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Venlalic(R) XL 225mg Tablets Last Updated on eMC 06-Feb-2013 View changes | DB Ashbourne Ltd Contact details Name of the medicinal product Qualitative and quantitative composition Pharmaceutical form Clinical particulars - 4.1 Therapeutic indications - 4.2 Posology and method of administration - 4.3 Contraindications - 4.4 Special warnings and precautions for use - 4.5 Interaction with other medicinal products and other forms of interaction - 4.6 Pregnancy, lactation and fertility - 4.7 Effects on ability to drive and use machines - 4.8 Undesirable effects - 4.9 Overdose Pharmacological properties - 5.1 Pharmacodynamic properties - 5.2 Pharmacokinetic properties - 5.3 Preclinical safety data Pharmaceutical particulars - 6.1 List of excipients - 6.2 Incompatibilities - 6.3 Shelf life - 6.4 Special precautions for storage - 6.5 Nature and contents of container - 6.6 Special precautions for disposal and other handling Marketing authorisation holder Marketing authorisation number(s) Date of first authorisation/renewal of the authorisation Date of revision of the text Major depressive episodesThe recommended starting dose for prolonged-release venlafaxine is 75 mg given once daily. Patients not responding to the initial 75 mg/day dose may benefit from dose increases up to a maximum dose of 375 mg/day. Dosage increases can be made at intervals of 2 weeks or more. If clinically warranted due to symptom severity, dose increases can be made at more frequent intervals, but not less than 4 days. Because of the risk of dose-related adverse effects, dose increments should be made only after a clinical evaluation (see section 4.4). The lowest effective dose should be maintained. Patients should be treated for a sufficient period of time, usually several months or longer. Treatment should be reassessed regularly on a case-by-case basis. Longer-term treatment may also be appropriate for prevention of recurrence of major depressive episodes (MDE). In most of the cases, the recommended dose in prevention of recurrence of MDE is the same as the one used during the current episode. Antidepressive medicinal products should continue for at least six months following remission. Social anxiety disorderThe recommended dose for prolonged-release venlafaxine is 75 mg given once daily. There is no evidence that higher doses confer any additional benefit. However, in individual patients not responding to the initial 75 mg/day, increases up to a maximum dose of 225 mg/day may be considered. Dosage increases can be made at intervals of 2 weeks or more. Because of the risk of dose-related adverse effects, dose increments should be made only after a clinical evaluation (see section 4.4). The lowest effective dose should be maintained. Patients should be treated for a sufficient period of time, usually several months or longer. Treatment should be reassessed regularly, on a case-by-case basis. Use in elderly patientsNo specific dose adjustments of venlafaxine are considered necessary based on patient age alone. However, caution should be exercised in treating the elderly (e.g., due to the possibility of renal impairment, the potential for changes in neurotransmitter sensitivity and affinity occurring with aging). The lowest effective dose should always be used, and patients should be carefully monitored when an increase in the dose is required. Use in children and adolescents under the age of 18 yearsVenlafaxine is not recommended for use in children and adolescents. Controlled clinical studies in children and adolescents with major depressive disorder failed to demonstrate efficacy and do not support the use of venlafaxine in these patients (see sections 4.4 and 4.8). The efficacy and safety of venlafaxine for other indications in children and adolescents under the age of 18 have not been established. Use in patients with hepatic impairmentIn patients with mild and moderate hepatic impairment, in general a 50% dose reduction should be considered. However, due to inter-individual variability in clearance, individualisation of dosage may be desirable. There are limited data in patients with severe hepatic impairment. Caution is advised, and a dose reduction by more than 50% should be considered. The potential benefit should be weighed against the risk in the treatment of patients with severe hepatic impairment. Use in patients with renal impairmentAlthough no change in dosage is necessary for patients with glomerular filtration rate (GFR) between 30-70 ml/minute, caution is advised. For patients that require haemodialysis and in patients with severe renal impairment (GFR < 30 ml/min), the dose should be reduced by 50 %. Because of inter-individual variability in clearance in these patients, individualisation of dosage may be desirable. Withdrawal symptoms seen on discontinuation of venlafaxineAbrupt discontinuation should be avoided. When stopping treatment with venlafaxine, the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions (see sections 4.4 and 4.8). