Venlafaxine STELLA

Venlafaxine STELLA

venlafaxine

Nhà sản xuất:

Stellapharm

Nhà phân phối:

Khuong Duy
Thông tin kê toa chi tiết tiếng Anh
Contents
Venlafaxine HCl.
Description
Capsule: Active ingredient: Venlafaxine (as venlafaxine hydrochloride) 37.5 mg.
MR-FC tablet: Active ingredient: Venlafaxine (as venlafaxine hydrochloride) 75 mg.
Excipients/Inactive Ingredients: Capsule: Lactose monohydrate, microcrystalline cellulose (comprecel M102), sodium glycolate starch, povidone K30, magnesium stearate.
MR-FC tablet: Microcrystalline cellulose, hypromellose, ethylcellulose, colloidal anhydrous silica, magnesium stearate, macrogol 400.
Action
Pharmacotherapeutic Group: Other antidepressants. ATC Code: N06AX16.
Pharmacology: Pharmacodynamics: The mechanism of the antidepressant action of venlafaxine in humans is believed to be associated with its potentiation of neurotransmitter activity in the CNS. Preclinical studies have shown that venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and ODV have no significant affinity for muscarinic, histaminergic or (alpha)-1 adrenergic receptors in vitro. Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative and cardiovascular effects seen with other psychotropic drugs. Venlafaxine and ODV do not possess monoamine oxidase (MAO) inhibitory activity.
Pharmacokinetics: Capsule: Venlafaxine is extensively metabolised, primarily to the active metabolite, O-desmethylvenlafaxine (ODV). Mean ± SD plasma half-lives of venlafaxine and ODV are 5 ± 2 hours and 11 ± 2 hours, respectively. Steady-state concentrations of venlafaxine and ODV are attained within 3 days of oral multiple dose therapy.
Absorption: At 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 capsules, 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 capsule, the prolonged release capsule provides a slower rate of absorption, but the same extent of absorption are compared with the immediate release tablet. Food does not affect the bioavailability of venlafaxine and ODV.
Distribution: Venlafaxine and ODV are minimally bound at therapeutic concentrations to human plasma proteins (27% and 30%, respectively).
Metabolism: Venlafaxine undergoes extensive hepatic metabolism. In vitro and in vivo studies indicate that venlafaxine is biotransformed to its major active metabolite, ODV, by CYP2D6; venlafaxine is metabolised to a minor, less active metabolite, N-desmethylvenlafaxine, by CYP3A4 and venlafaxine is a weak inhibitor of CYP2D6. Venlafaxine did not inhibit CYP1A2, CYP2C9, or CYP3A4.
Elimination: Venlafaxine 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.
MR-FC Tablet: Venlafaxine is readily absorbed from the gastrointestinal tract. After oral doses, it undergoes extensive first pass metabolism in the liver mainly to the active metabolite ODV; formation of ODV is mediated by the cytochrome P450 isoenzyme CYP2D6. The isoenzyme CYP3A4 is also involved in the metabolism of venlafaxine. Other metabolites include N-desmethylvenlafaxine and N,O-didesmethylvenlafaxine. 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. Venlafaxine is 27% and ODV 30% bound to plasma proteins. The mean elimination half-life of venlafaxine and ODV is about 5 and 11 hours, respectively. Venlafaxine is excreted mainly in the urine, mainly in the form of metabolites, either free or in conjugated form; about 2% is excreted in the faeces.
Indications/Uses
Treatment of major depressive episodes (generalised anxiety disorder, social anxiety disorder and panic disorder, with or without agoraphobia).
For prevention of recurrence of major depressive episodes.
Dosage/Direction for Use
Major depressive episodes: The recommended starting dose 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.
Generalised anxiety disorder: The recommended starting dose 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 225 mg/day. Dosage increases can be made at intervals of 2 weeks or more.
Social anxiety disorder: The recommended dose 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.
Panic disorder: It is recommended that a dose of 37.5 mg/day be used for 7 days. Dosage should then be increased to 75 mg/day. Patients not responding to the 75 mg/day dose may benefit from dose increases up to a maximum dose of 225 mg/day. Dosage increases can be made at intervals of 2 weeks or more.
Prevention of recurrence of major depressive episodes: Capsule: 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.
Use in elderly patients: Caution should be exercised in treating the elderly. The lowest effective dose should always be used, and patients should be carefully monitored when an increase in the dose is required.
Use in patients with hepatic/renal impairment: Capsule: Because of inter-individual variability in clearance in these patients, individualisation of dosage may be desirable.
Because of the risk of dose-related adverse effects, dose increments should be made only after a clinical evaluation. The lowest effective dose should be maintained.
Use in patients with hepatic impairment: MR-FC Tablet: In patients with mild and moderate hepatic impairment, in general a 50% dose reduction should be considered.
The potential benefit should be weighed against the risk in the treatment of patients with severe hepatic impairment.
Overdosage
Symptoms: Overdosage with venlafaxine has occurred predominantly in combination with alcohol and/or other drugs. Electrocardiogram changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation), sinus and ventricular tachycardia, bradycardia, hypotension, altered level of consciousness (ranging from somnolence to coma), rhabdomyolysis, seizures, vertigo, liver necrosis and death have been reported.
Treatment: Ensure an adequate airway, oxygenation and ventilation. Monitor cardiac rhythm and vital signs. Gastric lavage with a large bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients. Activated charcoal should be administered. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. No specific antidotes for venlafaxine are known.
Contraindications
Known hypersensitivity to venlafaxine hydrochloride or to any excipient/ingredient in the formulation.
Capsule: The high-risk cases of cardiac arrhythmias, uncontrolled hypertension.
Children and adolescents under the age of 18 years.
Pregnancy.
