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Sulfapyridine (Systemic)


VA CLASSIFICATION
Primary: DE890

Commonly used brand name(s): Dagenan.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Dermatitis herpetiformis suppressant—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Dermatitis herpetiformis (treatment)—Sulfapyridine is indicated as a secondary agent in the treatment of dermatitis herpetiformis (Duhring's disease). {01} {02} {06} {07} {08} {09} {10} {11} {12}

[Dermatosis, subcorneal pustular (treatment)]1—Sulfapyridine is used as a secondary agent in the treatment of subcorneal pustular dermatosis (Sneddon-Wilkinson disease). {07} {08} {09} {12}

[Pemphigoid (treatment)]1—Sulfapyridine is used as a secondary agent in the treatment of bullous pemphigoid. {07} {08} {09}

[Pyoderma gangrenosum (treatment)]1—Sulfapyridine is used as secondary agent in the treatment of pyoderma gangrenosum. {12}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    249.29

Mechanism of action/Effect:

Dermatitis herpetiformis—Unknown. {01} {12}

Absorption:

Absorption from gastrointestinal tract is slow and incomplete (approximately 60–80%). {01} {02} {04}

Distribution:

Sulfonamides readily cross the placenta {01}; sulfapyridine also crosses into the cerebrospinal fluid. {13}

Vol D=0.4 to 1.2 L per kg. {04}

Protein binding:

Variable (approximately 50%); acetylated metabolites are more highly protein bound than the free drug. Sulfonamides compete with bilirubin for binding to albumin. Kernicterus may develop in premature infants or neonates. Binding is decreased in patients with severely impaired renal function. {04} {13}

Biotransformation:

Hepatic; sulfapyridine is metabolized by acetylation and hydroxylation, followed by conjugation with glucuronic acid. Sulfapyridine is metabolized to inactive metabolites, which retain the toxicity of the parent compound. Metabolism is increased with renal function impairment and decreased with hepatic failure.

Half-life:

6 to 14 hours. {04}

Time to peak concentration:

4 to 6 hours following administration of a single dose. {01}

Duration of action:

Intermediate-acting sulfonamide. {02}

Elimination:
    Sulfapyridine and metabolites excreted primarily in urine; up to 80% of sulfapyridine may be reabsorbed by the renal tubules. {02}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients allergic to other sulfonamides may be allergic to this medication also. {01}

Patients allergic to furosemide, thiazide diuretics, sulfonylureas, or carbonic anhydrase inhibitors may be allergic to this medication also.

Carcinogenicity/Tumorigenicity

Long-term administration of sulfonamides in rats has been shown to result in thyroid malignancies. However, rats appear to be more susceptible to the goitrogenic effects of sulfonamides than do other animal species. {01}

Pregnancy/Reproduction
Fertility—
Sulfapyridine has been shown to cause oligospermia and infertility in men. {01}

Pregnancy—
Sulfapyridine crosses the placenta. Adequate and well-controlled studies in humans have not been done. However, sulfonamides may cause kernicterus in the neonate. Therefore, use is not recommended during pregnancy. {12}

Studies in rats and mice, given 7 to 25 times the human therapeutic dose orally, have shown that certain sulfonamides cause a significant increase in the incidence of cleft palate and other bony abnormalities. {01}

Breast-feeding

Sulfapyridine is excreted in breast milk in concentrations that are 30 to 60% of those in the maternal serum. Use is not recommended in nursing women since sulfonamides may cause kernicterus in nursing infants. {12}

Sulfonamides may cause hemolytic anemia in glucose-6-phosphate dehydrogenase (G6PD)–deficient neonates.

Pediatrics

Use is not recommended in pediatric patients since they do not usually develop dermatitis herpetiformis.


Geriatrics


No information is available on the relationship of age to the effects of sulfapyridine in geriatric patients.


