DESVENLAFAXINE ER tablet, film coated, extended release

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

DESVENLAFAXINE SUCCINATE (UNII: ZB22ENF0XR) (DESVENLAFAXINE - UNII:NG99554ANW)

Available from:

Direct_Rx

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Desvenlafaxine extended-release tablet is indicated for the treatment of adults with major depressive disorder (MDD) [see CLINICAL STUDIES (14)]. Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any excipients in the desvenlafaxine formulation. Angioedema has been reported in patients treated with desvenlafaxine [see ADVERSE REACTIONS (6.1)]. The use of MAOIs intended to treat psychiatric disorders with desvenlafaxine or within 7 days of stopping treatment with desvenlafaxine is contraindicated because of an increased risk of serotonin syndrome. The use of desvenlafaxine 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 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)]. 8.1 Pregnancy 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. Risk summary There are no published studies on desvenlafaxine 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 desvenlafaxine, 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 to 4% and 15 to 20%, respectively. Clinical Considerations 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 desvenlafaxine in the third trimester of pregnancy for drug discontinuation syndrome (see Data). Data Human 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 to 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 to 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 to 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 in the last month of pregnancy or through delivery, compared to unexposed women (adj RR 1.64 to 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)]. Animal Data: 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. 8.6 Lactation Risk Summary Available limited data from published literature show low levels of desvenlafaxine in human milk, and have not shown adverse reactions in breastfed infants (see Data). There are no data on the effects of desvenlafaxine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for desvenlafaxine and any potential adverse effects on the breastfed child from desvenlafaxine or from the underlying maternal condition. Data A lactation study was conducted in 10 breastfeeding women (at a mean of 4.3 months postpartum) who were being treated with a 50 to 150 mg daily dose of desvenlafaxine for postpartum depression. Sampling was performed at steady state (up to 8 samples) over a 24 hour dosing period, and included foremilk and hindmilk. The mean relative infant dose was calculated to be 6.8% (range of 5.5 to 8.1%). No adverse reactions were seen in the infants. 8.4 Pediatric Use The safety and effectiveness of desvenlafaxine have not been established in pediatric patients for the treatment of MDD. Antidepressants, such as desvenlafaxine, increase the risk of suicidal thoughts and behaviors in pediatric patients [see the BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1)]. Additional information describing clinical studies in which efficacy was not demonstrated in pediatric patients is approved for Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.'s PRISTIQ® (desvenlafaxine) Extended-Release Tablets. However, due to Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.'s marketing exclusivity rights, this product is not labeled with that pediatric information. Juvenile Animal Studies In a juvenile animal study, male and female rats were treated with desvenlafaxine (75, 225 and 675 mg/kg/day) starting on postnatal day (PND) 22 through 112. Behavioral deficits (longer time immobile in a motor activity test, longer time swimming in a straight channel test, and lack of habituation in an acoustic startle test) were observed in males and females but were reversed after a recovery period. A No Adverse Effect Level (NOAEL) was not identified for these deficits. The Low Adverse Effect Level (LOAEL) was 75 mg/kg/day which was associated with plasma exposure (AUC) twice the levels measured with a pediatric dose of 100 mg/day. In a second juvenile animal study, male and female rats were administered desvenlafaxine (75, 225 or 675 mg/kg/day) for 8 to 9 weeks starting on PND 22 and were mated with naïve counterparts. Delays in sexual maturation and decreased fertility, number of implantation sites and total live embryos were observed in treated females at all doses. The LOAEL for these findings is 75 mg/kg/day which was associated with an AUC twice the levels measured with a pediatric dose of 100 mg/day. These findings were reversed at the end of a 4-week recovery period. The relevance of these findings to humans is not known. 8.5 Geriatric Use Of the 4,158 patients in pre-marketing clinical studies with desvenlafaxine, 6% were 65 years of age or older. No overall differences in safety or efficacy were observed between these patients and younger patients; however, in the short-term placebo-controlled studies, there was a higher incidence of systolic orthostatic hypotension in patients ≥65 years of age compared to patients <65 years of age treated with desvenlafaxine [see ADVERSE REACTIONS (6.1)]. For elderly patients, possible reduced renal clearance of desvenlafaxine should be considered when determining dose [see DOSAGE AND ADMINISTRATION (2.2) and CLINICAL PHARMACOLOGY (12.3)]. SSRIs and SNRIs, including desvenlafaxine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see WARNINGS AND PRECAUTIONS (5.9)]. 8.7 Renal Impairment Adjust the maximum recommended dosage in patients with moderate or severe renal impairment (CLcr 15 to 50 mL/min, C-G), or end-stage renal disease (CLcr < 15 mL/min, C-G) [see DOSAGE AND ADMINISTRATION (2.2) and CLINICAL PHARMACOLOGY (12.3)]. 8.8 Hepatic Impairment Adjust the maximum recommended dosage in patients with moderate to severe hepatic impairment (Child-Pugh score 7 to 15) [see DOSAGE AND ADMINISTRATION (2.3) and CLINICAL PHARMACOLOGY (12.3)]. 9.1 Controlled Substance Desvenlafaxine is not a controlled substance.

