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Infectious-inflammatory diseases methenolone acetate caused by susceptible to malaria infections: Lower respiratory tract infections caused by Staphylococcus aureus (penitsillinazoprodutsiruyuschie strains), Acinetobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp., Serratia marcescens. Urinary tract infections (complicated and uncomplicated) caused by Enterococcus faecalis, Staphylococcus aureus (penitsillinazoprodutsiruyuschie strains), Enterobacter spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa. Intraabdominal infections caused by Enterococcus faecalis, Staphylococcus aureus (penitsillinazoprodutsiruyuschie strains), Staphylococcus epidermidis, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus spp., Pseudomonas aeruginosa, Bifidobacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp., Bacteroides spp., including B. fragilis, Fusobacterium spp.

  • Gynecological infections caused. Enterococcus faecalis, Staphylococcus aureus (strains penitsillinazoprodutsiruyuschie). Staphylococcus epidermidis, Escherichia coli, Streptococcus agalactiae (Streptococcus spp. Group B), Enterobacter spp., Gardnerella vaginalis, Klebsiella spp., Proteus spp., Bifidobacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp., Bacteroides spp. including B. fragilis.
  • Septicaemia. caused by Enterococcus faecalis, Staphylococcus aureus (penitsillinazoprodutsiruyuschie strains), Enterobacter spp., Escherichia coli, Kiebsiella spp., Serratia Spp .; Bacteroides spp., Including B. fragilis., Pseudomonas aeruginosa.
  • Bone and joint infections caused by Enterococcus faecalis, Staphylococcus aureus (penitsillinazoprodutsiruyuschie strains), Staphylococcus epidermidis, Enterobacter spp., Pseudomonas aeruginosa.
  • Infections of skin and soft tissue caused by Enterococcus faecalis, Staphylococcus aureus (penitsillinazoprodutsiruyuschie strains), Staphylococcus epidermidis, Acinetobacter spp., Enterobacter spp., Citrobacter spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa ; Serratia spp., Peptococcus spp., Peptostreptococcus spp., Bacteroides spp., Including B. fragilis, Fusobacterium spp.
  • Infective endocarditis caused by Staphylococcus aureus (penitsillinazoprodutsiruyuschie strains).

Prevention of postoperative complications.

Contraindications:

Hypersensitivity methenolone acetate to imipenem and / or cilastatin (other carbapenems and beta-lactam antibiotics), early childhood (up to 3 months), chronic renal insufficiency (creatinine clearance of 5 ml / min without hemodialysis), chronic renal failure in children weighing less than 30 kg, central nervous system infections in children.

Precautions: Diseases of the central nervous system, convulsions history, high convulsive readiness, anticonvulsant therapy with valproic acid (reducing the effectiveness of therapy), chronic renal insufficiency (creatinine clearance less than 5 ml / min), patients on hemodialysis, old age.

 

Pregnancy and lactation:
Use of the drug during pregnancy is methenolone acetate only permissible if the potential benefit of treatment to the mother outweighs the potential risk to the fetus. Imipenem and cilastatin penetrate in small quantities in breast milk, therefore it is necessary to resolve the issue of termination of breastfeeding at the time of treatment with the drug.

 

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Tsilaspen consists of two components:  imipenem, the representative of the class of beta-lactam antibiotics – carbapenems; cilastatin primobolan depot – specific inhibitor of renal dehydropeptidase, significantly increases the concentration of unchanged imipenem in the blood. Tsilastin has its own antibacterial activity, does not inhibit the beta-lactamase bacteria.
Imipenem is a highly effective inhibitor of bacterial cell wall synthesis and is bactericidal against a wide spectrum of pathogenic gram-positive and gram-negative microorganisms, both aerobic and anaerobic.
The stability of imipenem to cleavage by bacterial beta lactamases, including produced by Gram-positive and Gram-negative and penicillinase cephalosporinase ensures its effectiveness.
it is active against Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus faecalis and Bacteroides fragilis. Resistant to bacterial destruction of beta-lactamase, which makes it effective against many microorganisms, such as Pseudomonas aeruginosa, Serratia spp. and Enterobacter spp, which are resistant to most of the beta-lactam antibiotics..
Antibacterial spectrum includes primobolan depot virtually all clinically important pathogens.
Imipenem has a bactericidal effect in vivo primobolan depot on the following microorganisms: Gram-positive aerobes: Enterococcus faecalis, Staphylococcus aureus, including penitsillinazoprodutsiruyuschie strains, Staphylococcus epidermidis, including penitsillinazoprodutsiruyuschie strains, Streptococcus agalactiae (Streptococcus spp group in.), Streptococcus pneumoniae, Streptococcus pyogenes . Gram-negative aerobes: Acinetobacter spp, Citrobacter spp, Enterobacter spp, Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp…. , Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Serratia spp, including S. marcescens.. Gram-positive anaerobes: Bifidobacterium spp, Clostridium spp, Eubacterium spp, Peptococcus spp, Peptostreptococcus spp, Propionibacterium spp……

