Prednisolone

Pronunciation: (pred-NIS-oh-lone)

Class: Corticosteroid, Glucocorticoid Prednisolone

Trade Names:

Millipred

- Tablets 5 mg

ratio-Prednisolone (Canada)

Sandoz Prednisolone (Canada)

Prednisolone Acetate

Trade Names:

Econopred Plus

- Ophthalmic suspension 1%

Trade Names:

Flo-Pred
- Oral suspens
on 5 mg per 5 mL

- Oral suspension 15 mg per 5 mL

Trade Names:

Pred Forte

- Ophthalmic suspension 1%

Trade Names:

Pred Mild

- Ophthalmic suspension 0.12%

Trade Names:

Prelone

- Syrup 15 mg per 5 mL

Prednisolone Sodium Phosphate

Trade Names:

Orapred

- Oral solution 15 mg per 5 mL

- Orally disintegrating tablets 10 mg

- Orally disintegrating tablets 15 mg

- Orally disintegrating tablets 30 mg

Trade Names:

Pediapred

- Oral liquid 5 mg per 5 mL

Trade Names:

Prednisol

- Ophthalmic suspension 1%

Trade Names:

Veripred 20

- Solution 20 mg per 5 mL

Pharmacology

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Intermediate-acting glucocorticoid that depresses formation, release, and activity of endogenous mediators of inflammation, including prostaglandins, kinins, histamine, liposomal enzymes, and complement system. Also modifies body's immune response.

Pharmacokinetics

Absorption

Oral

Rapidly absorbed, reaching C max in 1 to 2 h. C max is approximately 336.8 ng•h/mL and AUC 0-t is approximately 1,946.8 ng•h/mL (15 mg).

Distribution

Plasma protein binding 70% to 90%. Vd is 0.22 to 0.7 L/kg.

Metabolism

Primarily hepatic.

Elimination

Excreted in the urine as sulfate and glucuronide conjugates. t ½ is 2 to 4 h.

Special Populations

Elderly

Mean unbound fraction of prednisolone was higher and V ss unbound prednisolone was reduced in elderly patients.

Indications and Usage

Oral

Allergic conditions; collagen diseases (eg, systemic lupus erythematous, acute rheumatic carditis); dermatologic diseases; edematous states; endocrine conditions; GI diseases; hematologic diseases; neoplastic conditions; neoplastic diseases; nervous system conditions (eg, acute exacerbations of multiple sclerosis); ophthalmic conditions; conditions related to organ transplantation; pulmonary disease (eg, asthma); renal condition (eg, nephrotic syndrome); rheumatologic conditions; specific infectious diseases including trichinosis with neurologic or myocardial involvement, tuberculous meningitis with subarachnoid block or impending block when used concomitantly with appropriate antituberculous chemotherapy; tuberculosis with pleural or pericardial effusion.
Ophthalmic Econopred Plus, Prednisol, Pred Forte

Treatment of steroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe.
Econopred Plus, Prednisol

Treatment of corneal injury from chemical, radiation, or thermal burns, or penetration of foreign bodies.
Pred Mild

Treatment of mild to moderate noninfectious allergic and inflammatory disorders of the lid, conjunctiva, cornea, and sclera (including chemical and thermal burns).

Dosage and Administration

Adults

PO 5 to 60 mg/day. Oral disintegrating tablet: 10 to 60 mg/day.

Children

PO Range of initial dose is 0.14 to 2 mg/kg/day in 3 or 4 divided doses (4 to 60 mg/m 2 /day).

Adults

Ophthalmic Econopred , Prednisol : 2 drops in affected eye(s) 4 times daily. In cases of bacterial infections, concomitant use of anti-infective agents is mandatory. Pred Forte , Pred Mild : Instill 1 to 2 drops into conjunctival sac 2 to 4 times daily. The dose frequency may be increased if necessary during the first 24 to 48 h.

Multiple Sclerosis

Adults

PO 200 mg/day for 1 wk, then 80 mg every other day for 1 mo.

Nephrotic Syndrome

Children

PO 60 mg/m 2 /day in 3 or 4 divided doses for 4 wk, followed by 4 wk of single dose alternate-day therapy at 40 mg/m 2 /day.

Asthma

Children

PO 1 to 2 m/kg/day in single or divided doses. A short course, or burst therapy, should be continued until children achieve a peak expiratory flow rate of 80% of their personal best or symptoms resolve, which usually requires 3 to 10 days of treatment, although it can take longer.

