SOMATOSTATIN GP PHARM 3 mg POWDER AND SOLVENT FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Somatostatin GP-Pharm 3 mg powder and solvent for solution for infusion EFG

Somatostatin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What Somatostatin GP-Pharm is and what it is used for
2. What you need to know before you use Somatostatin GP-Pharm
3. How to use Somatostatin GP-Pharm
4. Possible side effects
5. Storage of Somatostatin GP-Pharm
6. Contents of the pack and other information

1. What Somatostatin GP-Pharm is and what it is used for

Somatostatin is a polypeptide hormone consisting of fourteen amino acids, mainly identified in the hypothalamus and the digestive tract. Somatostatin GP-Pharm is a synthetic somatostatin identical to the natural one.

Somatostatin inhibits the secretion of numerous hormones such as somatotropin, corticotropin (ACTH), gastrin, insulin, and glucagon, as well as gastric and pancreatic secretions, both endocrine and exocrine. It also reduces the motility of the digestive tract and splanchnic blood flow.

Somatostatin GP-Pharm is indicated for:

• Treatment of digestive hemorrhages due to rupture of esophageal varices. It should always be applied in conjunction with other measures (sclerotherapy, surgery), which it complements but does not replace.
• Adjuvant in the treatment of pancreatic fistulas secreting at least 500 ml per day.

2. What you need to know before you use Somatostatin GP-Pharm

Do not use Somatostatin GP-Pharm:

• if you are allergic (hypersensitive) to the active substance or analogs of somatostatin or to any of the other components of this medicine (listed in section 6).
• if you are pregnant or breastfeeding.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Somatostatin GP-Pharm:

• if you have severe renal impairment (creatinine clearance ≤ 30 ml/min), you will be given half the recommended dose.
• the patient's blood glucose levels should be monitored at regular intervals (every 4-6 hours) when Somatostatin GP-Pharm is administered, as somatostatin has inhibitory effects on the release of glucagon and insulin.
• regular checks of renal function and plasma electrolytes should be performed, as treatment with Somatostatin GP-Pharm decreases the percentage of glomerular filtration, urine flow, and plasma sodium levels.
• Somatostatin GP-Pharm inhibits the secretion of other gastrointestinal hormones. Interruption of treatment may cause a rebound effect, especially in patients with fistulas; therefore, after healing, half the dose should be administered in a perfusion over the next 48 hours to prevent a rebound effect.
• if you are insulin-dependent, frequent blood glucose checks should be performed, as somatostatin has an inhibitory effect on insulin release.

In any case, your doctor will assess the convenience of using it in the hospital. Also, during treatment, you will be under strict medical observation at all times.

Other medicines and Somatostatin GP-Pharm

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Somatostatin may interact with drugs that influence the regulation of plasma glucose, plasma renin levels, and blood pressure.

The simultaneous administration of any form of sugar (including glucose, fructose, or total parenteral nutrition) may favor glycemic alterations and requires close monitoring of blood sugar. In some cases, insulin administration may be necessary.

Some cases of synergy (addition of effects) with cimetidine (a drug used to treat ulcers) have been described.

It prolongs the hypnotic effect (sedative) of barbiturates (drugs with sedative and hypnotic properties) and potentiates the action of penteprazol (a drug that reduces stomach acid secretion), so somatostatin should not be administered with these drugs, but rather, ongoing treatments should be suspended.

Using Somatostatin GP-Pharm with food and drinks

Cautious administration of any form of sugar is recommended (see Interaction of Somatostatin GP-Pharm with other medicines).

Pregnancy and breastfeeding:

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Somatostatin, due to its inhibitory action on growth hormone secretion, is contraindicated in pregnancy, during childbirth, and breastfeeding. In the case of administration to a breastfeeding mother, breastfeeding should be discontinued.

Driving and using machines:

Not applicable.

Somatostatin GP-Pharm contains sodium

This medicine contains less than 23 mg of sodium per dose; i.e., it is essentially "sodium-free).

