fluoxymesterone halotestin

fluoxymesterone halotestin

Fluoxymesterone halotestin – a recombinant fusion protein consisting of binding VEGF (vascular endothelial growth factor) portions of the extracellular domains VEGF receptor 1 and VEGF receptor 2, connected to the Fc domain (fragment capable of crystallization) Gl immunoglobulin (IgGl) human.Aflibercept produced by recombinant DNA techniques fluoxymesterone halotestin using an expression system ovary cells Chinese hamster ovary (CHO) K-1.Aflibercept is a chimeric glycoprotein having a molecular weight of 97 kDa.

Aflibercept soluble acts as “decoy receptors,” which binds to VEGF-A with a greater affinity than native receptors VEGF-A, except that it also binds to the cognate ligands VEGF-B and P1GF. Aflibercept binds human VEGF-A, VEGF-B and P1GF inert to form stable complexes which do not have biological activity. Acting as a “trap” for the ligands aflibercept prevents binding of endogenous ligands to their respective receptors, and thereby block the signaling through these receptors.

Aflibercept blocks VEGF receptor activation and proliferation of endothelial cells, thereby inhibiting the formation of new blood vessels that supply the tumor with oxygen and nutrients.

Application aflibercept mice xenografted tumors allotransplantirovannymi or inhibit the growth of various types of adenocarcinomas.

In patients with metastatic colorectal cancer who oxaliplatin-containing chemotherapy (with the previous fluoxymesterone halotestin administration of bevacizumab with or without prior administration of bevacizumab), chemotherapeutic regimens Zaltrap previously conducted ® / FOLFIRI [fluorouracil, irinotecan, calcium folinate] showcased the statistically significant increase in life expectancy compared to chemotherapy FOLFIRI scheme.

Pharmacokinetics

Absorption
In preclinical studies performed on the tumors models aflibercept bioactive dose correlated with the doses needed to create a circulating concentration in the systemic circulation free aflibercept excess circulating concentrations in the systemic circulation aflibercept associated with VEGF. Circulating concentration in the systemic circulation aflibercept VEGF associated with increasing the dose to increase until most of VEGF is not related. Further increasing the dose aflibercept leads to dose-dependent increase in the concentration of circulating in the systemic circulation free aflibercept and only a small further increase in concentration associated with VEGF aflibercept.
Patients drug Zaltrap ® is administered at a dose of 4 mg / kg body weight intravenously every 2 weeks, during which a place the excess concentration of circulating free aflibercept of concentration aflibercept associated with VEGF.
at the recommended dose of 4 mg / kg body weight once every two weeks, the concentration of free aflibercept, is close to the equilibrium concentrations were achieved during the second cycle of treatment with little or no accumulation (accumulation factor 1.2 in the equilibrium state, compared to the concentration of free aflibercept the first introduction).

Distribution
The volume of distribution of free aflibercept in equilibrium is 8 liters.

Metabolism
Since aflibercept is a protein, its metabolism studies have been conducted.
It is expected that aflibercept will split into small peptides and individual amino acids.

Elimination
circulating in the systemic circulation free aflibercept mainly binds to VEGF-family to form stable inactive complexes.
It is expected that, as with other major proteins associated with VEGF and free aflibercept will be gradually removed from the systemic circulation due to other biological mechanisms, such as proteolytic catabolism.
At doses higher than 2 mg / kg of free aflibercept clearance was 1.0 l / day with a terminal half-life – 6 days.
High-molecular proteins are not excreted by the kidneys, therefore it is expected that renal excretion aflibercept will be minimal.

Linearity / non-linearity of elimination
in relation to the target binding aflibercept with its “target” (endogenous of VEGF), free aflibercept at doses below 2 mg / kg showed a rapid (non-linear) decrease in its concentration in the systemic circulation, apparently associated with its high affinity binding endogenous VEGF. In the dose range from 2 to 9 mg / kg of free aflibercept clearance becomes linear, apparently by saturating the biological elimination mechanisms such as protein catabolism.

Special patient groups

Children
The pharmacokinetic profile aflibercept not established in children.

Elderly
Age has no effect on the pharmacokinetics of aflibercept.

