Rayos (Prednisone)
Dosage & administration
Individualize dosing based on disease severity and patient response. The timing of administration should take into account the delayed-release pharmacokinetics and the disease or condition being treated (
Individualize dosing based on disease severity and patient response. The timing of administration should take into account the delayed-release pharmacokinetics and the disease or condition being treated :
Dosage of RAYOS should be individualized according to the severity of the disease and the response of the patient. For pediatric patients, the recommended dosage should be governed by the same considerations rather than strict adherence to the ratio indicated by age or body weight.
The maximal activity of the adrenal cortex is between 2 am and 8 am and is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocorticoid activity the least when given at the time of maximal activity. RAYOS is a delayed-release formulation of prednisone which releases the active substance beginning approximately 4 hours after intake
The initial dosage of RAYOS may vary from 5 to 60 mg per day depending on the specific disease entity being treated. Patients currently on immediate release prednisone, prednisolone, or methylprednisolone should be switched to RAYOS at an equivalent dose based on relative potency (2.4).
In situations of less severity, lower doses will generally suffice while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period there is a lack of satisfactory clinical response, RAYOS should be discontinued and the patient transferred to other appropriate therapy. It should be emphasized that dosage requirements are variable and must be individualized on the basis of the disease under treatment and the response of the patient.
After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment. In this latter situation it may be necessary to increase the dosage of RAYOS for a period of time consistent with the patient's condition. If a period of spontaneous remission occurs in a chronic condition, treatment should be discontinued. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
Blood pressure, body weight, routine laboratory studies (including 2-hour postprandial blood glucose and serum potassium), and chest X-ray should be obtained at regular intervals during prolonged therapy with RAYOS. Upper GI X-rays are desirable in patients with known or suspected peptic ulcer disease.
RAYOS is for oral administration.
RAYOS should be taken daily with food
RAYOS tablets should not be broken, divided, or chewed because the delayed release of prednisone is dependent on an intact coating
For the purpose of comparison, one 5 mg RAYOS tablet is the equivalent milligram dosage of the following various corticosteroids:
| Betamethasone, 0.75 mg | Paramethasone, 2 mg |
| Cortisone, 25 mg | Prednisolone, 5 mg |
| Dexamethasone, 0.75 mg | Prednisone, 5 mg |
| Hydrocortisone, 20 mg | Triamcinolone, 4 mg |
| Methylprednisolone, 4 mg |
These dose relationships apply only to oral or intravenous administration of these compounds. When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.
Naturally occurring corticosteroids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs, such as prednisone, are primarily used for their potent anti-inflammatory effects in disorders of many organ systems.
Corticosteroids, such as prednisone, cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.
Prednisone is a synthetic adrenocortical steroid drug with predominantly corticosteroid properties. Some of these properties reproduce the physiological actions of endogenous glucocorticosteroids, but others do not necessarily reflect any of the adrenal hormones' normal functions; they are seen only after administration of large therapeutic doses of the drug. The pharmacological effects of prednisone which are due to its corticosteroid properties include: promotion of gluconeogenesis; increased deposition of glycogen in the liver; inhibition of the utilization of glucose; anti-insulin activity; increased catabolism of protein; increased lipolysis; stimulation of fat synthesis and storage; increased glomerular filtration rate and resulting increase in urinary excretion of urate (creatinine excretion remains unchanged); and increased calcium excretion.
Depressed production of eosinophils and lymphocytes occurs, but erythropoiesis and production of polymorphonuclear leukocytes are stimulated. Inflammatory processes (edema, fibrin deposition, capillary dilatation, migration of leukocytes and phagocytosis) and the later stages of wound healing (capillary proliferation, deposition of collagen, cicatrization) are inhibited.
Prednisone can stimulate secretion of various components of gastric juice. Suppression of the production of corticotropin may lead to suppression of endogenous corticosteroids. Prednisone has slight mineralocorticoid activity, whereby entry of sodium into cells and loss of intracellular potassium is stimulated. This is particularly evident in the kidney, where rapid ion exchange leads to sodium retention and hypertension.
