Consumer medicine information

Sandostatin

Octreotide

BRAND INFORMATION

Brand name

Sandostatin

Active ingredient

Octreotide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Sandostatin.

SUMMARY CMI

SANDOSTATIN®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using SANDOSTATIN?

SANDOSTATIN contains the active ingredient octreotide. SANDOSTATIN is used to block the production of excessive growth hormone and acts to reduce the amount of other chemicals and proteins that occur naturally in your body. This may be useful in treating certain types of cancers, excessive body part growth (acromegaly) and following surgery on your pancreas. For more information, see Section 1. Why am I using SANDOSTATIN? in the full CMI.

2. What should I know before I use SANDOSTATIN?

Do not use if you have ever had an allergic reaction to SANDOSTATIN or any of the ingredients listed at the end of the CMI.
Talk to your doctor if you have any other medical conditions such as problems with your liver, gall bladder, heart, or blood sugar. Tell your doctor if you take any other medicines or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I use SANDOSTATIN? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with SANDOSTATIN and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use SANDOSTATIN?

  • SANDOSTATIN is given by injection under the skin using special equipment designed to use the glass capsule (ampoule)
  • You may be able to take SANDOSTATIN at home, your doctor or nurse will show you how to do this and provide you with this equipment.

More instructions can be found in Section 4. How do I use SANDOSTATIN? in the full CMI.

5. What should I know while using SANDOSTATIN?

Things you should do
  • Remind any doctor, dentist, surgeon, pharmacist, or anesthetist that you are using SANDOSTATIN.
  • Attend any follow-up appointments to check how you are responding to treatment.
  • Take contraception (birth control) if your doctor tells you to in order to avoid becoming pregnant.
Things you should not do
  • Do not stop using this medicine suddenly.
  • Do not give this medicine to someone else.
Driving or using machines
  • SANDOSTATIN may make you feel dizzy, light-headed, or weak. Do not drive or do anything else that would require your attention.
Drinking alcohol
  • SANDOSTATIN may make you feel dizzy, light-headed, or weak. You should avoid alcohol while on treatment with SANDOSTATIN.
Looking after your medicine
  • SANDOSTATIN should generally be kept in the fridge (set between 2 - 8°C). Do NOT freeze it.
  • SANDOSTATIN can also be stored for up to 2 weeks at room temperature (below 30°C) for daily use. If the ampoules have not been kept in the fridge for more than 2 weeks, throw them away.

For more information, see Section 5. What should I know while using SANDOSTATIN? in the full CMI.

6. Are there any side effects?

Some common side effects include diarrhoea, constipation, feeling gassy, stomach pain/discomfort or cramps, feeling or being sick, headaches, dizziness, gall stones, weight changes, high blood sugar, redness, itchiness, swelling or rash at injection site, redness elsewhere on the skin, hair loss, feeling tired, weak, anxious, or cold. Serious side effects include signs of an allergic reaction including shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, or other parts of the body; rash, itching or hives on the skin; severe stomach pain, tenderness or swelling; signs of liver disease including yellowing of skin or whites around eyes; changes to vision; passing much less urine or unable to pass urine when going to the toilet; trembling hands or balance problems; sweating more than normal; feeling faint/rapid heartbeat; bruising more than normal.
For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

SANDOSTATIN® (San-do-statin)

Active ingredient(s): Octreotide (ok-TREE-oh-tide)

Consumer Medicine Information (CMI)

This leaflet provides important information about using SANDOSTATIN. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using SANDOSTATIN.

Where to find information in this leaflet:

1. Why am I using SANDOSTATIN?
2. What should I know before I use SANDOSTATIN?
3. What if I am taking other medicines?
4. How do I use SANDOSTATIN?
5. What should I know while using SANDOSTATIN?
6. Are there any side effects?
7. Product details

1. Why am I using SANDOSTATIN?

SANDOSTATIN contains the active ingredient octreotide. SANDOSTATIN is an anti-growth hormone, meaning that it is used to block the production of excessive growth hormone that occurs naturally in your body. It also works to reduce the amount of other chemicals and proteins in your body that may be making you unwell.

SANDOSTATIN has three main uses.

  1. Treatment of acromegaly. This is a condition where the body produces too much hormone that controls the growth of your bones, organs, and tissues. SANDOSTATIN helps reduce the amount of this chemical in your body to relieve the effects of this condition which may include stiffness or pain in your joints and larger than normal bones in your hand and feet.
  2. Relieve the effects of some types of cancer (uncontrolled cell growth) including carcinoid syndrome (tumour of the gut/lungs) and VIPoma (tumour of the gut) such as diarrhoea.
  3. In people who are having surgery on their pancreas to help reduce the chance of having problems after the surgery.