Sex
Despite the differences in the clearance of free aflibercept and volume of distribution in men and women, there was no gender-related differences in its systemic exposure when used in a dose of 4 mg / kg body weight.

Body Mass Index
Body mass effect on the clearance of free aflibercept and volume of distribution, as in patients with a body weight> 100 kg was observed increase in systemic exposure aflibercept 29%.

Race
Race and ethnicity had no effect on the pharmacokinetics of aflibercept.

Patients with hepatic insufficiency
formal studies on the use of Zaltrap drug in patients with hepatic impairment have been conducted. In patients with mild (concentration of total bilirubin <1.5 ULN [upper limit of normal] for any values of aspartate aminotransferase activity [the ACT] and medium (concentration of total bilirubin> 1.5-3 ULN at any values of ACT) hepatic activity failure showed no change in the clearance aflibercept. There are no data on the pharmacokinetics of aflibercept in patients with severe degrees of hepatic impairment (total bilirubin concentration in the blood of> 3 × ULN at any values of ACT activity).

Patients with renal insufficiency
No official studies on the use of the drug Zaltrap ® in patients with renal impairment have been conducted. There were no differences in the systemic exposure (area under the concentration-time curve “concentration-time» [AUC]) aflibercept free patients with renal failure at various degrees of application of the drug Zaltrap 4 mg / kg body weight.

Indications

Metastatic colorectal cancer (MKRR) (in adults), resistant to oxaliplatin-containing chemotherapy or progressive after its use (drug Zaltrap in combination with the regime, including irinotecan, fluorouracil, calcium folinate (FOLFIRI)).

Contraindications

  • Hypersensitivity to aflibercept or any of the excipients Zaltrap drug.
  • Heavy bleeding.
  • Hypertension is not amenable to medical correction.
  • Chronic heart failure class III-IV (according to NYHA classification).
  • Severe hepatic insufficiency (lack of data on the application).
  • Ophthalmic application or intravitreal (in connection with hyperosmotic properties Zaltrap drug ® ).
  • Pregnancy.
  • The period of breastfeeding.
  • Children and teens under 18 years (due to lack of sufficient experience in the application).

Contraindications to the use of irinotecan, fluorouracil and calcium foliinata cm. In the instructions for use.

Carefully

  • Severe renal failure.
  • Arterial hypertension.
  • Clinically significant cardiovascular disease (ischemic heart disease, chronic heart failure, I-II NYHA class classification).
  • Elderly age.
  • The general condition of> 2 points on the rating scale to assess the general condition of the patient’s ECOG (Eastern Cooperative Oncology Group).

Pregnancy and breast-feeding

Pregnancy

Data on the use of aflibercept in pregnant women are missing. Studies in animals have revealed aflibercept embryotoxic and teratogenic effects. Since angiogenesis is important for fetal development, inhibition of angiogenesis when administered drug Zaltrap ® can lead to adverse effects for the development of pregnancy.

The use of the drug Zaltrap ® during pregnancy and in women who may become pregnant is not recommended.

Women of childbearing age should be advised to avoid becoming pregnant during treatment with Zaltrap, and they should be informed of the potential for adverse effects of the drug Zaltrap ® on the fetus.

Women of childbearing potential and fertile males must use effective methods of contraception during treatment and for at least for up to 6 months after the last dose of treatment.

There is a possibility of impaired fertility in men and women during treatment aflibercept (based on data from studies conducted on monkeys, males and females which aflibercept caused impaired fertility, completely reversible after 8-18 weeks).

Period breastfeeding

Clinical studies to evaluate the effects of the drug Zaltrap on production of breast milk, the allocation of aflibercept in breast milk and its effects on infants have been conducted.

It is not known whether aflibercept excels in human breast milk. However, due to the fact that we can not yet rule out the possibility of penetration aflibercept into breast milk and because of the possibility of serious adverse reactions caused by aflibercept in infants, it is necessary or not to breastfeed, or do not use the drug Zaltrap (depending on the importance of the drug to the mother).

Dosing and Administration

Zaltrap drug is administered as a 1 hour intravenous infusion followed by chemotherapeutic regimen FOLFIRI.
The recommended dose Zaltrap drug used in combination with a chemotherapeutic regime FOLFIRI, is 4 mg / kg body weight.