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate. For oral use. It is recommended that venlafaxine prolonged-release tablets be taken with food, at approximately the same time each day. Tablets must be swallowed whole with fluid and not divided, crushed, chewed, or dissolved. Patients treated with venlafaxine immediate-release tablets may be switched to venlafaxine prolonged-release tablets at the nearest equivalent daily dosage. For example, venlafaxine immediate-release tablets 37.5 mg twice daily may be switched to venlafaxine prolonged-release tablets 75 mg once daily. Individual dosage adjustments may be necessary. The prolonged-release tablet keeps its shape during the whole digestion releasing the active ingredient and is eliminated intact in the faeces. Suicide/suicidal thoughts or clinical worseningDepression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery. Other psychiatric conditions for which venlafaxine is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders. Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old. Close supervision of patients, and in particular those at high risk, should accompany drug therapy, especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour, and to seek medical advice immediately if these symptoms present. Use in children and adolescents under 18 years of ageVenlafaxine should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking. Serotonin syndromeAs with other serotonergic agents, development of a potentially life-threatening serotonin-syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions, may occur with venlafaxine treatment, particularly with concomitant use of other serotonergic agents (including SSRIs, SNRIs and triptans), with agents that impair metabolism of serotonin such as MAO-inhibitors(e.g. methylene blue), or with antipsychotics or other dopamine antagonists (see sections 4.3 and 4.5). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea). Serotonin syndrome in its most severe form, can resemble NMS, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs and mental status changes. If concomitant treatment with venlafaxine and other agents that may affect the serotonergic and/or dopaminergic neurotransmitter systems is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of venlafaxine with serotonin precursors (such as tryptophan supplements) is not recommended. Narrow-angle glaucomaMydriasis may occur in association with venlafaxine. It is recommended that patients with raised intraocular pressure or patients at risk for acute narrow-angle glaucoma (angle-closure glaucoma) be closely monitored. Blood pressureDose-related increases in blood pressure have been commonly reported with venlafaxine. In some cases, severely elevated blood pressure requiring immediate treatment has been reported in postmarketing experience. All patients should be carefully screened for high blood pressure and pre-existing hypertension should be controlled before initation of treatment. Blood pressure should be reviewed periodically, after initiation of treatment and after dose increases. Caution should be exercised in patients whose underlying conditions might be compromised by increases in blood pressure, e.g., those with impaired cardiac function. Heart rateIncreases in heart rate can occur, particularly with higher doses. Caution should be exercised in patients whose underlying conditions might be compromised by increases in heart rate. Cardiac disease and risk of arrhythmiaVenlafaxine has not been evaluated in patients with a recent history of myocardial infarction or unstable heart disease. Therefore, it should be used with caution in these patients. In postmarketing experience, fatal cardiac arrhythmias have been reported with the use of venlafaxine, especially in overdose. The balance of risks and benefits should be considered before prescribing venlafaxine to patients at high risk of serious cardiac arrhythmia. ConvulsionsConvulsions may occur with venlafaxine therapy. As with all antidepressants, venlafaxine should be introduced with caution in patients with a history of convulsions, and concerned patients should be closely monitored. Treatment should be discontinued in any patient who develops seizures. HyponatraemiaCases of hyponatraemia and/or the Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion may occur with venlafaxine. This has most frequently been reported in volume-depleted or dehydrated patients. Elderly patients, patients taking diuretics, and patients who are otherwise volume-depleted may be at greater risk for this event. Abnormal bleedingMedicinal products that inhibit serotonin uptake may lead to reduced platelet function. The risk of skin and mucous membrane bleeding, including gastrointestinal haemorrhage, may be increased in patients taking venlafaxine. As with other serotonin-reuptake inhibitors, venlafaxine should be used cautiously in patients predisposed to bleeding, including patients on anticoagulants and platelet inhibitors. Serum cholesterolClinically relevant increases in serum cholesterol were recorded in 5.3% of venlafaxine-treated patients and 0.0% of placebo-treated patients treated for at least 3 months in placebo-controlled clinical trials. Measurement of serum cholesterol levels should be considered during long-term treatment. Co-administration with weight loss agentsThe safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established. Co-administration of venlafaxine and weight loss agents is not recommended. Venlafaxine is not indicated for weight loss alone or in combination with other products. Mania/hypomaniaMania/hypomania may occur in a small proportion of patients with mood disorders who have received antidepressants, including venlafaxine. As with other antidepressants, venlafaxine should be used cautiously in patients with a history or family history of bipolar disorder. AggressionAggression may occur in a small number of patients who have received antidepressants, including venlafaxine. This has been reported under initiation, dose