Velcade instructions for use
- Velcade instructions for use
- Form of preparation, its composition and packaging
- Mechanism of action
- When appointed?
- When and to whom to use is not recommended
- Mode of application
- Symptoms of overdose and their treatment.
- Interaction of Velcade with other drugs.
- Features of Velcade application in pregnancy and lactation
- Side effects
- How and where to store?
- Conditions of leave from pharmacies
- Velcade price
Farm Group: Velcade belongs to the group of drugs for the treatment of tumors.
Form of preparation, its composition and packaging
Velcade is available as a lyophilized powder, which is used to prepare a solution for intravenous and subcutaneous injections.
The powder is in a glass vial, a volume of 10 ml, packed in a blister and embedded in a cardboard box.
1 bottle of the drug contains bortezomiba 3.5 mg and mannitol 35 mg as excipients.
Mechanism of action
Bortezomib - a substance that reversibly inhibits the production of 26S-proteasome in the cells of all mammals. The 26S-proteasome is a protein complex that acts on proteins associated with ubiquitin. This mechanism is involved in maintaining the constancy of the intracellular environment. Inhibition of the proteasome, through a series of cascade reactions leads to disruption of homeostasis and subsequently to cell death.
In in vivo tests, the drug slowed the growth of cells in simulated tumors, including in multiple myeloma.
Intravenous bortezomib is administered at doses of 1 mg / m2 and 1.3 mg / m2. The maximum concentration in the blood is 57 and 112 ng / ml, respectively. With repeated administration, these figures increase, and ranges between 67-106 and 89-120 ng / ml.
After administration, the drug is intensively distributed across all tissues, binding to plasma proteins is approximately 83%.
In the metabolism of the active substance, the isoenzymes CYP3A4, CYP2C19 and CYP1A2 play a direct role. At the same time, the metabolites formed do not show the pharmacological action characteristic of bortezomib.
The ways of excretion of the drug in humans have not been studied. Half-life with repeated injections is greater than in the primary, and ranges between 40-193 hours.
The effect on the pharmacokinetics of Velcade's age, race, and sex of the patient has not been studied.
In the treatment of cancer patients with concomitant disorders of the liver, the need to adjust the dose depends on the degree of severity of organ dysfunction. For mild violations of the liver, there is no need to change the dose of Velcade. For moderate to severe disorders, it is worthwhile to reduce dosage and closely monitor the therapy process.
The pharmacokinetic characteristics of Velcade administered in different doses and in different ways does not change in the case of abnormalities in kidney function, regardless of the severity of the organ dysfunction.
The preparation Velcade is prescribed for:
- multiple myeloma
- mantial cell lymphoma, provided that the patient has already received at least 1 treatment line.
When and to whom to use is not recommended
Velcade is contraindicated in the following cases:
- individual intolerance to bortezomib, boron and / or mannitol
- pregnancy and lactation
- children's age
- diseases of the pericardium
Extreme caution should be observed when using Velcade with:
- middle and severe liver dysfunction
- severe kidney dysfunction
- convulsive syndrome, epilepsy
- tendency to fainting
- neuropathies of diabetic origin
- dehydration caused by vomiting or diarrhea
- risk of heart failure.
Velcade is intended only for intravenous and subcutaneous injections. It is inadmissible to administer internally, since lethal outcomes have been fixed.
For intravenous administration, a solution is prepared at a concentration of 1 mg / ml, for subcutaneous 2.5 mg / ml.
Concentration should be calculated very carefully, as it differs for different routes of administration.
Intravenous administration is carried out for 3-5 seconds or subcutaneously. The starting dose is 1.3 mg / m 2 with a multiplicity of 2 times a week. Therapy is carried out for 2 weeks (4 injections), then observe a 10-day break. Be sure to observe a 72-hour break between injections.
Evaluate the clinical outcome of therapy only after 3 or 5 courses of treatment. If a full therapeutic result has been achieved, it is worthwhile to conduct two more courses to fix it.
If therapy fails to produce sufficient results, Velcome's combined treatment with dexamethasone in high dosages may be prescribed by specialists. With each injection, 40 mg of dexamethasone are administered orally, dividing this amount into two doses. The first half is taken orally on the day of Velcade's injection, and the second half on the next day.
All concomitant changes in the patient's condition during the period of taking the drug should be carefully monitored and accompanied by a change in the dosage and the frequency of treatment.
Mode of application
Velcade refers to drugs for the treatment of tumors, so it must be treated with great care. Preparation of a solution for injection requires compliance with the rules of sterility. It is necessary to avoid contact of the solution with the skin, for this it is worth using gloves and other protective clothing elements. Do not mix Velcade with other medicines except saline (sodium chloride 0.9%).
For intravenous administration, 3.5 ml of physiological saline solution per bottle of Velcade is taken as the solvent. Thus, the concentration of the prepared solution is 1 mg / ml. It is necessary to monitor the quality of the resulting liquid - it must be colorless and transparent, without any mechanical inclusions. If any deviation from these standards is observed, the solution can not be used for injections. The introduction is performed intravenously via a catheter for 3-5 seconds, then the catheter is washed with saline.
