Description of the active substance:
This information is a reference and it is not enough that the drug was prescribed by a doctor. .
PHARMACHOLOGIC EFFECT
Antidepressant, a reuptake inhibitor of serotonin and norepinephrine (norepinephrine). Slightly inhibits the seizure of dopamine, does not have a significant affinity for histamine, dopamine, cholinergic and adrenergic receptors. The mechanism of action of duloxetine is to inhibit the reuptake of serotonin and norepinephrine (norepinephrine). Duloxetine has a central mechanism for suppressing the pain syndrome, which is primarily manifested by an increase in the threshold of pain sensitivity in the pain syndrome of neuropathic etiology.
PHARMACOKINETICS
After oral administration, duloxetine is well absorbed from the digestive tract, suction begins 2 hours after ingestion, C max is reached 6 hours after ingestion.Admission simultaneously with food increases the time to reach C max to 10 h, which reduces the degree of absorption (by about 10%), but does not affect the value of C max .
Binding to plasma proteins is high (more than 90%), mainly with albumin and? 1- globulin. Disturbances from the liver or kidneys do not affect the degree of binding to proteins. Duloxetine is actively biotransformed with the participation of isoenzymes CYP2D6 and CYP1A2, which catalyze the formation of two major metabolites (glucuron conjugate 4-hydroxyduloxetine, sulfate conjugate 5-hydroxy, 6-methoxyduloxetine). Circulating metabolites do not have pharmacological activity. T 1/2 is 12 hours. The average clearance of duloxetine is 101 l / h. It is excreted in the urine in the form of metabolites.
In patients with terminal stage of chronic renal failure who are on hemodialysis, the values ​​of C max and AUC of duloxetine increased 2-fold. In this regard, it should be considered the expediency of reducing the dose of the drug in patients with clinically manifested impairment of renal function.
In patients with clinical signs of hepatic insufficiency, a slowdown in the metabolism and elimination of duloxetine can be observed. After a single dose of 20 mg duloxetine in 6 patients with cirrhosis and mild hepatic impairment (class B on the Child-Pugh scale), the duration of T 1/2 of duloxetine was approximately 15% higher than in healthy people of the corresponding sex and age with fivefold increase in the average value of AUC. Despite the fact that C max in patients with cirrhosis was the same as in healthy people, T 1/2 is approximately 3 times larger.
INDICATIONS
Depression, a painful form of diabetic neuropathy.
DOSING MODE
The recommended initial dose is 60 mg 1 time / day.
If necessary, you can increase the daily dose from 60 mg to a maximum dose of 120 mg / day in 2 divided doses.
In patients with severe renal dysfunction (CK <30 ml / min), the initial dose should be 30 mg 1 time / day. In patients with impaired liver function, the initial dose of the drug should be reduced or the frequency of administration reduced.
SIDE EFFECT
From the side of the central nervous system: often - dizziness (except vertigo), sleep disturbances (drowsiness or insomnia), headache (headache was less common than with placebo); sometimes - tremor, weakness, blurred vision, lethargy, anxiety, yawning; very rarely - glaucoma, mydriasis, visual impairment, agitation, disorientation.
On the part of the digestive system: often - dry mouth, nausea, constipation; sometimes - diarrhea, vomiting, decreased appetite, change in taste, impaired liver function; very rarely - hepatitis, jaundice, increased activity of alkaline phosphatase, ALT, AST and bilirubin levels; belching, gastroenteritis, stomatitis.
From the musculoskeletal system: sometimes - muscle tension and / or twitching; very rarely - bruxism .
From the cardiovascular system: sometimes - palpitation; very rarely - orthostatic hypotension, syncope (especially at the beginning of therapy), tachycardia, increased blood pressure, cold extremities.
On the part of the reproductive system: sometimes - anorgasmia, decreased libido, delay and violation of ejaculation, erectile dysfunction.
From the urinary system: sometimes - difficulty urinating; very rarely - nocturia.
Other: sometimes - weight loss, increased sweating, hot flashes, night sweats; very rarely anaphylactic reactions, thirst, hyponatremia, chills, angioedema, rash, Stevens-Johnson syndrome, urticaria, poor health, feeling hot and / or cold, weight gain, dehydration, photosensitivity. With cancellation, dizziness, nausea, and headache were often noted. In patients with a painful form of diabetic neuropathy, there may be a slight increase in fasting blood glucose.
CONTRAINDICATIONS
Uncompensated closed-angle glaucoma, concomitant use with MAO inhibitors, increased sensitivity to duloxetine.