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Rayos prescribing information
Warnings and Precautions, Immunosuppression and Increased Risk of Infection (Corticosteroids, including RAYOS, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can:
Corticosteroid-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages. Monitor for the development of infection and consider RAYOS withdrawal or dosage reduction as needed. Tuberculosis If RAYOS is used to treat a condition in patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Closely monitor such patients for reactivation. During prolonged RAYOS therapy, patients with latent tuberculosis or tuberculin reactivity should receive chemoprophylaxis. Varicella Zoster and Measles Viral Infections Varicella and measles can have a serious or even fatal course in non-immune patients taking corticosteroids, including RAYOS. In corticosteroid-treated patients who have not had these diseases or are non-immune, particular care should be taken to avoid exposure to varicella and measles:
Hepatitis B Virus Reactivation Hepatitis B virus reactivation can occur in patients who are hepatitis B carriers treated with immunosuppressive dosages of corticosteroids, including RAYOS. Reactivation can also occur infrequently in corticosteroid-treated patients who appear to have resolved hepatitis B infection. Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treatment with RAYOS. For patients who show evidence of hepatitis B infection, recommend consultation with physicians with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy. Fungal Infections Corticosteroids, including RAYOS, may exacerbate systemic fungal infections; therefore, avoid RAYOS use in the presence of such infections unless RAYOS is needed to control drug reactions. For patients on chronic RAYOS therapy who develop systemic fungal infections, RAYOS withdrawal or dosage reduction is recommended. Amebiasis Corticosteroids, including RAYOS, may activate latent amebiasis. Therefore, it is recommended that latent amebiasis or active amebiasis be ruled out before initiating RAYOS in patients who have spent time in the tropics or patients with unexplained diarrhea. Strongyloides Infestation Corticosteroids, including RAYOS, should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. Cerebral Malaria Avoid corticosteroids, including RAYOS, in patients with cerebral malaria. | 03/2024 |
RAYOS is indicated in the treatment of the following diseases or conditions:
Individualize dosing based on disease severity and patient response. The timing of administration should take into account the delayed-release pharmacokinetics and the disease or condition being treated (
Individualize dosing based on disease severity and patient response. The timing of administration should take into account the delayed-release pharmacokinetics and the disease or condition being treated :
- Initial dose: RAYOS 5 mg administered once per day. Patients currently on immediate-release prednisone, prednisolone, or methylprednisolone should be switched to RAYOS at an equivalent dose based on relative potency.
- Maintenance dose: Use lowest dosage that will maintain an adequate clinical response.
- Discontinuation: Withdraw gradually if discontinuing long-term or high-dose therapy.
- RAYOS should be taken daily with food.
- RAYOS should be swallowed whole and not broken, divided, or chewed.
Dosage of RAYOS should be individualized according to the severity of the disease and the response of the patient. For pediatric patients, the recommended dosage should be governed by the same considerations rather than strict adherence to the ratio indicated by age or body weight.
The maximal activity of the adrenal cortex is between 2 am and 8 am and is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocorticoid activity the least when given at the time of maximal activity. RAYOS is a delayed-release formulation of prednisone which releases the active substance beginning approximately 4 hours after intake
The initial dosage of RAYOS may vary from 5 to 60 mg per day depending on the specific disease entity being treated. Patients currently on immediate release prednisone, prednisolone, or methylprednisolone should be switched to RAYOS at an equivalent dose based on relative potency (2.4).
In situations of less severity, lower doses will generally suffice while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period there is a lack of satisfactory clinical response, RAYOS should be discontinued and the patient transferred to other appropriate therapy. It should be emphasized that dosage requirements are variable and must be individualized on the basis of the disease under treatment and the response of the patient.
After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment. In this latter situation it may be necessary to increase the dosage of RAYOS for a period of time consistent with the patient's condition. If a period of spontaneous remission occurs in a chronic condition, treatment should be discontinued. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
Blood pressure, body weight, routine laboratory studies (including 2-hour postprandial blood glucose and serum potassium), and chest X-ray should be obtained at regular intervals during prolonged therapy with RAYOS. Upper GI X-rays are desirable in patients with known or suspected peptic ulcer disease.
