Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

apotex corp. - fentanyl (unii: uf599785jz) (fentanyl - unii:uf599785jz) - fentanyl 12 ug in 1 h - fentanyl transdermal system is indicated for the management of severe and persistent pain that requires an extended treatment with a daily opioid analgesic and for which alternative treatment options are inadequate. patients considered opioid-tolerant are those who are taking, for one week or longer, at least 60　mg morphine per day, 25 mcg transdermal fentanyl per hour, 30　mg oral oxycodone per day, 8　mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations [see warnings and precautions (5.1)] , reserve fentanyl transdermal system for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be ot

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

remedyrepack inc. - mirtazapine (unii: a051q2099q) (mirtazapine - unii:a051q2099q) - mirtazapine tablets are indicated for the treatment of major depressive disorder.   the efficacy of mirtazapine tablets in the treatment of major depressive disorder was established in 6-week controlled trials of outpatients whose diagnoses corresponded most closely to the diagnostic and statistical manual of mental disorders – 3rd edition (dsm-iii) category of major depressive disorder (see clinical pharmacology ).  a major depressive episode (dsm-iv) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt, or suicidal ideation.  the effectivenes

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

apotex corp - paroxetine hydrochloride (unii: x2els050d8) (paroxetine - unii:41vrh5220h) - paxil is indicated in adults for the treatment of: - major depressive disorder (mdd) - obsessive compulsive disorder (ocd) - panic disorder (pd) - social anxiety disorder (sad) - generalized anxiety disorder (gad) - posttraumatic stress disorder (ptsd)   paxil is contraindicated in patients: - taking, or within 14 days of stopping, maois (including the maois linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see warnings and precautions (5.2), drug interactions (7)]. - taking thioridazine because of risk of qt prolongation [see warnings and precautions (5. 3) and drug interactions (7)] - taking pimozide because of risk of qt prolongation [see warnings and precautions (5.3), drug interactions (7)]. with known hypersensitivity (e.g., anaphylaxis, angioedema, stevens-johnson syndrome) to paroxetine or any of the inactive ingredients in paxil [see adverse reactions (6.1), (6.2)]. risk summary based on data from published observational studies, exposure to ssris, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see warnings and precautions (5.5) and clinical considerations] . epidemiological studies have shown that infants exposed to paroxetine in the first trimester of pregnancy have an increased risk of congenital malformations, particularly cardiovascular malformations. if paroxetine is used during pregnancy, or if the patient becomes pregnant while taking paroxetine, advise the patient of the potential hazard to the fetus. clinical considerations unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant [see warnings and precautions (5.7)]. for - a study based on swedish national registry data demonstrated that infants exposed to paroxetine during pregnancy (n = 815) had an increased risk of cardiovascular malformations (2% risk in paroxetine-exposed infants) compared to the entire registry population (1% risk), for an odds ratio (or) of 1.8 (95% confidence interval 1.1 to 2.8). no increase in the risk of overall congenital malformations was seen in the paroxetine-exposed infants. the cardiac malformations in the paroxetine-exposed infants were primarily ventricular septal defects (vsds) and atrial septal defects (asds). septal defects range in severity from those that resolve spontaneously to those which require surgery. - a separate retrospective cohort study from the united states (united healthcare data) evaluated 5,956 infants of mothers dispensed antidepressants during the first trimester (n = 815 for paroxetine). this study showed a trend towards an increased risk for cardiovascular malformations for paroxetine (risk of 1.5%) compared to other antidepressants (risk of 1%), for an or of 1.5 (95% confidence interval 0.8 to 2.9). of the 12 paroxetine-exposed infants with cardiovascular malformations, 9 had vsds. this study also suggested an increased risk of overall major congenital malformations including cardiovascular defects for paroxetine (4% risk) compared to other (2% risk) antidepressants (or 1.8; 95% confidence interval 1.2 to 2.8). - two large case-control studies using separate databases, each with >9,000 birth defect cases and >4,000 controls, found that maternal use of paroxetine during the first trimester of pregnancy was associated with a 2- to 3-fold increased risk of right ventricular outflow tract obstructions. in one study the or was 2.5 (95% confidence interval, 1 to 6, 7 exposed infants) and in the other study the or was 3.3 (95% confidence interval, 1.3 to 8.8, 6 exposed infants). other studies have found varying results as to whether there was an increased risk of overall, cardiovascular, or specific congenital malformations. a meta-analysis of epidemiological data over a 16-year period (1992 to 2008) on first trimester paroxetine use in pregnancy and congenital malformations included the above-noted studies in addition to others (n = 17 studies that included overall malformations and n = 14 studies that included cardiovascular malformations; n = 20 distinct studies). while subject to limitations, this meta-analysis suggested an increased occurrence of cardiovascular malformations (prevalence odds ratio [por] 1.5; 95% confidence interval 1.2 to 1.9) and overall malformations (por 1.2; 95% confidence interval 1.1 to 1.4) with paroxetine use during the first trimester. it was not possible in this meta-analysis to determine the extent to which the observed prevalence of cardiovascular malformations might have contributed to that of overall malformations, nor was it possible to determine whether any specific types of cardiovascular malformations might have contributed to the observed prevalence of all cardiovascular malformations. unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant [see warnings and precautions (5.7)]. for women who intend to become pregnant or are in their first trimester of pregnancy, paroxetine should only be initiated after consideration of the other available treatment options [see warnings and precautions (5.4)] . treatment of pregnant women during their third trimester: neonates exposed to ssris or serotonin and norepinephrine reuptake inhibitors (snris), including paxil, 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)] . exposure to ssris in late 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. in a retrospective case-control study of 377 women whose infants were born with pphn and 836 women whose infants were born healthy, the risk for developing pphn was approximately six-fold higher for infants exposed to ssris after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. there have also been postmarketing reports of premature births in pregnant women exposed to paroxetine or other ssris. when treating a pregnant woman with paroxetine during the third trimester, the physician should carefully consider both the potential risks and benefits of treatment. a prospective longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy. the 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 use of paxil in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.5)]. animal findings reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. these doses are approximately 6 (rat) and less than 2 (rabbit) times the maximum recommended human dose (mrhd – 75 mg) on an mg/m2 basis. these studies have revealed no evidence of developmental effects. however, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. this effect occurred at a dose of 1 mg/kg/day which is than the mrhd on an mg/m2 basis. the no‑effect dose for rat pup mortality was not determined. the cause of these deaths is not known. like many other drugs, paroxetine is secreted in human milk. because of the potential for serious adverse reactions in breastfeeding children from paxil, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for paxil and any potential adverse effects on the breastfed child from paxil or from underlying maternal condition. the safety and effectiveness of paxil in pediatric patients have not been established [see box warning] . effectiveness was not demonstrated in three placebo-controlled trials in 752 paxil-treated pediatric patients with mdd.  antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see boxed warning, warnings and precautions (5.1)] . decreased appetite and weight loss have been observed in association with the use of ssris. in placebo-controlled clinical trials conducted with pediatric patients, the following adverse reactions were reported in at least 2% of pediatric patients treated with paxil and occurred at a rate at least twice that for pediatric patients receiving placebo: emotional lability (including self-harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating, hyperkinesia, and agitation. adverse reactions upon discontinuation of treatment with paxil in the pediatric clinical trials that included a taper phase regimen, which occurred in at least 2% of patients and at a rate at least twice that of placebo, were: emotional lability (including suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness, dizziness, nausea, and abdominal pain . in premarketing clinical trials with paxil, 17% of patients treated with paxil (approximately 700) were 65 years of age or older. pharmacokinetic studies revealed a decreased clearance in the elderly, and a lower starting dose is recommended;, however, no overall differences in safety or effectiveness were observed between elderly and younger patients [see dosage and administration (2.4), clinical pharmacology (12.3)] . ssris including paxil, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.7)] . increased plasma concentrations of paroxetine occur in patients with renal and hepatic impairment. the initial dosage of paxil should be reduced in patients with severe renal impairment and in patients with severe hepatic impairment [see dosage and administration (2.4), clinical pharmacology (12.3)] .