PREGNANCY AND LACTATION
The use of the drug during pregnancy is possible only in cases where the intended use for the mother exceeds the potential risk to the fetus, because clinical experience with duloxetine in pregnancy is not enough.
If you need to use the drug during lactation, you should decide whether to stop breastfeeding (due to lack of experience).
Patients should be warned that in the event of the onset or planning of pregnancy during the period of duloxetine, they must inform their doctor.
APPLICATION FOR FUNCTIONS OF THE LIVER
Use with caution in case of impaired renal function. In patients with severe renal dysfunction (CK <30 ml / min), the initial dose should be 30 mg 1 time / day.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use with caution in case of impaired liver function. In patients with impaired liver function, the initial dose of the drug should be reduced or the frequency of administration reduced.
SPECIAL INSTRUCTIONS
Use with caution in exacerbating manic / hypomanic conditions, epileptic seizures, mydriasis, impaired liver or kidney function, in patients with a tendency to suicidal attempts.
In the appointment of serotonin reuptake inhibitors in combination with MAO inhibitors, severe reactions, sometimes with a fatal outcome (hyperthermia, rigidity, myoclonus, various disorders with possible sharp fluctuations in vital signs of the body and changes in mental status, including pronounced agitation with the transition to delirium and to whom). Such reactions are also possible in cases where the serotonin reuptake inhibitor was abolished shortly before the appointment of MAO inhibitors (possibly the development of symptoms, including those characteristic of malignant neuroleptic syndrome).
Effects of combined use of duloxetine and MAO inhibitors have not been evaluated in either humans or animals. The use of duloxetine concomitantly with MAO inhibitors or in the period up to 14 days after their cancellation is not recommended. Duloxetine is an inhibitor of serotonin reuptake, and norepinephrine (noradrenaline). MAO inhibitors should not be prescribed for at least 5 days after duloxetine cancellation.
Use with caution in patients with manic episodes in an anamnesis, as well as with epileptic seizures in the anamnesis.
Depressive conditions are accompanied by a high risk of suicidal behavior. As a consequence, patients diagnosed with depression who are taking duloxetine should inform the doctor of any disturbing thoughts and feelings.
Against the background of the use of the drug, the development of mydriasis is possible, caution should be exercised in prescribing duloxetine to patients with increased intraocular pressure or in persons at risk of developing acute, closed-angle glaucoma.
In patients with hypertension and / or other cardiovascular diseases, it is recommended to monitor blood pressure.
Impact on the ability to drive vehicles and manage mechanisms
Patients taking duloxetine should be careful in dealing with potentially dangerous activities (due to the possible occurrence of drowsiness).
DRUG INTERACTION
Simultaneous use of duloxetine (in a dose of 60 mg 2 times / day) did not significantly affect the pharmacokinetics of theophylline metabolized by CYP1A2.Duloxetine is unlikely to have a clinically significant effect on the metabolism of other drugs - CYP1A2 substrates.
Simultaneous administration of duloxetine with potential inhibitors of CYP1A2 (eg, fluoroquinolones) may increase the concentration of duloxetine because CYP1A2 is involved in the metabolism of duloxetine (the appointment of such a combination requires caution and reduced duloxetine doses).
The potent inhibitor of CYP1A2 fluvoxamine (when administered at a dose of 100 mg 1 time / day) reduced the average plasma clearance of duloxetine by approximately 77%.
When prescribing duloxetine with drugs metabolized by CYP2D6 and having a narrow therapeutic index, caution should be exercised (because duloxetine is a mild inhibitor of CYP2D6). With simultaneous application with duloxetine at a dose of 60 mg 2 times / day, the AUC of desipramine (substrate CYP2D6) is increased 3-fold. Simultaneous application with duloxetine (40 mg twice daily) increased the stable portion of the AUC of tolterodine (used at a dose of 2 mg 2 times / day) by 71%, but did not affect the pharmacokinetics of the 5-hydroxyl metabolite. The simultaneous use of duloxetine with potential inhibitors of CYP2D6 can lead to an increase in duloxetine concentrations. Paroxetine (when applied at a dose of 20 mg 1 time / day) reduced the average clearance of duloxetine by about 37%. Care should be taken when using duloxetine with CYP2D6 inhibitors (for example, with selective serotonin reuptake inhibitors).
With the simultaneous use of duloxetine and other drugs that affect the central nervous system and have a similar mechanism of action (including ethanol and ethanol-containing drugs), there may be a mutual enhancement of effects (this combination requires caution).
Duloxetine is largely associated with plasma proteins, so simultaneous use with other drugs, highly binding to plasma proteins, can lead to an increase in the concentration of free fractions of both drugs.
