One Capsule contains: Active ingredient: anadrol vs dbol 10 mg Excipients: soybean oil, beeswax yellow, soybean oil hydrogenated, soybean oil is partially hydrogenated; capsule shell: glycerol 85% gelatin, Karion 83 (potato starch hydrolyzed mannitol sorbitol), titanium dioxide (E171), yellow iron oxide colorant (E172), iron oxide red dye (E172).

Description
Soft gelatin capsules oval 8.8-11.2 mm long with a diameter of 5.8-8.2 mm; one half of the capsule yellow-orange, opaque; the other half – the reddish-brown, opaque.
The contents of the capsules – the suspension from yellow to greenish-yellow color.

Pharmacotherapeutic group
antitumor agent

pharmacological properties

Pharmacodynamics
anadrol vs dbol (fully transretinoevaya acid) is a natural metabolite of retinol and retinoids belongs to a class, which includes natural and synthetic versions. anadrol vs dbol induces differentiation and inhibits proliferation of transformed hematopoietic cells, including myeloid leukemia in humans. The mechanism of action in acute promyelocytic leukemia, may be to change the binding of trans-retinoic acid nuclear receptors of retinoic acid, the α-retinoic acid receptor fusion also varies due to the protein PML.

Pharmacokinetics
anadrol vs dbol is an endogenous metabolite of vitamin A and is normally present in plasma. After oral administration of anadrol vs dbol is well absorbed, and maximum plasma concentrations are achieved over 3 h. The absorption of anadrol vs dbol is characterized by significant variability in the same and in different patients. Connection with the plasma protein anadrol vs dbol high. After reaching peak plasma concentration decreases, the average half-life is equal to 0.7 hours. After a single dose of 40 mg of the drug concentration in the plasma is returned to endogenous levels in 7-12 hours. Repeated reception cumulation anadrol vs dbol does not occur in the tissues of the drug is not delayed.
The main route of elimination (60%) is the excretion via the kidneys as metabolites formed during oxidation and glucuronidation. anadrol vs dbol isomerized to 13-cis-retinoic acid and is oxidized to 4-oxo-metabolites. Metabolites have a longer half-life than the anadrol vs dbol and its possible accumulation in small quantities.
Chronic administration of the drug concentration in plasma may be significantly reduced, probably due to the induction of cytochrome P450 enzyme system, which increases the clearance of the drug and reduces the bioavailability after oral administration.

Pharmacokinetics in special patient groups
Pharmacokinetics of anadrol vs dbol in patients with impaired renal or hepatic function has not been investigated.

Indications
induction of remission in acute promyelocytic leukemia (APL; classification FAB-AML-M3). Vesanoid can be assigned previously untreated patients, patients with relapsed or refractory to standard chemotherapy (daunorubicin and cytarabine or its analogues).

Contraindications
: Hypersensitivity to anadrol vs dbol or any other component of the drug.
Pregnancy and lactation.
Simultaneous intake of vitamin A.

Precautions
Simultaneous administration of tetracyclines, antifibrinolytic drugs and tablet gestagensoderzhaschih contraceptives (mini-pill).

Dosage and administration
The daily dose is 45 mg / m² body surface orally in two divided doses. For adults it is approximately 8 capsules. For children it is recommended the same dose, unless severe toxic effects occur. The dose should be reduced if the child appear expressed headaches.
Treatment should be continued from 30 to 90 days to reach complete remission. After that, you should immediately go to the standard scheme of consolidation chemotherapy, for example, three courses of daunorubicin and cytarabine at intervals of 5-6 weeks.
If remission was achieved with monotherapy Vesanoidom, change the dose of chemotherapy in the appointment is not necessary.

Special dosage
Due to the lack of pharmacokinetic data Vesanoida in patients with renal and / or hepatic impairment, the dose of the drug for these patients should be reduced to 25 mg / m².

Side effects of
the treatment recommended doses Vesanoida most common side effects are symptoms of hypervitaminosis A, which also occur in the treatment of other retinoids. On the part of the skin and its appendages: dry skin, erythema, rash, itching, sweating, alopecia, cheilitis, dryness of mucous membranes mouth, nose, conjunctiva and other mucous membranes with or without signs of inflammation;rarely, ulceration of the genital mucosa, Sweet’s syndrome, erythema nodosum. On the part of the central nervous system: headache, intracranial hypertension (mainly in children), fever, chills, dizziness, confusion, anxiety, agitation, depression, paresthesia , insomnia, weakness. From the senses: visual and hearing impairment. On the part of the musculoskeletal system : bone pain, chest pain; rare: myositis. On the part of the gastrointestinal tract : nausea, vomiting, abdominal pain, diarrhea, constipation, loss of appetite, pancreatitis. On the part of metabolism, liver and kidney : increased triglycerides, cholesterol, serum creatinine, increased activity transaminases (ALT, AST); individual cases of hypercalcemia. On the part of the respiratory system: pleural effusion, dyspnea, respiratory failure, bronchospasm. Cardio-vascular system: arrhythmias, flushing, edema, individual thrombosis events (venous and arterial). From the hematopoietic system: rare cases of thrombocytosis expressed basophilia with clinically manifested gipergistaminemiey or without it, mostly in patients with the rare APL variant with basophilic differentiation. from the side of the body as a whole: . rare cases of cutaneous vasculitis“retinoic acid syndrome” in the APL . Many patients with APL (25%) during treatment with anadrol vs dbol there retinoic acid syndrome (IBS). CRK is characterized by fever, dyspnea, acute respiratory distress syndrome, the occurrence of pulmonary infiltrates, hypotension, pleural and pericardial effusions, edema, weight gain, hepatic, renal and multi-organ failure. IBS is often accompanied by hyperskeocytosis and can lead to death. The decision to interrupt or continue therapy should be based on an assessment of the ratio of the benefits of treatment and the severity of side effects. For information on the use of anadrol vs dbol in children is limited. There are reports of increased rates of toxic effects in children receiving anadrol vs dbol, particularly intracranial hypertension.

