Dapfix - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 41.56 mg, lactose monohydrate 50.14 mg, sodium carboxymethyl starch 13.5 mg, povidone (K30) 1.125 mg, iron dye oxide yellow 0.06 mg, iron oxide red oxide 0.06 mg, magnesium stearate 1.125 mg.

Each 50 mg tablet contains:

active substance: venlafaxine hydrochloride 56.57 mg is equivalent to 50 mg of venlafaxine;

Excipients: cellulose microcrystalline 55.41 mg, lactose monohydrate 66.85 mg, carboxymethyl starch sodium 18.0 mg, povidone (K30) 1.5 mg, iron oxide oxide yellow 0.081 mg, iron oxide red oxide 0.081 mg, magnesium stearate 1.5 mg.

Each 75 mg tablet contains:

active substance: venlafaxine hydrochloride 84.86 mg is equivalent to 75 mg of venlafaxine;

Excipients: cellulose microcrystalline 83.12 mg, lactose monohydrate 100.28 mg, sodium carboxymethyl starch 27.0 mg, povidone (K30) 2.25 mg, iron dye oxide yellow 0.012 mg, iron oxide dye red 0.012 mg, magnesium stearate 2.25 mg.

Description:

Tablets 37.5 mg: bice pink with a weak yellowish, shade of color with white impregnations, round, biconvex tablets with embossing "RDY" on one side and "546" on the other side.

50 mg tablets: bice pink with a weak yellowish hue of color with white impregnations, round, biconcave tablets with embossing "RDY"on one side and "547" on the other side.

Tablets 75 mg: bice pink with a weak yellowish hue of color with white impregnated, round, biconvex tablets with embossing "RDY" on one side and "548" on the other side.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X.16 Venlafaxine

N.06.A.X Other antidepressants

Pharmacodynamics:

Antidepressant. By chemical structure venlafaxine can not be attributed to any known class of antidepressants (tricyclic, tetracyclic or other). It has two active enantiomeric racemic forms. Venlafaxine and its active metabolite O-desmethylvenlafaxine (EFA) are potent inhibitors of the reuptake of serotonin and norepinephrine and weak inhibitors of dopamine reuptake. It is believed that the mechanism of antidepressant action is associated with an increase in neurotransmitter activity in the central nervous system (CNS). On the inhibition of serotonin reuptake venlafaxine is inferior to selective serotonin reuptake inhibitors. Venlafaxine and O-desmethylvenlafaxine reduce beta-adrenergic reactions. Venlafaxine has no affinity for m- and n-cholinergic receptors, histamine H₁receptors and α₁-adrenoceptors of the brain. Venlafaxine does not suppress MAO activity.Has no affinity for opioid, benzodiazepine, phencyclidine or N-methyl-daspartate (NMDA) receptors.

Pharmacokinetics:

Absorption - 92%, does not depend on food intake. Bioavailability is 40-45%, which is associated with presystemic metabolism. After a single dose of tablets in a dose of 25 to 150 mg, the time to reach the maximum concentration (TC_m_Oh) - 2,1-2,4 h, the maximum concentration (C_m_Oh) - 37-163 ng / ml. The equilibrium concentration in plasma (Css) of venlafaxine and O-desmethylvenlafaxine is reached within 3 days of admission. The connection with plasma proteins of venlafaxine and O-desmethylvenlafaxine is 27 and 30%, respectively.

The area under the pharmacokinetic curve (AUC) and fluctuations in plasma concentrations of venlafaxine and O-desmethylvenlafaxine are comparable when given equal daily doses of venlafaxine in 2 or 3 doses.

Venlafaxine undergoes a pronounced metabolism in the liver involving cytochrome P450 (isoenzyme CYP2D6) with the formation of an active metabolite of O-desmethylvenlafaxine. Primarily (87%), kidneys are excreted for 48 hours (in unchanged form - 5%, in the form of unconjugated O desmethylvenlafaxine - 29%, conjugated O-desmethylvenlafaxine - 26%, other inactive metabolites - 27%).

