Means, deplete catecholamines (reserpine, inhibitors), since they can cause severe bradycardia and hypotension.
Calcium channel blockers (verapamil, diltiazem) and antiarrhythmic drugs (especially class 1), because they can provoke severe hypotension and heart failure. Intravenous administration of these drugs in conjunction with taking carvedilol is contraindicated.
Tri tren side effects agonists (due to the possibility of hypertension, severe reflex bradycardia and asystole, and reducing beta-adrenoceptor blocking action of carvedilol).
- Clonidine and carvedilol may enhance each other’s ability to lower blood pressure and heart rate. In a joint application removal should be gradual, starting with carvedilol, then a few days could be gradually stopped receiving clonidine
- Digoxin (slows atrioventricular conduction);
- Insulin and hypoglycemic agents for oral use (due to increased hypotensive effect and masking symptoms of hypoglycemia);
- Nitrates and antihypertensives (clonidine, guanethidine, alpha-methyldopa, guanfacine, etc.) – Due to increased hypotensive effect and reduce the heart rate;
- The means for anesthesia (due to their negative inotropic action and hypotensive effect);
- Agents affecting the central nervous system (hypnotics, tranquilizers, tricyclic antidepressants, and ethyl alcohol) due to the possibility of mutual reinforcement effects;
- Nonsteroidal anti-inflammatory drugs (due to the reduction of hypotensive action due to decreased production of prostaglandins);
- Ergotamine (to take into account ergotamine vasoconstrictor effect);
- Xanthine derivatives (aminophylline, theophylline) – due to the reduction of beta-adrenoceptor blocking action.
Since carvedilol undergoes oxidative metabolism, the pharmacokinetics may change when the induction or inhibition of the enzyme cytochrome P 450. Therefore, the effect should be taken into account:
- Rifampicin (there is 70% reduction in the carvedilol concentration in the serum);
- Barbiturates (reduced effect of carvedilol)
- Cimetidine (increased bioavailability Carvedilol 30%);
- Digoxin (increases concentration of digoxin in the blood plasma);
- Inhibitors isoenzyme tri tren side effects (quinidine, fluoxetine, paroxetine, propafenone) can assume increasing concentrations of R (+) enantiomer of carvedilol;
- Cyclosporine (cyclosporine metabolism of carvedilol delay)
Patients with severe heart failure, with electrolyte imbalance, with a reduced level of blood pressure (less than 100 mm Hg) or in the elderly should be kept under close medical supervision for 2 hours after taking the first dose or after receiving the first dose increased, due to the risk of a sudden drop in blood pressure, orthostatic hypotension and syncope. The risk of these complications can be reduced with the appointment of the drug in the small initial doses and receiving it during the meal.
The dose should be reduced if the patient is marked bradycardia (heart rate less than 55 beats per minute)
Appointment of carvedilol in patients receiving cardiac glycosides, diuretics and / or angiotensin converting enzyme inhibitors for heart failure requires special care.
patients with heart failure if they initial systolic blood pressure less . Art. or are associated diseases – coronary heart disease, peripheral vascular disease or renal dysfunction, should frequently check the condition of the urinary system, because the treatment may affect renal function (usually temporarily). If marked inhibition of renal function, Talliton dose should be reduced or treatment should be discontinued.
In patients with angina tri tren side effects indiscriminate beta-blockers can cause chest pain. Although α 1 adrenoblokiruyuschee effect can prevent this action.
The appointment of the drug in unstable angina, as well as atrioventricular block I degree, requires attention, frequent ECG and careful medical monitoring of patients.
Treatment of patients with peripheral arterial disease requires attention and care. Like other beta-blockers, carvedilol may mask the symptoms of hypoglycaemia and adversely affect carbohydrate metabolism. In accordance with this treatment carvedilol diabetics require special attention and more frequent measurement of blood sugar. Furthermore, Talliton contains sucrose in its composition, which should also be taken into account when treating patients with diabetes.
