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  • CLASSES

    Corticosteroids, Inhalant
    Topical Nasal Corticosteroids

    DEA CLASS

    Rx

    DESCRIPTION

    Non-halogenated glucocorticoid; similar potency as beclomethasone and budesonide; low systemic absorption
    Intranasal formulation used for seasonal/perennial allergic rhinitis; oral inhalational formulation for asthma
    Used off-label for exercise-induced bronchospasm prevention

    COMMON BRAND NAMES

    Alvesco, Omnaris, Zetonna

    HOW SUPPLIED

    Alvesco/Ciclesonide Respiratory (Inhalation) Aer Met: 1actuation, 80mcg, 160mcg
    Ciclesonide Nasal Pwd Met: 1actuation, 37mcg
    Ciclesonide/Omnaris Nasal Spray Met: 1actuation, 50mcg

    DOSAGE & INDICATIONS

    For the treatment of nasal symptoms associated with seasonal and perennial allergic rhinitis.
    For seasonal allergic rhinitis.
    Intranasal dosage (nasal spray delivering 50 mcg/spray; e.g., Omnaris)
    Adults, Adolescents, And Children >= 6 years

     200 mcg intranasally once daily administered as 2 sprays in each nostril.

    Intranasal dosage (nasal aerosol delivering 37 mcg/spray; e.g., Zetonna)
    Adults, Adolescents, and Children > = 12 years

    1 spray in each nostril once daily.

    For perennial allergic rhinitis.
    Intranasal dosage (nasal spray delivering 50 mcg/spray; e.g., Omnaris)
    Adults, Adolescents, and Children >= 12 years

    200 mcg intranasally once daily administered as 2 sprays in each nostril.

    Intranasal dosage (nasal aerosol delivering 37 mcg/spray; e.g., Zetonna)
    Adults, Adolescents, and Children > = 12 years

    1 spray in each nostril once daily.

    For the maintenance treatment of asthma as prophylactic therapy.
    For patients previously receiving bronchodilators alone.
    Oral inhalation dosage (inhalation aerosol in strengths of 80 mcg/actuation and 160 mcg/actuation; e.g., Alvesco)
    Adults, Adolescents, and Children >= 12 years

    Initially, 80 mcg by oral inhalation twice daily. For those without an adequate response after 4 weeks, higher doses may provide additional symptom control. The maximum recommended dose is 160 mcg twice daily. Maximum benefit may not be achieved for 4 weeks or longer after initiation. Titrate to lowest effective dose upon stabilization.

    For patients previously receiving inhaled corticosteroids.
    Oral inhalation dosage (inhalation aerosol in strengths of 80 mcg/actuation and 160 mcg/actuation; e.g., Alvesco)
    Adults, Adolescents, and Children >= 12 years

    Initially, 80 mcg by oral inhalation twice daily. For those without an adequate response after 4 weeks, higher doses may provide additional symptom control. The maximum recommended dose is 320 mcg twice daily. Maximum benefit may not be achieved for 4 weeks or longer after initiation. Titrate to lowest effective dose upon stabilization.

    For patients previously receiving oral corticosteroids.
    NOTE: The manufacturer recommends that prednisone should be reduced no faster than 2.5 mg/day weekly, beginning after at least 1 week of therapy with ciclesonide. Patients should be carefully monitored for signs of asthma instability, including monitoring of serial objective measures of airflow, and for signs of adrenal insufficiency during steroid taper and following discontinuation of oral corticosteroid therapy.
    Oral inhalation dosage (inhalation aerosol in strengths of 80 mcg/actuation and 160 mcg/actuation; e.g., Alvesco)
    Adults, Adolescents, and Children >= 12 years

    Initially, 320 mcg by oral inhalation twice daily. For those without an adequate response after 4 weeks, higher doses may provide additional symptom control. The maximum recommended dose is 320 mcg twice daily. Maximum benefit may not be achieved for 4 weeks or longer after initiation. Titrate to lowest effective dose upon stabilization.

    For the maintenance treatment of asthma in children†.
    Oral inhalation dosage (inhalation aerosol in strengths of 80 mcg/actuation and 160 mcg/actuation; e.g., Alvesco)
    Children 4-11 years of age†

    40 to 160 mcg by oral inhalation once daily was effective in children with persistent asthma. Discontinuation rates for all doses were similar to placebo.

    For exercise-induced bronchospasm prophylaxis†.
    Oral inhalation dosage
    Adults

    80 mcg by oral inhalation twice daily. Dosage increases up to a total of 320 mcg daily have resulted in continuing improvement of FEV1 over time. The maximum dosage is 640 mcg daily. The American Thoracic Society recommends daily administration of an inhaled corticosteroid (ICS) such as ciclesonide in patients who continue to have exercise-induced symptoms despite using an inhaled short-acting beta-2 agonist (SABA) before exercise, or in those who require daily (or more frequent) SABA use. In clinical practice, ICSs may be a first-line choice for a controller agent to be added to SABAs; leukotriene receptor antagonists may also be used. The choice between the 2 classes must be made on an individual basis considering patient preferences and baseline lung function. Patients with exercise-induced bronchospasm (EIB) associated with greater airway inflammation (e.g., asthma) may benefit more from ICS therapy. The dose and duration of ciclesonide therapy for the treatment of EIB was evaluated in a double-blind, randomized, cross-over study. Two parallel arms compared 4 doses of ciclesonide (40 mcg, 160 mcg, 80 mcg, and 320 mcg) over 3 weeks in patients 12 to 27 years of age with asthma (FEV1 baseline greater than 70% of predicted). A standardized exercise treadmill challenge was performed weekly, with FEV1 measured up to 30 minutes following exercise. There was a significant reduction in the severity of EIB over time with ciclesonide therapy. A significant reduction in the maximum decrease in FEV1 occurred as soon as 1 week after therapy initiation for all regimens (p < 0.05) except the lowest dose (40 mcg). The mean +/- SEM decrease in the maximum reduction in FEV1 at 1 week was 9% +/- 2.6% (95% CI 3.9 to 14%) in the 40 mcg/80 mcg arm compared to 8.7% +/- 2.5% (95% CI 3.7 to 13.7%) in the 160 mcg/320 mcg arm. A linear reduction continued in the 160/320 arm during subsequent weeks of treatment, while no further reduction occurred in the 40/80 arm.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    200 mcg intranasally (2 sprays in each nostril) daily (Omnaris); 74 mcg intranasally (1 spray in each nostril) daily (Zetonna); 640 mcg/day by oral inhalation.

