a) Chronic ingestion may produce hypertension.
b) Hypertension was reported in premature infants following administration of high doses of dexamethasone for treatment of chronic lung disease (Stark et al, 2001).

a) Sterile meningitis, arachnoiditis, or pachymeningitis may occur following intraspinal injection of methylPREDNISolone acetate, which has been associated with the polyethylene glycol content of the preparation (Nelson, 1988).

a) CASE REPORT: A 13-year-old boy experienced headaches, back pain, and blurred vision following fluticasone nasal spray therapy, 50 mcg to each nostril once daily, for treatment of hay fever. Examination showed bilaterally swollen optic discs and a right sixth nerve palsy. Fluorescein angiography showed leakage of dye from optic discs, indicating bilateral papilloedema. The patient's symptoms disappeared following discontinuation of the fluticasone (Bond et al, 2001).

a) Chronic toxicity may produce psychosis. Higher doses over shorter periods of time, as seen with predniSONE and pulse methylPREDNISolone therapies, has produced psychosis and hallucinations (Ayoub et al, 1983; Ayoub et al, 1983a; Ahmad & Rasul, 1999).
b) CASE SERIES: Acute psychotic reactions were noted following mean daily doses of 59.5 mg of predniSONE in hospitalized patients (Anon, 1972).
c) CASE REPORT: A 72-year-old man developed an altered mental status, including disorganized thinking, confusion, agitation, and psychosis followed by dementia, after chronically taking predniSONE, 100 mg/day for 3 months. An MRI showed mild frontal and superior temporal atrophy and a PET scan indicated diffuse cerebral hypometabolism, but other laboratory studies, including serologic and CSF testing, were all within normal limits. Due to the absence of an infectious, inflammatory, or toxic metabolic cause, a preliminary diagnosis of an Alzheimer-type neurodegenerative disease was made. However, tapering of the patient's predniSONE with eventual cessation of therapy resulted in significant improvement in almost all cognitive functions (Sacks & Shulman, 2005).

a) NEONATES: In a study, conducted to determine the influence of postnatal systemic dexamethasone treatment for neonatal chronic lung disease on subsequent brain growth and development in premature infants, it was determined that systemic dexamethasone administration caused a 22% reduction in total cerebral tissue volume as compared with total cerebral tissue volume in infants not treated with dexamethasone. Cerebral cortical gray matter volume was also reduced by 35% in premature infants treated with dexamethasone as compared with infants not treated with dexamethasone. These findings suggest an impairment in brain growth which may subsequently have a deleterious effect on neurodevelopmental outcome following neonatal administration of dexamethasone (Murphy et al, 2001).
b) NEONATES: Barrington (2001) performed a systematic review of randomized controlled trials of the use of corticosteroids in premature neonates. All included studies evaluated neurodevelopmental outcome in these children at least one year of age. The use of corticosteroids was found to increase the incidence of cerebral palsy and neurodevelopmental impairment (Barrington, 2001) .

a) CASE REPORT: A 59-year-old man experienced intractable hiccups following high-dose oral dexamethasone administration (40 mg daily for 4 days per month). The hiccups started 12 hours after the first dose of dexamethasone and continued throughout the cycle until 1 day after his last dose. The hiccups would then completely disappear until the patient's next cycle of dexamethasone. The hiccups resolved when metoclopramide (10 mg orally every 6 hours) was administered concurrently with the dexamethasone (Cersosimo & Brophy, 1998).

a) Spontaneous gastrointestinal perforation, without evidence of necrotizing enterocolitis, was reported in 13% (n=111) of premature infants who received high-dose dexamethasone for treatment of chronic lung disease as compared with 4% (n=109) of premature infants who did not receive dexamethasone (Stark et al, 2001).

a) CASE SERIES/CHRONIC EXPOSURE: Hepatomegaly developed in 5 of 6 infants with Cushing's syndrome and adrenocortical insufficiency after exposure to large amounts of topical corticosteroids (1 to 10 tubes of clobetasol propionate and diflucortolone valerate for 1.5 to 5 months). Three patients also developed hepatosteatosis. All patients were treated with hydrocortisone to prevent glucocorticoid withdrawal syndrome. After 1 to 14 months of follow-up, serum cortisol and ACTH levels of the patients were within normal range. One patient died of disseminated Cytomegalovirus infection. An autopsy revealed macrovesicular fat accumulation in hepatocytes (Guven et al, 2007).

a) Systemic eosinophilia, with some patients showing signs of clinical vasculitis consistent with Churg-Strauss syndrome, have been reported following inhalation therapy with fluticasone (Anon , 1999). The majority of these cases occurred after oral corticosteroid therapy was reduced or discontinued.

a) Chronic toxicity can cause muscle wasting and weakness. Severe cases of acute myopathy from high-dose IV corticosteroid therapy have been described (MacFarlane & Rosenthal, 1977; Van Marle & Woods, 1980; Knox et al, 1986; Williams et al, 1988).
b) Acute myopathy is characterized by involvement of proximal and distal muscles, may involve ocular and respiratory muscles, marked elevation in CPK, and may result in quadriparesis (Prod Info PredniSONE oral solution, tablets, 2009; Prod Info DEXAMETHASONE INTENSOL oral solution, concentrate, 2007).
c) Chronic myopathy involves primarily proximal muscles, with a normal or slightly elevated CPK, and evidence of type IIB fiber atrophy on biopsy (Williams et al, 1988).

a) Compression fractures of the vertebra from osteoporosis and aseptic necrosis of the femoral heads (Prod Info SOLU-MEDROL IV, IM injection, 2010; Prod Info PredniSONE oral solution, tablets, 2009; Prod Info DEXAMETHASONE INTENSOL oral solution, concentrate, 2007).

a) Chronic toxicity involves manifestations of the physiologic effects including Cushingoid appearance, muscle weakness, and osteoporosis.
b) CASE REPORT: Cushing's Syndrome was reported following excessive use of betamethasone nasal drops (130 mL in 10 weeks) (Stevens, 1988). Partial adrenal suppression was described in an 8-year-old girl treated therapeutically with inhaled triamcinolone acetonide (Hollman & Allen, 1988).
c) CASE REPORT: Suppression of plasma cortisol levels by more than 50% following topical ocular corticosteroid therapy and a case of Cushing's syndrome in a 4 year old girl following repeated treatments with dexamethasone ophthalmic drops has been reported (Adler et al, 1982; Busch & Migeon, 1968; Musson & Sloan, 1968).
d) CASE REPORT: Factitious Cushing's syndrome (Cushing's syndrome caused by exogenous glucocorticoid abuse) was reported in a 33-year-old woman following chronic abuse of predniSONE. With continued predniSONE use, the patient subsequently developed pulmonary aspergillosis and died. It is believed that immunosuppression caused by chronic corticosteroid use resulted in the development of a fatal fungal infection (Kansagara et al, 2006).
e) CASE SERIES: Six infants (aged, 3 to 8 months) who were treated with large amounts of topical corticosteroids (1 to 10 tubes of clobetasol propionate or diflucortolone valerate for 1.5 to 5 months) for diaper dermatitis developed Cushing's syndrome and adrenocortical insufficiency. Hepatomegaly and hepatosteatosis were observed in 5 and 3 patients, respectively. All patients were treated with hydrocortisone to prevent glucocorticoid withdrawal syndrome. After 1 to 14 months of follow-up, serum cortisol and ACTH levels of the patients were within the normal range. One patient died of disseminated Cytomegalovirus infection (Guven et al, 2007).

