Gold Compounds (Systemic)

This monograph includes information on the following:

1) Auranofin
2) Aurothioglucose
3) Gold Sodium Thiomalate


INN:
Gold Sodium Thiomalate—Sodium Aurothiomalate

VA CLASSIFICATION
Primary: MS109

Commonly used brand name(s): Myochrysine3; Ridaura1; Solganal2.

A commonly used name for gold sodium thiomalate is
sodium aurothiomalate.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antirheumatic (disease-modifying)—

Indications

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

Accepted

Arthritis, rheumatoid (treatment) or
Arthritis, juvenile (treatment)—Auranofin is indicated in the treatment of adult rheumatoid arthritis and is used in the treatment of [juvenile arthritis]1{02} Aurothioglucose and gold sodium thiomalate are indicated in the treatment of adult or juvenile rheumatoid arthritis.{02} These agents are usually used for treating patients who show evidence of continued or additional disease activity despite conservative therapy, e.g., with salicylates (especially aspirin) or other nonsteroidal anti-inflammatory agents, glucocorticoids, etc.{05} Gold compounds may induce remission or suppression of rheumatoid arthritis.{05} In chronic advanced rheumatoid arthritis, they may prevent further damage to affected joints; however, they do not reverse existing damage.{06}

[Arthritis, psoriatic (treatment) ]1or
[Felty"s syndrome (treatment)]1—Gold compounds are used in the treatment of these rheumatic conditions.{06}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Auranofin: 678.48{13}
    Aurothioglucose: 392.18{02}
    Gold sodium thiomalate: 758.16{13}

Mechanism of action/Effect:

The predominant clinical effect of the gold compounds appears to be suppression of the synovitis of the active stage of rheumatoid disease.{05} The precise mechanism of anti-inflammatory effect is unknown, but it has been suggested that these agents alter cellular mechanisms by inhibiting sulfhydryl systems.{05} Other proposed mechanisms for gold compounds" effects in patients with rheumatoid arthritis include alteration or inhibition of various enzyme systems{05} , suppression of the phagocytic activity of macrophages and polymorphonuclear leukocytes, alteration of immune response, and alteration of collagen biosynthesis.{05} In vitro , the gold compounds have been shown to inhibit prostaglandin synthesis.{05}

Absorption:

Approximately 25% of the gold in a dose of auranofin is absorbed from the gastrointestinal tract.{01}

Protein binding:

Auranofin—Moderate. In blood, approximately 60% of the gold is bound to plasma proteins; the remainder is present in red blood cells.{01}

Aurothioglucose and

Gold sodium thiomalate—Very high; to plasma proteins only.{02}{05}

Biotransformation:

Auranofin—Metabolized so rapidly that the intact molecule has not been detected in blood.{01}

Aurothioglucose and

Gold sodium thiomalate—The metabolic fate is unknown, but it is believed that these compounds are not broken down to elemental gold.{07}

Half-life:


Elimination:


Oral (determined [as gold] after reaching steady-state blood concentrations) —

Blood—21 to 31 days; average 26 days.{01}

Tissue (body)—42 to 128 days; average 80 days.{01}



Parenteral—

Dependent on dose and duration of therapy.{05}



Onset of action:

Oral—Usually 3 to 4 months but up to 6 months in some patients.{04}

Parenteral—At least 6 to 8 weeks.{03}

Time to steady-state blood concentration

Auranofin (measured as blood gold concentration)—3 months.{04}

Steady-state blood concentration

Auranofin—Blood gold concentrations of about 68 mcg per mL are achieved with administration of 6 mg per day.{01}

Elimination:
    Oral—60% of the absorbed gold (15% of the administered dose) is excreted in the urine; the remainder of the dose is excreted in the feces.{01}
    Parenteral—60 to 90% renal, very slowly; 10 to 40% fecal, mostly via biliary secretion.{05}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to gold or other heavy metals may be sensitive to this medication also.{02}{03}

Patients sensitive to sesame products may also be sensitive to the sesame oil vehicle of parenteral aurothioglucose.{02}

Patients intolerant of parabens may be intolerant of parenteral aurothioglucose, which may contain propylparaben.{02}