    Geriatric

    200 mcg intranasally (2 sprays in each nostril) daily(Omnaris); 74 mcg intranasally (1 spray in each nostril) daily (Zetonna); 640 mcg/day by oral inhalation.

    Adolescents

    200 mcg intranasally (2 sprays in each nostril) daily (Omnaris); 74 mcg intranasally (1 spray in each nostril) daily (Zetonna); 640 mcg/day by oral inhalation.

    Children

    >= 12: 200 mcg intranasally (2 sprays in each nostril) daily (Omnaris); 74 mcg intranasally (1 spray in each nostril) daily (Zetonna); 640 mcg/day by oral inhalation.
    6—11 years: 200 mcg intranasally (2 sprays in each nostril) daily (Omnaris). Safe and effective use has not been established for nasal aerosol (Zetonna) or oral inhalation; however, doses up to 160 mcg/day via oral inhalation have been used off-label for asthma.
    4—5 years: Safety and efficacy have not been established; however, doses up to 160 mcg/day via oral inhalation have been used off-label for asthma.
    < 4 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dosage adjustments in hepatic impairment are not necessary.

    Renal Impairment

    Patients with renal impairment have not been studied. However, due to low oral bioavailability and low renal clearance of the drug, it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Inhalation Administration
    Oral Inhalation Administration

    For oral inhalation use only.
    Each metered actuation delivers 80 mcg/spray or 160 mcg/spray depending on the product selected.
    Prime the inhaler prior to the initial use by releasing 3 sprays into the air away from the face and other people.
    If the inhaler is not used for more than 10 consecutive days, it should be primed by releasing 3 sprays into the air.
    The canister contains a dose counter. The inhaler should be discarded after the counter reads zero; although the canister is still operational and may contain medication, the accuracy of medication delivery cannot be assured.
    When the dose indicator shows a red zone, approximately 20 inhalations are left, and a refill is required.
    Instruct patient on proper inhalation technique.
    To avoid the spread of infection, do not use the inhaler for more than one person.

    Intranasal Inhalation Administration

    Ciclesonide nasal spray (Omnaris):
    For intranasal use only.
    Prior to first use, shake the inhaler gently and prime the pump by actuating 8 times.
    If not used in 4 consecutive days, shake gently and prime with one spray or until fine mist appears.
    Product should be discarded after 120 sprays following initial priming, or 4 months after removal from pouch.
    Blow nose gently if needed. Insert spray tip into nostril, and close the other nostril with finger. With head slightly tilted forward and bottle upright, press pump quickly and firmly while inhaling through nose. Avoid spraying into eyes and directly onto the nasal septum. After administration, wipe the applicator tip with a clean tissue and replace dust cap. If applicator is clogged or needs further cleaning, remove nasal applicator and rinse with warm water. Dry and replace applicator and prime the unit with one spray or until a fine mist appears; then replace cap. To avoid the spread of infection, do not use the container for more than one person.
     
    Ciclesonide nasal aerosol (Zetonna):
    For intranasal use only.
    Prior to first use or if not used in 10 consecutive days, shake the inhaler gently and prime the pump by actuating 3 times.
    Product should be discarded after 60 sprays following initial priming, or when the dose indicator reads zero.
    Clean the nose piece weekly by wiping with a clean, dry tissue or cloth; do not wash or put any part of the canister or applicator in water.
    Blow nose gently if needed. Insert spray tip into nostril, and close the other nostril with finger. With head slightly tilted back and bottle upright, press pump quickly and firmly while inhaling through nose. Avoid spraying into eyes and directly onto the nasal septum. To avoid the spread of infection, do not use the container for more than one person.

    STORAGE

    Alvesco:
    - Exposure to temperatures above 120 degrees F may cause bursting
    - For best results, product should be at room temperature before use
    - Keep away from heat and flame
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Omnaris:
    - Do not freeze
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Zetonna:
    - Exposure to temperatures above 120 degrees F may cause bursting
    - For best results, product should be at room temperature before use
    - Keep away from heat and flame
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Corticosteroid hypersensitivity

    Ciclesonide is contraindicated for use in patients with a hypersensitivity to ciclesonide or any of its inactive ingredients. Hypersensitivity reactions, including contact dermatitis or angioedema, may occur. Cross-reactivity with other corticosteroids is also possible; therefore the drug should generally be avoided in those with a corticosteroid hypersensitivity.

    Acute bronchospasm, status asthmaticus

    The orally inhaled formulation of ciclesonide is contraindicated in patients with status asthmaticus, or other types of acute bronchospasm for which immediate, intensive therapy is warranted. Patients should be advised that ciclesonide is not to be used as a bronchodilator and is not indicated for relief of acute bronchospasm.

    Adrenal insufficiency, hypothalamic-pituitary-adrenal (HPA) suppression

    There are no adequately conducted studies in adults and adolescents that assess the effect of ciclesonide nasal spray on adrenal function. Studies in pediatric and adult populations comparing inhaled ciclesonide with inhaled budesonide indicated that ciclesonide was not associated with significant urinary cortisol suppression at low dosages. Although the risk of developing hypothalamic-pituitary-adrenal (HPA) suppression is very low with inhaled corticosteroids, patients should be monitored for this systemic effect. Particular care is needed for patients who are transferred from systemic to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic to less systemically absorbed inhaled corticosteroids. Patients receiving ciclesonide may require initiation or resumption of systemic corticosteroids during periods of stress or during severe asthma attacks.

