Serotonin and norepinephrine reuptake inhibitor. It slightly inhibits dopamine uptake, has no significant affinity for histamine and dopamine, cholinergic and adrenergic receptors. The mechanism of therapeutic effect of duloxetine in depression is due to inhibition of the reuptake of serotonin and norepinephrine and, as a result, an increase in serotonergic and noradrenergic neurotransmission in the central nervous system. Duloxetine also normalizes the pain threshold in some experimental models of neuropathic and inflammatory pain and reduces the severity of pain in the chronic pain model. The analgesic effect of duloxetine is probably due to a slowdown in the transmission of nociceptive impulses to the central nervous system.
Duloxetine is well absorbed after oral administration. The maximum concentration in blood plasma is reached 6 hours after administration. Simultaneous food intake slows down absorption, the period when the maximum concentration in the blood is reached increases from 6 to 10 hours, and absorption decreases (by about 11%).
Duloxetine is significantly bound to plasma proteins (more than 90%).
Duloxetine is extensively metabolized in the body, metabolites are excreted mainly in the urine. The isoenzymes CYP 2D6 and CYP 1A2 catalyze the formation of two major metabolites of duloxetine (glucuronide combined with 4-hydroxyduloxetine, sulfate combined with 5-hydroxy, methoxy-duloxetine). The resulting metabolites do not have pharmacological activity.
The half-life of duloxetine is 12 hours. The average clearance of duloxetine from blood plasma is 101 l / h.
In patients with end-stage renal failure who are constantly on dialysis, there is a two-fold increase in the concentration of duloxetine in blood plasma and an increase in AUC compared with healthy individuals. Therefore, in patients with chronic renal failure, duloxetine is prescribed in a lower initial dose.
The use of the drug Duloxetine
For depression and diabetic neuropathy, it is prescribed orally at a dose of 60 mg once a day daily, regardless of food intake. In some patients, a higher dose may be recommended (up to a maximum of -120 mg / day in 2 divided doses). The possibility of administration in doses exceeding 120 mg / day has not been studied.
The initial dosage for patients in the final stage of renal failure (creatinine clearance ≤30 ml / min) is 30 mg 1 time per day daily.
Patients with cirrhosis are prescribed at a lower initial dose or at longer intervals between doses.
No dose adjustment of duloxetine in elderly or advanced patients is required. In patients younger than 18 years of age, the effects of duloxetine have not been studied.
Side effects of Duloxetine
In clinical trials, adverse events such as constipation, nausea, dry mouth, dizziness, increased fatigue, insomnia and headache (≥10%) were noted. Less commonly (with a frequency of ≤10%, but ≥1%) - tachycardia, dyspepsia, vomiting, loss of appetite, drowsiness, tremor, lethargy, sweating, feeling hot, yawning. On the part of the reproductive system, there were impaired ejaculation and erection (with a frequency of ≤10%, but ≥1%), a decrease in libido and anorgasmia. Rarely (≤1%, but ≥0.1%) - gastroenteritis, stomatitis, increased blood pressure, weight gain, muscle tension, taste and vision impairment, agitation, urinary retention.
Treatment with duloxetine in placebo-controlled clinical trials was associated with a slight increase compared with placebo in the levels of AlAT, AsAT and KFK.
In clinical trials of duloxetine for the treatment of diabetic neuropathy, the average duration of diabetes mellitus was approximately 11 years, the average initial concentration of fasting serum glucose was up to 163 mg / dl, and the average initial concentration of glycosylated hemoglobin was 7.80%. In these studies, there was a slight increase in the initial fasting blood glucose concentration after 12 weeks in patients taking duloxetine compared with placebo, in the usual regimen for 52 weeks. There were no changes in glycosylated hemoglobin, patient body weight, lipid concentration (cholesterol, LDL, HDL, TG) or any side effects associated with diabetes.
According to post-marketing studies, the following side effects were noted:
on the part of the organ of vision: very rarely (≤0.01%) - glaucoma,
from the hepatobiliary system: very rarely (≤0.01%) - hepatitis, jaundice,
from the immune system: very rarely (≤0.01%) - anaphylactic reactions,
from laboratory indicators: very rarely (≤0.01%) - increased activity of AlAT, AcAT, alkaline phosphatase, blood bilirubin level,
from the side of metabolism: very rarely (≤0.01%) - hyponatremia,
on the skin side: rarely (0.01-0.1%) - rash, very rarely (≤0.01%) - angioedema, Stevens-Johnson syndrome, urticaria,
from the cardiovascular system: very rarely (≤0.01%) - orthostatic hypotension and syncope (especially at the beginning of treatment).
Special instructions for the use of the drug Duloxetine
Patients with a high risk of suicide during treatment should be closely monitored, since before the onset of severe remission, the possibility of suicidal attempts is not excluded.
The use of duloxetine in patients under the age of 18 has not been studied, therefore, it should not be prescribed to persons of this age group.
As in the case of the use of other drugs acting on the central nervous system, in patients with manic syndrome, history of seizures, duloxetine must be used with caution.
