Octreorom

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OКTREOROM (OCTREOROM)

Composition:

Active substance: octreotide;

1 ml of solution contains 0.1 mg octreotide (as octreotide acetate);

Excipients: lactic acid, mannitol, 1 M solution of sodium hydrocarbonate, water for injections.

Pharmaceutical form.

Solution for injection and infusion.

Main physicochemical properties: clear solution.

Pharmacotherapeutic group. Hormonal preparations for systemic use, excluding sex hormones and insulin. Hypothalamic and pituitary hormones and their analogues. Hypothalamic hormones. Somatostatin and analogues. Octreotide.

ATC code H01C B02.

Pharmacological properties.

Pharmacodynamics.

Octreotide is a synthetic octapeptide, a derivative of the natural hormone somatostatin, with similar pharmacological effects but significantly longer duration of action. The drug suppresses pathologically increased secretion of growth hormone (GH), as well as peptides and serotonin produced by the gastroenteropancreatic endocrine system.

In animals, octreotide is a more potent inhibitor of growth hormone, glucagon, and insulin release than somatostatin, with greater selectivity in suppressing growth hormone and glucagon.

In healthy individuals, octreotide suppresses:

• Growth hormone secretion stimulated by arginine, exercise-induced hypoglycemia, and insulin;
• Food-stimulated secretion of insulin, glucagon, gastrin, and other peptides of the gastroenteropancreatic endocrine system, as well as arginine-stimulated secretion of insulin and glucagon;
• Thyrotropin-releasing hormone (TRH)-stimulated secretion of thyroid-stimulating hormone (TSH).

Unlike somatostatin, octreotide suppresses growth hormone (GH) more than insulin, and its administration is not associated with rebound hypersecretion of hormones (i.e., GH in patients with acromegaly).

In patients with acromegaly, octreotide reduces plasma concentrations of GH and insulin-like growth factor-1 (IGF-1). Suppression of GH by 50% or more is observed in 90% of patients; reduction of GH plasma levels to below 5 ng/mL is achieved in approximately half of the patients. In most patients with acromegaly, octreotide significantly reduces the severity of symptoms such as headache, skin and soft tissue swelling, increased sweating, joint pain, and paresthesias. In patients with large GH-secreting pituitary adenomas, octreotide treatment may lead to some reduction in tumor size.

In patients with functional endocrine tumors of the gastrointestinal tract and pancreas, octreotide, due to its various endocrine effects, alters several clinical characteristics. Clinical and symptomatic improvement is observed in patients who still have tumor-related symptoms despite prior treatments, which may include surgery, hepatic artery embolization, and various chemotherapy regimens such as streptozotocin and 5-fluorouracil.

Effects of octreotide in tumors of different types are described below

Carcinoid tumors

In carcinoid tumors, octreotide administration may reduce the severity of symptoms such as flushing and diarrhea, often accompanied by decreased plasma serotonin concentration and reduced urinary excretion of 5-hydroxyindoleacetic acid.

VIPomas

In tumors characterized by overproduction of vasoactive intestinal peptide (VIP), octreotide administration reduces severe secretory diarrhea typical of this condition in most patients, thereby improving quality of life. Concurrently, associated electrolyte imbalances such as hypokalemia are reduced, allowing discontinuation of enteral and parenteral fluid and electrolyte supplementation. Computed tomography data indicate that in some patients, tumor progression slows or stops, and tumor size may even decrease, particularly liver metastases. Clinical improvement is usually accompanied by reduced (sometimes normalized) plasma concentrations of vasoactive intestinal peptide (VIP).

Glucagonomas

In glucagonomas, octreotide administration markedly reduces necrolytic migratory erythema, a characteristic feature of this condition, in most cases. Octreotide has no significant effect on mild diabetes mellitus commonly observed in glucagonomas and usually does not reduce the need for insulin or oral hypoglycemic agents. In patients suffering from diarrhea, octreotide helps reduce it, accompanied by weight gain. Octreotide often causes a rapid decrease in plasma glucagon concentration, although this effect is not sustained in most cases during prolonged treatment. Nevertheless, symptomatic improvement remains stable over a long period.