a) CASE REPORT: A 46-year-old woman developed Cushing's syndrome 6 weeks after an accidental overdose administration of 200 mg triamcinolone acetonide (a dose considered to be 2.5 to 5 times higher than usually recommended) (Schweitzer et al, 2000). The patient gradually recovered following administration of mifepristone.

a) Adrenal insufficiency can occur when long-term chronic ingestion is discontinued.
b) CASE SERIES: Four children who were treated with high dose inhaled fluticasone (500 to 1500 micrograms daily) developed adrenal insufficiency and hypoglycemia during periods of intercurrent illness (Drake et al, 2002).
c) CASE SERIES: Six infants (aged, 3 to 8 months) who were treated with large amounts of topical corticosteroids (1 to 10 tubes of clobetasol propionate or diflucortolone valerate for 1.5 to 5 months) for diaper dermatitis developed Cushing's syndrome and adrenocortical insufficiency. Hepatomegaly and hepatosteatosis were observed in 5 and 3 patients, respectively. All patients were treated with hydrocortisone to prevent glucocorticoid withdrawal syndrome. After 1 to 14 months of follow-up, serum cortisol and ACTH levels of the patients were within the normal range. One patient died of disseminated Cytomegalovirus infection (Guven et al, 2007).
d) CASE REPORTS: Two patients developed adrenal insufficiency following long-term administration of topical corticosteroids, applied to large areas of the body including the groin and armpits to treat chronic skin conditions (Bockle et al, 2014).

a) CASE REPORT: A 15-year-old girl ingested 36 mg dexamethasone and 12 diazepam tablets. Three days later she developed fever (39.2 degrees Celsius) followed rapidly by shock (blood pressure 70/50 mmHg, pulse 125/min), confusion, hyponatremia (sodium 130 mmol/L) and hyperkalemia (5.2 mmol/L). Signs and symptoms and laboratory abnormalities resolved rapidly after administration of 80 mg methylPREDNISolone. Blood cortisol and corticotropin studies were not reported (Naumovski et al, 2003).

a) Growth suppression can occur in children (Prod Info SOLU-MEDROL IV, IM injection, 2010; Prod Info PredniSONE oral solution, tablets, 2009; Prod Info DEXAMETHASONE INTENSOL oral solution, concentrate, 2007).

a) Anaphylaxis has been reported after intravenous methylPREDNISolone therapy (Mendelsohn et al, 1974; Freedman et al, 1981; Rao et al, 1982; Pryse-Phillips et al, 1984; McNamara, 1986; Doezema, 1987) even in patients with no history of atopy or asthma (John et al, 1989).
b) CASE SERIES: Similar reactions were described in 29 patients after IV, IM, intra-articular, or soft-tissue hydrocortisone injections (Peller & Bardana, 1985). The succinate esters of hydrocortisone or methylPREDNISolone have been most frequently implicated.

a) CASE REPORT: A 33-year-old woman presented with septic shock, hepatic and renal failure, and hypoxemic respiratory failure. Despite aggressive supportive therapy, the patient died within 12 hours of post-presentation. An autopsy revealed that she had invasive pulmonary aspergillosis. A review of her medical history indicated that she had presented eight months previously with signs and symptoms consistent with Cushing's syndrome. A search of the patient's home following her death revealed multiple bottles of predniSONE (20 mg). It is believed that chronic predniSONE abuse by the patient resulted in immunosuppression leading to the development of a fatal fungal infection (Kansagara et al, 2006).

a) At the time of this review, no data were available to assess the teratogenic potential of this agent. Maternal use is not expected to result in fetal exposure to ciprofloxacin hydrochloride and fluocinolone acetonide, because the combination is negligibly absorbed through otic administration (Prod Info OTOVEL(R) otic solution, 2016).

a) At the time of this review, no data were available to assess the teratogenic potential of this agent (Prod Info DERMASORB(TM) AF COMPLETE KIT topical cream, 2013).

a) At the time of this review, no data were available to access the teratogenic potential of this agent. Tretinoin, a component of this drug, has been linked with embryofetal death, altered fetal growth, congenital malformations, and potential neurologic deficits when administered systemically. Although, human data have not confirmed an increased risk of teratogenic abnormalities with topical administration of tretinoin (Prod Info TRI-LUMA(R) topical cream, 2013).

a) Use of a long-acting beta-2 agonist (LABA) combined with inhaled corticosteroids (ICS) showed no increased risk of congenital malformation when compared with higher doses of ICS monotherapy when used during the first trimester of pregnancy. Overall, major malformations were reported in 7.4% of newborns in both subcohorts within the first year of life. Major congenital malformations were reported in 6.9% of cases treated with a LABA plus low-dose ICS (0 to 250 mcg) versus 7.2% with medium dose (250 to 500 mcg) ICS monotherapy. In severe asthma cases, major congenital malformations were reported in 7.1% of cases treated with a LABA plus medium dose ICS versus 9.6% with high dose ICS (greater than 500 mcg) monotherapy. Cardiac malformations were the most commonly reported malformations. A nonsignificant 20% higher risk of major malformations was reported in women treated with a LABA plus medium dose ICS compared with high-dose ICS monotherapy (Eltonsy et al, 2015).
b) According to a population-based cohort study of 13,280 pregnancies, higher doses of inhaled corticosteroids (ICS) were associated with an increased risk of congenital malformations when used during the first trimester of pregnancy. Among 10,099 pregnant women with asthma treated with beclomethasone dipropionate, budesonide, fluticasone propionate, flunisolide, or triamcinolone acetonide (expressed in beclomethasone dipropionate-chlorfluorocarbone equivalent), congenital malformations associated with ICS use were reported in 9.6% of nonusers, 9% of those using greater than 0 to 1000 mcg/day (average, 186 mcg/day), and 14.3% of those using greater than 1000 mcg/day (average, 1470 mcg/day) during the first trimester; major malformations (generally musculoskeletal and cardiac) were reported in 5.9%, 5.7%, and 9.7%, respectively. Women using doses greater than 1000 mcg/day had a significant 63% increased risk of delivering an infant with a malformation compared with women using 1000 mcg/day or less, while those using 1000 mcg/day or less did not have an increased risk over nonusers. When adjusted for multiple pregnancy and the use of long-acting beta-2 agonist during the first trimester, the increase in risk for congenital malformations in those receiving ICS doses of greater than 1000 mcg/day was a nonsignificant 56%; the increase in risk for major malformations was a non significant 68% (Blais et al, 2009).

a) Immunological incompetence occurred in a neonate born to a 19-year-old mother who had received predniSONE 30 mg daily throughout pregnancy for chronic glomerulonephritis. During the first week of life, lymph nodes in the neonate were not palpable and serum immunoglobulins were low. Thymic shadow could not be seen on x-ray and the infant exhibited moderate lymphopenia. Fewer lymphocytes than normal survived in culture following phytohemagglutinin stimulation, but large blastoid cells were observed. CMV antibody titer on cord blood was 1:32. No specific therapy was administered and cytomegalic virus continued to be isolated from the urine for a period of 1 year. At 1 year, there was almost complete recovery of the immune system with the exception of serum IgA which remained undetectable (Cote et al, 1974).
b) Neonatal pancytopenia with severe combined immunodeficiency occurred in a preterm infant following maternal administration of azathioprine and predniSONE throughout pregnancy (DeWitte et al, 1984).