Carvedilol may mask symptoms of increased thyroid function. With the sudden cancellation of the drug will probably gain hyperthyroidism and possible thyrotoxic crisis.
Treatment Talliton patients with established pheochromocytoma should not begin until the appropriate therapeutic blockade of the alpha-adrenergic receptors.
Treatment Talliton psoriasis patients requires an assessment of the benefit / risk as carvedilol may enhance disease or trigger the onset of symptoms.
Talliton each tablet contains 50 mg of lactose. This amount should be taken into account when lactase deficiency, galactosemia and malabsorption syndrome tri tren side effects.
Each tablet Talliton contains 12.5 mg of sucrose. This may be important in diabetes, hereditary fructose intolerance, glucose malabsorption / galactose or deficit sucrase / isomaltase.
Termination treatment should gradually reducing the dose.
Patients who use contact lenses should be warned that carvedilol reduces production of tear fluid.
The use Talliton during pregnancy and during breast-feeding newborns contraindicated. If necessary, use during lactation should be excluded trenbolone hex breastfeeding.
Dosing and Administration
The tablets taken orally. Should be swallowed whole and drink plenty of fluids. When essentsialnoy hypertension : The recommended starting once a day for 2 days (one tablet of 12.5 mg in the morning and one tablet of 6.25 mg twice daily – one morning and one evening). The recommended maintenance dose is 25 mg Talliton (one tablet of 25 mg in the morning and one tablet of 12.5 mg twice a day – one in the morning and the other -vecherom). In the case of an unsatisfactory trenbolone hex result, but not earlier than 14 days of treatment, the dose can be increased to a maximum – 50 mg per day (one tablet of 25 mg twice a day – morning and evening). The maximum single dose of 25 mg, and the daily dose should not exceed 50 mg. Chronic stable angina pectoris : The recommended initial dose – 12.5 mg twice a day (morning and evening) during the first two days. The recommended maintenance dose – 25 mg twice a day (morning and evening). In the case of unsatisfactory results, but not earlier than 14 days of treatment, the dose can be increased to a maximum – 50 mg twice daily (two tablets of 25 mg in the morning and two tablets in the evening). Congestive heart failure : the dose should be adjusted individually, while increasing carry out a thorough dose monitoring.
The dose is selected based on each individual case. It is necessary to observe the condition of the patient within 2-3 hours after the first or after receiving the first dose is increased. Additional application requires a stable clinical condition. Dose and administration of other drugs, such as digoxin, diuretics and inhibitors, must be recorded to the destination. Patients must take the tablets during the meal (to reduce the risk of orthostatic hypotension) The recommended starting dose of 3,125 mg twice a day for 14 days (½ tablets of 6.25 mg in the morning and evening). If the patient tolerated the treatment well and there is a need to increase the dose can be 6.25 mg twice a day (one tablet of 6.25 mg in the morning and one -vecherom). Possible subsequent increase in the dose of 12.5 mg twice a day (one tablet of 12.5 mg in the morning and evening), then up to 25 mg twice a day (one tablet of 25 mg in the morning and evening). Patients administered the maximum tolerated dose. The maximum recommended dose – 25 mg twice a day (one tablet of 25 mg in the morning and one – in the evening) for patients weighing up to 85 kg and 50 mg twice daily (two tablets of 25 mg in the morning and two in the evening) for patients weighing more than 85 kg. Patients with heart failure to prevent orthostatic hypotension it is recommended to take the drug during meals. At the beginning of the treatment and to increase each dose condition of patients should be monitored as possible worsening of heart failure. May develop fluid retention, and due to the vasodilator trenbolone hex and lethargy. When fluid retention should increase the dose of diuretics, in addition, may require temporary dose reduction Talliton. In some cases, treatment should be temporarily suspend Talliton.
