Clinical Worsening of Depressive Symptoms, Unusual Changes in Behavior, and Suicidality: Desvenlafaxine succinate is an SNRI, a class of medicines that may be used to treat depression. All patients treated with desvenlafaxine should be monitored appropriately and observed closely for clinical worsening and suicidality. Patients, their families and caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression and suicidal ideation, especially when initiating therapy or during any change in dose or dosage regimen. The risk of suicide attempt must be considered, especially in depressed patients, and the smallest quantity of drug, consistent with good patient management, should be provided to reduce the risk of overdose.
Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are strong predictors of suicide. Pooled analyses of short-term placebo-controlled trials of antidepressant medicines (SSRIs and others) showed that these medicines increase the risk of suicidality in children, adolescents and young adults (18-24 years) with major depression and other psychiatric disorders.
Mania/Hypomania: In clinical trials, mania was reported for 0.1% of patients treated with desvenlafaxine. As with all antidepressants, desvenlafaxine should be used cautiously in patients with a history or family history of mania or hypomania (see Adverse Reactions).
Serotonin Syndrome: As with other serotonergic agents, the development of a potentially life-threatening serotonin syndrome may occur with desvenlafaxine treatment, particularly with concomitant use of other serotonergic drugs (including SSRIs, SNRIs and triptans) and with drugs that impair metabolism of serotonin (including MAOIs). Serotonin syndrome symptoms may include mental status changes (eg, agitation, hallucinations and coma), autonomic instability (eg, tachycardia, labile blood pressure and hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination) and/or gastrointestinal symptoms (eg, nausea, vomiting and diarrhea) (see Interactions).
If concomitant treatment with desvenlafaxine and an SSRI, another SNRI or a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
The concomitant use of desvenlafaxine with serotonin precursors (eg, tryptophan supplements) is not recommended.
Narrow-Angle Glaucoma: Mydriasis has been reported in association with desvenlafaxine; therefore, patients with raised intraocular pressure or those at risk of acute narrow-angle glaucoma (angle-closure glaucoma) should be monitored (see Adverse Reactions).
Co-Administration of Drugs Containing Venlafaxine and/or Desvenlafaxine: Products containing desvenlafaxine succinate should not be used concomitantly with products containing venlafaxine HCl or other products containing desvenlafaxine succinate.
Effects on Blood Pressure: Increases in blood pressure were observed in some patients in clinical trials, particularly with higher doses. Preexisting hypertension should be controlled before treatment with desvenlafaxine. Patients receiving desvenlafaxine should have regular monitoring of blood pressure. Cases of elevated blood pressure requiring immediate treatment have been reported with desvenlafaxine. Sustained blood pressure increases could have adverse consequences. For patients who experience a sustained increase in blood pressure while receiving desvenlafaxine, either dose reduction or discontinuation should be considered.
Caution should be exercised in treating patients with underlying conditions that might be compromised by increases in blood pressure (see Adverse Reactions).
Cardiovascular/Cerebrovascular: Caution is advised in administering desvenlafaxine to patients with cardiovascular, cerebrovascular or lipid metabolism disorders. Increases in blood pressure and heart rate were observed in clinical trials with desvenlafaxine. Desvenlafaxine has not been evaluated systematically in patients with a recent history of myocardial infarction, unstable heart disease, uncontrolled hypertension or cerebrovascular disease. Patients with these diagnoses, except for cerebrovascular disease, were excluded from clinical trials (see Adverse Reactions).
Serum Lipids: Dose-related elevations in fasting serum total cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides were observed in clinical trials. Measurement of serum lipids should be considered during treatment with desvenlafaxine (see Adverse Reactions).
Seizures: Cases of seizure were reported in pre-marketing clinical trials with desvenlafaxine. Desvenlafaxine has not been systematically evaluated in patients with a seizure disorder. Desvenlafaxine should be prescribed with caution in patients with a seizure disorder (see Adverse Reactions).
Discontinuation Effects: During marketing of SNRIs and SSRIs, there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: Dysphoric mood, irritability, agitation, dizziness, sensory disturbances (paraesthesias eg, electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus and seizures. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms.
Patients should be monitored when discontinuing treatment with desvenlafaxine. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible.
Abnormal Bleeding: Drugs that inhibit serotonin uptake in platelets may lead to abnormalities of platelet aggregation. As with other agents that inhibit serotonin-reuptake, desvenlafaxine should be used cautiously in patients predisposed to bleeding.
Hyponatremia: Cases of hyponatremia and/or the syndrome of inappropriate antidiuretic hormone (SIADH) secretion have been described with SNRIs and SSRIs, usually in volume-depleted or dehydrated patients, including elderly patients and patients taking diuretics (see Adverse Reactions).
Effects on the Ability to Drive or Operate Machinery: Since any CNS-active drug may impair judgment, thinking or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that desvenlafaxine therapy does not adversely affect their ability to engage in such activities.
Use in Pregnancy: The safety of desvenlafaxine in human pregnancy has not been established. Desvenlafaxine must only be administered to pregnant women 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.
Complications, including the need for respiratory support, tube feeding or prolonged hospitalization, have been reported in neonates exposed to SNRIs or SSRIs, late in the 3rd trimester. Such complications can arise immediately upon delivery.
Use in Lactation: Desvenlafaxine (O-desmethylvenlafaxine) is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from desvenlafaxine, a decision should be made whether or not to discontinue the drug, taking into account the importance of the drug to the mother. Administer desvenlafaxine to lactating women only if the expected benefits outweigh the possible risks.