There have been reports of the appearance of mydriasis in connection with the administration of duloxetine, therefore, use of duloxetine in patients with increased intraocular pressure or in case of the risk of developing acute narrow-angle glaucoma should be used with caution.
It was reported an increase in the concentration of duloxetine in blood plasma in patients with severe renal failure (creatinine clearance ≤30 ml / min) or severe liver failure. Such patients are advised to prescribe duloxetine at a lower initial dose.
In some patients, taking duloxetine leads to an increase in blood pressure. In patients with hypertension (arterial hypertension) and / or other diseases of the cardiovascular system, it is recommended to monitor blood pressure.
In clinical studies, an increase in the activity of liver enzymes in the blood was noted. In most patients receiving duloxetine, this increase was transient and disappeared after discontinuation of duloxetine. A significant increase in the activity of liver enzymes (more than 10 times higher than normal) or liver damage with cholestasis, or a significant increase in enzyme activity in combination with liver damage was rare, in some cases it was associated with alcohol abuse.
Duloxetine did not have a mutagenic effect in experiments in vitro and in vivo.
Adequate and well-controlled studies of the effects of duloxetine in pregnant women have not been conducted, so its use during pregnancy is not recommended.
Duloxetine is excreted in breast milk. The approximate daily dose in an infant is 0.14% of the dose for a nursing woman (mg / kg). The safety of duloxetine in infants has not been established, so breastfeeding while taking duloxetine is not recommended.
During treatment with duloxetine, patients should refrain from potentially dangerous activities that require increased attention and speed of psychomotor reactions.
Drug interactions Duloxetine
Duloxetine should not be prescribed simultaneously with MAO inhibitors or within at least 14 days after discontinuation of treatment with MAO inhibitors. Given the half-life of duloxetine, MAO inhibitors should also not be prescribed for at least 5 days after discontinuation of duloxetine.
In clinical studies with the simultaneous administration of theophylline, a CYP 1A2 substrate with duloxetine at a dose of 60 mg 2 times a day, no significant changes in their pharmacokinetics were noted. These results suggest that duloxetine is unlikely to have a clinically significant effect on the metabolism of CYP 1A2 substrates.
Since CYP 1A2 is involved in the metabolism of duloxetine, the simultaneous use of duloxetine with active inhibitors of CYP 1A2 can lead to an increase in the concentration of duloxetine in blood plasma. Fluvoxamine (at a dose of 100 mg once a day), being an active inhibitor of CYP 1A2, reduces the clearance of duloxetine from blood plasma by approximately 77%. In this regard, when prescribing duloxetine with CYP 1A2 inhibitors (some quinolone antibacterial agents), it is advisable to prescribe duloxetine in a lower dose.
Duloxetine is a moderate inhibitor of CYP 2D6. When prescribing duloxetine at a dose of 60 mg 2 times a day with a single dose of desipramine, which is a substrate of CYP 2D6, AUC of desipramine increases 3 times. The simultaneous administration of duloxetine (at a dose of 40 mg 2 times a day) increases the stationary AUC of tolterodine (2 mg 2 times a day) by 71%, but does not affect the pharmacokinetics of the 5-hydroxyl metabolite. In this regard, caution is required when prescribing duloxetine with CYP 2D6 inhibitors, which have a narrow therapeutic index.
Since CYP 2D6 is involved in the metabolism of duloxetine, the simultaneous use of duloxetine with active inhibitors of CYP 2D6 can lead to an increase in the concentration of duloxetine in the blood. Paroxetine (at a dose of 20 mg once a day) reduces the clearance of duloxetine from blood plasma by approximately 37%. In this regard, caution is required when prescribing duloxetine with CYP 2D6 inhibitors.
When prescribing duloxetine in combination with other drugs that affect the central nervous system, especially with a similar mechanism of action, caution should be exercised.
Duloxetine binds to blood plasma proteins (90%), therefore, the administration of duloxetine to a patient taking other drugs that significantly bind to blood plasma proteins can lead to an increase in the free concentration of any of these drugs.
Overdose of Duloxetine, symptoms and treatment
Clinical evidence for an overdose of duloxetine is limited. There were cases of overdose of the drug (up to 1400 mg), including in combination with other drugs, but they did not lead to death.
In animal experiments, the main manifestations of toxicity in overdose were noted by the central nervous system and gastrointestinal tract. These included symptoms such as tremors, clonic convulsions, ataxia, vomiting, and anorexia.
The specific antidote is not known. Immediately after an overdose, gastric lavage and the appointment of activated charcoal are indicated. Ensure airway. It is recommended to monitor the main vital signs, primarily cardiac activity, and if necessary, symptomatic and supportive therapy. Duloxetine has a large volume of distribution, and therefore forced diuresis, hemoperfusion and metabolic perfusion in case of an overdose are ineffective.
Duloxetine is classified as antidepressants from the group of selective reuptake inhibitors norepinephrine and serotonin.
The molecular weight of the chemical compound = 297.4 grams per mole.