Venlafaxine must be discontinued for at least 7 days before starting treatment with an irreversible MAOI.
Venlafaxine must not be initiated for at least 14 days after discontinuation of treatment with an irreversible MAOI.
MR-FC Tablet: Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated.
Special Precautions
Patients with a recent history of myocardial infarction or whose condition might be exacerbated by an increase in heart rate. Due to the risk of dose-related increases in blood pressure, blood pressure measurement should be performed regularly during therapy.
Measurement of serum-cholesterol levels should also be considered with long-term treatment.
Venlafaxine should be used with caution in patients with moderate to severe hepatic or renal impairment and dosage adjustment may be necessary.
It should also be used with caution in patients with a history of epilepsy and avoided in those with unstable disease; it should be stopped in any patient developing a seizure or if there is an increase in seizure frequency.
Caution is also advised in patients with a history of bleeding disorders or of hypomania or mania.
Patients with raised intra-ocular pressure or at risk of angle-closure glaucoma should be monitored closely.
Patients who develop a rash, urticaria, or related allergic reaction with venlafaxine should be advised to contact their doctor.
Patients, especially the elderly, should be warned of the risk of dizziness or unsteadiness due to orthostatic hypotension.
Symptoms reported on abrupt withdrawal or dose reduction of venlafaxine include fatigue, somnolence, headache, nausea, vomiting, anorexia, palpitations, dizziness, dry mouth, diarrhoea, insomnia, agitation, anxiety, nervousness, confusion, hypomania, paraesthesia, sweating, and vertigo.
Capsule: Venlafaxine STADA 37.5 mg contains lactose and therefore this medicine should not be taken by patients with rare hereditary problems of galactose intolerance, total lactase deficiency or Glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: As with other antidepressants, venlafaxine may impair performance of skilled tasks and, if affected, patients should not drive or operate machinery.
Use In Pregnancy & Lactation
Pregnancy: In rats, there was a decrease in pup weight, an increase in stillborn pups, and an increase in pup deaths during the first 5 days of lactation, when dosing began during pregnancy and continued until weaning. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Lactation: Venlafaxine and ODV have been reported to be excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Adverse Reactions
Most frequently (ADR ≥1/10): Nausea, headache, insomnia, somnolence, dry mouth, dizziness, constipation, sexual dysfunction, asthenia, sweating, and nervousness.
Other common adverse effects (1/100 ≤ ADR <1/10): Anorexia, diarrhoea, dyspepsia, abdominal pain, anxiety, urinary frequency, visual disturbances, vasodilatation, vomiting, tremor, paraesthesia, chills or fever, palpitations, weight gain or loss, increase serum cholesterol, agitation, abnormal dreams, confusion, arthralgia, myalgia, tinnitus, pruritus, dyspnoea and skin rashes. Dose-related increases in blood pressure have also been observed in some patients.
Less common reported side-effects (1/1000 ≤ ADR <1/100): Reversible increases in liver enzymes, orthostatic hypotension, syncope, arrhythmias, tachycardia, mucous membrane bleeding, ecchymosis, hallucinations, bruxism, muscle spasm, myoclonus, alopecia, altered taste, urinary retention, menorrhagia, angioedema, and photosensitivity reactions.
Convulsions, galactorrhoea, haemorrhage including gastrointestinal bleeding, anaphylaxis, hepatitis, erythema multiforme, Stevens-Johnson syndrome, ataxia, dysarthria, extrapyramidal disorders including psychomotor restlessness and akathisia, and activation of mania or hypomania have been reported rarely (1/10,000 ≤ ADR <1/1000). Other rare adverse effects include blood dyscrasias such as agranulocytosis, aplastic anaemia, neutropenia, pancytopenia, and thrombocytopenia, prolongation of the QT interval and torsade de pointes, ventricular tachycardia or fibrillation, rhabdomyolysis, delirium, pancreatitis, and pulmonary eosinophilia.
Aggressive behaviour has developed with venlafaxine treatment particularly at the start and when stopping therapy. Suicidal ideation has been reported, particularly in children. Hyponatraemia possibly due to inappropriate secretion of antidiuretic hormone has been associated with the use of antidepressants, particularly in the elderly.
Drug Interactions
CYP3A4 inhibitor: Concomitant use of CYP3A4 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, voriconazole, posaconazole, ketoconazole, nelfinavir, ritonavir, saquinavir and 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.
Lithium: Serotonin syndrome may occur with the concomitant use of venlafaxine and lithium.
Monoamine Oxidase Inhibitors (MAOIs): Adverse reactions, some of which were serious, have been reported in patients who have recently been discontinued from a monoamine oxidase inhibitor (MAOI) and started on venlafaxine, or inverse. These reactions have included tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures and death. Therefore, it is recommended that venlafaxine not be used in combination with an MAOI or within at least 14 days of discontinuing treatment with an MAOI. Based on the half-life of venlafaxine, at least 7 days should be allowed after stopping venlafaxine before starting a MAOI.
CNS-active drugs: Caution is advised if the concomitant administration of venlafaxine and other CNS-active drugs is required.
Caution For Usage
Incompatibilities: In the absence of incompatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage
Store in a well-closed container, in dry place. Do not store above 30°C.
Shelf-Life: 24 months from the date of manufacturing.
MIMS Class
Antidepressants
ATC Classification
N06AX16 - venlafaxine ; Belongs to the class of other antidepressants.
Presentation/Packing
Cap 37.5 mg (hard-gelatin, capsule size No. 2, dark pink cap and body, imprinted logo "

Click on icon to see table/diagram/image

" with edible white ink on the cap, containing white or off-white powder) x 3 x 10's, 6 x 10's. MR-FC tab 75 mg (white, oblong-shaped, biconvex, plain on both sides) x 2 x 14's.
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