Chemotherapeutic diagram FOLFIRI:
the first day of the cycle – simultaneous intravenous infusion via the Y-shaped catheter is irinotecan at a dose of 180 mg / m for 90 minutes and calcium folinate (left and dextrorotatory racemates) at a dose of 400 mg / m 2 for 2 hours, followed by intravenous (bolus) administration of fluorouracil at 400 mg / m 2 , followed by a continuous intravenous infusion of fluorouracil at a dose of 2400 mg / m 2 for 46 hours. The
chemotherapy cycles repeated every 2 weeks.
Treatment with the drug Zaltrap should continue until disease progression development or unacceptable toxicity.

Recommendations for a sharp correction and dosing / deferral treatment

Treatment with Zaltrap ® should be discontinued:
– the development of heavy bleeding;
– the development of perforating the wall of the gastrointestinal tract (GIT);
– the formation of a fistula;
– the development of hypertensive crisis or hypertensive encephalopathy;
– the development of arterial thromboembolic complications;
– in the development of nephrotic syndrome or thrombotic microangiopathy;
– the development of severe hypersensitivity reactions (including bronchospasm, dyspnea, angioedema, anaphylaxis);
– in violation of the healing of wounds requiring medical intervention;
– the development of the syndrome of reversible posterior encephalopathy (SOZE), also known as reversible posterior leukoencephalopathy (SLDF).
at least 4 weeks prior to elective surgery should suspend treatment with Zaltrap.

halotestin tablets

halotestin tablets

In vivo and halotestin tablets in vitro halotestin tablets inhibits the release of mediators (histamine, leukotrienes, prostaglandins and platelet activating factor) of the cells involved in type I allergic reactions (mast cells, eosinophils, basophils and neutrophils). halotestin tablets inhibits the chemotaxis, activation and degranulation of eosinophils and stabilizes cell membranes by inhibiting phosphodiesterase and reducing cyclo-AMP. halotestin tablets also blocks H 1 – histamine receptors.

Dosing and Administration
Adults, patients over the age of 65, children older than 3 years.: For I drop into the conjunctival sac 2 times a day
in patients over the age of 65 years do not need a correction mode.

Side effect On the part of the organ of vision: Burning eyes, corneal epithelial erosion point (frequency of 1 to 2%). Reduced visual acuity with instillation of the drug, the syndrome of “dry” eye, conjunctivitis, eye pain, subconjunctival hemorrhage, photophobia, disorders of the age (incidence <1%), for example, edema and hyperemia of the eyelids, itching, etc. On the side body as a whole: headache, drowsiness, skin rash, eczema, urticaria, allergic reactions, dry mouth (incidence <1%).

 

Overdose
Data on overdose of the drug available.
Eye drops Zaditen safe if accidentally swallowed, as in 5 ml of solution contains 1.25 mg of halotestin tablets, which is 60% of the maximum oral daily dose for children over 3 years. When administered orally at a dose of halotestin tablets and 20 mg were not marked by the development of serious symptoms.

Interaction with other drugs
The data on the interaction of Zaditen eye drops with other drugs are not available.

Specific guidance
Zaditen, eye drops contains as a preservative benzalkonium chloride, which is able to penetrate into the material of soft contact lenses. The drug is used only after removal of contact lenses. Putting contact lenses 15 minutes after instillation.
All eye drops, which include benzalkonium chloride can discolour soft contact lenses. With the opening of the original packaging is broken sterile dropper bottle. To prevent contamination of the drug solution by instillation, patients should avoid contact tip of the dropper bottle with skin and eyes.
If necessary, the instillation of several drugs in the conjunctival cavity preparations should be applied at least 5 minutes separately with an interval.

Effects on ability to drive vehicles and use machines
In the development of blurred vision, drowsiness during treatment Zaditekom patients should give up the road management or using machinery.

Product form
Eye drops 0.25 mg / ml to 5 ml plastic bottle dropper white. 1 bottle with instruction on use in carton box.

Storage conditions
Store at temperatures up to 25 ° C.
Keep out of reach of children.