Dental

The leukopenic and thrombocytopenic effects of sulfapyridine may result in an increased incidence of certain microbial infections, delayed healing, and gingival bleeding. If leukopenia or thrombocytopenia occurs, dental work should be deferred until blood counts have returned to normal. Patients should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Anticoagulants, coumarin- or indandione-derivative or{05}
» Anticonvulsants, hydantoin or{05}
» Antidiabetic agents, oral{05}    (may be displaced from protein-binding sites and/or metabolism may be inhibited by sulfonamides, resulting in increased or prolonged effects and/or toxicity; dosage adjustments may be necessary during and after sulfonamide therapy)


Bone marrow depressants (See Appendix II )    (concurrent use of sulfapyridine with bone marrow depressants may increase the leukopenic and/or thrombocytopenic effects of these medications; if concurrent use is required, close observation for myelotoxic effects should be considered)


» Hemolytics, other (See Appendix II )    (concurrent use with sulfapyridine may increase the potential for toxic side effects)


» Hepatotoxic medications, other (See Appendix II )    (concurrent use with sulfonamides may result in an increased incidence of hepatotoxicity; patients, especially those on prolonged administration or those with a history of liver disease, should be carefully monitored)


» Methotrexate or
Phenylbutazone or
Sulfinpyrazone    (the effects of these medications may be potentiated during concurrent use with sulfonamides because of displacement from plasma protein-binding sites; phenylbutazone has also been reported to potentiate the effects of sulfonamides)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Bentiromide    (administration of sulfonamides during a bentiromide test period will invalidate test results since sulfonamides are also metabolized to arylamines and will thus increase the percent of PABA recovered; discontinuation of sulfonamides at least 3 days prior to the administration of bentiromide is recommended)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Allergy to sulfapyridine, other sulfonamides, furosemide, thiazide diuretics, sulfonylureas, or carbonic anhydrase inhibitors
» Blood dyscrasias    (sulfapyridine may cause agranulocytosis, aplastic anemia, or other blood dyscrasias)


» Glucose-6-phosphate dehydrogenase (G6PD) deficiency{01}    (sulfapyridine may cause hemolytic anemia in G6PD-deficient patients)


» Hepatic function impairment{01}    (sulfonamides are metabolized in the liver and may cause hepatitis)


» Porphyria    (sulfonamides may precipitate an acute attack of porphyria)


» Renal function impairment{01}    (sulfapyridine is excreted primarily through the kidneys)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Complete blood counts (CBCs){01}    (may be required prior to and monthly during treatment to detect blood dyscrasias in patients on prolonged therapy; therapy should be discontinued if a significant decrease in the count of any formed blood elements occurs)


» Glucose-6-phosphate dehydrogenase (G6PD) determinations{12}    (are recommended prior to treatment in Caucasians of Mediterranean origin, Orientals, and blacks; if a deficiency is found, sulfapyridine should be given with caution since hemolytic effects may be exacerbated in these patients; dosage adjustments and/or discontinuation of the medication may be required)


Urinalyses{01}    (may be required prior to and periodically during treatment to detect crystalluria and/or urinary calculi formation in patients on long-term or high-dose therapy and in patients with impaired renal function)




Side/Adverse Effects

Note: Fatalities have occurred, although rarely, due to severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, other blood dyscrasias, and hypersensitivity reactions. Therapy should be discontinued at the first appearance of skin rash or any serious side/adverse effects. {01}
Sulfapyridine has been shown to cause oligospermia and infertility in men. {01}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent {01}
    
Headache, continuing
    
hypersensitivity (itching; skin rash; fever)
    
photosensitivity (increased sensitivity of skin to sunlight)

Incidence less frequent
    
Blood dyscrasias (pale skin; sore throat; unusual bleeding or bruising; unusual tiredness or weakness)
    
hepatitis (yellow eyes or skin)
    
Lyell's syndrome or Stevens-Johnson syndrome (aching of joints and muscles; difficulty in swallowing; redness, blistering, peeling, or loosening of skin; unusual tiredness or weakness)

Incidence rare
    
Crystalluria or hematuria (blood in urine; lower back pain; pain or burning while urinating)
    
goiter or thyroid function disturbance (swelling of front part of neck)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent {01}
    
Gastrointestinal disturbances (diarrhea; anorexia; nausea or vomiting)





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Sulfapyridine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Allergies to other sulfonamides, furosemide, thiazide diuretics, sulfonylureas, or carbonic anhydrase inhibitors

Pregnancy—Crosses the placenta; not recommended during pregnancy since sulfonamides may cause kernicterus in the neonate





Breast-feeding—Excreted in breast milk; not recommended in nursing women since sulfonamides may cause kernicterus in nursing infants