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

apotex corp - sirolimus (unii: w36zg6ft64) (sirolimus - unii:w36zg6ft64) - sirolimus oral solution is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. in patients at low-to moderate-immunologic risk , it is recommended that sirolimus oral solution be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see dosage and administration (2.2) ]. in patients at high-immunologic risk (defined as black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [pra; peak pra level > 80%]), it is recommended that sirolimus oral solution be used in combination with cyclosporine and corticosteroids for the first year following transplantation [see dosage and administration (2.3) , clinical studies (14.3) ]. cyclosporine withdrawal has not been studied in patients with banff grade 3 acute rejection or vascular rejection prior to cyclosporine withdraw

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

apotex corp. - icatibant acetate (unii: 325o8467xk) (icatibant - unii:7pg89g35q7) - icatibant injection is indicated for the treatment of acute attacks of hereditary angioedema (hae) in adults 18 years of age and older. none. risk summary available data from published literature and the pharmacovigilance database with icatibant injection use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. in animal reproduction studies, icatibant, administered by the subcutaneous route during the period of organogenesis, did not cause structural abnormalities in rats or rabbits; however, premature birth and abortion were observed in rabbits at doses approximately 0.025 times the maximum recommended human dose (mrhd) and higher. decreased embryofetal survival was observed in rabbits at a subcutaneous dose that was 13 times the mrhd. in a pre- and post-natal development study in rats, delayed parturition was observed at subcutaneous doses 0.5 times the mrhd and higher, which resulted in deaths of dams at doses 2 times the mrhd and higher. fetal death and early pup deaths were observed with doses 2 times the mrhd ( see data ). 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. data animal data in an embryo-fetal development study with rats that received icatibant from gestation days 7 to 18, there was no evidence of any treatment-related structural abnormalities or effects on embryo-fetal survival with maternal doses up to 2.7 times the mrhd (on a mg/m 2 basis with maternal subcutaneous doses up to 25 mg/kg/day). in a fertility and early embryonic development study with rats, icatibant increased pre­implantation loss at a dose that was 7 times the mrhd (on an auc basis at a maternal dose of 10 mg/kg/day). in an embryo-fetal development study with rabbits that received icatibant from gestation days 7 to 18, premature birth and abortion rates increased at doses approximately 0.025 times the mrhd and higher (on a mg/m 2 basis at maternal subcutaneous doses of 0.1 mg/kg and higher). icatibant treatment resulted in dose-related decreases of total implantations and total number of live fetuses as well as dose-related increases of percent pre-implantation loss at a dose that was 13 times the mrhd (on an auc basis with a maternal subcutaneous dose of 10 mg/kg/day). there was no evidence of any treatment-related structural abnormalities with maternal doses up to 13 times the mrhd (on an auc basis with maternal subcutaneous doses up to 10 mg/kg/day). in a pre- and post-natal development study in the rat, dams received icatibant by the subcutaneous route at doses of 1, 3, and 10 mg/kg/day from gestation day 6 to post-partum (ppd) day 20. delayed parturition was observed at doses 0.5 times the mrhd and higher (on an auc basis with maternal subcutaneous doses of 1 mg/kg/day and higher), which resulted in deaths of dams at doses 2 times the mrhd and higher (on an auc basis with maternal subcutaneous doses of 3 mg/kg/day and higher). fetal death and increased pup deaths through ppd 4 were observed with doses 2 times the mrhd (on an auc with a maternal subcutaneous dose of 3 mg/kg/day and higher). impairment of pup righting reflex and decreased pup hair growth were also observed at 7 times the mrhd (on an auc basis with a maternal dose of 10 mg/kg). icatibant and the m2 metabolite were found in maternal milk following subcutaneous administration of icatibant. the no effect dose for f1 pups was identified at a dose 0.5 times the mrhd (on an auc basis with a maternal subcutaneous dose of 1 mg/kg/day). a no effect dose was not identified for f 0 maternal toxicity. risk summary there are no data on the presence of icatibant in human milk, the effects on the breastfed infant, or the effects on milk production. icatibant and the m2 metabolite were found in rat milk following subcutaneous administration of icatibant (  see data  ). when a drug is present in animal milk, it is likely that the drug will be present in human milk. however, systemic absorption of icatibant in infants is not expected after oral exposure through breast milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for icatibant injection and any potential adverse effects on the breastfed child from icatibant injection or from the underlying maternal condition. data animal data icatibant is excreted into the milk of lactating rats at concentrations that sometimes slightly exceeded those measured in the maternal plasma. safety and effectiveness in pediatric patients below the age of 18 years have not been established. juvenile toxicity data subcutaneous daily administration of icatibant to young rats during the juvenile period of development (postnatal days 22-70) delayed the sexual maturation of male reproductive tissues (atrophy of testes and epididymides) at exposures approximating one-third or greater the mrhd on a mg/m 2 basis. impaired fertility and reproductive performance were also observed in male rats at the end of the postnatal treatment period at exposures approximating the mrhd or greater on a mg/m 2 basis. no effects were observed in females at exposures approximating 3-fold the mrhd on a mg/m 2 basis. the observed tissue findings in males were consistent with those seen in sexually mature rats and dogs and are attributed to antagonism of the bradykinin b2 receptor and subsequent effects on gonadotropins. the observed effects may be a consequence of daily icatibant administration. toxicity to the testis did not occur in dogs treated twice a week for 9 months [see carcinogenesis, mutagenesis, impairment of