3. How to use Somatostatin GP-Pharm

Follow the instructions for this medicine exactly as indicated by your doctor. In case of doubt, consult your doctor again.

Given its short half-life, 1 to 2 minutes, Somatostatin GP-Pharm should be administered through continuous and uniform intravenous perfusion to maintain plasma levels.

Somatostatin GP-Pharm should be reconstituted with physiological serum immediately before use and the resulting solution added to the perfusion fluid.

Patients should be closely monitored after treatment interruption.

Adults:

The recommended dose is 3.5 micrograms/kg/hour, or normally 6 mg/24 hours for a 75 kg patient, administered as a continuous perfusion of 250 micrograms/hour. The rate should be adjusted to 12 hours or 24 hours (for 3 mg and 6 mg, respectively).

Elderly patients:

Dose adjustment is recommended in elderly patients with severe renal impairment (see below, patients with renal impairment).

Children and adolescents:

Adequate clinical studies have not been conducted to establish the safety and efficacy of Somatostatin GP-Pharm in children and adolescents. Therefore, its use is not recommended in this patient population.

Patients with severe renal impairment:

The dose should be reduced to 1.75 micrograms/kg/hour in a continuous perfusion and 1.75 micrograms/kg for a loading dose.

Patients with hepatic impairment:

No dose adjustment is necessary in patients with hepatic impairment only.

In the treatment of gastrointestinal hemorrhages and esophageal variceal rupture, immediately after starting continuous perfusion, a loading dose of 250 micrograms should be administered through slow intravenous injection over a period of about 3 minutes to avoid the appearance of nausea and sensation of heat. DURING THE ADMINISTRATION OF THE LOADING DOSE, BLOOD PRESSURE SHOULD BE CLOSELY MONITORED. For this indication, the minimum treatment duration is 48 hours and the maximum duration is 120 hours (5 days).

Pancreatic fistulas require more prolonged treatment, and no initial loading dose is necessary. Fistula closure is usually achieved in most patients between 7 and 14 days of treatment, although shorter or longer periods are possible. It should be noted that while somatostatin reduces fistula output and may facilitate skin care around the stoma, it does not increase the number of fistula closures and therefore does not reduce the proportion of patients who ultimately require surgical closure. It also does not replace standard treatment measures. To avoid possible rebound effects after healing, half the dose (1.75 micrograms/kg/hour) should be infused over the next 48 hours.

If you use more Somatostatin GP-Pharm than you should

No cases of somatostatin overdose have been described.

If necessary, interrupt the perfusion and administer symptomatic treatment. There is no known specific antidote.

In case of overdose or accidental ingestion, consult the Toxicological Information Service, indicating the medicine and the amount ingested. Tel. 915 620 420.

If you forget to use Somatostatin GP-Pharm

Do not use a double dose to make up for forgotten doses.

If you stop using Somatostatin GP-Pharm

Abrupt or inadequate interruption of perfusion may cause a secretory rebound effect.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Common side effects (may affect up to 1 in 10 people) are: abdominal pain, nausea, hyperglycemia (elevated blood glucose), and flushing.

Uncommon side effects (may affect up to 1 in 100 people) are: diarrhea, decreased blood glucose (hypoglycemia), decreased heart rate (bradycardia), decreased blood pressure (hypotension), and increased blood pressure (hypertension).

Side effects for which there are no data to determine frequency are: atrioventricular block, arrhythmia, ventricular extrasystole, and vomiting.

At the start of perfusion, hypoglycemia may occur, followed possibly after 2 to 3 hours by an elevation of blood glucose due to alterations in the balance of counterregulatory hormones insulin and glucagon. Therefore, blood glucose levels should be monitored at regular intervals and simultaneous administration of any form of sugar (including glucose solutions) should be avoided. Insulin administration may be necessary.

Abrupt interruption of perfusion may cause a rebound effect, especially in the treatment of patients with fistulas.