2. What should I know before I use SANDOSTATIN?

Warnings

Do not use SANDOSTATIN if:

  • you are allergic to octreotide, or any of the ingredients listed at the end of this leaflet.

Always check the ingredients to make sure you can use this medicine.

Check with your doctor if you:

  • have previously had or currently have gallstones
  • have previously had or currently have diabetes
  • have previously had or currently have liver problems
  • have previously had or currently have pancreas problems
  • have previously had or currently have low vitamin B12
  • are taking medication to treat high blood pressure
  • are taking medication to manage fluid retention/electrolytes

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Monitoring

Before commencing treatment, your doctor may send you for blood/urine tests. They may refer you to specialist appointments to check on your gall bladder, thyroid, or liver function. They may also monitor you throughout treatment to see how your body is responding and whether your dose may need to change.

Some tests, such as blood sugar, you may also be required to do which can be done from home.

Gallstones

Using SANDOSTATIN, especially if you must use it for a long time may cause gallstones. Your doctor will want to know if you have gallstones currently or have experienced things like fever, chills, stomach pain, or a yellowing of the skin/eyes because of gallstones in the past. Your doctor will likely send you for an ultrasound of the gallbladder before treatment and throughout treatment.

Diabetes

SANDOSTATIN can affect your blood sugar. If you are a diabetic or may be at risk of developing diabetes, your doctor may want to closely monitor your blood sugar levels using special equipment. If you are currently taking insulin, your doctor may alter your dose.

Liver function

If you have liver scarring or problems with your liver, your doctor may adjust your dose. Your body may take more time than expected to handle the medicine for each dose.

Pancreas function

Your doctor may wish to check your pancreatic enzyme function.

Nutrition

Your doctor may want to check your vitamin B12 levels in your blood. SANDOSTATIN may also change how your body handles fat in your diet. Your doctor may refer you to a dietician.

Heart function and blood pressure

Your doctor may change your dose of SANDOSTATIN if you are taking medicines to control blood pressure or electrolytes.

Pregnancy and breastfeeding

Check with your doctor if you are pregnant, think you may be pregnant or intend to become pregnant. There is limited information on using SANDOSTATIN while pregnant or when trying to have a baby.

Talk to your doctor if you are breastfeeding or intend to breastfeed. It is not known whether SANDOSTATIN passes through breast milk and may harm your baby.

Contraception

Your doctor may request that you take an effective contraception (birth control) to prevent pregnancy.

Children

There is very little information on the use of SANDOSTATIN in children.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins, or supplements that you buy without a prescription from your pharmacy, supermarket, or health food shop.

Some medicines may interfere with SANDOSTATIN and affect how it works. These can include:

  • Medicines to control your blood pressure (e.g., beta-blockers)
  • Medicines to control fluid retention or electrolytes (e.g., calcium blockers)
  • Medicines to treat heartburn/stomach ulcer (e.g., cimetidine)
  • Medicines used following transplant (e.g., cyclosporin)
  • Medicines used to treat pituitary gland tumours (e.g., bromocriptine)
  • Medicines used to treat irregular heartbeat (e.g., quinidine)
  • Medicines used to manage blood sugar (e.g., Insulin)

For you to more safely use SANDOSTATIN, your doctor may alter your dose of SANDOSTATIN or your other medications depending on what you are taking.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect SANDOSTATIN.

4. How do I use SANDOSTATIN?

How to use SANDOSTATIN

  • SANDOSTATIN is injected just under the skin. See section "How to inject SANDOSTATIN"
  • Your doctor will tell you how much SANDOSTATIN to take based on your condition and whether you may be taking other medications/have any other health conditions.
  • Follow the instructions provided and use SANDOSTATIN until your doctor tells you to stop.
  • If you do not understand how to use it properly and you are injecting it at home, ask your doctor for help.

How much to use

If you have acromegaly

  • Your doctor will usually start you on injections of between 0.05 to 0.1 mg taken every 8 or 12 hours.
  • Your doctor may adjust your dose depending on how well your body responds to treatment.

If you have Carcinoid syndrome and VIPoma

  • Your doctor will usually start you on injections of 0.05 mg once or twice a day.
  • Your doctor may adjust your dose depending on how well your body responds to treatment.