Carcinogenicity/Tumorigenicity

For auranofin—Renal tubular cell karyomegaly and cytomegaly, renal adenoma, and malignant renal epithelial tumors have been reported in rats receiving 1 and 2.5 mg per kg of body weight (mg/kg) per day (8 and 21 times the usual human dose, respectively) for 24 months. In another study, renal tubular epithelial tumors occurred in rats receiving 23 mg/kg per day (192 times the human dose) for 12 months. In a third study, no tumorigenicity was demonstrated in mice receiving 1, 3, or 9 mg/kg per day (8, 24, and 72 times the human dose, respectively) for 18 months.{01}

For aurothioglucose and gold sodium thiomalate—Renal adenoma and adenocarcinoma have been reported in rats with prolonged administration of frequent, high doses of parenteral gold compounds (2 mg per kg weekly for 45 weeks followed by 6 mg per kg daily for 47 weeks in one study; 3 mg per kg or 6 mg per kg daily for up to 2 years in a second study). The adenomas were similar to those produced in rats by chronic administration of other heavy metals such as lead or nickel. Renal adenoma has not been reported in humans receiving these medications therapeutically.{02}{03}

Mutagenicity

High concentrations (313 to 700 nanograms per mL) of auranofin increased the frequency of mutations in the mouse lymphoma forward mutation assay in the presence of a rat liver microsomal preparation. No mutagenic activity was observed in the Ames (salmonella) test, the forward and reverse mutation inducement assay with Saccharomyces , the in vitro transformation of BALB/T3 cell mouse assay, or the dominant lethal assay.{01}

Pregnancy/Reproduction
Fertility—
Studies in rats have shown that auranofin decreases litter size, probably because of maternal toxicity, when given in doses of 5 mg/kg per day (42 times the human dose) but not when given in doses of 2.5 mg/kg per day (21 times the human dose).{01}

Pregnancy—
For auranofin: Well-controlled and adequate studies in humans have not been done. However, studies in rabbits have shown that auranofin increases the incidence of resorptions and abortions, decreases fetal weight, and causes congenital abnormalities, mainly abdominal defects such as gastrochisis and umbilical hernia, when administered in doses of 0.5, 3, or 6 mg/kg per day (up to 50 times the usual human dose). Other studies in animals have shown that auranofin increases the incidence of resorptions and decreases fetal weight in rats receiving 5 mg/kg per day (42 times the human dose), probably because of maternal toxicity, but not in those receiving 2.5 mg/kg per day (21 times the human dose). Studies in mice receiving 5 mg/kg per day (42 times the human dose) showed no teratogenic effects{01}

FDA Pregnancy Category C.

For aurothioglucose and gold sodium thiomalate: Studies in humans have not been done. However, studies in animals have shown parenteral gold compounds to cause hydrocephalus and microphthalmia in rats (at a dose of 25 mg per kg per day from Day 6 through Day 15 of gestation); and gastrochisis; umbilical hernia; anomalies of the brain, heart, lung, and skeleton; microphthalmia; and limb defects in rabbits (at a dose of 20 to 45 mg per kg per day from Day 6 through Day 18 of gestation).{02}{03}

FDA Pregnancy Category C.

Breast-feeding

Problems in humans have not been documented. However, use by nursing mothers is not recommended because of the potential for serious adverse effects in the infant.{02} Parenterally administered gold is excreted in human breast milk and has been detected in the blood of a nursing infant. It is not known whether auranofin is excreted in human breast milk, but gold has been detected in the milk of lactating rats and mice following auranofin administration.{01}

Pediatrics

For auranofin—Although appropriate studies have not been done in the pediatric population{01}, auranofin is being used in the treatment of juvenile arthritis.

For aurothioglucose and gold sodium thiomalate—Studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of these medications in children.


Geriatrics


Studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of these medications in the elderly. However, elderly patients are more likely to have age-related renal function impairment, which may require caution in patients receiving gold compounds.


Dental

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

Gold compounds may cause glossitis, gingivitis, or stomatitis.{01}{02}{03}

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):

Bone marrow depressants {11} (See Appendix II) or
Dermatitis-causing medications, other {07} or
Hepatotoxic medications, other {11} (See Appendix II) or
Nephrotoxic medications, other {11} (See Appendix II)    (the possibility of additive toxicity should be considered if these medications are used concurrently with gold compounds)


» Penicillamine    (concurrent use of penicillamine with gold compounds may be especially likely to increase the risk of serious hematologic and/or renal adverse effects; concurrent use is not recommended)

{02}{03}

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 physiology/laboratory test values
Hematocrit and
Hemoglobin concentration and
Platelet count and
White blood cell count    (may be decreased {01}{02}{03})


Liver function tests    (abnormalities may occur {01}{02}{03})


