Velcade - Instructions For Use, Price, Reviews, Analogs, Doses

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Welcade

Velcade: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacodynamics and pharmacokinetics
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Drug interactions
14. 14. Analogs
15. 15. Terms and conditions of storage
16. 16. Terms of dispensing from pharmacies
17. 17. Reviews
18. 18. Price in pharmacies

Latin name: Velcade

ATX code: L01XX32

Active ingredient: Bortezomib (Bortezomib)

Manufacturer: Ben Venue Laboratories Inc. (USA), Pierre Fabre Medicament Production (France), BSP Pharmaceuticals S.r.l. (Italy), Pharmstandard-UfaVITA (Russia)

Description and photo update: 2019-05-08

Velcade is an antineoplastic agent.

Release form and composition

Dosage form - lyophilisate for preparation of a solution for intravenous (IV) and subcutaneous (s / c) administration: white or almost white lyophilized mass or powder (in a blister 1 glass bottle with a capacity of 10 ml, in a cardboard box 1 blister).

The active ingredient of Velcade is bortezomib (PS-341), in 1 bottle - 3.5 mg.

Auxiliary components: mannitol, nitrogen.

Pharmacodynamics and pharmacokinetics

Bortezomib, the active ingredient of the drug, is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that cleaves proteins linked to ubiquitin. This ubiquitin-proteasome pathway is key in the regulation of the concentration of certain cellular proteins and ultimately maintains intracellular homeostasis. By suppressing the activity of the proteasome, such selective proteolysis is prevented, which can affect entire cascades of signal transduction reactions in the cell. If the self-regulation mechanism is violated, the cell may die. In experiments on living cells, bortezomib slowed tumor growth in a variety of experimental models, including multiple myeloma.

In experiments in vitro, on living tissues in an artificial environment and in animal models, the drug inhibited the function of osteoclasts and increased the activity and differentiation of osteoblasts. Similar effects were observed in patients with multiple myeloma and multiple foci of osteolysis who received Velcade.

When the drug is administered intravenously at doses of 1 mg / m² and 1.3 mg / m² to patients with multiple myeloma, the maximum plasma concentrations of bortezomib are 57 ng / ml and 112 ng / ml, respectively. With subsequent injections of Velcade, the maximum plasma concentrations are in the ranges 67-106 ng / ml (with a dose of 1 mg / m²) and 89-120 ng / ml (with a dose of 1.3 mg / m²). The half-life of bortezomib with repeated administration is in the range of 40-193 hours.

After the first dose, Velcade is excreted faster than with repeated infusions. The average total clearance after the first injection is 102 l / h and 112 l / h for doses of 1 mg / m² and 1.3 mg / m², respectively, and after repeated injections - 15 l / h and 32 l / h.

The maximum concentration of the active substance after subcutaneous administration of the drug is lower than after intravenous administration.

Bortezomib is believed to be extensively distributed in peripheral tissues. At a concentration of 100-1000 ng / ml, the drug is about 83% bound to plasma proteins. The fraction associated with plasma proteins does not depend on the concentration of bortezomib.

The metabolism of the drug in vitro is mainly carried out by the following cytochrome P450 isoenzymes: CYP1A2, CYP3A4 and CYP2C19. The main metabolic pathway is the elimination of boron atoms and the formation of two metabolites, which are hydroxylated later with the formation of other metabolites. The drug metabolites are unable to inhibit the 26S proteasome.

Excretion routes of the drug in humans have not been studied.

No information is available on the effects of age, race, and gender on Velcade pharmacokinetics.

In patients with mild hepatic dysfunction, the pharmacokinetics of bortezomib did not change. With moderate or severe impairment of liver function, there is an increase in AUC (area under the concentration-time curve) by 60% compared with patients with normal liver function. For patients with moderate and severe hepatic impairment, it is recommended to reduce the initial dose of the drug. Such patients should be under constant supervision.

Intravenous administration of bortezomib at doses of 0.7–1.3 mg / m² twice a week to patients with impaired renal function of varying severity (including patients on dialysis) did not significantly change the pharmacokinetics of the drug.

Indications for use

• Mantle cell lymphoma in patients with at least 1-line previous therapy;
• Multiple myeloma.

