Octreotide depot, lyophilizate 20 mg

How to take, the dosage

V/m, deep into the gluteal muscle. For repeated injections the left and right sides should be alternated. Suspension should be prepared immediately before injection. On the day of injection, the bottle with the drug and the ampoule with the solvent can be kept at room temperature.

In the treatment of acromegaly in patients for whom p/c administration of Octreotide provides adequate control of disease manifestations, the recommended starting dose of Octreotide Depot is 20 mg every 4 weeks for 3 months. Treatment with Octreotide depot may be started the day after the last p/c injection of Octreotide. Subsequently, the dose is adjusted taking into account the serum concentrations of growth hormone and IGF-1 as well as clinical symptoms. If after 3 months of therapy the adequate clinical and biochemical effect was not achieved (in particular, if concentrations of growth hormone are higher than 2.5 µg/L), the dose can be increased up to 30 mg given every 4 weeks.

In cases where, after 3 months of treatment with Octreotide Depot at a dose of 20 mg, there is a steady decrease in serum concentration of growth hormone below 1 µg/L, normalization of IGF-1 concentration and disappearance of reversible acromegaly symptoms, the dose of Octreotide Depot may be reduced to 10 mg. However, in these patients receiving a relatively low dose of Octreotide Depot, serum concentrations of growth hormone and IGF-1 as well as symptoms of the disease should continue to be closely monitored.

Patients receiving a stable dose of Octreotide Depot should have their growth hormone and IGF-1 concentrations determined every 6 months.

Patients in whom surgical treatment and radiation therapy are ineffective or ineffective, as well as patients who require short-term treatment between courses of radiation therapy until its full effect develops, are recommended to have a trial course of treatment with Octreotide injections by injection to evaluate its effectiveness and overall tolerability and only then switch to Octreotide Depot according to the above scheme.

In the treatment of endocrine tumors of the gastrointestinal tract and pancreas in patients for whom pInjection of Octreotide provides adequate control of disease manifestations, the recommended starting dose of Octreotide Depot is 20 mg every 4 weeks. Pc administration of Octreotide should be continued for an additional 2 weeks after the first administration of Octreotide depot.

In patients who have not previously received Octreotide by injection, it is recommended that treatment be initiated with an injection of 0.1 mg of Octreotide three times daily for a relatively short period of time (approximately 2 weeks) to evaluate its effectiveness and overall tolerability. Only after that should Octreotide depot be administered according to the above scheme.

If therapy with Octreotide Depot for 3 months provides adequate control of clinical manifestations and biological markers of the disease, it is possible to reduce the dose of Octreotide Depot to 10 mg administered every 4 weeks.

In cases where only partial improvement has been achieved after 3 months of treatment with Octreotide Depot, the dose may be increased to 30 mg every 4 weeks. During treatment with Octreotide-depo on some days, clinical manifestations characteristic of endocrine tumors of the gastrointestinal tract and pancreas may worsen. In these cases, additional p/c injection of Octreotide at the dose used before the start of treatment with Octreotide-depo is recommended. This may occur primarily during the first 2 months of treatment until therapeutic plasma concentrations of Octreotide are achieved.

In the treatment of GERD, the recommended starting dose of Octreotide Depot is 20 mg every 4 weeks for 3 months. Thereafter, the dose is adjusted according to the dynamics of serum PSA concentrations and clinical symptoms. If after 3 months of treatment it was not possible to achieve adequate clinical and biochemical effect (decrease of PSA), the dose may be increased to 30 mg administered every 4 weeks.

The treatment with Octreotide depot is combined with the use of dexamethasone, which is administered orally according to the following regimen: 4 mg/d for 1 month, then 2 mg/d for 2 weeks, then 1 mg/d (maintenance dose).

The treatment with Octreotide depot and dexamethasone is combined with the use of a GnRH analogue in patients who were previously treated with medication-assisted antiandrogen therapy. In this case the injection of the GnRH analogue (depo-form) is carried out once every 4 weeks.

Patients receiving Octreotide depot should have their PSA concentrations determined every month.

In patients with impaired renal function, hepatic function and elderly patients there is no need to adjust the dosing regimen of Octreotide depot.

In order to prevent acute postoperative pancreatitis, Octreotide Depot in a dose of 10 or 20 mg is administered once no earlier than 5 days and no later than 10 days before the intended surgical intervention.