changes and discontinuation of treatment. As with other antidepressants, venlafaxine should be used cautiously in patients with a history of aggression. Discontinuation of treatmentWithdrawal symptoms, when treatment is discontinued, are common, particularly if discontinuation is abrupt (see section 4.8). In clinical trials, adverse events seen on treatment discontinuation (tapering and post-tapering) occurred in approximately 31% of patients treated with venlafaxine and 17% of patients taking placebo. The risk of withdrawal symptoms may be dependent on several factors, including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor and headache are the most commonly reported reactions. Generally, these symptoms are mild to moderate; however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose. Generally, these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that venlafaxine should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs (see section 4.2). Akathisia/psychomotor restlessnessThe use of venlafaxine has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental. Dry mouthDry mouth is reported in 10% of patients treated with venlafaxine. This may increase the risk of caries, and patients should be advised upon the importance of dental hygiene. DiabetesIn patients with diabetes, treatment with an SSRI or venlafaxine may alter glycaemic control. Insulin and/or oral antidiabetic dosage may need to be adjusted. Potential for gastrointestinal obstructionBecause the Venlalic XL prolonged-release tablet is nondeformable and does not appreciably change in shape in the gastrointestinal (GI) tract, it should not ordinarily be administered to patients with pre-existing severe GI narrowing (pathologic or iatrogenic) or in patients with dysphagia or significant difficulty in swallowing tablets. There have been rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of drugs in nondeformable prolonged-release formulations. Due to the prolonged-release design of the tablet, Venlalic XL prolonged-release tablets should only be used in patients who are able to swallow the tablet whole (see section 4.2). Venlalic XL prolonged-release tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Serotonin syndromeAs with other serotonergic agents, serotonin syndrome, a potentially life-threatening condition, may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system (including triptans, SSRIs, SNRIs, lithium, sibutramine, tramadol, or St. John's Wort [Hypericum perforatum]), with medicinal agents that impair metabolism of serotonin (such as MAOIs e.g. methylene blue), or with serotonin precursors (such as tryptophan supplements). If concomitant treatment of venlafaxine and an SSRI, an SNRI or a serotonin receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of venlafaxine with serotonin precursors (such as tryptophan supplements) is not recommended (see section 4.4). CNS-active substancesThe risk of using venlafaxine in combination with other CNS-active substances has not been systematically evaluated. Consequently, caution is advised when venlafaxine is taken in combination with other CNS-active substances. EthanolVenlafaxine has been shown not to increase the impairment of mental and motor skills caused by ethanol. However, as with all CNS-active substances, patients should be advised to avoid alcohol consumption. Effect of other medicinal products on venlafaxine Ketoconazole (CYP3A4 inhibitor)A pharmacokinetic study with ketoconazole in CYP2D6 extensive (EM) and poor metabolisers (PM) resulted in higher AUC of venlafaxine (70% and 21% in CYP2D6 PM and EM subjects, respectively) and O-desmethylvenlafaxine (33% and 23% in CYP2D6 PM and EM subjects, respectively) following administration of ketoconazole. Concomitant use of CYP3A4 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, voriconazole, posaconazole, ketoconazole, nelfinavir, ritonavir, saquinavir, telithromycin) and venlafaxine may increase levels of venlafaxine and O-desmethylvenlafaxine. Therefore, caution is advised if a patient's therapy includes a CYP3A4 inhibitor and venlafaxine concomitantly. Effect of venlafaxine on other medicinal products LithiumSerotonin syndrome may occur with the concomitant use of venlafaxine and lithium (see Serotonin syndrome). DiazepamVenlafaxine has no effects on the pharmacokinetics and pharmacodynamics of diazepam and its active metabolite, desmethyldiazepam. Diazepam does not appear to affect the pharmacokinetics of either venlafaxine or O-desmethylvenlafaxine. It is unknown whether a pharmacokinetic and/or pharmacodynamic interaction with other benzodiazepines exists. ImipramineVenlafaxine did not affect the pharmacokinetics of imipramine and 2-OH-imipramine. There was a dose-dependent increase of 2-OH-desipramine AUC by 2.5 to 4.5-fold when venlafaxine 75 mg to 150 mg daily was administered. Imipramine did not affect the pharmacokinetics of venlafaxine and O-desmethylvenlafaxine. The clinical significance of this interaction is unknown. Caution should be exercised with co-administration of venlafaxine and imipramine. HaloperidolA pharmacokinetic study with haloperidol has shown a 42% decrease in total oral clearance, a 70% increase in AUC, an 88% increase in Cmax, but no change in half-life for haloperidol. This should be taken into account in patients treated with haloperidol and venlafaxine concomitantly. The clinical significance of this interaction is unknown. RisperidoneVenlafaxine increased the risperidone AUC by 50%, but did not significantly alter the pharmacokinetic