In general, the adverse reaction profile of venlafaxine (in placebo-controlled clinical studies) 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 Warnings and Precautions ( 5.3, 5.10, 5.11) and Use in Specific Populations ( 8.4) ].
In pediatric clinical studies, the adverse reaction, suicidal ideation, was observed.
Particularly, the following adverse reactions were observed in pediatric patients: abdominal pain, agitation, dyspepsia, ecchymosis, epistaxis, and myalgia.
The following adverse reactions have been identified during postapproval use of venlafaxine hydrochloride extended-release capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:
Body as a whole
QT prolongation, ventricular fibrillation, ventricular tachycardia (including torsade de pointes), takotsubo cardiomyopathy
Mucous membrane bleeding [ see Warnings and Precautions ( 5.4) ], blood dyscrasias (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia), prolonged bleeding time, thrombocytopenia
Hyponatremia [ see Warnings and Precautions ( 5.9) ], Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion [ see Warnings and Precautions ( 5.9) ], abnormal liver function tests, hepatitis, prolactin increased
Neuroleptic Malignant Syndrome (NMS) [ see Warnings and Precautions ( 5.2) ], serotonergic syndrome [ see Warnings and Precautions ( 5.2) ], delirium, extrapyramidal reactions (including dystonia and dyskinesia), impaired coordination and balance, tardive dyskinesia
Dyspnea, interstitial lung disease, pulmonary eosinophilia [ see Warnings and Precautions ( 5.12) ]
Skin and appendages
Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme
Angle-closure glaucoma [ see Warnings and Precautions ( 5.5) ]
The risk of using venlafaxine in combination with other CNS-active drugs has not been systematically evaluated. Consequently, caution is advised when venlafaxine hydrochloride extended-release capsules are taken in combination with other CNS- active drugs.
Adverse reactions, some of which were serious, have been reported in patients who have recently been discontinued from an MAOI and started on antidepressants with pharmacological properties similar to venlafaxine hydrochloride extended-release capsules (SNRIs or SSRIs), or who have recently had SNRI or SSRI therapy discontinued prior to initiation of an MAOI [ see Dosage and Administration ( 2.9), Contraindications ( 4.2) and Warnings and Precautions ( 5.2) ].
Based on the mechanism of action of venlafaxine hydrochloride extended-release capsules and the potential for serotonin syndrome, caution is advised when venlafaxine hydrochloride extended-release capsules are coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, SSRIs, other SNRIs, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, tramadol, or St. John’s wort. If concomitant treatment with venlafaxine hydrochloride extended-release capsules and these drugs is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of venlafaxine hydrochloride extended-release capsules with tryptophan supplements is not recommended [ see Dosage and Administration ( 2.9), Contraindications ( 4.2), and Warnings and Precautions ( 5.2) ].
Serotonin release by platelets plays an important role in hemostasis. The use of psychotropic drugs that interfere with serotonin reuptake is associated with the occurrence of upper gastrointestinal bleeding and concurrent use of an NSAID or aspirin may potentiate this risk of bleeding [ see Warnings and Precautions ( 5.4) ]. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs and SNRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when venlafaxine hydrochloride extended-release capsules are initiated or discontinued.
The safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established. Coadministration of venlafaxine hydrochloride extended-release capsules and weight loss agents is not recommended. Venlafaxine hydrochloride extended-release capsules are not indicated for weight loss alone or in combination with other products.
* No dose adjustment on coadministration with CYP2D6 inhibitors (Fig 3 and Metabolism Section 12.3)
* Data for 2-OH desipramine were not plotted to enhance clarity; the fold change and 90% CI for C max and AUC of 2-OH desipramine were 6.6 (5.5, 7.9) and 4.4 (3.8, 5), respectively.
*: Administration of venlafaxine in a stable regimen did not exaggerate the psychomotor and psychometric effects induced by ethanol in these same subjects when they were not receiving venlafaxine.
False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking venlafaxine. This is due to lack of specificity of the screening tests. False positive test results may be expected for several days following discontinuation of venlafaxine therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish venlafaxine from PCP and amphetamine.
Venlafaxine did not cause malformations in offspring of rats or rabbits given doses up to 2.5 times (rat) or 4 times (rabbit) the maximum recommended human daily dose on a mg/m 2 basis. However, 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. The cause of these deaths is not known. These effects occurred at 2.5 times (mg/m 2) the maximum human daily dose. The no effect dose for rat pup mortality was 0.25 times the human dose on a mg/m 2 basis. In reproductive developmental studies in rats and rabbits with O-desmethylvenlafaxine (ODV), the major human metabolite of venlafaxine, evidence of teratogenicity was not observed at exposure margins of 13 in rats and 0.3 in rabbits. There are no adequate and well-controlled studies in pregnant women. Venlafaxine hydrochloride extended-release capsules should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Neonates exposed to venlafaxine hydrochloride extended-release capsules, other SNRIs, or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs, or possibly a drug discontinuation syndrome. It should be noted, that in some cases the clinical picture is consistent with serotonin syndrome [ see Warnings and Precautions ( 5.2) and Drug Interactions ( 7.3) ]. When treating a pregnant woman with venlafaxine hydrochloride extended-release capsules during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.
Venlafaxine and ODV have been reported to be excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from venlafaxine hydrochloride extended-release capsules, 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.
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