a) In a study involving 2014 infants whose mothers used inhaled budesonide for asthma in early pregnancy, increased rates of congenital malformations were not observed. The percentage of infants with a congenital malformation (3.8%), following exposure to budesonide in utero, was very similar to the population rate (3.5%) (Kallen et al, 1999).

a) Antenatal administration of betamethasone for prevention of neonatal respiratory distress syndrome did not appear to have any adverse effects on growth or on sensorineural, cognitive, or lung function in children and on up to adulthood (Dessens et al, 2000; Doyle et al, 2000; Whitelaw & Thoresen, 2000).

a) At the time of this review, no data were available to assess the teratogenic potential of this agent (Prod Info Vytone(TM) Cream with aloe topical cream, 2013).

a) A prospective controlled study was conducted to evaluate the safety of corticosteroids during pregnancy and involved 311 pregnant women who were treated with glucocorticosteroids (GCS) during their pregnancies, and 790 women in the control group. The majority of women were treated with corticosteroids during the first trimester of pregnancy only (65.4%), 8.4% were treated during their first and second trimesters, and 26.2% were treated throughout pregnancy. PredniSONE was the prescribed corticosteroid in 70% of the women in the GCS group. The results of the study showed that 12 of 262 live births (4.6%) in the GCS group developed major congenital anomalies (ie, ventricular septal defect, patent ductus arteriosus, hearing impairment, congenital dysplasia of the hip, esophageal atresia, spina bifida, bilateral agenesis of kidneys) as compared with 19 of 728 live births (2.6%) in the control group (nonsignificant 75% increased risk), indicating that there was no significant difference in the rate of major anomalies between the 2 groups (Gur et al, 2004).
b) In two clinical studies investigating the outcome of 101 pregnancies in which women received beclomethasone and/or predniSONE for severe asthma, the prevalence of congenital malformations was within the expected range for all births (Fitzsimons, 1986; Greenberger & Patterson, 1983). The incidence of premature deliveries and low birth weight infants was slightly increased above expected (Fitzsimons, 1986).
c) A controlled trial in women with asthma comparing patients treated with corticosteroids during pregnancy and those not treated did not reveal an increased incidence of birth defects in those who received steroids (Schatz et al, 1975).

a) In animal studies, dose-dependent gross injury (characterized by red foci) of the adrenal gland occurred in fetuses following maternal inhaled doses of 180 times the maximum recommended human daily inhalation dose (MRHDID) and higher during organogenesis from gestation day 6 to 15. However, no external or skeletal malformations or embryolethality were observed in fetuses following maternal inhaled doses up to 440 times the MRHDID. Teratogenic effects (increased incidence of cleft palate) occurred following subQ maternal doses of 0.75 times the MRHDID and higher from gestation day 1 to 18. External or skeletal malformations occurred with subQ maternal doses of 0.75 times the MRHDID and higher during organogenesis from gestation day 7 to 16 (Prod Info QVAR(R) inhalation aerosol, 2014).

a) Betamethasone dipropionate was teratogenic in animals, including umbilical hernias, cephalocele, and cleft palate, when administered intramuscularly at a dose of 0.05 mg/kg (Prod Info DIPROLENE(R) topical ointment, 2014; Prod Info DIPROLENE(R) topical lotion, 2014; Prod Info DIPROLENE(R) AF topical cream, 2014).

a) Budesonide is embryocidal and teratogenic in animals. In embryofetal development studies, the subQ administration of budesonide up to 1.2 times the recommended human intrarectal dose based on body surface area resulted in skeletal abnormalities, decreased pup weights, and increased fetal loss (Prod Info ENTOCORT(R) EC oral capsules, 2016; Prod Info UCERIS(R) rectal foam, 2014). In another study, the administration of approximately 0.07 times the maximum recommended human dose on a body surface area basis in rats decreased prenatal and neonatal pup viability (Prod Info ENTOCORT(R) EC oral capsules, 2016).

a) No teratogenicity or other fetal effects occurred in animals at oral ciclesonide doses approximately 120 times and 10 times the maximum human daily dose following intranasal and inhalation administration, respectively, in adults. Clinical experience with pharmacologic doses of corticosteroids suggest that teratogenicity may be more prevalent in animals than in humans (Prod Info ALVESCO(R) oral inhalation aerosol, 2008; Prod Info OMNARIS(TM) nasal spray, 2006).
b) Cleft palate, skeletal abnormalities including incomplete ossifications, and skin effects were reported in animals following SubQ administration of ciclesonide at doses of less than the maximum human daily inhalation dose. There was no toxicity observed at doses less than 1 mcg/kg/day (Prod Info ZETONNA(TM) nasal aerosol, 2012; Prod Info ALVESCO(R) oral inhalation aerosol, 2008).

a) There are no adequate or well controlled studies of clobetasol use in human pregnancy. During animal studies, administration of corticosteroids, at relatively low levels, has resulted in teratogenic effects. Administration of subQ clobetasol at approximately 0.01 and 0.33 times the human topical dose resulted in fetotoxicity and teratogenicity, including cleft palate and skeletal abnormalities. Administration of clobetasol 3 and 10 mcg/kg (approximately 0.001 and 0.003 times the human topical dose, respectively) resulted in teratogenic effects such as cleft palate, cranioschisis, and skeletal abnormalities (Prod Info TEMOVATE(R) E topical cream, 2012).

a) Animal studies showed teratogenic effects. Topical dexamethasone given to animals at approximately 3 to 4 times the recommended human dose resulted in embryofetal lethality, cleft palate, intestinal anomalies, intestinal aplasia, gastroschisis, and hypoplastic kidneys. (Prod Info OZURDEX(R) intravitreal implant, 2014).

a) Fluorometholone has demonstrated teratogenicity and embryolethality in animal studies with low multiples of the human ocular dose. Ocular administration daily on days 6 to 18 of gestation resulted in dose-related fetal loss and fetal abnormalities, including cleft palate, deformed rib cage, anomalous limbs, and neural abnormalities (eg, encephalocele, craniorachischisis, spina bifida) (Prod Info FML FORTE(R) ophthalmic suspension, 2013; Prod Info FML(R) ophthalmic suspension, 2013).

a) In animal studies, there has been a higher incidence of cleft palate with corticosteroid use (Prod Info SOLU-MEDROL IV, IM injection, 2010), particularly with high doses of methylPREDNISolone (Walker, 1971; Walker, 1967; Pinsky & DiGeorge, 1965).

