Romiplostim-Geropharm (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Geropharm, LLC (Russia)

ATC Code

B02BX04 (Romiplostim)

Active Substance

Romiplostim (Rec.INN registered by WHO)

Dosage Forms

	Romiplostim-Geropharm	Lyophilisate for preparation of solution for subcutaneous administration 250 mcg
		Lyophilisate for preparation of solution for subcutaneous administration 500 mcg

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for subcutaneous administration

* Each vial contains an additional amount of the drug to ensure the extraction and administration of 250 mcg of romiplostim.

250 mcg – vials – carton packs – By prescription

Lyophilisate for preparation of solution for subcutaneous administration

* Each vial contains an additional amount of the drug to ensure the extraction and administration of 500 mcg of romiplostim.

500 mcg – vials – carton packs – By prescription

Clinical-Pharmacological Group

Thrombopoiesis stimulant

Pharmacotherapeutic Group

Hemostatic agents; vitamin K and other hemostatic agents; other systemic hemostatic agents

Pharmacological Action

Thrombopoiesis stimulant. Romiplostim is a representative of the class of thrombopoietin mimetics. It is an Fc-peptide fusion protein (peptibody) that signals and activates intracellular transcriptional pathways of the thrombopoietin receptor (also known as c-Mpl) to increase platelet production. The peptibody molecule consists of the Fc domain of human IgG1, in which each signaling chain subunit is covalently linked to the C-terminus of a peptide chain containing 2 thrombopoietin receptor-binding domains. Romiplostim is produced using recombinant DNA technology in an Escherichia coli culture.

Romiplostim increases platelet production by binding to and activating the thrombopoietin receptor, a mechanism similar to that of endogenous thrombopoietin. The thrombopoietin receptor is predominantly expressed on cells of the myeloid lineage, such as megakaryocyte progenitor cells, megakaryocytes, and platelets.

Clinical studies have shown that Romiplostim causes a dose-dependent increase in platelet count in patients with idiopathic thrombocytopenic purpura.

Pharmacokinetics

The plasma concentration of the active substance is characterized by individual variability and does not correlate with the administered dose.

The V_d and clearance of romiplostim are nonlinear because Romiplostim binds to thrombopoietin receptors and megakaryocytes, which determines its distribution in the body.

In patients with idiopathic thrombocytopenic purpura who received Romiplostim weekly for a long time (mean treatment duration was 39 weeks) in a dose range of 3-15 mcg/kg, the pharmacokinetic study showed T_max ranged from 7 h to 50 h after administration. T_1/2 ranged from 1 to 34 days.

Indications

Treatment of idiopathic thrombocytopenic purpura in adult patients with or without a spleen who have not responded to previous therapy with corticosteroids or immunoglobulins.

Treatment of chronic idiopathic thrombocytopenic purpura in children aged 1 year and older with or without a spleen who have not responded to previous therapy with corticosteroids or immunoglobulins.

ICD codes

Dosage Regimen

Administered subcutaneously. The initial dose is 1 mcg/kg of actual body weight, weekly, until the platelet count stabilizes at 50 × 10⁹/L or more for at least 4 weeks without dose adjustment. The dose is then adjusted depending on the platelet count in the blood. The duration of romiplostim use is determined individually, depending on the platelet count in the blood and the response to treatment.

To determine the dose in children aged 1 to 17 years, the child’s body weight should be monitored.

Adverse Reactions

From the hematopoietic system common – low platelet count in the blood (relapse of thrombocytopenia and bleeding after treatment discontinuation); increased platelet count in the blood, which may increase the risk of blood clotting (thrombotic/thromboembolic complications), bone marrow disorders, including increased bone marrow fiber content (increased reticulin deposition); uncommon – excessive thrombocythemia (due to overdose), which may increase the risk of blood clotting; decreased platelet count (due to insufficient dose), which may increase the risk of bleeding (medication errors); uncommon – bone marrow hematopoiesis suppression, myelofibrosis, enlarged spleen (splenomegaly); frequency unknown – increased blast cell count and worsening of myelodysplastic syndrome to acute myeloid leukemia, which is a type of malignant blood disease (progression of pre-existing myelodysplastic syndrome to acute myeloid leukemia).

From the digestive system common – nausea, diarrhea, abdominal pain, indigestion, constipation; uncommon – vomiting, bad breath, dysphagia, gastroesophageal reflux disease, blood in stool, abdominal discomfort, ulcerative lesions of the oral mucosa, tooth discoloration.

From the respiratory system very common – upper respiratory tract infections; common – pulmonary embolism; uncommon – nosebleed, cough, pharyngolaryngeal pain.

From the immune system very common – allergic reactions.