Product summary:

Desvenlafaxine extended-release tablets are available as follows: 50 mg, light pink, biconvex, round shaped film-coated tablets, debossed with "LU" on one side and "S61" on the other side. bottle of 30 tablets in unit-of-use package bottle of 90 tablets in unit-of-use package , bottle of 500 tablets 100 mg, reddish-orange, biconvex, round shaped film-coated tablets, debossed with "LU" on one side and "S62" on the other side. bottle of 30 tablets in unit-of-use package bottle of 90 tablets in unit-of-use package bottle of 500 tablets Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Each tablet contains 76 mg or 152 mg of desvenlafaxine succinate monohydrate equivalent to 50 mg or 100 mg of desvenlafaxine, respectively.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

DESVENLAFAXINE ER- DESVENLAFAXINE ER TABLET, FILM COATED, EXTENDED
RELEASE
Direct_Rx
----------
MEDICATION GUIDE
Desvenlafaxine (des-VEN-la-FAX-een)
Extended-Release Tablets
Read this Medication Guide before you start taking Desvenlafaxine
Extended-Release Tablets and each
time you get a refill. There may be new information. This information
does not take the place of talking to
your healthcare provider about your medical condition or treatment.
What is the most important information I should know about
desvenlafaxine
extended-release tablets?
Desvenlafaxine extended-release tablets can cause serious side
effects, including:
Increased risk of suicidal thoughts or actions in some children and
young adults within the first few
months of treatment. Desvenlafaxine extended-release tablets is not
for use in children.
Depression or other serious mental illnesses are the most important
causes of suicidal thoughts or actions.
How can I watch for and try to prevent suicidal thoughts and actions?
Pay close attention to any changes, especially sudden changes, in
mood, behaviors, thoughts, or feelings.
This is very important when an antidepressant medicine is started or
when the dose is changed.
Call the healthcare provider right away to report new or sudden
changes in mood, behavior, thoughts, or
feelings.
Keep all follow-up visits with the healthcare provider as scheduled.
Call the healthcare provider between
visits as needed, especially if you have concerns about symptoms.
Call your healthcare provider right away if you have any of the
following symptoms, especially if they
are new, worse, or worry you:
thoughts about suicide or dying
attempts to commit suicide
new or worse depression
new or worse anxiety
feeling very agitated or restless
panic attacks
trouble sleeping (insomnia)
new or worse irritability
acting aggressive, being angry, or violent
acting on dangerous impulses
an extreme increase in activity and talking (mania)
other unusual changes in behavior or mood
What is desvenlafaxine extended-release tablets?
Desve

Summary of Product characteristics

DESVENLAFAXINE ER- DESVENLAFAXINE ER TABLET, FILM COATED, EXTENDED
RELEASE
DIRECT_RX
----------
DESVENLAFAXINE ER
Desvenlafaxine extended-release tablet is indicated for the treatment
of adults with
major depressive disorder (MDD) [see CLINICAL STUDIES (14)].
2.1 General Instructions for Use
The recommended dose for desvenlafaxine extended-release tablets are
50 mg once
daily, with or without food. The 50 mg dose is both a starting dose
and the therapeutic
dose. Desvenlafaxine extended-release tablets should be taken at
approximately the
same time each day. Tablets must be swallowed whole with fluid and not
divided,
crushed, chewed, or dissolved.
In clinical studies, doses of 10 mg to 400 mg per day were studied. In
clinical studies,
doses of 50 mg to 400 mg per day were shown to be effective, although
no additional
benefit was demonstrated at doses greater than 50 mg per day and
adverse reactions
and discontinuations were more frequent at higher doses.
The 25 mg per day dose is intended for a gradual reduction in dose
when discontinuing
treatment. When discontinuing therapy, gradual dose reduction is
recommended
whenever possible to minimize discontinuation symptoms [see DOSAGE AND
ADMINISTRATION (2.5) and WARNINGS AND PRECAUTIONS (5.7)].
2.2 Dosage Recommendations for Patients with Renal Impairment
The maximum recommended dose in patients with moderate renal
impairment (24-hr
creatinine clearance [ClCr] = 30 to 50 mL/min, Cockcroft-Gault [C-G])
is 50 mg per day.
The maximum recommended dose in patients with severe renal impairment
(ClCr15 to
29 mL/min, C-G) or end-stage renal disease (ESRD, ClCr <15 mL/min,
C-G) is 25 mg
every day or 50 mg every other day. Supplemental doses should not be
given to
patients after dialysis [see USE IN SPECIFIC POPULATIONS (8.6) and
CLINICAL
PHARMACOLOGY (12.3)].
2.3 Dosage Recommendations for Patients with Hepatic Impairment
The recommended dose in patients with moderate to severe hepatic
impairment (Child-
Pugh score 7 to 15) is 50 mg per day. Dose escalation above 100 mg per
da