    Fungal infection, herpes infection, infection, tuberculosis, viral infection

    In clinical studies with ciclesonide nasal spray, development of localized infections of the nose and pharynx with Candida albicans were rare. In clinical studies with ciclesonide oral inhalation aerosol, localized infections with Candida albicans occurred in the mouth and pharynx in approximately 1% of patients. Development of a Candida infection or other fungal infection may require discontinuation of ciclesonide treatment. It is advisable to periodically assess the patient for evidence of Candida infection or other signs of adverse effects on the nasal mucosa during chronic treatment with intranasal ciclesonide. Corticosteroids can reactivate tuberculosis. Therefore, ciclesonide should be used only when necessary in patients with tuberculosis infections of the respiratory tract. Corticosteroid therapy can mask the symptoms of infection. Exposure to corticosteroids should be avoided, if possible, in patients with untreated local or systemic fungal or bacterial infections, systemic parasitic or viral infection, ocular herpes simplex, or active herpes infection.

    Vaccination

    Corticosteroid therapy usually does not contraindicate vaccination with live-virus vaccines when such therapy is administered by aerosol. The immunosuppressive effects of steroid treatments differ, but many clinicians consider a dose equivalent to either 2 mg/kg or a total dose equivalent to 20 mg/day of prednisone as sufficiently immunosuppressive to raise concern about the safety of immunization with live-virus vaccines. Intranasal and oral inhalational ciclesonide have a low systemic bioavailability; therefore, significant systemic effects are not expected.

    Measles, varicella

    Due to a low systemic bioavailability following inhalational and intranasal administration, ciclesonide is not expected to produce significant systemic effects. However, it should be noted that administration of corticosteroids may result in more serious or even fatal varicella (chickenpox) or measles infection in susceptible pediatric patients or adults. In addition, the use of immunosuppressants such as corticosteroids may increase the likelihood of various infections; although the exact association between specific doses, routes, and duration of administration and the development of infection is unknown. Susceptible individuals should be instructed on the risks and avoidance of exposure to infection while receiving a corticosteroid. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated; if chickenpox develops, treatment with antiviral agents may be considered. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated.

    Children, growth inhibition, increased intracranial pressure

    Ciclesonide is not indicated for children less than 6 years of age. Children and adolescents receiving inhaled ciclesonide should be monitored closely for growth inhibition; controlled clinical studies have shown that intranasal and orally inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients. It is important to note that lack of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) suppression is not an absolute indicator of systemic corticosteroid exposure and subsequent growth velocity reductions. Short term administration (2 weeks) of orally inhaled ciclesonide appears similar to placebo in terms of reduction in growth velocity. However, the long-term effects on growth velocity and adult height associated with the drug or other corticosteroids are unknown. Therefore, the growth of pediatric patients receiving ciclesonide should be monitored routinely. The benefits of chronic treatment with ciclesonide should be weighed against the potential adverse effects in children as well as the potential advantages of non-steroid therapies. To minimize the effects of intranasal or orally inhaled corticosteroids, each patient should be titrated to the lowest effective dose. Pediatric patients may be more susceptible to developing systemic toxicity; adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of intranasal and orally inhaled corticosteroid formulations in young patients.

    Infants, neonates, pregnancy

    Ciclesonide is classified as FDA pregnancy risk category C.  There are no adequate and well-controlled studies in pregnant women. Animal studies with rats have shown no teratogenicity or other fetal effects following oral administration of doses up to 35 times the maximum human daily intranasal dose. However, the oral bioavailability of the prodrug and the active metabolite is negligible. Subcutaneous administration of doses less than the maximum human dose in rabbits has been associated with fetal toxicity, including fetal loss, reduced fetal weight, cleft palate, skeletal abnormalities, and unspecified skin effects. It is not known whether ciclesonide crosses the human placenta. Ciclesonide has a relatively low molecular weight (540.7), but both the prodrug and the active metabolite are highly protein bound (>= 99%). Hypoadrenalism may occur in neonates born of mothers receiving corticosteroids during pregnancy. Such neonates and infants should be closely monitored. Corticosteroid treatment may not be necessary during pregnancy due to a natural increase in corticosteroid production. However, poorly controlled maternal asthma also poses risk to the mother and the fetus. If inhaled corticosteroids are necessary for the control of asthma symptoms and exacerbations, the National Asthma Education and Prevention Program Expert Panel recommends the use of inhaled budesonide because there are more data available describing its use in human pregnancy. If therapy with ciclesonide is considered during pregnancy, the drug should be used only if the benefits of treatment outweigh the potential risk to the fetus.

    Breast-feeding

    According to the manufacturer, caution should be used when administering ciclesonide to women who are breast-feeding. It is not known whether ciclesonide is excreted into human milk. Other corticosteroids are excreted into breast milk. Ciclesonide has a relatively low molecular weight (540.7), but both the prodrug and the active metabolite are highly protein bound (>= 99%), which suggests that minimal amounts will be excreted into breast milk. In addition, ciclesonide has low oral bioavailability (< 1%). Although ciclesonide is not specifically addressed, the American Academy of Pediatrics considers the use of some other corticosteroids, such as prednisone, usually compatible with breast-feeding. Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy and lactation according to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group. However, due to greater availability of data in pregnancy, budesonide is the preferred agent in this population. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Cushing's syndrome

    Use of excessive dosages of corticosteroids by various routes may result in hypercorticism, manifest as menstrual irregularities, acneiform lesions, or cushingoid symptoms. Although intranasal and oral inhalational ciclesonide have a low systemic bioavailability, it may be advisable to avoid use if possible in those with Cushing's syndrome.

    Nasal septal perforation, nasal surgery, nasal trauma

    Nasal septal perforation has been reported after use of intranasal ciclesonide. Patients should be examined prior to initiating therapy with intranasal ciclesonide and periodically throughout treatment for the presence of perforations or ulcerations in the nasal cavity. If perforations, erosion, or ulcers of the nasal cavity develop, ciclesonide should be discontinued. Avoid spraying intranasal ciclesonide directly on the nasal septum. Due to the inhibitory effects of glucocorticoids on wound healing, avoid using intranasal ciclesonide in patients with a recent history of nasal surgery, nasal trauma, or nasal septal perforation/ulcers until healed.

    Osteoporosis

    Detrimental effects on bone metabolism, such as osteoporosis are expected to be much lower with inhaled, rather than systemically administered corticosteroids. Some patients receiving inhaled steroids may be at increased risk of bone loss compared to healthy individuals. The effect of ciclesonide on osteoporosis is not known; therefore, ciclesonide should be used cautiously in patients with osteoporosis despite the low systemic bioavailability.