a) Increased fetal malformations and decreased fetal growth were evident following administration of mometasone furoate. Dystocia and related complications were seen when the drug was given late in gestation (Prod Info DULERA(R) inhalation aerosol, 2010; Prod Info ASMANEX(R) HFA inhalation aerosol, 2014). However, history of corticosteroids has shown that some animals are more prone to teratogenic effects from corticosteroid exposure than humans (Prod Info ASMANEX(R) HFA inhalation aerosol, 2014). Topical dermal doses that were approximately 6 times and 3 times the maximum recommended human dose (MRHD) resulted in umbilical hernia and delayed ossification, respectively. Cleft palate and decreased fetal survival were evident with subcutaneous doses that were approximately one-third and 1 time the MRHD, respectively; no toxic effects were seen at a dose that was one-tenth the MRHD. In other studies, multiple malformations, such as flexed front paws, gallbladder agenesis, umbilical hernia, and hydrocephaly, were evident with topical dermal doses that were approximately 3 times the MRHD. Oral administration of mometasone furoate led to cleft palate and/or head malformations at a dose less than the MRHD; furthermore, most litters were aborted or resorbed at a dose that was twice the MRHD (Prod Info ASMANEX(R) HFA inhalation aerosol, 2014; Prod Info DULERA(R) inhalation aerosol, 2010)

a) Fetal deaths and decreased fetal weights were noted in the offspring of pregnant animals following topical application of fluocinolone acetonide/hydroquinone/tretinoin cream in a clinical study. In pregnant animals treated topically during organogenesis, teratogenic effects consistent with tretinoin administration included cleft palate, protruding tongue, open eyes, retinal folding or dysplasia, and umbilical hernia in exposed offspring. Topical therapy with a 10-fold dilution of fluocinolone acetonide/hydroquinone/tretinoin cream showed increases in stillborns, lower body weights, and delayed preputial separations. Postnatal behavioral effects consistent with gestational exposure to retinoic acids included increased overall activity in some litters on day 22 and in all exposed litters at 5 weeks. Clinical dosing comparisons are not possible in animal studies using dermal application (Prod Info TRI-LUMA(R) topical cream, 2013).

a) During animal studies, there were no reports of teratogenic effects in animals administered inhaled fluticasone at approximately 4 times and equal to the maximum recommended human dose (MRHD). Additionally, there were no reports of perinatal or postnatal developmental effects with inhaled fluticasone doses approximately equal to the MRHD (Prod Info ARNUITY(TM) ELLIPTA(R) oral inhalation powder, 2014).

a) There are no adequate or well-controlled studies of budesonide use in pregnant women (Prod Info ENTOCORT(R) EC oral capsules, 2016; Prod Info UCERIS(R) rectal foam, 2014).

a) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy in humans. Maternal use is not expected to result in fetal exposure to ciprofloxacin hydrochloride and fluocinolone acetonide, because the combination is negligibly absorbed through otic administration (Prod Info OTOVEL(R) otic solution, 2016).

a) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy in humans (Prod Info DERMASORB(TM) AF COMPLETE KIT topical cream, 2013).

1) Cortisone (Prod Info Cortone(R), 1997)
2) PrednisoLONE (Prod Info Flo-Pred oral suspension , 2011; Prod Info Orapred ODT(R) orally disintegrating tablets, 2010)
3) PredniSONE oral delayed-release tablets (Prod Info RAYOS oral delayed-release tablets, 2012)

1) Beclomethasone (Prod Info QVAR(R) inhalation aerosol, 2014)
2) Betamethasone (Prod Info CELESTONE(R)SOLUSPAN(R) injectable suspension, 2008)
3) Betamethasone dipropionate (Prod Info DIPROLENE(R) topical ointment, 2014; Prod Info DIPROLENE(R) topical lotion, 2014; Prod Info DIPROLENE(R) AF topical cream, 2014)
4) Betamethasone valerate (Prod Info betamethasone valerate topical cream, topical lotion, topical ointment, 2013; Prod Info Luxiq(R) topical foam, 2013)
5) Budesonide rectal foam (Prod Info UCERIS(R) rectal foam, 2014)
6) Ciclesonide (Prod Info ZETONNA(TM) nasal aerosol, 2012)
7) Clioquinol/hydrocortisone (Prod Info DERMASORB(TM) AF COMPLETE KIT topical cream, 2013)
8) Clobetasol (Prod Info Embeline(TM) Scalp Application topical solution, 2010; Prod Info TEMOVATE(R) E topical cream, 2012)
9) Corticotropin (Prod Info HP ACTHAR(R) GEL injection, 2006)
10) Cosyntropin (Prod Info cosyntropin IV injection, 2008)
11) Dexamethasone (Prod Info OZURDEX(R) intravitreal implant, 2014)
12) Fluocinolone (Prod Info SYNALAR(R) topical solution, 2012)
13) Fluocinolone acetonide/hydroquinone/tretinoin (Prod Info TRI-LUMA(R) topical cream, 2013)
14) Fluocinonide (Prod Info VANOS(R) 0.1% topical cream, 2011)
15) Fluorometholone (Prod Info FML FORTE(R) ophthalmic suspension, 2013; Prod Info FML(R) ophthalmic suspension, 2013)
16) Fluticasone furoate (Prod Info ARNUITY(TM) ELLIPTA(R) oral inhalation powder, 2014)
17) Fluticasone furoate/Vilanterol (Prod Info BREO(TM) ELLIPTA(TM) oral inhalation powder, 2013)
18) Hydrocortisone (Prod Info LOCOID(R) topical cream, ointment, solution, 2010)
19) Hydrocortisone/iodoquinol (Prod Info Vytone(TM) Cream with aloe topical cream, 2013)
20) Hydrocortisone sodium succinate (Prod Info SOLU-CORTEF(R) intravenous injection, intramuscular injection, 2014)
21) Loteprednol (Prod Info Lotemax(R) ophthalmic ointment, 2011)
22) MethylPREDNISolone (Prod Info SOLU-MEDROL(R) IV, IM injection, 2011)
23) Mometasone (Prod Info ASMANEX(R) HFA inhalation aerosol, 2014)
24) PredniSONE oral solution and immediate-release tablets (Prod Info PredniSONE oral solution, tablets, 2009)
25) Rimexolone (Prod Info VEXOL(R) ophthalmic suspension, 2002)
26) Triamcinolone (Prod Info KENALOG(R)-40 intramuscular intra-articular suspension for injection, 2011)

1) Acyclovir/hydrocortisone topical cream (Prod Info XERESE(TM) topical cream 5%/1%, 2010)
2) Budesonide inhalation powder (Prod Info PULMICORT FLEXHALER(TM) inhalation powder, 2010)
3) Budesonide inhalation suspension (Prod Info PULMICORT RESPULES(R) inhalation suspension, 2010)
4) Budesonide nasal spray (Prod Info RHINOCORT AQUA(R) nasal spray, 2010)

a) In two clinical studies investigating the outcome of 101 pregnancies in which women received beclomethasone and/or predniSONE for severe asthma, in utero exposure to high-dose predniSONE therapy (greater than 40 mg/day) increased the rate of spontaneous abortion by 11%, intrauterine fetal death by 27%, and perinatal mortality (Little & B, 1997).

a) Thirteen women became pregnant during treatment with topical fluocinolone acetonide/hydroquinone/tretinoin cream in clinical trials. Outcomes included births of 3 apparently healthy babies, 1 pregnancy termination, and 1 miscarriage. The remaining outcomes were unknown. Epidemiologic studies of topical tretinoin do not show an increased incidence of birth defects, though neurologic or cognitive impairments may not be detected (Prod Info TRI-LUMA(R) topical cream, 2013).

a) There are no adequate or well controlled studies of fluticasone use during human pregnancy. Although teratogenic effects have not been reported with fluticasone, corticosteroids have been associated with teratogenicity during animal studies. Due to the risk of adverse effects and because animal studies are not always indicative of human response, the manufacturer recommends the use of fluticasone during pregnancy only if the potential maternal benefit outweighs the potential fetal risk. Women should contact their healthcare provider if pregnancy occurs (Prod Info ARNUITY(TM) ELLIPTA(R) oral inhalation powder, 2014).