Shelf life
2 years. Shelf life after opening the vial -1 months.
The drug should not be used after the expiration date.

fluoxymesterone

fluoxymesterone

In studies fluoxymesterone in vitro fluoxymesterone provides ingibiruyushee action on glucosylceramide synthase at IC50 concentrations in the 20-37 micromolar. Furthermore, in experiments in vitro it has also been found to influence its ipgibiruyuschee nelizosomalnuyu glyukoziltseramidazu.In fluoxymesterone as a result of hereditary metabolic disorders is no natural degradation of glucosylceramide, which leads to the accumulation of substances in the lysosomes and is accompanied by pathological changes in many organs. fluoxymesterone okazyvetsya glyukoziltseramidsintazu inhibitory effect on that enzyme is responsible for the first step of the synthesis of most glycolipids. Glyukoziltssramidsiitazy Inhibitory effect underlies substratsnizhayuschey treatment of Gaucher disease.

Niemann-Pick disease type C (sphingomyelin lipidosis) – a very rare disease that develops as a result of violation of intracellular transport of lipids and manifesting neurodegenerative changes. The disease is characterized by a consistently progressive course, high lethality. It is believed that neurological changes in disease Niemann-Pick type C develops secondary to the accumulation of glycosphingolipids in neuronal and glial cells.

Pharmacokinetics

Farmakokinetichsskie fluoxymesteronea parameters studied in healthy volunteers, a limited number of patients with Gaucher disease type 1, in patients with Fabry disease, HIV-infected patients, in adults and children with Niemann-Pick disease type C and Gaucher disease type 3. Suction

Farmakokinetichsskie fluoxymesteronea parameters are directly proportional to the dose and time dependent. In healthy volunteers when administered fluoxymesterone is rapidly absorbed. The maximum concentration (Cmax ) is determined in blood plasma after about 2 h. The absolute bioavailability of fluoxymesteronea not installed. When co-administered the drug with food its absorption rate decreases (C max is decreased by 36% and the time to reach C max (t max ) is increased by 2 hours), the degree of absorption of the drug when receiving it from the food was not significantly reduced (area under the curve “concentration -time »(AUC) is reduced by 14%).

Distribution

fluoxymesteronea volume of distribution is 83 liters. fluoxymesterone does not bind to plasma proteins.

Metabolism and excretion

fluoxymesterone is derived mainly (70-80% of the administered dose) through the kidneys in unchanged form. Clearance (CL / F) of fluoxymesteronea 230 ± 39 ml / min, poluvyvedepiya period averages 6-7 hours. In healthy volunteers after oral administration of 100 mg of 14 C-labeled fluoxymesteronea it found that 83% of the radioactivity eliminated via the kidneys and 12% – in the intestine.

The main metabolite found in the urine, – fluoxymesteronea glucuronide, it is 5% of the dose fluoxymesteronea. Half-life of the radioactive material is 150 hours, it is assumed the presence of one or more metabolites with very long half-life. Metabolite, which would have a duration of action is not set, however, may occur, and its accumulation if the concentration exceeds the concentration fluoxymesteronea in equilibrium.

Farmakokinetichsskie indicators fluoxymesteronea in adult patients with type 1 Gaucher disease and Niemann-Pick disease type C do not differ from those in healthy volunteers.

Farmakokinetichsskie parameters studied in children with type 3 Gaucher disease in 3-15 years of age, children with Niemann-Pick disease type C aged 5-16 years. Application fluoxymesteronea in children at a dose of 200 mg, with a correction depending on body surface area, accompanied by an almost twofold increase in C max and AUC compared with the corresponding values of C max and AUC after administration of 100 mg fluoxymesteronea in Gaucher disease type 1 and also showed a linear dependence . At equilibrium concentration fluoxymesteronea 6 in the cerebrospinal fluid of patients with the disease type 3 Gosche was 31.4 – 67.2% contained in blood plasma.

Pharmacokinetics in special groups

Demographic parameters
, demographic parameters such as the IOL, age, race, and body mass index did not have a clinically significant effect on the parameters farmakokinetichsskie fluoxymesteronea. Accordingly, the correction of the dose according to the above parameters required.

Elderly patients
Farmakokinetichsskie fluoxymesteronea parameters in patients older than 70 years have not been studied.

Patients with hepatic insufficiency
Due to the fact that fluoxymesterone is not metabolized by the liver, farmakokinetichsskie fluoxymesteronea parameters have not been studied in patients with hepatic insufficiency.

