Vilazodone

Concomitant administration of vilazodone and moderate CYP3A4 inhibitors (e.g., erythromycin) can result in increased plasma vilazodone concentrations. During concurrent administration with moderate inhibitors of CYP3A4 (e.g., erythromycin), the dosage of vilazodone should be reduced to 20 mg once daily in patients experiencing intolerable adverse effects.

Concomitant administration of vilazodone and potent CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) can increase plasma vilazodone concentrations by approximately 50%. The manufacturer states that the dosage of vilazodone should be reduced to 20 mg once daily if administered concomitantly with a potent CYP3A4 inhibitor.

Potentially serious, sometimes fatal adverse reactions may occur in patients who are receiving or have recently received a monoamine oxidase (MAO) inhibitor and then initiate therapy with antidepressant(s) that are pharmacologically similar to vilazodone (e.g., SSRIs), or in those who received SSRI therapy shortly before initiation of an MAO inhibitor. Concomitant use of MAO inhibitors with vilazodone is contraindicated. In addition, at least 2 weeks should elapse between discontinuance of an MAO inhibitor and initiation of vilazodone and vice versa.

Linezolid, an anti-infective agent that is also a reversible MAO inhibitor, has been associated with drug interactions resulting in serotonin syndrome, including some associated with SSRIs. Because of this potential risk, linezolid generally should not be used in patients receiving vilazodone. While the US Food and Drug Administration (FDA) has not received reports of serotonin syndrome with concomitant use of linezolid and vilazodone to date, the risk is considered comparable to that with SSRIs. However, the FDA states that certain life-threatening or urgent situations may necessitate immediate linezolid treatment in a patient receiving a serotonergic drug. In such emergency situations, the availability of alternative anti-infectives should be considered and the benefits of linezolid should be weighed against the risk of serotonin syndrome. If linezolid is indicated in such emergency situations, vilazodone must be immediately discontinued and the patient monitored for symptoms of CNS toxicity for 2 weeks or until 24 hours after the last linezolid dose, whichever comes first. Treatment with vilazodone may be resumed 24 hours after the last linezolid dose. If nonemergency use of linezolid is being planned for a patient receiving vilazodone, vilazodone should be withheld for at least 2 weeks prior to initiating linezolid. Treatment with vilazodone should not be initiated in a patient receiving linezolid; when necessary, vilazodone may be started 24 hours after the last linezolid dose.

For more Interactions (Complete) data for Vilazodone (13 total), please visit the HSDB record page.

IDENTIFICATION AND USE: Vilazodone is a white to off-white solid that is formulated into film-coated tablets. Vilazodone is a combined selective serotonin-reuptake inhibitor and serotonin type 1-A (5-hydroxytryptamine (5-HT1A) receptor partial agonist. It is used for the treatment of major depressive disorder in adults. HUMAN EXPOSURE AND TOXICITY: In clinical trials toxic effects of vilazodone at 200-280 mg included serotonin syndrome, lethargy, restlessness, hallucinations, and disorientation. Serotonin syndrome, a potentially life-threatening toxicity has also been reported at therapeutic doses. Serotonin syndrome symptoms may include mental status changes (agitation, hallucinations, delirium, and coma), autonomic instability (tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (nausea, vomiting, diarrhea). While serotonin syndrome has been reported during vilazodone monotherapy, it is a particular concern when used with other serotonergic drugs and with drugs that impair metabolism of serotonin (in particular, monamine oxidase inhibitors (MAOIs). The concomitant use of vilazdone with MAOIs intended to treat psychiatric disorders is contraindicated. Vilazodone is also not approved for use in pediatric patients. Pooled analyses of short-term placebo-controlled studies of antidepressant drugs (selective serotonin reuptake inhibitors and others) showed that these drugs increase the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Also, some neonates exposed to serotonegic antidepressants (including vilazodone) late in the third trimester of pregnancy 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. In some cases, the clinical picture is consistent with serotonin syndrome. Infants exposed to vilazodone in pregnancy may also have an increased risk for persistent pulmonary hypertension of the newborn, a rare heart and lung condition associated with substantial neonatal morbidity and mortality. ANIMAL STUDIES: Vilazodone caused some developmental toxicity in rats, but was not teratogenic in rats or rabbits. When vilazodone was administered to pregnant rats at an oral dose of 30 times the maximum recommended human dose during the period of organogenesis and throughout pregnancy and lactation, the number of live born pups was decreased. There was an increase in early postnatal pup mortality, and among surviving pups there was decreased body weight, delayed maturation, and decreased fertility in adulthood. There was some maternal toxicity at this dose.

/SIGNS AND SYMPTOMS/ There is limited clinical experience regarding human overdosage with Viibryd. Four patients and 1 patient's child experienced an overdose of Viibryd; all recovered. The adverse reactions associated with overdose of Viibryd at doses of 200-280 mg as observed in clinical trials included serotonin syndrome, lethargy, restlessness, hallucinations, and disorientation.

