced by sustained irritant effects at the injection sites, enhanced by the
acidic lactic acid/mannitol vehicle. This non-specific tissue reaction appeared
to be particular to rats. Neoplastic lesions were observed neither in mice receiving
daily s.c. injections of Sandostatin® at doses up to 2 mg/kg for 98 weeks, nor in dogs
which were treated with daily s.c. doses of the drug for 52 weeks.
The 116 week carcinogenicity study in rats with s.c. Sandostatin® also revealed
uterine endometrial adenocarcinomas, their incidence reaching statistical significance
at the highest s.c. dose level of 1.25 mg/kg per day. The finding was associated with an
increased incidence of endometritis, a decreased number of ovarian corpora lutea, a reduction
in mammary adenomas and the presence of uterine glandular and luminal dilation, suggesting
a state of hormonal imbalance. The available information clearly indicates that the findings
of endocrine-mediated tumours in rats are species-specific and are not relevant for the use of
the drug in humans.
Reproduction toxicity
Fertility as well as pre-, peri- and post-natal studies in female rats revealed
no adverse effects on reproductive performance and development of the offspring,
when s.c. doses of up to 1 mg/kg body weight per day were administered.
Some retardation of the physiological growth noted in pups was transient
and attributable to GH inhibition brought about by excessive pharmacodynamic activity.
6. Pharmaceutical particulars
6.1 List of excipients
Vial
Poly (DL-lactide-co-glycolide) 78.35% of nominal fill weight; sterile mannitol 17.0% of nominal fill weight.
Prefilled syringe
One prefilled syringe (solvent for parenteral use), containing: sodium carboxymethylcellulose 12.5 mg, mannitol 15 mg; water for injection qs ad 2.5 mL.
Information might differ in some countries.
6.2 Incompatibilities
Sandostatin® LAR® microspheres for injection is to be used as a single dose container, without any dilution with other products. Therefore, no compatibility data with other products have been generated.
6.3 Shelf life
3 years.
Information might differ in some countries.
6.4 Special precautions for 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.
Information might differ in some countries.
Sandostatin® LAR® must be kept out of the reach and sight of children.
6.5 Nature and contents of container
The microspheres are packaged in a 5 mL glass vial, with a Teflon-faced rubber stopper and sealed with an aluminium flip-off seal.
The vehicle is packaged in a pre-filled glass syringe which is closed with two rubber stoppers (a front and a plunger stopper).
Two needles [40 mm (1.5 inch), 19 gauge].
Country specific.
Special precautions for disposal
Any unused product or waste material should be disposed of in accordance with local requirements.
6.6 Instructions for use/handling
Instructions for intramuscular injection of Sandostatin® LAR®
FOR DEEP INTRAGLUTEAL INJECTION ONLY
Content: |
One vial containing Sandostatin® LAR®
|
One prefilled syringe containing vehicle solution + two needles
|
Follow the instructions below carefully to ensure complete saturation of the powder and its uniform suspension before i.m. injection.
Sandostatin® LAR® suspension must only be prepared immediately before administration. Sandostatin® LAR® should only be administered by a trained health professional.
| Allow the Sandostatin® LAR® vial and the vehicle syringe to reach room temperature.
Remove the cap from vial containing Sandostatin® LAR®. Assure that the powder is settled at the bottom of the vial by lightly tapping the vial. |
| Remove the cap from the vehicle syringe. Attach one of the supplied needles to the vehicle syringe. |
| Disinfect the rubber stopper of the vial with an alcohol swab. Insert the needle through the centre of the rubber stopper of the Sandostatin® LAR® vial. |
| Without disturbing the Sandostatin® LAR® powder, gently inject all the vehicle into the vial by running the vehicle down the inside wall of the vial. Do not inject the vehicle directly into the powder. Withdraw the needle from the vial. |
| Do not disturb the vial until the vehicle has totally wetted the Sandostatin® LAR® powder (at least 2 to 5 minutes). Without inverting the vial check the powder on the walls and bottom of the vial. If dry spots exist, allow undisturbed wetting to continue. At this stage, prepare the patient for injection. |
| Once complete wetting has occurred, the vial should be moderately swirled for about 30 to 60 seconds until a uniform milky suspension is achieved.
Do not vigorously shake the vial as this may cause the suspension to flocculate, making it unusable. |
| Immediately re-insert the needle through the rubber stopper and then, with the bevel down and the vial tipped at approximately 45 degree angle, slowly draw the contents of the vial into the syringe. Do not invert the vial when filling the syringe as this may affect the amount withdrawn.
It is normal for a small amount of suspension to remain on the walls and bottom of the vial. This is a calculated overfill. |
| Immediately change the needle (supplied). |
| Administration must occur immediately after the suspension has been prepared. Gently invert the syringe as needed to maintain a uniform suspension. Eliminate air from syringe. |
| Disinfect the injection site with an alcohol swab.
Insert needle into right or left gluteus and draw back to ensure that no blood vessel has been penetrated. Inject slowly i.m. by deep intragluteal injection with steady pressure. If the needle blocks, attach a new needle of the same diameter [1.1 mm, 19 gauge].
Sandostatin® LAR® must be given only by deep intragluteal injection, never i.v. If a blood vessel has been penetrated, attach a new needle and select another injection site. |
Recommendation for the management of patients during Sandostatin® LAR® treatment with respect to the development of gallstones
- Patients should undergo a baseline ultrasound examination of the gallbladder prior to commencing octreotide treatment.
- Periodic repeat ultrasound examination of the gallbladder should be performed, preferably at about 6-month intervals, throughout Sandostatin® LAR® treatment.
- If stones are already present before the start of therapy, the potential benefit of Sandostatin® LAR® should be assessed against the potential risks associated with the gallstones. There is no evidence at present that Sandostatin® LAR® adversely affects the course or prognosis of pre-existing gallstones.
- Management of patients who develop gallstones in association with Sandostatin® LAR®:
- Asymptomatic gallstones
Sandostatin® LAR® may be continued, depending on re-assessment of the benefit/risk ratio. Either way, no action is required except to continue monitoring, with increased frequency if this is considered necessary.
- Symptomatic gallstones
Sandostatin® LAR® may be either stopped or continued, depending on re-assessment of the benefit/risk ratio. Either way, the gallstones should be treated like any other symptomatic gallstones. Medically, this may include combined bile acid therapy (e.g. chenodeoxycholic acid together with ursodeoxycholic acid [UDCA] or monotherapy with ursodeoxycholic acid (UDCA) associated with ultrasound monitoring until the stones have completely disappeared. For posology and treatment duration, please consult the locally approved prescribing information for CDCA and/or UDCA.
