Sulfacetamide and Prednisolone

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Ointment, ophthalmic: Blephamide: Sulfacetamide sodium 10% and prednisolone acetate 0.2% (3.5 g)

Solution, ophthalmic [drops]: Sulfacetamide sodium 10% and prednisolone sodium phosphate 0.25% (5 mL, 10 mL)

Suspension, ophthalmic [drops]: Blephamide: Sulfacetamide sodium 10% and prednisolone acetate 0.2% (5 mL, 10 mL) [contains benzalkonium chloride]

Pharmacology

Mechanism of Action

Interferes with bacterial growth by inhibiting bacterial folic acid synthesis through competitive antagonism of PABA; decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability; suppresses the immune system by reducing activity and volume of the lymphatic system

Use: Labeled Indications

Inflammatory ocular conditions: Treatment of steroid-responsive inflammatory ocular conditions (where either a superficial bacterial ocular infection or the risk of bacterial ocular infection exists) of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe; chronic anterior uveitis; corneal injury from chemical, radiation, or thermal burns; penetration of foreign bodies

Contraindications

Hypersensitivity to sulfacetamide, prednisolone, other sulfonamides or corticosteroids, or any component of the formulation; viral diseases (including epithelial herpes simplex keratitis [dendritic keratitis], vaccinia, varicella) of the cornea or conjunctiva; fungal diseases of ocular structures; mycobacterial ocular infections

Note: Although the FDA-approved product labeling states this medication is contraindicated with other sulfonamide-containing drug classes, the scientific basis of this statement has been challenged. See "Warnings/Precautions" for more detail.

Canadian labeling: Additional contraindications (not in US labeling): Purulent untreated ocular infections.

Dosage and Administration

Dosing: Adult

Inflammatory ocular conditions: Ophthalmic:

Ointment: Apply ~¹/₂ inch ribbon to lower conjunctival sac 3 to 4 times daily and 1 to 2 times at night

Solution: Instill 2 drops every 4 hours

Suspension: Instill 2 drops every 4 hours during the day and at bedtime

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Inflammatory ocular conditions: Children ≥6 years and Adolescents: Ophthalmic: Refer to adult dosing.

Administration

For topical ophthalmic use only; to avoid contamination, do not touch container tip to eyelids or other surfaces when placing drops or ointment in eyes. Do not apply with silver preparations. Discontinue if symptoms do not improve after 2 days. No more than 20 mL or 8 g should be prescribed without proper re-evaluation of the patient.

Ointment: Apply into pocket between eyeball and lower lid; patient should look downward before closing eye.

Solution/Suspension: Tilt head back, instill into the conjunctival sac and close eye(s). Apply light finger pressure on lacrimal sac for 1 minute following instillation. Shake the suspension well before using.

Storage

Ointment: Store at 15°C to 25˚C (59°F to 77°F).

Solution, suspension: Do not freeze; protect from light. May darken on prolonged standing or exposure to heat and light. Do not use if darkened; yellowing does not affect activity.

Solution: Store at 15°C to 25˚C (59°F to 77°F).

Suspension: Store at 8°C to 24˚C (46°F to 75°F) in upright position.

Drug Interactions

Nonsteroidal Anti-Inflammatory Agents (Ophthalmic): May enhance the adverse/toxic effect of Corticosteroids (Ophthalmic). Healing of ophthalmic tissue during concomitant administration of ophthalmic products may be delayed. Monitor therapy

Ritodrine: Corticosteroids may enhance the adverse/toxic effect of Ritodrine. Monitor therapy

Adverse Reactions

Frequency not defined. Also see individual agents.

Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis

Hematologic & oncologic: Agranulocytosis, aplastic anemia

Hepatic: Fulminant hepatic necrosis

Hypersensitivity: Hypersensitivity reaction

Infection: Secondary infection (bacterial, fungal)

Local: Local irritation

Ophthalmic: Accommodation disturbance, anterior uveitis (acute), blepharoptosis, eye perforation, glaucoma, increased intraocular pressure, mydriasis, optic nerve damage (infrequent), subcapsular posterior cataract

Miscellaneous: Wound healing impairment

<1%, postmarketing, and/or case reports: Hypercorticoidism (systemic)

Warnings/Precautions

Concerns related to adverse effects:

• Blood dyscrasias: Severe reactions including agranulocytosis, aplastic anemia, and other blood dyscrasias have occurred with sulfonamides (regardless of route); fatalities have occurred (rare). Discontinue at the first sign of serious reaction.
• Dermatologic reactions: Severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have occurred with sulfonamides (regardless of route); fatalities have occurred (rare). Discontinue at first sign of rash.
• Hepatic necrosis: Severe reactions, including fulminant hepatic necrosis have occurred with sulfonamides (regardless of route); fatalities have occurred (rare). Discontinue at first sign of serious reaction.
• Hypersensitivity reactions: Hypersensitivity reactions, skin rash, or other serious reactions may occur; discontinue at the first sign of hypersensitivity reaction. Cross sensitivity among corticosteroids has occurred.
• Infection: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), or prolong or exacerbate viral infections. Corticosteroids should not be used to treat ocular herpes simplex; use extreme caution in patients with a history of ocular herpes simplex. Fungal infection should be suspected in any patient with persistent corneal ulceration who has received corticosteroids.
• Ocular effects: Prolonged use of steroids may result in posterior subcapsular cataract formation and may increase intraocular pressure, resulting in ocular hypertension/glaucoma with damage to the optic nerve, defects in visual acuity, and fields of vision. Acute anterior uveitis may occur in susceptible patients, primarily black patients. Use with caution in patients with glaucoma (steroids increase intraocular pressure). Perforation may occur with topical steroids in diseases which thin the cornea or sclera. Intraocular pressure should be monitored if this product is used >10 days.
• Sulfonamide ("sulfa") allergy: Traditionally, concerns for cross-reactivity have extended to all compounds containing the sulfonamide structure (SO₂NH₂). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur, or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides and antibiotic sulfonamides. A nonantibiotic sulfonamide compound which contains the arylamine structure and therefore may cross-react with antibiotic sulfonamides is sulfasalazine (Zawodniak 2010). T-cell–mediated (type IV) reactions (eg, maculopapular rash) are less understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Dry eye: Use with caution in patients with severe dry eye.

Special populations:

• Cataract surgery patients: Use following cataract surgery may delay healing or increase the incidence of bleb formation.
• Contact lens wearers: May contain benzalkonium chloride, which may be adsorbed by contact lenses; contact lenses should not be worn during treatment of ophthalmologic infections.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Administration: For ophthalmic use only; not for injection into the eye. Do not use concurrently with silver preparations.
• Appropriate use: Re-evaluate if signs and symptoms do not improve after 2 days. Use of >20 mL (solution/suspension) or 8 g (ointment) should only be done following proper re-examination of the patient (eg, slit-lamp biomicroscopy, fluorescein staining). Not effective in Sjogren keratoconjunctivitis or mustard gas keratitis.
• Discontinuation of therapy: In chronic conditions, withdraw therapy with gradual tapering of dose.
• P-aminobenzoic acid: May be present in purulent exudates and may reduce the effectiveness of sulfonamides.

Monitoring Parameters

Signs and symptoms of improvement after 2 days of therapy; signs and symptoms of secondary infection; intraocular pressure in patients with glaucoma or with prolonged use (≥10 days); periodic exam of lens with prolonged use

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination. Use of systemic sulfonamides during pregnancy may cause kernicterus in the newborn. See individual agents.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience dizziness. Have patient report immediately to prescriber signs of a severe sulfonamide reaction (rash; red, swollen, blistered, or peeling skin; red or irritated eyes; mouth, throat, nose, or eye sores; fever, chills, or sore throat; cough that is new or worse; loss of strength and energy; any bruising or bleeding; or signs of liver problems like dark urine, fatigue, lack of appetite, nausea or abdominal pain, light-colored stools, vomiting, or yellow skin), sensitivity to light, vision changes, eye pain, or severe eye irritation (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.