Venlafaxine and O-desmethylvenlafaxine enter the breast milk.Does not cause drug dependence and addiction. Pharmacokinetic parameters do not depend on sex and age.

With hepatic and / or renal failure from moderate to severe, there was a decrease in the metabolism of venlafaxine and elimination of O-desmethylvenlafaxine, which led to an increase in their C_m_Oh, decrease in clearance and elongation of the half-life (T_1/2). Decrease in the total clearance of the drug was most pronounced in patients with creatinine clearance below 30 ml / min.

Indications:

Treatment of depression.

Prevention of recurrence of depression.

Contraindications:Hypersensitivity to the components of the drug, simultaneous administration of monoamine oxidase (MAO) inhibitors, lactase deficiency, lactose intolerance, glucose-galactose malabsorption, age to 18 years, severe violations of the liver function, severe renal dysfunction (creatinine clearance less than 10 ml / min), pregnancy, lactation (breastfeeding).

Carefully:

Recently suffered myocardial infarction, unstable angina, arterial hypertension, tachycardia, history of convulsions, intraocular hypertension, angle-closure glaucoma, manic conditions in the anamnesis,hyponatremia, hypovolaemia, dehydration, simultaneous reception of diuretics, suicidal tendencies, predisposition to hemorrhages in the skin and bleeding from the mucous membranes, renal failure (creatinine clearance more than 10 ml / min), hepatic insufficiency.

Pregnancy and lactation:

Application during pregnancy (or suspected pregnancy) is contraindicated. Women of childbearing age should apply reliable methods of contraception during the treatment with the drug and immediately consult a doctor in case of pregnancy or pregnancy planning.

Venlafaxine and the metabolite O-desmethylvenlafaxine enter the breast milk. The safety of these substances for newborns is not proven, so if you need to take the drug during lactation, you should decide whether to stop breastfeeding. If the mother's treatment was completed shortly before the birth, a newborn can have withdrawal symptoms.

Dosing and Administration:

Inside, together with food, it is desirable at the same time, without chewing and washing with liquid. The recommended starting dose is 37.5 mg 2 times a day.If necessary, the dose can be increased at intervals of not less than 4 days by 75 mg / day. The recommended dose for moderate depression is 225 mg / day in 3 divided doses, with a severe depression, the maximum permissible daily dose is 375 mg for 3 doses.

Cancellation of the drug should be carried out gradually to avoid the syndrome of "withdrawal": in the course of treatment for 6 weeks or more, the period of gradual withdrawal of the drug should be at least 2 weeks and depends on the dose, duration of therapy and individual characteristics of the patient (during clinical tests the dose was reduced on 75 mg once a week).

In case of impaired renal function (glomerular filtration rate - 10-70 ml / min) daily dose should be reduced by 25-50%.

With hemodialysis The daily dose should be reduced by 50%, the drug should be taken after the end of the hemodialysis session.

In patients with moderate hepatic impairment the daily dose should be reduced by 50% or more.

Side effects:

Depending on the frequency of occurrence, the following groups of side effects are distinguished: frequent - more than 1%, infrequent - 0,1-1%, rare - 0,01-0,1%, very rare - less than 0,01%.

From the nervous system: often - dizziness, asthenia, weakness, insomnia, "nightmarish" dreams, increased nervous excitability, paresthesia, hypertonic muscles, tremor, sedation; infrequently - apathy, hallucinations, myoclonus, syncope; rarely - cramps, mania, malignant neuroleptic syndrome.

From the side of the cardiovascular system: often - increased blood pressure (BP), hyperemia of the skin; infrequently - a decrease in blood pressure, postural hypotension, tachycardia.

From the digestive system: often - decreased appetite, nausea, vomiting, infrequent bruxism (involuntary grinding of teeth), increased activity of "liver" transaminases; rarely - hepatitis.

From the genitourinary system: often - decreased libido, erectile dysfunction and / or ejaculation, anorgasmia, menorrhagia, urination disorder; infrequently - urinary retention, violation of orgasm in women.