Gastrinomas/Zollinger–Ellison syndrome

Therapy with proton pump inhibitors or H2-receptor antagonists can reduce gastric acid secretion. However, diarrhea, another major symptom, may not be adequately relieved by proton pump inhibitors or H2-receptor blockers. In some patients, octreotide may further reduce gastric acid hypersecretion and alleviate symptoms, including diarrhea, by suppressing elevated gastrin levels.

Insulinomas

In patients with insulinomas, octreotide reduces immunoreactive insulin levels in blood. This effect, however, may be short-lived—approximately 2 hours. In patients with resectable tumors, octreotide may help restore and maintain normoglycemia in the preoperative period. In patients with unresectable benign or malignant tumors, glycemic control may improve even without sustained reduction in blood insulin levels.

Complications following pancreatic surgery

In patients undergoing pancreatic surgery, administration of octreotide during and after surgery reduces the frequency of typical postoperative complications (e.g., pancreatic fistulas, abscesses, sepsis, postoperative acute pancreatitis).

Gastrointestinal variceal bleeding

In patients with liver cirrhosis and bleeding from esophageal and gastric varices, octreotide administration in combination with specific treatments (e.g., sclerotherapy) leads to more effective control of bleeding, reduced incidence of early rebleeding, decreased transfusion requirements, and improved 5-day survival. Although the exact mechanism of action of octreotide is not fully established, it is believed that the drug reduces splanchnic blood flow by inhibiting vasodilatory hormones such as VIP and glucagon.

Pharmacokinetics.

Absorption

After subcutaneous administration, octreotide is rapidly and completely absorbed. Maximum plasma concentration is reached within 30 minutes.

Distribution

Plasma protein binding is 65%. Binding of octreotide to blood cells is negligible. Volume of distribution is 0.27 L/kg.

Elimination

Total clearance is 160 mL/min. Elimination half-life after subcutaneous injection is 100 minutes. After intravenous administration, the drug is eliminated in two phases, with half-lives of 10 and 90 minutes, respectively. The majority of the administered peptide dose is excreted in feces; approximately 32% is excreted unchanged in urine.

Special patient populations

Renal impairment

Impaired renal function does not affect the overall exposure (area under the concentration-time curve) of subcutaneously administered octreotide.

Hepatic impairment

Elimination capacity may be reduced in patients with liver cirrhosis, but not in patients with hepatic steatosis.

Clinical characteristics.

Indications.

• Acromegaly — for controlling the main manifestations of the disease and reducing plasma levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) in cases where surgical treatment and radiotherapy have not provided sufficient effect. Octreotide is also indicated for the treatment of patients with acromegaly who have refused surgery or have contraindications to it, as well as for short-term treatment during intervals between courses of radiotherapy until its full effect develops.
• Relief of symptoms associated with endocrine tumors of the gastrointestinal tract (GI) and pancreas:
  • carcinoid tumors with carcinoid syndrome;
  • VIPomas (tumors characterized by hyperproduction of vasoactive intestinal peptide);
  • glucagonomas;
  • gastrinomas/Zollinger–Ellison syndrome — usually in combination with histamine H2-receptor antagonists or proton pump inhibitors;
  • insulinomas (for control of hypoglycemia in the preoperative period, as well as for maintenance therapy);
  • somatoliberinomas (tumors characterized by hyperproduction of growth hormone-releasing factor).

Octreotide is not an antitumor agent, and its use cannot lead to cure in this group of patients.

• Prevention of complications following pancreatic surgery.
• Stopping bleeding and preventing recurrent bleeding from esophageal varices in patients with liver cirrhosis — in combination with specific therapeutic measures, e.g., endoscopic sclerotherapy.

Contraindications.

Hypersensitivity to octreotide or to any of the excipients of the drug.

Interaction with other medicinal products and other forms of interaction.

Dosage adjustment of medicinal products such as β-adrenergic blockers, calcium channel blockers, or agents used to control fluid and electrolyte balance may be required when used concomitantly with octreotide (see section "Special precautions").

Dosage adjustment of insulin and antidiabetic medicinal products may be required when used concomitantly with octreotide (see section "Special precautions").

It has been established that octreotide reduces intestinal absorption of cyclosporine and delays absorption of cimetidine.

Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine.