Patients with renal impairment
Limited data, obtained in patients with Fabry disease and impaired renal function exhibit a decrease in clearance fluoxymesteronea as deterioration of renal function. In mild and medium-severe renal insufficiency fluoxymesteronea clearance decreased by 40% and 60%, respectively. Data in severe renal insufficiency limited to two patients (creatinine clearance was 18-29 ml / min), however, can not be extrapolated towards lower values. These data suggest a decrease in clearance of 70% or lower in patients with severe renal failure.

Indications

  • For oral treatment of adult patients with type 1 Gaucher disease and mild to moderate severity, which does not fit the enzyme replacement therapy.
  • For the treatment of progressive neurological symptoms in adults and children with Niemann-Pick disease type C.

Contraindications

  • Hypersensitivity to any component of the drug.
  • Severe renal insufficiency (creatinine clearance <30 mL / min / 1.73 m 2 ).
  • Children under 18 years of age in patients with Gaucher disease type 1 (no clinical experience).
  • Adult patients older than 70 years (no clinical experience).

Carefully

 

  • Hepatic and moderate renal insufficiency (creatinine clearance 30-50 ml / min / 1.73 m 2 ).
  • In children with Niemann-Pick disease type C up to 4 years (application experience is limited).

Application of pregnancy and during breastfeeding

fluoxymesteronea controlled studies in pregnant women have been conducted. Experimental studies suggest the presence of at fluoxymesteronea reproductive toxicity, including obstructed labor. The potential risk in humans is unknown. fluoxymesterone crosses the placental barrier, fluoxymesterone should not be used during pregnancy. Women of childbearing age should use reliable methods of contraception. Not known whether fluoxymesterone passes into breast milk arrives. Zaveska The drug should not be given during lactation.

Dosing and Administration

Zaveska The drug, taken orally, regardless of food intake.
Treatment with Zaveska should carry a doctor, having sufficient experience in treatment of diseases of “accumulation”. In type 1 Gaucher disease in adults The recommended starting dose is 100 mg 3 times a day at regular intervals. Dose can be reduced to 100 mg 1-2 times a day in patients with diarrhea or tremor.

When disease Niemann-Pick type C in adults and children 12 years and older the recommended starting dose is 200 mg 3 times a day.
Children under 12 years of age the dose is calculated on the basis of body surface area.

halotestin cycle

halotestin cycle

Antitumor agent from the halotestin cycle group of anthracycline antibiotics. Incorporating into the DNA molecule, idarubicin interacts with topoisomerase II and inhibits nucleic acid synthesis; It is highly lipophilic and has a higher rate of penetration into the cells and less cross-resistance in comparison with doxorubicin and daunorubicin.The main metabolite idarubicin – idarubitsinol – exhibits antitumor activity and has less severe cardiotoxicity than idarubicin.

At intake absorption – high; time to halotestin cycle maximum concentration – 2-4 hr .; bioavailability – 18-39%. When administered intravenously, the maximum concentration achieved within a few minutes. The half-life after oral administration – 10-35 hours, after intravenous administration -. 11-25 hours Idarurubitsin is rapidly metabolized to the active metabolite idarubitsinola, which is characterized by a long half-life (33-60 hours of ingestion, and 41-69 hours after intravenous injection ). It writes mainly in the bile in the form idarubitsinola and kidneys (1-2% unchanged and 4.6% in the form idarubitsinola).Capture idarubicin nucleated blood cells and bone marrow of leukemia patients is very fast and almost coincides with his appearance in the blood plasma. Idarubicin idarubitsinola concentration and in nucleated blood cells and the bone marrow is more than 100-200 times higher than corresponding concentrations in plasma.

Idarubicin and rate of excretion of idarubitsinola blood cells and plasma substantially coincides (idarubicin terminal half-life of the cell is about 15 hours, and idarubitsinola – about 72 hours).

Indications

  • Acute nelimfoblastnyh or myeloid leukemia in adults (first-line therapy for induction of remission and at relapse or refractory cases).
  • Acute lymphoblastic leukemia in adults and children (second-line therapy).
  • Advanced breast cancer (with the ineffectiveness of halotestin cycle first-line chemotherapy not including anthracyclines).