    Geriatric

    It is unknown if geriatric patients respond differently to ciclesonide than younger adults. However, due to the possibility of decreased hepatic, renal, or cardiac function, it is advisable to initiate treatment with the lowest effective dose, and titrate slowly as clinically indicated. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). The OBRA guidelines caution that orally inhaled corticosteroids, such as ciclesonide, can cause throat irritation and oral candidiasis, particularly if the mouth is not rinsed after administration.

    Cataracts, glaucoma, increased intraocular pressure

    Corticosteroids are well known to cause cataracts and can exacerbate glaucoma during long-term administration. In clinical trials of ciclesonide nasal spray in adults and adolescents for up to 52 weeks, and children 2—11 years for up to 12 weeks, there were no significant differences in intraocular pressure changes or ophthalmologic evaluation (including evaluation of cataract formation) compared with placebo. However, rare instances of cataracts, glaucoma, and increased intraocular pressure have been reported following the intranasal administration of other corticosteroids. Glaucoma, increased intraocular pressure, and cataracts have been reported in patients receiving orally inhaled ciclesonide. Corticosteroids should be used cautiously in patients with glaucoma or family history of glaucoma, or other visual disturbances. It is advisable for patients receiving chronic treatment with ciclesonide to receive a periodic ophthalmic assessment, including an evaluation for cataract formation, changes in vision, or worsening of glaucoma.

    ADVERSE REACTIONS

    Severe

    angioedema / Rapid / 0-1.0
    nasal septum perforation / Delayed / 0-0.1
    bronchospasm / Rapid / Incidence not known

    Moderate

    dysphonia / Delayed / 0-1.0
    candidiasis / Delayed / 0-1.0
    contact dermatitis / Delayed / 0-1.0
    cataracts / Delayed / Incidence not known
    hypothalamic-pituitary-adrenal (HPA) suppression / Delayed / Incidence not known
    growth inhibition / Delayed / Incidence not known
    osteopenia / Delayed / Incidence not known

    Mild

    headache / Early / 3.0-11.0
    pharyngitis / Delayed / 3.0-10.5
    epistaxis / Delayed / 4.9-6.0
    nasal irritation / Early / 3.2-5.7
    sinusitis / Delayed / 3.1-5.5
    xerostomia / Early / 0-1.0
    cough / Delayed / 0-1.0
    rhinitis / Early / 3.0
    infection / Delayed / 2.0
    nausea / Early / 2.0
    abdominal pain / Early / 3.0
    otalgia / Early / 3.0
    arthralgia / Delayed / 3.0
    nasal congestion / Early / 3.0
    back pain / Delayed / 3.0
    influenza / Delayed / 2.0

