Prednisone

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Indications and dosage

  • Bullous diseases.
    • Pemphigus vulgaris: start prednisone at 1 mg/kg daily up to 2 mg/kg daily in divided doses.
    • Bullous pemphigoid: 1 mg/kg daily for 3–6 months or less.
    • Cicatricial pemphigoid: 1–1.5 mg/kg daily.
  • Autoimmune connective tissue diseases.
    • Lupus erythematosus: 20 mg prednisone every other day up to 60 mg daily may be required.
    • Dermatomyositis: 1 mg/kg/day tapered to 50% over 6 months and to zero over 2–3 years.
    • Eosinophilic fasciitis: 1–2 mg/kg daily tapered over 6–24 months as tolerated.
    • Systemic sclerosis (selected patients) .
    • Morphea (rapidly progressive): 1mg/kg/day, maximum 50 mg/day ,  systemic corticosteroids do not improve established Sclerosis and disease activity may rebound following discontinuation.
  • Vasculitis
    • Cutaneous small vessel vasculitis: up to 1 mg/kg/day for rapid control of progressive cutaneous disease.
    • Microscopic polyangiitis: 1 mg/kg/day  prednisone are initially utilized, with addition of cyclophosphamide for patients with signifcant organ involvement.
    • Generalized granulomatosis with polyangiitis: 1 mg/kg/day of prednisone + oral daily cyclophosphamide.
    • Classic polyarteritis nodosa: 1 mg/kg/day of prednisone with the dose tapered over 6 months.
    • Wells syndrome: 10–80 mg daily, tapering the dose over one month is generally well tolerated.
  • Neutrophilic dermatoses
    • Pyoderma gangrenosum: 40–60 mg daily of prednisone, tapered over 1 month to low-dose alternate-day therapy,  as initial therapy.
    • Behçet’s disease (severe mucocutaneous disease) :40–80 mg po daily usual starting dose (intermittent with taper).
    • Behçet’s disease (systemic disease):60–120 mg po daily usual starting dose (including split-dose), with taper to alternate days.
    • Sweet’s syndrome: 0.5–1.0 mg/kg/day  for 2–6 weeks.
    • Bowel-associated dermatosis–arthritis syndrome(severe):40–60 mg daily.
  • Dermatitis/papulosquamous dermatoses.
    • contact dermatitis: 20 mg doses twice a day for 7 to 14 days (for adults).
    • Idiopathic erythroderma: 1–2 mg/kg/day and a maintenance dose of 0.5 mg/kg/day or less , psoriasis is excluded.
    • Generalized lichen planus: 40–60 mg daily and tapered over 4–6 weeks.
  • Others
    • Acne fulminans: prednisone 0.5–1 mg/kg/day as monotherapy for at least 2–4 weeks, followed by low-dose isotretinoin (0.1 mg/kg/day) after the acute Inflammation subsides, after at least 4 weeks of this combination, the isotretinoin dose can be slowly increased and the prednisone tapered over a period of 1–2 months.
    • Solid facial edema: 10–30 mg/day.
    • Adrenal saha syndrome: nightly dose of 7.5 mg for 2 months, subsequently reduced to 5 mg nightly for 2 months and then 2.5 mg nightly until 6 Months of treatment are completed.
    • Type 1 lepra reaction: 20–60 mg per day.
    • Stevens–johnson syndrome/ten (controversial).
    • Severe erythema multiforme (controversial): early (0.5–1 mg/kg/day).
    • Polymorphous light eruption: 0.5–1 mg/kg may be used during the initial seven to ten days of phototherapy to minimize photoexacerbation.
    • Life or function-threatening hemangiomas: 2–3 mg/kg/day usually maintained until cessation of growth or shrinkage occurs, followed by a gradual taper.
    • Pseudofolliculitis barbae(recalcitrant): 45–60 mg every morning for 7–10 days.
    • Adult-onset still disease: 40–60 mg prednisone daily.
    • Relapsing polychondritis: 0.5–1 mg/kg/day; higher range doses are given if there is visceral involvement.
    • Sarcoidosis(systemic): 0.5–1 mg/kg/day for 4–6 weeks, followed by a slow taper.
    • Chronic urticaria: :(30–50 mg daily) to achieve good initial control, short term mangement.
    • Drug reaction with eosinophilia and systemic symptoms (dress):1–2 mg/kg/day.