Contraindications

  • Hypersensitivity to idarubicin and / or other components of the drug as well as other anthracyclines and anthracenediones.
  • Severe hepatic or renal insufficiency.
  • Severe heart failure.
  • Recent myocardial infarction.
  • Clinically significant arrhythmias.
  • Persistent myelosuppression.
  • Prior therapy with maximum cumulative doses of idarubicin and / or other anthracyclines or anthracenediones.
  • Pregnancy and lactation.

Precautions
Myocarditis, chicken pox, shingles, gout or urate nephrolithiasis (in history), infection, leukopenia, thrombocytopenia, advanced age (over 60 years).

Dosing and Administration
The drug is administered intravenously (very slowly) for 5-10 minutes. Zavedos should enter through the tube system for intravenous administration To reduce the halotestin cycle risk of extravasation (during infusion of 0.9% sodium chloride solution). The capsules are taken orally, washed down with a little water. It can be taken with food. The capsule should be swallowed whole (not crack, does not dissolve, do not chew).

  • Acute nonlymphoblastic leukemia (ONLL)
    Adults – 12 mg / m2 intravenously every day for 3 days (in combination with cytarabine) or 8 mg / m2 daily for 5 days either alone or in combination with other anticancer agents. If not, intravenous idarubicin prescribed orally 30 mg / m2 per day for 3 days either alone, or 15 – 30 mg / m daily for 3 days in combination with other drugs protivoleykoznymi.
  • Acute lymphoblastic leukemia (ALL)
    Adults 12 mg / m2, children – 10 mg / m2 intravenously every day for 3 days in a monotherapy.
  • Common breast cancer
    drug is administered orally in the form of monotherapy calculation 45 mg / m in one day, or 15 mg / m2 per day for 3 days every 3-4 weeks depending upon hematologic status of the patient. In drug combination chemotherapy is applied in a dose of 35 mg / m for one day.

All of the circuits to be used considering hematologic status of the patient, and doses of other cytotoxic drugs used in combination therapy.

If abnormal liver or kidney function for use Zavedosa data are limited. When elevated levels of bilirubin and / or serum creatinine is recommended to use the drug in reduced doses.

When the concentration of bilirubin in the serum within 1.2-2 mg dose anthracycline% usually lower by 50% than 2 mg% – drug overturned.

Preparation of solution: as a solvent for the drug is only Zavedos water for injection in an amount of 5 ml per 5 mg idarubicin.

Side effect

Cardio-vascular system: phlebitis, thrombophlebitis and thromboembolism, including pulmonary embolism. A manifestation of early (acute) cardiotoxicity of idarubicin is mainly sinus halotestin cycle tachycardia and / or abnormalities on the ECG (nonspecific ST-T of the teeth)., Can also be observed tachyarrhythmia (including ventricular arrhythmias and ventricular tachycardia), a bradycardia, atrioventricular block and bundle branch block . These phenomena are rarely clinically significant, do not require discontinuation of therapy and medication is not always a predictor of later delayed cardiotoxicity. Late (delayed) cardiotoxicity usually develops during the last course of therapy or within a few months or years after completion of therapy. Late cardiomyopathy manifested decrease left ventricular ejection fraction and / or symptoms of congestive heart failure (CHF) (dyspnea, pulmonary edema, hypostatic edema, cardiomegaly and hepatomegaly, oliguria, ascites, pleural effusion, gallop rhythm). Also, the phenomenon can be observed subacute (pericarditis / myocarditis). The most severe form of anthracycline-induced cardiomyopathy is a life-threatening congestive heart failure, which limits the total dose of the drug.

Hematopoietic system: leukopenia, neutropenia, thrombocytopenia, anemia. The number of neutrophils and platelets usually reaches the lowest values for 10-14 day after administration, the restoration of blood picture is observed in the third week.

Dose-dependent reversible leukopenia and neutropenia are the manifestation of toxicity, which limits the dose of the drug. . The clinical manifestation of severe myelosuppression may be fever, infections, sepsis / septicemia, septic shock, hemorrhage and tissue hypoxia.

