Studies in patients, showed similar pharmacokinetic parameters of abacavir, lamivudine and zidovudine when used in a fixed combination (zidovudine + lamivudine) in conjunction. In addition, these parameters are similar to those which were obtained in the investigation of bioequivalence in healthy volunteers. A comparative study of bioequivalence and combination of lamivudine 150 mg zidovudine 300 mg tablets taken together on an empty stomach, as well as the impact assessment food on the rate and extent of absorption. It is shown that in the fasting Combivir bioequivalent lamivudine 150 mg in combination with zidovudine 300 mg, used as single agents. A comparative study of bioequivalence and combinations of lamivudine 150 mg zidovudine 300 mg and abacavir dose 300 mg, taken together, as well as the assessment of the impact of food on the rate and extent of absorption. Results of the analysis parameters indicate bioequivalent lamivudine 150 mg in combination p28 pancake mix with zidovudine 300 mg and abacavir 300 mg of individual drugs, and the reception food did not lead to clinically meaningful changes in pharmacokinetics parameters. Absorption When administered lamivudine, abacavir and zidovudine is rapidly and well absorbed from the gastrointestinal tract. The absolute bioavailability of lamivudine, abacavir and zidovudine after ingestion in adults is 80-85%, respectively, 83% and 60-70%. Food intake reduces the rate of absorption of Trizivir active substances, resulting in a slight decrease in the maximum concentration and an increase in the time to reach maximum concentration for approximately 1 hour, but is not reflected in the area under “concentration-time” . These changes pharmacokinetic parameters are not clinically significant trenbolone side effects, so Trizivir can be taken with food or on an empty stomach. Distribution The volume of distribution of lamivudine, abacavir and zidovudine when administered intravenously is an average of 1.3, 0.8 and 1.6 l / kg respectively.Lamivudine anabol tablets 5mg/1000 methandienone basic protein binding to plasma, albumin, slightly ( in vitro at least 36% serum albumin), and therefore pharmacokinetics of lamivudine is linear. Zidovudine is bound to plasma proteins at 34-38%.According to studies in vitro , in therapeutic doses abacavir binds to serum proteins to approximately 49%.
The interaction Trizivir active ingredients with other drugs by their displacement from the compound to plasma proteins is unlikely. Thus should also not enter into such a variant interaction with drugs, which are mediated by displacement of their connection with the plasma proteins. Lamivudine, zidovudine and abacavir penetrate the blood-brain barrier and is found in the cerebrospinal fluid. The ratio of the concentration of lamivudine and zidovudine serum to the appropriate concentration of the drug in theafter 2 to 4 hours after ingestion of an average of about 0.12 to 0.5 for lamivudine and zidovudine. The true extent of penetration of lamivudine , as well as the clinical significance of this phenomenon has not yet been established. According to studies patients, abacavir penetrates well into anabol tablets 5mg/1000 methandienone, and the tren side effects of abacavir in is 30-44% of abacavir in plasma. In Phase 1 clinical trial to study the pharmacokinetics of abacavir indicated that at 1.5 hours after administration of a dose of abacavir 300 mg 2 times a day, its concentration in anabol tablets 5mg/1000 methandienone is 0.14 g / ml.When applying abacavir 600 mg 2 times a day, its concentration in increased from 0.13 ug / ml after 0.5-1 hours after administration, up to 0.74 g / mL within 3-4 hours.
Gentamicin is a broad-spectrum antibiotic of the aminoglycoside. Bactericidal and provides highly effective topical treatment of primary and secondary bacterial infections of the skin. Active against gram-negative bacteria: Pseudomonas aeruginosa, Aerobacter aerogenes, Escherichia coli, anaerober abbau methandienone pneumoniae; gramopolozhitelnyh bacteria: Streptococcus spp, Staphylococcus aureus (coagulase-positive and coagulase-negative strains have penicillinase)..
dermatoses, complicated infections caused by pathogens sensitive to the drug, or if you suspect such infection, including – simple and allergic dermatitis, atopic dermatitis (including atopic dermatitis), limited atopic dermatitis, eczema, ringworm (tinea , candidiasis, pityriasis versicolor), especially in the localization in the groin area and large folds of the skin; simple chronic zoster (restricted neurodermatitis).
: Hypersensitivity to any component of the drug, lupus, cutaneous manifestations of syphilis, chickenpox, herpes simplex, skin reactions after vaccination, open wounds, children’s age (up to 2 years).
of pregnancy (especially in I trimester), children (> 2 years), long-term treatment, the use of large areas of the skin, or in violation of skin integrity, the use of occlusive dressings (especially in children).
