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Velaxin
Velaxin is a drug from the category of antidepressants.
Pharmacodynamics
The antidepressant properties of venlafaxine are associated with the potentiation of neurotransmitter activity in the CNS region.
Venlafaxine with its main decay product (O-desmethylvenlafaxine - EFA) is a strong inhibitor medication for reverse serotonin and norepinephrine capture of the aspartate type. In addition, these substances are able to inhibit the process of reverse dopamine capture with the help of neurons.
The active drug component, together with EFA, in case of a single or multiple use, reduces the manifestations of β-adrenergic type. With similar effectiveness, they also affect reverse neurotransmitter capture. In this case, venlafaxine does not exert an overwhelming influence on the activity of MAO agents.
In addition, venlafaxine does not have an affinity for phencyclidine, benzodiazepine, as well as opiate or NMDA endings, and does not affect the release of norepinephrine through the brain tissue.
Pharmacokinetics
About 92% of the substance is absorbed after a single-dose capsule intake. When using capsules with a prolonged release type, the peak values of the active component and its metabolite inside the plasma are observed in the period, respectively 6.0 ± 1.5, and also 8.8 ± 2.2 hours.
The rate of absorption of a substance is slower than the analogous values of its elimination. Therefore, the actual half-life when using capsules with a prolonged release type (15 ± 6 hours) can be considered as a whole a half-absorption period, replacing them with a real half-life (5 ± 2 hours) that develops when the drug is used to release the immediate type.
In the case of receiving equal daily dosages of drugs in the form of immediate-action tablets or capsules with a prolonged effect, the effect of both the active ingredient and the metabolite was similar for both forms of the drug. Fluctuations in plasma values of drugs were slightly lower when using capsules with prolonged action. Because of this, prolonged capsules have a reduced rate of absorption, but while its (suction) volume remains the same as that of tablets with immediate effect.
Excretion of venlafaxine with its decay products is mainly carried out through the kidneys. About 87% of the component is excreted in the urine in a period of 48 hours (unchanged components, conjugated and unconjugated EFA or other secondary decay products are withdrawn).
The half-life of venlafaxine with its active decay product (B-desmethylvenlafaxine) is prolonged in people with liver / kidney failure.
The use of capsules with prolonged effect together with food does not affect the absorption of the components of the drug.
Contraindications
Among the main contraindications:
- intolerance of the constituent elements of the drug;
- combined use with drugs-inhibitors MAO, and also in the period of 2 weeks after the completion of the application of the latter;
- it is required to cancel the use of venlafaxine no later than 1 week before the start of treatment with the use of any drug from the MAOI category;
- increased blood pressure in severe form (180/115 or more before the start of treatment);
- the presence of glaucoma;
- problems with urination due to insufficient outflow of urine (eg, with prostate diseases);
- kidney / liver failure in severe degree;
- There have been no studies on the efficacy and safety of drug use in children, so they are not allowed to take medicine.
Side effects of the velaxin
Taking capsules can cause such side effects:
- reactions from the CCC: often there is an expansion of blood vessels (mainly in the form of redness on the face or hot flushes), as well as an increase in blood pressure. Sometimes tachycardia develops, orthostatic collapse and blood pressure level decreases. Individual fibrillation of the ventricles, rapid heart rate, prolongation of the QT-interval, loss of consciousness and ventricular tachycardia (this includes arrhythmia of the pirouette type);
- disorders of the gastrointestinal tract: often there is constipation, vomiting, worsening of appetite and nausea. Sometimes there may be a gnashing of teeth;
- manifestations of the lymph and blood flow: occasionally there are bleeding in the mucous (for example, in the gastrointestinal tract) and ecchymosis. In some cases, the bleeding period may increase and thrombocytopenia develop. Perhaps the emergence of bloody dyscrasia (this includes neutropenic and pancytopenia, agranulocytosis and aplastic anemia);
- disorders of nutritional metabolism and metabolism: often there is a decrease in weight and an increase in serum cholesterol. Less often there is hyponatremia, there is a deviation of functional hepatic values and weight gain. Occasionally there is diarrhea, hepatitis, pancreatitis and ADH hypersecretion syndrome, and the prolactin index increases;