profile of the total active moiety (risperidone plus 9-hydroxyrisperidone). The clinical significance of this interaction is unknown. MetoprololConcomitant administration of venlafaxine and metoprolol to healthy volunteers in a pharmacokinetic interaction study for both medicinal products resulted in an increase of plasma concentrations of metoprolol by approximately 30-40% without altering the plasma concentrations of its active metabolite, a-hydroxymetoprolol. The clinical relevance of this finding in hypertensive patients is unknown. Metoprolol did not alter the pharmacokinetic profile of venlafaxine or its active metabolite, O-desmethylvenlafaxine. Caution should be exercised with co-administration of venlafaxine and metoprolol. IndinavirA pharmacokinetic study with indinavir has shown a 28% decrease in AUC and a 36% decrease in Cmax for indinavir. Indinavir did not affect the pharmacokinetics of venlafaxine and O-desmethylvenlafaxine. The clinical significance of this interaction is unknown. PregnancyThere are no adequate data from the use of venlafaxine in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Venlafaxine must only be administered to pregnant women if the expected benefits outweigh any possible risk. As with other serotonin reuptake inhibitors (SSRIs/SNRIs), discontinuation symptoms may occur in the newborns if venlafaxine is used until or shortly before birth. Some newborns exposed to venlafaxine late in the third trimester have developed complications requiring tube-feeding, respiratory support or prolonged hospitalisation. Such complications can arise immediately upon delivery. Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Although no studies have investigated an association of PPHN to SNRI treatment, this potential risk cannot be ruled out with Venlalic XL prolonged-release tablet taking into account the related mechanism of action (inhibition of the re-uptake of serotonin). The following symptoms may be observed in neonates if the mother has used an SSRI/SNRI late in pregnancy: irritability, tremor, hypotonia, persistent crying, and difficulty in sucking or in sleeping. These symptoms may be due to either serotonergic effects or exposure symptoms. In the majority of cases, these complications are observed immediately or within 24 hours after partus. LactationVenlafaxine and its active metabolite, O-desmethylvenlafaxine, are excreted in breast milk. There have been post-marketing reports of breast-fed infants who experienced crying, irritability, and abnormal sleep patterns. Symptoms consistent with venlafaxine drug discontinuation have also been reported after stopping breast-feeding. A risk to the suckling child cannot be excluded. Therefore, a decision to continue/discontinue breast-feeding or to continue/discontinue therapy with venlafaxine should be made, taking into account the benefit of breast-feeding to the child and the benefit of venlafaxine therapy to the woman. Paediatric patientsIn general, the adverse reaction profile of venlafaxine (in placebo-controlled clinical trials) in children and adolescents (ages 6 to 17) was similar to that seen for adults. As with adults, decreased appetite, weight loss, increased blood pressure, and increased serum cholesterol were observed (see section 4.4). In paediatric clinical trials the adverse reaction suicidal ideation was observed. There were also increased reports of hostility and, especially in major depressive disorder, self-harm. Particularly, the following adverse reactions were observed in paediatric patients: abdominal pain, agitation, dyspepsia, ecchymosis, epistaxis, and myalgia. Recommended treatmentGeneral supportive and symptomatic measures are recommended; cardiac rhythm and vital signs must be monitored. When there is a risk of aspiration, induction of emesis is not recommended. Gastric lavage may be indicated if performed soon after ingestion or in symptomatic patients. Administration of activated charcoal may also limit absorption of the active substance. Forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. No specific antidotes for venlafaxine are known. Major depressive episodesThe efficacy of venlafaxine immediate-release as a treatment for major depressive episodes was demonstrated in five randomised, double-blind, placebo-controlled, short-term trials ranging from 4 to 6 weeks duration, for doses up to 375 mg/day. The efficacy of venlafaxine prolonged-release as a treatment for major depressive episodes was established in two placebo-controlled, short-term studies for 8 and 12 weeks duration, which included a dose range of 75 to 225 mg/day. In one longer-term study, adult outpatients who had responded during an 8-week open trial on venlafaxine prolonged-release (75, 150, or 225 mg) were randomised to continuation of their same venlafaxine prolonged-release dose or to placebo, for up to 26 weeks of observation for relapse. In a second longer-term study, the efficacy of venlafaxine in prevention of recurrent depressive episodes for a 12-month period was established in a placebo-controlled double-blind clinical trial in adult outpatients with recurrent major depressive episodes who had responded to venlafaxine treatment (100 to 200 mg/day, on a b.i.d. schedule) on the last episode of depression. Social anxiety disorderThe efficacy of venlafaxine as a treatment for social anxiety disorder was established in four double-blind, parallel-group, 12-week, multi-center, placebo-controlled, flexible-dose studies and one double-blind, parallel-group, 