Use during pregnancy and lactation
The use of triderm during pregnancy anaerober abbau methandienone is possible only when the intended benefits to the mother outweighs the potential risk to the fetus.
It is not known whether the components of the drug are excreted in breast milk. When assigning triderm during lactation should decide the issue of termination of breastfeeding.
Dosage and administration
Ointment Triderm should be applied a thin layer on the entire surface of the affected skin and surrounding tissue twice a day – morning and night. To be effective, treatment should be applied ointment Triderm regularly.
The duration of treatment depends on the size and location of the lesion, as well as the response of the patient.
If clinical improvement does not occur after 3-4 weeks of treatment, it can serve as a pretext for further diagnosis.
Very rarely, when applying triderm observed: burning sensation, erythema, exudation, pigmentation disorders and itching.
Adverse reactions, occurring in the application of local corticosteroids (especially when using occlusive dressings): burning sensation, itching, dryness, folliculitis, hypertrichosis, acne , hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria.
Adverse reactions due to clotrimazole : erythema, tingling, blistering, peeling, local swelling, itching, hives, skin irritation.
Adverse reactions caused by gentamicin : transient skin irritation (erythema, itching) usually does not require discontinuation of treatment.
Overdose Symptoms :. Prolonged use of local corticosteroids in high doses may suppress adrenal function with the development of secondary adrenal insufficiency and Cushing’s symptoms, including Cushing’s syndrome Overdose clotrimazole topically its application does not lead to the appearance of any symptoms. When a single overdose of gentamicin showing any symptoms are not expected. Long-term treatment with gentamicin in high doses can lead to growth insensitive flora. treatment : symptomatic. Acute symptoms of Cushing’s usually reversible. If necessary, a correction of electrolyte imbalance. In case of chronic toxicity SSC recommended the phasing .
Ointment Triderm is not intended for use in ophthalmology.
Prolonged use of topical antibiotics may sometimes lead to the growth of resistant organisms. In this case, and if irritation, sensitization or superinfection during treatment ointment, treatment should cease and prescribe appropriate therapy. There were cross-allergic reactions to aminoglycoside antibiotics.
Any side effects that occur with the use of systemic corticosteroids, including inhibition of the function of the adrenal cortex, can be marked and the local application , particularly in children.
Systemic absorption of corticosteroids or gentamicin in the local application will be higher if the treatment It will be carried out on large areas of skin or at use of occlusive dressings, especially with long-term treatment or in violation of skin integrity. It is necessary to avoid the application of gentamicin on open wounds and damaged skin. Otherwise, it may cause side effects typical of gentamicin when administered systemically. Observe proper precautions in such cases, especially when treating children.
With long-term use of the drug is recommended anaerober abbau methandienone cancellation of his postepennno. Use in pediatric drug Babies prescribed only under strict indications and under medical supervision, as may develop systemic side effects associated with betamethasone. When using triderm, like many other drugs for topical application on the basis of corticosteroids on large surfaces and / or occlusive dressing may suppress the function of the hypothalamic-adrenal gipofizo- system, you may experience slow excretion of growth hormone, and increased intracranial pressure.
Increases myocardial sensitivity to cardiac glycosides with potassium or magnesium deficiency.
At simultaneous reception with mineral and glucocorticoids and laxatives may increase potassium excretion.
It enhances the effect of antihypertensive drugs methandienone. In high methandionone doses, may potentiate the toxic effect of aminoglycoside antibiotics, cisplatin; nephrotoxic effects of cephalosporins and cardio- and neurotoxic effects of lithium.
Effect on vehicle driving and operating machinery.
At the initial stage is not recommended to drive vehicles methandionone and mechanisms to serve because of the possibility of dizziness.
Following oral torasemide anabol dianabol methandrostenolone/ methandienone rapidly and almost completely absorbed in the gastrointestinal tract. Torasemide maximum plasma concentration observed after 1-2 hours after administration. Bioavailability is approximately 80-91% and more edema. Contact with blood plasma proteins – 99%. The volume of distribution is 16 liters. It is metabolized in the liver by cytochrome system . The of torasemide and its metabolites anastrozole bodybuilding in healthy volunteers is 3-4 hours. Torasemide total clearance of 40 ml / min and renal clearance.
Contraindications: Hypersensitivity to torasemide, and sulfonamides; anuria; hepatic coma and prekomatosnoe condition, chronic renal failure with progressive azotemia, arrhythmia, hypotension, pregnancy, lactation (no data on the use during lactation), age 18 years (effectiveness and safety not installed).
