United States - English - NLM (National Library of Medicine)

solco healthcare us,llc - methylphenidate hydrochloride (unii: 4b3sc438hi) (methylphenidate - unii:207zz9qz49) - methylphenidate hydrochloride tablets are indicated for the treatment of: pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adhd medications, including methylphenidate hydrochloride tablets, during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for adhd medications at 1-866-961-2388 or visit https://womensmentalhealth.org/adhd-medications/. risk summary published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. there may be risks to the fetus associated with the use of cns stimulants use during pregnancy (see clinical considerations) . no effects on morphological development were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits during organogenesis at doses up to 10 an

United States - English - NLM (National Library of Medicine)

ncs healthcare of ky, llc dba vangard labs - paroxetine hydrochloride (unii: x2els050d8) (paroxetine - unii:41vrh5220h) - paroxetine 20 mg - major depressive disorder: paroxetine tablets are indicated for the treatment of major depressive disorder. the efficacy of paroxetine tablets in the treatment of a major depressive episode was established in 6-week controlled trials of outpatients whose diagnoses corresponded most closely to the dsm-iii category of major depressive disorder (see clinical pharmacology: clinical trials). a major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation. the effects of paroxetine tablets in hospitalized depressed patients have not been adequately studied.

Malaysia - English - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

a. menarini singapore pte. ltd. - solcoseryl,dried,protein-free,biologica* -

Malaysia - English - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

a. menarini singapore pte. ltd. - solcoseryl,dried,protein-free,biologica* -

Malaysia - English - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

a. menarini singapore pte. ltd. - solcoseryl 120 concentrate -

United States - English - NLM (National Library of Medicine)