At recommended doses, the drug is generally well tolerated, but in some cases may cause side effects: On the part of the central nervous system : headache, syncope, dizziness, fatigue, rarely – depressed mood, sleep disturbance, paresthesia Cardio-vascular system : orthostatic hypotension, bradycardia, marked reduction in blood pressure, angina, rarely – a violation of the peripheral circulation (cold extremities), “intermittent” claudication or Raynaud’s syndrome, peripheral edema, atrioventricular block, the progression of heart failure of the respiratory system : dyspnea, bronchospasm. seldom – nasal congestion From the gastrointestinal tract : dry mouth, nausea, diarrhea, abdominal pain. rarely – constipation, vomiting, increased activity of “liver” transaminases. On the part of the skin : allergic rash, hives, itching, worsening of trenbolone hex psoriatic lesions, it is very rare – anaphylactoid reactions From the blood : leukopenia, thrombocytopenia. Other : rarely – pain in the extremities, a decrease production of tear fluid, eye irritation, urinary disorders, renal failure, influenza-like syndrome. As with other beta-blockers may occur latently current diabetes or worsen its symptoms.
Overdose Symptoms : may develop severe hypotension, bradycardia, heart failure, cardiogenic shock, cardiac arrest. Treatment : success can be gastric lavage or administration of emetics, if they are carried out within a few hours after taking the drug. Overdose trenbolone hex requires intensive treatment. The patient should be in the raised position. Antidote beta-adrenoceptor blocking action is ortsiprenalin or isoprenaline 0.5-1 mg intravenously and / or glucagon in a dose of 1-5 mg (maximum dose 10 mg). Severe hypotension treated with parenteral fluids and repeated administration of epinephrine in a dose of 5-10 mg (or intravenous infusion at a rate of 5 g / min). For the treatment of excessive bradycardia atropine administered intravenously at a dose of 0,5-2 mg. In order to maintain cardiac function: Glucagon – 1-10 mg intravenously quickly for 30 seconds, after which a constant infusion rate of 2-5 mg / hour. If the predominant peripheral vasodilator effect (warm extremities, in addition to significant hypotension), you must assign norepinephrine in repeated doses for 5-10 mg, or in the form of infusion -. 5 g / min for the relief of bronchospasm prescribe beta-agonists (as aerosol or intravenously) or aminophylline intravenously. If you develop seizures, it is recommended the slow introduction of diazepam or clonazepam. In severe cases of intoxication when dominated shock symptoms antidote treatment should continue until the patient’s condition has stabilized, considering the half-life of carvedilol (6-10 hours).
Following oral administration, carvedilol is rapidly absorbed from the gastrointestinal tract. It is metabolized in the “first” pass through the liver, its bioavailability is about 25%. The maximum plasma concentration is reached about 1 hour after ingestion of the drug. The pharmacokinetics of carvedilol is linear (plasma concentrations proportional to the dose). Concomitant food has no effect on the bioavailability of carvedilol and its maximum concentration in plasma, but may increase the time to maximum blood concentration.
What is tren is a lipophilic compound, its binding to plasma proteins reaches 98-99%. The apparent volume of distribution is approximately 2 l / kg and is largely increased by cirrhosis of the liver. Metabolism of Carvedilol is metabolized primarily in the liver, primarily due to the formation of glucuronides. Demethylation and hydroxylation of the phenyl ring results in the formation of active metabolites with three beta adrenoblokiruyuschey activity. 4-hydroxy metabolite, beta-blocker, is 13 times more active carvedilol. At the same time, active metabolites are weaker vasodilator and two gidroksikarbazolovyh more metabolite are strong antioxidants compared to the parent compound. The average half-life of carvedilol – 6-10 hours and plasma clearance Carvedilol is released mainly in the bile. Carvedilol and its metabolites can cross the placenta and are excreted in the mother’s milk. Carvedilol is practically not removed from blood by hemodialysis. Specific categories of patients Elderly patients : The concentration of carvedilol in plasma in elderly patients is 50% higher than in the young. Patients with renal impairment : Since carvedilol is derived mainly what is tren through the gastrointestinal tract, impairment of renal function is not accompanied by his cumulation. Patients with liver disease : in liver cirrhosis the bioavailability of carvedilol in 4 times, and the maximum plasma concentration – 5 times higher than normal.