    DRUG INTERACTIONS

    Abatacept: (Moderate) Concomitant use of immunosuppressives, as well as long-term corticosteroids, may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Acetazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with acetazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    Acetohexamide: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Adalimumab: (Moderate) Closely monitor for the development of signs and symptoms of infection if coadministration of a corticosteroid with adalimumab is necessary. Adalimumab treatment increases the risk for serious infections that may lead to hospitalization or death. Patients taking concomitant immunosuppressants including corticosteroids may be at greater risk of infection.
    Albiglutide: (Moderate) When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Aldesleukin, IL-2: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Alemtuzumab: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Alogliptin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Alogliptin; Metformin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Alogliptin; Pioglitazone: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Alpha-glucosidase Inhibitors: (Moderate) Systemic corticosteroids increase blood glucose levels. Because of this action, a potential pharmacodynamic interaction exists between corticosteroids and acarbose. Patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of acarbose.
    Altretamine: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
    Ambenonium Chloride: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
    Amphotericin B lipid complex (ABLC): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
    Amphotericin B liposomal (LAmB): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
    Amphotericin B: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
    Anthracyclines: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Antithymocyte Globulin: (Moderate) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Antitumor antibiotics: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Argatroban: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Arsenic Trioxide: (Major) Because electrolyte abnormalities increase the risk of QT interval prolongation and serious arrhythmias, avoid the concomitant use of arsenic trioxide with drugs that may cause electrolyte abnormalities, particularly hypokalemia and hypomagnesemia. Examples of drugs that may cause electrolyte abnormalities include corticosteroids. If concomitant drug use is unavoidable, frequently monitor serum electrolytes (and replace as necessary) and electrocardiograms.
    Asparaginase Erwinia chrysanthemi: (Moderate) Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions.
    Aspirin, ASA: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Carisoprodol: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Dipyridamole: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Omeprazole: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Oxycodone: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Pravastatin: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Atazanavir: (Moderate) Coadministration of ciclesonide with atazanavir may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Atazanavir; Cobicistat: (Moderate) Coadministration of ciclesonide with atazanavir may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. (Moderate) Coadministration of ciclesonide with cobicistat may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; cobicistat is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Atenolol; Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Atracurium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Azacitidine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Azathioprine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Azilsartan; Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Bacillus Calmette-Guerin Vaccine, BCG: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Basiliximab: (Minor) Because systemically administered corticosteroids have immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Bendroflumethiazide; Nadolol: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Bepridil: (Moderate) Hypokalemia-producing agents, including corticosteroids, may increase the risk of bepridil-induced arrhythmias and should therefore be administered cautiously in patients receiving bepridil therapy.
    Bevacizumab: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Bismuth Subsalicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Bortezomib: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Bupropion: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. The manufacturer recommends low initial dosing and slow dosage titration if these combinations must be used; the patient should be closely monitored.
    Bupropion; Naltrexone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. The manufacturer recommends low initial dosing and slow dosage titration if these combinations must be used; the patient should be closely monitored.
    Canagliflozin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Canagliflozin; Metformin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Capecitabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbetapentane; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbinoxamine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carmustine, BCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Chlorambucil: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Chlorothiazide: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Chlorpheniramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Chlorpropamide: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Chlorthalidone; Clonidine: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Choline Salicylate; Magnesium Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Cimetidine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Cisatracurium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Citalopram: (Major) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and corticosteroids. It should be noted that CYP3A4 is one of the isoenzymes involved in the metabolism of citalopram, and dexamethasone is an inducer of this isoenzyme. In theory, decreased efficacy of citalopram is possible during combined use with dexamethasone; however, because citalopram is metabolized by multiple enzyme systems, induction of one pathway may not appreciably increase citalopram clearance.
    Clindamycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Clofarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Cobicistat: (Moderate) Coadministration of ciclesonide with cobicistat may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; cobicistat is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of ciclesonide with cobicistat may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; cobicistat is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of ciclesonide with cobicistat may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; cobicistat is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Cod Liver Oil: (Minor) A relationship of functional antagonism exists between vitamin D analogs, which promote calcium absorption, and corticosteroids, which inhibit calcium absorption. Therapeutic effect of cod liver oil should be monitored when used concomitantly with corticosteroids.
    Codeine; Phenylephrine; Promethazine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Cytarabine, ARA-C: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Dapagliflozin: (Moderate) Systemic corticosteroids increase blood glucose levels; a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. Blood lactate concentrations and the lactate to pyruvate ratio increased when metformin was coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with an increased risk of lactic acidosis, so patients on metformin concurrently with systemic steroids should be monitored closely.
    Dapagliflozin; Metformin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. (Moderate) Systemic corticosteroids increase blood glucose levels; a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. Blood lactate concentrations and the lactate to pyruvate ratio increased when metformin was coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with an increased risk of lactic acidosis, so patients on metformin concurrently with systemic steroids should be monitored closely.
    Dapagliflozin; Saxagliptin: (Moderate) Systemic corticosteroids increase blood glucose levels. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. (Moderate) Systemic corticosteroids increase blood glucose levels; a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. Blood lactate concentrations and the lactate to pyruvate ratio increased when metformin was coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with an increased risk of lactic acidosis, so patients on metformin concurrently with systemic steroids should be monitored closely.
    Darunavir: (Moderate) Coadministration of ciclesonide with darunavir may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; darunavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Darunavir; Cobicistat: (Moderate) Coadministration of ciclesonide with cobicistat may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; cobicistat is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. (Moderate) Coadministration of ciclesonide with darunavir may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; darunavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Coadministration of ciclesonide with ritonavir may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; ritonavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Decitabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Denileukin Diftitox: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Denosumab: (Moderate) The safety and efficacy of denosumab use in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with denosumab may be at a greater risk of developing an infection.
    Desmopressin: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Dextran: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Digoxin: (Moderate) Hypokalemia, hypomagnesemia, or hypercalcemia increase digoxin's effect. Corticosteroids can precipitate digoxin toxicity via their effect on electrolyte balance. It is recommended that serum potassium, magnesium, and calcium be monitored regularly in patients receiving digoxin.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Dofetilide: (Major) Corticosteroids can cause increases in blood pressure, sodium and water retention, and hypokalemia, predisposing patients to interactions with certain other medications. Corticosteroid-induced hypokalemia could also enhance the proarrhythmic effects of dofetilide.
    Doxacurium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Droperidol: (Moderate) Caution is advised when using droperidol in combination with corticosteroids which may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias.
    Dulaglutide: (Moderate) When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Echinacea: (Moderate) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to immunosuppressant drugs like corticosteroids. For some patients who are using corticosteroids for serious illness, such as cancer or organ transplant, this potential interaction may result in the preferable avoidance of Echinacea. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources.
    Econazole: (Minor) In vitro studies indicate that corticosteroids inhibit the antifungal activity of econazole against C. albicans in a concentration-dependent manner. When the concentration of the corticosteroid was equal to or greater than that of econazole on a weight basis, the antifungal activity of econazole was substantially inhibited. When the corticosteroid concentration was one-tenth that of econazole, no inhibition of antifungal activity was observed.
    Efalizumab: (Major) Patients receiving immunosuppressives should not receive concurrent therapy with efalizumab because of the possibility of increased infections and malignancies.
    Empagliflozin: (Moderate) Systemic corticosteroids increase blood glucose levels. Because of this action, a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Empagliflozin; Linagliptin: (Moderate) Systemic corticosteroids increase blood glucose levels. Because of this action, a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Empagliflozin; Metformin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. (Moderate) Systemic corticosteroids increase blood glucose levels. Because of this action, a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Ephedrine: (Moderate) Ephedrine may enhance the metabolic clearance of corticosteroids. Decreased blood concentrations and lessened physiologic activity may necessitate an increase in corticosteroid dosage.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Estramustine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Estrogens: (Moderate) Estrogens have been associated with elevated serum concentrations of corticosteroid binding globulin (CBG), leading to increased total circulating corticosteroids, although the free concentrations of these hormones may be lower; the clinical significance is not known. Estrogens are CYP3A4 substrates and dexamethasone is a CYP3A4 inducer; concomitant use may decrease the clinical efficacy of estrogens. Patients should be monitored for signs of decreased clinical effects of estrogens (e.g., breakthrough bleeding), oral contraceptives, or non-oral combination contraceptives if these drugs are used together.
    Exenatide: (Moderate) When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Floxuridine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluconazole: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluorouracil, 5-FU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluoxymesterone: (Moderate) Coadministration of corticosteroids and fluoxymesterone may increase the risk of edema, especially in patients with underlying cardiac or hepatic disease. Corticosteroids with greater mineralocorticoid activity, such as fludrocortisone, may be more likely to cause edema. Administer these drugs in combination with caution.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Gallium Ga 68 Dotatate: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Gemcitabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Gentamicin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Glimepiride: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glimepiride; Pioglitazone: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glimepiride; Rosiglitazone: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glipizide: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glipizide; Metformin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glyburide: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glyburide; Metformin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glycerol Phenylbutyrate: (Moderate) Corticosteroids may induce elevated blood ammonia concentrations. Corticosteroids should be used with caution in patients receiving glycerol phenylbutyrate. Monitor ammonia concentrations closely.
    Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Halofantrine: (Major) Due to the risks of cardiac toxicity of halofantrine in patients with hypokalemia and/or hypomagnesemia, the use of halofantrine should be avoided in combination with agents that may lead to electrolyte losses, such as corticosteroids.
    Haloperidol: (Major) QT prolongation has been observed during haloperidol treatment. Use of haloperidol and medications known to cause electrolyte imbalance may increase the risk of QT prolongation. Therefore, caution is advisable during concurrent use of haloperidol and corticosteroids. Topical corticosteroids are less likely to interact.
    Hemin: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Corticosteroids increase the activity of this enzyme should not be used with hemin.
    Heparin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Hetastarch: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. (Moderate) Patients receiving corticosteroids during propranolol therapy may be at increased risk of hypoglycemia due to the loss of counter-regulatory cortisol response. This effect may be more pronounced in infants and young children. If concurrent use is necessary, carefully monitor vital signs and blood glucose concentrations as clinically indicated.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Hydroxyurea: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Ibritumomab Tiuxetan: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Ifosfamide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Incretin Mimetics: (Moderate) When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Indapamide: (Moderate) Additive hypokalemia may occur when indapamide is coadministered with other drugs with a significant risk of hypokalemia such as systemic corticosteroids. Coadminister with caution and careful monitoring.
    Insulin Degludec; Liraglutide: (Moderate) When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Insulin Glargine; Lixisenatide: (Moderate) When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Insulins: (Moderate) Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Interferon Alfa-2a: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Interferon Alfa-2b: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Interferon Alfa-2b; Ribavirin: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Intranasal Influenza Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Isoproterenol: (Moderate) The risk of cardiac toxicity with isoproterenol in asthma patients appears to be increased with the coadministration of corticosteroids. Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05 to 2.7 mcg/kg/min have caused clinical deterioration, myocardial infarction (necrosis), congestive heart failure and death.
    Isotretinoin: (Minor) Both isotretinoin and corticosteroids can cause osteoporosis during chronic use. Patients receiving systemic corticosteroids should receive isotretinoin therapy with caution.
    Itraconazole: (Moderate) Monitor for steroid-related adverse effects if coadministration of ciclesonide and itraconazole is necessary. Ciclesonide is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the AUC of the active metabolite of ciclesonide, des-ciclesonide, by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged.
    Ketoconazole: (Minor) Potent inhibitors of CYP3A4 may increase serum concentrations of ciclesonide and its active metabolite des-ciclesonide. In a drug interaction study, orally inhaled ciclesonide coadministered with oral ketoconazole increased the AUC of des-ciclesonide by approximately 3.6-fold at steady state, while concentrations of ciclesonide remained unchanged.