fertility (13.1) ] . clinical studies of icatibant injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. elderly patients are likely to have increased systemic exposure to icatibant injection compared to younger (18-45 years) patients [see clinical pharmacology (12.3) ] . since other reported clinical experience has not identified differences in efficacy and safety between elderly and younger patients, no dose adjustment is recommended. icatibant injection was studied in patients with mild to moderate (child pugh scores of 5 to 8) hepatic impairment. no change in systemic exposure is noted in these patient populations. no dose adjustment is required in patients with hepatic impairment [see clinical pharmacology (12.3) ] . although a formal renal impairment study has not been conducted, 10 of 37 patients treated with icatibant injection had hepatorenal syndrome with glomerular filtration rate (gfr) below 60 ml/min. icatibant injection is cleared non-renally and hence it is not expected to show any change in systemic exposure in patients with impaired renal function. no dose adjustment is required in patients with renal impairment [see clinical pharmacology (12.3) ] . icatibant (eye-kat-i-bant) injection, for subcutaneous use step 1. preparing your dose of icatibant injection - wash your hands with soap and water. - you will need the following supplies: your icatibant injection carton that includes 1 single-dose icatibant injection prefilled syringe and 1 needle. 1 alcohol wipe the medicine inside your icatibant injection prefilled syringe should be clear and colorless. do not use your icatibant injection prefilled syringe if the solution contains particles, is cloudy, or has an unusual color. - your icatibant injection carton that includes 1 single-dose icatibant injection prefilled syringe and 1 needle. - 1 alcohol wipe - the medicine inside your icatibant injection prefilled syringe should be clear and colorless. do not use your icatibant injection prefilled syringe if the solution contains particles, is cloudy, or has an unusual color. figure a                                                                             step 2. remove the prefilled syringe and needle from the carton. see figure b . figure b                                                                             step 3. remove the seal from the needle cap (the needle should remain inside the protective needle cap until ready to use). see figure c . figure c                                                                            step 4. remove the protective cap from the end of the pre-filled syringe by unscrewing the cap. hold the syringe firmly . carefully attach the needle to the prefilled syringe containing the colorless icatibant injection solution. see figure d . figure d                                                                           step 5. firmly screw the needle on the prefilled syringe. be careful not to remove the needle from the needle cap. see figure e . figure e                                                                        preparing the injection site step 6. choose the injection site. the injection site should be a fold of skin on your stomach, about 2 to 4 inches (5 to 10 cm) below your belly button on either side. see figure f . the area you choose for injection should be at least 2 inches (5 cm) away from any scars. do not choose an area that is bruised, swollen, or painful. figure f                                                                          step 7. clean your icatibant injection site with an alcohol wipe and allow it to dry. see figure g . figure g                                                                           injecting your icatibant injection step 8. remove the needle from the needle cap by holding the needle cap and carefully pulling the syringe . do not pull up on the plunger. see figure h . figure h                                                                               step 9. hold the icatibant injection prefilled syringe in 1 hand, between your fingers and thumb. see figure i . figure i                                                                             step 10. use your other hand to gently pinch the fold of skin you cleaned with the alcohol wipe between your thumb and fingers for your injection. see figure j . figure j                                                                            step 11. hold the syringe between a 45-to-90 degree angle to your skin with the needle facing the fold of skin you are holding. see figure k . figure k                                                                             step 12. hold the fold of skin. bring the syringe to the skin and quickly insert the needle into the skin fold. see figure l . figure l                                                                               step 13. push the plunger, at the top of the syringe, for at least 30 seconds until no icatibant injection is in the syringe. see figure m . figure m                                                                         step 14. release the skin fold and gently pull the needle out. see figure n . figure n                                                                           disposal of your used icatibant injection prefilled syringe step 15. place your used icatibant injection syringe, with the needle attached, in an fda-cleared sharps disposal container right away after use. do not throw away (dispose of) loose needles and syringes in your household trash. if you do not have an fda-cleared sharps disposal container, you may use a household container that is: - made of a heavy-duty plastic, - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use, - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and syringes. for more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the fda's website at: http://www.fda.gov/safesharpsdisposal . do not dispose of your sharps disposal container in your household trash unless your community guidelines permit this. do not recycle your used sharps disposal container. figure o                                                                          manufactured by: nang kuang pharmaceutical co., ltd. no.1001, zhongshan rd., xinhua dist., tainan city 71243, taiwan distributed by: apotex corp. weston, florida 33326 this patient information and instructions for use have been approved by the u.s. food and drug administration. revised: february 2024 issued: 022924-02 2620000000u595

