Desfoxine

Desvenlafaxine succinate monohydrate.

Each tablet contains Desvenlafaxine succinate monohydrate equivalent to Desvenlafaxine 50 mg.

Pharmacology: Pharmacodynamics: Desvenlafaxine succinate is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) that potentiates these neurotransmitters in the CNS. Desvenlafaxine is the major active metabolite of venlafaxine, which is also used to treat major depressive disorders.
Pharmacokinetics: Absorption: The absolute oral bioavailability of Desvenlafaxine is approximately 80%. Food has no clinically significant effect. The mean time to peak plasma concentrations of Desvenlafaxine after oral administration of extended-release tablets was approximately 7.5 hours.
Distribution: The protein binding of Desvenlafaxine is low (30%) and is not dependent on drug concentration. Volume of distribution is 3.4 L/kg.
Metabolism: Desvenlafaxine is principally metabolized via conjugation by uridine disphosphoglucuronosyl-transferase (UGT) isoenzymes and, to a lesser extent through oxidation (by the cytochrome P-450 [CYP] 3A4 isoenzyme). The drug minimally inhibits CYP2D6 isoenzyme and does not inhibit the CYP1A2, 2A6, 2C8, 2C9, or 2C19 isoenzymes. Desvenlafaxine is not an inhibitor of CYP3A4. Nor is it an inducer of CYP3A4.
Excretion: The mean terminal half-life of Desvenlafaxine is approximately 11 hours. Approximately 45% of a single oral dose of Desvenlafaxine is eliminated unchanged in the urine at 72 hours, approximately 19% of the dose is excreted as the glucuronide metabolite, and less than 5% is excreted as the oxidative metabolite (N,O-didesmethylvenlafaxine).

For the acute and maintenance treatment of major depressive disorder (MDD).
For the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause e.g., hot flushes.

Recommended Dose: Adults: Major depressive disorder: The recommended usual and maintenance dose is 50 mg once daily, with or without food. If dose increases are indicated for individual patients, they should occur gradually and at intervals of not less than 7 days. It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy. Patients should be periodically reassessed to determine the need for continued treatment.
Vasomotor symptoms associated with menopause: The recommended dose is 100 mg once daily, with or without food. It is recommended to start at 50 mg/day for up to 7 days, to allow patients to adjust to the medicine before increasing to 100 mg/day.
Pediatric: Safety and effectiveness of Desvenlafaxine in pediatric patients younger than 18 years old have not been established.
Dosage in hepatic impairment: The recommended Desvenlafaxine dosage is 50 mg given once daily. Dosages exceeding 100 mg daily are not recommended.
Dosage in renal impairment: In patient with mild renal impairment, Desvenlafaxine dosage adjustment is not necessary.
In patient with moderate renal impairment (creatinine clearance of 30-50 mL/minute), the recommended dosage is 50 mg given once daily.
In patient with severe renal impairment (creatinine clearance less than 30 mL/minute) or end-stage renal disease, the dosage is 50 mg given every other day.
Dosage in elderly: No dosage adjustment is required solely on the basis of age; however, possible reduced renal clearance of Desvenlafaxine should be considered when determining dose.
Mode of administration: Desvenlafaxine succinate is administered orally once daily with or without food at approximately the same time each day. Extended-release tablet of the drug should be swallowed whole with fluid and not be divided, crushed, chewed, or dissolved.

No specific antidotes for Desvenlafaxine are known. Induction of emesis is not recommended. Because of the moderate volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. 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.

This drug is contraindicated in patients with hypersensitivity to Desvenlafaxine succinate, venlafaxine hydrochloride, or any ingredients in the formulation; in patient with concurrent or recent (i.e., within 2 weeks) therapy with a monoamine oxidase (MAO) inhibitor. In addition, at least 2 weeks should elapse between discontinuance of a MAO-inhibitor and initiation of Desvenlafaxine and at least 7 days should elapse between discontinuance of Desvenlafaxine and initiation of MAO inhibitor therapy.

1. Worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior may occur in both adult and pediatric. All patients being treated with antidepressants be appropriately monitored and closely observed for clinical worsening, suicidality, and unusual changes in behavior, particularly during initiation of therapy and during periods of dosage adjustments.
2. Suicide risks should be monitored in patients with SNRIs, regardless of the indication.
3. Desvenlafaxine succinate is not approved for use in pediatric patients.

