Октреотид

Octreotide® Instruction for use (English)

Solutio Octreotidi 0,005%; 0,01% - 1ml. In box 5 amp.
Registration number No: P No. 002374/01-2003

International nonproprietary name: octreotide

Dosage form: solution for injections

Composition

• Octreotide (as a free peptide), 50 mg or 100 mg;
• Sodium chloride, 9g;
• water for injections, up to 1 liter.

Description: a clear colorless liquid; odorless.

Pharmacotherapeutic group: somatostatin (H01CB02)

PHARMACOLOGICAL ACTIVITY

Octreotide is a synthetic octapeptide that is a derivative of the natural hormone somatostatin and has the pharmacological effects similar to the latter, which are of much longer action. The drug suppresses the pathologically enhanced secretion of growth hormone, as well as peptides and serotonin, which are produced in the gastro-entero-pancreatic endocrine system.

In patients operated on the pancreas, the intraoperative and postoperative use of Octreotide reduces the incidence of typical postoperative complications (such as pancreatic fistulas, abscesses, sepsis, acute postoperative pancreatitis).

Pharmacokinetics.

After subcutaneous administration, Octreotide is rapidly and completely absorbed. The maximum plasma concentration of the drug is achieved within 30 min.

Its plasma protein binding is 65%. The binding of Octreotide to blood forming elements is extremely slight. The volume of distribution is 0.27 l/kg.

Total clearance is 160 ml/min. About 32% are excreted via kidneys unchanged. After subcutaneous administration of the drug, its half-life (T_1/2) is 100 min. After intravenous injection, the drug is eliminated in two phases with T_1/2 with 10 and 90 min, respectively. In elderly patients, clearance decreases and T_1/2 increases. In severe renal failure, clearance halved.

INDICATIONS FOR USE

• the prevention and treatment of complications following operations on abdominal organs;
• hemostasis and the prevention of esophageal variceal re-hemorrhage in patients with hepatic cirrhosis;
• treatment of acute pancreatitis;
• arrest of ulcerative hemorrhages.

CONTRAINDICATIONS

Hypersensitivity to the components of the drug.
With caution in cholelithiasis, diabetes mellitus, pregnancy, lactation.

DOSAGE AND ADMINISTRATION

For the treatment of acute pancreatitis, the drug is subcutaneously injected in a dose of 100 μg thrice daily for 5 days. It may be given in a dose of as high as 1200 μg/day, by using the intravenous route of administration.

For the prevention of complications following operation on the pancreas, the first dose of 100-200 μg is subcutaneously injected an hour before laparotomy; then after surgery, 100-200 μg is cubcutaneously injected thrice daily for 7 consecutive days.

To arrest esophageal variceal hemorrhage, the drug is intravenously administered in a dose of 25-50 μg/h as prolonged infusions for 5 days. In elderly patients, the reduction of the dose of Octreotide is not required.

To arrest ulcerative hemorrhage, the drug is intravenously injected in a dose of 25 μg/hour as infusions for 5 days.

ADVERSE REACTIONS

Gastrointestinal, pancreatic, hepatic, and cholecystic: there may be anorexia, nausea, vomiting, spastic abdominal pain, a sensation of abdominal distention, excessive gas formation, loose stool, diarrhea, and steatorrhea. Although fecal fat excretion may increase, there is no envidence for that prolonged octreotide treatment may lead to the development of impaired absorption (malabsorption). In rare cases, there may be phenomena that mimics acute ileus.

There are known some cases of acute hepatitis without cholestasis, as well as hyperbilirubinemia in combination with the enhanced activity of alkaline phosphatase, gamma-glutamyltransferase and, to a less extent, other transaminases.

The long use of octreotide may give rise to cholelithogenesis.

Foreign references report about rare cases of acute pancreatitis that developed in the first hours or days of the use of Octreotide (Sandostatin) and disappeared after its discontinuance.

Cardiovascular: occasionally, arrhythmia, bradycardia.

Carbohydrate metabolic: there may be glucose intolerance after meals (due to the drug-induced suppression of insulin secretion), hypoglycemia; rarely, prolonged therapy may cause persistent hyperglycemia.

Local: there may be pain, a sensation of itch or burning, redness, and swelling at the site of injection (they usually disappear within 15 min).

Other: allergic reactions, alopecia.

OVERDOSAGE

They may be the following symptoms: a short-term reduction in heart rate, a sensation of facial flush, spastic abdominal pain, diarrhea, nausea, a sensation of empty stomach.
Treatment: symptomatic.

DRUG INTERACTIONS

Octreotide reduces the absorption of cimetidine, cyclosporin.

The doses of concomitantly used diuretics, beta-adrenoblockers, calcium blockers, insulin, oral hypoglycemic drugs should be adjusted.

With co-administration of octreotide and bromocriptine, the bioavailability of the latter increases.

The drugs that are metabolized by cytochrome P450 enzymes and have a narrow therapeutic range of doses should be cautiously used.

PRECAUTIONS

In patients with diabetes mellitus who receive insulin, octreotide may reduce insulin needs.

If choleliths are detected before treatment, a decision on the use of octreotide is taken individually depending on the ratio of the drug’s potential therapeutic effect to the possible risk factors associated with the stones in the gallbladder.

Gastrointestinal adverse reactions may be diminished if octreotide injects are made at meal intervals or before sleep.

To ameliorate the signs of discomfort at the site of injection, the solution of the drug should be brought to room temperature before injection and administered in less volume. Several injections made at the same site at short intervals should be avoided.

USE IN PREGNANCY AND LACTATION

No adequate and controlled human studies have been performed. The drug is used during pregnancy and lactation if this absolutely indicated, by taking into account a risk/benefit ratio, i.e. when expected maternal benefits overweigh possible fetal risks. The category of its fetal effect is B.

How supplied: 1 ml in an ampoule; 5 ampoules in a blister, 1 or 2 blisters in a package. 5 or 10 ampoules in a pack.

Storage: List B. Store in a light-protected place at a temperature of 8° to 20°; keep out of the reach of children.

Shelf-life: 5 years. Do not use after its expiry.

Dispensing: to be prescribed.

Manufacturer:

“Pharm-Sintez” CJSC,
15 Vavilov St., Moscow 117132, Russia.