Contraindications

• Lesion of the pericardium;
• Acute forms of infiltrative and diffuse lung pathologies;
• Childhood;
• The period of pregnancy and breastfeeding;
• Hypersensitivity to boron, mannitol, bortezomib.

According to the instructions, Velcade should be used with caution in patients with severe renal impairment, moderate to severe liver dysfunction, a history of seizures or epilepsy, a history of diabetic neuropathy, fainting, dehydration after vomiting or diarrhea, at the risk of developing chronic heart failure, concurrent taking antihypertensive drugs, constipation; in combination with oral hypoglycemic agents, substrates of the CYP2C9 isoenzyme, inhibitors or substrates of the CYP3A4 isoenzyme.

Instructions for the use of Velcade: method and dosage

Velcade is indicated for intravenous and subcutaneous administration.

Handling the drug requires caution, adherence to strict rules of asepsis. Treatment should take place in a stationary environment, with the involvement of specialists who have experience in handling anticancer drugs.

Only 0.9% sodium chloride solution can be used to dissolve the lyophilisate. The finished solution should have a transparent, colorless structure, in case of color change or the presence of any inclusions in it, it cannot be used.

The concentration of the solution for intravenous administration should be 1 mg / ml, therefore the contents of the vial should be dissolved in 3.5 ml of 0.9% sodium chloride solution. The finished solution is injected through a central venous or peripheral catheter by intravenous bolus injection for 3-5 seconds. After the procedure, the catheter should be flushed with 0.9% sodium chloride solution.

The concentration of the solution for subcutaneous administration should be 2.5 mg / ml, therefore 1.4 ml of 0.9% sodium chloride solution should be added to the contents of the vial. Subcutaneous injection is indicated in the right or left thigh or abdomen with constant alternation and no closer than 2.5 cm from the previous injection site. Do not make subcutaneous injection into sensitive or damaged areas of the body. When local reactions appear, you should switch to intravenous administration or reduce the concentration of the solution to 1 mg / ml.

For monotherapy, intravenous jet and subcutaneous administration of Velcade is indicated.

Recommended dosage: the initial dose is 1.3 mg per 1 m ² of body surface on days 1, 4, 8 and 11 for 2 weeks, from 12 to 21 days - a 10-day break. An interval of at least 72 hours should be observed between procedures (administration of doses).

The degree of clinical response is assessed after 3 and 5 cycles of therapy; upon reaching a complete clinical response, it is additionally recommended to carry out two cycles of treatment.

If more than 8 treatment cycles are prescribed, a standard or maintenance therapy regimen can be used, in which the drug is administered for 4 weeks on days 1, 8, 15 and 22, followed by a rest period of 13 days (from 23 to 35).

In the absence of a clinical response, disease progression after 2 cycles or stabilization of the disease after 4 cycles, it is possible to prescribe the drug in combination with high doses of dexamethasone. Dexamethasone is prescribed at a dose of 40 mg orally with each dose of Velcade, which is divided into 2 doses: 20 mg on the day of drug administration and 20 mg on the first day after administration. Thus, within 3 weeks, the patient takes a total dose of dexamethasone in the amount of 160 mg (on days 1, 2, 4, 5, 8, 9, 11 and 12).

In case of development of any non-hematological toxic effect of the 3rd degree (except for neuropathy) or hematological toxicity of the 4th degree, treatment should be suspended until the complete absence of symptoms of toxicity. The therapy should be resumed at a dose reduced by 25%.

When peripheral sensory neuropathy and / or neuropathic pain appears on the background of Velcade therapy, the dose of the drug is adjusted in accordance with the severity of the pathology. At grade 1 (without loss of function and pain), peripheral neuropathy is not corrected, at grade 1 with pain and dysfunction (grade 2) - the dose of the drug is reduced to 1 mg per 1 m ² of body surface, at grade 2 with pain and grade 3 (violation of daily activity) - therapy should be suspended until toxicity disappears completely. Then the treatment is resumed at a dose of 0.7 mg per 1 m ² with a frequency of administration once a week. At 4 degrees of severity of peripheral neuropathy, the drug should be discontinued.

With a history of severe neuropathy, Velcade should be prescribed only after a thorough assessment of the risk-benefit ratio of therapy.

Dose adjustment is not required in case of renal failure (patients on dialysis, the drug is administered after the dialysis procedure).

