Intriv

Intriv is an antidepressant. Contains the component duloxetine, which is included in the MI and IORP groups. The substance slows down the dopamine uptake weakly and does not have a significant affinity for dopamine, adrenergic, histamine and cholinergic endings.

The effects of duloxetine during urinary incontinence therapy due to stress are due to the slowing of the reverse neuronal uptake of norepinephrine with serotonin inside the CNS (cerebrospinal sacral region). As a result, there is an increase in the performance of these elements inside the vesicle synapses.

Indications Intrigue

It is used in the case of HCH in women (involuntary urination during sneezing, coughing, lifting heavy objects, physical exertion and other actions, against the background of which there is a sudden increase in pressure inside the peritoneum).

Release form

The release of the therapeutic component is realized in capsules with a volume of 20 or 40 mg, 14 or 28 each in a pack.

Pharmacodynamics

During laboratory tests with the participation of animals, it was found that under the action of drugs, stimulation of the nerve located inside the sphincter striated urethral muscle is enhanced. Such an effect is manifested in the form of an 8-fold increase in the EMG activity of the muscle only at the stage of urinary secretion.

In women, this effect causes increased contractions of the urethra and maintains the sphincter tone at the stage of urinary secretion. This may explain the high efficacy of duloxetine in clinical therapy in women with HCH.

[1], [2], [3], [4], [5], [6]

Pharmacokinetics

Suction.

After ingestion, duloxetine is well absorbed. Cmax values are noted after 6 hours. Eating food slows down the period of absorption - it takes 10 hours to reach the Cmax level; the degree of absorption is also reduced (by about 11%).

Distribution processes.

The drug is well synthesized with intraplasma protein (> 90%); mainly with albumin and α-1 acid glycoprotein. At the same time, protein synthesis does not impair renal or hepatic function.

Exchange processes.

Duloxetine undergoes active metabolism, and its metabolic components are mostly excreted in the urine.

The elements of CYP2D6, as well as CYP1A2, stimulate the formation of 2 main metabolic components (glucuronic conjugates of 4-hydroxiduloxetine - the sulfate conjugate of 5-hydroxy, as well as 6-methoxydioxetine). At the same time circulating metabolic elements do not possess medicinal activity.

Excretion.

The term half-life of the drug is 12 hours. The average plasma clearance of a substance is 101 liters per hour.

[7]

Dosing and administration

The drug is prescribed in a dosage of 40 mg, 2 times a day, every day, without reference to the use of food. After a period of 0.5–1 months of treatment, treatment should be evaluated.

Individual patients may be recommended to use at the initial stage 20 mg of a substance 2-fold per day (in a period of 14 days) in order to reduce the probability of the appearance of early negative symptoms.

[12], [13], [14], [15]

Use Intrigue during pregnancy

Appropriate testing regarding the effect of Intriv on the course of pregnancy has not been performed, which is why it is prescribed for the specified period only with careful assessment of possible risks and benefits.

Duloxetine is able to be excreted with the mother's milk - per day the child in mg / kg receives about 0.14% of the dosage of the medicine taken by the woman. There is no information as to whether the medication is safe for an infant, therefore it should not be used during breastfeeding.

Contraindications

It is contraindicated to use the drug with a strong intolerance against duloxetine.

The drug is not used in combination with IMAO, as well as for at least 2 weeks from the end of the last application. Given the term half-life of duloxetine, an MAOI is prohibited to use for at least 5 days after the end of therapy with Intriv.

[8], [9]

Side effects Intrigue

During clinical tests, nausea, fatigue and dryness of the oral mucous membranes were mainly observed.

Sometimes headaches, insomnia, or drowsiness, lethargy, dizziness, and, in addition, agitation, sleep disturbances, anxiety, and coldness, appeared. Paresthesias, hyperhidrosis, tremor, facial flushing and weakening of the libido were also observed; in addition, vomiting, diarrhea, loss of appetite, abdominal pain and visual clouding occurred.

Occasionally, stomatitis, gastritis, or gastroenteritis and flatulence, as well as belching, weight gain, and odor and mouth odor, developed. In addition, mydriasis, attention disorder, hypothyroidism, fever, dehydration, tachycardia, earache, yawning, pain and muscle tension, and thirst appeared. At the same time, laryngitis, bruxism, visual and gustatory disorders, poor health, strange dreams, hyperemia and night hyperhidrosis, apathy and disorientation developed. The symptoms of menopause, dysuria with nocturia, strange orgasm and urinary retention also developed. It was noted that urine acquired an unusual odor, an increase in Xc and liver, as well as blood pressure levels.

Nausea, dizziness and headaches usually passed after the abolition of the use of drugs.