    L-Asparaginase Escherichia coli: (Moderate) Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions.
    Levetiracetam: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Levomethadyl: (Major) Caution is advised when using levomethadyl in combination with other agents, such as corticosteroids, that may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia.
    Linagliptin; Metformin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Liraglutide: (Moderate) When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Lisdexamfetamine: (Minor) The amphetamines may interfere with laboratory tests for the determination of corticosteroids. Plasma cortisol concentrations may be increased, especially during evening hours. Amphetamines may also interfere with urinary steroid determinations.
    Live Vaccines: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Lixisenatide: (Moderate) When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Lomustine, CCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Loop diuretics: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Lopinavir; Ritonavir: (Moderate) Coadministration of ciclesonide with ritonavir may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; ritonavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Magnesium Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Mannitol: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Measles/Mumps/Rubella Vaccines, MMR: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Mecasermin rinfabate: (Moderate) Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1. Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored.
    Mecasermin, Recombinant, rh-IGF-1: (Moderate) Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1. Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored.
    Meglitinides: (Moderate) Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Melphalan: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Mepenzolate: (Minor) Anticholinergics, such as mepenzolate, antagonize the effects of antiglaucoma agents. Mepenzolate is contraindicated in patients with glaucoma and therefore should not be coadministered with medications being prescribed for the treatment of glaucoma. In addition, anticholinergic drugs taken concurrently with corticosteroids in the presence of increased intraocular pressure may be hazardous.
    Metformin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Metformin; Pioglitazone: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Metformin; Repaglinide: (Moderate) Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Metformin; Rosiglitazone: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Metformin; Saxagliptin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. (Moderate) Systemic corticosteroids increase blood glucose levels. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Metformin; Sitagliptin: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. (Moderate) Systemic corticosteroids increase blood glucose levels. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Methazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with methazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. The chronic use of corticosteroids may augment calcium excretion with methazolamide leading to increased risk for hypocalcemia and/or osteoporosis.
    Methenamine; Sodium Acid Phosphate: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Methoxsalen: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Methyclothiazide: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Metolazone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Micafungin: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. Patients who are taking immunosuppressives such as the corticosteroids with micafungin concomitantly may have additive risks for infection or other side effects. In a pharmacokinetic trial, micafungin had no effect on the pharmacokinetics of prednisolone. Acute intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of micafungin (200 mg) and oral prednisolone (20 mg). This reaction was transient, and the subject did not develop significant anemia.
    Mitoxantrone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Mivacurium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Moxifloxacin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Muromonab-CD3: (Major) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections. Close clinical monitoring is advised with concurrent use; in the presence of serious infections, continuation of the corticosteroid or immunosuppressive agent may be necessary but should be accompanied by appropriate antimicrobial therapies as indicated.
    Natalizumab: (Major) Ordinarily, patients receiving chronic immunosuppressant therapy should not be treated with natalizumab. Treatment recommendations for combined corticosteroid therapy are dependent on the underlying indication for natalizumab therapy. Corticosteroids should be tapered in those patients with Crohn's disease who are on chronic corticosteroids when they start natalizumab therapy, as soon as a therapeutic benefit has occurred. If the patient cannot discontinue systemic corticosteroids within 6 months, discontinue natalizumab. The concomitant use of natalizumab and corticosteroids may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy, over the risk observed with use of natalizumab alone. In multiple sclerosis (MS) clinical trials, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in natalizumab-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids. Short courses of steroid use during natalizumab, such as when they are needed for MS relapse treatment, appear to be acceptable for use concurrently.
    Nateglinide: (Moderate) Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Nelarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Neostigmine: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
    Neuromuscular blockers: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Nonsteroidal antiinflammatory drugs: (Moderate) Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged concomitant administration should be avoided. Concomitant use of corticosteroids appears to increase the risk of adverse GI events due to NSAIDs. Corticosteroids can have profound effects on sodium-potassium balance; NSAIDs also can affect sodium and fluid balance. Monitor serum potassium concentrations; potassium supplementation may be necessary. In addition, NSAIDs may mask fever, pain, swelling and other signs and symptoms of an infection; use NSAIDs with caution in patients receiving immunosuppressant dosages of corticosteroids. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Coadministration of ciclesonide with ritonavir may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; ritonavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Ondansetron: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Oxymetholone: (Moderate) Concomitant use of oxymetholone with corticosteroids or corticotropin, ACTH may cause increased edema. Manage edema with diuretic and/or digitalis therapy.
    Pancuronium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Pegaspargase: (Moderate) Concomitant use of pegaspargase with corticosteroids can result in additive hyperglycemia. Insulin therapy may be required in some cases.
    Penicillamine: (Major) Agents such as immunosuppressives have adverse reactions similar to those of penicillamine. Concomitant use of penicillamine with these agents is contraindicated because of the increased risk of developing severe hematologic and renal toxicity.
    Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Phenylephrine; Promethazine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Phosphorus Salts: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Photosensitizing agents: (Minor) Corticosteroids administered systemically prior to or concomitantly with photosensitizing agents may decrease the efficacy of photodynamic therapy.
    Physostigmine: (Minor) Corticosteroids may interact with cholinesterase inhibitors, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
    Pimozide: (Moderate) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Use of pimozide and medications known to cause electrolyte imbalance may increase the risk of QT prolongation. Therefore, caution is advisable during concurrent use of pimozide and corticosteroids. Topical corticosteroids are less likely to interact. According to the manufacturer, potassium deficiencies should be correctly prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
    Potassium Phosphate; Sodium Phosphate: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Potassium Salts: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Potassium: (Moderate) Corticotropin can cause alterations in serum potassium levels. The use of potassium salts or supplements would be expected to alter the effects of corticotropin on serum potassium levels. Also, there have been reports of generalized tonic-clonic seizures and/or loss of consciousness associated with use of bowel preparation products in patients with no prior history of seizure disorder. Therefore, magnesium sulfate; potassium sulfate; sodium sulfate should be administered with caution during concurrent use of medications that lower the seizure threshold such as systemic corticosteroids.
    Potassium-sparing diuretics: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Pramlintide: (Moderate) Systemic corticosteroids increase blood glucose levels. Because of this action, a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations.
    Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations.
    Propranolol: (Moderate) Patients receiving corticosteroids during propranolol therapy may be at increased risk of hypoglycemia due to the loss of counter-regulatory cortisol response. This effect may be more pronounced in infants and young children. If concurrent use is necessary, carefully monitor vital signs and blood glucose concentrations as clinically indicated.
    Purine analogs: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
    Pyridostigmine: (Minor) Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
    Pyrimidine analogs: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Quetiapine: (Major) QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance. Therefore, caution is advisable during concurrent use of quetiapine and corticosteroids.
    Rapacuronium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Repaglinide: (Moderate) Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Ritodrine: (Major) Ritodrine has caused maternal pulmonary edema, which appears more often in patients treated concomitantly with corticosteroids. Patients so treated should be closely monitored in the hospital.
    Ritonavir: (Moderate) Coadministration of ciclesonide with ritonavir may cause elevated ciclesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Ciclesonide is a CYP3A4 substrate; ritonavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Rituximab: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy.
    Rituximab; Hyaluronidase: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy.
    Rocuronium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Rotavirus Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Rubella Virus Vaccine Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Salicylates: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Salsalate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Saxagliptin: (Moderate) Systemic corticosteroids increase blood glucose levels. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Simvastatin; Sitagliptin: (Moderate) Systemic corticosteroids increase blood glucose levels. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Sitagliptin: (Moderate) Systemic corticosteroids increase blood glucose levels. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Smallpox Vaccine, Vaccinia Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Sodium Benzoate; Sodium Phenylacetate: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
    Sodium Chloride: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Sodium Phenylbutyrate: (Moderate) The concurrent use of corticosteroids with sodium phenylbutyrate may increase plasma ammonia levels (hyperammonemia) by causing the breakdown of body protein. Patients with urea cycle disorders being treated with sodium phenylbutyrate usually should not receive regular treatment with corticosteroids.
    Somatropin, rh-GH: (Moderate) Corticosteroids can retard bone growth and therefore, can inhibit the growth-promoting effects of somatropin. If corticosteroid therapy is required, the corticosteroid dose should be carefully adjusted.
    Succinylcholine: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Sulfonylureas: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Taxanes: (Moderate) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. In addition, Cabazitaxel is a CYP3A4 substrate and concomitant use with strong CYP3A4 inducers such as dexamethasone may lead to reduced concentrations of cabazitaxel. Avoid concomitant use of cabazitaxel and strong CYP3A4 inducers. Consider alternative therapies with low enzyme induction potential.
    Telbivudine: (Moderate) The risk of myopathy may be increased if corticosteroids are coadministered with telbivudine. Monitor patients for any signs or symptoms of unexplained muscle pain, tenderness, or weakness, particularly during periods of upward dosage titration.
    Testosterone: (Moderate) Coadministration of corticosteroids and testosterone may increase the risk of edema, especially in patients with underlying cardiac or hepatic disease. Corticosteroids with greater mineralocorticoid activity, such as fludrocortisone, may be more likely to cause edema. Administer these drugs in combination with caution.
    Thiazide diuretics: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Thiazolidinediones: (Moderate) Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Thyroid hormones: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Tobramycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Tolazamide: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Tolbutamide: (Moderate) Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Tositumomab: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Trastuzumab: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Tretinoin, ATRA: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Tubocurarine: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Typhoid Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Vancomycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Varicella-Zoster Virus Vaccine, Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Vecuronium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Vigabatrin: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Vinblastine: (Minor) Use caution when administering vinblastine concurrently with a CYP3A4 inducer such as dexamethasone. Vinblastine is metabolized by CYP3A4 and dexamethasone may decrease vinblastine plasma concentrations. In addition, because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections. Close clinical monitoring is advised with concurrent use; in the presence of serious infections, continuation of the corticosteroid or immunosuppressive agent may be necessary but should be accompanied by appropriate antimicrobial therapies as indicated.
    Vincristine Liposomal: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Vorinostat: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
    Warfarin: (Moderate) The effect of corticosteroids on oral anticoagulants (e.g., warfarin) is variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with corticosteroids; however, limited published data exist, and the mechanism of the interaction is not well described. High-dose corticosteroids appear to pose a greater risk for increased anticoagulant effect. In addition, corticosteroids have been associated with a risk of peptic ulcer and gastrointestinal bleeding. Thus corticosteroids should be used cautiously and with appropriate clinical monitoring in patients receiving oral anticoagulants; coagulation indices (e.g., INR, etc.) should be monitored to maintain the desired anticoagulant effect. During high-dose corticosteroid administration, daily laboratory monitoring may be desirable.
    Yellow Fever Vaccine, Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as corticosteroids.
    Zileuton: (Minor) Zileuton is metabolized by the cytochrome P450 isoenzyme 3A4. Although administration of zileuton with other drugs metabolized by CYP3A4 has not been studied, zileuton may inhibit CYP3A4 isoenzymes. Zileuton could potentially compete with other CYP3A4 substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    According to the manufacturer, caution should be used when administering ciclesonide to women who are breast-feeding. It is not known whether ciclesonide is excreted into human milk. Other corticosteroids are excreted into breast milk. Ciclesonide has a relatively low molecular weight (540.7), but both the prodrug and the active metabolite are highly protein bound (>= 99%), which suggests that minimal amounts will be excreted into breast milk. In addition, ciclesonide has low oral bioavailability (< 1%). Although ciclesonide is not specifically addressed, the American Academy of Pediatrics considers the use of some other corticosteroids, such as prednisone, usually compatible with breast-feeding. Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy and lactation according to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group. However, due to greater availability of data in pregnancy, budesonide is the preferred agent in this population. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Ciclesonide is a non-halogenated glucocorticoid. The exact mechanism by which ciclesonide treats allergic rhinitis symptoms is not known. Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. Des-ciclesonide, the active metabolite of ciclesonide, has anti-inflammatory activity with affinity for the glucocorticoid receptor that is 120 times higher than the parent compound. In general, glucocorticoids inhibit the activity of a variety of cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators involved in allergic and nonallergic/irritant-mediated inflammation (e.g., histamine, eicosanoids, leukotrienes, and cytokines). At the molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. Subsequent to binding, transcription and, ultimately, protein synthesis are affected. The result can include inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. The anti-inflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Some of the net effects include reduction in edema or scar tissue as well as a general suppression in immune response. The numerous adverse effects related to corticosteroid use usually depend on the dose administered and the duration of therapy.
     