If you have recently had surgery on your pancreas

  • Your doctor will usually start you on injections of 0.1 mg usually given three times a day for one week, starting about an hour before the operation.
  • Your doctor may adjust your dose depending on how well your body responds to treatment.

When to use SANDOSTATIN

  • SANDOSTATIN should be injected in between meals or at bedtime. Avoid having a meal close to when you are injecting as it may upset your stomach.

Before you inject SANDOSTATIN at home

  • Your doctor or nurse will show you how to do this. It is important that you can do this when they send you home with it.
  • Make sure the ampoule is at room temperature before you use it. If it has been in the fridge, take it out half an hour before using it. You can warm it up in your hand but don't try to heat it in the microwave.
  • Check the liquid in the glass capsule (ampoule) - it should be clear and colourless.
  • You must not take SANDOSTATIN if the capsules show floating pieces (particles), or the liquid is discoloured (see section "Getting rid of unwanted medicine").

Injecting SANDOSTATIN at home

  • Inject SANDOSTATIN the same way your doctor or nurse has shown you with the equipment they provide you.
  • Choose a new site each time you need to inject (avoid injecting in the same place during back-to-back treatments).
  • The upper arms, thighs and abdomen are good areas for injection.

After you receive your injection of SANDOSTATIN

  • Throw away the glass capsule (ampoule) that was used. Each capsule may only be used once.
  • If you notice pain, stinging, tingling, burning, redness or swelling at the injection site after the injection, gently rub the site for a few seconds. If it persists into the day and it worries you, talk to your doctor.

If you forget to use SANDOSTATIN

Inject the dose as soon as you remember, and then go back to using it as you would normally.

Do not take a double dose to make up for the dose you missed. This may increase the chance of you getting an unwanted effect.

If you use too much SANDOSTATIN

If you think that you have used too much SANDOSTATIN, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

Some of the symptoms of taking too much SANDOSTATIN may include irregular heartbeat, low blood pressure, cardiac arrest, brain hypoxia (lower level of oxygen than normal going to your brain), severe upper stomach pain, yellow skin, and eyes, feeling sick/vomiting, loss of appetite, diarrhoea, weakness, tiredness, lack of energy, weight loss, abdominal swelling, discomfort, painful muscle cramps and changes to heart rhythm.

5. What should I know while using SANDOSTATIN?

Things you should do

  • Keep all your appointments, including those for specialists so that your overall health and response to treatment can be monitored.
  • Complete blood/urine tests requested by your doctor promptly.
  • Ensure you take an effective form of contraception if your doctor asks you to.

Call your doctor straight away if you:

  • You are pregnant or think you may be pregnant.

Remind any doctor, dentist, surgeon, anaesthetist, or pharmacist you visit that you are using SANDOSTATIN.

Things you should not do

  • Do not stop using this medicine suddenly.
  • Do not give this medicine to someone else.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how SANDOSTATIN affects you.

SANDOSTATIN may make you feel dizzy, light-headed, or weak. Do not drive or do anything else that would require your attention.

Drinking alcohol

Tell your doctor if you drink alcohol.

SANDOSTATIN may make you feel dizzy, light-headed, or weak. You should avoid alcohol while on treatment with SANDOSTATIN.

Looking after your medicine

Keep the ampoules (glass capsules) in their original container inside the carton until it is time to use them. Follow the instructions in the carton on how to take care of your medicine properly.

You should store SANDOSTATIN in the fridge (set between 2 - 8°C). Do NOT freeze it.

SANDOSTATIN can also be stored for up to 2 weeks at room temperature (below 30°C) for day-to-day use. Any ampoules that have not been used within this time must be thrown away if they have not been kept in the fridge.

Store it in a cool dry place away from moisture, heat, or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on windowsills.

Keep it where young children cannot reach it.

When to discard your medicine

  • if the pack has been out of the fridge for more than 2 weeks, take it to a pharmacy for disposal.
  • if there is any leftover from the glass capsule after you have opened it and taken the injection, it can be thrown away.