Among other adverse events:

• endocrine dysfunction: a single disorder of excretion of ADH occurs;
• cardiac pathology: a single supraventricular arrhythmia develops;
• eye damage: glaucoma is rarely observed;
• disorders of the hepatobiliary system: jaundice or hepatitis appears singly;
• Immune signs: single intolerance or anaphylactic symptoms;
• change in test results: the values of alkaline phosphatase, bilirubin, ALT and AST increase individually;
• problems with digestive function and metabolism: hyponatremia appears singly;
• lesions of the musculoskeletal structure: trismism is singly noted;
• violations associated with the work of NA: single observed serotonin intoxication, extrapyramidal manifestations and convulsions;
• problems with mental function: hallucinations occasionally appear. Single - mania;
• urinary related lesions: urinary retention occurs occasionally;
• disorders affecting the subcutaneous layer and the epidermis: occasionally rashes. The urticaria, angioedema or SSD appears singly;
• vascular disorders: orthostatic collapse and syncope (especially at the initial stage of therapy), as well as hypertensive crisis develops individually.

[10], [11]

Overdose

Clinical information regarding duloxetine poisoning is limited. There are data on the use of high portions - up to 1.4 g of one drug (or in combination with other medicines), but this did not lead to serious complications. The manifestations of overdose (mainly when combined with other drugs) include drowsiness, convulsions, serotonin intoxication and vomiting.

The drug has no antidote. For serotonin intoxication, specific treatment procedures are performed (temperature monitoring and use of cyproheptadine). It is also necessary to free the respiratory tract. It is necessary to monitor the basic functions of the body and the work of the heart, as well as to conduct appropriate supportive and symptomatic measures. It is appropriate to perform gastric lavage immediately after taking the drug or as a symptomatic procedure. To reduce the absorption of intriva possible by taking activated charcoal. Duloxetine has a high distribution volume, which is why hemoperfusion with forced diuresis, as well as exchange perfusion will not be effective.

[16]

Interactions with other drugs

Medicines whose metabolic processes occur with the participation of CYP1A2.

Clinical studies of the combined use of the substrate element CYP1A2 - theophylline - and duloxetine (60 mg 2 times a day, every day) showed that they do not have a significant effect on each other's pharmacokinetics. From this we can conclude that Intriv most likely will not have a noticeable effect on the metabolic processes of substrates of the CYP1A2 component. 

Substances that slow down the activity of CYP1A2.

Because CYP1A2 is a participant in duloxetine metabolism, combining the drug with substances that slow down CYP1A2 will most likely increase the duloxetine levels.

Fluvoxamine is a potent inhibitor of CYP1A2 activity (used 1 time per day in a 0.1 g serving), so it reduces plasma duloxetine values to approximately 77%. Because of this, in the case of a combination of these drugs (for example, with individual quinolones), some precautionary measures must be observed - for example, to reduce the dosage of duloxetine.

Drugs in which CYP2D6 is involved in the metabolism.

The duloxetine component moderately slows down CYP2D6 activity. If it is taken in a portion of 60 mg 2 times a day, in combination with 1-fold use of desipramine (substrate CYP2D6), the AUC level of the latter increases threefold.

The use of the drug (40 mg 2 times a day) increases the stationary AUC values of tolterodine by 71% (2 mg 2 times a day), without changing the pharmacokinetics of the 5-hydroxyl metabolic element. Because of this, co-administration of drugs with inhibitors of the CYP2D6 component having a narrow drug index should be carried out with extreme caution.

Means that slow down the action of CYP2D6.

Because CYP2D6 is involved in the metabolism of duloxetine, the combination of such substances causes an increase in the latter.

The introduction of paroxetine (20 mg per day 1 times) reduces the level of plasma clearance of duloxetine by approximately 37%. Because of this, such a combination of drugs prescribed with great caution.

Medications affecting the function of the central nervous system.

The introduction of duloxetine combined with other drugs affecting the work of the central nervous system, especially with a similar principle of influence (this includes alcohol) should be carried out with great caution.

Use together with other drugs that have a serotonergic effect may cause serotonin intoxication.

Drugs that have a high rate of intraplasma synthesis with protein.

Synthesis of duloxetine with protein is> 90%, which is why using with other drugs with a high level of such synthesis can cause an increase in free indices of any of these medicines.

[17], [18], [19], [20]

Storage conditions

Intriv must be kept in a place closed to children. The temperature level is not higher than 30 ° С.

[21]

Shelf life

Intriv can be applied within a 2-year term from the moment the medicinal element is manufactured.

Application for children

In persons younger than 18 years of age, the effect of duloxetine has not been studied, therefore, this age subgroup is not prescribed.

[22]

Analogs

Analogs of drugs are drugs Duloksenta, Dyukset with Shimoda, as well as Dulot and Simbalta.

 

[23], [24]