Cymbalta 30 Mg 28 Tablets ingredient Duloxetine

PHARMACEUTICAL FORM

Capsule (contains enteric coated micropellets)

Cymbalta 30 mg capsule is printed in opaque white color "30 mg" opaque blue colored cap "9543"

5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties

Pharmacotherapeutic group (ATC code: N06AX21): Other Antidepressants
5.2. Pharmacokinetic properties

Steady-state plasma concentrations are generally achieved after 3 days of dosing. Duloxetine metabolizes in the liver. The two cytokines responsible for the metabolism are P450 isoenzyme CYP2D6 and CYP1A2.

Absorbation

Duloxetine administered orally is well absorbed from the gastrointestinal tract. An average of 2 hours delay is considered until absorption begins, and maximum plasma concentrations (Cmax) are reached after 6 hours of dosing. Although foods do not affect the C max value of duloxetine, the time to peak concentration increases from 6 hours to 10 hours and reduces the amount of absorption (EAA) by about 10%. Compared to morning hours, there is a 3 hour delay in the absorption of duloxetine in the evening hours and an increase of three times in the visible clearance.

Distribution

The volume of distribution is about 1640 L. Duloxetine binds to plasma proteins (> 90%) in humans, primarily albumin and al-acid glycoprotein. The interaction of duloxetine with other drugs that bind high in the protein has not been fully evaluated. Renal or hepatic failure does not affect the level of binding of duloxetine to plasma proteins.

biotransformation

Studies conducted after the oral administration of 14C-labeled duloxetine have determined the biotransformation and disposition of duloxetine in humans. Duloxetine constitutes about 3% of total radioactive labeled material in the plasma; this ratio indicates that duloxetine undergoes intense metabolism and converts into a large number of metabolites. The main biotransformation routes of duloxetine are oxidation of the naphthyl ring following conjugation and reoxidation. In vitro experiments, both CYP2D6 and CYP1A2 catalyze the oxidation of the naphthyl ring. The metabolites found in the plasma are 4-hydroxy duloxetine glucuronate and 5-hydroxy, 6-methoxy duloxetine sulfate.

Elimination

The elimination half-life of duloxetine is about 12 hours (8-17 hours) and its pharmacokinetic properties are proportional to the dose in the therapeutic range. Several additional metabolites have been identified in the process, some of which are eliminated only by minor excretion. There is duloxetine that is unchanged only in trace amounts (dose <1%). Most of the doses of duloxetine (70%) are found as duloxetine metabolites in urine; up to 20% of the drug is excreted.

Characteristics of patients

Gender

The elimination half-life of duloxetine in females and males is similar. You do not have to do dose adjustments by sex.

Age

When the pharmacokinetics of duloxetine were compared between healthy elderly women aged 65 to 77 years and healthy middle-aged women aged 32 to 50 years given a single dose of 40 mg, there was no difference in Cmax values ​​but slightly higher (about 25%) and half-life 4 hour is longer. In studies evaluating population pharmacokinetics, clearance was reduced by about 1% per year in the 25-75 age range, with age being only a small percentage as predicted factor in terms of patient variability. There is no need to adjust the dose according to the age of the patient (see section 4.2 "Posology and method of administration").

Smoking

It is observed that in smokers the bioequivalence of duloxetine (EAA) is reduced by about one third. Dosage adjustment is not recommended for smokers.

Race

No specific pharmacokinetic study has been conducted to investigate the effects of races. Kidney / Liver Failure

Data on the effects of duloxetine on people with end stage renal disease are limited. In individuals with intermittent chronic hemodialysis and end stage renal disease, the Cmax and EAA values ​​determined after a single dose of 60 mg duloxetine were found to be approximately 100% higher than those with normal renal function. However, it was seen that the breakthrough half-life was similar in both groups. It has been observed that 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy-duloxetine sulfate, which are major metabolites in circulation, increase urinary EAA values ​​about 7-9 times and it is expected that there will be more increase in EAA with multiple doses. Therefore, duloxetine is not recommended for patients with end stage renal disease (requiring dialysis) or severe renal insufficiency (estimated creatinine clearance <30 mL / min) (see section 4.2 "Posology and Practice Shape"). Population pharmacokinetic analyzes indicate that mild to moderate renal dysfunction (estimated creatinine clearance 30-80 mL / min) is not a significant effect on the apparent clearance of duloxetine.

Duloxetine metabolism and excretion are less in patients with clinically insufficient liver function. Six cirrhotic patients with moderate hepatic impairment (Child-Pugh Class B) received 20 mg, Mean plasma Duloxetine clearance was found to be 15% of the value in healthy individuals with similar age and gender, and the mean exposure dose (EAA) was increased 5-fold after a single dose of duloxetine. Although the Cmax value in cirrhotic patients is similar, the half-life is about 3 times longer (see section 4.4 "Special warnings and precautions for use" and section 4.2 "Posology and practice"). The pharmacokinetics of duloxetine and its metabolites have not been investigated in patients with mild to severe hepatic impairment. Preclinical safety data Carcinogenic effect: Duloxetine was administered to mice and rats along with the diet for 2 years. In female mice given duloxetine at a dose of 140 mg / kg / day (11 times the recommended maximum human dose [MRHD (maximum recommended human dose), 60 mg / kg] and 120 mg / adenomas and carcinomas were detected. The effect-unobserved dose was 50 mg / kg / day (4 times the MRHD and 2 times the human dose of 120 mg / day based on mg / m). In male rats given duloxetine at doses up to 100 mg / kg / day (8 times MRHD and 4 times 120 mg / day human dose based on mg / m), the incidence of tumor incidence did not increase. In mice, 27 mg / kg / day (6 times the MRHD and 3 times the human dose of 120 mg / day based on mg / m) up to 36 mg / kg / day in men and 4 times the dose of 120 mg / did not increase the incidence of tumor metastasis. Mutagenic effect: Duloxetine was not mutagenic in the in vitro bacterial reverse mutation test (Ames test) and did not cause clastogenic effects in the in vivo chromosomal aberration test with mouse bone marrow cells. It has also been determined that duloxetine does not induce genotoxic effects in in vitro advanced gene mutation measurements in mouse lymphoma cells or in untreated DNA synthesis (UDS) measurements in primary rat hepatocytes, and did not initiate sister chromatid exchange in in vivo experiments in bone marrow of Chinese hamster. Effect on Fertility: Male or female rats were fed duloxetine orally administered at doses up to 45 mg / kg / day (recommended maximum human dose 60 mg / day 7 times and 120 mg / day human dose 4 times based on mg / m)