Precautions: diabetes mellitus, gout, disorders of water and electrolyte balance, impaired liver function, cirrhosis, predisposed to hyperuricemia.
Dosage and administration . Inside Adults: Oedema: 5 mg 1 time per day. If necessary, the dose can be gradually increased to 1 20 mg once a day. In some cases it is recommended to anabol dianabol methandrostenolone/ methandienone per day. Congestive heart failure: 5 – 20 mg 1 time per day. If necessary, the daily dose can be gradually increased (doubling it), to a maximum of 200 mg. Chronic renal failure: The initial dose is 20 mg per day. If necessary, this dose can be gradually increased (doubling it), before reaching the diuretic effect clinical equipoise definition. The maximum daily dose – 200 mg. Cirrhosis: 5 – 10 mg 1 time per day. If necessary, the dose can be gradually increased (doubling it), to achieve an appropriate diuretic effect. There has been no properly controlled studies in patients with liver disease with doses of 40 mg per day. Primary hypertension: 2.5 mg orally 1 time day. If necessary, the dose can be gradually increased up to 5 mg per day. According to studies, a dose in excess of 5 mg per day did not lead to further decrease blood pressure. The maximum effect is achieved after about twelve weeks of continuous treatment. Elderly patients: Elderly patients do not require a special adaptation of the dose. Children: There are no data regarding the use o in children.
Food does not affect the absorption , so the drug can be taken regardless of meals.
Side effects: From the side of blood: in some cases, may experience changes in blood biochemical parameters: reduction in the number of red blood cells and white blood cells and platelets, hypovolemia, electrolyte imbalance, hypokalemia, increased uric acid in the blood serum glucose and lipids. Increased levels of certain liver enzymes, eg gamma-GT. With the cardiovascular system: in some cases, due to the thickening of the blood, having blood circulation disorders and thromboembolism, lowering blood pressure of blood. On the part of the digestive tract: the various dysfunctions of gastrointestinal -kishechnogo tract phenyl propanoate, loss of appetite, and in some cases may develop pancreatitis. On the part of the kidney and urinary tract infections: acute urinary retention, increased levels of urea and creatinine in plasma. On the part of the central nervous system: headache, dizziness, weakness, drowsiness , confusion, seizures and limb paresthesia. Allergic reactions: itching, rash and photosensitivity. From the senses: visual disturbances, tinnitus, deafness. Other: dry mouth.
Overdose symptoms – typical picture of poisoning do not. In case of overdose – forced urination, accompanied by hypovolemia, electrolyte imbalance, followed by a fall in blood pressure, drowsiness, confusion, collapse. Gastrointestinal disorders may be observed. A anabol dianabol methandrostenolone/ methandienones pecific antidote androgel coupon is not known. Symptomatic treatment involves the reduction of the dose or stop the drug and at the same time replenishing the loss of fluids and electrolytes.
After oral administration of levonorgestrel is rapidly and completely absorbed, its maximum concentration in plasma is about 2 ng / ml, is reached in about 1 hour. After a single oral administration of 0.125 mg of levonorgestrel, together with 0.03 mg of ethinyl estradiol (which corresponds to the highest content of levonorgestrel in a three phase formulation), the highest concentration in the serum component of 4.3 ng / ml, was determined in about 1 hour.
Levonorgestrel binds to serum albumin and globulin, sex hormone binding . The free form is only 1.4% of the total serum concentrations, whereas 55% of the specifically bound to metandienone and about 40% – to albumin. As a result of the induction of the synthesis of ethynyl estradiol binding protein fraction associated increases, while the fraction bound to albumin is reduced. The apparent volume of distribution of levonorgestrel – about 128 l after a single oral tablet Trigestrela containing a higher dose of levonorgestrel.
The equilibrium concentration.
On the pharmacokinetics of levonorgestrel affects concentration in the serum, which is for a 21-day course of Trigestrela increased approximately 2-fold. As a result, the daily ingestion of levonorgestrel serum concentration increases to about 2 times, and the equilibrium concentration is reached in the second half of the course. The volume of distribution at steady state clearance and reduced to 52 l and 0.5 ml / min / kg.
Levonorgestrel is completely metabolized characteristic of sex hormones by metabolizing. After a single oral dose of levonorgestrel high plasma clearance .
Concentration levonorgestrel serum undergoes biphasic decrease. The half-life in the terminal phase is about 22 hours as unchanged Levonorgestrel is not displayed, but only as metabolites via the kidneys and intestines with the half-life of about 24 hours at a ratio of approximately 1: 1..