Getting rid of any unwanted medicine

  • If your glass capsules (ampoules) are discolored or have floating pieces (particles) in it, take it to your pharmacist to exchange it.
  • If your doctor tells you that you no longer need to use this medicine or it is out of date, damaged or shows signs of tampering, take it to any pharmacy for safe disposal.
  • Do not use this medicine after the expiry date or if you have not kept it in the fridge for more than 2 weeks. Take it to a pharmacy for safe disposal.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Skin problems
  • Swelling, redness, rash, swelling or itching at the site of injection.
  • Flushing (redness) of the skin elsewhere.
Stomach problems
  • Indigestion, cramps, discomfort
  • Bloating, wind
  • Constipation/diarrhoea
  • Loss of appetite
General wellbeing
  • Feeling sick, vomiting
  • Headache
  • Feeling dizzy or lightheaded
  • Feeling tired or weak
Mood and body changes
  • Faster heart rate
  • Change in weight
  • Feeling cold
  • Increased sweating
  • Feeling anxious
  • Swelling of hands or feet from fluid.
  • Thyroid changes
  • Temporary hair loss
Speak to your doctor if you have any of these less serious side effects and they worry you.
Tell your doctor if anything is making you feel unwell.

Serious side effects

Serious side effectsWhat to do
Signs of an allergic reaction
  • Sudden onset of rash, hives, itching, blisters that are spreading
  • Swelling of the face, lips and tongue or other parts of the body
  • Wheezing, difficulty breathing, unable to catch your breath.
Stomach problems
  • Severe stomach pain, swelling, tenderness.
Liver problems
  • Yellow skin and eyes, feeling generally unwell
  • Fever accompanied by feeling sick or vomiting
Kidney problems
  • Yellow skin and eyes, feeling generally unwell
Blood sugar/pancreas problems
  • Sweating more than normal, feeling weak, tired, or trembling.
  • Feeling dizzy, weak, hungry
  • Fast or irregular heartbeat
  • Passing large amounts of urine that is discolored/feeling very thirsty.
  • Changes to vision
Blood problems
  • Bruising more easily than normal
  • Increased bleeding from wound
Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
You may require medical treatment.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription. SANDOSTATIN ampoules contain 0.05 mg, 0.1 mg or 0.5 mg of the active ingredient, octreotide (as octreotide acetate).

What SANDOSTATIN contains

Active ingredient
(main ingredient)		Octreotide (as octreotide acetate)
Other ingredients
(inactive ingredients)
  • lactic acid
  • mannitol
  • sodium bicarbonate
  • water for injections
Potential allergens-

Do not take this medicine if you are allergic to any of these ingredients.

What SANDOSTATIN looks like

SANDOSTATIN solution for injection is a clear and colourless liquid. The solution is filled into a 1 mL colourless glass ampoule (glass capsule) with two colour coded rings and a one-point cut.

SANDOSTATIN solution for injection is available in three strengths in boxes that contain 5 ampoules:

  • 0.05 mg ampoules, box of 5 (AUST R 42192)
  • 0.1 mg ampoules, box of 5 (AUST R 42193)
  • 0.5 mg ampoules, box of 5 (AUST R 42191)

Who distributes SANDOSTATIN

Novartis Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone 1800 671 203
® = Registered Trademark

This leaflet was prepared in June 2024.

Internal document code

(sas110624c) based on PI (sas110624i)

Published by MIMS August 2024

BRAND INFORMATION

Brand name

Sandostatin

Active ingredient

Octreotide

Schedule

S4

 

1 Name of Medicine

Octreotide.

2 Qualitative and Quantitative Composition

Each 1 mL ampoule contains 0.05 mg, 0.1 mg or 0.5 mg octreotide (present as acetate).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection. The solution for injection is clear and colourless.

4 Clinical Particulars

4.1 Therapeutic Indications

For symptomatic control and reduction of growth hormone and IGF-1 plasma levels in patients with acromegaly, including those who are inadequately controlled by surgery, radiotherapy, or dopamine agonist treatment. Sandostatin treatment is also indicated in acromegalic patients unfit or unwilling to undergo surgery, or in the interim period until radiotherapy becomes fully effective.
For the relief of symptoms associated with the following functional tumours of the gastro-entero-pancreatic endocrine system:
carcinoid tumours with features of the carcinoid syndrome;
vasoactive intestinal peptide secreting tumours (VIPomas).
Sandostatin is not curative in these patients.
For reduction of the incidence of complications following pancreatic surgery.

4.2 Dose and Method of Administration

Acromegaly.