With a mild degree of liver dysfunction, a change in the initial dose is not required. In case of moderate and severe liver dysfunction, the dose of Velcade should be reduced to 0.7 mg per 1 m ² of body surface in the first cycle, in the following cycles the drug is prescribed depending on tolerance - increased to 1 mg per 1 m ² or reduced to 0, 5 mg per 1 m ².

In combination therapy, intravenous or subcutaneous administration of Velcade is combined with the ingestion of melphalan and prednisone. Treatment involves 9 six-week cycles, of which from 1 to 4 the drug is used 2 times a week (days 1, 4, 8, 11, 22, 25, 29 and 32), and from 5 to 9 cycles - once a week (days 1, 8, 22 and 29). The dose of the drug is prescribed and adjusted by the attending physician, taking into account the indicators of the content of platelets, neutrophils and non-hematological toxicity.

Side effects

• Hematopoietic system and lymphatic system: very often - anemia, neutropenia, thrombocytopenia; often - lymphopenia, leukopenia; infrequently - febrile neutropenia, pancytopenia, hemolytic anemia, lymphadenopathy, thrombocytopenic purpura; rarely - syndrome of disseminated intravascular coagulation;
• Digestive system: very often - nausea, decreased appetite, vomiting, constipation, diarrhea; often - dry mouth, stomatitis, abdominal pain, dyspepsia, flatulence, loose stools, hiccups, pain in the pharynx and throat; infrequently - increased appetite, colitis, belching, acute pancreatitis, paralytic intestinal obstruction, melena, enteritis, gastrointestinal bleeding, dysphagia, pain in the spleen area, gastritis, esophagitis, gastroesophageal reflux, hypersecretion of the salivary glands, petechiae on the mucous membranes, petechiae tongue, tongue ulceration, discoloration of the tongue; rarely - ischemic colitis;
• Cardiovascular system: often - a decrease or increase in blood pressure (BP), arrhythmia, palpitations, angina pectoris, orthostatic and postural hypotension, cardiogenic shock, cardiac arrest, myocardial infarction, ventricular hypokinesia, exacerbation and development of chronic heart failure, pulmonary edema (including acute), complete atrioventricular block, stopping the sinus node, tachycardia, atrial fibrillation, hematoma, phlebitis; infrequently - bradycardia, atrial flutter, intracerebral bleeding, subarachnoid hemorrhage, intracranial hemorrhage, stroke, vasculitis, pulmonary hypertension, pulmonary congestion, ecchymosis, petechiae, purpura, vein swelling, discoloration of veins, hot flushes, rarely - cardiac tamponade, decreased left ventricular ejection fraction, pericarditis,embolism of peripheral vessels and / or pulmonary artery, ventricular arrhythmias;
• Respiratory system: very often - shortness of breath; often - cough, nosebleeds, rhinorrhea, shortness of breath during physical exertion; infrequently - hypoxia, respiratory arrest, pleural effusion, respiratory alkalosis, bronchospasm, rhinitis, tachypnea, nasal congestion, wheezing, hoarseness, lung hyperventilation, chest pain, hemoptysis, tightness in the throat, orthopnea, sinus pain; rarely - pneumonia (including interstitial), pneumonitis, acute respiratory failure syndrome, pulmonary hypertension, acute diffuse infiltrative lung damage, alveolar hemorrhage in the lung, respiratory failure;
• Hepatobiliary system: infrequently - hypoproteinemia, liver hemorrhage, hepatitis, increased activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hyperbilirubinemia; rarely - liver failure;
• Mental disorders: often - insomnia, depression, anxiety, confusion; infrequently - sleep disturbances, delirium, changes in mental status, agitation, hallucinations, irritability, agitation, unusual dreams, mood swings;
• Nervous system: very often - headache, peripheral neuropathy, paresthesia; often - dizziness (excluding vertigo), tremor, polyneuropathy, dysesthesia, taste perversion, hypesthesia; infrequently - convulsions, paraplegia, motor peripheral neuropathy, paresis, loss of taste, impaired concentration, drowsiness, jerky movements, cognitive disorders, postural dizziness, speech disorders, mononeuropathy, restless legs syndrome, fainting; rarely - autonomic neuropathy, encephalopathy, leukoencephalopathic syndrome (reversible);
• Urinary system: often - dysuria, impaired renal function; infrequently - renal failure (including acute), renal colic, oliguria, hematuria, frequent urination, urinary incontinence, urinary retention, proteinuria, difficulty urinating, back pain;
• Sense organs: often - pain in the eyes, decreased clarity of vision, vertigo; infrequently - visual impairment, bleeding in the eye, dry eyes, photophobia, conjunctivitis, eye irritation, conjunctival hyperemia, increased lacrimation, hearing impairment, ringing in the ears; rarely - optic neuropathy, ophthalmic herpes, blindness, bilateral deafness;
• Immune system: infrequently - hypersensitivity; rarely - Quincke's edema;
• Endocrine system: infrequently - violation of the secretion of antidiuretic hormone;
• Metabolism: often - hyperglycemia, hypokalemia, dehydration; infrequently - cachexia, hypercalcemia, hyperuricemia, hyperkalemia, hypernatremia, hypocalcemia, hypoglycemia, hyponatremia, vitamin B12 deficiency, hypophosphatemia, hypomagnesemia;
• Musculoskeletal system: very often - myalgia; often - bone pain, muscle weakness, musculoskeletal pain, muscle cramps, limb pain, back pain, arthralgia; infrequently - muscle spasms, muscle twitching, muscle stiffness, stiff joint mobility, joint swelling, pain in the jaws;
• Reproductive system: infrequently - erectile dysfunction, testicular pain;
• Dermatological reactions: very often - skin rash; often - rash, itching, urticaria, periorbital edema, redness, dry skin, eczema, increased sweating; infrequently - generalized itching, photosensitivity, erythematous rash, bruising, macular rash, psoriasis, papular rash, dermatitis, generalized rash, facial edema, eyelid edema, alopecia, skin pigmentation changes, nail damage, atopic dermatitis, changes in the structure of night sweats, night sweats nodules on the skin, ichthyosis; rarely Sweet's syndrome; very rarely - toxic epidermal necrolysis, Stevens-Johnson syndrome;
• Laboratory indicators: often - increased activity of lactate dehydrogenase in the blood; infrequently - an increase in the activity of alkaline phosphatase, gamma-glutamyltransferase, blood amylase, the level of C-reactive protein, the concentration of urea in the blood, a decrease in the concentration of bicarbonates in the blood;
• Others: very often - fever, severe fatigue, herpes zoster (including disseminated); often - flu-like symptoms, edema, weakness, asthenia, a feeling of malaise, peripheral edema, the appearance of a secondary infection; infrequently - chills, neuralgia, feeling of pressure and / or discomfort in the chest, groin pain, weight gain, tumor lysis syndrome, complications from the catheter; rarely - septic shock, herpetic meningoencephalitis; very rarely - progressive multifocal leukoencephalopathy;
• Local reactions: infrequently - phlebitis, hyperemia, burning sensation, pain at the injection site; with extravasation - inflammation of the subcutaneous fat.