- essential hypertension – either alone or in combination with a diuretic
- stable angina
- Chronic heart failure *, in combination with a diuretic, digoxin or angiotensin converting enzyme inhibitors
- Hypersensitivity to the drug
- Heart failure in decompensation stage
- conduction disorders (sick sinus syndrome, sinoatrial block, atrioventricular block degree II-III), except for patients with artificial pacemaker
- Severe bradycardia (heart rate less than 50 beats per minute)
- Arterial hypotension (systolic blood pressure less than 85 mmHg)
- Cardiogenic shock
- Bronchial asthma
- Severe hepatic dysfunction
- Metabolic acidosis what is tren
- Children under the age of 18 years (due to lack of clinical application experience)
- Sharing intravenous verapamil, diltiazem or other antiarrhythmics (especially antiarrhythmics class I) (see. Also “Interactions”).
Precautions : (see also special instructions)
- Chronic obstructive pulmonary disease;
- Prinzmetal angina;
- Hypoglycemia, hyperthyroidism;
- Pheochromocytoma (only stabilized the appointment of alpha-blockers)
- Occlusive peripheral vascular disease;
- Atrioventricular block of I degree;
- Unstable angina;
- Impaired renal function;
- Myasthenia gravis;
- In the treatment of α 1 adrenoblokatorami or α 2 -adrenomimetikami;
- The combined use of what is treninhibitors .
The main expected manifestations of overdose include bone marrow suppression, peripheral neuropathy and mucositis. Currently, the antidote is not known to docetaxel. In the case of an overdose the patient should be hospitalized in a specialized unit and closely monitor vital organ function. Patients should be as soon as possible to appoint a tri tren side effects. If necessary – symptomatic therapy.
Interaction with other drugs
Studies in vitro have shown that the drug biotransformation may be changed while the application substances inducing or inhibiting cytochrome system or metabolized by cytochrome system, such as cyclosporine, terfenadine, ketoconazole, erythromycin and troleandomycin. Therefore caution should be exercised with concomitant administration of these drugs, given the opportunity to express interaction.
In vitro drugs strongly bind to proteins, such as erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylate, sulfamethoxazole and sodium valproate, have no effect on protein binding of docetaxel. Dexamethasone has no effect on the degree of binding to plasma proteins docetaxel. Docetaxel has no effect on protein binding of digitoxin.
When used in combination with docetaxel, doxorubicin, docetaxel clearance increases while maintaining its efficacy. In this doxorubicin clearance level and doxorubicinol in plasma not menyaetsya.Klirens carboplatin in combination therapy with docetaxel increases by 50% than when carboplatin monotherapy.
The effects of docetaxel n the pharmacokinetics of the main metabolite of capecitabine and the effect of capecitabine on the pharmacokinetics of docetaxel have been identified.
Taxotere treatment should be carried out only under the supervision of a physician with experience in cancer chemotherapy in a specialized hospital.
There should be careful monitoring of the blood count in patients receiving therapy with Taxotere. If severe neutropenia tri tren side effects during a course of therapy is recommended to reduce dose for subsequent courses or use appropriate symptomatic measures. Continue to follow-up treatment possible after recovery of neutrophils to 1500 cells / mm.
C to identify hypersensitivity reactions, patients should be monitored closely, especially during the first and second infusions. The development of hypersensitivity reactions is possible on the very first minute infusion of Taxotere. Mild symptoms of hypersensitivity (localized redness of the face or skin reactions) do not require interruption of drug administration. Severe hypersensitivity reactions (lowering blood pressure, bronchospasm or generalized rash / erythema), demand the immediate lifting of administration and appropriate therapeutic interventions for relief of these complications. Reuse of Taxotere in these patients is not permitted.
