Intriv

Intriv is an antidepressant. It contains the component duloxetine, which is included in the SSRI and SNRI groups. The substance weakly slows down dopamine uptake and does not have significant affinity for dopamine, adrenergic, histamine and cholinergic endings.

The effect of duloxetine in the treatment of stress urinary incontinence is due to the slowing of the neuronal reuptake of norepinephrine with serotonin within the CNS (spinal-sacral region). As a result, there is an increase in the indices of these elements within the synaptic vesicles.

Indications Intriva

It is used in cases of involuntary urination in women (involuntary urination during sneezing, coughing, lifting heavy objects, physical exertion and other actions that result in a sudden increase in pressure inside the peritoneum).

Release form

The therapeutic component is released in capsules of 20 or 40 mg, 14 or 28 pieces per pack.

Pharmacodynamics

During laboratory tests involving animals, it was found that the drug increases stimulation of the nerve located inside the striated urethral sphincter muscle. This effect manifests itself as an 8-fold increase in EMG activity of the muscle only at the stage of urinary retention.

In women, this effect causes increased contractions of the urethra and maintains the tone of the sphincter at the stage of urinary retention. This may explain the high efficiency of the substance duloxetine in clinical therapy in women suffering from NCH.

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Pharmacokinetics

Suction.

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

Distribution processes.

The drug is well synthesized with intraplasmic protein (>90%); mainly with albumins, as well as α-1 acid glycoprotein. At the same time, protein synthesis does not cause deterioration of renal or hepatic function.

Exchange processes.

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

CYP2D6 and CYP1A2 elements stimulate the formation of 2 main metabolic components (glucuronic conjugates of 4-hydroxyduloxetine - sulfate conjugate of 5-hydroxy, and 6-methoxyduloxetine). At the same time, the circulating metabolic elements do not have medicinal activity.

Excretion.

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

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Dosing and administration

The medication is prescribed in a dosage of 40 mg, 2 times a day, every day, without reference to food intake. After 0.5-1 month of therapy, it is necessary to evaluate the treatment.

Some patients may be recommended to take 20 mg of the substance 2 times a day (over a 14-day period) at the initial stage to reduce the likelihood of early negative symptoms.

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Use Intriva during pregnancy

There are no relevant tests on the effect of Intriva on pregnancy, which is why it is prescribed during this period only with a careful assessment of the possible risks and benefits.

Duloxetine can be excreted in breast milk - per day, the child receives about 0.14% of the dosage of the drug taken by the woman in mg / kg. There is no data on whether the drug is safe for a breastfed baby, so it should not be used during breastfeeding.

Contraindications

The use of the drug is contraindicated in case of severe intolerance to duloxetine.

The drug is not used in combination with MAOIs, as well as for at least 2 weeks after the end of the latter. Given the half-life of duloxetine, MAOIs are prohibited for use for at least 5 days after the end of therapy with Intriva.

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Side effects Intriva

During clinical trials, the main side effects noted were nausea, fatigue and dry mouth.

Headaches, insomnia or drowsiness, lethargy, dizziness, and agitation, sleep disturbances, anxiety, and a feeling of cold sometimes occurred. Paresthesia, hyperhidrosis, tremor, facial flushing, and decreased libido were also observed; vomiting, diarrhea, decreased appetite, abdominal pain, and blurred vision also occurred.

Stomatitis, gastritis or gastroenteritis and flatulence developed occasionally, as did belching, weight gain or loss and bad breath. In addition, mydriasis, attention deficit disorder, hypothyroidism, feeling of heat, dehydration, tachycardia, ear pain, yawning, muscle pain and tension, and thirst developed. Along with this, laryngitis, bruxism, visual and taste disorders, malaise, strange dreams, hyperemia and night hyperhidrosis, apathy and disorientation developed. Menopausal symptoms, dysuria with nocturia, strange orgasm and urinary retention also developed. Urine acquired an unusual odor, increased cholesterol and liver values, and blood pressure levels.

Nausea, dizziness, and headaches usually resolved after discontinuation of the drug.