Initially 0.05-0.1 mg by subcutaneous injection every 8 or 12 hours. Dosage adjustment should be based on monthly assessment of GH and IGF-1 levels (target: GH < 2.5 nanogram/mL; IGF-1 within normal range) and on clinical symptoms, and on tolerability. In most patients the optimal daily dose will be 0.2 to 0.3 mg. A maximum dose of 1.5 mg/day should not be exceeded. For patients on a stable dose of Sandostatin, assessment of biochemical markers should be made periodically.
If no relevant reduction of GH levels and no improvement of clinical symptoms have been achieved within three months of starting treatment with Sandostatin, therapy should be discontinued.

Gastro-entero-pancreatic endocrine tumours.

Initially 0.05 mg once or twice daily by subcutaneous injection. Depending on clinical response, the effect on levels of circulating tumour products, and on tolerability, dosage can be gradually increased to 0.2 mg three times daily. Under exceptional circumstances higher doses may be required, however experience with doses above 750 microgram/day is limited.
Maintenance doses can be variable, depending on differences in tumour activity and rate of progression.

Complications following pancreatic surgery.

0.1 mg three times daily by subcutaneous injection for seven consecutive days, starting on the day of operation at least one hour before laparotomy.

Method of administration.

Patients who are to self-administer the drug by subcutaneous injection must receive precise directions from the physician or the nurse.
To reduce local discomfort, it is recommended that the solution reaches room temperature before injection. Multiple injections at short intervals at the same site should be avoided.
Single use. Contains no antimicrobial agent. Ampoules should be opened just prior to administration and any unused portion discarded.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration. Do not use if particulates and/or discolouration are observed.

Use in the elderly.

In elderly patients treated with Sandostatin, there was no evidence for reduced tolerability or altered dosage requirements.

Use in children.

Experience with Sandostatin in children is very limited.

4.3 Contraindications

Hypersensitivity to octreotide or to any component of the formulation.

4.4 Special Warnings and Precautions for Use

Pancreatic function.

Pancreatic exocrine insufficiency (PEI) has been observed in some patients receiving octreotide therapy for gastroenteropancreatic neuroendocrine tumours. Symptoms of PEI can include steatorrhea, loose stools, abdominal bloating, and weight loss. Screening and appropriate treatment for PEI according to clinical guidelines should be considered in symptomatic patients.

Cardiovascular related events.

Cases of bradycardia have been reported (frequency: common). Medical review including dose adjustment of this agent and dose adjustments of drugs such as beta-blockers, calcium channel blockers, or agents to control fluid and electrolyte balance, may be necessary.

Development of gallstones.

Cholelithiasis is a very common event during Sandostatin treatment and may be associated with cholecystitis and biliary duct dilatation (see Section 4.8 Adverse Effects (Undesirable Effects)). 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 6 to 12 monthly intervals during Sandostatin therapy is therefore recommended.

GH secreting pituitary tumours.

As GH secreting pituitary tumours may sometimes expand, thereby 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 may be advisable.

Gastro-entero-pancreatic endocrine tumours.

In the treatment of gastro-entero-pancreatic endocrine tumours, sudden escape from symptomatic control by Sandostatin may occur infrequently, with rapid recurrence of severe symptoms.

Effects on glucose regulation.

In patients with concomitant hypersecretion of insulin, Sandostatin, because of its greater relative potency in inhibiting secretion of growth hormone and glucagon than of insulin, and its shorter duration of action on inhibition of the latter, may increase the depth of, and prolong the duration of hypoglycaemia. Such patients should be closely observed on introduction of Sandostatin therapy and at each change of dosage. Marked fluctuations of blood glucose concentration may possibly be reduced by more frequent administration of Sandostatin.
Patients with type I diabetes mellitus requiring insulin therapy may have their insulin requirements reduced by administration of Sandostatin. In non-diabetic patients and patients with type II diabetes mellitus who have partially intact insulin reserves, Sandostatin administration can result in prandial increases in glycaemia (see Section 4.8 Adverse Effects (Undesirable Effects)). It is therefore recommended to monitor glucose tolerance and antidiabetic treatment.

Oesophageal varices.

Sandostatin administration to patients who have concomitant bleeding gastro-oesophageal varices due to underlying hepatic cirrhosis increases the risk of development of insulin dependent diabetes or of changes in insulin requirements in the presence of pre-existing diabetes. Therefore, appropriate monitoring of blood glucose levels is mandatory.

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.

Thyroid function.

Thyroid function should be monitored in patients receiving prolonged treatment with octreotide.

Use in hepatic impairment.

In patients with liver cirrhosis, the half-life of the drug may be increased. If this occurs, adjustment of the maintenance dose may be considered.