Available in capsules and tablets, in a dosage of 30 and 60 mg.
Most often found in formulations hydrochloride.
Pharmacodynamics and pharmacokinetics
The tool prevents re-capture serotonin and norepinephrine, partially - dopamine. Due to this, these neurotransmitters accumulate, and their transmission in the central nervous system increases. The substance suppresses pain, increases the threshold of pain sensitivity for pain developed as a result of neuropathy.
The drug is rapidly absorbed after oral administration. The maximum concentration of a substance in the blood is achieved within two hours. Parallel meal lengthens the time to reach maximum concentration up to 10 hours. Over 90% of the drug binds to plasma proteins, albumin and glycoprotein. In patients with kidney and liver diseases, the degree of binding to plasma proteins does not change.
Duloxetine is metabolized, metabolites are not active. 4-Hydroxyduloxetine Glucuronic Conjugate and 5-hydroxy-6-methoxyduloxetine sulfate conjugate excreted by the kidneys. Metabolism occurs with the participation of CYP1A2 and CYP2D6. The half-life of the drug is approximately 11-12 hours.
In women, the excretion of metabolites and the metabolism of the drug is slower than in men. Also, in middle-aged and elderly patients, the area under the “time-concentration” curve and the time of elimination of the substance from the body increase. However, dosage adjustment is not performed. Hepatic insufficiency leads to a slowdown in clearance of the drug. At the terminal stage renal failure, the maximum concentration is doubled.
Duloxetine is not prescribed:
- with uncompensated angle glaucoma,
- in conjunction with MAO inhibitors, CYP1A2 inhibitors,
- at allergies on this substance
- patients with severe liver failure,
- in severe renal failurepatients on hemodialysis,
- uncontrolled patients arterial hypertension,
- during breastfeeding,
- children under 18 years old.
During treatment with this antidepressant often develop:
- headaches, tremor, drowsiness, dizziness, paresthesia, insomnia, vivid dreams, agitation,
- anxiety, lethargy, nausea,
- diarrheavomiting, dry mouth, constipation, indigestion,
- increased gas formation, pain in the epigastric region,
- decreased sexual desire, lack of erection, anorgasmia,
- tides, palpitations, tinnitus, decreased visual acuity, yawning,
- muscle cramps, stiffness, pain in muscles and bones, allergic rashes, sweatingespecially at night
- lack of appetite, weight loss, fatigue.
Less commonly, the following side effects may occur:
- nervousness, inability to concentrate, dyskinesiaapathy bruxism,
- stomatitisburping hepatitisincreased activity of liver enzymes,
- anuria, dysuria, nocturia, polyuriaproblems with urination, decreased sexual function and desire,
- gastroenteritis, gastritis, taste distortion, hypersensitivity reactions,
- fainting tachycardiadecrease or increase blood pressurecold hands and toes,
- mydriasispain in the ears vertigoblood from the nose, feeling of pressure in the throat,
- hypersensitivity to light, subcutaneous hemorrhage, hives, contact dermatitiscold, sticky sweat, involuntary muscle twitching,
- hyperglycemia (at diabetes), laryngitis, weight gain, gait instability, thirst, chills, level increase creatine phosphokinase.
- aggressive behavior, mania, anger, cramps, psychomotor agitation,
- serotonin syndrome, attempts to commit suicide, thoughts of suicide, hallucinations,
- bad breath, blood in the stool, jaundice, liver failure, a change in the smell of urine and symptoms of menopause, hypertensive crisis,
- atrial fibrillation, supraventricular arrhythmia,
- mydriasis, glaucoma, lockjaw, dehydration,
- hyponatremia, hypercholesterolemiapain in the sternum anaphylactoid reactions.
With a sharp cessation of substance intake occurs withdrawal syndrome: dizzinessparesthesia insomnia, vivid dreams, anxiety, vomiting, tremorincreased irritability vertigo and sweating.
Duloxetine, instructions for use (Method and dosage)
Treatment begins with a dosage of 60 mg, take it once a day. Then you can gradually increase the dosage to 0.12 g per day (taken twice a day).
In severe renal failure Do not take more than 30 mg of the substance per day. With liver failure, the initial dosage is reduced and the frequency of administration is reduced.
When combined with Duloxetine theophylline the pharmacokinetics of the latter drug does not significantly change.
Use of a substance with inhibitors CYP1A2 may lead to an increase in the plasma concentration of the drug. For example, fluvoxamine reduces the intensity of plasma clearance by approximately 75%. It is recommended to combine the medicine with caution desipramine, tolterodine and other means in the metabolism of which is involved CYP2D6.
Potential Inhibitors CYP2D6 may cause an increase in the concentration of duloxetine.
With extreme caution, combine this drug with other antidepressants, in particular Paroxetine. Its clearance is reduced.
The combined reception of means with benzodiazepines, Phenobarbital, antipsychotic drugs and antihistamines, with ethanol Not recommended.
With caution, combine the drug with drugs that have a high degree of binding to plasma proteins.