a) Embryolethal effects (increased fetal resorptions) and decreased pup survival were observed in mice with subQ maternal doses of 2.3 times the maximum recommended human dose and higher from gestation day 1 to 13. Embryolethality (increased fetal resorptions) occurred in rabbits with subQ maternal doses of 0.75 times the maximum recommended human dose and higher during organogenesis from gestation day 7 to 16 (Prod Info QVAR(R) inhalation aerosol, 2014)

a) The subcutaneous administration of budesonide to animals at doses up to 1.2 times the human intrarectal dose based on body surface area resulted in skeletal abnormalities, decreased pup weights, and increased fetal loss (Prod Info ENTOCORT(R) EC oral capsules, 2016; Prod Info UCERIS(R) rectal foam, 2014).

a) In animal studies, subcutaneous ciclesonide administration at doses less than the MHDD led to fetal toxicity, including fetal loss and reductions in fetal weight, The no-effect dose was 1 mcg/kg. Clinical experience with pharmacologic doses of corticosteroids suggest that teratogenicity may be more prevalent in some animals than in humans (Prod Info ZETONNA(TM) nasal aerosol, 2012; Prod Info ALVESCO(R) oral inhalation aerosol, 2008).

a) In animal studies, subcutaneous administration of mometasone furoate at doses that were approximately 8 times the maximum recommended human dose (MRHD) resulted in prolonged and difficult labor, with fewer live births, lower birth weight, and reduced early survival; these effects were not seen at doses that resulted in one-half of this exposure. Oral administration of mometasone furoate led to increased resorptions at a dose less than the MRHD; furthermore, most litters were aborted or resorbed at a dose that was twice the MRHD (Prod Info ASMANEX(R) HFA inhalation aerosol, 2014; Prod Info DULERA(R) inhalation aerosol, 2010)

a) Fetal deaths and decreased fetal weights were noted in the offspring of pregnant animals following topical application of fluocinolone acetonide/hydroquinone/tretinoin cream. Topical therapy with a 10-fold dilution of fluocinolone acetonide/hydroquinone/tretinoin cream resulted in increases in stillborn pups, lower pup body weights, and delayed preputial separations. Postnatal behavioral effects consistent with gestational exposure to retinoic acids included increased overall activity in some litters on day 22 and in all exposed litters at 5 weeks. Clinical dosing comparisons are not possible in animal studies using dermal application (Prod Info TRI-LUMA(R) topical cream, 2013).

a) Exercise caution when administering beclomethasone dipropionate to a nursing woman, as corticosteroids are excreted into human milk (Prod Info QVAR(R) inhalation aerosol, 2014). However, inhaled corticosteroids, including beclomethasone, result in low maternal serum concentrations, and therefore should present little or no risk to the nursing infant (Ellsworth, 1994). Corticosteroid use is considered compatible with breastfeeding by the WHO, although it is recommended that the infant be monitored (Anon, 2002).

a) Corticosteroids, when administered systemically, appear in human breast milk. In sufficient quantities, this could result in growth suppression, interfere with endogenous corticosteroid production, or cause other adverse events for the nursing infant. Caution should be taken when breastfeeding women are taking pharmacologic doses of corticosteroids (Prod Info DIPROLENE(R) topical ointment, 2014; Prod Info DIPROLENE(R) topical lotion, 2014; Prod Info DIPROLENE(R) AF topical cream, 2014).

a) Corticosteroids, when administered systemically, appear in human breast milk. In sufficient quantities, this could result in growth suppression, interfere with endogenous corticosteroid production, or cause other adverse events for the nursing infant. Caution should be taken when breastfeeding women are taking pharmacologic doses of corticosteroids (Prod Info betamethasone valerate topical cream, topical lotion, topical ointment, 2013; Prod Info Luxiq(R) topical foam, 2013)

a) Budesonide is secreted into human breast milk. One study of lactating women with asthma receiving budesonide (800 mcg total daily) via inhalation reported that the estimated oral daily dose of budesonide from breast milk to the infant was equivalent to 0.3% to 1% of the dose inhaled by the mother. Oral therapeutic doses of budesonide exposure in a nursing infant may be up to 10 times higher than budesonide inhalation exposure (Prod Info ENTOCORT(R) EC oral capsules, 2016). .
b) Since the inhalation of dry budesonide powder has been shown to lead to low budesonide concentrations in human breast milk, intrarectally administered budesonide is likely excreted into human breast milk as well (Prod Info UCERIS(R) rectal foam, 2014)

a) Although breastfeeding is not expected to result in infant exposure to ciprofloxacin hydrochloride and fluocinolone acetonide, use caution when administering this combination to a mother who is breastfeeding, because it is unknown whether ciprofloxacin hydrochloride/fluocinolone acetonide is excreted into human breast milk (Prod Info OTOVEL(R) otic solution, 2016).

a) Lactation studies with clobetasol have not yet been conducted. No reports describing the use of clobetasol during human lactation are available and the effects on the nursing infant from exposure to the drug in milk are unknown. Systemic corticosteroids are detectable in small quantities in breast milk and may cause adverse effects (eg, growth suppression). It is unknown if topical corticosteroid administration can result in systemic absorption. Because many drugs are excreted in human milk, the manufacturer recommends the use of caution when prescribing topical corticosteroids to a nursing woman (Prod Info TEMOVATE(R) E topical cream, 2012).

a) Corticosteroids, when administered systemically, appear in human breast milk. In sufficient quantities, this could result in growth suppression, interfere with endogenous corticosteroid production, or cause other adverse events for the nursing infant. Caution should be taken when breastfeeding women are taking pharmacologic doses of corticosteroids (Prod Info OZURDEX(R) intravitreal implant, 2014). The World Health Organization considers dexamethasone compatible with breastfeeding in a single dose, while no information is available regarding prolonged use (Anon, 2002).

a) No reports describing the use of topical or intravitreal fluocinolone during human lactation are available, and the effects on the nursing infant from exposure to the drug in milk are unknown. The extent of topical corticosteroid excretion in breast milk has not been determined. Systemic steroids appear in human milk. Although the quantities are not likely to create a deleterious effect on the infant (Prod Info SYNALAR(R) topical solution, 2012), it could potentially suppress growth, alter endogenous corticosteroid production or cause other detrimental effects (Prod Info Retisert(TM), 2005; Prod Info Capex(R), 2002). Fluocinolone should therefore be used cautiously in a breastfeeding woman (Prod Info SYNALAR(R) topical solution, 2012; Prod Info Retisert(TM), 2005; Prod Info Capex(R), 2002).

a) Corticosteroids are excreted in human milk when administered systemically. It is not known if fluocinolone acetonide/hydroquinone/tretinoin is present in human milk following topical therapy, and the potential for adverse effects in the nursing infant from exposure to this drug is unknown. Until additional data are available, use caution with its use in women who are nursing. Avoid contact of fluocinolone acetonide/hydroquinone/tretinoin with the nursing infant (Prod Info TRI-LUMA(R) topical cream, 2013).

a) Based on the World Health Organization recommendation, hydrocortisone is compatible with breastfeeding in single dose use, but there is no data available regarding prolonged use (Anon, 2002). Systemically administered corticosteroids appear in human milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other unexpected effects. Because of the potential for serious adverse reactions in nursing infants, it is recommended to either discontinue nursing or discontinue hydrocortisone, considering the importance of the drug to the mother (Prod Info SOLU-CORTEF(R) intravenous injection, intramuscular injection, 2014).