With the similarity of the safety indicators for the use of Velcade in the treatment of mantle cell lymphoma and multiple myeloma, a significant difference between them is that nausea, vomiting, neutropenia, thrombocytopenia, anemia, fever are more often observed in patients with multiple myeloma, and rash, pruritus, peripheral neuropathy - in patients with mantle cell lymphoma.

Overdose

When the recommended dose of Velcade is exceeded by more than two times, there is an acute drop in blood pressure and fatal thrombocytopenia.

In case of an overdose of the drug, it is recommended to carefully monitor the indicators of the patient's vital functions and conduct appropriate therapy to maintain normal blood pressure and body temperature (inotropic and / or vasoconstrictor drugs, infusion therapy). There is no specific antidote.

special instructions

Treatment should be supervised by a physician with practical experience in cancer chemotherapy.

Intrathecal administration of Velcade is fatal.

The drug cannot be mixed with other drugs, the only exception is 0.9% sodium chloride solution.

Before starting therapy and during each cycle, it is necessary to carry out a complete blood test with counting the platelet count and leukocyte count.

The use of Velcade most often causes the development of transient thrombocytopenia, with the greatest decrease in platelet levels by the 11th day of the cycle. If the number of platelets is less than 25,000 / μl, therapy should be suspended. Treatment of hematological toxicity involves the use of colony-stimulating factors, transfusion of erythrocyte and platelet mass. After the level of platelets in the blood is restored, the use of the drug can be continued after a careful assessment of the intended benefits and risks of therapy.