General Advice

* Alternate-day therapy, a corticosteroid dosing regimen in which twice the usual daily dose is administered every other day, is used to provide patients requiring long-term pharmacologic dose treatment with the beneficial effects of prednisolone while minimizing certain adverse reactions (eg, pituitary-adrenal suppression, Cushingoid state, growth suppression in children).
* Do not break or use partial orally disintegrating tablets.
* Ophthalmic suspensions: Shake well before using.
* Ophthalmic use: If signs and symptoms do not improve after 2 days, re-evaluate the patient.
* Ophthalmic use: Care should be taken not to discontinue prematurely.

Storage/Stability

Oral tablets

Store at 68° to 77°F. Protect oral disintegrating tablets from moisture.

Orapred , Veripred 20

Store at 36° to 46°F.

Prelone

Store at 59° to 86°F.

Pediapred

Store at 39° to 77°F. May be refrigerated.

Ophthalmic suspension Econopred , Prednisol

Store at 46° to 75°F in an upright position.

Flo-Pred

Store at 68° to 77°F.

Pred Forte

Store at temperatures up to 75°F in an upright position. Protect from freezing.

Pred Mild

Store at 59° to 86°F in an upright position. Protect from freezing.

Drug Interactions


Ciclosporin plasma concentration of prednisolone increased by ciclosporin
Ritonavir plasma concentration of prednisolone possibly increased by ritonavir
Prednisolone belongs to Corticosteroids and will have the following interactions:
Interactions do not generally apply to corticosteroids used for topical action (including inhalation) unless specified

ACE inhibitors corticosteroids antagonise hypotensive effect of ACE inhibitors
acetazolamide increased risk of hypokalaemia when corticosteroids given with acetazolamide
Adrenergic Neurone blockers corticosteroids antagonise hypotensive effect of adrenergic neurone blockers
Alpha­­ blockers corticosteroids antagonise hypotensive effect of alpha-blockers
Amphotericin increased risk of hypokalaemia when corticosteroids given with amphotericin —avoid concomitant use unless corticosteroids needed to control reactions Close monitoring required with concomitant administration of nephrotoxic drugs or cytotoxics
Angiotensin-II receptor antagonists corticosteroids antagonise hypotensive effect of angiotensin-II receptor antagonists
Antidiabetics corticosteroids antagonise hypoglycaemic effect of antidiabetics
Aspirin increased risk of gastro-intestinal bleeding and ulceration when corticosteroids given with aspirin , also corticosteroids reduce plasma concentration of salicylate
Barbiturates metabolism of corticosteroids accelerated by barbiturates (reduced effect)
Beta-blockers corticosteroids antagonise hypotensive effect of beta-blockers Since systemic absorption may follow topical application of beta-blockers to the eye the possibility of interactions, in particular, with drugs such as verapamil should be borne in mind
Calcium salts corticosteroids reduce absorption of calcium salts see also Antacids
Calcium-channel blockers corticosteroids antagonise hypotensive effect of calcium-channel blockers Dihydropyridine calcium-channel blockers include amlodipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine, and nisoldipine
Carbamazepine metabolism of corticosteroids accelerated by carbamazepine (reduced effect)
Cardiac glycosides increased risk of hypokalaemia when corticosteroids given with cardiac glycosides
Clonidine corticosteroids antagonise hypotensive effect of clonidine
Coumarins corticosteroids may enhance or reduce anticoagulant effect of coumarins (high-dose corticosteroids enhance anticoagulant effect) Change in patient's clinical condition, particularly associated with liver disease, intercurrent illness, or drug administration, necessitates more frequent testing. Major changes in diet (especially involving salads and vegetables) and in alcohol consumption may also affect anticoagulant control
Diazoxide corticosteroids antagonise hypotensive effect of diazoxide
Diuretics corticosteroids antagonise diuretic effect of diuretics
loop diuretics increased risk of hypokalaemia when corticosteroids given with loop diuretics
Diuretics, Thiazide and related increased risk of hypokalaemia when corticosteroids given with thiazides and related diuretics
Erythromycin metabolism of corticosteroids possibly inhibited by erythromycin Interactions do not apply to small amounts of erythromycin used topically
Hydralazine corticosteroids antagonise hypotensive effect
of hydralazine
Itraconazole metabolism of corticosteroids possibly inhibited by itraconazole
Ketoconazole metabolism of corticosteroids possibly inhibited by ketoconazole
Methotrexate increased risk of haematological toxicity when corticosteroids given with methotrexate
Methyldopa corticosteroids antagonise hypotensive effect of methyldopa
Mifepristone effect of corticosteroids (including inhaled corticosteroids) may be reduced for 3–4 days after mifepristone
Minoxidil corticosteroids antagonise hypotensive effect of minoxidil
Moxonidine corticosteroids antagonise hypotensive effect of moxonidine
Nitrates corticosteroids antagonise hypotensive effect of nitrates
NSAIDs increased risk of gastro-intestinal bleeding and ulceration when corticosteroids given with NSAIDs See also Aspirin. Interactions do not generally apply to topical NSAIDs
Oestrogens plasma concentration of corticosteroids increased by oral contraceptives containing oestrogens Interactions of combined oral contraceptives may also apply to combined contraceptive patches; in case of hormone replacement therapy low dose unlikely to induce interactions
Phenytoin metabolism of corticosteroids accelerated by phenytoin (reduced effect)
Primidone metabolism of corticosteroids accelerated by primidone (reduced effect)
Rifamycins metabolism of corticosteroids accelerated by rifamycins (reduced effect)
Ritonavir plasma concentration of corticosteroids possibly increased by ritonavir
Sodium Benzoate corticosteroids possibly reduce effects of sodium benzoate
Sodium Nitroprusside corticosteroids antagonise hypotensive effect of sodium nitroprusside
Sodium Phenylbutyrate corticosteroids possibly reduce effects of sodium phenylbutyrate
Somatropin corticosteroids may inhibit growth-promoting effect of somatropin
Sympathomimetics. increased risk of hypokalaemia when corticosteroids given with high doses of beta2 sympathomimetics.
Theophylline increased risk of hypokalaemia when corticosteroids given with theophylline
Vaccines. high doses of corticosteroids impair immune response to vaccines , avoid concomitant use with live vaccines.