It is highly recommended not to take this drug in conjunction with selective inhibitorsMAO, even with reversible MAO inhibitors, moclobemide. This can lead to development. hyperthermia, myoclonusmuscle rigidity, sharp fluctuations in vital indicators, comaup to death.
Combined medication with anticoagulants and antiplatelet drugs leads to the development of bleeding. When combined with Warfarin INR may rise.
Rarely develops serotonin syndrome when using other SSRIs in combination with a medicine. Care must be taken when treating with tricyclic antidepressants, Amitriptyline, clomipramine, Venlafaxine, hypericum, triptanam, pethidine, Tramadol and Tryptophan.
Despite the rather flattering reviews of doctors about this drug, in patients the opinion about it is often the opposite. Many people write that the drug is poorly tolerated, serious side effects develop, withdrawal syndrome is strong when treatment is interrupted, the effect comes slowly, sometimes after several months of administration.
Some reviews of Duloxetine preparations:
- “... This is the latest generation of antidepressants, the medicine has a double effect, it helps patients with neurological diseases, depression, pain, and has a very wide scope of clinical use. Patients whom I appointed him are satisfied”,
- “... I’ve been drinking medicine for almost a year now, I was lucky with the side effects - they are not there. True, I recently tried to abruptly stop taking it; there was a withdrawal syndrome. Now it’s starting again, it suits me”,
- “... She lost a lot of weight from this remedy, languid, her head hurts constantly. Everything is being treated, being treated, but to no avail, I don’t know how to continue to live with it”.
Dosage 30 mg
One enteric capsule contains:
duloxetine, pellets 176.5 mg, including: duloxetine hydrochloride 33.68 mg, calculated as duloxetine 30 mg, hypromellose E5 (hydroxypropyl methyl cellulose) 10.54 mg, hypromellose HP55 (hydroxypropyl methyl cellulose) 15.51 mg, starch 44.09 mg, mannitol 47.3 mg, sodium lauryl sulfate 5.22 mg, sucrose 17.46 mg, titanium dioxide 1.15 mg, cetyl alcohol 1.55 mg,
Hard gelatin capsule No. 3:
case - dye blue patented V, titanium dioxide, gelatin,
cap - patented blue dye V, titanium dioxide, gelatin.
Dosage 60 mg
One enteric capsule contains:
duloxetine, 353 mg pellets, including: duloxetine hydrochloride 67.36 mg, in terms of duloxetine 60 mg, hypromellose E5 (hydroxypropyl methyl cellulose) 21.08 mg, hypromellose HP55 (hydroxypropyl methyl cellulose) 31.02 mg, starch 88.18 mg, mannitol 94.6 mg, sodium lauryl sulfate 10.44 mg, sucrose 34.92 mg, titanium dioxide 2.3 mg, cetyl alcohol 3.1 mg,
Hard gelatin capsule No. 1:
case - dye blue patented V, titanium dioxide, gelatin,
cap - patented blue dye V, titanium dioxide, gelatin.
Duloxetine is well absorbed when taken orally. Absorption begins 2 hours after taking the drug. Maximum concentration (Cmax) is achieved 6 hours after taking the drug.
Eating does not affect the maximum concentration of the drug, but increases the time to reach the maximum concentration (TSmax) from 6 to 10 hours, which indirectly reduces the degree of absorption (approximately 11%).
Duloxetine binds well to plasma proteins (> 90%), mainly with albumin and 1-acid glycoprotein, but disorders of the liver or kidneys do not affect the degree of protein binding.
Duloxetine is actively metabolized and its metabolites are mainly excreted in the urine. Both the CYP2D6 isoenzyme and the CYP1A2 isoenzyme catalyze the formation of two main metabolites (4-hydroxyduloxetine glucuronic conjugate, 5-hydroxy sulfate conjugate, 6-methoxyduloxetine).
Circulating metabolites do not have pharmacological activity.
The half-life (T 1/2 ) Duloxetine is 12 hours. The average clearance of duloxetine is 101 l / h.
Individual patient groups
despite the fact that differences in pharmacokinetics between men and women have been identified (the average clearance of duloxetine is lower in women), these differences are not so large that there is a need for dose adjustment depending on gender.
despite the fact that differences in pharmacokinetics between middle-aged and elderly patients have been identified (the area under the concentration / time curve (AUC) is higher and the duration T 1/2 the drug is greater in the elderly), these differences are not enough to change the dose depending only on the age of the patients.
in patients with severe renal impairment (end-stage chronic renal failure - chronic renal failure) undergoing hemodialysis, C valuesmax and AUC of duloxetine increased by 2 times. In this regard, the feasibility of reducing the dose of the drug in patients with clinically expressed impaired renal function should be considered.
- Impaired liver function:
in patients with clinical signs of liver failure, a slowdown in metabolism and excretion of duloxetine may be observed. After a single dose of 20 mg of duloxetine in 6 patients with cirrhosis of the liver with moderate impaired liver function (Class B on the Child-Pugh scale), duration T 1/2 Duloxetine was approximately 15% higher than in healthy people of the same gender and age with a five-fold increase in average exposure. Despite the fact that Cmax in patients with cirrhosis was the same as in healthy people, T 1/2 was about 3 times longer.