Use in renal impairment.

Impaired renal function did not affect the total exposure (AUC) to octreotide when administered subcutaneously. Therefore, no dose adjustment of Sandostatin is necessary.

Use in the elderly.

In elderly patients treated with Sandostatin, there was no evidence for reduced tolerability or altered dosage requirements.

Paediatric use.

Experience with Sandostatin in children is very limited.

Effects on laboratory tests.

See Section 4.4, Nutrition earlier in this section.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Many patients with carcinoid syndrome or VIPomas being treated with Sandostatin have also been or are being treated with many other drugs to control the symptomatology or progression of the disease, including chemotherapeutic agents, H2-antagonists, antimotility agents, drugs affecting glycaemic states, solutions for electrolyte and fluid support or hyperalimentation, antihypertensive diuretics and anti-diarrhoeal agents.
Octreotide has been reported to produce a reduction in the intestinal absorption of cyclosporin, and a delay in that of cimetidine.
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine.
Limited published data indicate that somatostatin analogues might decrease the metabolic clearance of compounds known to be metabolised by cytochrome P450 enzymes, possibly due to the suppression of growth hormone. Since it cannot be excluded that octreotide may have this effect, other drugs which are mainly metabolised by CYP3A4 and which have a low therapeutic index (e.g. quinidine) should be used with caution.
Since octreotide has also been associated with alterations in nutrient absorption, its effect on absorption of any orally administered drugs should be carefully considered.
Where symptoms are severe and Sandostatin therapy is added to other therapies used to control glycaemic states such as sulphonylureas, insulin, diazoxide, and to beta-blockers, calcium channel blockers or agents for the control of fluid and electrolyte balance, patients must be monitored closely and adjustment made in the other therapies as the symptoms of the disease are controlled. Evidence currently available suggests these imbalances in fluid and electrolytes or glycaemic states are secondary to correction of pre-existing abnormalities and not to a direct metabolic action of Sandostatin. Adjustment of the dosage of drugs, such as insulin, affecting glucose metabolism may be required during Sandostatin therapy (see Section 4.4 Special Warnings and Precautions for Use, Effects on glucose regulation).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

It is not known whether octreotide has an effect on human fertility. Reproduction studies have been performed in rats and rabbits at doses up to 1 mg/kg octreotide and have revealed no evidence of any adverse effect of subcutaneous octreotide on fertility or morphogenesis (see Section 4.6, Use in pregnancy).
(Category C)
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.
Sandostatin should only be prescribed to pregnant women under compelling circumstances.
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. Female patients of childbearing potential should be advised to use adequate contraception if necessary during treatment with octreotide.
Reproduction studies have been performed in rats and rabbits at doses up to 1 mg/kg and have revealed no evidence of any adverse effect of Sandostatin on fertility or morphogenesis. Foetal and postnatal growth retardation was seen in rats, probably due to suppression of growth hormone.
 It is unknown whether octreotide is transferred into human breast milk. Animal studies have shown transfer of octreotide in breast milk. Patients should not breastfeed during Sandostatin treatment.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

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. 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.

Tabulated summary of adverse drug reactions from clinical trials.

Adverse drug reactions (see Table 1) are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with 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.
Flushing and oedema, events attributable to the underlying condition, have been observed.

Adverse drug reactions from spontaneous reports and literature cases (frequency not known).

The following adverse drug reactions (Table 2) have been derived from post-marketing experience with octreotide via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorised as not known. ADRs are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness.

Description of selected adverse drug reactions.

Gastrointestinal disorders and nutrition.

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.
Occurrence of gastrointestinal side effects may be reduced by avoiding meals around the time of Sandostatin s.c. administration, that is, by injecting between meals or on retiring to bed.

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. Development of gallstones has been reported in 15-30% of long-term recipients of Sandostatin. The prevalence in the general population (aged 40 to 60 years) is estimated from reviews to be about 5-20%. The presence of gallstones or biliary sludge in Sandostatin-treated patients is largely asymptomatic. Symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery.

Injection site reactions.

Local reactions may occur and include pain, a sensation of stinging, tingling or burning at the site of injection, with redness, swelling, irritation and rash. They rarely last 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.

Cardiac disorders.

Bradycardia is a common adverse reaction with somatostatin analogues. In both acromegalic and carcinoid syndrome patients, arrhythmia and 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 were observed. 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, Cardiovascular related events).

Pancreatitis.