For a general warning on live vaccines and high doses of corticosteroids or other immunosuppressive drugs.




Contraindications

Oral

Hypersensitivity to corticosteroids or any component of the product; systemic fungal infections; administration of live, or live, attenuated vaccines in patients receiving immunosuppressive doses.

Ophthalmic

Most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella; mycobacterial infection of the eye and fungal diseases of the ocular structure; acute untreated purulent ocular infections; hypersensitivity to other corticosteroids or any component of the product.

Adverse Reactions

Cardiovascular

Bradycardia; cardiac arrest; cardiac arrhythmias; cardiac enlargement; CHF; circulatory collapse; elevated BP; fat embolism; hypertension; hypertrophic cardiomyopathy in premature infants; myocardial rupture following recent MI; pulmonary edema; syncope; tachycardia; thromboembolism; thrombophlebitis; vasculitis.

CNS

Arachnoiditis; behavioral and mood changes; convulsions; depression; emotional instability; euphoria; headache; increased appetite; increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of therapy; insomnia; malaise; meningitis; mood swings; neuritis; neuropathy; paraparesis/paraplegia; paresthesia; personality changes; sensory disturbances; vertigo.

Dermatologic

Acne; allergic dermatitis; cutaneous and subcutaneous atrophy; dry scalp; edema; facial erythema; hyper- or hypopigmentation; impaired wound healing; increased sweating; petechiae and ecchymosis; rash; sterile abscess; striae; suppressed reactions to skin tests; thin fragile skin; thinning scalp hair; urticaria.

EENT

Exophthalmos; glaucoma; increased IOP; posterior subcapsular cataracts.

Ophthalmic use

Acute anterior uveitis; conjunctival hyperemia; conjunctivitis; corneal ulcers; delayed wound healing; glaucoma; increased IOP; keratitis; loss of accommodation; mydriasis; optic nerve damage; perforation of the globe; posterior subcapsular cataract formation; ptosis; secondary ocular infection (eg, bacterial, viral).

GI

Abdominal distention; elevation in serum liver enzymes levels; hepatomegaly; hiccups; nausea; pancreatitis; peptic ulcer with possible perforation and hemorrhage; ulcerative esophagitis.

Endocrine

Abnormal fat deposits; decreased carbohydrate tolerance; development of Cushingoid state; hirsutism; manifestations of latent diabetes mellitus and increased requirement for insulin and oral hypoglycemic agents in diabetes; menstrual irregularities; moon facies; secondary adrenocortical and pituitary unresponsiveness (particularly during stress, as in trauma, surgery, or illness); suppression of growth in children.

Genitourinary

Alteration in motility and number of spermatozoa.

Hypersensitivity

Anaphylactoid reaction; anaphylaxis; angioedema.

Metabolic-Nutritional

Alterations in blood glucose; fluid retention; hypokalemic alkalosis; negative nitrogen balance due to catabolism; potassium loss; sodium retention; weight gain.

Musculoskeletal

Aseptic necrosis of femoral and humeral heads; charcot-like arthropathy; loss of muscle mass; muscle weakness; osteoporosis; pathologic fracture of long bones; steroid myopathy; tendon rupture; vertebral compression fractures.