- A painful form of peripheral diabetic neuropathy,
- Generalized anxiety disorder,
- Chronic pain of the musculoskeletal system (including those caused by fibromyalgia, chronic buolevoy syndrome in the lower back and with osteoarthritis of the knee joint).
Pregnancy and lactation
Due to insufficient experience with duloxetine during pregnancy, the drug should be prescribed only if the potential benefit to the mother significantly exceeds the potential risk to the fetus. Patients should be warned that in the event of pregnancy or planning pregnancy during treatment with Duloxetine, they need to inform their doctor.
Epidemiological evidence suggests that the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, especially in the later stages, may increase the risk of persistent pulmonary hypertension in newborns. Despite the lack of research on the relationship of persistent pulmonary hypertension in newborns and the use of SSRIs, the potential risk cannot be excluded, given the mechanism of action of duloxetine (inhibition of serotonin reuptake).
As with the appointment of other serotonergic drugs, the "withdrawal" syndrome can be observed in newborns in the case of the use of duloxetine by the mother in late pregnancy. The “withdrawal” syndrome includes the following symptoms: low blood pressure, tremor, increased neuro-reflex irritability syndrome, feeding difficulties, respiratory distress syndrome, cramps. Most symptoms were observed during childbirth or in the first few days after birth.
Due to the fact that duloxetine passes into breast milk (the concentration in the fetus is about 0.14% of the mother’s concentration based on mg / kg of body weight), breast-feeding during duloxetine therapy is not recommended.
Dosage and administration
Inside. Capsules should be swallowed whole without chewing or crushing. Do not add the drug to food or mix it with liquids, as this can damage the enteric coating of pellets.
The recommended initial dose of the drug is 60 mg 1 time per day, regardless of the meal.
In some patients, in order to achieve a good result, it is necessary to increase the dose from 60 mg once a day to a maximum dose of 120 mg per day in two divided doses. A systematic assessment of taking the drug in a dose of over 120 mg was not carried out.
In patients with renal failure:
the initial dose should be 30 mg once a day in patients with severe renal impairment (end-stage CRF, creatinine clearance 10%)
often - 1/100 appointments (> 1% and 0.1% and 0.01% and 15.
Infrequently: hyperglycemia (especially often observed in patients with diabetes mellitus).
Rarely: dehydration, hyponatremia, syndrome of inadequate secretion of antidiuretic hormone 6.
Very common: insomnia 11.
Often: agitation 10, anxiety, unusual dreams 20, decreased libido (including loss of libido), impaired orgasm (including anorgasmia).
Infrequently: suicidal thoughts 5.22, sleep disturbances, bruxism, disorientation 19, apathy.
Rarely: suicidal behavior 5.22, mania, hallucinations, aggression and hostility 4.
Disorders of the nervous system
Very often: dizziness, headache, drowsiness 12.
Often: tremor, paresthesia 18.
Infrequently: myoclonus, akathisia 22, increased irritability, impaired attention, lethargy, dysgeusia, dyskinesia, restless legs syndrome, decreased quality of sleep.
Rarely: serotonin syndrome 6, convulsions 1, psychomotor agitation 6, extrapyramidal disorders.
Violations of the organ of vision
Often: blurred vision.
Infrequently: mydriasis, visual impairment.
Rarely: glaucoma, dry eyes.
Hearing impairment and labyrinthine disorders
Often: tinnitus 1.
Infrequently: vertigo, earache.
Infrequently: tachycardia, supraventricular arrhythmia, mainly atrial fibrillation.
Often: hyperemia (including hot flashes).
Infrequently: hypertension 3.22, increased blood pressure 3.14, cold extremities, orthostatic hypotension, fainting.
Rarely: hypertensive crisis 3.6.
Disorders of the respiratory system, chest and mediastinal organs
Often: yawning, pain in the oropharynx.
Infrequently: a feeling of tightness in the throat, nosebleeds.
Very often: dry mouth (12.8%), nausea (24.3%), constipation.
Often: diarrhea, vomiting, dyspepsia (including abdominal discomfort), flatulence, abdominal pain 9.
Infrequently: gastrointestinal bleeding 7, gastroenteritis, gastritis, belching, dysphagia.
Rarely: stomatitis, halitosis, hematochesia.
Violations of the liver and biliary tract
Infrequently: hepatitis 3, acute liver damage.
Rarely: liver failure 6, jaundice 6.
Disorders of the skin and subcutaneous tissue
Often: increased sweating, rash, itching.
Infrequently: night sweats, urticaria, contact dermatitis, cold sweat, photosensitivity, increased tendency to bruise.
Rarely: Stevens-Johnson syndrome 6, angioedema 6.
Very rare: tissue contusion.
Musculoskeletal and connective tissue disorders
Often: musculoskeletal pain 17, stiffness of muscles 16, muscle cramps.
Infrequently: muscle cramps.
