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Cymbalta

Cymbalta
Cymbalta has an antidepressant effect. Duloxetine is an antidepressant, serotonin and norepinephrine reuptake inhibitor, and weakly suppresses dopamine uptake, without significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors.

Brand: Duloxetine

Availability: In Stock
Average Delivery Time: 9 Days
Exp. Date: November 2023
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Product description

Pharmacological action of Cymbalta 

Buy Cymbalta in Canada

Antidepressant, serotonin and norepinephrine reuptake inhibitor (norepinephrine). It weakly 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 suppress the reuptake of serotonin and norepinephrine (norepinephrine). Duloxetine has a central mechanism for suppressing pain syndrome, which is primarily manifested by an increase in the pain sensitivity threshold in pain syndrome of neuropathic etiology.

Pharmacokinetics

Treatment of depression with Cymbalta

After oral administration, duloxetine is well absorbed from the gastrointestinal tract, absorption begins 2 hours after administration, Cmax is achieved 6 hours after administration. Consumption simultaneously with food increases the time to reach Cmax up to 10 hours, which reduces the degree of absorption (by about 10%), but does not affect the value of Cmax.

Plasma protein binding is high (over 90%), mainly with albumin and α1-globulin. Liver or kidney abnormalities do not affect protein binding. Duloxetine is actively biotransformed with the participation of isoenzymes CYP2D6 and CYP1A2, which catalyze the formation of two main metabolites (glucuronic conjugate of 4-hydroxyduloxetine, sulfate conjugate of 5-hydroxy, 6-methoxyduloxetine). Circulating metabolites have no pharmacological activity. T1/2 is 12 hours. The average clearance of duloxetine is 101 l / h. It is excreted in the urine as metabolites.

In patients with end-stage chronic renal failure on hemodialysis, the values ​​of Cmax and AUC of duloxetine increased by 2 times. In this regard, the advisability of reducing the dose of the drug in patients with clinically severe renal impairment should be considered.

In patients with clinical signs of hepatic failure, a slowdown in metabolism and excretion of duloxetine may be observed. After a single dose of duloxetine at a dose of 20 mg in 6 patients with cirrhosis of the liver and moderate hepatic impairment (class B on the Child-Pugh scale), the duration of T1/2 of duloxetine was approximately 15% higher than in healthy people of the corresponding sex and age with five-fold increase in the average AUC. Despite the fact that the Cmax in patients with cirrhosis was the same as in healthy people, T1/2 is approximately 3 times higher.

Indications of the active substances of the drug Cymbalta®

Depression, painful form of diabetic neuropathy.

Dosage regimen of Cymbalta 

Cymbalta anti-depression drug packaging

The recommended starting 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 impairment (CC <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 should be reduced.

Contraindications to use

Uncompensated angle-closure glaucoma, simultaneous use with MAO inhibitors, hypersensitivity to duloxetine.

Use during pregnancy and lactation

Use of the drug during pregnancy is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus, because clinical experience with duloxetine during pregnancy is insufficient.

If it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be resolved (due to lack of experience in use).

Patients should be warned that in the event of a pregnancy or planning a pregnancy while using duloxetine, they need to inform their doctor about it.

Application for violations of liver function

Use with caution in violation of liver function. In patients with impaired liver function, the initial dose of the drug should be reduced or the frequency of administration should be reduced.

Application for impaired renal function Use with

caution in impaired renal function. In patients with severe renal impairment (CC <30 ml / min), the initial dose should be 30 mg 1 time / day.

Special instructions

Use with caution in exacerbation of a manic / hypomanic state, epileptic seizures, mydriasis, impaired liver or kidney function, in patients with a tendency to suicidal attempts.

When prescribing serotonin reuptake inhibitors in combination with MAO inhibitors, there have been cases of serious reactions, sometimes fatal (hyperthermia, rigidity, myoclonus, various disorders with possible sharp fluctuations in the indicators of vital body functions and changes in mental status, including pronounced excitement with the transition to delirium and to whom). Such reactions are also possible in cases where the serotonin reuptake inhibitor was canceled shortly before the appointment of MAO inhibitors (symptoms may develop, including those characteristic of neuroleptic malignant syndrome).