    In the treatment of asthma, corticosteroids block the late phase allergic response to allergens. Mediators involved in the pathogenesis of asthma include histamine, leukotrienes (slow releasing substance of anaphylaxis, SRS-A), eosinophil chemotactic factor of anaphylaxis (ECF-A), neutrophil chemotactic factor (NCF), cytokines, hydroxyeicosatetraenoic acids, prostaglandin-generating factor of anaphylaxis (PGF-A), prostaglandins, major basic protein, bradykinin, adenosine, peroxides, and superoxide anions. Different cell types are responsible for release of these mediators including airway epithelium, eosinophils, basophils, lung parenchyma, lymphocytes, macrophages, mast cells, neutrophils, and platelets. Corticosteroids inhibit the release of these mediators as well as inhibit IgE synthesis, attenuate mucous secretion and eicosanoid generation, up-regulate beta-receptors, promote vasoconstriction, and suppress inflammatory cell influx and inflammatory processes. Clinical effects in asthma include a reduction in bronchial hyperresponsiveness to allergens, a decreased number of asthma exacerbations, and an improvement in FEV-1, peak-flow rate, and respiratory symptoms. Since corticosteroid effects take several hours to days to become clinically noticeable, they are ineffective for primary treatment of severe acute bronchospastic attacks or for status asthmaticus. Inhaled corticosteroids have no bronchodilatory properties. Cortisol suppression following administration of ciclesonide by oral inhalation appears negligible.