Use in children—Not recommended since pediatric patients do not usually develop dermatitis herpetiformis

Other medications, especially anticoagulants (coumarin- or indandione-derivative), anticonvulsants (hydantoin), antidiabetic agents (oral), hemolytics, hepatotoxic medications, and methotrexate
Other medical problems, especially blood dyscrasias, G6PD deficiency, hepatic function impairment, porphyria, and renal function impairment

Proper use of this medication
» Maintaining adequate fluid intake to help prevent crystalluria and urinary calculi formation

For dermatitis herpetiformis
Possible need for a strict, gluten-free diet in the treatment of dermatitis herpetiformis

Using for 6 to 12 months may be required before reducing the dose or discontinuing medication

» Proper dosing
Missed dose: Taking as soon as possible if symptoms return or worsen; not taking if symptoms do not return or worsen

» Proper storage

Precautions while using this medication
» Regular visits to physician to check blood counts in patients on long-term therapy

Checking with physician if no improvement within a few days

Using caution in use of regular toothbrushes, dental floss, and toothpicks; deferring dental work until blood counts have returned to normal; checking with doctor or dentist concerning proper oral hygiene

» Possible photosensitivity reactions; using sunscreen lotion or avoiding unprotected exposure to sun or use of sunlamp

Possible interference with bentiromide diagnostic test for pancreatic function


Side/adverse effects
Signs of potential side effects, especially blood dyscrasias, crystalluria or hematuria, goiter or thyroid function disturbance, headache (continuing), hepatitis, hypersensitivity, Lyell's syndrome or Stevens-Johnson syndrome, or photosensitivity


General Dosing Information
Fluid intake should be sufficient to maintain a urine output of at least 1200 to 1500 mL per day in adults, to prevent crystalluria and urinary calculi formation. {01} {02} {06}

If dermatitis herpetiformis recurs, increased dosage may be required. The maintenance dose should not exceed the minimum effective dose. {01}

In the treatment of dermatitis herpetiformis, use of a strict, gluten-free diet for 6 to 12 months may allow a reduction in dose or discontinuation of sulfapyridine. {06} {07} {09} {10}


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

SULFAPYRIDINE TABLETS USP

Usual adult and adolescent dose
Dermatitis herpetiformis
Oral, initially 250 mg to 1 gram four times a day until improvement occurs. Daily dosage should then be reduced by 250- to 500-mg decrements every three days until a symptom-free maintenance dose is achieved. {01} {12}

Note: Sulfapyridine may also be given two times a day in evenly divided doses. {12}


[Dermatosis, subcorneal pustular]1
Oral, 500 mg two times a day to 750 mg four times a day. {07}

[Pemphigoid]1
Oral, 1 gram three times a day. {08}


Usual adult prescribing limits
Dermatitis herpetiformis—Up to 6 grams daily. {02} {06} {09}

Usual pediatric dose
Use is not recommended in pediatric patients since they do not usually develop dermatitis herpetiformis. {12}

Strength(s) usually available
U.S.—


500 mg (Rx)[Generic]

Canada—


500 mg (Rx) [Dagenan][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container.

Auxiliary labeling:
   • Take with a full glass of water.
   • Avoid too much sun or use of sunlamp.



Revised: 02/01/1993



References
  1. Package insert, Sulfapyridine (Lilly), Rev 2/12/86, Rec 12/23/88.
  1. CPS 1988, Sulfapyridine (generic), p 876.
  1. Personal communication (Eli Lilly)—now made by Jacobus Pharm, 8/29/90.
  1. Klotz U. Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid. Clin Pharmacokinet 1985; 10: 285-302.
  1. Hansten, Horn, editors. Drug interactions. 6th ed. 1989: 106, 146, 171.
  1. AMA drug evaluations. 6th ed. 1024.
  1. Dermatology in general medicine. 3rd ed. Vol 1, 581, 596, 603.
  1. Andrews' diseases of the skin. 7th ed. 581-600, 604.
  1. Current dermatology therapy, 1982: 62-4, 119-21, 450-1, 607.
  1. Cecil, editor. Textbook of medicine. 18th ed. 2331.
  1. Conn's current therapy. 1988: 728-9.
  1. Panel comments, 3/29/89.
  1. Martindale's extra pharmacopeia. 13th ed. 1989: 309.
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