Limited published data indicate that somatostatin analogs may reduce the metabolic clearance of substances metabolized by cytochrome P450 enzymes, possibly due to inhibition of GH secretion. Since such an effect of octreotide cannot be excluded, caution should be exercised when using other drugs primarily metabolized by CYP3A4, as well as drugs with a narrow therapeutic index (e.g., quinidine, terfenadine).

Concomitant use with radiolabeled somatostatin analogs

Somatostatin and its analogs, such as octreotide, bind competitively to somatostatin receptors and may thus affect the efficacy of radiolabeled somatostatin analogs.

Administration of octreotide should be avoided within 24 hours prior to administration of lutetium (177Lu) oxodotreotide, a radiopharmaceutical agent that binds to somatostatin receptors.

Special precautions for use.

General

Since pituitary tumors secreting GH may occasionally enlarge, causing serious complications (e.g., visual field defects), careful monitoring of all patients is essential. If signs of tumor enlargement occur, the need for alternative treatment should be considered.

The therapeutic effect of lowering GH levels and normalizing IGF-1 concentrations in women with acromegaly may potentially restore fertility. During treatment with octreotide, women of childbearing potential should be advised to use adequate contraceptive methods (see also section "Use during pregnancy or breastfeeding").

Thyroid function should be monitored in patients receiving long-term octreotide therapy.

Liver function should be monitored during octreotide therapy.

Cardiovascular effects

Bradycardia has been frequently reported. Dose adjustments of drugs such as β-blockers, calcium channel blockers, and agents affecting fluid and electrolyte balance may be required (see section "Interaction with other medicinal products and other forms of interaction").

Cases of atrioventricular block (including complete atrioventricular block) have been observed in patients receiving high-dose continuous infusion (100 micrograms/hour) and in patients receiving intravenous bolus octreotide (50 micrograms bolus followed by 50 micrograms/hour continuous infusion). Therefore, the maximum dose of 50 micrograms/hour should not be exceeded (see section "Dosage and administration"). Patients receiving high-dose intravenous octreotide should be under appropriate cardiac monitoring.

Gallbladder-related effects

Cholelithiasis is frequently observed during octreotide therapy and may be associated with cholecystitis and bile duct dilation (see section "Adverse reactions"). In addition, cases of cholangitis as a complication of cholelithiasis have been reported in patients receiving octreotide in the post-marketing period. Therefore, ultrasound examination of the gallbladder is recommended before initiating octreotide therapy and approximately every 6–12 months during treatment.

Gastrointestinal and pancreatic endocrine tumors

During treatment of gastrointestinal and pancreatic endocrine tumors, a sudden loss of symptomatic control by octreotide, accompanied by rapid return of severe symptoms, may rarely occur. If treatment is discontinued, symptoms may worsen or recur.

Glucose metabolism

Due to its inhibitory effects on growth hormone, glucagon, and insulin, octreotide may affect glucose regulation. Glucose tolerance after food intake may be impaired, and persistent hyperglycemia may develop in some cases with continuous drug administration. Hypoglycemia may also occur.

In patients with insulinomas, hypoglycemia may become more intense and prolonged during octreotide treatment due to its relatively stronger inhibitory effect on GH and glucagon secretion compared to insulin, as well as due to its shorter inhibitory effect on insulin secretion. These patients should be closely monitored at the beginning of octreotide therapy and with each dose adjustment. Fluctuations in blood glucose concentration may be reduced by more frequent administration of lower doses of octreotide.

Insulin or oral hypoglycemic agent requirements in patients with type 1 diabetes may decrease under the influence of octreotide. In non-diabetic patients and in patients with type 2 diabetes who have partially intact insulin reserve, octreotide administration may lead to increased postprandial glycemia. Careful monitoring of glucose tolerance and antidiabetic therapy is recommended.

Esophageal varices

Since bleeding from esophageal varices may increase the risk of developing insulin-dependent diabetes or may alter insulin requirements in diabetic patients, appropriate monitoring of blood glucose concentration is mandatory.

Local reactions

In a 52-week toxicity study in rats, sarcomas were observed at the subcutaneous injection site, predominantly in males, but only at the highest dose (approximately 8 times the maximum human dose based on body surface area). In a 52-week toxicity study in dogs, no hyperplastic or neoplastic changes at the subcutaneous injection site were observed. There are no reports of tumor development at the injection site in patients treated with octreotide for up to 15 years. All available data indicate that the findings in rats are species-specific and not relevant to the use of the drug in humans.