Acute pancreatitis has been reported in rare instances. Generally, the effect is seen within the first hours or days of Sandostatin treatment and resolves on withdrawal of the drug. In addition, pancreatitis may develop in patients on long-term Sandostatin treatment who develop gallstones.

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.

Thrombocytopenia.

Thrombocytopenia has been reported during post-marketing experience, particularly during treatment with Sandostatin (i.v.) in patients with cirrhosis of the liver. This is reversible after discontinuation of treatment.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

A limited number of accidental overdoses of Sandostatin in adults and children have been reported. In adults, the doses ranged from 2,400-6,000 microgram/day administered by continuous infusion (100-250 microgram/hour) over a period of 1 to 2 weeks or 3000 microgram/day (1000 microgram t.i.d. for 2 days) administered subcutaneously. Some of the adverse events reported included arrhythmia, hypotension, cardiac arrest, brain hypoxia, pancreatitis, hepatitis steatosis, diarrhoea, weakness, lethargy, weight loss, hepatomegaly and lactic acidosis.
Atrioventricular blocks (including complete atrioventricular block) were reported in patients receiving higher doses of continuous infusion (100 microgram/hour) and/or bolus of Sandostatin intravenously (50 microgram bolus followed by 50 microgram/hour continuous infusion).
In children, when Sandostatin was administered intravenously at a dose of 3000 microgram/day (500 microgram/hour) for 6 hours, mild hyperglycaemia was reported.

Treatment.

The management of overdosage is symptomatic. Patients who received higher than recommended doses of intravenous octreotide are at increased risk of higher degree atrioventricular blocks and should be kept under appropriate cardiac monitoring.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

Pharmacotherapeutic group: anti-growth hormone. ATC code: H01CB02.

5.1 Pharmacodynamic Properties

Mechanism of action.

Octreotide is a synthetic octapeptide analogue of naturally occurring somatostatin with similar pharmacological effects but with a considerably prolonged duration of action. It inhibits the secretion of serotonin and the gastro-entero-pancreatic peptides: gastrin, vasoactive intestinal peptide, insulin, glucagon, secretin, motilin, and pancreatic polypeptide; and of growth hormone (GH). Sandostatin, like somatostatin, decreases splanchnic blood flow.
In animals, octreotide is a more potent inhibitor of growth hormone, 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 growth hormone (GH) stimulated by arginine, exercise and insulin induced hypoglycaemia;
postprandial 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 secretion 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 (including those who have failed to respond to surgery, radiation or dopamine agonist treatment), Sandostatin lowers plasma levels of GH and insulin-like growth factor-1/somatomedin C (IGF-1). A reduction in plasma GH (by 50% or more) occurs in almost all patients, and a plasma GH < 5 nanogram/mL can be achieved in about half of the cases. Most patients with symptoms such as headache, skin and soft tissue swelling, hyperhidrosis, arthralgia, paraesthesia report a reduction in these symptoms. In patients with a large pituitary adenoma, Sandostatin treatment may result in some shrinkage of the tumour mass.
In patients with functional tumours of the gastro-entero-pancreatic endocrine system, Sandostatin, because of its diverse endocrine effects, modifies different clinical features. Clinical improvement and symptomatic benefit occur in patients who have severe symptoms related to their tumours despite previous therapies which include surgery, hepatic artery embolisation and various chemotherapies, e.g. streptozotocin and 5-fluorouracil.
Sandostatin's effects in the different tumour types are as follows:

Carcinoid tumours.

Administration of Sandostatin may result in improvement of symptoms, particularly of flush episodes and severe diarrhoea. In some cases this is accompanied by a fall in plasma serotonin and reduced urinary excretion of 5-hydroxyindole acetic acid. In the event of no beneficial response to Sandostatin treatment, continuation of therapy beyond one week at the maximum tolerated dose is not recommended, although in nonresponders no serious sustained adverse drug effects have been reported.

Vasoactive intestinal peptide secreting tumours (VIPomas).