a) The amount of prednisoLONE, the active metabolite of predniSONE, that the nursing infant could receive in a feeding is estimated to be a maximum of 0.5% of the weight-adjusted maternal single dose (Bennett, 1996). In 6 lactating women who received maintenance therapy with prednisoLONE 10 mg to 80 mg orally per day, milk concentrations ranged from 5% to 25% of maternal plasma levels. Doses of 20 mg or less resulted in a peak milk to plasma ratio of approximately 0.1, while doses of 30 mg or more resulted in a peak milk to plasma ratio of approximately 0.2. Peak milk levels were reached about an hour after dosing. The authors estimate that the infant would receive less than 0.1% of an 80 mg prednisoLONE dose taken by the mother, corresponding to less than 10% of the infant's endogenous production of cortisol, a quantity with limited, if any, clinical significance (Ost et al, 1985).
b) Systemically administered corticosteroids are known to be excreted in human milk. Exposing the nursing infant to predniSONE could result in growth suppression, interference with production of endogenous corticosteroids or other undesired effects (Prod Info RAYOS oral delayed-release tablets, 2012; Prod Info PredniSONE oral solution, tablets, 2009). However, the amount of corticosteroid found in breast milk is negligible when the mother receives predniSONE 20 mg daily or less. The dose received by the infant can be minimized by avoiding breastfeeding for 3 to 4 hours after a dose (Anderson, 1987a). Most clinicians consider prednisoLONE, predniSONE, and methylPREDNISolone as the agents of choice for systemic corticoid treatment during breastfeeding (Schaefer, 2001).

a) One study suggests that the amount of corticosteroid excreted in breast milk is negligible when the mother receives methylPREDNISolone 8 mg daily or less. The dose received by the infant can be minimized by avoiding breastfeeding during the first 3 to 4 hours following the dose (Anderson, 1987).

a) Several reports have indicated no adverse effects in breastfeeding infants after the mothers received predniSONE or prednisoLONE, the active metabolite of predniSONE (Ito et al, 1993; Moretti et al, 2003; Thiagarajan et al, 2001; Nyberg et al, 1998).

a) The administration of approximately 0.07 times the maximum recommended human dose on a body surface area basis in rats decreased pup viability during lactation (Prod Info ENTOCORT(R) EC oral capsules, 2016).

a) In lactating animals, ciclesonide administration resulted in minimal, but detectable, levels of ciclesonide in breast milk (Prod Info ZETONNA(TM) nasal aerosol, 2012; Prod Info ALVESCO(R) oral inhalation aerosol, 2008; Prod Info OMNARIS(TM) nasal spray, 2006).

a) Formoterol was excreted in the milk of lactating animals (Prod Info DULERA(R) inhalation aerosol, 2010).

a) At the time of this review, no data were available to assess the potential effects on fertility from exposure to this agent (Prod Info DIPROLENE(R) topical ointment, 2014; Prod Info DIPROLENE(R) topical lotion, 2014; Prod Info DIPROLENE(R) AF topical cream, 2014).

a) At the time of this review, no data were available to assess the potential effects on fertility from exposure to this agent (Prod Info betamethasone valerate topical cream, topical lotion, topical ointment, 2013; Prod Info Luxiq(R) topical foam, 2013)

a) At the time of this review, no data were available to assess the potential effects on fertility from exposure to this agent. Fertility effects are not expected, because the combination is negligibly absorbed through otic administration at the recommended dosage (Prod Info OTOVEL(R) otic solution, 2016).

a) At the time of this review, no data were available to assess the potential effects on fertility from exposure to this agent (Prod Info DERMASORB(TM) AF COMPLETE KIT topical cream, 2013).

a) At the time of this review, no data were available to assess the potential effects in fertility from exposure to this product (Prod Info OZURDEX(R) intravitreal implant, 2014).

a) At the time of this review, no data were available to assess the potential effects in fertility from exposure to this combination product (Prod Info TRI-LUMA(R) topical cream, 2013).

a) At the time of this review, no data were available to assess the potential effects in fertility from exposure to this product (Prod Info Vytone(TM) Cream with aloe topical cream, 2013).

a) In animal studies, decreased conception rates occurred at an oral dose of about 250 times the maximum recommended human daily inhaled dose (MRHDID) on a mg/m(2) basis. Fertility impairment, characterized by inhibition of the estrous cycle, was observed following an oral dose of about 25 times the MRHDID. However, no inhibition of the estrous cycle occurred with 12 months of inhaled beclomethasone dipropionate at a dose of approximately 17 times the MRHDID (Prod Info QVAR(R) inhalation aerosol, 2014).

a) The administration of approximately 0.07 times the maximum recommended human dose on a body surface area basis did not adversely affect fertility in rats (Prod Info ENTOCORT(R) EC oral capsules, 2016). The subQ administration of budesonide at 0.20 times the recommended intrarectal dose based on body surface area did not affect fertility in rats (Prod Info UCERIS(R) rectal foam, 2014).

a) Clobetasol propionate was subcutaneously administered to male and female animals at doses up to 50 mcg/kg/day. Males and females were administered clobetasol propionate 70 days and 15 days prior to mating, respectively. Administration continued for females through gestation day 7. Dosage levels less than 12.5 mcg/kg/day were considered the no-observed-effect-level for both paternal and maternal toxicity due to decreased weight gain, increased seminal vesicles, reduced number of estrous cycles, and an increase in nonviable embryos at higher doses (Prod Info CLOBEX(R) topical shampoo, 2012).

a) Topical therapy with a 10-fold dilution of fluocinolone acetonide/hydroquinone/tretinoin cream in pregnant rats revealed no effects on the traditional parameters used to assess fertility. However, topical treatment of male minipigs with the full-strength of fluocinolone acetonide/hydroquinone/tretinoin for 6 months caused small testes and severe hypospermia (Prod Info TRI-LUMA(R) topical cream, 2013).

a) Fertility impairment and effect on mating performance was not observed in a fertility and reproductive study in males and females that were administered subQ doses up to 0.7 times the maximum therapeutic human dose (Prod Info LOCOID(R) topical lotion, 2014).

a) Fertility impairment was not observed in reproductive studies in animals administered subQ doses up to approximately 8 times the maximum recommended human dose on an AUC basis (Prod Info ASMANEX(R) HFA inhalation aerosol, 2014).

a) The carcinogenic potential of clobetasol propionate has not been evaluated in long-term animal studies (Prod Info Olux-E(R) topical foam, 2010).

a) The carcinogenic potential of rimexolone has not been evaluated in long-term animal studies (Prod Info VEXOL(R) ophthalmic suspension, 2002).

a) No evidence of carcinogenicity was noted in rats exposed to the highest doses of beclomethasone dipropionate (approximately 70 and 120 times the maximum recommended daily intranasal dose in adults and children, respectively, on a mg/m(2) basis) for a total of 95 weeks (13 weeks at inhalation doses up to 0.4 mg/kg/day and 82 weeks at combined oral and inhalation doses up to 2.4 mg/kg/day) (Prod Info QNASL(TM) nasal aerosol, 2014).

a) MICE: No carcinogenicity was observed when betamethasone was given up to 24 months to female mice in topical doses up to 8.5 mcg/kg/day (approximately 26 mcg/m(2)/day) and male mice in topical doses up to 12.9 mcg/kg/day (approximately 39 mcg/m(2)/day) (Prod Info TACLONEX(R) topical ointment, 2014).
b) RATS: No carcinogenicity was observed when betamethasone was given to rats for up to 24 months in oral doses up to 200 mcg/kg/day (approximately 1200 mcg/m(2)/day) (Prod Info TACLONEX(R) topical ointment, 2014).