RAYOS is for oral administration.
RAYOS should be taken daily with food
RAYOS tablets should not be broken, divided, or chewed because the delayed release of prednisone is dependent on an intact coating
For the purpose of comparison, one 5 mg RAYOS tablet is the equivalent milligram dosage of the following various corticosteroids:
| Betamethasone, 0.75 mg | Paramethasone, 2 mg |
| Cortisone, 25 mg | Prednisolone, 5 mg |
| Dexamethasone, 0.75 mg | Prednisone, 5 mg |
| Hydrocortisone, 20 mg | Triamcinolone, 4 mg |
| Methylprednisolone, 4 mg |
These dose relationships apply only to oral or intravenous administration of these compounds. When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.
Naturally occurring corticosteroids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs, such as prednisone, are primarily used for their potent anti-inflammatory effects in disorders of many organ systems.
Corticosteroids, such as prednisone, cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.
Prednisone is a synthetic adrenocortical steroid drug with predominantly corticosteroid properties. Some of these properties reproduce the physiological actions of endogenous glucocorticosteroids, but others do not necessarily reflect any of the adrenal hormones' normal functions; they are seen only after administration of large therapeutic doses of the drug. The pharmacological effects of prednisone which are due to its corticosteroid properties include: promotion of gluconeogenesis; increased deposition of glycogen in the liver; inhibition of the utilization of glucose; anti-insulin activity; increased catabolism of protein; increased lipolysis; stimulation of fat synthesis and storage; increased glomerular filtration rate and resulting increase in urinary excretion of urate (creatinine excretion remains unchanged); and increased calcium excretion.
Depressed production of eosinophils and lymphocytes occurs, but erythropoiesis and production of polymorphonuclear leukocytes are stimulated. Inflammatory processes (edema, fibrin deposition, capillary dilatation, migration of leukocytes and phagocytosis) and the later stages of wound healing (capillary proliferation, deposition of collagen, cicatrization) are inhibited.
Prednisone can stimulate secretion of various components of gastric juice. Suppression of the production of corticotropin may lead to suppression of endogenous corticosteroids. Prednisone has slight mineralocorticoid activity, whereby entry of sodium into cells and loss of intracellular potassium is stimulated. This is particularly evident in the kidney, where rapid ion exchange leads to sodium retention and hypertension.
- Initial dose: RAYOS 5 mg administered once per day. Patients currently on immediate-release prednisone, prednisolone, or methylprednisolone should be switched to RAYOS at an equivalent dose based on relative potency. (,
2.1 Recommended DosingDosage of RAYOS should be individualized according to the severity of the disease and the response of the patient. For pediatric patients, the recommended dosage should be governed by the same considerations rather than strict adherence to the ratio indicated by age or body weight.
The maximal activity of the adrenal cortex is between 2 am and 8 am and is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocorticoid activity the least when given at the time of maximal activity. RAYOS is a delayed-release formulation of prednisone which releases the active substance beginning approximately 4 hours after intake
[see Clinical Pharmacology (12.3)]. The timing of RAYOS administration should take into account the delayed-release pharmacokinetics and the disease or condition being treated.The initial dosage of RAYOS may vary from 5 to 60 mg per day depending on the specific disease entity being treated. Patients currently on immediate release prednisone, prednisolone, or methylprednisolone should be switched to RAYOS at an equivalent dose based on relative potency (2.4).
In situations of less severity, lower doses will generally suffice while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period there is a lack of satisfactory clinical response, RAYOS should be discontinued and the patient transferred to other appropriate therapy. It should be emphasized that dosage requirements are variable and must be individualized on the basis of the disease under treatment and the response of the patient.
