"A placebo is a substance, such as a pill or shot, that doesn't contain any active medicine. Scientists typically use placebos as controls in research studies. This helps them understand how much of a medicine's effects are due to the drug itself,"...
The following adverse reactions are discussed in greater detail in other sections of the label.
- Clinical Worsening and Suicide Risk [see WARNINGS AND PRECAUTIONS]
- Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]
- Seizure [see WARNINGS AND PRECAUTIONS]
- Abnormal Bleeding [see WARNINGS AND PRECAUTIONS]
- Activation of Mania/Hypomania [see WARNINGS AND PRECAUTIONS]
- Discontinuation of Treatment with VIIBRYD [see WARNINGS AND PRECAUTIONS]
- Hyponatremia [see WARNINGS AND PRECAUTIONS]
- Angle Closure Glaucoma [see WARNINGS AND PRECAUTIONS]
Clinical Studies Experience
The most commonly observed adverse reactions in VIIBRYD-treated MDD patients in placebo-controlled studies (incidence ≥ 5% and at least twice the rate of placebo) were: diarrhea, nausea, vomiting, and insomnia.
The safety of VIIBRYD was evaluated in 2,177 patients (1870 years of age) diagnosed with MDD who participated in clinical studies, representing 552 patient-years of exposure. In an open-label 52 week study at 40 mg daily, 599 patients were exposed to VIIBRYD for a total of 348 patient-years.
The information presented in these sections was derived from studies of VIIBRYD 40 mg daily in major depressive disorder including: 1) 2 placebo-controlled 8-week studies in 861 patients, including 436 receiving vilazodone; and 2) an open-label 52-week study of 599 patients. These studies included a titration period of 10 mg daily for 7 days followed by 20 mg daily for 7 days. In these clinical trials, VIIBRYD was administered with food.
Because clinical trials are conducted under widely varying conditions and varying lengths of time, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect rates observed in practice.
Adverse Reactions Reported As Reasons For Discontinuation Of Treatment
In the placebo-controlled studies of MDD there was no single adverse reaction leading to discontinuation in > 1% of the patients. Overall, 7.1% of the patients who received VIIBRYD discontinued treatment due to an adverse reaction, compared with 3.2% of placebo-treated patients in these studies.
Common Adverse Reactions In Placebo-Controlled MDD Studies
Table 2 shows the incidence of common adverse reactions that occurred in ≥ 2% of VIIBRYD-treated MDD patients (and greater than in placebo-treated patients) in the placebo-controlled studies.
Table 2: Common Adverse Reactions Occurring in
≥ 2% of VIIBRYD-treated Patients and > Placebotreated Patients
|System Organ Class
|VIIBRYD 40 mg/day
N = 436
N = 433
|Nervous system disorders|
|Libido decreased||4||< 1|
|Restlessness *||3||< 1|
|Feeling jittery||2||< 1|
|Musculoskeletal and connective tissue disorders|
|Reproductive system and breast disorders|
|Metabolism and nutrition disorders|
akathisia, and restless legs syndrome
**Includes orgasm abnormal and anorgasmia
***Male patients only (Placebo n=182; VIIBRYD n=170)
Table 3: Sexual Adverse
Reactions: Percentage in the Placebo-Controlled Studies
|Decreased libido||5||0||3||< 1|
|Sexual dysfunction||2||0||< 1||< 1|
|- Not applicable
VIIBRYD has not been associated with any clinically important changes in laboratory test parameters in serum chemistry (including liver function tests), hematology and urinalysis, as measured in placebo-controlled studies. These studies include analysis of (1) mean change from baseline and (2) the proportion of patients meeting criteria for potentially clinically significant changes from baseline. Results from a 52-week open-label study were consistent with the findings from the placebo-controlled studies.
VIIBRYD has not been associated with any clinically significant effect on ECG parameters, including QT, QTc, PR and QRS intervals, or with any arrhythmogenic potential. ECGs were evaluated in a thorough QTc study at doses up to 80 mg daily with food and in the placebo-controlled studies [see CLINICAL PHARMACOLOGY].
VIIBRYD has not been associated with any clinically significant effect on vital signs, including systolic and diastolic blood pressure and heart rate, as measured in placebo-controlled studies. These studies included analyses of (1) change from baseline, and (2) the proportion of patients meeting criteria for potentially clinically significant changes from baseline. Results from a 52-week open-label study were consistent with the findings from the placebo-controlled studies.
VIIBRYD had no effect on body weight as measured by the mean change from baseline in the 8-week, placebo-controlled studies. The mean changes in weight were +0.16 kg in the VIIBRYD group and +0.18 kg in the placebo group. The proportions of patients with a weight gain ≥ 7% were 0.9% in the VIIBRYD group and 1.2% in the placebo group. The proportions of patients with a weight decrease ≥ 7% were 1.4% in the VIIBRYD group and 1.4% in the placebo group.
Other Adverse Reactions Observed In Clinical Studies
The following listing does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo.
Reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients:
Cardiac disorders: infrequent: ventricular extrasystoles
Eye disorders: frequent: vision blurred, dry eye; infrequent: cataracts
General disorders: infrequent: feeling abnormal
Metabolism and nutrition disorders: frequent: decreased appetite
Nervous System: frequent: sedation, migraine; infrequent: dysgeusia
Psychiatric disorders: infrequent: panic attack, mania
Renal and Urinary disorder: infrequent: pollakiuria
The following adverse reactions have been identified during postapproval use of VIIBRYD. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure. These events include:
General Disorders and administrative site conditions -irritability
Psychiatric Disorders - hallucinations, suicide attempt, suicidal ideation
Read the Viibryd (vilazodone hydrochloride) Side Effects Center for a complete guide to possible side effects
Central Nervous System (CNS)-Active Agents
The risk of using VIIBRYD in combination with other CNS-active drugs has not been systematically evaluated. Consequently, use caution when VIIBRYD is prescribed in combination with other CNS-active drugs.
Monoamine Oxidase Inhibitors (MAOIs)
Drugs That Interfere With Hemostasis (e.g., NSAIDs, Aspirin, and Warfarin)
Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of case-control and cohort design have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. These studies have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. 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 VIIBRYD is initiated or discontinued [see WARNINGS AND PRECAUTIONS].
Potential For Other Drugs To Affect Vilazodone
Figure 1 : Impact of other drugs on Vilazodone PK
Inhibitors of CYP3A4
Metabolism by CYP3A4 is a major elimination pathway for vilazodone. Concomitant use of VIIBRYD and strong inhibitors of CYP3A4 (e.g., ketoconazole) can increase vilazodone plasma concentrations by approximately 50% (see Figure 1). The VIIBRYD dose should be reduced to 20 mg if co-administered with a strong inhibitor of CYP3A4. During co-administration with moderate inhibitors of CYP3A4 (e.g., erythromycin), the VIIBRYD dose should be reduced to 20 mg for patients with intolerable adverse events. No dose adjustment is recommended when VIIBRYD is coadministered with mild inhibitors of CYP3A4 (e.g., cimetidine) [see DOSAGE AND ADMINISTRATION].
Inducers of CYP3A4
Based on clinical response, consider increasing the dose of VIIBRYD up to 2-fold when concomitantly used with strong CYP3A4 inducers (e.g., carbamazepine) for greater than 14 days. The maximum daily dose should not exceed 80 mg. Concomitant use of VIIBRYD with strong inducers of CYP3A4 (e.g., carbamazepine) can decrease vilazodone systemic exposure by approximately 45% (see Figure 1). If CYP3A4 inducers are discontinued, reduce the VIIBRYD dose to the original level in 14 days [see DOSAGE AND ADMINISTRATION].
Inhibitors of other CYP enzymes
Concomitant administration of VIIBRYD with inhibitors of CYP2C19 and CYP2D6 is not expected to alter plasma concentrations of vilazodone. These isoforms are minor elimination pathways in the metabolism of vilazodone. In vitro studies have shown that CYP1A2, CYP2A6, CYP2C9 and CYP2E1 have minimal contribution to the metabolism of vilazodone.
Potential For Vilazodone To Affect Other Drugs
Drugs metabolized by CYP1A2, CYP2C9, CYP2D6, CYP3A4 or CYP2C19
Coadministration of VIIBRYD with substrates for CYP1A2, CYP2C9, CYP3A4, or CYP2D6 is unlikely to result in clinically significant changes in the concentrations of the CYP substrates. A study in healthy subjects found that VIIBRYD (20 mg/day for 8-10 days) had no effect on the pharmacokinetics of caffeine, flurbiprofen, nifedipine or debrisoquine, probes for CYP1A2, CYP2C9, CYP3A4, and CYP2D6, respectively. VIIBRYD coadministration with mephenytoin to healthy subjects resulted in a small (11%) increase in mephenytoin biotransformation, suggestive of a minor induction of CYP2C19. In vitro studies have shown that VIIBRYD is a moderate inhibitor of CYP2C19 and CYP2D6.
Drugs metabolized by CYP2C8
Coadministration of VIIBRYD with a CYP2C8 substrate may lead to an increase in concentration of the other drug. In vitro studies suggest that VIIBRYD may inhibit the biotransformation of substrates of CYP2C8. The effect of VIIBRYD on CYP2C8 activity has not been tested in vivo.
Induction of CYP isoforms
VIIBRYD did not induce CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 or 3A5 in an in vitro study in cultured human hepatocytes. Chronic administration of vilazodone is unlikely to induce the metabolism of drugs metabolized by these major CYP isoforms.
Drugs Highly Bound To Plasma Protein
The interaction between vilazodone and other highly protein-bound drugs has not been evaluated. Because vilazodone is highly bound to plasma protein, administration of VIIBRYD to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug.
There are postmarketing reports of serotonin syndrome with concomitant use of a serotonergic antidepressant and a triptan. If concomitant treatment with VIIBRYD and a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases [see WARNINGS AND PRECAUTIONS].
As with other psychotropic medications, the use of alcohol by patients taking VIIBRYD is not recommended, because of the potential for pharmacodynamic interactions.
Drug Abuse And Dependence
VIIBRYD is not a controlled substance.
Abuse And Dependence
VIIBRYD has been systematically studied in animals and did not demonstrate abuse or dependence potential. While VIIBRYD has not been systematically studied in humans for its potential for abuse, there was no suggested evidence of drug-seeking behavior in the clinical studies. However, it is not possible to predict on the basis of clinical experience the extent to which a CNS active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of VIIBRYD (e.g., development of tolerance, drug-seeking behavior, increases in dose).
Read the Viibryd Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 8/11/2014
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