Gram negative anaerobes : .. Bacteroides spp, including B. fragilis, Fusobacterium spp Imipenem has a bactericidal effect in vitro on the following microorganisms: Gram-positive aerobes: Bacillus spp, Listeria monocytogenes, Nocardia spp, “Staphylococcus saprophyticus, Streptococcus spp… . Groups C, G and viridans Gram-negative aerobes: the Aeromonas hydrophila, of Alcaligenes spp, Capnocytophaga spp, of Haemophilus ducreyi, of Neisseria gonorrhoeae, including strains penitsillinazoprodutsiruyuschie, Pasteurella spp .., Providencia stuartii. ..Gram-negative anaerobes: Prevotella bivia, Prevotella disiens, Prevotella melaninogenica ., Veillonella spp Unaffected: .. Enterococcus faecium, methicillin-resistant spp Staphylococcus, Xanthomonas maltophilia, Pseudomonas cepacia in vitro acts synergistically with aminoglycosides against some strains of Pseudomonas aeruginosa.
Imipenem quickly and well distributed in most tissues and body fluids. The highest concentrations are achieved in pleural fluid, peritoneal, and interstitial fluids and the reproductive organs (testes, prostate gland, vagina, uterus, ovaries). At low concentrations found in the cerebrospinal fluid. The volume of distribution in adults – 0.23-0.31 L / kg in children 2-12 years of age – 0.7 l / kg in the newborn – 0.4-0.5l / kg. Blocking kanaptsevoy imipenem cilastatin secretion leads to inhibition of its renal metabolism and accumulation in the urine in unchanged form. Cilastatin is metabolized to N-acetyl compounds. The on / in the introduction of the primobolan depot of imipenem and cilastatin in adults – 1 hour, children 2-12 years – 1-1.2 hours, in newborns the T ½ imipenem – 1.7-2.4 hours, cilastatin – 3.8-8.4 hours; with impaired renal function the T ½ . imipenem – 2.9-4 hours, cilastatin – 13.3-17.1 hours Report mostly kidneys (70-76% within 10 hours) through glomerular filtration rate (⅔) and active tubular secretion (⅓); 1-2% is excreted in the intestine and 20-25% – by extrarenal (mechanism unknown). Quickly and efficiently (73-90%) is derived by hemodialysis (as a result of a 3-hour session intermittent hemofiltration removes 75% of the administered dose).

 