solco healthcare us, llc - escitalopram oxalate (unii: 5u85dbw7lo) (escitalopram - unii:4o4s742any) - escitalopram 5 mg - escitalopram is indicated for the treatment of: additional pediatric use information is approved for abbvie inc.’s lexapro (escitalopram) tablets and lexapro (escitalopram) oral solution. however, due to abbvie inc.’s marketing exclusivity rights, this drug product is not labeled with that information. escitalopram tablets are contraindicated in patients: 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 (5.7) and clinical considerations]. available data from published epidemiologic studies and postmarketing reports have not established an increased risk of major birth defects or miscarriage. there are risks of persistent pulmonary hypertension of the newborn (pphn) (see data) and poor neonatal adaptation (see clinical considerations) with exposure to selective serotonin reuptake inhibitors (ssris), including escitalopram, during pregnancy. there are risks associated with untreated depression in pregnancy (see clinical considerations). in animal reproduction studies, both escitalopram and racemic citalopram have been shown to have adverse effects on embryo/fetal and postnatal development, including fetal structural abnormalities, when administered at doses greater than human therapeutic doses (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 the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal risk and/or embryo/fetal risk women who discontinue antidepressants are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective longitudinal study of 201 pregnant women with a history of major depression, who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of escitalopram in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.7)] . fetal/neonatal adverse reactions neonates exposed to ssris or snris, including escitalopram, late in 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)] . data human data exposure to ssris, particularly later in pregnancy, may increase the risk for pphn. pphn occurs in 1-2 per 1000 live births in the general populations and is associated with substantial neonatal morbidity and mortality. animal data in a rat embryo/fetal development study, oral administration of escitalopram (56, 112, or 150 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased fetal body weight and associated delays in ossification at the two higher doses [approximately ≥ 55 times the maximum recommended human dose (mrhd) of 20 mg/day on a mg/m2 basis]. maternal toxicity (clinical signs and decreased body weight gain and food consumption), mild at 56 mg/kg/day, was present at all dose levels. the developmental no-effect dose of 56 mg/kg/day is approximately 27 times the mrhd of 20 mg on a mg/m2 basis. no malformations were observed at any of the doses tested (as high as 73 times the mrhd on a mg/m2 basis). when female rats were treated with escitalopram (6, 12, 24, or 48 mg/kg/day) during pregnancy and through weaning, slightly increased offspring mortality and growth retardation were noted at 48 mg/kg/day which is approximately 23 times the mrhd of 20 mg on a mg/m2 basis. slight maternal toxicity (clinical signs and decreased body weight gain and food consumption) was seen at this dose. slightly increased offspring mortality was also seen at 24 mg/kg/day. the no-effect dose was 12 mg/kg/day which is approximately 6 times the mrhd of 20 mg on a mg/m2 basis. in two rat embryo/fetal development studies, oral administration of racemic citalopram (32, 56, or 112 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased embryo/fetal growth and survival and an increased incidence of fetal abnormalities (including cardiovascular and skeletal defects) at the high dose, which is approximately 18 times the mrhd of 60 mg/day on a mg/m2 basis. this dose was also associated with maternal toxicity (clinical signs, decreased body weight gain). the developmental no-effect dose was 56 mg/kg/day is approximately 9 times the mrhd on a mg/m2 basis. in a rabbit study, no adverse effects on embryo/fetal development were observed at doses of racemic citalopram of up to 16 mg/kg/day, or approximately 5 times the mrhd on a mg/m2 basis. thus, developmental effects of racemic citalopram were observed at a maternally toxic dose in the rat and were not observed in the rabbit. when female rats were treated with racemic citalopram (4.8, 12.8, or 32 mg/kg/day) from late gestation through weaning, increased offspring mortality during the first 4 days after birth and persistent offspring growth retardation were observed at the highest dose, which is approximately 5 times the mrhd of 60 mg on a mg/m2 basis. the no-effect dose was 12.8 mg/kg/day is approximately 2 times the mrhd on a mg/m 2 basis. similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, approximately 4 times the mrhd on a mg/m2 basis. a no-effect dose was not determined in that study. risk summary data from the published literature report the presence of escitalopram and desmethylescitalopram in human milk (see data ). there are reports of excessive sedation, restlessness, agitation, poor feeding and poor weight gain in infants exposed to escitalopram, through breast milk (see clinical considerations ). there are no data on the effects of escitalopram or its metabolites on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for escitalopram and any potential adverse effects on the breastfed child from escitalopram