Nutrition

Octreotide may impair fat absorption from food in some patients.

Decreased vitamin B12 levels and abnormal Schilling test results have been observed in some patients receiving octreotide therapy. Vitamin B12 levels should be monitored during Octreorom treatment in patients with a history of vitamin B12 deficiency.

Pancreatic function

Exocrine pancreatic insufficiency (EPI) has been observed in some patients receiving octreotide therapy for gastroenteropancreatic neuroendocrine tumors. Symptoms of EPI may include steatorrhea, loose stools, abdominal bloating, and weight loss. Screening and appropriate management of EPI according to clinical guidelines should be considered in symptomatic patients.

Sodium content

Octreorom contains less than 1 mmol (23 mg) of sodium, i.e., the preparation is essentially "sodium-free".

Use during pregnancy or breastfeeding.

Pregnancy

There is limited data (fewer than 300 outcomes) on octreotide treatment in pregnant women, but pregnancy outcomes are unknown in approximately one-third of cases. Most reports were from post-marketing use of octreotide, more than 50% of which involved pregnant patients with acromegaly. Most women received octreotide during the first trimester at doses of 100–1200 mcg/day as subcutaneous octreotide or 10–40 mg/month as octreotide LAR.

Congenital anomalies in the child were reported in approximately 4% of pregnancies with known outcomes. No association with octreotide use was established in these cases.

Animal studies did not reveal any direct or indirect harmful effects on reproductive performance.

As a precautionary measure, use of Octreorom during pregnancy is not recommended (see section "Special precautions for use").

Breastfeeding

It is unknown whether octreotide passes into human breast milk. Excretion of octreotide into breast milk has been observed in animal studies. Breastfeeding should not be continued during treatment with Octreorom.

Fertility

It is unknown whether octreotide affects human fertility. In male offspring of females treated with octreotide during pregnancy and lactation, delayed testicular descent was observed. However, in experimental studies, octreotide did not affect fertility in male and female rats at doses up to 1 mg/kg body weight per day.

Ability to influence reaction speed while driving or operating machinery.

Octreorom has no or negligible influence on the ability to drive or operate machinery. Patients should be advised to exercise caution when driving or operating machinery if they experience dizziness, asthenia/fatigue, or headache during treatment with Octreorom.

Method of Administration and Dosage

Dosage

In acromegaly, initially administer the drug subcutaneously at 0.05–0.1 mg every 8 or 12 hours. Subsequently, dose selection should be based on monthly measurements of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, clinical symptom assessment, and drug tolerability (target hormone concentrations: GH < 2.5 ng/mL, IGF-1 within normal range). For most patients, the optimal daily dose is 0.3 mg. The maximum daily dose is 1.5 mg, which should not be exceeded. In patients receiving a stable dose of Octreorel, GH and IGF-1 concentrations should be monitored every 6 months.

If adequate reduction in GH levels and improvement in clinical symptoms are not observed within 3 months of treatment with Octreorel, therapy should be discontinued.

In gastrointestinal and pancreatic endocrine tumors, administer the drug subcutaneously at an initial dose of 0.05 mg 1–2 times daily. Subsequently, depending on the achieved clinical effect, influence on tumor hormone levels (in carcinoid tumors, urinary excretion of 5-hydroxyindoleacetic acid), and tolerability, the dose may be gradually increased to 0.1–0.2 mg three times daily. Higher doses may be required in exceptional cases.

Maintenance doses should be individually adjusted.

If no improvement occurs within one week of treatment with Octreorel at the maximum tolerated dose in carcinoid tumors, further therapy is not recommended.

For prevention of complications after pancreatic surgery, administer the drug subcutaneously at 0.1 mg three times daily for 7 consecutive days, starting on the day of surgery (at least 1 hour before laparotomy).

In bleeding from esophageal varices, administer the drug at a dose of 25 mcg/hour by continuous intravenous infusion for 5 days. Octreorel may be diluted with 0.9% sodium chloride solution.