After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment. In this latter situation it may be necessary to increase the dosage of RAYOS for a period of time consistent with the patient's condition. If a period of spontaneous remission occurs in a chronic condition, treatment should be discontinued. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
)2.4 Corticosteroid Comparison ChartFor the purpose of comparison, one 5 mg RAYOS tablet is the equivalent milligram dosage of the following various corticosteroids:
Betamethasone, 0.75 mg Paramethasone, 2 mg Cortisone, 25 mg Prednisolone, 5 mg Dexamethasone, 0.75 mg Prednisone, 5 mg Hydrocortisone, 20 mg Triamcinolone, 4 mg Methylprednisolone, 4 mg These dose relationships apply only to oral or intravenous administration of these compounds. When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.
- Maintenance dose: Use lowest dosage that will maintain an adequate clinical response. ()
2.1 Recommended DosingDosage of RAYOS should be individualized according to the severity of the disease and the response of the patient. For pediatric patients, the recommended dosage should be governed by the same considerations rather than strict adherence to the ratio indicated by age or body weight.
The maximal activity of the adrenal cortex is between 2 am and 8 am and is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocorticoid activity the least when given at the time of maximal activity. RAYOS is a delayed-release formulation of prednisone which releases the active substance beginning approximately 4 hours after intake
[see Clinical Pharmacology (12.3)]. The timing of RAYOS administration should take into account the delayed-release pharmacokinetics and the disease or condition being treated.The initial dosage of RAYOS may vary from 5 to 60 mg per day depending on the specific disease entity being treated. Patients currently on immediate release prednisone, prednisolone, or methylprednisolone should be switched to RAYOS at an equivalent dose based on relative potency (2.4).
In situations of less severity, lower doses will generally suffice while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period there is a lack of satisfactory clinical response, RAYOS should be discontinued and the patient transferred to other appropriate therapy. It should be emphasized that dosage requirements are variable and must be individualized on the basis of the disease under treatment and the response of the patient.
After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment. In this latter situation it may be necessary to increase the dosage of RAYOS for a period of time consistent with the patient's condition. If a period of spontaneous remission occurs in a chronic condition, treatment should be discontinued. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
- Discontinuation: Withdraw gradually if discontinuing long-term or high-dose therapy. ()
2.1 Recommended DosingDosage of RAYOS should be individualized according to the severity of the disease and the response of the patient. For pediatric patients, the recommended dosage should be governed by the same considerations rather than strict adherence to the ratio indicated by age or body weight.
The maximal activity of the adrenal cortex is between 2 am and 8 am and is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocorticoid activity the least when given at the time of maximal activity. RAYOS is a delayed-release formulation of prednisone which releases the active substance beginning approximately 4 hours after intake
[see Clinical Pharmacology (12.3)]. The timing of RAYOS administration should take into account the delayed-release pharmacokinetics and the disease or condition being treated.The initial dosage of RAYOS may vary from 5 to 60 mg per day depending on the specific disease entity being treated. Patients currently on immediate release prednisone, prednisolone, or methylprednisolone should be switched to RAYOS at an equivalent dose based on relative potency (2.4).
In situations of less severity, lower doses will generally suffice while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period there is a lack of satisfactory clinical response, RAYOS should be discontinued and the patient transferred to other appropriate therapy. It should be emphasized that dosage requirements are variable and must be individualized on the basis of the disease under treatment and the response of the patient.
After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment. In this latter situation it may be necessary to increase the dosage of RAYOS for a period of time consistent with the patient's condition. If a period of spontaneous remission occurs in a chronic condition, treatment should be discontinued. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
- RAYOS should be taken daily with food. (,
2.3 Method of AdministrationRAYOS is for oral administration.
RAYOS should be taken daily with food
[see Clinical Pharmacology (12.3)].RAYOS tablets should not be broken, divided, or chewed because the delayed release of prednisone is dependent on an intact coating
[see Description (11)].)12.3 PharmacokineticsThe pharmacokinetic profile of RAYOS has an approximately 4-hour lag time from that of immediate-release prednisone formulations. While the pharmacokinetic profile of RAYOS when given with food differs in terms of lag time from IR prednisone, its absorption, distribution, and elimination processes are comparable.