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

apotex corp. - emtricitabine (unii: g70b4etf4s) (emtricitabine - unii:g70b4etf4s), tenofovir disoproxil fumarate (unii: ott9j7900i) (tenofovir anhydrous - unii:w4hfe001u5) - emtricitabine and tenofovir disoproxil fumarate tablets, are indicated in combination with other antiretroviral agents for the treatment of hiv-1 infection in adults and pediatric patients weighing at least 17 kg [see clinical studies (14)]. emtricitabine and tenofovir disoproxil fumarate tablets are indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (prep) to reduce the risk of sexually acquired hiv-1 infection. individuals must have a negative hiv-1 test immediately prior to initiating emtricitabine and tenofovir disoproxil fumarate tablets for hiv-1 prep [see dosage and administration (2.2), warnings and precautions (5.2)]. emtricitabine and tenofovir disoproxil fumarate tablets for hiv-1 prep is contraindicated in individuals with unknown or positive hiv-1 status [see warnings and precautions (5.2)]. pregnancy exposure registry   there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to emtricitabine and tenofovir disoproxil

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

apotex corp. - buprenorphine (unii: 40d3scr4gz) (buprenorphine - unii:40d3scr4gz) - buprenorphine transdermal system is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse and misuse with opioids, even at recommended doses, and because of the greater risk of overdose and death with extended-release opioid formulations [see warnings and precautions ( 5.1)] , reserve buprenorphine transdermal system for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - buprenorphine transdermal system is not indicated as an as-needed (prn) analgesic buprenorphine transdermal system is contraindicated in patients with: - significant respiratory depression [see warnings and precautions ( 5.3)] - acute or severe bronchial asthma