In patients with cirrhosis and bleeding from gastric and esophageal varices, good response to Octreorel has been observed with a stable dose of up to 50 mcg/hour as a continuous intravenous infusion for 5 days.

Use in patients with renal impairment

Renal impairment does not affect the overall exposure (area under the concentration-time curve [AUC]) of octreotide administered by subcutaneous injection. Therefore, dose adjustment of Octreorel is not required.

Use in patients with hepatic impairment

In patients with liver cirrhosis, the elimination half-life of the drug may be prolonged, necessitating adjustment of the maintenance dose.

Use in elderly patients

There is no evidence of reduced tolerability or need for dose adjustment in elderly patients receiving treatment with Octreorel.

Method of Administration

Octreorel may be administered directly by subcutaneous injection or by intravenous infusion after dilution.

The vial (50 mcg/1 mL or 100 mcg/1 mL) is intended for single use only; it should be opened immediately before administration, and any unused contents must be discarded.

Subcutaneous administration. A patient intending to self-administer the drug by subcutaneous injection must receive precise instructions from a physician or nurse.

To reduce local discomfort, it is recommended to wait until the solution reaches room temperature before administration. Repeated injections at the same site with short intervals should be avoided.

Intravenous infusion. Parenteral medicinal products should be carefully inspected for changes in color and presence of particulate matter before administration. Prior to intravenous infusion, the drug must be diluted. Octreorel maintains chemical and physical stability for 24 hours in sterile 0.9% sodium chloride solution or sterile 5% dextrose (glucose) in water. However, since Octreorel may affect glucose homeostasis, 0.9% sodium chloride solution is preferred over dextrose solution. The diluted solution maintains physical and chemical stability for at least 24 hours at temperatures up to 25°C. From a microbiological standpoint, the diluted solution should be used immediately. If not used immediately, the responsibility for duration and conditions of storage prior to use lies with the user.

Storage conditions after opening and after dilution

Octreotide maintains chemical and physical stability for 24 hours at 25°C in sterile 0.9% sodium chloride solution or sterile 5% dextrose (glucose) in water. However, since octreotide may affect glucose homeostasis, 0.9% sodium chloride solution is recommended over dextrose solution.

From a microbiological standpoint, unless the method of opening/dilution excludes the risk of microbial contamination, the diluted solution should be used immediately.

If the solution is not used immediately, the responsibility for duration and conditions of storage prior to use lies with the user.

Children

Octreorel is contraindicated in children due to lack of clinical experience.

Overdose

Limited cases of accidental octreotide overdose in adults and children have been reported. In adults, doses ranging from 2400–6000 mcg/day were administered via continuous infusion (100–250 mcg/hour) or subcutaneously (1500 mcg three times daily). Adverse events reported include arrhythmia, arterial hypotension, cardiac arrest, cerebral hypoxia, pancreatitis, hepatic steatosis, diarrhea, weakness, somnolence, weight loss, hepatomegaly, and lactic acidosis. Atrioventricular block (including complete atrioventricular block) has been reported in patients receiving higher doses of continuous infusion (100 mcg/hour) and/or bolus intravenous administration (50 mcg bolus followed by 50 mcg/hour continuous infusion).

In children, doses ranged from 50–3000 mcg/day administered via continuous infusion (2.1–500 mcg/hour) or subcutaneously (50–100 mcg). The only adverse event reported was mild hyperglycemia.

In cancer patients receiving octreotide at doses of 3000–30,000 mcg/day as individual subcutaneous doses, no unexpected adverse events were observed.

Treatment is symptomatic. Patients who have received intravenous octreotide at doses exceeding the recommended dose are at increased risk of developing higher-degree atrioventricular blocks and should be under appropriate cardiac monitoring.

Adverse Reactions

Short description of the drug safety profile

The most common adverse reactions associated with octreotide treatment involve the gastrointestinal tract, nervous system, liver and gallbladder, as well as metabolism and nutrition.

The adverse reactions most frequently reported during clinical trials with octreotide were: diarrhea, abdominal pain, nausea, flatulence, headache, cholelithiasis, hyperglycemia, and constipation. Other commonly reported adverse reactions included: dizziness, local pain, biliary concretions, thyroid dysfunction (e.g., decreased levels of thyroid-stimulating hormone, decreased total T4 levels, and decreased free T4 levels), loose stools, impaired glucose tolerance, vomiting, asthenia, and hypoglycemia.