AbsorptionPrednisone is released from RAYOS when taken with food approximately 4 hours after oral ingestion. This causes a delay in the time until peak plasma concentrations (Tmax) are achieved. Median Tmaxof RAYOS in 27 healthy male subjects was 6.0 - 6.5 hours compared to 2.0 hours for an immediate-release (IR) formulation. Subsequently, prednisone was absorbed at the same rate as the IR formulation. Peak plasma concentrations (Cmax) and exposure, as indicated by AUC0-lastand AUC0--∞, were comparable for both prednisone IR and RAYOS administered 2.5 hours after a light meal or with normal meal (Figure 1).
Figure 1. Mean Plasma Levels of Prednisone After a Single Dose of 5 mg Prednisone Administered as a 5 mg RAYOS Tablet or a 5 mg Immediate-Release (IR) Tablet A: 5 mg IR tablet under fasting conditions, administered at 2 am, B: 5 mg RAYOS, administered 2.5 hours after a light evening meal, and C: 5 mg RAYOS administered immediately after dinner. 
In a study with 24 healthy subjects, oral absorption of prednisone from RAYOS was significantly affected by the intake of food. Under standard fasting conditions, both the maximum plasma concentration (Cmax) and the bioavailability of RAYOS were significantly lower than under fed conditions, shortly after intake of a high fat meal.
RAYOS at dose levels of 1 mg, 2 mg, and 5 mg showed dose-proportionality in terms of peak and systemic exposure (Cmax, AUC0-∞, and AUC0-last) for the parent drug prednisone as well as for the active metabolite prednisolone.
Figure 1 MetabolismPrednisone is completely converted to the active metabolite prednisolone, which is further metabolized mainly in the liver and excreted in the urine as sulfate and glucuronide conjugates. The exposure of prednisolone is 4-6 fold higher than that of prednisone.
ExcretionThe terminal half-life of both prednisone and prednisolone from the administration of RAYOS was 2-3 hours, which is comparable to that from the IR formulation.
Special PopulationsThe effects of gender, age, renal impairment, and hepatic impairment on the pharmacokinetics of prednisone or prednisolone after administration of RAYOS have not been evaluated.
- RAYOS should be swallowed whole and not broken, divided, or chewed. ()
2.3 Method of AdministrationRAYOS is for oral administration.
RAYOS should be taken daily with food
[see Clinical Pharmacology (12.3)].RAYOS tablets should not be broken, divided, or chewed because the delayed release of prednisone is dependent on an intact coating
[see Description (11)].
Delayed-release Tablets
- RAYOS 1 mg prednisone: Pale yellowish-white, round, unscored delayed-release tablet embossed with "NP 1" on one side.
- RAYOS 2 mg prednisone: Yellowish-white, round, unscored delayed-release tablet embossed with "NP 2" on one side.
- RAYOS 5 mg prednisone: Light yellow, round, unscored delayed-release tablet embossed with "NP 5" on one side.
Based on findings from human and animal studies, corticosteroids, including RAYOS, can cause fetal harm when administered to a pregnant woman
Published epidemiological studies on the association between prednisolone and fetal outcomes have reported inconsistent findings and have important methodological limitations. Multiple cohort and case-controlled studies in humans suggest that maternal corticosteroid use during the first trimester increases the incidence of cleft lip with or without cleft palate from about 1/1000 infants to 3-5/1000 infants; however, a risk for orofacial clefts has not been observed in all studies. Methodological limitations of these studies include non-randomized design, retrospective data collection, and the inability to control for confounders such as underlying maternal disease and use of concomitant medications.
Two prospective case control studies showed decreased birth weight in infants exposed to maternal corticosteroids in utero. In humans, the risk of decreased birth weight appears to be dose related and may be minimized by administering lower corticosteroid doses. It is likely that underlying maternal conditions contribute to intrauterine growth restriction and decreased birth weight, but it is unclear to what extent these maternal conditions contribute to the increased risk of orofacial clefts.