/SIGNS AND SYMPTOMS/ Potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with antidepressants alone, but particularly with concurrent use of other serotonergic drugs (including serotonin (5-hydroxytryptamine; 5-HT) type 1 receptor agonists (triptans)), drugs that impair the metabolism of serotonin (e.g., MAO inhibitors), or antipsychotics or other dopamine antagonists. Manifestations of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea). In its most severe form, serotonin syndrome may resemble NMS, which is characterized by hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation in vital signs, and mental status changes. Patients receiving vilazodone should be monitored for the development of serotonin syndrome or NMS-like signs and symptoms. Concurrent or recent (i.e., within 2 weeks) therapy with MAO inhibitors intended to treat depression is contraindicated. If concurrent therapy with vilazodone and a 5-HT1 receptor agonist (triptan) is clinically warranted, the patient should be observed carefully, particularly during initiation of therapy, when dosage is increased, or when another serotonergic agent is initiated. Concomitant use of vilazodone and serotonin precursors (e.g., tryptophan) is not recommended. If signs and symptoms of serotonin syndrome or NMS occur, treatment with vilazodone and any concurrently administered serotonergic or antidopaminergic agents, including antipsychotic agents, should be immediately discontinued and supportive and symptomatic treatment initiated.

/SIGNS AND SYMPTOMS/ Infants exposed to selective serotonin-reuptake inhibitors (SSRIs) in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1-2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Several recent epidemiologic studies suggest a positive statistical association between SSRI use (including Viibryd) in pregnancy and PPHN. Other studies do not show a significant statistical association.

/SIGNS AND SYMPTOMS/ Neonates exposed to Viibryd and other selective serotonin-reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs), 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

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ When vilazodone was administered to pregnant rats at an oral dose of 30 times the MRHD during the period of organogenesis and throughout pregnancy and lactation, the number of live born pups was decreased. There was an increase in early postnatal pup mortality, and among surviving pups there was decreased body weight, delayed maturation, and decreased fertility in adulthood. There was some maternal toxicity at this dose. These effects were not seen at 6 times the MRHD.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ No teratogenic effects were observed when vilazodone was given to pregnant rats or rabbits during the period of organogenesis at oral doses up to 200 and 36 mg/kg/day, respectively. These doses are 48 and 17 times, in rats and rabbits, respectively, the maximum recommended human dose (MRHD) of 40 mg on a mg/m2 basis. Fetal body weight gain was reduced, and skeletal ossification was delayed in both rats and rabbits at these doses; these effects were not observed at doses up to 10 times the MRHD in rats or 4 times the MRHD in rabbits.

/ALTERNATIVE and IN VITRO TESTS/ Vilazodone is a novel compound with combined high affinity and selectivity for the 5-hydroxytryptamine (5-HT) transporter and 5-HT(1A) receptors.Vilazodone was tested as a prototype compound, which benefits from dual pharmacological effects that could increase extracellular 5-HT to levels higher than those produced by conventional selective serotonin reuptake inhibitors (SSRIs). In Sf9 cells, vilazodone increased guanosine 5'-O-(3-[(35)S]thiotriphosphate) binding to 69% of the magnitude of the full 5-HT(1A) receptor agonist R-(1)-trans-8-hydroxy-2-[N-n-propyl-N-(39-iodo-29-propenyl)] aminotetralin (8-OH-PIPAT), indicating that it is a partial agonist at 5-HT(1A) receptors. Acute, systemic administration of vilazodone produced a larger maximal increase of extracellular 5-HT than the SSRI fluoxetine in both the ventral hippocampus (HPv) (558 versus 274%) and the frontal cortex (FC) (527 versus 165%). Regional differences in the response to the two drugs were also observed. These effects may be attributed to the differential regulation of 5-HT release in the HPv and FC by 5-HT(1A) autoreceptors. When challenged with the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), vilazodone-induced increases in extracellular 5-HT were greatly reduced in the HPv but to a lesser extent in the FC. In behavioral studies, vilazodone produced antidepressant-like effects in the forced swimming test in both rats and mice but only within a narrow dosage range. Like fluoxetine, vilazodone did not produce the symptoms of the 5-HT behavioral syndrome in rats but, unlike fluoxetine, pretreatment with vilazodone blocked expression of the 5-HT behavioral syndrome induced by 8-OH-DPAT. Taken together, the results show that vilazodone augments extracellular 5-HT levels in forebrain regions to a greater extent than fluoxetine. At higher doses, however, weak efficacy of vilazodone at postsynaptic 5-HT(1A) receptors may inhibit the expression of rodent antidepressant-like behaviors.

Vilazodone has not been systematically evaluated in patients with seizure disorders; such patients were excluded from clinical studies. As with other antidepressants, vilazodone should be used with caution in patients with a history of seizure disorder

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

No specific antidotes for vilazodone are known. In case of an overdose, provide supportive care, including close medical supervision and monitoring. Treatment should consist of those general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdose. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. ... Removal of vilazodone by dialysis has not been studied; however, the high volume of distribution of vilazodone suggests that dialysis will not be effective in reducing vilazodone plasma concentrations.

◉ Summary of Use during Lactation

◈ What is vilazodone?

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including vilazodone hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Vilazodone hydrochloride/

Antidepressant

MEDICATION

Preparation: H. Bottcher et al., German patent 4333254; eidem, United States of America patent 5532241 (1995, 1996 both to Merck Patent GmbH).

From hydrochloride-saturated 2-propanol /Vilazodone hydrochloride/