List of adverse reactions in tabular form

The information on adverse reactions listed in Table 1 was obtained from clinical trials of octreotide.

Adverse reactions to the drug (Table 1) are presented by frequency: 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 case reports. Within each frequency category, adverse reactions are listed according to severity.

Adverse reactions reported during clinical trials

Table 1

Post-marketing studies

Adverse reactions listed in Table 2 have been reported voluntarily in spontaneous reports, and it is not always possible to reliably determine their frequency or establish a causal relationship to the use of the medicinal product.

Adverse reactions reported in spontaneous reports

Table 2

Description of individual adverse reactions

Biliary system disorders

Somatostatin analogues have been shown to inhibit gallbladder contractility and reduce bile secretion, which may lead to gallbladder pathology and sludge formation. Gallstone development has been observed in 15–30% of patients receiving long-term subcutaneous octreotide. The prevalence of this condition in the general population (aged 40–60 years) is 5–20%. Gallstone formation is usually asymptomatic. If symptoms occur, therapy with bile acid dissolution agents or surgical intervention should be considered.

Gastrointestinal disorders

In isolated cases, gastrointestinal adverse reactions may mimic acute intestinal obstruction—progressive abdominal distension, severe epigastric pain, abdominal tenderness, and rigidity.

It is known that the frequency of gastrointestinal adverse reactions decreases with continued treatment.

Gastrointestinal side effects may be minimized by avoiding food intake before or immediately after subcutaneous administration of octreotide. The drug should be administered between meals or at bedtime.

Hypersensitivity and anaphylactic reactions

During the post-marketing period, cases of hypersensitivity and allergic reactions have been reported. When such reactions occur, they predominantly affect the skin, and less frequently the oral cavity and respiratory tract. Isolated cases of anaphylactic shock have been reported.

Local reactions

Pain or sensations of pricking, pinching, or burning at the site of subcutaneous injection, accompanied by redness and swelling, rarely last longer than 15 minutes. Local discomfort may be reduced by allowing the solution to reach room temperature before injection or by administering a smaller volume of a more concentrated solution.

Metabolism and nutrition disorders

Although fecal fat excretion may increase, there are currently no data indicating that long-term octreotide treatment leads to nutritional deficiencies due to malabsorption.

Pancreatic disorders

Very rarely, acute pancreatitis has been reported. This phenomenon usually occurs within the first hours or days after subcutaneous octreotide administration and resolves upon discontinuation of the drug. Additionally, pancreatitis secondary to cholelithiasis may occur in patients receiving long-term subcutaneous octreotide.

Cardiovascular system disorders

Bradycardia is a common adverse reaction during treatment with somatostatin analogues. In patients with acromegaly and carcinoid syndrome, the following ECG changes have been observed: prolongation of the QT interval, axis deviation, early repolarization, low voltage, R/S transition, early R-wave progression, and non-specific ST-T wave changes. The relationship between these findings and octreotide has not been established, as many of these patients have underlying cardiovascular disease (see section "Special precautions").

Thrombocytopenia

During the post-marketing period, cases of thrombocytopenia, particularly in patients with liver cirrhosis receiving octreotide (intravenously), have been reported. This effect was reversible upon discontinuation of the drug.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after drug authorization is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

Store in the original packaging to protect from light at 2 to 8 °C.

Keep out of reach of children.

Storage conditions after opening and after reconstitution are described in the section "Instructions for use, handling and disposal".

Incompatibilities

This medicinal product must not be mixed with other medicinal products except those specified in the section "Instructions for use, handling and disposal". Octreotide acetate is not stable in solutions for total parenteral nutrition.

Packaging

1 ml in a vial, 3, 5, or 10 vials in a blister pack; 1 pack or 2 packs (with 10 vials) in a cardboard box.

Prescription status

Prescription only.

Manufacturer

C.T. ROMPHARM COMPANY S.R.L.

Manufacturer's address and location of operations

Str. Eroilor No. 1A, Otopeni, 075100, Ilfov County, Romania – Rompharm 1 and Rompharm 2 buildings