- disorders in the work of the National Assembly: often weakening of libido, muscle hypertonia, dizziness, and in addition sleep disorders, tremor and paresthesia, dry mouth mucosa, sensation of nervousness, sedation and insomnia, as well as akathisia and balance coordination problems. Less common are hallucinations, a feeling of apathy, myoclonia and serotonin intoxication. Occasionally manic manifestations, seizures, extrapyramidal syndromes (including dyskinesias and dystonia), ZNS (including symptoms similar to CNS), and in addition rhabdomyolysis, late dyskinesia, epileptic seizures and ear noise. Perhaps the development of delirium or psychomotor agitation;
- mental disorders: often there is insomnia, a sense of depersonalization and confusion, and besides strange dreams. Perhaps the emergence of thoughts about suicide and the development of suicidal behavior;
- respiratory system reaction: mainly yawning develops. Possible occurrence of eosinophilia pulmonary type;
- manifestations of the skin: often there is hyperhidrosis (also at night). Less often there is itching, alopecia and rashes. Occasionally there are Lyell or Stevens-Johnson syndromes and erythema polyforma;
- reactions of the senses: often observed mydriasis, a disorder of accommodation or vision and glaucoma. Disturbance of taste buds appears less often;
- disorders in the system of urination and kidneys: often there is dysuria (usually there are difficulties at the beginning of urination). Occasionally, there is a delay in urination;
- disorders in the area of mammary glands and reproductive organs: often men develop an ejaculation disorder and impotence; women develop anorgasmia and menstrual cycle disorders that develop due to an increase in the number of irregular bleeding (eg, in metrorrhagia or menorrhagia);
- systemic manifestations: there is a general feeling of fatigue or weakness, and in addition anaphylaxis, fever and photosensitivity.
Dosing and administration
Capsule medicines should be consumed with food, swallowing whole and washing down with water. Do not crush, open or chew the capsule, but also put it in the water. Reception is carried out once a day at about the same time - in the morning or in the evening.
In the state of depression, it is required to take 75 mg of the drug per day. In case of such necessity, it is possible to increase the dosage to 150 mg once a day after the 2-week course of use. This is done to obtain a subsequent clinical improvement. With a mild degree of disease, the daily dose is allowed to be increased to 225 mg, and at a severe degree to 375 mg. Any increase in dosage is required after every 2 weeks or longer (generally after a minimum of 4 days) - by 37.5-75 mg.
In the case of using Velaxin in a dosage of 75 mg, the antidepressant effect of drugs was observed after the end of 2 weeks of therapy.
In the treatment of anxiety disorders of generalized type, as well as social phobias.
During the treatment of individual anxiety disorders (among which social phobia) per day, it is recommended to take 75 mg of the drug. If this is required to obtain a stronger drug effect, after 2 weeks of treatment it is allowed to increase the daily dosage to 150 mg. Also, it is allowed to raise to 225 mg per day. Increase in dosage is required after every 2 weeks of therapy (or longer, but not less than 4 days later) - by 75 mg.
In the case of taking drugs at a rate of 75 mg, the anxiolytic effect develops after the first medical week.
To prevent the development of relapses or with a supportive type of treatment.
Doctors recommend treating depressive episodes in a period of at least six months.
With a supportive form of treatment, and in addition to preventing the occurrence of relapses or new depressive episodes, doses similar to those that were effective in treating an ordinary depressive episode are often used. The doctor is required constantly, at least 1 time in the period of 3 months to determine the degree of effectiveness of a prolonged therapeutic course.
Completion of venlafaxine use.
During the end of the use of the drug, it is required to gradually reduce its dose. When using Velaxin for more than 6 weeks, you should lower the dosage for at least 2 weeks.
The time interval required to gradually reduce the dosage depends on the size of the dose taken during therapy, and also on the duration of the course and the individual tolerability of the patient.
Inadequate kidney or liver.
People with kidney failure, in which the GFR is> 30 ml / minute, do not need to change the dose. With a GFR <30 ml / minute, the daily dose of the drug should be reduced by 50%. People on hemodialysis should also reduce the daily dosage of drugs by 50%. In this case, Velaxin should be taken at the end of the treatment procedure.
People with a moderate liver failure of a daily dose also reduce by 50%. Sometimes a reduction of more than 50% is required.