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

apotex corp. - ambrisentan (unii: hw6nv07qec) (ambrisentan - unii:hw6nv07qec) - ambrisentan tablets are indicated for the treatment of pulmonary arterial hypertension (pah) (who group 1): - to improve exercise ability and delay clinical worsening. studies establishing effectiveness included predominantly patients with who functional class ii–iii symptoms and etiologies of idiopathic or heritable pah (60%) or pah associated with connective tissue diseases (34%). ambrisentan tablets may cause fetal harm when administered to a pregnant female. ambrisentan tablets are contraindicated in females who are pregnant. ambrisentan was consistently shown to have teratogenic effects when administered to animals. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see warnings and precautions (5.1, 5.2) and use in specific populations (8.1)] . ambrisentan tablets are contraindicated in patients with idiopathic pulmonary fibrosis (ipf), including ipf patients with pulmonary hypertension (who group 3) [see clinical studies (14.4)]. risk summary based on data from animal reproduction studies, ambrisentan may cause fetal harm when administered to a pregnant woman and is contraindicated during pregnancy. there are limited data on ambrisentan use in pregnant women. in animal reproduction studies, ambrisentan was teratogenic in rats and rabbits at doses which resulted in exposures of 3.5 and 1.7 times, respectively, the human dose of 10 mg per day [see animal data] . if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential hazard to a fetus [see contraindications (4.1), warnings and precautions (5.1)]. 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. data animal data ambrisentan was teratogenic at oral dosages of ≥15 mg/kg/day (auc 51.7 h•mcg/ml) in rats and ≥7 mg/kg/day (24.7 h•mcg/ml) in rabbits; it was not studied at lower dosages. these dosages are of 3.5 and 1.7 times, respectively, the human dose of 10 mg per day (14.8 h•mcg/ml) based on auc. in both species, there were abnormalities of the lower jaw and hard and soft palate, malformation of the heart and great vessels, and failure of formation of the thymus and thyroid. a preclinical study in rats has shown decreased survival of newborn pups (mid and high dosages) and effects on testicle size and fertility of pups (high dosage) following maternal treatment with ambrisentan from late gestation through weaning. the mid and high dosages were 51 x, and 170 x (on a mg/m2  body surface area basis) the maximum oral human dose of 10 mg and an average adult body weight of 70 kg. these effects were absent at a maternal dosage 17 x the human dose based on mg/m2 . risk summary it is not known whether ambrisentan is present in human milk. because many drugs are present in human milk and because of the potential for serious adverse reactions in breastfed infants from ambrisentan, a decision should be made whether to discontinue breastfeeding or discontinue ambrisentan tablets, taking into account the importance of the drug to the mother. pregnancy testing female patients of reproductive potential must have a negative pregnancy test prior to initiation of treatment, monthly pregnancy test during treatment, and pregnancy test 1 month after stopping treatment with ambrisentan tablets. advise patients to contact their healthcare provider if they become pregnant or suspect they may be pregnant. perform a pregnancy test if pregnancy is suspected for any reason. for positive pregnancy tests, counsel patient on the potential risk to the fetus and patient options [see boxed warning and dosage and administration (2.2)]. contraception female patients of reproductive potential must use acceptable methods of contraception during treatment with ambrisentan tablets and for 1 month after stopping treatment with ambrisentan tablets. patients may choose one highly effective form of contraception (intrauterine device (iud), contraceptive implant, or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods). if a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method. counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling [see boxed warning]. infertility   males in a 6-month study of another endothelin receptor antagonist, bosentan, 25 male patients with who functional class iii and iv pah and normal baseline sperm count were evaluated for effects on testicular function. there was a decline in sperm count of at least 50% in 25% of the patients after 3 or 6 months of treatment with bosentan. one patient developed marked oligospermia at 3 months, and the sperm count remained low with 2 follow-up measurements over the subsequent 6 weeks. bosentan was discontinued and after 2 months the sperm count had returned to baseline levels. in 22 patients who completed 6 months of treatment, sperm count remained within the normal range and no changes in sperm morphology, sperm motility, or hormone levels were observed. based on these findings and preclinical data [see nonclinical toxicology (13.1)] from endothelin receptor antagonists, it cannot be excluded that endothelin receptor antagonists such as ambrisentan have an adverse effect on spermatogenesis. counsel patients about the potential effects on fertility [see warnings and precautions (5.5)]. safety and effectiveness of ambrisentan tablets in pediatric patients have not been established.   juvenile animal data   in juvenile rats administered ambrisentan orally once daily during postnatal day 7 to 26, 36, or 62, a decrease in brain weight (−3% to −8%) with no morphologic or neurobehavioral changes occurred after breathing sounds, apnea, and hypoxia were observed, at exposures approximately 1.8 to 7.0 times human pediatric exposures at 10 mg, based on auc. in the two placebo-controlled clinical studies of ambrisentan tablets, 21% of patients were ≥65 years old and 5% were ≥75 years old. the elderly (age ≥65 years) showed less improvement in walk distances with ambrisentan tablets than younger patients did, but the results of such subgroup analyses must be interpreted cautiously. peripheral edema was more common in the elderly than in younger patients. the impact of renal impairment on the pharmacokinetics of ambrisentan has been examined using a population pharmacokinetic approach in pah patients with creatinine clearances ranging between 20 and 150 ml/min. there was no significant impact of mild or moderate renal impairment on exposure to ambrisentan [see clinical pharmacology (12.3)] . dose adjustment of ambrisentan tablets in patients with mild or moderate renal impairment is therefore not required. there is no information on the exposure to ambrisentan in patients with severe renal impairment. the impact of hemodialysis on the disposition of ambrisentan has not been investigated. pre-existing hepatic impairment the influence of pre-existing hepatic impairment on the pharmacokinetics of ambrisentan has not been evaluated. because there is in vitro and in vivo evidence of significant metabolic and biliary contribution to the elimination of ambrisentan, hepatic impairment might be expected to have significant effects on the pharmacokinetics of ambrisentan [see clinical pharmacology (12.3)] . ambrisentan is not recommended in patients with moderate or severe hepatic impairment. there is no information on the use of ambrisentan in patients with mild pre-existing impaired liver function; however, exposure to ambrisentan may be increased in these patients. elevation of liver transaminases other endothelin receptor antagonists (eras) have been associated with aminotransferase (ast, alt) elevations, hepatotoxicity, and cases of liver failure [see adverse reactions (6.1, 6.2)]. in patients who develop hepatic impairment after ambrisentan tablets initiation, the cause of liver injury should be fully investigated. discontinue ambrisentan tablets if elevations of liver aminotransferases are >5 × uln or if elevations are accompanied by bilirubin >2 × uln, or by signs or symptoms of liver dysfunction and other causes are excluded.