    PHARMACOKINETICS

    Ciclesonide is administered by intranasal inhalation or oral inhalation.  Although not administered orally in clinical practice, ciclesonide and it's active metabolite, des-ciclesonide, have a low oral bioavailability (less than 1%) due to low gastrointestinal absorption and high first-pass metabolism. Following intravenous administration of ciclesonide 800 mcg, the volumes of distribution of ciclesonide and des-ciclesonide were approximately 2.9 L/kg and 12.1 L/kg, respectively. The percentage of ciclesonide and des-ciclesonide bound to human plasma proteins averaged at or above 99% each, with less than 1% of unbound drug detected in the systemic circulation. Des-ciclesonide is not significantly bound to human transcortin.
     
    Esterases in the nasal and lung mucosa hydrolyze ciclesonide to a biologically active metabolite, des-ciclesonide. Des-ciclesonide undergoes further metabolism in the liver to additional metabolites primarily via CYP3A4, and by CYP2D6 as a minor pathway. Approximately 19.3% of an intravenous dose is accounted for by ciclesonide or des-ciclesonide; the remainder may consist of unidentified metabolites. The mean half-life of ciclesonide and des-ciclesonide is 0.71 hours and 6—7 hours, respectively. Ciclesonide is predominantly excreted via the feces (66%) indicating that excretion through bile is a major route of elimination. Approximately 20% or less is excreted in the urine.

    Inhalation Route

    The onset of action following intranasal administration is 24—48 hours, with additional desired effects observed after 1—2 weeks in those with seasonal allergic rhinitis and 5 weeks in those with perennial allergic rhinitis. Although intranasal administration of ciclesonide at recommended doses results in negligible serum concentrations, des-ciclesonide, the active metabolite of ciclesonide, is detected in the serum of some patients. However, in one study in healthy adults treated for two weeks with daily dose of 200 mcg or less, detectable serum levels of des-ciclesonide were not observed. Serum concentrations of ciclesonide and des-ciclesonide were measured and compared following oral inhalation of 1280 mcg and intravenous administration of 800 mcg. The absolute bioavailability of ciclesonide was 22% and the relative systemic exposure of des-ciclesonide was 63%.