a) In a 2-year study in Sprague-Dawley rats, no tumorigenicity was reported in female rats administered oral budesonide doses up to 50 mcg/kg (approximately 0.05 times the maximum recommended human dose (MRHD) on a mg/m(2) basis). In a 91-week study, no treatment-related carcinogenicity was observed in mice administered budesonide at oral doses up to 200 mcg/kg (approximately 0.1 times the MRHD on a mg/m(2) basis) (Prod Info ENTOCORT(R) EC oral capsules, 2011).

a) No carcinogenic effects were noted in mice with ciclesonide oral doses up to 900 mcg/kg (approximately 60 times the maximum recommended human daily intranasal dose (MRHDID) in adults on a mcg/m(2) basis) or in rats of inhalation doses up to 193 mcg/kg (approximately 25 times the MRHDID in adults and adolescents 12 years of age or older on a mcg/m(2) basis) for 104 weeks (Prod Info ZETONNA(TM) nasal aerosol, 2012).

a) Carcinogenic effects were not observed in rats administered topical clobetasol propionate for 2 years at concentrations up to 0.005% (corresponding to doses up to 11 mcg/kg/day). Concentrations of clobetasol propionate up to 0.001% topically administered to hairless mice 5 days per week, did not increase the formation rate of UV-light induced skin tumors after a period of 40 weeks (Prod Info CLOBEX(R) topical shampoo, 2012).

a) Topical application of fluocinolone/hydroquinone/tretinoin in fixed combinations equivalent to 10%, 50%, 100% and 150% of the clinical concentrations on male and female CD-1 mice did not result in significant changes in tumor incidence after 24 months (Prod Info TRI-LUMA(R) topical cream, 2013).

a) No carcinogenicity was observed when fluticasone furoate was given up to 2 years to rats at inhaled doses of up to 9 mcg/kg/day and to mice at inhaled doses of up to 19 mcg/kg/day (both doses less than the maximum recommended human daily inhalation dose on a mcg/m(2) basis) (Prod Info ARNUITY(TM) ELLIPTA(R) oral inhalation powder, 2014).

a) PrednisoLONE 3 mg/kg (equal to 29 mg in a 60-kg human on a mg/m(2) basis) did not induce tumors when administered by oral gavage 1, 2, 4.5, or 9 times per month in female Sprague-Dawley rats during an 18-month study (Prod Info Flo-Pred oral suspension , 2011).

a) Monitor vital signs, fluid and electrolyte status as indicated.
b) Monitor neurologic status as indicated in symptomatic patients.

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.

a) ALBUTEROL

a) Consider systemic corticosteroids in patients with significant bronchospasm.
b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).

a) DIPHENHYDRAMINE

a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).

a) EPINEPHRINE

a) OXYGEN: 5 to 10 liters/minute via high flow mask.
b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).

a) CARDIAC MONITOR: All complicated cases.
b) IV ACCESS: Routine in all complicated cases.

a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.

a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).

a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.

a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).

a) MIFEPRISTONE: Mifepristone was used to treat hypertension and proximal muscle weakness, associated with Cushing's syndrome, in a patient who accidentally received an overdose of 200 milligrams triamcinolone acetonide. The dosage regimen given, of mifepristone, was 200 milligrams orally daily for 11 days, 600 milligrams orally on days 12 and 13, and 200 milligrams orally for 5 days (Schweitzer et al, 2000).

a) Previous therapy with bronchodilators alone: 100 mcg inhaled orally twice daily; MAX: 500 mcg twice daily (Prod Info FLOVENT(R) DISKUS(R) oral inhalation powder, 2014)
b) Previous therapy with inhaled corticosteroids: 100 to 250 mcg inhaled orally twice daily; MAX: 500 mcg twice daily (Prod Info FLOVENT(R) DISKUS(R) oral inhalation powder, 2014)
c) Previous therapy with oral corticosteroids: 500 to 1,000 mcg inhaled orally twice daily; MAX: 1,000 mcg twice daily (Prod Info FLOVENT(R) DISKUS(R) oral inhalation powder, 2014)

a) Previous therapy with bronchodilators alone: 88 mcg inhaled orally twice daily; MAX: 440 mcg twice daily (Prod Info FLOVENT(R) HFA inhalation aerosol, 2013)
b) Previous therapy with inhaled corticosteroids: 88 to 220 mcg inhaled orally twice daily; MAX: 440 mcg twice daily (Prod Info FLOVENT(R) HFA inhalation aerosol, 2013)
c) Previous therapy with oral corticosteroids: 440 mcg inhaled orally twice daily; MAX: 880 mcg twice daily (Prod Info FLOVENT(R) HFA inhalation aerosol, 2013)

a) One to two sprays per nostril daily; MAX: 2 sprays per nostril daily (OTC Product Information, as appeared on the labeling supplied by the U.S. FDA 07/2014)

a) Apply a thin film topically once or twice daily (Prod Info fluticasone propionate 0.05% topical cream, 2012)

a) Apply a thin film topically once daily (Prod Info CUTIVATE(R) topical lotion, 2015)

a) Apply a thin film topically twice daily (Prod Info fluticasone propionate 0.005% topical ointment, 2012)

a) INHALATION: The recommended dose is fluticasone furoate 100 mcg/vilanterol 25 mcg or fluticasone furoate 200 mcg/vilanterol 25 mcg inhalation once daily; MAX: fluticasone furoate 200 mcg/vilanterol 25 mcg inhalation once daily (Prod Info BREO(R) ELLIPTA(R) oral inhalation powder, 2015).

a) INHALATION: The recommended dose is fluticasone furoate 100 mcg/vilanterol 25 mcg inhalation once daily; MAX 1 inhalation daily of fluticasone furoate 100 mcg/vilanterol 25 mcg (Prod Info BREO(R) ELLIPTA(R) oral inhalation powder, 2015).

a) Apply to affected area 3 to 4 times daily (Prod Info Vytone(TM) Cream with aloe topical cream, 2013)

a) UNDER 6 YEARS: Safety and efficacy have not been established (Prod Info DYMISTA(R) nasal spray suspension, 2015).
b) 6 YEARS AND OLDER: 1 spray in each nostril twice daily (Prod Info DYMISTA(R) nasal spray suspension, 2015)

a) 12 YEARS OF AGE AND OLDER: 2 sprays (80 mcg/spray) in each nostril once daily (total dose 320 mcg/day). MAX, 4 nasal aerosol sprays per day (Prod Info QNASL(TM) nasal aerosol, 2014)
b) 4 TO 11 YEARS: 1 spray (80 mcg) in each nostril once daily (total dose 160 mcg/day); MAX: 2 nasal aerosol sprays per day (Prod Info QNASL(TM) nasal aerosol, 2014)
c) LESS THAN 4 YEARS: Safety and efficacy have not been established (Prod Info QNASL(TM) nasal aerosol, 2012).

a) 12 YEARS OF AGE AND OLDER: 1 or 2 inhalations (42 mcg/inhalation) in each nostril 2 times daily (usual dose 168 to 336 mcg/day) (Prod Info BECONASE AQ(R) nasal spray, 2005)
b) 6 TO 12 YEARS OF AGE: 1 inhalation (42 mcg) in each nostril 2 times per day (Prod Info BECONASE AQ(R) nasal spray, 2005)
c) LESS THAN 6 YEARS OF AGE: Safety and efficacy have not been established (Prod Info BECONASE AQ(R) nasal spray, 2005).