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

apotex corp - varenicline tartrate (unii: 82269asb48) (varenicline - unii:w6hs99o8zo) - varenicline tablets are indicated for use as an aid to smoking cessation treatment. varenicline tablets are contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to varenicline.   risk summary   available data have not suggested an increased risk for major birth defects following exposure to varenicline in pregnancy, compared with women who smoke [see data]. smoking during pregnancy is associated with maternal, fetal, and neonatal risks (see clinical considerations). in animal studies, varenicline did not result in major malformations but caused decreased fetal weights in rabbits when dosed during organogenesis at exposures equivalent to 50 times the exposure at the maximum recommended human dose (mrhd). additionally, administration of varenicline to pregnant rats during organogenesis through lactation produced developmental toxicity in offspring at maternal exposures equivalent to 36 times human exposure at the mrhd [see data] . the estimated background risk of oral clefts is increased by approximately 30% in infants of women who smoke during pregnancy, compared to pregnant women who do not smoke. the background risk of other major birth defects and miscarriage for the indicated population are unknown. in the us 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 smoking during pregnancy causes increased risks of orofacial clefts, premature rupture of membranes, placenta previa, placental abruption, ectopic pregnancy, fetal growth restriction and low birth weight, stillbirth, preterm delivery and shortened gestation, neonatal death, sudden infant death syndrome and reduction of lung function in infants. it is not known whether quitting smoking with varenicline tablets during pregnancy reduces these risks.   data   human data a population-based observational cohort study using the national registers of denmark and sweden compared pregnancy and birth outcomes among women exposed to varenicline (n=335, includes 317 first trimester exposed) with women who smoked during pregnancy (n=78,412) and with non-smoking pregnant women (n=806,438). the prevalence of major malformations, the primary outcome, was similar in all groups, including between smoking and non-smoking groups. the prevalence of adverse perinatal outcomes in the varenicline-exposed cohort was not greater than in the cohort of women who smoked, and differed somewhat between the three cohorts. the prevalences of the primary and secondary outcomes are shown in table 6. table 6. summary of primary and secondary outcomes for three birth cohorts *included only live births in the cohorts. prevalence among first trimester varenicline-exposed pregnancies (11/317 [3.5%]). **there was a lag in death data in denmark, so the cohorts were smaller. the study limitations include the inability to capture malformations in pregnancies that do not result in a live birth, and possible misclassification of outcome and of exposure to varenicline or to smoking.   other small epidemiological studies of pregnant women exposed to varenicline did not identify an association with major malformations, consistent with the danish and swedish observational cohort study. methodological limitations of these studies include small samples and lack of adequate controls.   overall, available studies cannot definitely establish or exclude any varenicline-associated risk during pregnancy.   animal data pregnant rats and rabbits received varenicline succinate during organogenesis at oral doses up to 15 and 30 mg/kg/day, respectively. while no fetal structural abnormalities occurred in either species, maternal toxicity, characterized by reduced body weight gain, and reduced fetal weights occurred in rabbits at the highest dose (exposures 50 times the human exposure at the mrhd of 1 mg twice daily based on auc). fetal weight reduction did not occur in rabbits at exposures 23 times the human exposure at the mrhd based on auc.   in a pre- and postnatal development study, pregnant rats received up to 15 mg/kg/day of oral varenicline succinate from organogenesis through lactation. maternal toxicity, characterized by a decrease in body weight gain was observed at 15 mg/kg/day (36 times the human exposure at the mrhd based on auc). however, decreased fertility and increased auditory startle response occurred in offspring at the highest maternal dose of 15 mg/kg/day. risk summary   there are no data on the presence of varenicline in human milk, the effects on the breastfed infant, or the effects on milk production. in animal studies varenicline was present in milk of  lactating rats [see data]. however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. the lack of clinical data during lactation precludes a clear determination of the risk of varenicline tablets to an infant during lactation; however the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for varenicline tablets and any potential adverse effects on the breastfed child from varenicline tablets or from the underlying maternal condition.   