Overdose 

In case of overdose appear reversible symptoms of the hypervitaminosis A (headache, nausea, vomiting, signs of skin lesions and mucous membranes). The dose recommended for patients with acute promyelocytic leukemia, is 1/4 of the dose, the maximum tolerated by patients with solid tumors, and is less than the maximum tolerated dose for children. No specific treatment of overdose, it is important that the patient was admitted to the hematology department.

Interactions with other drugs
Because Vesanoid is metabolized by the hepatic cytochrome P450 system, it is possible to change the pharmacokinetics while taking drugs that are inducers or inhibitors of this enzyme system. For drugs that stimulate the activity of hepatic cytochrome P450 enzyme system include rifampicin, glucocorticoids, phenobarbital and pentobarbital. Drugs that suppress the activity of hepatic P450 enzyme system include ketoconazole, cimetidine, erythromycin, verapamil, diltiazem and cyclosporine. Data that would indicate a change in the effectiveness or toxicity of these drugs while the use of anadrol vs dbol, no.Information about the possible pharmacokinetic interaction between anadrol vs dbol and daunorubicin and cytarabine absent. Antifibrinolytic agent such as tranexamic acid, aminocaproic acid and aprotinin: in patients concomitantly receiving anadrol vs dbol and antifibrinolytic agents are described rare cases of thrombotic complications with fatal consequences. In the appointment of anadrol vs dbol, along with these drugs need to be cautious. Tetracyclines: systemic retinoid therapy can lead to intracranial hypertension. Since tetracycline drugs also can increase intracranial pressure, they should not be given concurrently with anadrol vs dbol. Vitamin A: Like other retinoids, Vesanoid is contraindicated in combination with vitamin A iz-za gain symptoms of hypervitaminosis A. Tablet gestagensoderzhaschie contraceptives (mini-pill): while taking Vesanoida and mini-pill contraceptive reliability of action minipill decreases.

Cautions 

Vesanoid should be administered only to patients with acute promyelocytic leukemia under the close supervision of a hematologist or oncologist. Prevention retinoic acid syndrome (IBS) patients hyperskeocytosis arising on monotherapy Vesanoidom, is connected in anthracycline chemotherapy doses adequate indicator controlled leukocytes as follows:

 

  • co-administration of chemotherapy and therapy Vesanoidom when the number of white blood cells to exceed 5000 in 1 mm at the start of treatment;
  • connection of chemotherapy in adequate doses to treat Vesanoidom in patients with leukocyte count less than 5000 in 1 mm at the time of appointment Vesanoida and increasing the number of leukocytes in the background of his admission to: ≥ 6000 in 1 mm – for 1-6 days of treatment ≥10 000 1 l – 7-10 days of treatment ≥15 000 in 1 mm – at 11-28 days of therapy
    in the event of the earliest symptoms of IBS should start treatment with dexamethasone (10 mg every 12 hours for up to 3 days or until the relief of IBS) .
    in moderate and severe IBS should consider temporary interruption of therapy Vesanoidom.
    As in the first month of therapy there is the risk of thrombosis, caution should be exercised when treating patients with a combination of Vesanoida and antifibrinolytic drugs such as tranexamic acid, aminocaproic acid or aprotinin.
    Systemic retinoids therapy It can lead to intracranial hypertension. Vesanoid should not be administered in combination with drugs that increase intracranial pressure, such as tetracyclines.
    During Vesanoidom therapy in patients with acute promyelocytic leukemia should be performed symptomatic therapy, such as bleeding and infection prevention. It is necessary to frequently monitor blood count, coagulation indicators of liver function, and the concentration of triglycerides and cholesterol.
    In simultaneous reception Vesanoida and tablets gestagensoderzhaschih contraceptives (mini-pill), the latter is not a reliable method of contraception.
    Vesanoid has a strong teratogenic.
    During therapy Vesanoidom and at least for 3 months after the need to use a reliable barrier method of contraception.Women of childbearing age during treatment should be carried out tests for pregnancy at least 1 time per month.

    Effects on ability to drive transport and work with machines and mechanisms
    Some side effects Vesanoida, such as dizziness or severe headache, may adversely affect the patients’ ability to drive vehicles or to engage in other potentially hazardous activities that require high concentration and quickness psychomotor reactions.