Violations of the kidneys and urinary tract
Often: increased urination.
Infrequently: urinary retention, dysuria, difficulty starting urination, nocturia, polyuria, decreased urine flow.
Seldom: unusual smell of urine.
Violations of the genitals and mammary gland
Often: erectile dysfunction.
Infrequently: violation of ejaculation 21, delayed ejaculation, sexual dysfunction, gynecological bleeding, irregular menstruation, pain in the testicles.
Rarely: symptoms of menopause, galactorrhea, hyperprolactinemia.
General disorders and disorders at the injection site
Very often: fatigue 13.
Often: falls 8, change in taste.
Infrequently: chest pain 22, atypical sensations, hunger, thirst, chills, malaise, sensation of heat, impaired gait.
Laboratory and instrumental data
Often: weight loss.
Infrequently: an increase in body weight, an increase in the concentration of alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin, creatine phosphokinase, pathological deviation of liver enzymes, an increase in the concentration of potassium in the blood.
Seldom: increase in concentration of cholesterol in blood.
1 Cases of seizures and tinnitus were also noted after completion of treatment with duloxetine.
2 Orthostatic hypotension and syncope were noted especially at the beginning of treatment.
3 See “Special instructions”.
4 Cases of aggression and hostility were noted especially at the beginning of treatment with duloxetine or after its completion.
5 Cases of suicidal thoughts or suicidal behavior were noted during treatment with duloxetine or in the early period after completion of treatment.
6 Estimated frequency of adverse reaction. Not observed during clinical trials.
7 Also includes hemorrhagic diarrhea, bleeding from the lower gastrointestinal tract, vomiting of blood, hemorrhoidal bleeding, melena, rectal bleeding, ulcerative bleeding.
8 Falls were more common in old age (≥ 65 years).
9 Including pain in the upper and lower abdomen, tension of the anterior abdominal wall, abdominal discomfort, gastrointestinal pain.
10 Including internal trembling, motor anxiety, tension, psychomotor agitation.
11 Including awakenings in the middle of the night, early morning awakening, difficulty falling asleep.
12 Including hypersomnia, sedation.
13 Including asthenia.
14 Including an increase in systolic blood pressure, diastolic pressure, systolic hypertension, diastolic hypertension, hypertension, hypertension.
15 Including anorexia.
16 Including muscle rigidity.
17 Including myalgia and neck pain.
18 Including hypesthesia, facial area hypesthesia, genital area hypesthesia, oral paresthesia, very rarely (19 Including confusion.
20 Including nightmares.
21 Including lack of ejaculation.
22 No statistically significant differences with placebo.
Withdrawal of duloxetine (especially at the same time) most often leads to the “withdrawal” syndrome, which includes the following symptoms: dizziness, sensory disturbances (including paresthesia), sleep disturbance (including insomnia and vivid dreams), weakness, drowsiness, agitation or anxiety, nausea and / or vomiting, tremors, headache, irritability, diarrhea, hyperhidrosis, and vertigo.
In general, when taking SSRIs and serotonin and norepinephrine reuptake inhibitors (SSRIs), these phenomena have a weak or moderate severity and limited character. However, in some patients, these phenomena may be more severe and / or prolonged.
With short-term administration of duloxetine (up to 12 weeks), patients with a painful form of peripheral diabetic neuropathy showed a slight increase in fasting blood glucose while maintaining a stable concentration of glycosylated hemoglobin, both in those taking duloxetine and in the placebo group. With prolonged therapy with duloxetine (up to 52 weeks), there was a slight increase in the concentration of glycosylated hemoglobin, which was 0.3% higher than the increase in the corresponding indicator in patients receiving another treatment. Regarding fasting glucose and total cholesterol in the blood, patients taking duloxetine showed a slight increase in these indicators compared with a small decrease observed in the control group of patients.
The corrected (relative to heart rate) QT interval in patients taking duloxetine did not differ from that in the placebo group. There were no clinically significant differences between the QT, PR, QRS, or QTcB intervals in the group of patients taking duloxetine and the placebo group.
Duloxetine - instructions for use, reviews of the drug and analogues
Duloxetine, a third-generation psychotropic drug, is a selective inhibitor of serotonin and norepinephrine reuptake. Unlike psychotropic drugs of the first and second generation, Duloxetine does not affect all mediators of the brain. The drug selectively suppresses the uptake of 5-hydroxytryptamine, dopamine and norepinephrine, since disturbances in their work cause depression.
The medication is a relatively new pharmacological agent that practically does not have a hypnotic effect. According to the instructions, Duloxetine has a wide scope and is considered the safest heterocyclic psychotropic medication. First of all, Duloxetine is used in psychiatry to treat depressive disorders.
Instructions for use Duloxetine: dosages and rules for admission
According to the instructions, therapy should be started with 60 mg of Duloxetine per day. With this dosage, the drug is taken 1 time per day. If necessary, the dosage is increased to 120 mg, but this amount of the substance must be divided into 2 doses. It is not recommended to use more than 120 mg of the drug per day.
