Sulfadiazine

Name: Sulfadiazine

Dosing & Uses

Dosage Forms & Strengths

tablet

  • 500mg

Load

2-4 g PO

Maintenance

2-4 g/day divided 3-6x/day PO

Prophylaxis of Recurrent Rheumatic Fever

>30 kg: 1 g/day

<30 kg: 500 mg/day

Toxoplasmosis

Given with Pyrimethamine & Folinic Acid

1-1.5 g QID us. for 3-4 weeks

Prophylaxis (in patients with HIV): 0.5-1 g q6hr with pyrimethamine (25-75 mg/day PO) & folinic acid (10-25 mg/day PO)

Other Information

Asymptomatic meningococcal carriers: 1 g BID x2 days

Monitor: renal function, CBC

Other Indications & Uses

Burkholderia pseudomallei, Chlamydia trachomatis,Nocardia asteroides & brasiliensis, Mycobacterium smegmatis, Mycobacterium chelonae, Mycobacterium fortuitum

First Line:Mycobacterium smegmatis, Nocardia asteroides & brasiliensis

Dosage Forms & Strengths

tablet

  • 500mg

Load (>2 Months Old)

75 mg/kg PO OR 

2 g/sq.meter PO

Maintenance (>2 Months Old)

150 mg/kg/day divided q4- 6hr PO, OR 

4 g/sq. meter/day divided q4 -6hr PO

No more than 6 g/day

Toxoplasmosis

Given with pyrimethamine and folinic acid

100-200 mg/kg/day divided q6hr PO x3-4 weeks 

Infants <2 months old: 25 mg/kg/day divided QID PO

Prophylaxis (in patients with HIV): 85-120 mg/kg/day divided BID, TID or QID with pyrimethamine (1 mg/kg or 15 mg/sq.meter daily-maximum dose 25 mg) & folinic acid (5 mg every third day)

Congenital Toxoplasmosis

Given with pyrimethamine and folinic acid

100 mg/kg/day divided q6hr PO x 12 months 

Other Information

Prophylaxis of recurrent rheumatic fever: see Adult Dosing

Monitor: renal function, CBC

Pregnancy & Lactation

Pregnancy Category: C

Lactation: enters breast milk; risk of kernicterus if infant <2 mo

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

What should I discuss with my healthcare provider before taking sulfadiazine?

You should not use this medicine if you are allergic to any sulfa drug.

Do not use sulfadiazine during late pregnancy, just before you deliver.

Do not use if you are breast-feeding a baby.

Do not give sulfadiazine to a child younger than 2 months old without a doctor's advice.

To make sure sulfadiazine is safe for you, tell your doctor if you have:

  • kidney disease;

  • liver disease;

  • asthma, severe allergies; or

  • a genetic enzyme deficiency called glucose-6-phosphate dehydrogenase (G6PD) deficiency.

FDA pregnancy category C. It is not known whether sulfadiazine will be harmful to an unborn baby. Sulfadiazine can cause severe jaundice that could lead to brain damage in your newborn if you take this medicine just before childbirth. Tell your doctor if you are pregnant.

Sulfadiazine can pass into breast milk and may harm a nursing baby. Do not breast-feed while using sulfadiazine.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Sulfadiazine side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • sudden weakness or ill feeling, fever, chills, sore throat, swollen glands, joint pain, mouth sores, red or swollen gums, trouble swallowing;

  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;

  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

  • increased or decreased urinating, pain in your side or lower back;

  • hallucinations, seizure (convulsions);

  • liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

  • severe skin reaction--swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

  • nausea, vomiting, diarrhea, stomach pain, loss of appetite;

  • headache, ringing in your ears;

  • dizziness, spinning sensation, loss of balance or coordination;

  • numbness, tingling, or burning pain in your hands or feet;

  • sleep problems (insomnia); or

  • depressed mood.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Sulfadiazine Pharmacokinetics

Absorption

Bioavailability

Readily absorbed from GI tract.123

Peak plasma concentrations attained within 3–7 hours.123 b Considerable interindividual variations in plasma sulfadiazine concentrations attained with a given dosage.123

