Desvenlafaxine: uses, appearance and warnings

Desvenlafaxine extended-release tablets are indicated for the treatment of adults with major depressive disorder (MDD) [see Clinical Studies (14) ]. Desvenlafaxine Extended-Release Tablets are a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of adults with major depressive disorder (MDD) ( 1 ).

25 mg Tablet: Brown colored, round shaped convex, film coated tablet debossed with "˄" on one side and plain on the other side. A41 50 mg Tablet: Pink colored, round shaped convex, film coated tablet debossed with "˄" on one side and plain on the other side. A42 100 mg Tablet: Beige colored, round shaped convex, film coated tablet debossed with "˄" on one side and plain on the other side. A43 Desvenlafaxine Extended-Release Tablets: 25 mg, 50 mg and 100 mg ( 3 ). Each tablet contains 38 mg, 76 mg or 152 mg of desvenlafaxine succinate equivalent to 25 mg, 50 mg or 100 mg of desvenlafaxine, respectively ( 3 ).

Desvenlafaxine extended-release tablets are available as follows: 25 mg, brown colored, round shaped convex, film coated tablet debossed with "˄" on one side and plain on the other side A41 NDC 72888-175-30, bottle of 30 tablets NDC 72888-175-90, bottle of 90 tablets NDC 72888-175-05, bottle of 500 tablets NDC 72888-175-00, bottle of 1000 tablets 50 mg, pink colored, round shaped convex, film coated tablet debossed with "˄" on one side and plain on the other side A42 NDC 72888-143-30, bottle of 30 tablets NDC 72888-143-90, bottle of 90 tablets NDC 72888-143-05, bottle of 500 tablets NDC 72888-143-00, bottle of 1000 tablets 100 mg, beige colored, round shaped convex, film coated tablet debossed with "˄" on one side and plain on the other side A43 NDC 72888-144-30, bottle of 30 tablets NDC 72888-144-90, bottle of 90 tablets NDC 72888-144-05, bottle of 500 tablets NDC 72888-144-00, bottle of 1000 tablets Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature] . Each tablet contains 38 mg, 76 mg or 152 mg of desvenlafaxine succinate equivalent to 25 mg, 50 mg or 100 mg of desvenlafaxine, respectively.

Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any excipients in the desvenlafaxine extended-release tablets formulation. Angioedema has been reported in patients treated with desvenlafaxine extended-release tablets [see Adverse Reactions (6.1) ] . The use of MAOIs intended to treat psychiatric disorders with desvenlafaxine extended-release tablets or within 7 days of stopping treatment with desvenlafaxine extended-release tablets is contraindicated because of an increased risk of serotonin syndrome. The use of desvenlafaxine extended-release tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.7) and Warnings and Precautions (5.2) ]. Starting desvenlafaxine extended-release tablets in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration (2.8) and Warnings and Precautions (5.2) ]. Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or any excipients in the desvenlafaxine extended-release tablets formulation ( 4 ). Serotonin Syndrome and MAOIs : Do not use MAOIs intended to treat psychiatric disorders with desvenlafaxine extended-release tablets or within 7 days of stopping treatment with desvenlafaxine extended-release tablets. Do not use desvenlafaxine extended-release tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start desvenlafaxine extended-release tablets in a patient who is being treated with linezolid or intravenous methylene blue ( 4 ).

Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If it occurs, discontinue desvenlafaxine extended-release tablets and serotonergic agents and initiate supportive treatment ( 5.2 ). Elevated Blood Pressure: Control hypertension before initiating treatment. Monitor blood pressure regularly during treatment ( 5.3 ). Increased Risk of Bleeding: Concomitant use of aspirin, NSAIDs, other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk ( 5.4 ). Angle Closure Glaucoma: Avoid use of antidepressants, including desvenlafaxine extended-release tablets, in patients with untreated anatomically narrow angles treated ( 5.5 ). Activation of Mania/Hypomania: Use cautiously in patients with Bipolar Disorder. Caution patients about risk of activation of mania/hypomania ( 5.6 ). Discontinuation Syndrome: Taper dose when possible and monitor for discontinuation symptoms ( 5.7 ). Seizure: Can occur. Use cautiously in patients with seizure disorder ( 5.8 ). Hyponatremia: Can occur in association with SIADH ( 5.9 ). Interstitial Lung Disease and Eosinophilic Pneumonia: Can occur ( 5.10 ). Sexual Dysfunction: Desvenlafaxine extended-release tablets may cause symptoms of sexual dysfunction ( 5.11 ). 5.1 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients Patients with MDD, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled studies of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled studies in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short- term studies of 9 antidepressant drugs in over 4,400 patients. The pooled analyses of placebo- controlled studies in adults with MDD or other psychiatric disorders included a total of 295 short-term studies (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1,000 patients treated) are provided in Table 1. Table 1 Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1,000 Patients Treated Increases Compared to Placebo <18 14 additional cases 18 to 24 5 additional cases Decreases Compared to Placebo 25 to 64 1 fewer case ≥65 6 fewer cases No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance studies in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms [see Dosage and Administration (2.4) , Warnings and Precautions (5.7) ] . …

The following adverse reactions are discussed in greater detail in other sections of the label. Hypersensitivity [see Contraindications (4) ] Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients [see Warnings and Precautions (5.1) ] Serotonin Syndrome [see Warnings and Precautions (5.2) ] Elevated Blood Pressure [see Warnings and Precautions (5.3) ] Increased Risk of Bleeding [see Warnings and Precautions (5.4) ] Angle Closure Glaucoma [see Warnings and Precautions (5.5) ] Activation of Mania/Hypomania [see Warnings and Precautions (5.6) ] Discontinuation Syndrome [see Warnings and Precautions (5.7) ] Seizure [see Warnings and Precautions (5.8) ] Hyponatremia [see Warnings and Precautions (5.9) ] Interstitial Lung Disease and Eosinophilic Pneumonia [see Warnings and Precautions (5.10) ] Sexual Dysfunction [see Warnings and Precautions (5.11) ] Most common adverse reactio …

7.1 Drugs Having Clinically Important Interactions with Desvenlafaxine Extended-Release Tablets Table 8: Clinically Important Drug Interactions with Desvenlafaxine Extended-Release Tablets Monoamine Oxidase Inhibitors (MAOI) Clinical Impact The concomitant use of SSRIs and SNRIs including desvenlafaxine extended-release tablets with MAOIs increases the risk of serotonin syndrome. Intervention Concomitant use of desvenlafaxine extended-release tablets is contraindicated: With an MAOI intended to treat psychiatric disorders or within 7 days of stopping treatment with desvenlafaxine extended-release tablets. Within 14 days of stopping an MAOI intended to treat psychiatric disorders. In a patient who is being treated with linezolid or intravenous methylene blue. [see Dosage and Administration (2.7) , Contraindications (4) and Warnings and Precautions (5.2) ]. …