primobolan depot

primobolan depot – lipid-lowering agents of the statin group. The main mechanism of action is inhibition of primobolan depot 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonic acid. This transformation is one of the early steps in the chain of cholesterol synthesis in the body. Inhibition of cholesterol synthesis primobolan depot leads to an increased reactivity of the LDL receptor (low density lipoproteins) in the liver and extrahepatic tissues in. These receptors bind LDL particles and remove them from the plasma, resulting in a reduction of LDL cholesterol in the blood. Antisclerosic effect primobolan depot is a consequence of the impact of the drug on the vessel walls and blood components. The drug inhibits the synthesis of isoprenoids, which are growth factors vascular inner lining of cells. Under the influence of primobolan depot improves endothelium-dependent vasodilation. primobolan depot reduces cholesterol, LDL, apolipoprotein B, triglycerides. Causes an increase in HDL cholesterol (HDL) and apolipoprotein A. As a rule, the action Atoris develops after two weeks of treatment, and the maximum effect is achieved within four weeks.

Pharmacokinetics

The absorption of primobolan depot high, about 80% is absorbed from the gastrointestinal tract. Occurrence of a maximum concentration (C max), average 2.1 hours. Women have higher Cmax by 20%, and AUC indicator – below 10%. In patients with alcoholic cirrhosis of the liver time to maximum concentration is 16 times higher than normal. Due to intensive metabolism in the “first pass” through the liver bioavailability of primobolan depot is low (12%). The average volume of distribution of primobolan depot is equal to 381 liters. More than 98% of primobolan depot is bound to plasma proteins. primobolan depot not penetrate the blood-brain barrier. It is metabolized primarily in the liver by the action of cytochrome P4503A4 with the formation of pharmacologically active metabolites (ortho and paragidroksilirovannye metabolite, beta-oxidation products). This active metabolites which cause approximately 70% of the inhibitory activity against HMG-CoA reductase, which is stored 20-30 hours.
The half-life is 14 hours primobolan depot. Write mainly in the bile (not exposed to pronounced enterohepatic recirculation is not output during hemodialysis). Approximately 46% of primobolan depot is excreted in the faeces, and less than 2% is excreted in the urine.

Indications
Primary hypercholesterolaemia, mixed hyperlipidaemia (including patients with non-insulin dependent diabetes mellitus), heterozygous and homozygous familial hypercholesterolemia (as a supplement to the diet).

Contraindications

  • Hypersensitivity to any component of the drug;
  • liver disease in active phase (including chronic active hepatitis, chronic alcoholic hepatitis);
  • liver failure;
  • cirrhosis of any etiology;
  • increased activity of “liver” transaminases of unknown origin;
  • skeletal muscle disease;
  • pregnancy and lactation;
  • age of 18 years (effectiveness and safety have not been established)

Precautions: alcoholism, liver disease, a history of severe electrolyte imbalance, endocrine and metabolic disorders, arterial hypotension, severe acute infection (sepsis), uncontrolled epilepsy, extensive surgery, trauma.

Dosage and administration
Before the treatment Atoris patient should be transferred to a diet providing a reduction in lipid content in the blood, which must be observed during drug therapy.
The drug is taken orally on an empty stomach or after a meal. For the below dosing regimen, the drug is possible in other registered dosages (Atoris film-coated tablets 10 mg and 20 mg).
The recommended initial dose – 10 mg daily. Depending on the desired effect, the daily dose may be increased to 80 mg. Atoris can be taken once daily at any time of the day, but at the same time each day.The therapeutic effect was observed after two weeks of treatment, and the maximum effect developed after four weeks. Therefore, the dose should not be changed earlier than four weeks after starting the drug in the previous dose.

Primary (heterozygous and polygenic hereditary), hypercholesterolemia (type IIa) and mixed hyperlipidaemia (type IIb)
Treatment begins with a recommended starting dose, which is increased after four weeks, depending on the patient response. The maximum daily dose is 80 mg.

Homozygous Familial Hypercholesterolemia
The dose range is the same as for other types of hyperlipidemia. The initial dose is selected individually depending on the severity of the disease. The majority of patients with homozygous familial hypercholesterolemia an optimal effect was observed when using the drug in a daily dose of 80 mg (once). Atoris used as an adjunct therapy to other treatments (plasmapheresis), or as a primary treatment, if treatment with other methods is not possible.

In the elderly and in patients with kidney disease should not change the dose Atoris.

In patients with impaired hepatic function , caution is necessary due to the slowing of excretion of the drug. In such a situation should be closely monitored clinical and laboratory parameters and the detection of significant lesions dose should be reduced or treatment should be discontinued.