Precautions

Monitor

Body weight, BP, routine laboratory studies, including 2-hour postprandial blood glucose and serum potassium, and a chest x-ray, should be obtained at regular intervals during prolonged therapy. Monitor linear growth of infants and children on prolonged therapy. Upper GI x-rays are desirable in patients with known or suspected peptic ulcer disease. If ophthalmic product is used for more than 10 days or oral product more than 6 wk, routinely monitor IOP.

Pregnancy

Category C .

Flo-Pred

Category D .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established (ophthalmic).

Elderly

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Hypersensitivity

Reactions may occur, including anaphylaxis.

Renal Function

Use drug with caution.

Adrenal suppression

Prolonged therapy may lead to hypothalamic-pituitary-adrenal suppression.

Bone density

Bone formation may be decreased and bone resorption may be increased. Long-term use in children can have negative effects on growth and development.

Cardiovascular effects

Use drug with great caution in patient who has suffered recent MI.

Cardiovascular/renal function

Prednisolone may cause elevation of BP, salt and water retention, and increased excretion of calcium and potassium.

Cerebral malaria

Do not use.

Fetal effects

Can cause fetal harm when administered to pregnant women. Use during the first trimester of pregnancy has been associated with an increased risk of orofacial clefts, intrauterine growth restriction, and decreased birth weight.

GI disorders

Risk of GI perforation in patients with certain GI disorders may be increased (eg, active or latent peptic ulcers).

Infections

Signs of infection may be masked. Host-defense mechanisms may be decreased, allowing dissemination of infection. Risk of reactivation or exacerbation of latent infection may be increased.

Kaposis sarcoma

Has been reported in patients receiving corticosteroid therapy, usually for chronic conditions.

Long-term ophthalmic local use

Fungal infections of the cornea are particularly prone to develop with chronic use of corticosteroids, and fungal infections should be suspected in any persistent corneal ulceration.

Mood and behavior disturbances

Use may be associated with CNS effects ranging from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. Existing emotional instability or psychotic tendencies may be aggravated.

Ocular effects

Use systemic drug with caution in ocular herpes simplex because of possible corneal perforation.

Ophthalmic effects

Prolonged use may produce posterior subcapsular cataracts and glaucoma with possible damage to the optic nerve, and may enhance the establishment of secondary ocular infections due to fungi or viruses. Use with caution in patients with glaucoma. Do not use in the treatment of optic neuritis.

Stress

Increased dosage of rapidly acting corticosteroid may be needed before, during, and after stressful situations.

Surgery

Use after cataract surgery may delay healing and increase the incidence of bleb formation.

Threadworm infestation

Use with great care.

Thyroid status

Changes in thyroid status may necessitate adjustments in prednisolone dosage.

Tuberculosis

Restrict use to those cases of fulminating or disseminated tuberculosis in which prednisolone is used for management of the disease in conjunction with an appropriate antituberculous regimen.

Withdrawal

Abrupt discontinuation may result in adrenal insufficiency.

Overdosage

Symptoms

The effects of ingestion of large quantities over a short period of time have not been reported.

Patient Information

* Advise patient to take single daily or alternate-day doses in morning before 9 am and to take multiple doses at evenly-spaced intervals throughout day.
* Instruct patient to take medication with meals or snacks to avoid GI irritation.
* Caution patient not to take drug with aspirin or other OTC medications containing salicylates unless directed by health care provider.
* Instruct patient to check weight at home daily at same time of day.
* Advise patient on chronic steroid therapy to wear medical identification (eg, card, bracelet) indicating condition and drug regimen.
* Remind patient to wash hands before and after ophthalmic instillation.
* Teach patient correct method for instilling eye drops.
* Instruct patient not to rub eyes or touch dropper into eye.
* Inform patient of increased appetite and counsel patient on appropriate diet management (ie, diet high in protein, calcium, and potassium but low in sodium and carbohydrates).
* Advise family that medication may slow growth in children.
* Inform patient of the possible adverse reactions of moonface, mood swings, and increased emotions.
* Teach patient to monitor for infection, eye burning, or increased bruising.
* Instruct patient not to drive soon after using eye drops because vision may be blurred initially.
* Inform patient that ophthalmic preparation may cause sensitivity to bright light and recommend use of sunglasses to minimize this effect.
* Instruct patient to report the following symptoms to health care provider: black, tarry stools; menstrual irregularities; muscle weakness; prolonged sore throat, fever, cold, or infection; puffing of face; swelling of lower extremities; unusual weight gain; vomiting of blood.
* Tell patient to notify health care provider if the following symptoms occur after dosage reduction or withdrawal of therapy: anorexia, diarrhea, dizziness, fatigue, low blood sugar, nausea, vomiting, weakness, weight loss.