6-month, placebo-controlled, fixed/flexible-dose study in adult outpatients. Patients received doses in a range of 75 to 225 mg/day. There was no evidence for any greater effectiveness of the 150 to 225 mg/day group compared to the 75 mg/day group in the 6-month study. AbsorptionAt least 92% of venlafaxine is absorbed following single oral doses of immediate-release venlafaxine. Absolute bioavailability is 40% to 45% due to presystemic metabolism. After immediate-release venlafaxine administration, the peak plasma concentrations of venlafaxine and ODV occur in 2 and 3 hours, respectively. Following the administration of venlafaxine prolonged-release form, peak plasma concentrations of venlafaxine and ODV are attained within 5.5 hours and 9 hours, respectively. When equal daily doses of venlafaxine are administered as either an immediate-release tablet or prolonged-release form, the prolonged-release form provides a slower rate of absorption, but the same extent of absorption compared with the immediate-release form. Food does not affect the bioavailability of venlafaxine and ODV. DistributionVenlafaxine and ODV are minimally bound at therapeutic concentrations to human plasma proteins (27% and 30%, respectively). The volume of distribution for venlafaxine at steady-state is 4.4±1.6 L/kg following intravenous administration. MetabolismVenlafaxine undergoes extensive hepatic metabolism. In vitro and in vivo studies indicate that venlafaxine is biotransformed to its major active metabolite, ODV, by CYP2D6. In vitro and in vivo studies indicate that venlafaxine is metabolised to a minor, less active metabolite, N-desmethylvenlafaxine, by CYP3A4. In vitro and in vivo studies indicate that venlafaxine is a weak inhibitor of CYP2D6. Venlafaxine did not inhibit CYP1A2, CYP2C9, or CYP3A4. EliminationVenlafaxine and its metabolites are excreted primarily through the kidneys. Approximately 87% of a venlafaxine dose is recovered in the urine within 48 hours as either unchanged venlafaxine (5%), unconjugated ODV (29%), conjugated ODV (26%), or other minor inactive metabolites (27%). Mean ± SD plasma steady-state clearances of venlafaxine and ODV are 1.3±0.6 L/h/kg and 0.4±0.2 L/h/kg, respectively. Special populations Age and genderSubject age and gender do not significantly affect the pharmacokinetics of venlafaxine and ODV. CYP2D6 extensive/poor metabolisersPlasma concentrations of venlafaxine are higher in CYP2D6 poor metabolisers than extensive metabolisers. Because the total exposure (AUC) of venlafaxine and ODV is similar in poor and extensive metabolisers, there is no need for different venlafaxine dosing regimens for these two groups. Patients with hepatic impairmentIn Child-Pugh A (mildly hepatically impaired) and Child-Pugh B (moderately hepatically impaired) subjects, venlafaxine and ODV half-lives were prolonged compared to normal subjects. The oral clearance of both venlafaxine and ODV was reduced. A large degree of intersubject variability was noted. There are limited data in patients with severe hepatic impairment (see section 4.2). Patients with renal impairmentIn dialysis patients, venlafaxine elimination half-life was prolonged by about 180% and clearance reduced by about 57% compared to normal subjects, while ODV elimination half-life was prolonged by about 142% and clearance reduced by about 56%. Dosage adjustment is necessary in patients with severe renal impairment and in patients that require haemodialysis (see section 4.2). Core:Mannitol (E421)Povidone K-90Macrogol 400Cellulose microcrystallineColloidal anhydrous silicaMagnesium stearate Coat:Cellulose acetate Macrogol 400Opadry Y 30 18037 (mixture of hypromellose, lactose monohydrate, titanium dioxide (E171) and triacetin) DB Ashbourne Ltd The Rectory, Braybrooke Road , Arthingworth, Market Harborough, LE16 8JT Before you contact this company: often several companies will market medicines with the same active ingredient. Please check that this is the correct company before contacting them. Why? Active ingredients Legal categories This site uses cookies. By continuing to browse the site you are agreeing to our policy on the use of cookies. Find out more here.
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Seroxat tablete (20/30mg) – Uputa o lijeku Proizvođač: Belupo Samo na recept? DA Skoči na: » opis » primjena » doziranje » mjere opreza » napomene Opis SASTAV 1 SEROXATTM 20 mg tableta sadržava 20 mg paroksetina u obliku paroksetin-klorid hemihidrata. Pomoćne tvari: boja E171. 1 SEROXATTM 30 mg tableta sadržava 30 mg paroksetina u obliku paroksetin-klorid hemihidrata. Pomoćne tvari: boje E 171 i E132. FARMACEUTSKI OBLIK I VELIČINA PAKIRANJA Filmom obložena tableta. Blister s 10 tableta, 3 blistera u kutiji. FARMAKOTERAPIJSKA SKUPINA Paroksetin je antidepresiv iz skupine selektivnih inhibitora ponovne pohrane serotonina. NAČIN I MJESTO IZDAVANJA Na recept , u ljekarnama. ROK VALJANOSTI Otisnut je na pakiranju. Lijek se ne smije primijeniti nakon isteka roka valjanosti! NAČIN ČUVANJA LIJEKA Lijek treba čuvati pri temperaturi do 25°C. Lijek treba čuvati izvan dohvata djece! Primjena Terapijske indikacije Odrasli SEROXAT se primjenjuje u liječenju: - teške depresivne epizode - opsesivno kompulzivnog poremećaja - paničnog poremećaja sa ili bez agorafobije - socijalnog anksioznog poremećaja / socijalne fobije - posttraumatskog stresnog poremećaja - generaliziranog anksioznog poremećaja. Djeca/Adolescenti SEROXAT nije namijenjen za liječenje djece i adolescenata do 18 godina. Naime, kontrolirana klinička ispitivanja nisu dokazala