The following adverse reaction has been identified during post-approval use of PRISTIQ. 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:
Skin and subcutaneous tissue disorders – Stevens-Johnson syndrome
Gastrointestinal disorders – Pancreatitis acute
Cardiovascular system – Takotsubo cardiomyopathy
|Monoamine Oxidase Inhibitors (MAOI)|
|Clinical Impact||The concomitant use of SSRIs and SNRIs including PRISTIQ with MAOIs increases the risk of serotonin syndrome.|
|Intervention||Concomitant use of PRISTIQ is contraindicated: |
|Examples||selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue|
|Other Serotonergic Drugs|
|Clinical Impact||Concomitant use of PRISTIQ with other serotonergic drugs increases the risk of serotonin syndrome.|
|Intervention||Monitor for symptoms of serotonin syndrome when PRISTIQ is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems. If serotonin syndrome occurs, consider discontinuation of PRISTIQ and/or concomitant serotonergic drugs [see Warnings and Precautions (5.2)].|
|Examples||other SNRIs, SSRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, amphetamines, tryptophan, and St. John’s Wort|
|Drugs that Interfere with Hemostasis|
|Clinical Impact||Concomitant use of PRISTIQ with an antiplatelet or anticoagulant drug may potentiate the risk of bleeding. This may be due to the effect of PRISTIQ on the release of serotonin by platelets.|
|Intervention||Closely monitor for bleeding for patients receiving an antiplatelet or anticoagulant drug when PRISTIQ is initiated or discontinued [see Warnings and Precautions (5.4)].|
|Examples||NSAIDs, aspirin, and warfarin|
|Drugs that are Primarily Metabolized by CYP2D6|
|Clinical Impact||Concomitant use of PRISTIQ increases Cmax and AUC of a drug primarily metabolized by CYP2D6 which may increase the risk of toxicity of the CYP2D6 substrate drug [see Clinical Pharmacology (12.3)].|
|Intervention||Original dose should be taken when co-administered with PRISTIQ 100 mg or lower. Reduce the dose of these drugs by up to one-half if co-administered with 400 mg of PRISTIQ.|
|Examples||desipramine, atomoxetine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine|
Based on pharmacokinetic studies, no dosage adjustment is required for drugs that are mainly metabolized by CYP3A4 (e.g., midazolam), or for drugs that are metabolized by both CYP2D6 and CYP3A4 (e.g., tamoxifen, aripiprazole), when administered concomitantly with PRISTIQ [see Clinical Pharmacology (12.3)].
A clinical study has shown that PRISTIQ 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 PRISTIQ.
False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking desvenlafaxine. This is due to lack of specificity of the screening tests. False positive test results may be expected for several days following discontinuation of desvenlafaxine therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish desvenlafaxine from PCP and amphetamine.
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185.
There are no published studies on PRISTIQ in pregnant women; however published epidemiologic studies of pregnant women exposed to venlafaxine, the parent compound, have not reported a clear association with adverse developmental outcomes (see Data). There are risks associated with untreated depression in pregnancy and with exposure to SNRIs and SSRIs, including PRISTIQ, during pregnancy (see Clinical Considerations).
In reproductive developmental studies in rats and rabbits treated with desvenlafaxine succinate, there was no evidence of teratogenicity at a plasma exposure (AUC) that is up to 19-times (rats) and 0.5-times (rabbits) the exposure at an adult human dose of 100 mg per day. However, fetotoxicity and pup deaths were observed in rats at 4.5-times the AUC exposure observed with an adult human dose of 100 mg per day.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Disease-Associated Maternal and/or Embryo/Fetal Risk
A prospective longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy, showed that women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication.
Maternal Adverse Reactions
Exposure to SNRIs in mid to late pregnancy may increase the risk for preeclampsia, and exposure to SNRIs near delivery may increase the risk for postpartum hemorrhage.
Fetal/Neonatal Adverse Reactions
Exposure to SNRIs or SSRIs in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding. Monitor neonates who were exposed to PRISTIQ in the third trimester of pregnancy for drug discontinuation syndrome (see Data).
Published epidemiological studies of pregnant women exposed to the parent compound venlafaxine have not reported a clear association with major birth defects or miscarriage. Methodological limitations of these observational studies include possible exposure and outcome misclassification, lack of adequate controls, adjustment for confounders, and confirmatory studies; therefore, these studies cannot establish or exclude any drug-associated risk during pregnancy.
Retrospective cohort studies based on claims data have shown an association between venlafaxine use and preeclampsia, compared to depressed women who did not take an antidepressant during pregnancy. One study that assessed venlafaxine exposure in the second trimester or first half of the third trimester and preeclampsia showed an increased risk compared to unexposed depressed women [adjusted (adj) RR 1.57, 95% CI 1.29–1.91]. Preeclampsia was observed at venlafaxine doses equal to or greater than 75 mg/day and a duration of treatment >30 days. Another study that assessed venlafaxine exposure in gestational weeks 10–20 and preeclampsia showed an increased risk at doses equal to or greater than 150 mg/day. Available data are limited by possible outcome misclassification and possible confounding due to depression severity and other confounders.
Retrospective cohort studies based on claims data have suggested an association between venlafaxine use near the time of delivery or through delivery and postpartum hemorrhage. One study showed an increased risk for postpartum hemorrhage when venlafaxine exposure occurred through delivery, compared to unexposed depressed women [adj RR 2.24 (95% CI 1.69–2.97)]. There was no increased risk in women who were exposed to venlafaxine earlier in pregnancy. Limitations of this study include possible confounding due to depression severity and other confounders. Another study showed an increased risk for postpartum hemorrhage when SNRI exposure occurred for at least 15 days in the last month of pregnancy or through delivery, compared to unexposed women (adj RR 1.64–1.76). The results of this study may be confounded by the effects of depression.
Neonates exposed to 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)].
When desvenlafaxine succinate was administered orally to pregnant rats and rabbits during the period of organogenesis at doses up to 300 mg/kg/day and 75 mg/kg/day, respectively, no teratogenic effects were observed. These doses were associated with a plasma exposure (AUC) 19 times (rats) and 0.5 times (rabbits) the AUC exposure at an adult human dose of 100 mg per day. However, fetal weights were decreased and skeletal ossification was delayed in rats in association with maternal toxicity at the highest dose, with an AUC exposure at the no-effect dose that is 4.5-times the AUC exposure at an adult human dose of 100 mg per day.
When desvenlafaxine succinate was administered orally to pregnant rats throughout gestation and lactation, there was a decrease in pup weights and an increase in pup deaths during the first four days of lactation at the highest dose of 300 mg/kg/day. The cause of these deaths is not known. The AUC exposure at the no-effect dose for rat pup mortality was 4.5-times the AUC exposure at an adult human dose of 100 mg per day. Post-weaning growth and reproductive performance of the progeny were not affected by maternal treatment with desvenlafaxine succinate at exposures 19 times the AUC exposure at an adult human dose of 100 mg per day.
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