Exists in blood as free, conjugated, and protein-bound drug; only the free form is microbiologically active.123

Distribution

Extent

Distributed into most body tissues; appears to freely cross cell membranes.a

Distributed into CSF.123 Free and total CSF concentrations may reach 32–65 and 40–60% of concurrent blood concentrations, respectively.123 Higher sulfonamide CSF concentrations may be reached if meninges are inflamed.a

Crosses placenta.123

Distributed into milk.123

Plasma Protein Binding

38–48%.123

Elimination

Metabolism

Liver; undergoes N4-acetylation (up to 40%).b

Elimination Route

Excreted principally in urine in the N4-acetylated form (about 15–40%) and unchanged (about 43–60%).123 a Approximately 50% of a single dose is excreted in the urine within 24 hours; 60–85% can be recovered within 72 hours.123 a

Half-life

About 7–17 hours.b

Before Using sulfadiazine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For sulfadiazine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to sulfadiazine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Because of sulfadiazine's toxicity, use in infants younger than 2 months of age is not recommended.

Geriatric

No information is available on the relationship of age to the effects of sulfadiazine in geriatric patients. However, elderly patients are more likely to have age-related kidney and liver problems, which may require caution in patients receiving sulfadiazine.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using sulfadiazine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking sulfadiazine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using sulfadiazine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Methenamine

Using sulfadiazine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acetohexamide
  • Aminolevulinic Acid
  • Cyclosporine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of sulfadiazine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Asthma or
  • Blood problems (e.g., agranulocytosis, aplastic anemia) or
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency (an enzyme problem) or
  • Kidney disease or
  • Liver disease—Use with caution. May have an increased chance of side effects.

Precautions While Using sulfadiazine

If your symptoms do not improve within a few days or if they become worse, check with your doctor.

Check with your doctor right away if you have fever, chills, pale skin, pinpoint red or purple spots on the skin, sore throat, pain in the upper stomach, or yellow eyes or skin. These may be symptoms of a serious blood problem.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

How do I store and/or throw out Sulfadiazine?

  • Store tablets at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Protect from light.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Precautions

General

Sulfonamides should be given with caution to patients with impaired renal or hepatic function and to those with severe allergy or bronchial asthma.

Hemolysis may occur in individuals deficient in glucose-6-phosphate dehydrogenase. This reaction is dose related.

Adequate fluid intake must be maintained in order to prevent crystalluria and stone formation.

Information for Patients

Patients should be instructed to drink an eight ounce glass of water with each dose of medication and at frequent intervals throughout the day. Caution patients to report promptly the onset of sore throat, fever, pallor, purpura or jaundice when taking this drug, since these may be early indications of serious blood disorders.

Laboratory Tests

Complete blood counts and urinalyses with careful microscopic examinations should be done frequently in patients receiving sulfonamides.

Drug Interactions

Administration of a sulfonamide may increase the effect of oral anticoagulants and methotrexate, probably by displacement of these drugs from binding sites on plasma albumin. Potentiation of the action of sulfonylurea hypoglycemic agents, thiazide diuretics and uricosuric agents may also be noted. This may also be due to displacement of the drugs from albumin or a pharmacodynamic mechanism may play a role. Conversely, agents such as indomethacin, probenecid and salicylates may displace sulfonamides from plasma albumin and increase the concentrations of free drug in plasma.

Carcinogenesis, Mutagenesis, Impairment of Fertility

The sulfonamides bear certain chemical similarities to some goitrogens. Rats appear to be especially susceptible to the goitrogenic effects of sulfonamides and long-term administration has produced thyroid malignancies in rats.

Pregnancy

Teratogenic Effects

Pregnancy Category C

The safe use of sulfonamides in pregnancy has not been established. The teratogenic potential of most sulfonamides has not been thoroughly investigated in either animals or humans. However, a significant increase in the incidence of cleft palate and other bony abnormalities in offspring has been observed when certain sulfonamides of the short, intermediate and long acting types were given to pregnant rats and mice in high oral doses (7 to 25 times the human therapeutic dose).