Use with caution in patients with a personal or family history of mania or hypomania.
Potentially life-threatening serotonin syndrome has occurred with SNRIs, particularly when used combination with other serotonergic agents (e.g. triptans, tricyclic antidepressants [TCAs], fentanyl, lithium, tramadol, buspirone, St. John's wort, tryptophan) or agents that impair metabolism of serotonin (e.g. MAOIs intended to treat psychiatric disorders, linezolid, methylene blue IV). Closely monitor patients for signs of serotonin syndrome, such as mental status changes (e.g. agitation, hallucination, delirium, coma), autonomic instability (e.g. tachycardia, labile blood pressure, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g. tremor, rigidity, myoclonus, hyperreflexia), GI symptoms (e.g. nausea, vomiting, diarrhea), and/or seizures. Immediately discontinue treatment and any concomitant serotonergic agents if sign/symptom arise.
Desvenlafaxine may increase blood pressure and heart rate. Preexisting hypertension should be controlled before initiating Desvenlafaxine therapy and that regulate blood pressure monitoring be performed in patients receiving the drug. Desvenlafaxine should be used cautiously in patients with preexisting hypertension or other underlying conditions that may be compromised by increases in blood pressure. Dosage reduction or drug discontinuance should be considered in patients who experience a sustained increase in blood pressure during therapy.
Desvenlafaxine may increase the risk of bleeding events. Concurrent administration of aspirin, non-steroidal anti-inflammatory agents (NSAIDs), warfarin, and other anticoagulants may add to this risk. Patients be advised of the risk of bleeding associated with the concomitant use of Desvenlafaxine and aspirin or non-steroidal anti-inflammatory agents (NSAIDs), warfarin, or other drugs that affect coagulation or bleeding.
Desvenlafaxine may cause mild pupillary dilation and can lead to an episode of narrow-angle glaucoma. Therefore, patients with elevated intraocular pressure or those at risk of angle-closure glaucoma should be monitored during treatment of Desvenlafaxine.
Desvenlafaxine should be used with caution in patients with recent history of myocardial infarction, unstable heart disease, uncontrolled hypertension, tachyarrhythmias (e.g. atrial fibrillation) or other cardiovascular/cerebrovascular conditions.
Desvenlafaxine should be used with caution in patients with a seizure disorder.
Treatment with SSRIs and SNRIs, including Desvenlafaxine, may result in hyponatremia.
Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine have been reported rarely. The possibility of such adverse effects should be considered in patients treated with Desvenlafaxine who present with progressive dyspnea, cough, or chest discomfort.
Dose-dependent, possibly clinically significant increases in fasting serum total cholesterol, low-density lipoprotein (LDL), and triglycerides. Consider measuring serum lipid concentration during Desvenlafaxine therapy.
Abrupt discontinuance or dosage reduction of Desvenlafaxine has been associated with the appearance of withdrawal effects, including dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, fatigue, abnormal dreams, hyperhidrosis, tinnitus and seizures. Therefore, patients should be monitored for possible withdrawal symptoms when discontinuing Desvenlafaxine therapy. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.
Use in the Elderly: Elderly with concurrent use of diuretics likely increase risk of the development of syndrome of inappropriate secretion of antidiuretic hormone (SIADHs). Discontinue treatment in patients with symptomatic hyponatremia.

Pregnancy: The safety of Desvenlafaxine in human pregnancy has not been established. Desvenlafaxine must only be administered to pregnant woman if the expected benefits outweigh the possible risks. If Desvenlafaxine is used until, or shortly before birth, discontinuation effects in the newborn should be considered.
Some neonate exposed to Serotonin Norepinephrine reuptake inhibitors (SNRIs) or Selective serotonin reuptake inhibitors (SSRIs) late in the third trimester of pregnancy have developed complications that have sometimes been severe and required prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care in special-care nurseries. Such complications may arise immediately upon delivery.
Lactation: Desvenlafaxine is excreted into human milk. Because of the potential for serious adverse effects in nursing infants from Desvenlafaxine, discontinue nursing or the drug, considering the importance of the drug to the woman. Desvenlafaxine should only be administered to nursing woman if the expected benefits outweigh any possible risk.