After oral administration, ethinylestradiol is absorbed rapidly and completely. Maximum serum concentration equal to about 115 pg / ml, is reached in about 1.3 hours. Ethinylestradiol metabolized due to the effect of “primary” passing through the liver, resulting in its oral bioavailability averages about 45%, and there is considerable interindividual differences within 20-65%.
The equilibrium concentration.
The equilibrium concentration is reached after 1 week,
Ethinyl estradiol is almost completely (98%) binds to albumin. Ethinyl estradiol induces the synthesis of SHBG. The apparent volume of distribution of ethinylestradiol – about 3-8 l / kg.
Ethinylestradiol undergoes conjugation presistemna metandienone as in the mucosa of the small intestine and in the liver. The main pathway – aromatic hydroxylation. Clearance from plasma is 2.3-7 ml / min / kg.
of ethinyl estradiol concentration in the serum is reduced bi-phase; The first phase is characterized by a half-life of about 1 hour, and the second -. 10-20 h in an unmodified form of the organism is not displayed. Ethinyl estradiol metabolites are excreted by the liver and kidneys in the ratio 4: 6, with a half-life of about 24 hours.
drug Trigestrel should not be applied if any of the conditions listed below. If any of these conditions develop for the first time in patients receiving the drug should be immediately repealed:
Application with caution
if any of the conditions / risk factors mentioned below are currently available, it is necessary to correlate the potential risks and expected benefits of the use of combined oral contraceptives in each case:
Pregnancy and lactation
Trigestrel not appointed during pregnancy and lactation. If pregnancy is detected during the reception Trigestrel drug, the drug should be immediately abolished. Extensive epidemiological studies have revealed no increased risk of defects in children born to women treated with hormones prior to pregnancy or teratogenic effects when sex hormones were taken inadvertently in early pregnancy.
Receiving combined oral contraceptives can reduce the amount of breast milk and change its composition, therefore, as a rule, their use is not recommended during lactation.
small amounts of sex hormones and / or their metabolites may be excreted in breast milk, but there is no confirmation of their negative impact on infant health.
Dosing and Administration
The tablets should be taken orally in the order indicated on the package, every day at about the same time, with a little water. Take 1 tablet a day continuously for 21 days. Reception begins after the next pack 7dnevnogo tablet-free interval during which bleeding is usually the case “cancellation”.
The bleeding usually starts on day 2-3 after the last tablet and may not end before you start taking a new package.
How to start taking Trigestrela
Receiving Missed tablets
If the delay in receiving the drug was less than 12 hours, contraceptive protection is not reduced. The woman should take the tablet as soon as possible, as soon as remembered; It should be taken at the usual times. If the delay in the pill was more than 12 hours, contraceptive protection may be reduced. The more missed tablets and the closer to the pass 7-day tablet-free interval, the greater the likelihood of pregnancy. It is possible to be guided by the following two basic rules:
A woman can also interrupt taking the tablets from the current package. Then she should take a break for 7 days, including the day of skipping pills and start taking a new package.
If the woman misses pills, and then during a break in taking the drug she has no bleeding, “cancellation”, it is necessary to exclude pregnancy.
Recommendations in case of vomiting and diarrhea
If a woman has had vomiting or diarrhea within 4 hours after taking the pill, the absorption may be incomplete and should be additional contraceptive measures are taken. In these cases, you should be guided by the recommendations by skipping pills.
Changing the date of commencement menstrualnopodobnoe bleeding
To delay the onset menstrualnopodobnoe bleeding, the woman should continue taking the drug, using the last 10 tablets from other packaging Trigestrel drug, without making a break in the reception. Thus, the cycle may be extended for up to 10 days until the end of the second pack. Against the background of the drug from the second package, women may experience spotting or breakthrough uterine bleeding.Regular intake of the drug Trigestrel then resumed after the usual 7-day tablet-free interval. In order to move the first day of bleeding menstrualnopodobnoe on another day of the week, the woman should be reduced the next tablet-free interval to the desired number of days. The shorter the interval, the higher the risk that she will not be bleeding, “cancel” and, in the future, will be spotting or breakthrough bleeding while taking second pack (just as when she wanted to delay the onset of menstrualnopodobnoe bleeding).
Children and adolescents
Trigestrel indicated for use only after menarche.
When receiving combined oral contraceptives metandienone may experience irregular bleeding (spotting or breakthrough bleeding), especially during the first months of use. While taking combined oral contraceptives in women were observed and other undesirable effects, whose connection with the drug intake was not confirmed, but not refuted.
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