djelotvornost i ne podupiru primjenu paroksetina u liječenju velikog depresivnog poremećaja kod djece i adolescenata do 18 godina. Primjena paroksetina u djece mlađe od 7 godina nije ispitivana. Doziranje Doziranje i način primjene Preporuča se primjenjivati SEROXAT jednom dnevno, ujutro, uz jelo. Bolesnike s depresijom ili opsesivno kompulzivnim poremećajem treba liječiti dovoljno dugo kako bi osigurali nestanak simptoma bolesti. To može biti razdoblje od nekoliko mjeseci za depresiju, a još dulje za opsesivno kompulzivni i panični poremećaj. Teška depresivna edpizoda Preporučena doza je 20 mg paroksetina na dan. Poboljšanje obično nastupa nakon tjedan dana liječenja, ali u nekim slučajevima su potrebna i 2 tjedna. Bolesnicima koji ne odgovaraju na terapiju od 20 mg paroksetina na dan doza se povećava za po 10 mg u skladu s terapijskim učinkom lijeka, do maksimalne doze od 50 mg paroksetina na dan. Tri do četiri tjedna od početka liječenja doziranje se mora nadgledati i, ovisno o kliničkom odgovoru, korigirati. Opsesivno kompulzivni poremećaj Preporučena doza je 40 mg paroksetina na dan. Liječenje započinje s 20 mg paroksetina na dan, a doza se može postupno povećavati za po 10 mg u skladu s terapijskim učinkom lijeka, do postizanja preporučene dnevne doze. Najviša dnevna doza je 60 mg paroksetina. Panični poremećaj Preporučena doza je 40 mg paroksetina na dan. Liječenje započinje s 10 mg paroksetina na dan i doza se povećava za po 10 mg paroksetina, u skladu s terapijskim učinkom. Doza se može povećavati do najviše 60 mg paroksetina na dan. Niska početna doza se preporuča zbog izbjegavanja mogućeg pogoršanja simptoma panike do kojih općenito dolazi u ranoj fazi liječenja ovog poremećaja. Socijalni anksiozni poremećaj / Socijalna fobija Preporučena doza je 20 mg paroksetina na dan. Bolesnicima koji ne odgovaraju na terapiju od 20 mg paroksetina na dan doza se postupno povećava za po 10 mg, u skladu s terapijskim učinkom lijeka, do maksimalne doze od 50 mg paroksetina na dan. Liječnik treba ponovno ocijeniti korisnost primjene kod bolesnika koji dulje vrijeme uzimaju lijek. Posttraumatski stresni poremećaj Preporučena doza je 20 mg paroksetina na dan. Bolesnicima koji ne odgovaraju na terapiju od 20 mg paroksetina na dan doza se postupno povećava za po 10 mg, u skladu s terapijskim učinkom lijeka, do maksimalne doze od 50 mg paroksetina na dan. Liječnik treba ponovno ocijeniti korisnost primjene kod bolesnika koji dulje vrijeme uzimaju lijek. Generalizirani anksiozni poremećaj Preporučena doza je 20 mg paroksetina na dan. Bolesnicima koji ne odgovaraju na terapiju od 20 mg paroksetina na dan doza se postupno povećava za po 10 mg, u skladu s terapijskim učinkom lijeka, do maksimalne doze od 50 mg paroksetina na dan. Liječnik treba ponovno ocijeniti korisnost primjene kod bolesnika koji dulje vrijeme uzimaju lijek. Prestanak primjene paroksetina Kao i kod drugih psihoaktivnih lijekova, općenito treba izbjegavati nagli prestanak primjene. U nedavno provedenim kliničkim ispitivanjima kod odraslih i djece primijenjen je režim postupnog smanjivanja doze za po 10 mg paroksetina na dan u tjednim razmacima. Kada se dostigne doza paroksetina od 20 mg paroksetina na dan, bolesnik treba nastaviti uzimati lijek u toj dozi tijekom jednog tjedna prije potpunog prestanka terapije. Ukoliko se tijekom smanjivanja ili nakon prestanka terapije pojave simptomi koje bolesnik teško podnosi, treba razmotriti ponovnu primjenu prethodno propisane doze. Nakon toga liječnik može nastaviti smanjivati dozu, ali u još duljim vremenskim razmacima. Djeca i adolescenti (do 18 godina) Paroksetin nije namijenjen za liječenje djece i adolescenata mlađih od 18 godina. Primjena paroksetina u djece mlađe od 7 godina nije ispitivana. Stariji bolesnici U starijih bolesnika dolazi do povećanja koncentracije paroksetina u plazmi, ali raspon koncentracija poklapa se s onim u mlađih bolesnika. Liječenje treba početi s početnom dozom SEROXATA za odrasle koja se može povećavati do maksimalne doze od 40 mg paroksetina na dan. Bolesnici s poremećenom funkcijom bubrega / jetre U plazmi bolesnika s teško poremećenom funkcijom bubrega (klirens kreatinina manji od 30 ml/min) ili jetre javljaju se povećane koncentracije paroksetina. Stoga dozu SEROXATA treba svesti na donju granicu preporučenog raspona doziranja. Predoziranje Prema dostupnim podacima o predoziranju paroksetinom, očit je njegov povoljan profil neškodljivosti. Simptomi predoziranja paroksetinom uključuju, osim simptoma opisanih u poglavlju NUSPOJAVE, povraćanje, proširene zjenice, povišenu temperaturu, promjene krvnog tlaka, glavobolju, nevoljne mišićne kontrakcije, nemir, anksioznost i tahikardiju. Oporavak obično prolazi bez ozbiljnih posljedica čak i u slučaju uzimanja do 2000 mg paroksetina (bez kombinacije s drugim lijekovima). Stanje kome ili promjene u EKG-u su rijetko zabilježeni. Vrlo rijetko je zabilježen smrtni ishod, obično ako je paroksetin uziman istodobno s drugim psihotropnim lijekovima, sa ili bez alkohola. Nije poznat nikakav specifični antidot. Liječenje bi trebalo obuhvaćati općenite mjere koje se primjenjuju u liječenju predoziranja bilo kojim antidepresivom. Ako je moguće, treba isprazniti želudac izazivanjem povraćanja, ispiranjem, ili na oba načina. Nakon pražnjenja, može se dati 20 do 30 grama aktivnog ugljena svakih 4 do 6 sati tijekom prva 24 sata nakon uzimanja lijeka. Preporuča se dodatna njega s čestim kontrolama vitalnih funkcija i pažljivim promatranjem. Mjere opreza Liječenje SEROXATOM može se oprezno započeti 2 tjedna