During the period of treatment, rehydration therapy is indicated to maintain water-electrolyte balance; in case of vomiting or diarrhea, the use of appropriate funds is recommended.

Symptoms of peripheral neuropathy are weakness, hyperesthesia, hypesthesia, paresthesia, burning sensation and discomfort, neuropathic pain. With an increase in existing symptoms or the appearance of new symptoms, it is possible to reduce the dose and change the regimen of the drug with the appointment of maintenance therapy.

Caution is required when treating patients with a history of epilepsy or seizures.

Against the background of the use of Velcade, orthostatic hypotension often appears, sometimes with temporary loss of consciousness.

Particular care should be taken when treating patients with dehydration associated with vomiting or diarrhea, with a history of diabetic neuropathy and syncope, taking antihypertensive drugs. Patients should be informed about the need for immediate medical attention in case of dizziness, feeling of "lightness in the head" or fainting. In case of orthostatic hypotension, it is recommended to hydrate, administer sympathomimetics and / or glucocorticoids, and, if necessary, reduce the dose of antihypertensive drugs.

Patients with risk factors for heart failure or a history of heart disease should be closely monitored.

Patients with functional disorders of the liver should be prescribed at lower initial doses, accompanied by constant monitoring of treatment for the development of symptoms of toxicity.

It is possible to develop a reversible leukoencephalopathic syndrome, a neurological disorder accompanied by seizures, headache, increased blood pressure, confusion, lethargy, blindness and other neurological and visual disorders. When the diagnosis is confirmed by magnetic resonance imaging of the brain, the use of Velcade should be discontinued.

Due to the high risk of reactivation of the Varicella zoster virus, the use of the drug involves antiviral prophylaxis.

When symptoms of impaired lung function appear or worsen, it is necessary to diagnose and immediately prescribe appropriate therapy.

Since there is a risk of developing hyperuricemia due to tumor lysis syndrome, continuous measurement of serum creatinine and uric acid levels is recommended during treatment with Velcade. As a preventive measure, the patient is recommended to drink plenty of fluids, alkalinize urine, allopurinol.

With the simultaneous use of oral hypoglycemic agents, blood glucose should be regularly monitored and the dose of hypoglycemic drugs should be adjusted in a timely manner.

During the treatment period, it is recommended to use reliable methods of contraception.

Nursing staff should follow generally accepted rules for handling cytotoxic agents.

Due to the risk of dizziness, visual disturbances, fainting and other side effects during treatment with Velcade, patients are advised to refrain from driving vehicles and mechanisms.

Application during pregnancy and lactation

Velcade is contraindicated in pregnant and lactating women.

Pediatric use

The drug is not recommended for children and adolescents under 18 years of age, since there is no experience of using bortezomib in children.

With impaired renal function

There are no controlled studies of the drug in patients with impaired renal function, therefore, in such patients (especially with creatinine clearance less than 20 ml / min), Velcade is used with caution and only under medical supervision. If necessary, the issue of reducing the dose of the drug is being resolved.

For violations of liver function

There are no controlled studies of Welcade in patients with impaired liver function. In severe hepatic impairment, the elimination of bortezomib may be impaired and the likelihood of interactions with other drugs may increase. For such patients, the drug is prescribed with extreme caution, reducing the dose if necessary.

Drug interactions

The simultaneous use of other drugs against the background of Velcade therapy can only be prescribed by the attending physician.

Analogs

Velcade's analogues are: Bortezomib, Amilan-FS, Bartizar, Boramilan FS, Milanfor.

Terms and conditions of storage

Store at temperatures up to 30 ° C. Keep out of the reach of children.

Shelf life - 3 years, after dissolution - no more than 8 hours at temperatures up to 25 ° C.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Velcade

According to reviews, Velcade is a fairly effective drug in the treatment of myeloma. In many cases, thanks to the treatment carried out, it was possible to stop the further development of the disease.

At the same time, in the reviews there are reports of the development of side effects such as tremors, shortness of breath, increased or decreased blood pressure. However, in these cases, patients continued to use the drug, since it is not always possible to find an adequate analogue.

Price for Velcade in pharmacies

The drug is quite expensive. The price of Velcade in pharmacies ranges from 17,287 to 21,519 rubles per bottle.

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!