From the digestive system: nausea, vomiting, anorexia, dehydration, mucositis, stomatitis, esophagitis, abdominal pain, heartburn, erosion / ulceration, diarrhea, colitis (including neutropenic enterocolitis with perforation), increased activity of “liver” enzymes and increase in bilirubin serum. Occasionally on the background of oral Zavedosa observed the development of serious complications from the gastrointestinal tract (perforation, bleeding).

From the urinary system: red coloration of urine for 1 – 2 days after ingestion.

Skin and skin appendages: alopecia, rash, pruritus, hyperpigmentation of the skin and nails, hypersensitivity to irradiated skin ( ‘response to radiation “), urticaria, and peripheral erythema.

Allergic reactions: hot flashes to the face, anaphylaxis.

Local reactions: in contact with the drug under the skin – blistering, severe cellulitis, necrosis of the surrounding soft tissues.

Other: hyperuricemia due to rapid lysis of neoplastic cells ( “syndrome, tumor lysis”), secondary leukemia with or without preleykemicheskoy phase (often seen with anthracyclines in combination with a disruptor DNA antineoplastic agents structure) with a latent period of 1 to 3 years.

Overdose.
Symptoms: The symptoms of acute cardiotoxicity in the first 24 hours (late cardiotoxicity can occur several months after the overdose anthracyclines) and severe myelosuppression (within 1-2 weeks).Treatment: symptomatic.

Interaction with other medicinal products and other forms of interaction

Combination chemotherapy using Zavedosa and other drugs with similar effects can lead to additive toxic effect, particularly in relation to hemopoietic system / bone marrow and the gastrointestinal tract.

The additive myelosuppressive effects may also occur when radiation therapy was carried out against the background, or 2-3 weeks before therapy Zavedosom.

The combined use of cardiotoxic or other cardiovascular drugs (e.g., calcium channel blockers) requires careful monitoring of the heart functions during the treatment period.

Changes in liver function as a result of concomitant therapy can disrupt metabolism idarubicin and its pharmacokinetics, therapeutic efficacy and / or increase its toxicity.

In a joint application raises the risk of developing nephropathy with uricosuric drugs.

Zavedos ® should not be mixed with other drugs.

Pharmaceutical incompatible with any solutions with an alkaline pH – the destruction of idarubicin.

Do not mix with heparin – sedimentation.

Cautions
Zavedos ® should only be used under the supervision of a doctor who has experience of cytotoxic chemotherapy.

Before treatment, patients should Zavedosom fully recover from the acute signs of toxicity due to previous therapy with cytotoxic drugs, such as stomatitis, neutropenia, thrombocytopenia, and generalized infections. Prior to and during each cycle of therapy is necessary to carry out a blood test to count leukocyte formula.

To reduce the risk of severe toxic lesions of the heart is recommended prior to and during therapy Zavedosom regular monitoring of its functions (using the same assessment methodology throughout the whole observation period), including the assessment of left ventricular ejection fraction by echocardiography or multichannel radionuclide angiography and ECG monitoring. Monitoring of cardiac function must be particularly strict in patients with risk factors, and in patients receiving high cumulative doses of anthracyclines. If you find signs of cardiotoxicity Zavedosom treatment should be discontinued immediately. Risk factors for development of cardiac toxicity include cardiovascular disease in the active or latent phase, prior or concomitant radiotherapy of the mediastinum or pericardial area, previous therapy with other anthracyclines or anthracenediones, the simultaneous use of other drugs that suppress the contractile ability of the heart. However, cardiotoxicity due to the use halotestin cycle of the drug may occur at lower cumulative doses and regardless of the presence or absence of risk factors for cardiotoxicity. It is assumed that the toxicity of idarubicin and other anthracyclines and anthracenediones is additive.

Limiting cumulative doses by intravenous and oral administration Zavedosa ® has not yet been established. It reported cases of cardiomyopathy resulting from treatment with about 5% of patients with a cumulative intravenous dose of 150-290 mg / m2. Available data on the oral administration Zavedosa a total cumulative dose of 400 mg / m2 suggest a low probability of cardiotoxicity.

As the disruption of the liver and / or kidneys can affect the distribution of idarubicin, before and during treatment is necessary to monitor liver and kidney function (with the definition of bilirubin and serum creatinine).