During repeated treatments, the risk of hypersensitization (allergy) to somatostatin cannot be excluded.

If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet.

Reporting of side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines. Website: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Somatostatin GP-Pharm

Keep this medicine out of the sight and reach of children.

Store in a refrigerator at 2 to 8°C.

Validity period of reconstituted and diluted solutions:

After reconstitution with 1 ml of saline solution: Physical and chemical stability under conditions of use has been demonstrated for 24 hours at temperatures not exceeding 25°C.

After dilution: Physical and chemical stability under conditions of use has been demonstrated for 48 hours at temperatures not exceeding 25°C.

From a microbiological point of view, the product should be used immediately, unless the methods of dilution and reconstitution exclude the risk of microbiological contamination. If not used immediately, the storage times under conditions of use and the conditions prior to use will be the responsibility of the user.

Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Somatostatin GP-Pharm

The active substance is somatostatin. Each vial contains 3 mg of somatostatin (as hydrated acetate). The other components are hydrochloric acid or sodium hydroxide (for pH adjustment).

Each ampoule of solvent contains 1 ml of 0.9% sodium chloride solution. In the ampoules of solvent, the other components are hydrochloric acid (for pH adjustment) and water for injection.

Appearance of the product and pack contents

Somatostatin GP-Pharm is presented as a powder and solvent for solution for infusion. Each pack contains a vial and an ampoule of solvent. The clinical pack contains 25 vials and 25 ampoules of solvent.

Marketing authorization holder and manufacturer

GP-PHARM, S.A.

Pol. Ind. Els Vinyets-Els Fogars, 2. Ctra. C-244, Km 22

08777 Sant Quintí de Mediona – Barcelona

Spain

Date of last revision of this leaflet:07/2022

Other sources of information

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es

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This information is intended only for healthcare professionals:

Treatment should preferably be administered in the intensive care unit.

Patients under treatment with Somatostatin should be kept under strict medical observation. Perfusion should be administered slowly and continuously. When a 0.25 mg intravenous bolus is administered before perfusion, it should be infused slowly and continuously (over more than 3 minutes).

Somatostatin has a blocking action on the release of glucagon and insulin. Due to this action, blood glucose levels should be monitored at regular intervals of 4-6 hours during treatment; also, special attention should be paid to insulin-dependent patients.

It is recommended not to administer the drug with carbohydrates that require insulin for their metabolism and perfusion solutions containing glucose or fructose, to avoid glycemic alterations. In cases deemed appropriate, additional insulin doses may be administered.

Somatostatin produces inhibition of the intestinal absorption of certain nutrients. Therefore, parenteral nutrition should be administered concomitantly during prolonged treatment with Somatostatin.

In all cases, the patient should be monitored after withdrawal of the medicine.

Abrupt or inadequate interruption of perfusion may cause a secretory rebound effect.

During the 15 minutes following intravenous administration of the medicine, the patient should remain in a supine position.

Method of administration

1. Continuous perfusion administration:

1. The lyophilized powder should be reconstituted with 1 ml of physiological serum immediately before use. No special handling instructions are required, other than those for any injectable form.
2. This solution should be injected into the perfusion bottle.
3. Adjust the perfusion rate to the prescribed rate.

1. Administration of a 250 microgram loading dose

1. The 3 mg lyophilized powder should be reconstituted with 3 ml of physiological serum immediately before use (bearing in mind that the ampoule of solvent containing the product only contains 1 ml of physiological serum). No special handling instructions are required, other than those for any injectable form.
2. Take 0.25 mL of the obtained solution, corresponding to 250 micrograms, and inject it into the patient through slow intravenous injection over a period of about 3 minutes. If necessary, to facilitate bolus injection over 3 minutes, the 0.25 mL can be diluted with physiological serum up to an adequate volume (up to 5 mL).

Incompatibilities

Somatostatin is unstable at alkaline pH; therefore, its dissolution in solutions with a pH above 7.5 should be avoided.