6. PHARMACEUTICAL PROPERTIES
6.1. List of supporting materials

Capsule content:

Hypromellose, hydroxypropyl methylcellulose acetate succinate, sucrose, sugar spheres, talc, titanium dioxide (E171), triethyl citrate

Capsule sheath:

30 mg: Gelatin, sodium lauryl sulfate, titanium dioxide (E171), indigo carmin (E132), green food ink,

Green food ingredient content: Black iron oxide-synthetic (E172), yellow iron oxide-synthetic (E172), propylene glycol, shellac

Capsule cap lid color: 30 mg: Opaque blue

2. Things to watch out for before using CYMBALTA
DO NOT USE CYMBALTA in the following situations

if

• If you have allergies (hypersensitivity) to any of the other ingredients of Duloxetine or CYMBALTA

• If you are currently on other antidepressant drugs called monoamine oxidase inhibitor (MAOI) or have used it within the last 14 days (see "Use with other drugs" section below)

• If you have liver disease

• If you have serious kidney disease

• If you use fluvoxamine, ciprofloxacin and enoxacin

• If you are using other drugs that contain Duloxetine

• If you have uncontrollable high blood pressure

USE CYMBALTA CAREFULLY

The following are the reasons why CYMBALTA may not be suitable for you. If any of the following are present in you, talk to your doctor before using the pill: If

• If you are using other medications to treat depression

• If you have kidney disease

• If you have had epileptic seizures before

• If you suffer from manic or bipolar disorder or have suffered in the past

• If you have eye problems such as certain glaucoma types (increased pressures in the eye)

• If you have a bleeding disorder (tendency to bruise)

• You are younger than 18 years

• If you have high blood pressure

CYMBALTA may cause a feeling of restlessness or difficulty sitting or standing. If this happens to you, tell your doctor.

As with the other drugs (antidepressants) with a similar mechanism of action, suicidal thoughts and suicidal behavior were reported with duloxetine treatment or shortly after cessation of treatment. Depression indications; attempting to harm yourself or attempting suicide. Until the antidepressant effect is fully manifested, it is possible that symptoms of depression continue for the first few weeks of treatment. Since depression, anxiety, and other serious mental illnesses are the most important causes of suicidal thoughts and movements, there may be a greater risk of such symptoms in young adult patients with previous self-harming thoughts.

If you have any unpleasant thoughts or actions at any time, or if any, report them to your doctor immediately.

Use in children and adolescents under the age of 18: CYMBALTA should not normally be used in children and adolescents under the age of 18. When these drugs are used in patients under the age of 18, you should be aware of the increased risk of side effects such as suicide attempts, suicidal thoughts, and feelings of hostility (aggression, opposition, and anxiety). Nevertheless, your doctor may recommend CYMBALTA under the age of 18, believing it will be of benefit. If your doctor prescribes CYMBALTA to a patient under the age of 18, and you want to discuss this, please come back to your doctor. When patients under the age of 18 are taking CYMBALTA, any of the above mentioned symptoms will appear and you should inform your doctor if it gets worse. Long-term safety effects of CYMBALTA on growth, maturation, cognitive and behavioral development in this age group of patients have not yet been demonstrated.

Please consult your doctor if these reminders apply to you at any time in the past.

Use of CYMBALTA with food and drink

CYMBALTA can be used on hungry or tummy stomach. Although CYMBALTA does not deteriorate the effects of alcohol, care should be taken when taking alcohol while being treated with CYMBALTA.

Pregnancy

Consult your doctor or pharmacist before using this medication.

If you become pregnant while using CYMBALTA or plan to become pregnant, tell your doctor. You should only use CYMBALTA after discussing potential benefits and potential risks posed by your unborn child with your doctor.

If you notice that you are pregnant in the middle of your treatment, or if you plan to become pregnant, consult your doctor or pharmacist immediately.

Breast-feeding

Consult your doctor or pharmacist before using this medication. The use of lactating CYMBALTA is not recommended.

Vehicle and machine use

When using CYMBALTA, do not use the car or any machine.

Important information about certain substances in the content of CYMBALTA

CYMBALTA contains sucrose. If your doctor tells you that you are not tolerant to certain sugars, consult your doctor before taking this medicine.

Use with other medicines

Your doctor should decide whether you should use CYMBALTA with other medicines. Before you check with your doctor, do not start using any medication, including over-the-counter medicines and herbal medicines, and do not leave any medication you use.

Duloxetine, the main ingredient of CYMBALTA, can also be found in other medicines. Do not use with such drugs at the same time, inform your doctor.

Monoamine Oxidase Inhibitors (MAOI): Other antidepressants, also called monoamine oxidase inhibitors (MAOI)