or from the underlying maternal condition. clinical considerations infants exposed to escitalopram should be monitored for excess sedation, restlessness, agitation, poor feeding and poor weight gain. data a study of 8 nursing mothers on escitalopram with daily doses of 10-20 mg/day showed that exclusively breast-fed infants receive approximately 3.9% of the maternal weight-adjusted dose of escitalopram and 1.7% of the maternal weight-adjusted dose of desmethylcitalopram. major depressive disorder the safety and effectiveness of escitalopram for the treatment of major depressive disorder have been established in pediatric patients 12 years of age and older. use of escitalopram for this indication is supported by evidence from adequate and well-controlled studies in adults with additional evidence from an 8-week, flexible-dose, placebo-controlled study that compared escitalopram 10 mg to 20 mg once daily to placebo in pediatric patients 12 to 17 years of age with major depressive disorder [see clinical studies (14.1)] . the safety of escitalopram was similar to adult patients with mdd [see adverse reactions (6.1)] . the safety and effectiveness of escitalopram for the treatment of major depressive disorder have not been established in pediatric patients younger than 12 years of age. in a 24-week, open- label safety study in 118 pediatric patients aged 7 to 11 years who had major depressive disorder, the safety findings were consistent with the known safety and tolerability profile for escitalopram. generalized anxiety disorder the safety and effectiveness of escitalopram for the treatment of generalized anxiety disorder have not been established in pediatric patients younger than 7 years of age. antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see warnings and precautions (5.1)] . decreased appetite and weight loss have been observed in association with the use of ssris. consequently, regular monitoring of weight and growth should be performed in children and adolescents treated with an ssri such as escitalopram. juvenile animal toxicity data in a juvenile animal study, male and female rats were administered escitalopram at 5, 40, or 80 mg/kg/day by oral gavage from postnatal day (pnd) 21 to pnd 69. a delay in sexual maturation was observed in both males and females at ≥ 40 mg/kg/day with a no observed adverse effect level (noael) of 5 mg/kg/day. this noael was associated with plasma auc levels less than those measured at the maximum recommended dose (mrhd) in pediatrics (20 mg). however, there was no effect on reproductive function. increased motor activity (both ambulatory and fine movements) was observed in females prior to daily dosing at ≥ 40 mg/kg/day (3.5 times the mrhd based on auc levels). a reversible disruption of learning and memory function was observed in males at 80 mg/kg/day with a noael of 40 mg/kg/day, which was associated with an auc level 3.5 times those measured at the mrhd in pediatrics. there was no effect on learning and memory function in treated female rats. additional pediatric use information is approved for abbvie inc.’s lexapro (escitalopram) tablets and lexapro (escitalopram) oral solution. however, due to abbvie inc.’s marketing exclusivity rights, this drug product is not labeled with that information. approximately 69 patients (6%) of the 1,144 patients receiving escitalopram in controlled trials of escitalopram in major depressive disorder and gad were 60 years of age or older [see clinical studies (14.1, 14.2)] . the number of elderly patients in these trials was insufficient to adequately assess for possible differential efficacy and safety measures on the basis of age. nevertheless, greater sensitivity of some elderly individuals to effects of escitalopram cannot be ruled out. in two pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in subjects 65 years and older as compared to young subjects and cmax was unchanged [see clinical pharmacology (12.3)] . the recommended dosage of escitalopram for elderly patients is 10 mg daily [see dosage and administration (2.5)] . ssris, including escitalopram, 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 (5.6)] . of 4,422 patients in clinical studies of racemic citalopram, 1,357 were 60 and over, 1,034 were 65 and over, and 457 were 75 and over. 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 geriatric and younger patients, but again, greater sensitivity of some elderly individuals cannot be ruled out. increased citalopram exposure occurs in patients with hepatic impairment [see clinical pharmacology (12.3)] . the recommended dosage of escitalopram in patients with hepatic impairment is 10 mg daily [see dosage and administration (2.5)] . pharmacokinetics of escitalopram in patients with a creatinine clearance less than 20 ml/minute has not been evaluated. no dosage adjustment is necessary for patients with mild or moderate renal impairment [see dosage and administration (2.5), clinical pharmacology (12.3)] . physical and psychological dependence animal studies suggest that the abuse liability of racemic citalopram is low. escitalopram has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. the premarketing clinical experience with escitalopram did not reveal any drug-seeking behavior. however, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a cns-active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate escitalopram patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).