For subcutaneous administration, 1.4 ml of physiological saline is taken as a solvent, and a final preparation with a concentration of 2.5 mg / ml is prepared. Quality control is the same - colorlessness, transparency and the absence of mechanical inclusions. Any deviation serves as a reason for disposal of the solution, since it can not be used for injections. The place of administration is the skin of the hip or abdomen (right or left). Enter the drug subcutaneously. Each subsequent injection should be carried out to a new location with a minimum distance from the site of the previous injection of 2.5 cm. Do not inject into irritated, damaged areas, with bruises, or where it is difficult to insert the needle. If there is a local reaction to the drug, you can go to a solution of a lower concentration - 1 mg / ml or inject the drug intravenously.
Symptoms of overdose and their treatment.
Signs of an overdose of the drug is a sharp drop in blood pressure, a decrease in the number of platelets in the blood with a fatal outcome. These symptoms are observed when the dose is doubled.
Therapy of overdose state consists in careful monitoring of vital signs, work of organs, level of arterial pressure (use of intravenous infusions, appointment of vasoconstrictors), body temperature. Specific antidote to the drug is not established.
Interaction of Velcade with other drugs.
Bortezomib is a weak inhibitor of the isoenzymes CYP1A2, CYP2S9, CYP2S19, CYP2D6 and CYPZA4. Accordingly, it is necessary to be cautious when taking other medicines that can influence the activity of these substances. So ketoconazole, the oppressive isoenzyme CYP3A4 influences the pharmacokinetics of bortezomib, so joint intake of these drugs should be conducted under the attention of doctors. The same applies to taking Velcade and ritonavir together.
The effectiveness of Velcade therapy decreases when it is taken with rifampicin, carbamazepine, phenobarbital, phenytoin - strong inducers of CYP3A4 isoenzyme. Dexamethasone, however, exhibits less pronounced inducing ability for this substance, therefore it has no significant effect on the effectiveness of bortezomib.
Combined treatment with Velcade with melphane and prednisolone is acceptable, as the change in pharmacokinetic characteristics is insignificant.
When taking oral hypoglycemic agents, it is possible to change their activity with the development of both increase and decrease in blood sugar below the norm.
Cautiously use together with drugs from pressure, antiviral agents, statins.
Features of Velcade application in pregnancy and lactation
The use of Velcade during childbearing and breastfeeding is strictly prohibited.
From the hematopoietic organs: violation of laboratory indicators in the direction of reducing the number of cells - platelets, leukocytes, lymphocytes, neutrophils and other
From the heart and blood vessels: heart attack, heart failure, heart failure, rhythm disturbance, pulmonary edema, falling and rising blood pressure, slowing of the heart rhythm, cerebral hemorrhage, stroke, inflammation of the vessel wall, embolism of peripheral and central vessels.
On the part of the respiratory system: violation of the respiratory rate, dyspnea. Cough, rhinitis, pain in the chest, in the nasal sinuses, respiratory failure, hemorrhages in the alveoli.
On the part of the intestine: dyspepsia, worsening appetite, bloating, stomatitis, pain in the throat, inflammation of the stomach mucosa. Inflammation of the pancreas, increased salivation, changes in color and surface of the tongue, colitis.
On the part of the liver: inflammation, hemorrhage, increased bilirubin level in the blood, inadequate functioning of the body.
From the side of the central nervous system: neuropathies, convulsions , loss of consciousness, violations of taste perception, speech disturbance, tremor, memory impairment and attention.
From the side of the psyche: confused consciousness, alternation of excitement and oppression, depressive state, sleep disturbance, irritation.
On the part of the kidneys and other urinary organs: violation of urination, inadequate kidney function, urinary incontinence, blood and protein in the urine, changes in the amount of urine, pain in the lumbar spine.
From the ear: a violation of auditory function, ringing in the ears, deafness on both ears.
From the side of the eye: visual impairment, inflammation of the conjunctiva, dry mucosa, hemorrhage, blindness, herpes of the eye.
On the part of immunity: an allergic reaction - Quincke's edema , increased sensitivity to the ingredients of the drug.
From the side of metabolism: dehydration, violation of the level of potassium, sodium, calcium, magnesium, phosphorus and uric acid in the blood, exhaustion, insufficiency of vitamin B12.
From the musculoskeletal system: pain in muscles and joints, convulsions, spasms, twitching, impaired mobility of joints and their edema.
On the part of the reproductive system: violation of erection, pain in the testicles.
How and where to store?
Velcade is stored in the original packaging for 3 years from the date of release, at a temperature of up to 30 ° C. Keep away from children.
The prepared injectable solution can be stored in a vial or syringe for no more than 8 hours in a room with natural light, at a temperature of no higher than 25 ° C.
Conditions of leave from pharmacies
The drug belongs to the list of prescription drugs.
Velcade lyophilizate for injection 3mg - 55000-60000 rub.