Before the appointment Zavedosa capsules in patients with gastrointestinal disease with increased risk of bleeding and / or perforation, the physician must weigh the anticipated benefits of the drug and the risk of complications.

Patients taking Zavedos ® inside, must be monitored carefully as possible the development of gastrointestinal bleeding and severe mucosal damage.

In connection with the possible development of hyperuricemia in patients during therapy is recommended to determine the level of uric acid, potassium, calcium, phosphate, and serum creatinine. Hydration, urine alkalinisation, and prophylaxis with allopurinol minimize the risk of complications associated with tumor lysis syndrome.

After the introduction of the small-diameter vein or after re-injection into the same vein fleboskleroz may develop. The risk of phlebitis / thrombophlebitis at the injection site can be reduced by strict adherence to the recommendations on the introduction of the drug.

At the first signs of extravasation (burning or pain at the injection site) the infusion should be stopped immediately, and then resume the infusion into another vein until a full dose.

Men and women receiving therapy with Zavedos should use reliable methods of contraception.

When working with the preparation Zavedos ® is necessary to observe the rules of treatment with cytotoxic agents. Contaminated drug is recommended to treat the surface with a dilute solution of sodium hypochlorite solution (containing 1% available chlorine). If the product enters the skin – immediately produce copious water washing the skin halotestin cycle with soap and water or sodium bicarbonate; Eye contact – pull eyelids and produce rinsing eye (s) with plenty of water for at least 15 minutes.

Release form
Valium for drug of a solution for intravenous injection in vials of 5 mg. 1 bottle with instruction on use in carton box. Capsules of 5 mg, 10 mg or 25 mg. 1 capsule in a bottle of dark glass. 1 bottle with instruction on use in carton box.

Storage conditions
List B.
Valium for drug of a solution for intravenous administration: at a temperature no higher than 25 ° C out of reach of children. It is recommended to use the drug after the first opening, followed by reduction of the solvent.
Capsules: at a temperature no higher than 25 ° C out of reach of children.

Shelf life

  • Valium for drug of a solution for intravenous injection – 3 years.
  • Capsules – 3 years

Do not use after the expiration date printed on the package.

Conditions of supply of pharmacies
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halotestin side effects

halotestin side effects

Halotestin side effects – convenient product in the form of soft capsules containing Vaccinium macrocarpon extract promotes normal functioning of the urinary system.Optimally matched to the composition of the extract of the fruit of large-fruited cranberry (Vaccinium macrocarpon) (25: 1), a standardized content proanthocyanidins, helps to improve the functioning of the urinary system by facilitating the elimination of urinary tract bacteria E. coli.

Description
Soft Capsule oval brick-red color.

Composition

fruit extract Vaccinium macrocarpon (Vaccinium macrocarpon) (25: 1) – 220 mg. Excipients: triglycerides srednetsepochnye (vegetable oil) – 360 mg, soy lecithin (emulsifier) – 30 mg, ascorbic acid (an antioxidant) – 20 mg colloidal silicon dioxide (E 551) (stabilizer) – 10 mg. capsule shell: gelatin (pig) food – 126 mg of glycerol (plasticizer) – 60.76 mg titanium dioxide (E 171 ) (dye) – 0.84 mg iron oxide red (E 172) (dye) – 0.56 mg, purified water -. 200 mg Nutritional information

Dosing
halotestin side effects first 3 days take 1 capsule three times a day, followed by one capsule once a day.
The recommended course of a 2 to 4 weeks. If necessary, reception of biologically active additives to food halotestin side effects can be continued.
Before applying are encouraged to consult with your doctor.
The biologically active food supplement. It is not a medication.

Precautions
Do not exceed the recommended daily dose. halotestin side effects can not be a substitute for a full variety of food.

Contraindications
halotestin side effects should not be taken for persons with hypersensitivity to soya or to any other components of biologically active food supplements halotestin side effects.

Storage
Store in a dry, dark place at a temperature no higher than 25 ° C.
Keep out of reach of children.

Shelf life
2 years.
Do not use after the expiry date stated on the package.

Release form
12 soft capsules in blister foil Al / PVC / PVDC. At 1, 2, 3 or 5 blisters with a leaflet placed in a pile of cardboard.