United States - English - NLM (National Library of Medicine)

solco healthcare us, llc - nebivolol (unii: 030y90569u) (nebivolol - unii:030y90569u) - nebivolol tablets are indicated for the treatment of hypertension, to lower blood pressure [see clinical studies ( 14.1)]. nebivolol tablets may be used alone or in combination with other antihypertensive agents [see drug interactions ( 7)]. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including the class to which this drug principally belongs. there are no controlled trials demonstrating risk reduction with nebivolol tablets. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. nebivolol tablets are contraindicated in the following conditions: risk summary available data regarding use of nebivolol tablets in pregnant women are insufficient to determine whether there are drug-associated risks of adverse developmental outcomes. there are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy. the use of beta blockers during the third trimester of pregnancy may increase the risk of hypotension, bradycardia, hypoglycemia, and respiratory depression in the neonate [see clinical considerations]. oral administration of nebivolol to pregnant rats during organogenesis resulted in embryofetal and perinatal lethality at doses approximately equivalent to the maximum recommended human dose (mrhd). the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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. clinical considerations disease-associated maternal and/or embryo/fetal risk hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. fetal/neonatal adverse reactions neonates of women with hypertension, who are treated with beta-blockers during the third trimester of pregnancy, may be at increased risk for hypotension, bradycardia, hypoglycemia, and respiratory depression. observe newborns for symptoms of hypotension, bradycardia, hypoglycemia and respiratory depression and manage accordingly. data animal data nebivolol was shown to increase embryo-fetal and perinatal lethality in rats at approximately 1.2 times the mrhd or 40 mg/day on a mg/m2 basis. decreased pup body weights occurred at 1.25 and 2.5 mg/kg in rats, when exposed during the perinatal period (late gestation, parturition and lactation). at 5 mg/kg and higher doses (1.2 times the mrhd), prolonged gestation, dystocia and reduced maternal care were produced with corresponding increases in late fetal deaths and stillbirths and decreased birth weight, live litter size and pup survival. these events occurred only when nebivolol was given during the perinatal period (late gestation, parturition and lactation). insufficient numbers of pups survived at 5 mg/kg to evaluate the offspring for reproductive performance. in studies in which pregnant rats were given nebivolol during organogenesis, reduced fetal body weights were observed at maternally toxic doses of 20 and 40 mg/kg/day (5 and 10 times the mrhd), and small reversible delays in sternal and thoracic ossification associated with the reduced fetal body weights and a small increase in resorption occurred at 40 mg/kg/day (10 times the mrhd). no adverse effects on embryo-fetal viability, sex, weight or morphology were observed in studies in which nebivolol was given to pregnant rabbits at doses as high as 20 mg/kg/day (10 times the mrhd). risk summary there is no information regarding the presence of nebivolol in human milk, the effects on the breastfed infant, or the effects on milk production. nebivolol is present in rat milk [see data] . because of the potential for β-blockers to produce serious adverse reactions in nursing infants, especially bradycardia, nebivolol tablets are not recommended during nursing. data in lactating rats, maximum milk levels of unchanged nebivolol were observed at 4 hours after single and repeat doses of 2.5 mg/kg/day. the daily dose (mg/kg body weight) ingested by a rat pup is 0.3% of the dam dose for unchanged nebivolol. safety and effectiveness in pediatric patients have not been established. pediatric studies in ages newborn to 18 years old have not been conducted because of incomplete characterization of developmental toxicity and possible adverse effects on long-term fertility [see nonclinical toxicology (13.1)] . juvenile animal toxicity data daily oral doses of nebivolol to juvenile rats from post-natal day 14 to post-natal day 27 showed sudden unexplained death at exposures equal to those in human poor metabolizers given a single dose of 10 mg. no mortality was seen at half the adult human exposure. in surviving rats, cardiomyopathy was seen at exposures greater than or equal to the human exposure. male rat pups exposed to twice the human exposure showed decreases in total sperm count as well as decreases in the total and percentage of motile sperm. of the 2800 patients in the u.s. sponsored placebo-controlled clinical hypertension studies, 478 patients were 65 years of age or older. no overall differences in efficacy or in the incidence of adverse events were observed between older and younger patients. in a placebo-controlled trial of 2128 patients (1067 nebivolol tablets, 1061 placebo) over 70 years of age with chronic heart failure receiving a maximum dose of 10 mg per day for a median of 20 months, no worsening of heart failure was reported with nebivolol compared to placebo. however, if heart failure worsens consider discontinuation of nebivolol tablets.

