Rayos: (Prednisone) Delayed-release Tablets

Full Prescribing Information For Patients

The first and only delayed-release prednisone
for the treatment of RA and PMR

Circadian rhythms of rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR)

Circadian rhythm and RA

  • Symptoms of RA are highest in severity in the morning1-5
  • Interleukin-6 (IL-6), a key cytokine associated with RA inflammation, reaches its highest levels in the early morning2,5-7
  • Cortisol normally counteracts the effects of inflammatory cytokines, but in people with RA, there is a relative cortisol insufficiency in the early morning2,5,8
  • Rise of IL-6 Precedes RA Symptoms2

    Circadian rhythm and PMR

  • Morning stiffness associated with PMR suggests a link with early morning increases in cytokine production9
  • Elevated levels of IL-6 are a characteristic finding in patients
    with PMR10,11
  • A relative cortisol insufficiency is found in patients with PMR similar to that in patients with RA9
  • References:
    1. Harkness JAL, Richter MB, Panayi GS, et al. Circadian variation in disease activity in rheumatoid arthritis. Br Med J. 1982;284:551-554.
    2. Cutolo M, Seriolo B, Craviotto C, Pizzorni C, Sulli A. Circadian rhythms in RA. Ann Rheum Dis. 2003;62:593-596.
    3. Kowanko IC, Knapp MS, Pownall R, Swannell AJ. Domiciliary self-measurement in rheumatoid arthritis and the demonstration of circadian rhythmicity. Ann Rheum Dis. 1982;41:453-455.
    4. Labrecque G, Bureau J-P, Reinberg AE. Biological rhythms in the inflammatory response and in the effects of non-steroidal anti-inflammatory drugs. Pharmacol Ther. 1995;66:285-300.
    5. Crofford LJ, Kalogeras KT, Mastorakos G, et al. Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. J Clin Endocrinol Metab. 1997;82:1279-1283.
    6. Arvidson NG, Gudbjörnsson B, Elfman L, Rydén A-C, Tötterman TH, Hällgren R. Circadian rhythm of serum interleukin-6 in rheumatoid arthritis. Ann Rheum Dis. 1994;53:521-524.
    7. Perry MG, Kirwan JR, Jessop DS, Hunt LP. Overnight variations in cortisol, interleukin 6, tumour necrosis factor α and other cytokines in people with rheumatoid arthritis. Ann Rheum Dis. 2009;68:63-68.
    8. Gudbjörnsson B, Skogseid B, Oberg K, Wide L, Hällgren R. Intact adrenocorticotropic hormone secretion but impaired cortisol response in patients with active rheumatoid arthritis: effect of glucocorticoids. J Rheumatol. 1996;23:596-602.
    9. Spies CM, Cutolo M, Straub RH, Burmester G-R, Buttgereit F. More night than day—circadian rhythms in polymyalgia rheumatica and ankylosing spondylitis. J Rheumatol. 2010;37:894-899.
    10. Weyand CM, Fulbright JW, Evans JM, Hunder GG, Goronzy JJ. Corticosteroid requirements in polymyalgia rheumatica. Arch Intern Med. 1999;159:577-584.
    11. Straub RH, Glück T, Cutolo M, et al. The adrenal steroid status in relation to inflammatory cytokines (interleukin-6 and tumour necrosis factor) in polymyalgia rheumatica. Rheumatology. 2000;39:624-631.
    12. Buttgereit F, Mehta D, Kirwan J, et al. Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (CAPRA-2) [published online ahead of print May 5, 2012]. Ann Rheum Dis. doi:10.1136/annrheumdis-2011-201067.

    Due to the circadian rhythm of inflammation, chronotherapy—timing the dose of medication to coincide with the nocturnal rise of symptoms—may be appropriate for the treatment of both RA and PMR. 9,12

    CONTRAINDICATIONS

  • Known hypersensitivity to prednisone or any excipients in the formulation
  • WARNINGS AND PRECAUTIONS

  • Corticosteroids can cause hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome and hyperglycemia. Monitor patients for these conditions with chronic use. Taper doses gradually for withdrawal after chronic use
  • RAYOS may increase susceptibility to new infection and increase risk of exacerbation, dissemination or reactivation of latent infection. RAYOS may mask signs and symptoms of infection. The rate of infectious complications increases with increasing doses of corticosteroids
  • Corticosteroids can cause elevated blood pressure, salt and water retention and hypokalemia. Monitor blood pressure and sodium, potassium serum levels. RAYOS should be used with caution in patients with a history of recent myocardial infarction, congestive heart failure, hypertension or renal insufficiency
  • There is an increased risk of gastrointestinal (GI) perforation in patients with certain GI disorders. RAYOS may mask signs and symptoms of GI perforation
  • Corticosteroid use may be associated with behavioral and mood disturbances, including euphoria, insomnia, mood swings, personality changes, severe depression and psychosis. Existing conditions may be aggravated
  • Corticosteroid use may lead to inhibition of bone growth in children and adolescents and the development of osteoporosis at any age. Give special consideration to patients at increased risk of osteoporosis (eg, postmenopausal women) before initiating corticosteroid therapy, and bone density should be monitored in patients on long-term corticosteroid therapy
  • Prolonged use of corticosteroids may result in cataracts, infections and glaucoma. Monitor intraocular pressure if corticosteroid therapy is continued for more
    than 6 weeks
  • Do not administer live or attenuated vaccines to patients receiving immunosuppressive doses of corticosteroids
  • Long‐term use of corticosteroids can have negative effects on growth and development in children. Monitor pediatric patients on long‐term corticosteroid therapy
  • Fetal harm can occur with first trimester use of corticosteroids. Apprise women of potential harm to the fetus
  • ADVERSE REACTIONS

  • 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
  • INDICATIONS AND USAGE

    RAYOS is a corticosteroid indicated:
  • As an anti-inflammatory or immunosuppressive agent for certain allergic, dermatologic, gastrointestinal, hematologic, ophthalmologic, nervous system, renal, respiratory, rheumatologic, specific infectious diseases or conditions and organ transplantation
  • For the treatment of certain endocrine conditions
  • For palliation of certain neoplastic conditions
  • For a complete list of indications for RAYOS, please see the full Prescribing Information.

    For further information on RAYOS, please see full Prescribing Information at www.RAYOSrx.com/PI.

    *For eligible patients. Terms and Conditions apply. Please click here for more information.

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    RAYOS is a registered trademark of Horizon Pharma.
    May 2014. 0109RAY01
    www.horizonpharma.com