Regulations for suspension preparation and administration

• Prepare the drug only by injection;
• Prepare the suspension for injection by injection using the solvent provided immediately before administration;
• Before injection, the ampoule with the solvent and the bottle with the drug must be taken out of the refrigerator and brought to room temperature (requires 30-50 minutes);
• Vial with Octreotide-depo should be held strictly vertically. Gently tapping the vial to ensure that all lyophilizate is at the bottom of the vial;
• open the package with a syringe, attach a 1.2 × 50 mm needle to the syringe to draw the solvent;
• open the package with a syringe.
• open the solvent ampoule and draw the entire contents of the solvent ampoule into the syringe, set the syringe to a dose of 3.5 ml;
• remove the plastic cap from the vial containing the lyophilizate. Disinfect the rubber stopper of the bottle with an alcohol swab. Insert the needle into the vial with lyophilizate through the center of the rubber stopper and gently inject the solvent along the inner wall of the vial, without touching the contents of the vial with the needle. Take the syringe out of the vial;
• The vial should remain stationary until the lyophilizate is completely saturated with the solvent and the suspension is formed (about 3-5 minutes). After that, without turning the vial over, check the presence of dry lyophilizate on the walls and the bottom of the vial. If dry lyophilizate residue is found, leave the vial until it is completely saturated;
• After the healthcare professional is satisfied that there is no dry lyophilizate residue, the contents of the vial should be stirred gently with circular movements for 30-60 s until a homogeneous suspension is formed. Do not turn or shake the vial, this may cause flakes to fall out and the suspension to become unusable;
• Just insert the needle quickly through the rubber stopper into the vial. Then put the needle down and, tilting the vial at an angle of 45°, slowly draw the entire suspension into the syringe. Do not turn the vial upside down while filling. A small amount of the drug may remain on the walls and the bottom of the bottle. The consumption for the residue on the walls and the bottom of the vial is taken into account;
• After aspirating the suspension, change the needle with a pink pavilion for the needle with a green pavilion (0,8 × 40 mm), carefully turn the syringe upside down and remove the air from the syringe
• .
• inject the Octreotide-depo suspension immediately after preparation;
• The Octreotide-depo suspension must not be mixed with any other drug in the same syringe;
• disinfect the injection site with an alcohol swab. Insert the needle deep into the gluteal muscle, then pull the syringe piston back slightly to make sure there is no damage to the vessel. Slowly inject the suspension in/m with constant pressure on the syringe plunger;
• If it hits a blood vessel, change the injection site and the needle;
• If it hits a blood vessel, change the injection site and the needle;
• Introduce the suspension slowly, with constant pressure on the syringe plunger

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• If the needle is blocked, replace it with another needle of the same diameter;
• when injecting repeatedly, the left and right sides should be alternated.

Cautions for use

Pituitary tumors secreting growth hormone require close monitoring of patients because tumors can enlarge and develop serious complications such as narrowed visual fields. In these cases other treatment options should be considered.

In 15-30% of patients who receive Octreotide p/k for a long time, gallstones may occur. The prevalence in the general population (age 40-60 years) is 5-20%. The experience of long-term treatment with prolonged Octreotide in patients with acromegaly and tumors of the gastrointestinal tract and pancreas shows that prolonged Octreotide, compared to short-acting Octreotide, does not increase the frequency of gallstones formation. However, an ultrasound of the gallbladder is recommended before starting treatment with Octreotide depot and approximately every 6 months during treatment. Gallstones, if detected, are usually asymptomatic. If clinical symptoms are present, conservative treatment (e.g. use of bile acid preparations) or surgery is indicated.

In patients with type 1 diabetes mellitus, Octreotide Depot may affect glucose metabolism and therefore reduce the need for administered insulin. For patients with type 2 diabetes mellitus and patients without concomitant carbohydrate metabolism disorder, p/k injections of Octreotide may lead to postprandial glycemia. In this regard, it is recommended to monitor the blood glucose concentration regularly and, if necessary, to correct hypoglycemic therapy.

In patients with insulinomas during treatment with Octreotide an increase in severity and duration of hypoglycemia may be observed (this is due to a more pronounced suppressive effect on growth hormone and glucagon secretion than on insulin secretion, as well as a shorter duration of inhibitory effect on insulin secretion). Systematic follow-up of these patients is indicated.

Before prescribing octreotide, patients should have an initial ultrasound of the gallbladder.

An ultrasound of the gallbladder should be repeated during treatment with Octreotide depot, preferably at intervals of 6-12 months.

If gallstones are detected before treatment begins, the potential benefits of Octreotide depot therapy should be evaluated against the possible risks associated with the presence of gallstones.

There is currently no evidence that Octreotide Depot adversely affects the course or prognosis of pre-existing gallstone disease.

Management of patients whose gallstones form during treatment with Octreotide-depo

Asymptomatic gallstones. Use of Octreotide Depot can be discontinued or continued – according to a benefit/risk assessment. In either case, no other measures are required except to continue examinations, making them more frequent, if necessary.

Bladder stones with clinical symptoms. The use of Octreotide Depot can be discontinued or continued – according to the benefit/risk assessment. In any case, the patient should be treated as in other cases of gallstone disease with clinical manifestations. Medical treatment includes the use of combinations of bile acids (for example, chenodeoxycholic acid at a dose of 7.5 mg/kg/day combined with ursodeoxycholic acid at the same dose) under ultrasound monitoring until the stones have completely disappeared.

Interaction

Octreotide decreases intestinal absorption of cyclosporine and slows down absorption of cimetidine.

The bioavailability of Octreotide and bromocriptine is increased with concomitant use.

There is literature evidence that somatostatin analogues may decrease the metabolic clearance of substances metabolized by cytochrome P450 enzymes, which may be caused by growth hormone suppression. Because such effects of octreotide cannot be excluded, drugs metabolized by cytochrome P450 enzymes and with a narrow therapeutic range (quinidine and terfenadine) should be prescribed with caution.

Special Instructions

In pituitary tumors secreting GH, patients must be closely monitored, as tumors may increase in size and develop serious complications such as narrowing of the visual fields. In these cases, the need for other methods of treatment should be considered. In 15-30% of patients treated with Octreotide p/k for a long time, gallstones may occur.

The prevalence in the general population (age 40-60 years) is 5-20%. The experience of long-term treatment with prolonged-acting Octreotide in patients with acromegaly and tumors of the gastrointestinal tract and pancreas shows that prolonged-acting Octreotide, compared to short-acting Octreotide, does not increase the frequency of gallstones formation. However, an ultrasound examination of the gallbladder is recommended before starting treatment with Octreotide depot and approximately every 6 months during treatment.

The gallstones, if detected, are usually asymptomatic. If there are clinical symptoms, conservative treatment (such as the use of bile acids) or surgery is indicated. In patients with type 1 diabetes mellitus, Octreotide Depot may affect glucose metabolism and, therefore, reduce the need for injected insulin. For patients with type 2 diabetes mellitus and patients without concomitant carbohydrate metabolism disorder, p/c injections of Octreotide may result in postprandial glycemia.

In this regard, it is recommended to monitor glycemia levels regularly and, if necessary, to correct hypoglycemic therapy. In patients with insulinomas during treatment with Octreotide an increase in severity and duration of hypoglycemia may be noted (this is due to a more pronounced suppressive effect on GH and glucagon secretion than on insulin secretion as well as a shorter duration of inhibitory effect on insulin secretion).

Systematic follow-up of these patients is indicated. Patients should have an initial ultrasound of the gallbladder before prescribing Octreotide. During treatment with Octreotide depot, repeated ultrasounds of the gallbladder should be performed, preferably at intervals of 6-12 months.

If gallstones are detected before the start of treatment, the potential benefits of therapy with Octreotide Depot should be evaluated against the possible risks associated with the presence of gallstones. There is currently no evidence that Octreotide Depot adversely affects the course or prognosis of pre-existing gallstones.

Contraindications

Hypersensitivity to octreotide or other components of the drug.

With caution: cholelithiasis; diabetes mellitus; pregnancy and lactation.

Side effects

Local reactions: when injecting Octreotide-depo intramuscularly, pain, less often – swelling and rash at the injection site are possible (usually mild, short-lived).

Gastrointestinal disorders: anorexia, nausea, vomiting, spastic abdominal pain, abdominal distension, excessive gas, loose stools, diarrhea, steatorrhea. Although excretion of fat with feces may increase, to date there is no evidence that prolonged treatment with Octreotide may lead to the development of deficiency of some nutrients due to impaired absorption (malabsorption). In rare cases, phenomena resembling acute intestinal obstruction may be observed: progressive abdominal bloating, pronounced pain in the epigastric region, abdominal wall tension. Prolonged use of Octreotide-depo may lead to formation of gallstones in the gallbladder.

Pancreatic disorders: rare cases of acute pancreatitis developed during the first hours or days of use of Octreotide have been reported. With long-term use there have been cases of pancreatitis associated with cholelithiasis

Hepatic disorders: there have been isolated reports of the development of liver function disorders (acute hepatitis without cholestasis with normalization of transaminases after discontinuation of Octreotide); slow development of hyperbilirubinemia accompanied by elevation of ALP, GGT, and, to a lesser extent, other transaminases.

In metabolic disorders: since Octreotide Depot has an inhibitory effect on the formation of growth hormone, glucagon and insulin, it may affect glucose metabolism. Glucose tolerance may be decreased after a meal. With long-term use of Octreotidap/k, persistent hyperglycemia may develop in some cases. Hypoglycemic conditions have also been observed.

Others: in rare cases, temporary hair loss after administration of Octreotide, bradycardia, tachycardia, dyspnea, skin rash, anaphylaxis have been reported. There have been isolated reports of the development of hypersensitivity reactions.

Similarities

Sandostatin, Octreotide