Silver Sulphadiazine

D06B - Chemotherapeutics for dermatological use ATC D06BA01

JFDA label: Flamazine cream 1%

Mechanism of Action

Inhibitor of Dihydropteroate synthase — Bacterial dihydropteroate synthase inhibitor

Indications

Approved

Burn treatment

Contraindications

Source: Lexicomp

Hypersensitivity to silver sulfadiazine or any component of the formulation Absolute
pregnant women approaching or at term Absolute
premature infants or neonates ≤2 months of age. Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Hepatobiliary disorders (1)

Not Known Hepatitis

Renal and urinary disorders (1)

Not Known Interstitial nephritis

Blood and lymphatic system disorders (4)

Not Known Agranulocytosis · aplastic anemia · hemolytic anemia · leukopenia

Immune system disorders (1)

Not Known Hypersensitivity reaction (may be related to sulfa component)

Skin and subcutaneous tissue disorders (5)

Not Known Erythema multiforme · pruritus · skin discoloration · skin photosensitivity · skin rash

Dosing

Source: Lexicomp

Burn treatment: Topical: Apply to a thickness of 1/16 inch once or twice daily; reapply as needed to areas where the cream is removed by patient activity as the burned area should be covered with cream at all times. Continue use until healing has occurred or the burn site is ready for grafting. Do not discontinue therapy if the possibility of infection exists unless a significant adverse reaction has occurred.

(For additional information see "Silver sulfadiazine: Pediatric drug information") Burn treatment: Infants ≥2 months, Children, and Adolescents: Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling; use with caution; drug accumulation may occur.

Warnings & Precautions

Source: Lexicomp

Sulfonamide allergy

Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.

Superinfection

Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Fungal proliferation may rarely occur in and below the eschar.

Systemic effects

Systemic absorption may be significant and adverse reactions may occur. Disease-related concerns:

G6PD deficiency

Use with caution in patients with G6PD deficiency; hemolysis may occur.

Hepatic impairment

Use with caution in patients with hepatic impairment; sulfadiazine may accumulate.

Renal impairment

Use with caution in patients with renal impairment; sulfadiazine may accumulate. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Propylene glycol

Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). Other warnings/precautions:

Appropriate use

For topical use only. Avoid contact with eyes.

Pregnancy & Lactation

Pregnancy

Adverse events were not observed in animal reproduction studies. Because of the theoretical increased risk for hyperbilirubinemia and kernicterus, silver sulfadiazine is contraindicated for use near term, on premature infants, or on newborn infants during the first 2 months of life (refer to Sulfadiazine monograph).

Lactation

Contraindicated

It is not known if silver sulfadiazine is found in breast milk following topical application; however, sulfonamide serum concentrations may reach therapeutic levels following application to extensive areas. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother. Oral sulfadiazine is contraindicated in nursing mo

Monitoring

Clinical pearl	Serum electrolytes, urinalysis, renal function tests, CBC in patients with extensive burns on long-term treatment. Serum sulfa concentrations, if clinically indicated.

Chemistry & Properties

Formula	C10H9AgN4O2S
Molecular weight	357.14 g/mol
CAS	22199-08-2
PubChem CID	441244
InChIKey	`UEJSSZHHYBHCEL-UHFFFAOYSA-N`
logP	0.86

SMILES

Nc1ccc(S(=O)(=O)[N-]c2ncccn2)cc1.[Ag+]

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	1.015 h
Volume of distribution	0.437 L/kg
Protein binding	59.6%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C9	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
silverin cream.	Cream 1 %	30 g tube pack varies	MIDDLE EAST PHARMA&CHEMICAL IND/JORDAN	1.430
Flamazine cream	Cream 1 %w/w	50 g tube	Petra Drug Store	2.980
silverin cream	Cream 1 %	200 g tube pack varies	MIDDLE EAST PHARMA&CHEMICAL IND/JORDAN	5.040