Nursing Mothers

Sulfadiazine is contraindicated for use in nursing mothers because the sulfonamides cross the placenta, are excreted in breast milk and may cause kernicterus.

Because of the potential for serious adverse reactions in nursing infants from Sulfadiazine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. See CONTRAINDICATIONS.

Pediatric Use

Sulfadiazine is contraindicated in infants less than 2 months of age (except as adjunctive therapy with pyrimethamine in the treatment of congenital toxoplasmosis). See CONTRAINDICATIONSand DOSAGE AND ADMINISTRATION.

Adverse Reactions

Blood Dyscrasias

Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, hemolytic anemia, purpura, hypoprothrombinemia and methemoglobinemia.

Allergic Reactions

Erythema multiforme (Stevens-Johnson syndrome), generalized skin eruptions, epidermal necrolysis, urticaria, serum sickness, pruritus, exfoliative dermatitis, anaphylactoid reactions, periorbital edema, conjunctival and scleral injection, photosensitization, arthralgia, allergic myocarditis, drug fever and chills.

Gastrointestinal Reactions

Nausea, emesis, abdominal pains, hepatitis, diarrhea, anorexia, pancreatitis and stomatitis.

C.N.S. Reactions

Headache, peripheral neuritis, mental depression, convulsions, ataxia, hallucinations, tinnitus, vertigo and insomnia.

Renal

Crystalluria, stone formation, toxic nephrosis with oliguria and anuria; periarteritis nodosa and lupus erythematosus phenomenon have been noted.

Miscellaneous Reactions

The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Goiter production, diuresis, and hypoglycemia have occurred rarely in patients receiving sulfonamides. Cross-sensitivity may exist with these agents.

Sulfadiazine Dosage and Administration

SYSTEMIC SULFONAMIDES ARE CONTRAINDICATED IN INFANTS UNDER 2 MONTHS OF AGE except as adjunctive therapy with pyrimethamine in the treatment of congenital toxoplasmosis.

Usual Dosage for Infants over 2 Months of Age and Children

Initially, one-half the 24-hour dose. Maintenance, 150 mg/kg or 4 g/m2, divided into 4 to 6 doses, every 24 hours, with a maximum of 6 g every 24 hours. Rheumatic fever prophylaxis, under 30 kg (66 pounds), 500 mg every 24 hours; over 30 kg (66 pounds), 1 g every 24 hours.

Usual Adult Dosage

Initially, 2 g to 4 g. Maintenance, 2 g to 4 g, divided into 3 to 6 doses, every 24 hours.

Sulfadiazine Tablets USP, 500 mg x 30 Tablets - Label

NDC 0185-0757-30

Sulfadiazine Tablets, USP

500 mg

Rx only

30 Tablets

Sandoz

Sulfadiazine 
Sulfadiazine tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0185-0757
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Sulfadiazine (Sulfadiazine) Sulfadiazine 500 mg
Inactive Ingredients
Ingredient Name Strength
CROSCARMELLOSE SODIUM  
DOCUSATE SODIUM  
CELLULOSE, MICROCRYSTALLINE  
POVIDONES  
SODIUM BENZOATE  
SODIUM STARCH GLYCOLATE TYPE A POTATO  
STEARIC ACID  
Product Characteristics
Color WHITE Score no score
Shape CAPSULE Size 17mm
Flavor Imprint Code E757
Contains     
Packaging
# Item Code Package Description
1 NDC:0185-0757-30 30 TABLET in 1 BOTTLE
2 NDC:0185-0757-01 100 TABLET in 1 BOTTLE
3 NDC:0185-0757-10 1000 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA040091 07/29/1994
Labeler - Eon Labs, Inc. (012656273)
Revised: 03/2016   Eon Labs, Inc.

Dosing Adult

General dosing guidelines: Oral: 2 to 4 g/day in 3 to 6 divided doses

Rheumatic fever prophylaxis (off-label dose) (Gerber [AHA 2009]): Oral:

≤27 kg: 500 mg once daily

>27 kg: 1,000 mg once daily

Toxoplasma gondii encephalitis: Oral:

Manufacturer’s labeling: Initial: 2,000 to 4,000 mg; maintenance: 2,000 to 4,000 mg/day in 3 to 6 divided doses.