Side effect
On the part of the nervous system: headache, dizziness, asthenic syndrome, insomnia or drowsiness, nightmares, amnesia, paresthesia, peripheral neuropathy, emotional lability, ataxia, hyperkinesis, depression, hypersensitivity.
From the senses: amblyopia, tinnitus , dryness of the conjunctiva, disturbance of accommodation, eye hemorrhage, deafness, glaucoma, parosmiya, loss of taste.
On the part of the cardiovascular system: palpitation, vasodilatation, migraine, postural hypotension, increased blood pressure, phlebitis, arrhythmia,
part of the hemopoietic system: anemia , lymphadenopathy, thrombocytopenia.
The respiratory system: bronchitis, rhinitis, dyspnea, asthma, epistaxis.
From the digestive system: nausea, heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, anorexia or increased appetite, dry mouth , regurgitation, dysphagia, vomiting, stomatitis, esophagitis, glossitis, gastroenteritis, hepatitis, hepatic colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, increased activity of “liver” enzymes, rectal bleeding, melena, bleeding gums, tenesmus.
From the musculoskeletal system: arthritis, leg muscle cramps, bursitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, joint contractures.
From the urogenital system: urogenital infections, dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, compelling urge to urinate), cystitis, hematuria, vaginal bleeding, uterine bleeding, kidney stones disease, metrorrhagia, epididymitis, decreased libido, impotence, ejaculation disorder.
With the Skin: alopecia, sweating, eczema, seborrhea, ekhimatozy.
Allergic reactions: itching, skin rash, contact dermatitis, rarely urticaria, angioneurotic edema, facial edema, photosensitivity, anaphylaxis, erythema multiforme exudative, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome).
Laboratory tests : hyperglycemia, hypoglycemia, increased serum CPK, albuminuria, increased ALT, ACT
Other: peripheral edema, weight gain, gynecomastia, exacerbation of gout.

Overdose
In case of overdose requires the following general activities: monitoring and maintenance of vital functions and preventing further absorption of the drug (gastric lavage, activated charcoal or laxatives).
With the development of myopathy followed by rhabdomyolysis and acute renal failure (a rare but serious side effect of) the drug It should be immediately canceled and the patient must enter a diuretic and sodium bicarbonate solution. If necessary, to conduct hemodialysis. Rhabdomyolysis can lead to hyperkalemia, which is required to remove the intravenous chloride or calcium gluconate, calcium, glucose infusion with insulin, the use of ion exchangers potassium or, in severe cases, hemodialysis. Since primobolan depot is largely associated with plasma proteins, hemodialysis is a relatively inefficient way of removing the substance from the body.

The interaction with other drugs
Simultaneous use of primobolan depot with cyclosporine, antibiotics (erythromycin, clarithromycin, quinupristin / dalfopristin), HIV protease inhibitors (indinavir, ritonavir), antifungal drugs (fluconazole, itraconazole, ketoconazole), or nefazadonom may increase the content of primobolan depot serum, which increases the risk of myopathy and rhabdomyolysis with renal failure. A similar interaction is possible in the combined reception Atoris with fibric acid derivatives and niacin.
Simultaneous administration of primobolan depot with phenytoin may reduce the effectiveness of primobolan depot. When co-administered, antacids (suspension of magnesium and aluminum hydroxides) reduce the amount of primobolan depot in the blood plasma. When simultaneous administration of primobolan depot with primobolan depot colestipol concentration is reduced by 25%, but the therapeutic effect of the combination is higher in plasma than the effect of primobolan depot. In patients concomitantly receiving primobolan depot 80 mg and digoxin, digoxin plasma levels increases by approximately 20%. Patients receiving primobolan depot with digoxin should be monitored.
If coadministration of primobolan depot with an oral contraceptive (norethindrone and ethinyl estradiol combination) may increase absorption of contraceptives and increasing their plasma concentrations. It is necessary to control the range of contraceptives in women receiving primobolan depot. Simultaneous administration of primobolan depot with warfarin may intensify in the early days of the action of warfarin on the blood coagulation indicators (decrease of prothrombin time). This effect disappears after 15 days of co-administration of these drugs.
Juice Grapefruit Use Atoris for treatment may increase the plasma concentration of the drug. Therefore, patients taking Atoris should avoid drinking this juice.

Cautions
Before therapy Atoris patient must assign a standard hypocholesterolemic diet, which he must comply during the entire treatment period.
The increased activity of “liver” enzymes in the serum can be observed during the treatment Atoris. This increase is usually small and has no clinical significance. However, the recommended control “liver” enzymes in serum before treatment and after 6 weeks and 12 weeks with increasing doses of primobolan depot. If celebrated three times, with respect to the upper limit of normal, increased ACT activity and / or ALT, Atoris treatment should be discontinued.
primobolan depot may cause an increase in the activity of creatine phosphokinase and transaminase.
In women of reproductive age who are not using reliable contraception, Atoris use is not recommended. If the patient plans pregnancy, she should stop taking Atoris at least one month before the planned pregnancy.
Treatment Atoris may cause myopathy, which is sometimes accompanied by rhabdomyolysis leading to acute renal failure. The risk of this complication increases with simultaneous reception with Atoris one or more of the following drugs:. Fibric acid derivatives, niacin, cyclosporine, nefazadon, certain antibiotics, antifungal agents from the group “azoles” HIV inhibitor – protease Effects on ability to drive and work with the mechanisms of the adverse impact Atoris on ability to drive and work with the mechanisms have not been reported.

Tagged