Patients with a reduced glomerular filtration rate are prescribed 30 mg of the substance per day. With liver dysfunction, the initial dosage of an antidepressant should also be reduced or the interval for taking the drug should be increased.
The dosage regimen for elderly patients is not different.
The product is intended for internal use. Tablets are taken regardless of the meal, they must be swallowed with a small amount of liquid. Damage to capsules should be avoided.
Discontinue therapy gradually, over a period of 14 days. A sharp cessation of medication can lead to a deterioration in the patient's condition.
During treatment, alcohol abuse is prohibited. During treatment with Duloxetine, caution should be exercised while driving and other potentially dangerous activities.
The amount of the drug necessary for the occurrence of adverse reactions is purely individual, and depends on the compensatory capabilities of the body.
Duloxetine, like other heterocyclic antidepressants, is less toxic than tricyclic, but side effects are similar:
- cardiotoxicity is possible with prolonged use of the drug, but the risk is minimal,
- sedative effect (drowsiness, lethargy, lethargy, impaired attention and memory) is negligible,
- CNS stimulation (insomnia, irritability, anxiety) develops against the background of either long-term use or abrupt drug withdrawal, the risk is low,
- orthostatic hypotension may occur (due to alpha-blocking action), the risk is very low,
- M-anticholinergic action is also minimally expressed (dry mouth, peristalsis disturbance, urinary retention, accommodation disturbance, increased intraocular pressure, tachycardia).
For pregnant and lactation
An antidepressant can be prescribed during pregnancy only when the benefits to the material outweigh the risk to the baby, this is due to the lack of clinical experience with patients in the position. If a woman plans to conceive or it has come, then you must immediately inform your doctor.
The active substance penetrates unknown into breast milk, so it is recommended that you transfer to artificial feeding during lactation.
It is not recommended to exceed the daily dosage of 0.12 grams.
A dosage adjustment is necessary during the treatment of patients with chronic renal failure and liver failure.
Drug withdrawal is carried out gradually, there is a high risk of withdrawal syndrome.
After taking the medicine, there is no violation of psychomotor reactions, memory and other cognitive functions, but drowsiness often occurs. Therefore, driving a car and performing potentially hazardous activities is not recommended.
A complete analogue of Duloxetine - Symbalta.
Release form and composition
Dosage form Duloxetine Canon - enteric capsules: size No. 3 (30 mg) or No. 1 (60 mg), hard gelatin, with a body and a lid of blue color, contents - spherical microspheres from almost white to yellowish-white color (7, 10 , 14 or 15 pcs. In blisters, in a pack of cardboard 1, 2 or 4 packs of 7 capsules, or 2, 3 or 6 packs of 10 capsules, or 1, 2 or 6 packs of 14 capsules, or 2 or 4 packs of 15 capsules).
Composition 1 capsule:
- active substance: duloxetine - 30 or 60 mg,
- inactive components: titanium dioxide, mannitol, starch, cetyl alcohol, sodium lauryl sulfate, sucrose, hypromellose HP55 (hydroxypropyl methyl cellulose), hypromellose E5 (hydroxypropyl methyl cellulose),
- capsule composition: gelatin, titanium dioxide, patent blue dye V.
General information about the drug Duloxetine
Duloxetine is used to eliminate depression and pain during neurosis. The drug prevents the uptake of norepinephrine and serotonin by adrenergic neurons (suppresses the reuptake of these hormones). The drug has a weak effect on the capture of dopamine. The active substance blocks strong pain in neurotic disorders.
Medicinal group, INN, scope
The clinical and pharmacological group of the drug is a third-generation antidepressant. The international nonproprietary name is Duloxetin (Duloxetinum). The medication is used for specific lesions of the peripheral nervous system and various mood disorders. Due to its high efficiency and relative harmlessness, this medicine has gained a wide range of clinical applications.
Release form and prices for Duloxetine Canon
Duloxetine is made in the form of blue-white or blue-green gelatin capsules. On each capsule, a dosage (30 or 60 mg) and an identification number (9543 or 9542) are applied with liquid dye. Capsules are filled with smoky white or gray granules.
The cost of the drug Duloxetine Canon, manufactured by the Russian company Canonfarm Production:
|Dosage mg||Number of capsules||Name of pharmacy||City||Price, rubles|
|60||28||Beauty and Health Laboratory||Moscow||3407|
|60||28||Pharmacy 36.6||St. Petersburg||2037|
The active component in the composition of the drug is the substance duloxetine hydrochloride, which suppresses the central mechanism of pain sensitivity. In addition to the active ingredient, the composition of the capsules includes other substances:
- food coloring E171,
- amylose and amylopectin polysaccharides,
- sodium dodecyl sulfate,
- cane sugar,
- hypromellose HP55,
- hydrolyzed collagen protein,
- food supplement E131.
Indications and contraindications Duloxetine
Indications for use of this drug are:
- complications of diabetes in which the nervous system is affected,
The list of contraindications is also small. The drug is not used for:
- drug hypersensitivity
- simultaneously with antidepressants that suppress the enzyme monoamine oxidase.