clinical considerations   because there are no data on the presence of varenicline in human milk and the effects on the breastfed infant, breastfeeding women should monitor their infant for seizures and excessive vomiting, which are adverse reactions that have occurred in adults that may be clinically relevant in breastfeeding infants.   data   in a pre- and postnatal development study, pregnant rats received up to 15 mg/kg/day of oral varenicline succinate through gestation and lactation. mean serum concentrations of varenicline in the nursing pups were 5 to 22% of maternal serum concentrations. varenicline tablets are not recommended for use in pediatric patients 16 years of age or younger because its efficacy in this population was not demonstrated. single and multiple-dose pharmacokinetics of varenicline have been investigated in pediatric patients aged 12 to 17 years old (inclusive) and were approximately dose-proportional over the 0.5 mg to 2 mg daily dose range studied. steady-state systemic exposure in adolescent patients of bodyweight >55 kg, as assessed by auc (0-24), was comparable to that noted for the same doses in the adult population. when 0.5 mg bid was given, steady-state daily exposure of varenicline was, on average, higher (by approximately 40%) in adolescent patients with bodyweight ≤ 55 kg compared to that noted in the adult population.  the efficacy and safety of varenicline was evaluated in a randomized, double-blind, placebo-controlled study of 312 patients aged 12 to 19 years, who smoked an average of at least 5 cigarettes per day during the 30 days prior to recruitment, had a score of at least 4 on the fagerstrom test for nicotine dependence scale, and at least one previous failed quit attempt. patients were stratified by age (12 to 16 years of age, n = 216 and 17 to 19 years of age, n = 96) and by body weight (≤55 kg and >55 kg). patients were randomized to one of two doses of varenicline, adjusted by weight to provide plasma levels in the efficacious range (based on adult studies) and placebo. patients received treatment for 12 weeks, followed by a non-treatment period of 40 weeks, along with age-appropriate counseling throughout the study. results from this study showed that varenicline, at either dose studied, did not improve continuous abstinence rates at weeks 9 through 12 of treatment compared with placebo in subjects 12 to 19 years of age. the varenicline safety profile in this study was consistent with that observed in adult studies. a combined single- and multiple-dose pharmacokinetic study demonstrated that the pharmacokinetics of 1 mg varenicline given once daily or twice daily to 16 healthy elderly male and female smokers (aged 65 to 75 yrs) for 7 consecutive days was similar to that of younger subjects. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.   varenicline is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see dosage and administration (2.2)].     no dosage adjustment is recommended for elderly patients. varenicline is substantially eliminated by renal glomerular filtration along with active tubular secretion. dose reduction is not required in patients with mild to moderate renal impairment. for patients with severe renal impairment (estimated creatinine clearance <30 ml/min), and for patients with end-stage renal disease undergoing hemodialysis, dosage adjustment is needed [see dosage and administration (2.2). clinical pharmacology (12.3)]. varenicline is not a controlled substance. humans   fewer than 1 out of 1,000 patients reported euphoria in clinical trials with varenicline tablets. at higher doses (greater than 2 mg), varenicline tablets produced more frequent reports of gastrointestinal disturbances such as nausea and vomiting. there is no evidence of dose-escalation to maintain therapeutic effects in clinical studies, which suggests that tolerance does not develop. abrupt discontinuation of varenicline tablets was associated with an increase in irritability and sleep disturbances in up to 3% of patients. this suggests that, in some patients, varenicline may produce mild physical dependence which is not associated with addiction.   in a human laboratory abuse liability study, a single oral dose of 1 mg varenicline did not produce any significant positive or negative subjective responses in smokers. in non-smokers, 1 mg varenicline produced an increase in some positive subjective effects, but this was accompanied by an increase in negative adverse effects, especially nausea. a single oral dose of 3 mg varenicline uniformly produced unpleasant subjective responses in both smokers and non-smokers.   animals   studies in rodents have shown that varenicline produces behavioral responses similar to those produced by nicotine. in rats trained to discriminate nicotine from saline, varenicline produced full generalization to the nicotine cue. in self-administration studies, the degree to which varenicline substitutes for nicotine is dependent upon the requirement of the task. rats trained to self-administer nicotine under easy conditions continued to self-administer varenicline to a degree comparable to that of nicotine; however in a more demanding task, rats self-administered varenicline to a lesser extent than nicotine. varenicline pretreatment also reduced nicotine self-administration.