Prednisolone, the active metabolite of prednisone, administered during the period of organogenesis, has been shown to be teratogenic in rats, rabbits, hamsters, and mice with increased incidence of cleft palate in offspring. In teratogenicity studies, cleft palate along with elevation of fetal lethality (or increase in resorptions) and reductions in fetal body weight were seen in rats at maternal doses of 30 mg/kg (equivalent to 290 mg in a 60 kg individual based on mg/m2body surface comparison) and higher. Cleft palate was observed in mice at a maternal dose of 20 mg/kg (equivalent to 100 mg in a 60 kg individual based on mg/m2comparison). Additionally, constriction of the ductus arteriosus has been observed in fetuses of pregnant rats exposed to prednisolone. RAYOS was not formally evaluated in animal reproduction studies.
Prednisone can cause fetal harm when administered to a pregnant woman. Human studies suggest a small but inconsistent increased risk of orofacial clefts with use of corticosteroids during the first trimester of pregnancy. Published animal studies show prednisolone to be teratogenic in rats, rabbits, hamsters, and mice with increased incidence of cleft palate in offspring. Intrauterine growth restriction and decreased birth weight have also been reported with corticosteroid use during pregnancy, however, the underlying maternal condition may also contribute to these risks. If this drug is used during pregnancy, or if the patient becomes pregnant while using this drug, advise the patient about the potential harm to the fetus
Infants born to pregnant women who have received corticosteroids should be carefully monitored for signs and symptoms of hypoadrenalism
Published epidemiological studies on the association between prednisolone and fetal outcomes have reported inconsistent findings and have important methodological limitations. Multiple cohort and case-controlled studies in humans suggest that maternal corticosteroid use during the first trimester increases the incidence of cleft lip with or without cleft palate from about 1/1000 infants to 3-5/1000 infants; however, a risk for orofacial clefts has not been observed in all studies. Methodological limitations of these studies include non-randomized design, retrospective data collection, and the inability to control for confounders such as underlying maternal disease and use of concomitant medications.
Two prospective case control studies showed decreased birth weight in infants exposed to maternal corticosteroids in utero. In humans, the risk of decreased birth weight appears to be dose related and may be minimized by administering lower corticosteroid doses. It is likely that underlying maternal conditions contribute to intrauterine growth restriction and decreased birth weight, but it is unclear to what extent these maternal conditions contribute to the increased risk of orofacial clefts.
Prednisolone, the active metabolite of prednisone, administered during the period of organogenesis, has been shown to be teratogenic in rats, rabbits, hamsters, and mice with increased incidence of cleft palate in offspring. In teratogenicity studies, cleft palate along with elevation of fetal lethality (or increase in resorptions) and reductions in fetal body weight were seen in rats at maternal doses of 30 mg/kg (equivalent to 290 mg in a 60 kg individual based on mg/m2body surface comparison) and higher. Cleft palate was observed in mice at a maternal dose of 20 mg/kg (equivalent to 100 mg in a 60 kg individual based on mg/m2comparison). Additionally, constriction of the ductus arteriosus has been observed in fetuses of pregnant rats exposed to prednisolone. RAYOS was not formally evaluated in animal reproduction studies.
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinical recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
RAYOS is contraindicated in patients who have known hypersensitivity to prednisone or to any of the excipients. Rare instances of anaphylaxis have occurred in patients receiving corticosteroid therapy
Common adverse reactions for corticosteroids include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain.
Common adverse reactions for corticosteroids include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of RAYOS was evaluated in 375 rheumatoid arthritis patients in two controlled trials. Patients treated with RAYOS ranged in age from 20 to 80 years (median age 56 years), with 85% female, 99% Caucasian, 1% African-American, and < 1% Asian.
Patients received RAYOS 3 mg to 10 mg once daily at 10 pm; the majority (84%) received ≤ 5 mg. The clinical trial experience did not raise new safety concerns beyond those already established for immediate-release prednisone.
Adverse reactions have been identified during post approval use of RAYOS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The postmarketing experience has not raised new safety concerns beyond those already established for immediate-release prednisone.