nakon završetka liječenja ireverzibilnim MAO inhibitorima odnosno najmanje jedan dan nakon završetka liječenja reverzibilnim MAO inhibitorom. Dozu SEROXATA treba postupno povećavati do postizanja optimalnog odgovora. Mogućnost pokušaja samoubojstva predstavlja nerazdvojni dio velikog depresivnog poremećaja i može biti prisutna sve do postignuća značajnije remisije. Budući da do poboljšanja ne mora doći tijekom prvih nekoliko tjedana liječenja ili više, bolesnike treba strogo nadzirati tijekom liječenja i pratiti do nastupa poboljšanja. Ostala psihijatrijska stanja za koja se paroksetin propisuje, također mogu biti povezana s povećanim rizikom suicidalnog ponašanja. Mjere opreza koje se poduzimaju prilikom liječenja bolesnika s velikim depresivnim poremećajem treba poduzimati i kod liječenja bolesnika s ostalim duševnim poremećajima. U bolesnika u kojih su i prije početka liječenja zabilježena suicidalna ponašanja ili misli, odnosno u bolesnika s izraženim suicidalnim idejama te u mlađih bolesnika (u dobi 18 – 29 godina) postoji povećani rizik pojave suicidalnih misli i pokušaja samoubojstva te ih je potrebno strogo nadzirati tijekom liječenja. Bolesnike (i osobe koje o njima brinu) treba uputiti u potrebu praćenja pojavljivanja suicidalnih misli/ponašanja ili razmišljanja o samoozljeđivanju kako bi na vrijeme zatražili stručnu pomoć. Rijetko su tijekom liječenja paroksetinom, i obično ukoliko se primjenjivao istodobno s drugim serotoninergičkim i/ili neuroleptičkim lijekovima, zabilježeni slučajevi serotoninskog sindroma ili sindroma nalik neuroleptičkom malignom sindromu. U tim slučajevima, liječenje SEROXATOM treba odmah prekinuti te započeti sa simptomatskim liječenjem. U bolesnika sa srčanim smetnjama treba se držati uobičajenih mjera opreza. U bolesnika sa šećernom bolesti terapija inhibitorima ponovne pohrane serotonina može utjecati na kontrolu glikemije, stoga može biti potrebna prilagodba doze inzulina i/ili oralnih hipoglikemika. Kao i sve antidepresive, SEROXAT treba primjenjivati s oprezom u bolesnika s epilepsijom. U slučaju pojave epileptičkih napadaja liječenje SEROXATOM treba odmah prekinuti. SEROXAT nije namijenjen za liječenje depresivne epizode u sklopu bipolarnog afektivnog poremećaja. Kao i sve antidepresive, SEROXAT treba primjenjivati s oprezom u bolesnika u kojih je ranije dijagnosticirana manija. Prilikom primjene paroksetina zabilježeni su slučajevi krvarenja u koži (ekhimoze i purpura) i sluznicama (uključujući gastrointestinalno krvarenje). Stoga je nužan oprez pri primjeni SEROXATA kod bolesnika koji istodobno uzimaju lijekove koji povećavaju rizik krvarenja (npr. atipični antipsihotici i fenotijazini, većina tricikličkih antidepresiva, aspirin i nesteroidni protuupalni lijekovi), kao i kod bolesnika s poznatom sklonošću krvarenju ili s predisponirajućim stanjima te kod starijih bolesnika. Kao i ostale selektivne inhibitore ponovne pohrane serotonina, SEROXAT treba s oprezom primjenjivati u bolesnika s glaukomom uskog kuta. Hiponatremija je zabilježena rijetko, uglavnom u starijih osoba. Hiponatremija se obično povlači po prestanku uzimanja SEROXATA. Kontraindikacije SEROXAT se ne smije primjenjivati u bolesnika koji su preosjetljivi na paroksetin ili neki od pomoćnih sastojaka lijeka. SEROXAT se ne smije primjenjivati istodobno s inhibitorima monoaminooksidaze (MAO inhibitorima). Liječenje paroksetinom ne smije započeti unutar 2 tjedna od završetka liječenja ireverzibilnim MAO inhibitorima odnosno najmanje jedan dan nakon završetka liječenja reverzibilnim MAO inhibitorom, moklobemidom. Isto tako, liječenje MAO inhibitorima ne smije započeti unutar 2 tjedna od završetka liječenja paroksetinom (vidi INTERAKCIJE). SEROXAT se ne smije primjenjivati u kombinaciji s tioridazinom (vidi INTERAKCIJE). SEROXAT se ne smije primjenjivati istodobno s pimozidom. Trudnoća SEROXAT se ne smije primjenjivati u trudnica, osim ako prema procjeni liječnika, moguća korist za trudnicu prevladava moguće rizike za plod. Žene koje planiraju trudnoću ili koje zatrudne tijekom liječenja SEROXATOM trebaju se savjetovati sa svojim liječnikom. Nagli prekid primjene SEROXATA tijekom trudnoće treba izbjegavati. Dojenje Poznato je da se male količine paroksetina izlučuju u majčino mlijeko. Učinci paroksetina na dojenče nisu utvrđeni. Stoga se SEROXAT ne smije primjenjivati u dojilja, osim ako očekivana korist za majku prevladava mogući rizik za dojenče. Upravljanje vozilima i strojevima Kliničko iskustvo pokazalo je da liječenje paroksetinom nije povezano s poremećajem kognitivnih ni psihomotoričkih funkcija. Međutim, kao i kod svih psihoaktivnih lijekova, bolesnicima treba savjetovati oprez pri upravljanju vozilom ili strojevima. Djeca i adolescenti (do 18 godina) Liječenje antidepresivima je povezano s povećanim rizikom pojave suicidalnih misli i suicidalnog ponašanja u djece i adolescenata s velikom depresivnom epizodom kao i drugim duševnim poremećajima. Kontrolirana klinička ispitivanja nisu dokazala djelotvornost i dugotrajnu neškodljivost paroksetina te ne podupiru primjenu paroksetina u liječenju teške depresivne epizode kod djece i adolescenata do 18 godina. Djeca (mlađa od 7 godina) Učinkovitost i neškodljivost primjene paroksetina u djece mlađe od 7 godina nije ispitivana. Nuspojave Pri kontinuiranoj primjeni učestalost i intenzitet nekih od dolje navedenih nuspojava može se smanjiti te u većini slučajeva terapiju nije potrebno prekidati. Vrlo učestalo (>1/10) zabilježene nuspojave povezane s primjenom paroksetina bile su: - mučnina - seksualna disfunkcija Učestalo (1/100 – 1/10) su zabilježene: - pospanost, zijevanje - znojenje - tremor - astenija - povećanje tjelesne mase - suha usta - nesanica - omaglica, zamućenje vida - opstipacija - proljev - smanjeni apetit/anoreksija. Neučestalo (1/1000 – 1/100) su se javljala abnormalna krvarenja (uglavnom na koži i sluznicama): - zbunjenost - halucinacije - ekstrapiramidni poremećaji - sinusna tahikardija - osip, svrbež - retencija mokraće Rijetko (1/10000 – 1/100) su zabilježene sljedeće nuspojave: - hiponatrijemija - manične reakcije - uznemirenost - depersonalizacija - napadaji panike - akatizija - konvulzije - bradikardija - trombocitopenija - hiperprolaktinemija/galaktoreja Vrlo rijetko (manje od 1/10000) su zabilježene sljedeće nuspojave: - alergijske reakcije - sindrom neadekvatnog lučenja antidiuretskog hormona - serotoninski sindrom - akutni glaukom - gastroinestinalno krvarenje - periferni edemi - prijapizam - fotosenzitivne reakcije - poremećaji funkcije jetre - artralgija - mijalgija Zabilježene su i povišene vrijednosti jetrenih enzima. Treba razmotriti prekid terapije paroksetinom u slučaju dugotrajnije povišenih vrijednosti jetrenih enzima. Simptomi povezani s prestankom primjene paroksetina u odraslih Nagli prekid primjene često može izazvati pojavu sljedećih simptoma: - vrtoglavicu, poremećaje osjeta, poremećaje spavanja, tjeskobu, glavobolju. Neučestalo se mogu javiti: - uznemirenost, mučnina, znojenje, tremor, zbunjenost, proljev. U većine bolesnika opisane nuspojave su uglavnom bile blage do umjereno teške naravi te su prestale same od sebe. Međutim u nekih bolesnika mogu biti ozbiljne i/ili produljenog trajanja. Stoga se, u slučaju da primjena paroksetina više nije potrebna, preporuča prekid terapije uz postupno smanjivanje doze. Nuspojave zabilježene u kliničkim ispitivanjima u djece i adolescenata U kratkotrajnim kliničkim ispitivanjima u djece i adolescenata zabilježene su sljedeće nuspojave koje su se javljale u najmanje 2% bolesnika s najmanje dvostruko većom učestalošću u odnosu na placebo: - emocionalna labilnost (uključujući suicidalne misli, pokušaje samoubojstva, plačljivost i promjene raspoloženja), neprijateljsko ponašanje, smanjeni apetit, tremor, znojenje, hiperkinezija i uznemirenost. Suicidalne misli i pokušaji samoubojstva bili su uglavnom zabilježeni u kliničkim ispitivanjima u adolescenata s velikim depresivnim poremećajem. Pojačano neprijateljsko ponašanje obično se pojavljivalo u djece, najčešće mlađe od 12 godina, s opsesivnim kompulzivnim poremećajem. Simptomi povezani sa prestankom primjene paroksetina u djece i adolescenata. Po prestanku primjene paroksetina u djece i adolescenata češće su zabilježeni sljedeći simptomi: - emocionalna labilnost (uključujući suicidalne misli, pokušaje samoubojstva, promjene raspoloženja i plačljivost), nervoza, omaglice, mučnina i bol u trbuhu. U slučaju nuspojave treba se obratiti liječniku ili ljekarniku! Interakcije Ne preporuča se istodobno uzimanje SEROXATA i alkohola. Istodobna primjena paroksetina i serotoninergičkih lijekova (npr. MAO inhibitora, L-triptofana, triptana, tramadola, linezolida, inhibitora ponovne pohrane serotonina, litija i pripravaka gospine trave – Hypericum perforatum) može dovesti do povećanja pojave učinaka povezanih sa serotoninom. Na metabolizam i farmakokinetiku paroksetina mogu utjecati lijekovi koji induciraju ili inhibiraju jetrene enzime. Ako se paroksetin treba primjenjivati zajedno s nekim poznatim inhibitorom jetrenih enzima, treba razmotriti doziranje na donjoj granici raspona. Nije potrebno početno prilagođavanje doze ako će se lijek primjenjivati zajedno s nekim poznatim induktorom jetrenih enzima (kao npr. karbamazepinom, rifampicinom, fenobarbitonom i fenitoinom). Istodobna primjena paroksetina i antikonvulziva (karbamazepin, natrij-valproat i fenitoin) u bolesnika s epilepsijom ne utječe na njihov farmakokinetički/farmakodinamički profil. Svakodnevna primjena paroksetina značajno povisuje plazmatske razine prociklidina. Kao i ostali antidepresivi, uključujući i druge inhibitore ponovne pohrane serotonina, paroksetin inhibira jetreni enzim CYP2D6 što može dovesti do povećanih koncentracija u plazmi istodobno primijenjenih lijekova. To su neki triciklički antidepresivi (npr. imipramin, nortriptilin i dezipramin), fenotijazinski neuroleptici (npr. perfenazin i tioridazin), risperidon, atomoksetin, određeni antiaritmici iz skupine 1c (npr. propafenon i flekainid) i metoprolol (posebno u bolesnika sa zatajivanjem srca). Istodobna primjena paroksetina i oralnih antikoagulansa može dovesti do povećanja antikoagulantne aktivnosti i povećanja rizika krvarenja. Stoga, paroksetin treba primjenjivati s oprezom u bolesnika na terapiji oralnim antikoagulansima. Potreban je oprez prilikom istodobne primjene inhibitora ponovne pohrane serotonina i oralnih antikoagulansa te ostalih lijekova koji utječu na funkciju trombocita ili povećavaju rizik krvarenja (npr. atipični antipsihotici kao što je klozapin, fenotijazini, većina tricikličkih antidepresiva, acetilsalicilna kiselina, nesteroidni antireumatici, COX-2 inhibitori) kao i u bolesnika s prethodnim poremećajima zgrušavanja ili sklonosti krvarenju. Napomene IME I ADRESA NOSITELJA ODOBRENJA BELUPO lijekovi i kozmetika d.d., Ulica Danica 5, 48000 Koprivnica,Hrvatska IME I ADRESA PROIZVOĐAČA BELUPO lijekovi i kozmetika d.d.,Ulica Danica 5, 48000 Koprivnica, Hrvatska u suradnji s GlaxoSmithKline, Brentford, Velika Britanija. Amantilla Relax Značajno ublažava stres i tjeskobu. Tensilen Prirodno rješenje za stres, umor i iscrpljenost.