Cymbalta, 60 mg capsules 14 pcs

Symbalta has an antidepressant effect.

Pharmacodynamics

Duloxetine is an antidepressant, serotonin and norepinephrine reuptake inhibitor and weakly inhibits dopamine reuptake, with no significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors. The mechanism of action of duloxetine in the treatment of depression is to inhibit serotonin and norepinephrine reuptake, resulting in increased serotonergic and noradrenergic neurotransmission in the CNS.

Duloxetine has a central mechanism of pain syndrome suppression, which is primarily manifested by an increase in the threshold of pain sensitivity in pain syndrome of neuropathic etiology.

Pharmacokinetics

Intake. Duloxetine is well absorbed when taken orally. Absorption begins 2 h after taking the drug. C_max is reached 6 h after ingestion.

Eating does not affect the maximum concentration of the drug, but increases the time to reach C_max from 6 to 10 hours, which indirectly reduces the degree of absorption (approximately 11%).

Distribution. Duloxetine binds well to plasma proteins (>90%), mainly to albumin and α₁-globulin; hepatic or renal disorders have no effect on degree of protein binding.

Metabolism. Duloxetine is actively metabolized, and its metabolites are mainly excreted in the urine.

The CYP2D6 and CYP1A2 both catalyze the formation of two major metabolites (4-hydroxyduloxetine glucurone conjugate, 5-hydroxy-6-methoxyduloxetine sulfate conjugate).

Circulating metabolites have no pharmacological activity.

Evacuation. The duration of T_1/2 of duloxetine is 12 h. Average Cl of duloxetine is 101 l/h.

Separate patient groups

Gender: Although differences in pharmacokinetics have been found in men and women (mean clearance of duloxetine is lower in women), these differences are not so great as to necessitate a dose adjustment based on gender.

Age: Although differences in pharmacokinetics have been found in middle-aged and elderly patients (AUC is higher and duration of T_1/2 of the drug is longer in the elderly), these differences are not sufficient to change the dose based on patient age alone.

Kidney function impairment: In patients with severe renal impairment (terminal chronic renal failure) on hemodialysis, the C_max and AUC values of duloxetine were increased 2-fold. Therefore, consideration should be given to reducing the dose of the drug in patients with clinically significant impaired renal function.

Hepatic impairment: In patients with clinical signs of hepatic impairment there may be delayed metabolism and excretion of duloxetine. After a single dose of 20 mg duloxetine, 6 patients with cirrhosis and moderate hepatic impairment (Child-Pugh class B) had a T_1/2 duration of duloxetine approximately 15% longer than that of healthy subjects of the corresponding sex and age with a fivefold increase in mean AUC exposure. Although the C_max in cirrhotic patients was the same as in healthy subjects, the T_1/2 was about 3 times longer.

Indications

Depression; painful form of diabetic neuropathy.

Active ingredient

Composition

1 capsule contains:

the active ingredient:

duloxetine (as hydrochloride) 60 mg

excipients:

sucrose;

Hypromellose;

granulated sugar (not more than 91.5% sucrose, starch);

talc;

Hypromellose acetate succinate;

triethylcitrate;

white dye (titanium dioxide, hypromellose)

capsule shell:

indigo carmine; titanium dioxide; sodium lauryl sulfate; gelatin; iron oxide yellow dye (only for 60 mg capsules)

How to take, the dosage

Symbalta is prescribed orally, regardless of meals.

The capsules should be swallowed whole without chewing or crushing. Cymbalta should not be added to food or mixed with liquids as this may damage the capsule’s gut-soluble coating.

The recommended starting dose of Cymbalta is 60 mg once daily. If necessary, the dose may be increased to a maximum dose of 120 mg daily in 2 doses. There has been no systematic evaluation of Cymbalta doses above 120 mg.

In end-stage chronic renal failure (CKR less than 30 ml/min), the initial dose of Cymbalta is 30 mg once daily.

Interaction

Drugs metabolized by CYP1A2. Concomitant use of duloxetine (60 mg twice daily) had no significant effect on the pharmacokinetics of CYP1A2-metabolized theophylline. Duloxetine is unlikely to have a clinically significant effect on the metabolism of CYP1A2 substrates.

CYP1A2 inhibitors. Because CYP1A2 is involved in the metabolism of duloxetine, concomitant administration of duloxetine with potential CYP1A2 inhibitors is likely to increase duloxetine concentrations. The potent CYP1A2 inhibitor, fluvoxamine (100 mg once daily), reduced the mean plasma clearance of duloxetine by approximately 77%. Caution should be exercised when prescribing duloxetine with CYP1A2 inhibitors (e.g., some quinolone antibacterials) and using lower doses of duloxetine.