The biochemical characteristic of these tumours is overproduction of vaso-active intestinal peptide (VIP). In most cases, administration of Sandostatin 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.
In patients with carcinoid syndrome and VIPomas, the effect of Sandostatin LAR on tumour size, rate of growth and development of metastases has not been determined.
For patients undergoing pancreatic surgery, the peri- and post-operative administration of Sandostatin reduces the incidence of typical post-operative complications (e.g. pancreatic fistula, abscess and subsequent sepsis, post-operative acute pancreatitis).
A large multicentre study in patients with acute bleeding due to gastric or duodenal ulcer showed no benefit of Sandostatin over placebo in the control of haemorrhage.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

After subcutaneous injection, octreotide is absorbed rapidly and completely from the injection site. Peak concentrations of 5.5 nanogram/mL (100 microgram dose) were reached 0.4 hours after dosing. In a single dose study, the absolute bioavailability after s.c. administration was found to be significantly different for different doses, however the interindividual variability was large. Relative to an equivalent intravenous dose, the bioavailability of a subcutaneous dose was estimated to be 80-135%. This was established based on the respective plasma concentrations determined by a radioimmunoassay. Peak concentrations and area under the curve values were dose proportional both after s.c. or i.v. single doses up to 400 microgram and with multiple doses of 200 microgram three times a day (600 microgram/day). Clearance was reduced by about 66% suggesting nonlinear kinetics of the drug at daily doses of 600 microgram/day as compared to 150 microgram/day. The relative decrease in clearance with doses above 600 microgram/day is not defined.

Distribution.

The distribution of octreotide from plasma was rapid (t1/2α = 0.2 hour) and the volume of distribution after i.v. dosing was estimated to be 0.27 L/kg bodyweight. In blood, the distribution into the erythrocytes was found to be negligible and about 65% was bound in the plasma in a concentration independent manner. Binding was mainly to lipoprotein and, to a lesser extent, to albumin.

Excretion.

The elimination of octreotide from plasma had an apparent half-life of 1.5 hours compared with 1 to 3 minutes with the natural hormone. The duration of action of Sandostatin is variable but extends up to 12 hours depending upon the type of tumour. About 32% of the dose is excreted unchanged into the urine.

Effect of renal and hepatic dysfunction on pharmacokinetics.

Impaired renal function did not affect the total exposure (AUC) to octreotide administered as a subcutaneous injection. Therefore, no dose adjustment is necessary. In patients with severe renal failure requiring dialysis, clearance was reduced to about half that found in normal subjects (from approximately 10 L/hour to 4.5 L/hour).
The elimination capacity may be reduced in patients with liver cirrhosis (see Section 4.4 Special Warnings and Precautions for Use, Use in hepatic impairment), but not in patients with fatty liver disease.

5.3 Preclinical Safety Data

Genotoxicity.

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 (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy). 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.

Carcinogenicity.

In repeat dose toxicity studies in rats, of 52 weeks duration and longer, predominantly in males, sarcomas were noted at the subcutaneous injection site of octreotide in an acidic vehicle and at a lower incidence with the acidic vehicle alone. These did not occur in a mouse carcinogenicity study, nor did hyperplastic or neoplastic lesions occur at the subcutaneous injection site in a 52 week dog toxicity study. There have been no reports of tumour formation at the injection sites in patients treated for up to 15 years with Sandostatin. All information available at present indicates that the finding of injection site sarcomas in rats is species specific and has no significance for the use of the drug in humans. The 116 week rat carcinogenicity study also revealed uterine endometrial adenocarcinomas, their incidence reaching statistical significance at the highest dose of 1.25 mg/kg/day. The presence of endometritis coupled with the absence of corpora lutea, the reduction in mammary fibroadenomas, and the presence of uterine dilatation, suggest that the uterine tumours were associated with oestrogen dominance in the aged female rats, which does not occur in humans.

6 Pharmaceutical Particulars

6.1 List of Excipients

Excipients: lactic acid, mannitol, sodium bicarbonate, water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2 - 8°C. (Refrigerate. Do not freeze.) Protect from light. For day to day use Sandostatin may be stored at room temperature (below 30°C) for up to 2 weeks. Any ampoules unused after this period out of the refrigerator should be discarded.

6.5 Nature and Contents of Container

Sandostatin solution for injection is packed in a 1 mL colourless glass ampoule with two colour code rings and a one-point cut.
0.05 mg octreotide in 1 mL comes in a box of 5 ampoules.
0.1 mg octreotide in 1 mL comes in a box of 5 ampoules.
0.5 mg octreotide in 1 mL comes in a box of 5 ampoules.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical name: D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl -N-[2-hydroxy -1-(hydroxymethyl) propyl]-L -cysteinamide cyclic (2→7)-disulfide.
MW: 1019.3 (free peptide).

Chemical structure.


CAS number.

79517-01-4. (octreotide acetate).

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes