Octreotide - instructions for use, dose, side effects, contraindications

Octreotide - a synthetic octapeptide, a derivative of the natural hormone somatostatin, has similar pharmacological effects, but with a much longer duration of action. Octreotide suppresses both pathologically increased secretion of growth hormone (GH), and caused by arginine, exercise and insulin hypoglycemia. The drug inhibits the secretion of serotonin, gastrin, insulin and glucagon and other peptides produced in the gastroenteropancreatic endocrine system. In patients undergoing pancreatic surgery, the use of octreotide during and after surgery reduces the incidence of typical postoperative complications (acute postoperative pancreatitis, pancreatic fistula, abscesses, sepsis).

When bleeding from varicose veins of the esophagus and stomach in patients with cirrhosis of the liver, the use of octreotide as part of complex therapy leads to an effective stopping of bleeding, preventing early re-bleeding and improving survival. The mechanism of action of octreotide is associated with a decrease in organ blood flow by suppressing vasoactive hormones (vasoactiveintestinal peptide, glucagon).

Pharmacokinetics:

After subcutaneous administration octreotide quickly and completely absorbed. It is known that the maximum concentration in the plasma is reached within 30 minutes. Binding to plasma proteins is about 65%. The binding of octreotide to the formed elements of the blood is extremely insignificant.

Most of the drug is excreted by the intestine, about a third of the octreotide administered is excreted unchanged by the kidneys. The half-life (T_1/2) after subcutaneous (SC) injection for about 100 minutes. After intravenous (IV) injection, excretion is carried out in two phases. In elderly patients the clearance decreases, the half-life increases. In severe renal failure, the clearance is halved.

Indications:

- Preventive maintenance and treatment of complications after operations on a pancreas and gastroduodenal zone;

- as part of complex therapy to stop bleeding and prevent rebleeding from varicose veins of the esophagus in patients with cirrhosis of the liver;

- treatment of acute pancreatitis;

- stop bleeding for peptic ulcer and 12 duodenal ulcer.

Contraindications:

Hypersensitivity to the components of the drug.

Carefully:

Diabetes mellitus, cholelithiasis.

Pregnancy and lactation:

Adequate and controlled studies have not been conducted. Application during pregnancy and lactation only on absolute indications, taking into account the risk / benefit ratio, i.e. when the intended benefit to the mother exceeds the estimated risk for the fetus or infant.

Dosing and Administration:

When treatment of acute pancreatitis Octreotide injected sc in a dose of 100 mcg 3 times / day for 5-7 days. It is possible to appoint up to 1200 μg / day, the dose selection is based on the determination of the concentration of amylase, lipase, inflammatory blood cytokines.

For prevention of complications after operations on the pancreas The first dose of Octreotide is 100 μg injected sc for 1 hour before laparotomy; then after the operation, enter sc in 100 μg 3 times / day for 7 consecutive days.

For stop bleeding from varicose veins of the esophagus the drug is administered iv at a dose of 25 mcg / h in the form of continuous infusions for 5 days.

For stop bleeding with peptic ulcer and 12 duodenal ulcer it is recommended that Octreotide in the form of intravenous infusions in a dose of 25 mcg / h for 5 days.

In elderly patients, there is no need to reduce the dose of Octreotide.

Patients with impaired renal function correction of the dosage regimen octreotide is not required.

Patients with impaired hepatic function correction of the maintenance dose is recommended. there are data on the increase in T_1/2octreotide in patients with cirrhosis of the liver.

The experience with octreotide in children is very limited.

Rules for the preparation and administration of a solution

To reduce the effects of discomfort at the injection site, the Octreotide solution should be at room temperature before administration.

With n / to the introduction drug, several injections should be avoided in the same place at short intervals. Ampoules with the drug should be opened immediately before administration, unused amount of solution should be destroyed.

With iv introduction should carefully inspect the solution for transparency, the presence of particles, sediment, discoloration. Do not use the drug if it is cloudy, contains particles, sediment. Octreotide for 24 hours retains physical and chemical stability in a sterile 0.9% solution of sodium chloride at a temperature of 8 to 25 ° C. To avoid microbial contamination, dilute solutions should be used immediately after preparation. If the solution is not used immediately, it should be stored at a temperature of 2 to 8 ° C until it is applied. Before use, the solution should be held at room temperature.

The total time between dilution, storage in the refrigerator and the end of the administration of the solution should not exceed 24 hours.

If necessary, in / in the injection, the contents of one ampoule containing 300 μg octreotide should be diluted in 60 ml of 0.9% sodium chloride solution, the prepared solution should be injected intravenously into the drip. Infusions are repeated at the required frequency in accordance with the recommended duration of treatment. Octreotide can also be administered at lower concentrations.

Side effects:

Local Reactions: at the injection site, pain, itching or burning sensation, redness and swelling are possible (usually within 15 minutes).

From the gastrointestinal tract, pancreas, liver and gallbladder: possible - anorexia, nausea, vomiting, abdominal cramps, a sensation of bloating, excessive gas formation, loose stools, diarrhea and steatorrhea. Although the release of fat with feces may increase, there is no indication that prolonged treatment with octreotide can lead to impaired absorption (malabsorption). In rare cases, there may be phenomena reminiscent of acute intestinal obstruction: progressive bloating, severe pain in the epigastric region, stress of the abdominal wall.

Long-term use of octreotide can lead to the formation of stones in the gallbladder.

There are isolated cases of acute hepatitis without cholestasis (normalization of transaminases after octreotide abolition), as well as hyperbilirubinemia in combination with an increase in the activity of alkaline phosphatase, gamma-glutamyltransferase and other transaminases.

There are isolated reports of rare cases of acute pancreatitis that developed during the first hours or days of octreotide.

From the side of the cardiovascular system: in some cases - tachycardia, bradycardia.

From the side of metabolism: a violation of glucose tolerance after eatingoctreotide has an overwhelming effect on the formation of GR, glucagon and insulin), hypoglycemia; In rare cases, long-term treatment may develop persistent hyperglycemia.

Other: rarely - allergic reactions, alopecia; in some cases - anaphylactic reactions.

Overdose:

It is known that the administration of octreotide in a dose of up to 2000 micrograms in the form of a sc injection 3 times for several months was well tolerated.

The maximum single dose for iv bolus administration to an adult patient was 1000 μg. Symptoms such as decreased heart rate, blood flushes to the face, abdominal pain of a spastic nature, diarrhea, nausea, a feeling of emptiness in the stomach were noted. All these symptoms resolved within 24 hours of the administration of the drug.

One patient, by mistake with the method of prolonged infusion, was administered an excessive dose of octreotide 250 μg / h (instead of 25 μg / h), which was not accompanied by side effects.

In acute overdose, there were no life-threatening reactions.

Treatment: symptomatic therapy.

Interaction:

Octreotide reduces the absorption of cyclosporine, slows the absorption of cimetidine.

It is necessary to adjust the doses of simultaneously used diuretics, beta-blockers, blockers of "slow" calcium channels, insulin, oral hypoglycemic drugs.

With the simultaneous use of Octreotide and bromocriptine, the bioavailability of the latter increases.

Drugs metabolized by enzymes of the cytochrome P450 system and having a narrow therapeutic dose range (for example, quinidine, terfenadine) should be administered with caution.

Special instructions:

In patients with type 1 diabetes (receiving insulin), octreotide can reduce the need for insulin. In patients without a violation of carbohydrate metabolism and patients with type 2 diabetes, the administration of the drug may lead to postprandial glycemia. Patients with diabetes mellitus on the background of hypoglycemic therapy are encouraged to monitor blood glucose concentrations.

In some patients octreotide can change the absorption of fats in the intestine. Against the background of octreotide, a decrease in the content of cyanocobalamin (a vitamin B₁₂) and the deviation from the norm of the indices of the cyanocobalamin absorption test (Schilling test).

In patients with vitamin B deficiency₁₂ in the history of the use of octreotide is recommended to monitor the content of cyanocobalamin.

If bradycardia develops with the use of octreotide, it is necessary to reduce the dose of beta adrenoblockers, blockers of "slow" calcium channels or drugs that affect the water-electrolyte balance.

Before the appointment of octreotide, patients should undergo an initial ultrasound of the gallbladder.

If gallstones are detected before treatment, the question of the use of Octreotide is decided individually, depending on the ratio of the potential therapeutic effect of the drug and the possible risk factors associated with the presence of gallstones.

During treatment with octreotide, ultrasound of the gallbladder should be performed, with an interval of 6-12 months.

Management of patients whose gallstones are formed during treatment with octreotide

a) Asymptomatic stones of the gallbladder.

The use of octreotide can be discontinued or continued - according to the benefit / risk ratio estimate. In any case, no other measures are required, except to continue inspections, making them, if necessary, more frequent.

b) Stones of the gallbladder with clinical symptoms.

The use of octreotide can be discontinued or continued - according to the benefit / risk ratio estimate. In any case, the patient should be treated in the same way as in other cases of cholelithiasis with clinical manifestations.

Gastrointestinal side effects can be reduced if Octreotide injections are done in between meals or at bedtime.

It is necessary to correct the dosage regimen of concomitantly used diuretics, beta-blockers, slow calcium channel blockers, insulin, oral hypoglycemic agents, glucagon.

Effect on the ability to drive transp. cf. and fur:

To date, there is no evidence of the effect of octreotide on the ability to drive a car and work with mechanisms.

Form release / dosage:

Solution for intravenous and subcutaneous administration, 50 μg / ml, 100 μg / ml, 300 μg / ml.

Packaging:

When manufacturing at Nativa, Russia

1 ml per ampoule of neutral glass HC-1 or glass I hydrolytic class. It is possible to pack into ampoules having a ring of tension for opening or a break point.

5 ampoules per contour cell package from polymer film.

1 or 2 contiguous cell packs, ampoule opener or ampoule scarifier and instructions for use are placed in a cardboard box.

When you pack the solution into ampoules that have a tension ring for dissection, or into ampoules with a fracture point, the knife or scarifier is not injected into the ampoule.

In production at OAO Farm-standard-UfaVITA, Russia.

1 ml per ampoule of glass I hydrolytic class.

5 ampoules per circuit cell packaging made of polyvinylchloride film and aluminum foil or without foil.

1 or 2 contour squares, together with instructions for use, are placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003582/10

Date of registration:29.04.2010 / 07.07.2016

Expiration Date:Unlimited

The owner of the registration certificate:NATIVA, LLC NATIVA, LLC Russia

Manufacturer: & nbsp

FARMSTANDART-UFAVITA, JSC Russia

NATIVA, LLC Russia

Information update date: & nbsp02.06.2017

Illustrated instructions

Instructions

Octreotide (Octreotide)