The effects of the combined use of duloxetine and MAO inhibitors have not been evaluated in either humans or animals. The use of duloxetine concurrently with MAO inhibitors or in the period up to 14 days after their cancellation is not recommended, because duloxetine is a serotonin and norepinephrine (norepinephrine) reuptake inhibitor. MAO inhibitors should not be prescribed for at least 5 days after discontinuation of duloxetine.

Use with caution in patients with a history of manic episodes, as well as with a history of epileptic seizures.

Depressive states are accompanied by a high risk of developing suicidal behavior. As a consequence, patients diagnosed with depression taking duloxetine should inform the physician of any disturbing thoughts and feelings.

With the use of the drug, the development of mydriasis is possible, caution should be exercised when prescribing duloxetine to patients with increased intraocular pressure or in persons at risk of developing acute angle-closure glaucoma.

In patients with arterial hypertension and / or other diseases of the cardiovascular system, it is recommended to control blood pressure.

Influence on the ability to drive vehicles and control mechanisms

Patients taking duloxetine should be careful when engaging in potentially hazardous activities (due to the possible occurrence of drowsiness).

Drug interaction

Simultaneous use of duloxetine (at a dose of 60 mg 2 times / day) did not significantly affect the pharmacokinetics of theophylline, which is metabolized by CYP1A2. Duloxetine is unlikely to have a clinically significant effect on the metabolism of other drugs - CYP1A2 substrates.

Concomitant use of duloxetine with potential inhibitors of CYP1A2 (for example, fluoroquinolones) may lead to an increase in duloxetine concentration, because CYP1A2 is involved in the metabolism of duloxetine (the appointment of such a combination requires caution and reduced doses of duloxetine).

The potent CYP1A2 inhibitor fluvoxamine (when taken at a dose of 100 mg once a day) reduced the mean plasma clearance of duloxetine by about 77%.

Caution should be exercised when prescribing duloxetine with drugs metabolized by CYP2D6 and having a narrow therapeutic index (since duloxetine is a moderate inhibitor of CYP2D6). With simultaneous use with duloxetine at a dose of 60 mg 2 times / day, the AUC of desipramine (substrate CYP2D6) increases 3 times. Concomitant use with duloxetine (at a dose of 40 mg 2 times / day) increased the stable part of the AUC of tolterodine (used at a dose of 2 mg 2 times / day) by 71%, but had no effect on the pharmacokinetics of the 5-hydroxyl metabolite. Concomitant use of duloxetine with potential inhibitors of CYP2D6 may lead to an increase in duloxetine concentrations. Paroxetine (when used at a dose of 20 mg 1 time / day) reduced the mean clearance of duloxetine by about 37%. Caution should be exercised when using duloxetine with CYP2D6 inhibitors (for example, 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), mutual enhancement of the effects is possible (this combination requires caution).

Duloxetine is largely bound to plasma proteins, therefore, simultaneous use with other drugs that bind to plasma proteins to a high degree can lead to an increase in the concentration of free fractions of both drugs.


Side effect

From the side of the central nervous system: often - dizziness (except for vertigo), sleep disturbances (drowsiness or insomnia), headache (headache was noted less often than with placebo); sometimes - tremor, weakness, blurred vision, lethargy, anxiety, yawning; very rarely - glaucoma, mydriasis, visual impairment, agitation, disorientation.

From the digestive system: often - dry mouth, nausea, constipation; sometimes - diarrhea, vomiting, loss of appetite, change in taste, abnormal liver function indicators; very rarely - hepatitis, jaundice, increased ALP, ALT, AST and bilirubin levels; belching, gastroenteritis, stomatitis.

From the musculoskeletal system: sometimes - muscle tension and / or twitching; very rarely - bruxism.

From the side of the cardiovascular system: sometimes - palpitations; very rarely - orthostatic hypotension, syncope (especially at the beginning of therapy), tachycardia, increased blood pressure, cold extremities.

From the reproductive system: sometimes - anorgasmia, decreased libido, delay and impaired ejaculation, erectile dysfunction.

From the urinary system: sometimes - difficulty urinating; very rarely - nocturia.

Others: sometimes - weight loss, increased sweating, hot flashes, night sweats; very rarely - anaphylactic reactions, thirst, hyponatremia, chills, angioedema, rash, Stevens-Johnson syndrome, urticaria, feeling unwell, feeling hot and / or cold, weight gain, dehydration, photosensitization. When canceled, dizziness, nausea, and headache were often noted. Patients with painful diabetic neuropathy may experience a slight increase in fasting blood glucose.