Alternate dosing (HHS [OI adult 2016]):

Treatment of acute infection (duration of therapy: ≥6 weeks): 1,000 mg (<60 kg) or 1,500 mg (≥60 kg) every 6 hours in combination with pyrimethamine plus leucovorin calcium (preferred) or alternatively, may give 1,000 mg (<60 kg) or 1,500 mg (≥60 kg) every 6 hours in combination with atovaquone

Chronic maintenance: 2,000 to 4,000 mg/day in 2 to 4 divided doses in combination with pyrimethamine and leucovorin calcium (preferred) or alternatively, may give 2,000 to 4,000 mg/day in 2 to 4 divided doses in combination with atovaquone

Dosing Geriatric

Refer to adult dosing.

Monitoring Parameters

Perform culture and sensitivity testing prior to initiating therapy; frequent CBC and urinalysis during therapy; signs of serious blood disorders (sore throat, fever, pallor, purpura, dark urine, jaundice); CD4+ count in HIV-exposed/-positive patients treated for toxoplasmosis

For Healthcare Professionals

Applies to sulfadiazine: compounding powder, oral tablet

Hypersensitivity

Hypersensitivity side effects have included urticarial rash (most common), allergic myocarditis, anaphylactoid reactions, anaphylaxis, arthralgia, conjunctival and scleral injection, drug fever and chills, epidermal necrolysis, erythema multiforme, exfoliative dermatitis, generalized skin eruptions, periorbital edema, photosensitization, serum sickness, Stevens-Johnson syndrome, and urticaria.[Ref]

The use of sulfonamide antibiotics, including sulfadiazine, is associated with large increases in the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis, although these phenomena are rare as a whole.[Ref]

Hematologic

Hematologic side effects have included agranulocytosis (0.1%), aplastic anemia, hemolytic anemia (0.05%), hypoprothrombinemia, leukopenia, methemoglobinemia, and purpura.[Ref]

Hemolytic anemia occurs less often with sulfadiazine than with other sulfonamides. Aplastic anemia may be more likely in patients with poor bone marrow reserves.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea, vomiting, abdominal pain, diarrhea, anorexia, pancreatitis, and stomatitis.[Ref]

Hepatic

Hepatic side effects are rare but can be serious. Isolated cases of hepatitis and jaundice due to cholestasis have been associated with sulfadiazine. Elevated liver function tests (with a negative hepatitis panel) have been reported in at least one case associated with psychosis.[Ref]

Psychiatric

Psychosis associated with sulfadiazine and pyrimethamine therapy in patients with AIDS and CNS toxoplasmosis has been described in two separate case reports. In each case, tremulousness and disorientation developed within three days to two weeks after starting therapy, despite partial resolution of the size of the intracranial T gondii lesions. No other obvious cause for mental status changes was found. The delirium resolved upon discontinuation of therapy in each case, and was reproducible upon rechallenge. In one case, the patient had elevated liver function tests (hepatitis panel was negative), which were reversible upon discontinuation of therapy.[Ref]

Psychiatric side effects have rarely included frank psychosis in patients with AIDS and CNS toxoplasmosis. Tremulousness, disorientation, and delirium have been reported.[Ref]

Nervous system

Nervous system side effects have included ataxia, convulsions, hallucinations, headache, insomnia, mental depression, peripheral neuritis, tinnitus, and vertigo.[Ref]

Renal

Renal side effects have included crystalluria, lupus erythematosus, periarteritis nodosa, toxic nephrosis with oliguria and anuria, and acute renal failure secondary to crystalluria or tubulointerstitial nephritis.[Ref]

Genitourinary

In one case, analysis of the stone fragments showed a composition of 100% acetylated 2-sulfanilamidopyrimidine, a metabolite of sulfadiazine.[Ref]

Genitourinary side effects have included urolithiasis.[Ref]

Metabolic

Metabolic side effects have included hypoglycemia.[Ref]

Endocrine

Endocrine side effects associated with sulfonamides have rarely included diuresis, goiter production, and sialadenitis.[Ref]

Some side effects of sulfadiazine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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