Other side effects include:

• endocrine dysfunction: isolated cases of ADH secretion disorder;
• cardiac pathologies: supraventricular arrhythmia develops occasionally;
• eye damage: glaucoma is observed in isolated cases;
• disorders associated with the hepatobiliary system: jaundice or hepatitis appear occasionally;
• immune signs: intolerance or anaphylactic symptoms occur occasionally;
• changes in test results: the values of alkaline phosphatase, bilirubin, ALT and AST increase sporadically;
• problems with digestive function and metabolism: hyponatremia appears occasionally;
• lesions of the musculoskeletal structure: trismus is observed occasionally;
• disorders associated with the functioning of the nervous system: serotonin intoxication, extrapyramidal manifestations and seizures are observed occasionally;
• problems with mental function: hallucinations occasionally appear. Isolated cases – mania;
• Lesions associated with urination: urinary retention occasionally occurs;
• disorders affecting the subcutaneous layer and epidermis: rashes occur occasionally. Urticaria, Quincke's edema or SJS appear occasionally;
• vascular disorders: orthostatic collapse and syncope develop occasionally (especially at the initial stage of therapy), as well as hypertensive crisis.

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Overdose

Clinical information on duloxetine poisoning is limited. There are reports of high doses – up to 1.4 g of the drug alone (or in combination with other medications), but this did not lead to serious complications. Manifestations of overdose (mainly when combined with other drugs) include drowsiness, convulsions, serotonin intoxication and vomiting.

The drug has no antidote. In case of serotonin intoxication, specific treatment procedures are carried out (temperature monitoring and use of cyproheptadine). It is also necessary to clear the respiratory tract. It is necessary to monitor the main functions of the body and the work of the heart, as well as to carry out appropriate supportive and symptomatic measures. Gastric lavage is appropriate to perform immediately after taking the drug or as a symptomatic procedure. Absorption of Intriva can be reduced by taking activated carbon. Duloxetine has high distribution volume indicators, due to which hemoperfusion with forced diuresis, as well as exchange perfusion will not be effective.

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Interactions with other drugs

Medicines whose metabolic processes occur with the participation of CYP1A2.

Clinical studies of the combined use of the CYP1A2 substrate theophylline and duloxetine (60 mg twice daily) have shown that they do not significantly affect each other's pharmacokinetics. From this it can be concluded that Intriv is unlikely to have a noticeable effect on the metabolic processes of the CYP1A2 substrates.

Substances that inhibit CYP1A2 activity.

Because CYP1A2 is involved in duloxetine metabolism, combining the drug with substances that inhibit CYP1A2 will likely increase duloxetine levels.

Fluvoxamine is a potent inhibitor of CYP1A2 activity (used once daily in a 0.1 g dose), so it reduces plasma levels of duloxetine by approximately 77%. Therefore, when combining these drugs (for example, with individual quinolones), some precautions must be taken - for example, reducing the dosage of duloxetine.

Drugs in whose metabolism CYP2D6 is involved.

The component duloxetine moderately slows down the activity of CYP2D6. In case of its administration in a dose of 60 mg 2 times a day, in combination with 1-time administration of desipramine (a CYP2D6 substrate), the AUC level of the latter increases threefold.

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

Agents that inhibit the action of CYP2D6.

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

Administration of paroxetine (20 mg once daily) reduces the plasma clearance of duloxetine by approximately 37%. For this reason, this combination of drugs should be administered with great caution.

Medicines that affect the function of the central nervous system.

The administration of duloxetine in combination with other drugs that affect the central nervous system, especially those with a similar principle of action (this includes alcohol), should be carried out with great caution.

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

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

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

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Storage conditions

Intriv should be stored in a place out of reach of children. The temperature level should not exceed 30°C.

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Shelf life

Intriv can be used within a 2-year period from the date of production of the medicinal element.

Application for children

The effects of duloxetine have not been studied in individuals under 18 years of age, so it is not prescribed to this age subgroup.

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Analogues

Analogues of the drug are Duloxent, Duxet with Simoda, as well as Dulot and Simbalta.

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