Immune system disorders: hypersensitivity.
Metabolism and nutrition disorders: decreased appetite, hyponatremia.
Psychiatric disorders: insomnia, withdrawal syndrome, anxiety, nervousness, abnormal dreams, irritability, libido decreased, anorgasmia, depersonalization, orgasm abnormal, mania, hypomania, hallucination.
Nervous system disorders: headache, dizziness, somnolence, tremor, paraesthesia, disturbance in attention, dysgeusia, syncope, extrapyramidal disorder, serotonin syndrome, convulsion.
Eye disorders: vision blurred, mydriasis.
Ear and labyrinth disorders: vertigo, tinnitus.
Cardiac disorders: tachycardia, palpitation.
Vascular disorders: blood pressure increased, hot flush, orthostatic hypotension, peripheral coldness.
Respiratory, thoracic, and mediastinal disorders: yawning, epistaxis.
Gastrointestinal disorders: nausea, dry mouth, constipation, diarrhea, vomiting.
Skin and subcutaneous tissue disorders: hyperhidrosis, rash, alopecia, Stevens-Johnson syndrome, angioedema, photosensitivity reaction.
Musculoskeletal disorders: musculoskeletal stiffness.
Renal and urinary disorders: urinary retention, urinary hesitation, proteinuria.
Reproductive system disorders: erectile dysfunction, ejaculation delayed, ejaculation disorder, ejaculation failure, sexual dysfunction.
General disorders: fatigue, asthenia, chills, feeling jittery.
Others: liver function test abnormal, weight increased, weight decreased, blood cholesterol increased, blood triglycerides increased, blood prolactin increased.
Ischemic cardiac adverse events: There have been uncommon reports of ischemic cardiac events, including myocardial ischemia, myocardial infarction, and coronary occlusion requiring revascularization in patients receiving Desvenlafaxine who had underlying cardiac risk factors.
Discontinuation symptoms: Major depressive disorder: Adverse drug reactions reported in association with abrupt discontinuation, dose reduction or tapering of treatment in major depressive disorder include dizziness, withdrawal syndrome, nausea and headache. These symptoms generally occurred more frequently with higher doses and with longer duration of therapy.
Vasomotor symptoms associated with menopause: Adverse drug reactions reported in association with abrupt discontinuation, dose reduction or tapering of treatment in vasomotor symptoms include dizziness, headache, nausea, hot flush, insomnia, tinnitus, vertigo, diarrhea, vomiting and fatigue.

Desvenlafaxine minimally inhibits the cytochrome P-450 (CYP) 2D6 isoenzyme. Concomitant use of Desvenlafaxine with a drug metabolized by CYP2D6 may result in higher concentrations of that drug and decreased concentrations of its CYP2D6 metabolites.
The concurrent use of Desvenlafaxine with a drug metabolized by CYP3A4 can result in lower exposures to that drug.
Desvenlafaxine does not inhibit CYP isoenzymes 1A2, 2A6, 2C8, 2C9, and 2C19 in vitro and is unlikely to affect the pharmacokinetics of drugs that are metabolized by these CYP isoenzymes.
CYP3A4 is a minor pathway for the metabolism of Desvenlafaxine. The concurrent use of Desvenlafaxine with other potent CYP3A4 inhibitors may result in higher plasma concentrations of Desvenlafaxine.
Desvenlafaxine (100 mg daily) does not have a clinically relevant effect on drug metabolized by a combination of both CYP2D6 and CYP3A4 enzymes.
Based on in vitro data, drugs that inhibit CYP isozymes 1A1, 1A2, 2A6, 2D6, 2C8, 2C9, 2C19 and 2E1 are not expected to have significant impact on the pharmacokinetic profile of Desvenlafaxine.
The risk of using Desvenlafaxine in combination with other CNS-active drugs has not been systematically evaluated. Consequently, caution is advised when Desvenlafaxine is taken in combination with other CNS-active drugs.
Concomitant use of monoamine oxidase (MAO) inhibitors with Desvenlafaxine is contraindicated.
As with other serotonergic agents, serotonin syndrome, a potentially life-threatening condition, may occur with Desvenlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system (including triptans, SSRIs, other SNRIs, lithium, sibutramine, fentanyl and its analogues, tramadol, dextromethorphan, tapentadol, meperidine, methadone, pentazocine or St. John's wort), with drugs that impair metabolism of serotonin (such as MAOIs, including linezolid [an antibiotic which is a reversible non-selective MAOI] and methylene blue), or with serotonin precursors (such as tryptophan supplements). If concomitant treatment with Desvenlafaxine and an SSRI, an SNRI or a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, carefully observation of the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of Desvenlafaxine with serotonin precursor (such as tryptophan supplements) is not recommended.
If serotonin syndrome signs and symptoms occur, immediately discontinue treatment with Desvenlafaxine and any concurrently administered serotonergic or antidopaminergic agents and initiate supportive and symptomatic treatment.
In vitro, Desvenlafaxine is not a substrate or an inhibitor for the P-glycoprotein transporter.
Desvenlafaxine does not increase the impairment of mental and motor skills caused by ethanol.
However, as with all CNS-active drugs, patients should be advised to avoid alcohol consumption while taking Desvenlafaxine.
False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking Desvenlafaxine.
There are no clinical data establishing the risks and/or benefits of electroconvulsive therapy combined with Desvenlafaxine treatment for MDD.

Store below 30°C.

Antidepressants

N06AX23 - desvenlafaxine ; Belongs to the class of other antidepressants.

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