Caution should be taken in patients with the following symptoms:
- suicidal tendency
- affective insanity,
- history of seizures
- acute cornerstone glaucoma,
- kidney and liver dysfunction,
- arterial hypertension.
In addition, it is not recommended to take medication for patients whose age has not reached 18 years, since there is no data on the effectiveness and safety of the use of Duloxetine by patients of this group. For the same reason, the medicine is not prescribed during the period of gestation and breastfeeding.
Possible side effects of duloxetine and overdose
Among patients taking Duloxetine, drug tolerance was good. Side effects appear extremely rarely or occur at the beginning of treatment, and eventually pass on their own. But still, with the appearance of the following symptoms, you must consult a doctor to adjust the treatment:
- general weakness
- increase in heart rate,
- difficult and painful digestion,
- decreased appetite
- trembling limbs
- decrease in reaction rate,
- feeling of heat
- sexual dysfunction
- catarrh of the stomach and intestines,
- damage to the oral mucosa,
- high blood pressure
- weight gain
- muscle tension,
- taste disturbances,
- visual impairment
- motor anxiety
- urinary retention
- increased indicators of alanine aminotransferase, aspartate aminotransferase and creatine phosphokinase.
- increased intraocular pressure,
- inflammatory liver diseases, Gospel disease,
- anaphylactic reactions,
- violation of the water-electrolyte balance,
- pathological elements on the skin and mucous membranes,
- Quincke's edema, rashes on the skin and mucous membranes, urticaria,
- a sharp drop in blood pressure and fainting.
A fatal outcome due to exceeding the recommended dose was observed only with a joint medication with other drugs.
Overdose is expressed by the following symptoms:
- pain in the pit of stomach, vomiting,
- involuntary muscle contractions,
- increase in heart rate,
In case of an overdose, it is recommended to do a gastric lavage and take activated charcoal to reduce the absorption of the substance. In severe cases, hospitalization is recommended.
The opinion of doctors
Doctors consider this medicine an effective and cheaper domestic substitute for foreign antidepressants. Basically they leave positive reviews about the drug:
- Savenko L. M., psychiatrist: “Patients taking this drug literally come to life before our eyes. They become more mobile and self-confident. Compared with foreign counterparts, Duloxetine is inexpensive, so I often prescribe it to my patients, especially older ones. ”
- Rogachevsky R. Yu., Psychiatrist: “The medication is inferior to other antidepressants in its effectiveness, but it also has fewer side effects. "The remedy helps with depression, but affect inversion and transition to a hypomanic state with Duloxetine are not achieved."
Thus, doctors note the effectiveness of the drug in the fight against depression. But with more serious mental disorders, it may be necessary to use another remedy.
Reviews of patients taking the medication are not always positive. Many note the side effects that appear from treatment with the drug and its inefficiency. Others, on the contrary, note the good effect of the drug and easy tolerance:
- Diana, 22 years old: “I encountered side effects of the medication only at the beginning of therapy. Later, no negative manifestations arose. The antidepressant effect manifested itself quite quickly: everyday neuroses were gone, there was hope for the best. However, upon termination of therapy, I encountered a “withdrawal” syndrome, although the dose was reduced gradually. ”
- Peter, 32 years old: “The medication helped ease the symptoms of fibromyalgia: the pains decreased significantly, depression went away, and it became easier to concentrate. However, the drug made me very addicted and soon the normal dose simply stopped helping. ”
Duloxetine is a domestic antidepressant drug that copes well with depression of various origins. It is necessary to take this remedy with caution, as it causes addiction and "withdrawal" syndrome. Before use, it is important to consult a doctor.
Indications for use
- depressive disorders
- generalized anxiety disorder,
- pain form of peripheral diabetic neuropathy,
- chronic pain syndrome of the musculoskeletal system, including in the lower back, with osteoarthritis of the knee joint and due to fibromyalgia.
Instructions for use Duloxetine Canon: method and dosage
Duloxetine Canon is indicated for oral use. Capsules must be swallowed whole, without crushing, without chewing.Eating does not affect the effectiveness of the drug, but capsules should not be mixed with liquids or added to food, since damage to the enteric membrane is possible.
At the beginning of treatment, 60 mg is usually prescribed once a day. If necessary, increase the dose to 60 mg 2 times a day.
Patients with cirrhosis must reduce the initial dose or reduce the frequency of administration.
The initial dose of Duloxetine Canon for patients with severe renal impairment (creatinine clearance 10%, often from> 1% to 0.1% to 0.01% to
Duloxetine canon: prices in online pharmacies
Duloxetine Canon 30 mg enteric-soluble capsules 14 pcs.
DULOKSETIN CANON 30mg 14 pcs. enteric capsules
Duloxetine Canon 60 mg capsule, enteric, 28 pcs.
DULOKSETIN CANON 60mg 28 pcs. enteric capsules
Duloxetine Canon Caps. Ksh / sol 60mg n28
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes and does not replace the official instructions. Self-medication is dangerous to health!
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