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

apotex corp. - vilazodone hydrochloride (unii: u8htx2gk8j) (vilazodone - unii:s239o2oov3) - vilazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (mdd) in adults [see clinical studies (14)]. vilazodone hydrochloride tablets are contraindicated in: - patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (maois), including maois such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see warnings and precautions (5.2), drug interactions (7)] . 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 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants. risk summary based on data from published observational studies, exposure to ssris, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see warnings and precautions (5.3) and clinical considerations]. there are no adequate and well-controlled studies of vilazodone hydrochloride in pregnant women. the background risk of major birth defects and miscarriage for the indicated population is unknown. however, the background risk in the u.s. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. in animal reproduction studies, oral administration of vilazodone during the period of organogenesis at doses up to 48 and 17 times the maximum recommended human dose (mrhd) in rats and rabbits, respectively, resulted in decreased fetal body weight gain and delayed skeletal ossification but no teratogenic effects were observed. decreased fetal body weight and delayed skeletal ossification were not observed at doses up to 10 and 4 times the mrhd in rats and rabbits, respectively [see data] . clinical considerations disease-associated maternal and/or embryo/fetal risk a prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. the women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of vilazodone hydrochloride in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.3)]. fetal/neonatal adverse reactions exposure to ssris and snris, including vilazodone hydrochloride, in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (pphn). monitor neonates who were exposed to vilazodone hydrochloride in the third trimester of pregnancy for pphn and drug discontinuation syndrome [ see data)]. data human data third trimester exposure neonates exposed to ssris or snris late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. these findings are based on post-marketing reports. 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. in some cases, the clinical picture was consistent with serotonin syndrome [ see warnings and precautions (5.2)]. exposure during late pregnancy to ssris may have an increased risk for persistent pulmonary hypertension of the newborn (pphn). pphn occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. in a retrospective case-control study of 377 women whose infants were born with pphn and 836 women whose infants were born healthy, the risk for developing pphn was approximately six-fold higher for infants exposed to ssris after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. a study of 831,324 infants born in sweden in 1997 to 2005 found a pphn risk ratio of 2.4 (95% ci 1.2 to 4.3) associated with patient-reported maternal use of ssris "in early pregnancy" and a pphn risk ratio of 3.6 (95% ci 1.2 to 8.3) associated with a combination of patient-reported maternal use of ssris "in early pregnancy" and an antenatal ssri prescription "in later pregnancy." animal data 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. 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. risk summary there are no data on the presence of vilazodone in human milk, the effects of vilazodone on the breastfed infant, or the effects of the drug on milk production. however, vilazodone is excreted in rat milk [see data] . the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for vilazodone hydrochloride and any potential adverse effects on the breastfed child from vilazodone hydrochloride or from the underlying maternal condition. data animal data administration of vilazodone to lactating rats at an oral dose of 30 times the maximum recommended human dose (mrhd), resulted in early postnatal pup mortality, and among surviving pups there was decreased body weight and delayed maturation. the safety and effectiveness of vilazodone hydrochloride have not been established in pediatric patients for the treatment of mdd. efficacy was not demonstrated in two adequate and well controlled, 8-week studies including a total of 1,002 pediatric patients ages 7 years to 17 years of age with mdd. the following adverse reactions were reported in at least 5% of pediatric patients treated with vilazodone hydrochloride and occurred at a rate at least twice that for pediatric patients receiving placebo: nausea, vomiting, diarrhea, abdominal pain/discomfort, and dizziness. antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see boxed warning, warnings and precautions (5.1) , and adverse reactions (6.2)]. juvenile animal toxicity data in a juvenile animal study, male and female rats were treated with vilazodone (10, 50, and 200  mg/kg/day) starting on postnatal day (pnd) 21 through 90. a delay in the age of attainment of vaginal patency (i.e. sexual maturation) was observed in females starting at 50 mg/kg/day with a no observed adverse effect level (noael) of 10 mg/kg/day. this noael was associated with auc levels similar to those measured at a maximum dose tested in pediatrics (30 mg). adverse behavioral effects (lack of habituation in an acoustic startle test) were observed in males at 200 mg/kg and females starting at 50 mg/kg both during drug treatment and the recovery periods. the noael for this finding was 50 mg/kg for males and 10 mg/kg for females, which was associated with auc levels greater than (males) or similar (females), to those observed with the maximum dose tested in pediatric patients. an 8% decrease in femur mineral density was observed in female rats at 200 mg/kg, compared to the control group. the noael for this finding was 50 mg/kg, which was associated with an auc level greater than those measured at the maximum dose tested in pediatrics. based on a pharmacokinetic study, no dosage adjustment of vilazodone hydrochloride is recommended on the basis of age (see figure 3). results from pharmacokinetic study of a single 20 mg vilazodone hydrochloride dose in geriatric subjects (> 65 years-old) vs. younger subjects (24 to 55 years-old) demonstrated that the pharmacokinetics were generally similar between the two age groups [see clinical pharmacology (12.3)]. clinical studies of vilazodone hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. of the 3,007 patients in clinical studies with vilazodone hydrochloride, 65 (2.2%) were 65 years of age or older, and 378 (12.6%) were 55 to 64 years of age. in general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. serotonergic antidepressants have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.8)] . no other differences in adverse reactions were observed between geriatric and younger patients. no dosage adjustment of vilazodone hydrochloride is necessary on the basis of gender, renal function (mild to severe renal impairment, glomerular filtration rate: 15 to 90 ml/minute), or hepatic function (mild to severe hepatic impairment, child-pugh score: 5 to 15 [see clinical pharmacology (12.3)] . vilazodone hydrochloride is not a controlled substance. vilazodone hydrochloride has been systematically studied in animals and did not demonstrate abuse or dependence potential. while vilazodone hydrochloride 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.