Baseline Monitoring

  • Examination
    • Blood pressure, weight.
    • Height and weight plotted on a growth curve(in children).
    • Ophthalmoscopic examination for cataracts.
  • Lab
    • TB screening (strongly consider) tuberculin skin test (or IFN-γ-releasing assay), chest X-ray.
    • Fasting glucose and triglycerides; potassium level.

Follow Up Monitoring

  • Examination( At 1 month, then at least every 2–3 months)
    • Blood pressure, weight.
    • Height and weight plotted on a growth curve(in children).
    • History each visit for adverse effects.
    • Ophthalmologic examination for cataracts and glaucoma (At least every 6 months initially; at least every 12 months long-term).
  • Lab (At 1 month, then at least every 3–4 months while on pharmacologic dose CS)
    • Potassium levels.
    • Glucose levels (fasting).
    • Triglycerides (fasting).
  • Near time of cessation of long-term pharmacologic dose CS therapy (optional)
    • AM cortisol level (or another suitable test of adrenal function or the entire HPA axis).
  • Long term ttt
    • DEXA examination of the hip and lumbar spine(every 1–3 years).

Side effects

  • Metabolic effects
    • Hyperglycemia.
    • Hyperlipidemia.
    • Obesity.
    • Hypocalcemia.
    • Hypokalemic alkalosis.
    • Cushingoid changes.
  • Cardiovascular
    • Hypertension : sodium retention , vasoconstriction.
    • Peripheral edema.
    • Atherosclerosis.
    • Congestive heart failure : ↑ sodium retention, resultant fluid overload in predisposed individuals.
  • Hematologic
    • Leukocytosis.
    • Lymphopenia.
    • Eosinopenia.
    • Immunosuppression with increased risk of infections.
  • Nervous system
    • Mood, personality changes.
    • Psychiatric problems, psychosis.
    • Seizures.
    • Pseudotumor cerebri.
    • Peripheral neuropathy.
    • Epidural lipomatosis.
  • Musculoskeletal
    • Osteoporosis.
    • Osteonecrosis (e.g. hip).
    • Growth retardation.
    • Muscle atrophy.
    • Myopathy.
  • Hypothalamic–pituitary–adrenal (HPA) axis
    • Suppression.
    • Withdrawal syndrome .
    • Adrenal (addisonian) crisis.
  • Gynecologic, obstetric
    • Amenorrhea.
    • Fetal effects (rare adrenal insuffciency; cleft palate in animal studies).
  • Gastrointestinal effects
    • Nausea, vomiting.
    • Gastroesophageal reflux.
    • Peptic ulcer disease.
    • Intestinal perforation.
    • Pancreatitis.
    • Esophagitis (reflux or candidal)-Peptic ulcer disease : ↓ mucus production, ↑ acid production.
  • Ophthalmologic.
    • Cataracts.
    • Glaucoma.
    • Infection.
    • Hemorrhage.
    • Exophthalmos.
  • Cutaneous
    • Atrophy, striae, telangiectasia.
    • Vascular fragility, purpura.
    • Acne, acneiform eruptions.
    • Hirsutism.
    • Infections.

Contraindications

  • Absolute
    • Systemic fungal infections.
    • Herpes simplex keratitis.
    • Hypersensitivity (primarily occurs with ACTH, occasionally noted with IV preparations).
  • Relative
    • Cardiovascular: hypertension, CHF.
    • Central nervous system: prior psychosis, severe depression.
    • Gastrointestinal: active PUD, recent anastomosis.
    • Infections: active TB, positive tuberculin skin test.
    • Metabolic: diabetes mellitus.
    • Musculoskeletal: osteoporosis.
    • Ocular: cataracts, glaucoma.
    • Use of live vaccines.

Interactions

  • Cyclosporine May Reduce Clearance Of Prednisolone.
  • Decreased levels of steroids: barbiturates, phenytoin, ephedrine, rifampin, cholestyramine.
  • Increased levels of steroids: estrogens, ketoconazole, aspirin, nonsteroidal anti-inflammatory agents, macrolides.
  • Decreased levels of: warfarin, vaccines, antidiabetic agents, isoniazid.
  • Increased levels of: cyclosporin, potassium-depleting diuretics, digitalis.
  • Hypokalemia: potassium-depleting diuretics, digitalis, albuterol.
  • Weakness in myasthenia gravis: anticholinesterase agentsand Mifepristone is contraindicated in pt on long term corticosteroids.