Drugs that are metabolized by CYP2D6. Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine is taken at a dose of 60 mg twice daily along with a single dose of desipramine, a CYP2D6 substrate, the AUC of desipramine is increased 3-fold. Concomitant administration of duloxetine (40 mg 2 times daily) increased the stable portion of the AUC of tolterodine (2 mg 2 times daily) by 71%, but had no effect on the pharmacokinetics of the 5-hydroxylmetabolite. Thus, caution should be exercised when using duloxetine with drugs that are primarily metabolized by the CYP2D6 system and have a low therapeutic index.

CYP2D6 inhibitors. Because CYP2D6 is involved in the metabolism of duloxetine, concomitant use of duloxetine with potential CYP2D6 inhibitors may result in increased concentrations of duloxetine.

Paroxetine (20 mg once daily) reduced mean clearance of duloxetine by approximately 37%. Caution should be exercised when using duloxetine with CYP2D6 inhibitors (e.g., SSRIs).

Drugs affecting the CNS. Caution should be exercised when using duloxetine with other CNS-affecting drugs and agents, including alcohol, especially those with a similar mechanism of action.

Drugs that bind highly to blood proteins. Duloxetine binds significantly to plasma proteins (>90%). Therefore, prescribing duloxetine to a patient who is taking another drug that binds highly to plasma proteins may result in higher concentrations of free fractions of both drugs.

Special Instructions

MAO inhibitors. In patients receiving a serotonin reuptake inhibitor in combination with MAOI inhibitors, there have been cases of serious reactions, sometimes fatal, including hyperthermia, rigidity, myoclonus, peripheral disturbances with possible dramatic variations in vital signs and mental status changes, including severe agitation with a transition to delirium and coma.

These reactions have also been observed in patients in whom a serotonin reuptake inhibitor had been withdrawn shortly before administration of MAOIs. In some cases, patients experienced symptoms 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. Therefore, given that duloxetine is an inhibitor of both serotonin and norepinephrine reuptake, it is not recommended that duloxetine be taken in combination with MAO inhibitors or for at least 14 days after stopping treatment with MAO inhibitors. Based on the half-life of duloxetine, a break of at least 5 days should be taken after stopping duloxetine before taking MAO inhibitors.

An exacerbation of manic/hypomanic state: As with similar drugs that affect the CNS, duloxetine should be used with caution in patients with a history of manic episodes.

Epileptic seizures: As with analogous drugs that affect the CNS, duloxetine should be used with caution in patients with a history of epileptic seizures.

Mydriasis: cases of mydriasis have been observed with duloxetine, so caution should be exercised when prescribing duloxetine in patients with elevated intraocular pressure or risk of acute closed-angle glaucoma.

Hepatic or renal impairment:In patients with severe renal impairment (creatinine cl

Suicidal attempts: in depression there is a possibility of suicidal attempts, which may persist until sustained remission. Close monitoring of patients at risk is necessary.

Driving and performance of work requiring increased attention

Duloxetine studies have not shown impairment of psychomotor reactions, cognitive functions and memory. However, taking the drug may be accompanied by somnolence. Patients taking duloxetine should therefore be cautious when driving motor vehicles, including cars.

Contraindications

With caution:

Side effects

The most frequently (10%) reported findings in clinical trials were dizziness (except vertigo), dry mouth, nausea, constipation, sleep disturbances (drowsiness or insomnia), and headache. Headache was less frequent than with placebo.

Rarely (1 to

Dizziness, nausea, and headache were noted as frequent adverse effects of duloxetine withdrawal.

Mild increases in fasting blood glucose with duloxetine in patients with painful diabetic neuropathy may be observed.

Overdose

A few cases of overdose have been reported when up to 1400 mg of the drug was administered at one time, without fatal consequences. Overdose may be accompanied by the following symptoms: tremor, clonic convulsions, ataxia, vomiting and decreased appetite.

Treatment: no specific antidote is known. Cardiac monitoring and monitoring of basic vital signs along with symptomatic and supportive treatment is recommended.

Pregnancy use

Because of the lack of experience with the use of Cymbalta during pregnancy, the drug should only be prescribed during pregnancy if the potential benefit to the patient significantly exceeds the potential risk to the fetus. Patients should be warned that if they become pregnant or are planning to become pregnant while being treated with duloxetine, they should inform their physician.

In view of the lack of experience with duloxetine in women during breastfeeding, breastfeeding is not recommended during duloxetine therapy.

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