From the sense organs: often - a violation of accommodation, mydriasis, impaired vision; infrequent - a violation of taste perception.

Allergic reactions: infrequent - rash, photosensitivity; very rarely - multiforme exudative erythema (including Stevens-Johnson syndrome), anaphylaxis.

Laboratory indicators: infrequently - thrombocytopenia; rarely - increased bleeding time, hyponatremia; with prolonged intake and use of high doses - hypercholesterolemia.

Other: often - loss of body weight, hyperperespiration (including night); infrequently - ecchymosis, weight gain; rare - the syndrome of inadequate secretion of ADH, serotonin syndrome (nausea, vomiting, abdominal pain, diarrhea, flatulence, psychomotor agitation, tachycardia, hyperthermia, muscle rigidity, convulsions, myoclonus, sweating, impaired consciousness from delirium to sopor and coma with subsequent fatal outcome ).

If there is a syndrome of "cancellation": dizziness, headache, asthenia, fatigue, sleep disturbances (change in the nature of dreams, drowsiness or insomnia, difficulty falling asleep), hypomania, anxiety, increased nervous excitability, confusion, paresthesia, increased sweating, dry mouth, decreased appetite, nausea, vomiting, diarrhea (most of these reactions are slightly expressed and do not require treatment).

Overdose:

Symptoms: dizziness, lowering blood pressure, changes in ECG (lengthening interval Q-T, bundle branch blockade, QRS enlargement), sinus and ventricular tachycardia or bradycardia, impaired consciousness (from drowsiness to coma), convulsions and death.

Treatment: symptomatic; ECG monitoring and vital organs functions; at risk of aspiration, vomiting is not recommended; Washing (if an overdose has occurred recently, or the symptoms of an overdose persist); Activated carbon. The effectiveness of forced diuresis, dialysis, hemoperfusion and blood transfusion has not been proven; specific antidotes are unknown.

Interaction:

Incompatible with MAO inhibitors.

Reduces AUC indinavir by 28% and its C_m_Oh - by 36% (the clinical significance of the established interaction is unknown).

Increases the anticoagulant effect of warfarin.

Increases the effect of ethanol on psychomotor reactions.

When oral intake reduces the total clearance of haloperidol by 42%, increases it AUC by 70% and C_m_Oh by 88%.

Venlafaxine does not affect the pharmacokinetics of diazepam and its active metabolite, does not alter the pharmacological effects of diazepam.

Ketoconazole. Drugs, the metabolism of which occurs with the participation of cytochrome P450 isoenzymes: CYP2D6 converts venlafaxine in the active metabolite of EFA. Unlike many other antidepressants, the dose of venlafaxine can not be reduced with simultaneous administration with isoenzyme inhibitors CYP2D6, or in patients with a genetically determined decrease in isoenzyme activity CYP2D6, since the total concentration of active substance and metabolite (venlafaxine and EFA) will not change. The main way of removing venlafaxine involves metabolism with the participation of isoenzymes CYP2D6 and CYP3A4, therefore, special care should be taken when administering Dapfix® in combination with inhibitors of these isoenzymes. This drug interaction has not yet been investigated. Venlafaxine - relatively weak isoenzyme inhibitor CYP2D6 and does not suppress the activity of isoenzymes CYP1A2, CYP2C9 and CYP3A4; therefore, one should not expect its interaction with other drugs in the metabolism of which these isozymes participate.

Cimetidine suppresses the metabolism of the "first passage" of venlafaxine and does not affect the pharmacokinetics of O-desmethylvenlafaxine. In most patients, only a slight increase in the total pharmacological activity of venlafaxine and O-desmethylvenlafaxine is expected (more pronounced in elderly patients and in liver failure).

Has no effect on the pharmacokinetics of imipramine and 2-OH-imipramine, but the indices AUC, FROM_m_Oh and C_min desipramine increases by 35%, a AUC 2-OH-desipramine in 2.5-4.5 times.