a) 11 YEARS AND OLDER: 40 to 160 mcg twice a day; MAX 320 mcg twice daily (Prod Info QVAR(R) inhalation aerosol, 2005)
b) 5 TO 11 YEARS OF AGE: 40 mcg twice a day; MAX 80 mcg twice a day (Prod Info QVAR(R) inhalation aerosol, 2005)
c) LESS THAN 5 YEARS OF AGE: Safety and efficacy have not been established (Prod Info QVAR(R) inhalation aerosol, 2005).

a) Safety and efficacy has not been established in pediatric patients (Prod Info UCERIS(TM) oral extended release tablets, 2013).

a) Safety and efficacy have not been established in pediatric patients (Prod Info UCERIS(R) rectal foam, 2014).

a) 1 TO 8 YEARS OF AGE: 0.25 to 1 mg/day in single or divided doses; MAX 1 mg/day (Prod Info PULMICORT RESPULES(R) inhalation suspension, 2010)
b) 6 TO 12 MONTHS OF AGE: Safety and effectiveness have not been established (Prod Info PULMICORT RESPULES(R) inhalation suspension, 2010).

a) 6 YEARS AND OLDER: initial, 2 sprays/nostril twice daily or 4 sprays/nostril once a day in morning; MAX 4 sprays/nostril/day (Prod Info RHINOCORT(R) nasal inhaler, 2001)

a) 6 YEARS AND OLDER: 1 spray (64 mcg) per nostril once daily. MAX dose: 6 to less than 12 years, 2 sprays (128 mcg) per nostril once daily; 12 years and older, 4 sprays (256 mcg) per nostril once daily (Prod Info RHINOCORT AQUA(R) nasal spray, 2010).
b) LESS THAN 6 YEARS OF AGE: Safety and effectiveness have not been established (Prod Info RHINOCORT AQUA(R) nasal spray, 2010)

a) 8 YEARS AND OLDER WEIGHING MORE THAN 25 KG: 9 mg/day orally for up to 8 weeks, followed by 6 mg once daily for 2 weeks (Prod Info ENTOCORT(R) EC oral capsules, 2016).

a) 6 YEARS AND OLDER: 180 to 360 mcg twice daily; MAX 360 mcg twice daily (Prod Info PULMICORT FLEXHALER(TM) inhalation powder, 2010)
b) LESS THAN 6 YEARS OF AGE: Safety and effectiveness have not been established (Prod Info PULMICORT FLEXHALER(TM) inhalation powder, 2010).

a) 12 YEARS AND OLDER: 1 actuation (37 mcg/actuation) in each nostril once daily; MAX total daily dose of 1 actuation in each nostril (74 mcg/day) (Prod Info ZETONNA(TM) nasal aerosol, 2012).
b) LESS THAN 12 YEARS OF AGE: Safety and efficacy have not been established (Prod Info ZETONNA(TM) nasal aerosol, 2012).

a) 6 YEARS AND OLDER: 2 sprays (50 mcg/spray) in each nostril once daily; MAX total daily dose of 2 sprays in each nostril (200 mcg/day)(Prod Info OMNARIS(R) nasal spray, 2010)
b) The efficacy in the treatment of perennial allergic rhinitis has not been established in patients 11 years of age and younger. The efficacy in the treatment of seasonal allergic rhinitis has not been established in patients 5 years of age and younger (Prod Info OMNARIS(R) nasal spray, 2010).

a) 12 YEARS AND OLDER: 80 to 320 mcg oral inhalation twice daily; MAX, 320 mcg twice daily (Prod Info ALVESCO(R) oral inhalation aerosol, 2008)
b) LESS THAN 12 YEARS OF AGE: Safety and effectiveness have not been established (Prod Info ALVESCO(R) oral inhalation aerosol, 2008).

a) In patients not currently using inhaled corticosteroids, the recommended starting dose is 100 mcg inhaled orally once daily, not exceeding 1 dose per day. For other patients, the recommended dose is 100 or 200 mcg inhaled orally, based on current therapy and severity of disease. Dosing may be increased to a MAX of 200 mcg daily if there is a poor response after 2 weeks at 100 mcg daily. Do not exceed 1 dose daily (Prod Info ARNUITY(TM) ELLIPTA(R) oral inhalation powder, 2014).

a) 12 YEARS AND OLDER
b) 4 TO 11 YEARS

a) 12 YEARS AND OLDER
b) 4 TO 11 YEARS

a) 12 YEARS AND OLDER
b) 4 TO 11 YEARS

a) UP TO 3 MONTHS
b) 3 MONTHS AND OLDER

a) UP TO 3 MONTHS
b) 3 MONTHS AND OLDER

a) Safety and efficacy in pediatric patients have not been established (Prod Info fluticasone propionate 0.005% topical ointment, 2012).

a) PATIENTS AGED 12 YEARS AND OLDER: Apply to affected area 3 to 4 times daily (Prod Info Vytone(TM) Cream with aloe topical cream, 2013)
b) PATIENTS UNDER 12 YEARS OF AGE: Safety and efficacy have not been established (Prod Info Vytone(TM) Cream with aloe topical cream, 2013)

a) IM: Initial, 0.11 to 1.6 mg/kg/day in 3 or 4 divided doses (Prod Info KENALOG(R)-40 intramuscular intra-articular suspension for injection, 2011)
b) INTRAVITREAL: 4 mg/0.05 mL as a single dose (Prod Info TRIVARIS(TM) intravitreal, intra-articular, IM injectable suspension, 2008)

a) 6 YEARS AND OLDER: 1 to 2 metered sprays (55 mcg/spray) in each nostril once a day; MAX dose, 220 mcg/day (Prod Info triamcinolone acetonide intranasal spray, 2009; Prod Info Nasacort(R) AQ nasal spray, 2008)
b) 2 TO 5 YEARS: 1 metered spray (55 mcg/spray) in each nostril once a day (110 mcg/day); MAX dose, 110 mcg/day (Prod Info Nasacort(R) AQ nasal spray, 2008)
c) UNDER 2 YEARS: Safety and effectiveness have not been established (Prod Info Nasacort(R) AQ nasal spray, 2008).

a) DENTAL PASTE: Safety and effectiveness have not been established (Prod Info ORALONE(R) dental paste, 2010).
b) METERED-DOSE INHALER (6 TO 12 YEARS): 3 to 8 oral inhalations per day in divided doses; MAX, 12 inhalations (900 mcg) per day in divided doses (Prod Info AZMACORT(R) oral inhalation aerosol, 2007)

a) Apply to affected areas 2 to 4 times a day (Prod Info KENALOG(R) SPRAY topical aerosol, 2011; Prod Info triamcinolone acetonide 0.025%, 0.1% topical ointment, 2008; Prod Info triamcinolone acetonide 0.025%, 0.1% topical lotion, 2008; Prod Info triamcinolone acetonide 0.025%, 0.1%, 0.5% topical cream, 2008)

a) TRIAMCINOLONE: The serum triamcinolone acetonide concentration, in a 46-year-old woman, peaked at 9.49 micrograms/liter approximately 6 weeks after she accidentally received an overdose of 200 milligrams triamcinolone acetonide (Schweitzer et al, 2000).