Patients receiving docetaxel monotherapy at 100 mg / m 2, and having a high activity of serum transaminases is more than 1.5 times , combined with increased serum levels of alkaline phosphatase in more than 2.5 times , extremely high risk of developing serious side effects: sepsis, gastrointestinal bleeding, febrile neutropenia, infections, thrombocytopenia, stomatitis and asthenia. Due to such patients with elevated liver function indicators Taxotere recommended . Liver function tests should be determined before the start of therapy and before each subsequent cycle of therapy. Patients with elevated bilirubin and / or increased activity of tri tren side effectsin conjunction with increased levels of alkaline phosphatase more than 6 times the is not recommended to use Taxotere. At the moment, there are no data on the use of Taxotere in combination with other drugs in patients with impaired hepatic function.
In connection with the possibility of fluid retention, the need for careful monitoring of patients with pleural effusion, pericardial or ascites. When edema – the restriction of salt and fluid intake and diuretics.
In the combination therapy Taxotere, doxorubicin and cyclophosphamide risk of developing acute leukemia is comparable to the risk in the treatment regimen containing anthracycline / cyclophosphamide.
Men and women of childbearing age during treatment with Taxotere and for at least three months after cessation of therapy is necessary to use reliable methods of contraception.
Taxotere is an anticancer agent; As in the case of other potentially toxic substances must be careful when applying it and preparing solutions. It is recommended to use these gloves. If you concentrate, premix solution or infusion of Taxotere gets on your skin, it should immediately be washed thoroughly with soap and water. After contact with the concentrate, premix solution or infusion solution of tri tren side effects in the mucous membranes, they should be immediately and thoroughly rinse with water.
From the nervous system: peripheral neuropathy as a mild to moderate paresthesia, hyperesthesia, dysesthesia or pain including burning. Movement trenbolone disorders characterized by weakness. In case of these symptoms require dose adjustment. If symptoms persist, treatment should be discontinued. Rarely observed the development of seizures, and transient loss of consciousness.
Cardio-vascular system: cardiac arrhythmia (sinus tachycardia, atrial fibrillation), heart failure, high or low blood pressure. Occasionally there have been cases of venous thromboembolism and myocardial infarction.
From the hepato-biliary system: in patients receiving Taxotere monotherapy at a dose of 100 mg / m 2 , increased serum activity , and alkaline phosphatase concentration in serum bilirubin more than 2.5 times the upper limit of normal, says less than 5%. Very rarely there have been cases of hepatitis (fatal outcome was observed in patients with liver disease in history).
From the respiratory system: very rarely – acute respiratory distress syndrome, interstitial pneumonia, pulmonary fibrosis and increased reaction to radiation.
From the Musculoskeletal System: arthralgia, myalgia, muscle weakness. On the part of the organs of vision: rarely – the development tearing combined with conjunctivitis (or without it), transient visual disturbances (flashes of light in the eyes, the appearance of cattle), usually occurring during injection and development combined with hypersensitivity reactions, which usually disappear after cessation of infusion; very rarely, mainly in patients receiving the combination of other antineoplastic agents may develop occlusion of the tear duct, resulting in excessive tearing.
Reactions at the injection site : moderately trenbolone expressed and manifested in the form of hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis, hemorrhage or venous edema. Other: fatigue, shortness of breath, generalized or local pain, including chest pain, non-cardiac diseases and lungs. When using docetaxel (Taxotere) in combination with capecitabine is observed more frequent adverse events from the gastrointestinal tract, hand-jog syndrome (limb skin redness (hands and feet), followed by swelling and desquamation), dehydration, watery eyes, arthralgia, heavy thrombocytopenia and anemia, hyperbilirubinemia, but more rare development of severe neutropenia, alopecia, violations of the nails, fatigue, myalgia, edema of the lower extremities. Patients 60 years and older who received combination therapy with capecitabine and Taxotere, compared with younger patients, more frequent development toxicity grade 3-4.
Patients receiving combination treatment trenbolone and trastuzumab was found a higher rate of side effects and more frequent development toxicity grade 4, compared monotherapy. cases of heart failure were identified, especially in addition to therapy with anthracyclines (doxorubicin or epirubicin).
When using docetaxel in combination with cisplatin febrile neutropenia and / or neutropenic infection complications arise in the smaller percentage of cases when administered .