Raises the AUC risperidone by 32%, but does not significantly affect the total pharmacokinetic profile of the active components - risperidone plus 9-hydroxyrisperidone (the clinical significance of the revealed interaction is unknown).

Does not interact with lithium preparations, as well as preparations metabolized by isoenzymes CYP3A4, CYP1A2 and CYP2C9 (including, alprazolam, caffeine, carbamazepine, diazepam).

Does not affect the concentration in the plasma of drugs that have a high degree of binding to proteins.

Special instructions:

Taking venlafaxine is possible no earlier than 14 days after discontinuation of therapy with MAO inhibitors and should be discontinued no less than 7 days before any MAO inhibitor starts (it may develop or increase dizziness, nausea, vomiting, hyperpersia, skin flushing, tremor, myoclonus, hyperthermia, signs similar to malignant neuroleptic syndrome, seizures, up to fatal outcome).

In children, adolescents and young people (under 24 years) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when appointing venlafaxine or any other antidepressants in children, adolescents and young people (younger than 24 years), the risk of suicide and the benefits of their use should be correlated. In short-term studies in people over 24 years of age, the risk of suicide did not increase, but in people older than 65 years, it declined slightly. Any depressive disorder in itself increases the risk of suicide. Therefore, during treatment with antidepressants, all patients should be monitored for early detection of abnormalities or behavioral changes, as well as suicidal tendencies.

In patients with affective disorders in the treatment of antidepressants (including venlafaxine), hypomanic or manic conditions may occur. Like other antidepressants, venlafaxine should be administered with caution to patients with a history of mania. Such patients need medical supervision.

Dapfix (as well as other antidepressants) should be administered with caution to patients with epileptic seizures in the anamnesis. Treatment with venlafaxine should be interrupted if epileptic seizures occur.

With caution, it is recommended to use the drug in patients with tachyarrhythmia. Against the background of treatment with the drug, an increase in the number of heartbeats is possible, especially during high doses.

Some patients with venlafaxine received a dose-dependent increase in blood pressure, therefore regular monitoring of blood pressure is recommended, especially during the period of correction or increase in dose.

Patients, especially the elderly, should be warned about the possibility of dizziness and discomfort.

Like other serotonin reuptake inhibitors, venlafaxine can increase the risk of hemorrhages in the skin and bleeding from the mucous membranes. Care should be taken when treating patients who are predisposed to such conditions.

During the administration of the drug may be observed mydriasis, in connection with which it is recommended to control intraocular pressure in patients prone to its increase or with a closed-angle glaucoma.

On the background of treatment in patients with hypovolemia or in dehydrated patients (including elderly patients and taking diuretics), hyponatremia and / or the syndrome of inadequate secretion of antidiuretic hormone may develop.

In healthy volunteers, the drug had virtually no effect on the speed of psychomotor reactions, cognitive abilities and complex behavioral responses. However, given the possibility of significant side effects from the central nervous system, care should be taken during the treatment period when driving vehicles and engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

During treatment it is recommended to refrain from taking ethanol.

Form release / dosage:

Tablets, 37.5 mg, 50 mg and 75 mg.

Packaging:

For 10 tablets in PVC / PVDC / aluminum blister. For 1, 2 or 6 blisters with instructions for use in a pack of cardboard.

For 14 tablets in PVC / PVDC / aluminum blister. For 1 or 2 blisters with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000352

Date of registration:22.02.2011 / 28.02.2013

Expiration Date:22.02.2016

The owner of the registration certificate:Dr. Reddy's Laboratories Ltd.Dr. Reddy's Laboratories Ltd. India

Manufacturer: & nbsp

DR. REDDY`S LABORATORIES, LTD. India

Representation: & nbspDR REDDY'S LABORATORIS LTD. DR REDDY'S LABORATORIS LTD. India

Information update date: & nbsp18.03.2017

Illustrated instructions

Instructions

Dapfix® (Dapfix®)