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Inductors microsomal oxidation can induce liver microsomal metabolism of cyclophosphamide, which leads to increased formation of metabolites alikiliruyuschih, thereby reducing the half-life of  and increasing its activity. Methenolone, causing significant and long lasting inhibition of cholinesterase activity enhances the action of suxamethonium, and reduces or slows the metabolism of cocaine, thereby enhancing and / or increasing the duration of its effect and increasing the risk of toxicity. While the use of allopurinol, in addition, a toxic effect on the bone marrow may be intensified. With simultaneous use  and allopurinol, colchicine, probenecid, sulfinpyrazone may require dose adjustment protivopodagricakih drugs for the treatment of hyperuricemia and gout; urikozuricheskih protivopodagricakih use of drugs may increase the risk of kidney disease associated with increased production of uric acid by using cyclophosphamide.
Cyclophosphamide may increase the anticoagulant activity due to a decrease in the hepatic synthesis of coagulation factors and platelet disorders education, but can also reduce the anticoagulant activity through an unknown mechanism. As grapefruit methenolone contains a compound that may interfere with the activation of cyclophosphamide and thereby its effects, patients are not recommended to eat grapefruit or drink grapefruit juice from.  Enhances the cardiotoxicity of doxorubicin and daunorubicin. Other immunosuppressants (azathioprine, chlorambucil, glucocorticoids, cyclosporine, mercaptopurine, etc.) Increase the risk of infections and secondary tumors.
In an application of lovastatin in patients with heart transplantation may increase the risk of rhabdomyolysis and acute renal failure.
In combination with other myelosuppressive drugs or radiotherapy -. additive may bone marrow function oppression
simultaneous use of high-dose cytarabine, cyclophosphamide in preparation for bone marrow transplantation led to increased incidence of cardiomyopathy followed fatal.

Cautions
During treatment should regularly conduct blood tests (especially paying attention to the content of neutrophils and platelets) to assess the degree of myelosuppression as well as conduct regular urine test for the presence of red blood cells, the appearance of which may precede the development of hemorrhagic cystitis.
If signs of cystitis with micro- – or gross hematuria treatment  should be stopped.
By reducing the number of leukocytes < 2500 / l and / or platelet count < 100,000 / ml treatment cyclophosphamide should be stopped.
in the case of infection during therapy  treatment should be either interrupted or should be reduced dose. Women and men during treatment with methenolone should use reliable methods of contraception.
In the period of treatment should refrain from drinking alcohol. If during the first ten days after the operation carried out under general anesthesia, the patient is prescribed cyclophosphamide, is necessary to put notify the anesthesiologist.
The patient after adrenalectomy needs to adjust doses as the corticosteroids that are used for replacement therapy and drug Cyclophosphamide.

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There may also be hepatic encephalopathy. Skin and skin appendages : alopecia often develops. Hair regrowth begins after the completion of drug treatment or even during long-term treatment; hair may vary in their structure and color. Sometimes during primobolan results the treatment of a rash on the skin, pigmentation of the skin and nail changes. From the urinary system : Hemorrhagic urethritis / cystitis, renal tubular necrosis (until death), fibrosis of the bladder (including common) with a concomitant cystitis or without him. The urine may be detected by atypical epithelial cells of the bladder. When high doses of cyclophosphamide in rare cases, there may be impairment of renal function, hyperuricemia, nephropathy associated with increased formation of uric acid. Infections : in patients with severe immunosuppression may develop serious infections. On the side cardiovascular system : cardiotoxicity is observed at high doses of primobolan results of the drug for several days, usually as part of an intensive antitumor combination drug therapy or during organ transplantation. It is noted severe and sometimes fatal episodes of congestive heart failure caused by hemorrhagic myocarditis. The respiratory system : interstitial pulmonary fibrosis (when administered at high doses for a long time). Reproductive system : violation of oogenesis and spermatogenesis. The drug can cause sterility in both men and women, which in some cases can be irreversible.

A significant portion of women develop amenorrhea, regular menstruation is usually recovered within a few months after stopping treatment. In girls, as a result of treatment with cyclophosphamide during the prepubertal period, the secondary sexual characteristics develop normally and menstruation were normal; later they were able to conceive. In men, as a result of treatment, may develop oligospermia or azoospermia associated with increased gonadotropin levels in normal secretion of testosterone. Sexual desire and potency in these patients is not violated. In boys, during drug treatment in prepubertal, secondary sex, symptoms develop normally, however, can primobolan results be marked oligospermia or azoospermia, and increased secretion of gonadotropins. There may be varying degrees of testicular atrophy. Some patients with azoospermia due to a drug is reversible, but the restoration of impaired function may occur only a few years after stopping treatment. Allergic reactions : skin rash, hives, itchy skin, rarely -anafilakticheskie reaction; possible cross-sensitivity with other alkylating compounds. Other : a syndrome similar to the syndrome of inappropriate secretion of antidiuretic hormone (ADH); rush of blood to the skin of the face or facial flushing, headache, increased sweating; development of secondary malignancies.