From the musculoskeletal system common – arthralgia, myalgia, back pain, limb pain, muscle spasms; uncommon – muscle tension, muscle weakness, shoulder pain, muscle twitching.

From the nervous system: very common – headache; common – dizziness, paresthesia, insomnia; uncommon – myoclonus, dysgeusia, hypogeusia, decreased sensitivity, especially of the skin (synesthesia), peripheral neuropathy, transverse sinus thrombosis, depression, unusual dreams, vertigo.

From the skin and subcutaneous tissues common – skin flushing, redness, rash, ecchymosis; uncommon – alopecia, photosensitivity, acne, contact dermatitis, eczema, dry skin, erythema, exfoliative rash, abnormal hair growth, prurigo, subcutaneous hemorrhage or bleeding, papular rash, itchy skin rash, urticaria, skin nodules.

From the blood coagulation system : common – hematomas; uncommon – vaginal bleeding, rectal bleeding, oral bleeding, hemorrhage at the injection site.

From the cardiovascular system uncommon – heart attack (myocardial infarction), increased heart rate.

From the organ of vision uncommon – conjunctival hemorrhage, difficulty focusing, blurred vision, accommodation disorder, congestive disc or eye disorders, blindness, itchy eye, increased lacrimation, visual disturbance.

From metabolism : uncommon – weight loss, weight gain, alcohol intolerance, loss of appetite (anorexia or decreased appetite), dehydration, gout, unusual body odor.

General disorders common – weakness, fever, asthenia, peripheral edema.

Immunogenicity Romiplostim has immunogenic potential. Neutralizing antibodies to romiplostim were observed in 1 case and did not have a neutralizing effect on endogenous thrombopoietin.

Contraindications

Hypersensitivity to romiplostim, Escherichia coli products.

Use in Pregnancy and Lactation

Adequate and strictly controlled studies of the safety of romiplostim during pregnancy and lactation have not been conducted. Use is not recommended, except in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

It is not known whether Romiplostim is excreted in human breast milk. Use during breastfeeding is not recommended. When deciding to discontinue breastfeeding or romiplostim therapy, the benefit of breastfeeding for the child and the benefit of romiplostim therapy for the mother should be considered.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Pediatric Use

Contraindicated for use in children under 1 year of age.

Special Precautions

When using romiplostim as part of combination therapy with other drugs for the treatment of idiopathic thrombocytopenic purpura, platelet count should be monitored to avoid side effects associated with thrombocytosis or thrombocytopenia.

After discontinuation of romiplostim, a relapse of thrombocytopenia is possible, which increases the risk of bleeding, especially when romiplostim is discontinued in the presence of antithrombotic agents. Such patients require careful clinical monitoring and measures to prevent bleeding.

In idiopathic thrombocytopenic purpura, reticulin was detected in the bone marrow of some patients before and during treatment with romiplostim. It is believed that the increase in reticulin content in the bone marrow is due to an increase in the number of megakaryocytes in the bone marrow with subsequent release of cytokines. In clinical studies of romiplostim, no adverse reactions associated with increased reticulin, cases of chronic idiopathic myelofibrosis or secondary myelofibrosis were observed; after discontinuation of romiplostim, the reticulin content decreased. Increased reticulin content is determined by bone marrow biopsy.

Bone marrow biopsy is performed if necessary to confirm the diagnosis of idiopathic thrombocytopenic purpura and to exclude other diseases, such as myelodysplastic syndrome (MDS). When using romiplostim against the background of MDS, the number of blast cells may increase and MDS may transform into acute myeloid leukemia.

Before starting and during therapy with romiplostim, an extended peripheral blood analysis with a count of formed elements should be performed to identify morphological abnormalities in blood cells. If new or worsening existing morphological abnormalities or cytopenia appear, Romiplostim should be discontinued and a bone marrow biopsy considered. Cytogenetic analysis of the bone marrow is also recommended.

If loss or insufficient effectiveness of romiplostim to maintain an adequate platelet count occurs, it should be considered that the cause may be the appearance of neutralizing antibodies to romiplostim and an increase in reticulin content in the bone marrow.

Use with caution in patients with impaired liver or kidney function.

Use in pediatrics

Romiplostim is not recommended for use in children under 1 year of age.

Effect on the ability to drive vehicles and mechanisms

Some adverse reactions to romiplostim (e.g., dizziness attacks) may impair the ability to drive vehicles and operate machinery.

Drug Interactions

When used concomitantly with anticoagulants or antiplatelet agents, the risk of bleeding increases.

If the patient is taking corticosteroids, danazol and (or) azathioprine for the treatment of idiopathic thrombocytopenic purpura, the dose of these drugs can be either reduced or discontinued during the use of romiplostim.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.