Overdose
Manifestations of drug overdose: changes in the parameters of the ECG procedure (prolongation of the QT interval, BLNPG, and prolongation of the QRS complex), CT and ventricular tachycardia, lowering the level of AD, bradycardia, vertigo and mydriasis, as well as the appearance of seizures, vomiting and development of impaired consciousness (from the feeling of drowsiness to the state of coma). Often, such disorders and signs go by themselves.
When treating intoxication, it is required to maintain patency in the respiratory system, providing adequate oxygen saturation and ventilation.
It takes a long time to monitor heart rate and vital functions, and in addition to symptomatic and supportive treatment. Activated carbon can also be used. It is forbidden to induce vomiting, because there is a possibility of aspiration.
Interactions with other drugs
Medicines MAOI.
The combination of venlafaxine with MAOI preparations is prohibited.
There have been reports of serious side effects in people who stopped taking MAOIs shortly before starting venlafaxine or taking venlafaxine shortly before using MAOI. Among the reactions are convulsions, vomiting, tremor with nausea, as well as dizziness, profuse type sweating and fever, against which there were signs such as CNS and seizures, and sometimes death.
As a result, venlafaxine should be used at least 2 weeks after completion of therapy with MAOI.
It is recommended to observe a minimum of 14 days between the end of the use of circulating MAOI with moclobemide, as well as the initiation of venlafaxine therapy. When using MAOIs due to the adverse reactions described above, during this transfer of the patient to venlafaxine from moclobemide, this period should be at least 1 week.
Medicines that have an effect on the function of HC.
Taking into account the mechanism of medicinal action of Velaxin, and in addition to the risk of the appearance of serotonin intoxication, in the case of a combination of this drug with agents capable of influencing the transmission of nerve impulses of the serotonergic type (among them selective drugs-inhibitors of reverse serotonin capture, tripartine or lithium drugs), therapy is necessary to conduct with care.
Indinavir.
Taking the medication together with indinavir caused a decrease in the peak level and AUC values of the latter by 36% and 28%, respectively. In addition, indinavir had no effect on the pharmacokinetic characteristics of venlafaxine with EFA.
Warfarin.
In persons taking warfarin, with the onset of venlafaxine use, an increase in anticoagulant properties may be observed. In addition, there is an increase in the indices of PTV.
Haloperidol.
Since haloperidol is able to accumulate in the body, its effect can be enhanced.
Cimetidine.
Cimetidine in equilibrium values is able to inhibit the process of metabolism of venlafaxine on the first pass, but it does not have a significant effect on the formation and elimination of B-desmethyl-venlafaxine, located in the circulatory system in much more significant quantities. This allows us to conclude that a combination of the above medicines in a healthy person will not require a change in dosage. But in elderly people with a disorder in the liver, such a combination should be used cautiously, because there is no information on the interaction of drugs. In such a case, constant monitoring of the therapy process is required.
Medications that slow down the effect of the element CYP2D6.
Isoenzyme CYP2D6, which is responsible for the processes of genetic polymorphism, and affects the metabolism of a large number of antidepressants, converts venlafaxine substance into its main decay product - ODV. This creates the conditions for the development of the interaction of Velaxin with the inhibitory drugs of the element CYP2D6.
Interactions that reduce the amount of the active component transformed into ODV, in theory, can increase the values of the substance within the serum and decrease the indices of its active degradation product.
Ketoconazole (an inhibitory substance of element CYP3A4).
Tests of ketoconazole in fast as well as slow metabolizers of the CYP2D6 component showed that when using this drug, the venlafaxine AUC value rises (respectively, by 21% and 70%). The level of O-desmethylvenlafaxine is also increasing (by 23% and 33%, respectively).
Combination of drugs with inhibitors of CYP3A4 substance (among them itraconazole, clarithromycin with atazanavir and voriconazole, and in addition indinavir, saquinavir and posakonazol with nelfinavir and telithromycin, and ketoconazole with ritonavir) increases the performance of the active drug component and EFA. Because of this, it is required to combine with the above described drugs and Velaxin with caution.
Hypoglycemic and hypotensive drugs.
There is an increase in the indices of clozapine, which has a temporary connection with the development of side effects (this includes seizures), after the completion of venlafaxine use.
When taking venlafaxine, you must stop using alcohol.