Pregnancy &Lactation

  • Pregnancy
    • Pregnancy category: C (immediate release); D (delayed release).
    • There is little evidence that systemic corticosteroid use in pregnancy independently increases risks of preterm birth, low birth weight, or preeclampsia.
    • Currently, there is not enough evidence to determine whether systemic corticosteroids could contribute to gestational diabetes mellitus.
    • Maternal corticosteroid use during the first trimester may increases incidence of cleft lip with or without cleft palate.
    • When large glucocorticoid doses are used near the time of delivery, fetal HPA axis suppression occasionally occurs, resulting in a pseudo-addisonian neonate.
  • Lactation
    • Amounts of prednisone in breastmilk are very low.
    • American Academy of Pediatrics has determined that prednisone therapy is compatible with breastfeeding.
    • No adverse effect have been reported in breastfed infants with maternal use of any corticosteroid during breastfeeding.
    • With high maternal doses, the use of prednisolone instead of prednisone and avoiding breastfeeding for 4 hours after a dose theoretically should decrease the dose received by the infant.
    • However, these maneuvers are not necessary with short-term use.
    • High doses might occasionally cause temporary loss of milk supply.

Precautions

  • Abrupt cessation of long-term, high-dose prednisone therapy (risk of HPA axis complications such as an addisonian crisis) must be avoided.
  • Prolonged use is associated with increased risk of infection.
  • It may cause impairment of mineralocorticoid secretion; administer mineralocorticoid concomitantly.
  • Live-virus vaccines should not be administered to children receiving systemic corticosteroids at a dose equivalent to prednisone ≥20 mg/day, or ≥2 mg/kg/day in those weighing <10 kg; if treated for >2 weeks, administration of these vaccines should be delayed until 4 weeks after discontinuation.
  • Use with caution in cirrhosis, ocular herpes simplex, hypertension, diverticulitis, hypothyroidism, myasthenia gravis, peptic ulcer disease, osteoporosis, ulcerative colitis, psychotic tendencies, renal insufficiency, pregnancy, diabetes mellitus, congestive heart failure, thromboembolic disorders, GI disorders.
  • Long-term treatment associated with increased risk of osteoporosis, myopathy, delayed wound healing.
  • Adults receiving a systemic glucocorticoid equivalent to a prednisone dose of ≥ 2.5 mg/day for ≥ 3 months should be assessed for osteoprosis.
  • Patients receiving corticosteroids should avoid chickenpox or measles-infected persons if unvaccinated.
  • Latent tuberculosis may be reactivated (patients with positive tuberculin test should be monitored).
  • Pneumonia has been observed in patients receiving glucocorticoid therapy at a dose equivalent to ≥20 mg/day of prednisone for longer than a month who also have another cause of immunocompromise.
  • Methylprednisolone is preferred in hepatic impairment because prednisone must be converted to prednisolone in liver.
  • Prolonged corticosteroid use may result in elevated intraocular pressure, glaucoma, or cataracts.
  • May cause psychiatric disturbances; monitor for behavioral and mood changes; may exacerbate pre-existing psychiatric conditions.

Drug Info

  • The conversion of prednisone (prodrug) to prednisolone (active form) is dependent on a hepatic-based enzyme, which in end-stage liver disease may not produce therapeutically adequate quantities of the active drug form prednisolone.
  • The administration of prednisolone (rather than prednisone) to patients with advanced liver disease would be appropriate.
  • Prednisone have intermediate mineralocorticoid activity activity.
  • American Academy of Family Physicians (AAFP) state that administration of live virus vaccines usually is not contraindicated in patients receiving corticosteroid therapy as short-term (<2 weeks) treatment, in low-to-moderate dosages, as long-term alternate-day treatment with short-acting preparations, or in maintenance of physiologic dosages, such as, replacement therapy.
  • The rate of prednisone tapering depends on both features of the dermatosis (e.g. type, activity, severity) and adrenal recovery issues.
  • The prednisone dose can usually be tapered in 20 mg increments at doses greater than 60 mg/day, 10 mg increments between 30 and 60 mg/day, and 5 mg increments between 30 mg and the physiologic dose range.
  • Once the physiologic dose range of 5–7.5 mg/day of prednisone is reached, a more gradual reduction (e.g. in 1–2.5 mg increments) may be necessary to allow adrenal recovery.
  • Alternate morning therapy and doses equivalent to <10 mg/day of prednisone reduce the chance of opportunistic infection.

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