United States - English - NLM (National Library of Medicine)

solco healthcare us, llc - dimethyl fumarate (unii: fo2303mni2) (monomethyl fumarate - unii:45iub1px8r) - dimethyl fumarate delayed-release capsules are indicated for the treatment of relapsing forms of multiple sclerosis (ms), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. dimethyl fumarate delayed-release capsules are contraindicated in patients with known hypersensitivity to dimethyl fumarate or to any of the excipients of dimethyl fumarate delayed-release capsules. reactions have included anaphylaxis and angioedema [see warnings and precautions (5.1)]. risk summary there are no adequate data on the developmental risk associated with the use of dimethyl fumarate delayed-release capsules in pregnant women. in animals, adverse effects on offspring survival, growth, sexual maturation, and neurobehavioral function were observed when dimethyl fumarate (dmf) was administered during pregnancy and lactation at clinically relevant doses [see data] . 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. the background risk of major birth defects and miscarriage for the indicated population is unknown. animal data in rats administered dmf orally (25, 100, 250 mg/kg/day) throughout organogenesis, embryofetal toxicity (reduced fetal body weight and delayed ossification) were observed at the highest dose tested. this dose also produced evidence of maternal toxicity (reduced body weight). plasma exposure (auc) for monomethyl fumarate (mmf), the major circulating metabolite, at the no-effect dose is approximately three times that in humans at the recommended human dose (rhd) of 480 mg/day. in rabbits administered dmf orally (25, 75, and 150 mg/kg/day) throughout organogenesis, embryolethality and decreased maternal body weight were observed at the highest dose tested. the plasma auc for mmf at the no-effect dose is approximately 5 times that in humans at the rhd. oral administration of dmf (25, 100, and 250 mg/kg/day) to rats throughout organogenesis and lactation resulted in increased lethality, persistent reductions in body weight, delayed sexual maturation (male and female pups), and reduced testicular weight at the highest dose tested. neurobehavioral impairment was observed at all doses. a no-effect dose for developmental toxicity was not identified. the lowest dose tested was associated with plasma auc for mmf lower than that in humans at the rhd. risk summary there are no data on the presence of dmf or mmf in human milk. the effects on the breastfed infant and on milk production are unknown. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for dimethyl fumarate delayed-release capsules and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. safety and effectiveness in pediatric patients have not been established. clinical studies of dimethyl fumarate delayed-release capsules did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

United States - English - NLM (National Library of Medicine)

solco healthcare us, llc - tranylcypromine sulfate (unii: 7zat6es870) (tranylcypromine - unii:3e3v44j4z9) - tranylcypromine tablets are indicated for the treatment of major depressive disorder (mdd) in adult patients who have not responded adequately to other antidepressants. tranylcypromine tablets are not indicated for the initial treatment of mdd due to the potential for serious adverse reactions and drug interactions, and the need for dietary restrictions [see contraindications (4), warnings and precautions (5), and drug interactions (7)] . concomitant use of tranylcypromine tablets or use in rapid succession with the products in table 1 is contraindicated. such use may cause severe or life-threatening reactions such as hypertensive crises or serotonin syndrome [see drug interactions (7.1)] . medication-free periods between administration of tranylcypromine tablets and contraindicated agents are recommended [see dosage and administration (2.2) and

United States - English - NLM (National Library of Medicine)

solco healthcare us, llc. - roflumilast (unii: 0p6c6zop5u) (roflumilast - unii:0p6c6zop5u) - roflumilast is indicated as a treatment to reduce the risk of copd exacerbations in patients with severe copd associated with chronic bronchitis and a history of exacerbations. limitations of use roflumilast is not a bronchodilator and is not indicated for the relief of acute bronchospasm. the use of roflumilast is contraindicated in the following condition: moderate to severe liver impairment (child-pugh b or c) [see clinical pharmacology (12.3) and use in specific populations (8.6)] . risk summary there are no randomized clinical studies of roflumilast in pregnant women. in animal reproductive toxicity studies, roflumilast administered to pregnant rats and rabbits during the period of organogenesis produced no fetal structural abnormalities. the highest roflumilast dose in these studies was approximately 30 and 26 times, respectively, the maximum recommended human dose (mrhd). roflumilast induced post-implantation loss in rats at doses greater than or equal to approximately 10 times the mrhd. roflumilast in