Overdose
A specific antidote to an overdose of the drug is unknown. In cases of overdose should be used to support measures including appropriate primobolan results treatment of infections, manifestations of myelosuppression and / or cardiotoxicity.

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Cyclophosphamide metabolized mainly in the liver by the action of microsomal oxidase system, forming active alkylating metabolites methenolone enanthate), part of which is subjected to further transformation to inactive metabolites, some are transported into cells, where under the influence phosphatases are converted into metabolites possess cytotoxic action. The concentration of metabolites in the plasma reaches a maximum 2-3 hours after intravenous administration. Communication unchanged drug to plasma proteins is negligible (12-14%), but some metabolites bind more than 60%. Penetrates through the blood-brain barrier to a limited extent.
Cyclophosphamide is excreted mainly by the kidneys in the form of a metabolite, but 5 to 25% of the administered dose is excreted in the urine in an unmodified form as well as in the bile. The half-life is 3-12 hours.

Indications
Acute lymphoblastic and chronic lymphocytic leukemia, Hodgkin’s disease, non-Hodgkin’s lymphoma, multiple myeloma, breast cancer, ovarian, neuroblastoma, retinoblastoma, mycosis fungoides. Cyclophosphamide is also used in combination with other anticancer drugs for the treatment of lung cancer, germ cell tumors, cancer, cervical methenolone enanthate cancer, bladder cancer, soft tissue sarcoma, reticulosarcoma, Ewing’s sarcoma, Wilms tumor, prostatic cancer.
As immunosuppressive agents cyclophosphamide used in progressive autoimmune diseases (rheumatoid arthritis, psoriatic arthritis, collagen diseases, autoimmune hemolytic anemia, nephrotic syndrome) and for the suppression of transplant rejection reactions.

Contraindications

  • Hypersensitivity to cyclophosphamide or any other component of the formulation.
  • Severe violation of bone marrow function.
  • Cystitis.
  • Urinary retention.
  • Pregnancy and lactation.
  • Active infection.

Precautions : in severe diseases of the heart, liver and kidneys, adrenalectomy, gout (in history), nefrourolitiaze, methenolone enanthate suppression of bone marrow function, bone marrow infiltration by tumor cells prior to radiation or chemotherapy.

Dosing and Administration
Is administered intravenously or as an infusion, intramuscular injection.
Is part of many chemotherapy regimens, and therefore, the choice of a particular route of administration, regime and doses in each methenolone enanthate individual case should be guided by the data of literature.
The most common applied doses and regimens for adults and children:

When using cyclophosphamide in combination with other anticancer drugs may require dose reduction of both cyclophosphamide and other .

After addition of the solvent vial is shaken vigorously in order to completely dissolve the drug. If rapid and complete dissolution is not reached, the vial should be left to stand for several minutes.
To. solution for infusion of the drug to the resulting solution was added Cyclophosphamide Ringer’s, 0.9% sodium chloride solution or dextrose solution, so that the total liquid volume was approximately 500 ml.

Side effects Hematopoietic system : leukopenia, neutropenia; rarely, thrombocytopenia, anemia. The largest decrease in the number of white blood cells and platelets usually occurs 7-14 days of treatment.Recovery leukopenia usually begins 7-10 days after discontinuation of treatment. On the part of the digestive system : nausea, vomiting, anorexia, stomatitis, less often, discomfort or pain in the abdomen, diarrhea or constipation, there are isolated reports of the development of hemorrhagic colitis, jaundice. Rarely, abnormal liver function, manifested an increase in transaminases, alkaline phosphatase and bilirubin in blood serum. In 15-50% of patients receiving high, dose cyclophosphamide in combination with busulfan and. total irradiation during allogeneic bone marrow transplantation develop veno-occlusive disease of the liver. A similar reaction in very rare cases are also observed in patients receiving high doses of cyclophosphamide methenolone enanthate in patients with aplastic anemia. The syndrome usually develops within 1-3 weeks after transplantation of the bone marrow and is characterized by rapid weight gain, hepatomegaly, ascites and hyperbilirubinaemia.