Urine protein concentrations    (may be increased {01}{02}{03})


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).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Serious adverse effects associated with previous gold therapy, such as bone marrow aplasia or other severe hematologic disorders, exfoliative dermatitis, necrotizing enterocolitis, or pulmonary fibrosis, history of    (high risk of recurrence {01}{02}{03})


Risk-benefit should be considered when the following medical problems exist
» Blood dyscrasias or a history of agranulocytosis or hemorrhagic diathesis{02}
Blood dyscrasias, such as granulocytopenia or anemia caused by drug sensitivity, history of
Colitis—especially for auranofin{02}
» Debilitation, severe{02}{03}
Inadequate or compromised cerebral or cardiovascular circulation {02}
Renal disease, or history of{01}{02}
» Sensitivity to any of the gold compounds, history of{02}
» Sjögren's syndrome in rheumatoid arthritis
Skin rash{01}
» Systemic lupus erythematosus{02}{03}
» Urticaria or eczema{02}

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):

Hepatic function tests and{01}{02}{03}
Renal function tests{01}{02}{03}    (recommended prior to initiation of auranofin therapy and at appropriate intervals during therapy)

{01}{02}{03}
Platelet counts and{01}{02}{03}
Total white blood cell counts and{01}{02}{03}
Urinalyses, especially urinary protein determination    (recommended prior to therapy; urinalysis or urinary protein determination recommended prior to each injection and blood and platelet counts [or platelet estimations] recommended before every second injection; also, blood and platelet counts and urinalysis recommended at least monthly during auranofin administration )

{01}{02}{03}


Side/Adverse Effects

Table 1. Side/Adverse Effects



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:
Legend:
I =Auranofin
II=Aurothioglucose
III=Gold Sodium Thiomalate

I
 
II
 
III
 
Medical attention needed
Allergic reactions
Anaphylactic shock (changes in facial skin color; skin rash, hives, and/or itching; fast or irregular breathing; puffiness or swelling of the eyelids or around the eyes; shortness of breath, troubled breathing, tightness in chest, and/or wheezing; sudden, severe decrease in blood pressure and collapse)

U{10}

R{02}

R{03}
Angioedema without other signs and symptoms of nitritoid or allergic reaction (large hive-like swellings on face, eyelids, mouth, lips, and/or tongue)
R{10}
U{02}
U{03}
Nitritoid or allergic reaction, severe (difficulty in breathing or swallowing; fainting; slow heartbeat; large hive-like swellings on face, eyelids, mouth, lips, and/or tongue; thickening of tongue)—may occur up to 10 minutes after injection

 
R{02}
R{03}
Central nervous system (CNS)/Neurologic effects
Confusion
 
U{10}
U{02}
R{03}
Convulsions
 
U{10}
U{02}
R{03}
Encephalitis
 
U{10}
R{02}
U{03}
Electroencephalographic (EEG) abnormalities
 
U{10}
R{02}
U
Guillain-Barre syndrome (tingling, numbness, and weakness in arms, trunk, or face; problems with muscle coordination)
U{10}
U{02}
R{03}
Hallucinations
 
U{10}
U{02}
R{03}
Neuropathy, peripheral (numbness, tingling, pain, or weakness in hands or feet)
R{10}
R{02}
R{03}
Cutaneous/dermatologic effects
Dermatitis, allergic
(hives)
L{01}
U{02}
U{03}
(itching)—may occur first and indicate an impending cutaneous reaction
M {01}(17%)
M{02}
M{03}
(skin rash)—both papular and vesicular dermatitis have been reported with aurothioglucose; in some patients, skin rash may indicate toxicity rather than an allergic reaction; also, skin rash may be caused or aggravated by exposure to sunlight
M {01}(24%)
M{02}
M{03}
Dermatitis, exfoliative (fever with or without chills; red, thickened, or scaly skin; swollen and/or painful glands; unusual bruising)—may lead to alopecia and shedding of nails
U{01}
R{02}
R{03}
Hair loss without symptoms of exfoliative dermatitis
 
L{01}
U{02}
U{03}
Reddened skin
 
U{01}
M{02}
U{03}
Difficulty in swallowing without other symptoms of nitritoid or allergic reaction
R{01}
U{02}
U{03}
Fever
 
U{01}
R{02}
R{03}
Gastrointestinal effects
Enterocolitis, ulcerative (abdominal pain, cramping, or burning, severe; bloody or black tarry stools; vomiting of blood or material that looks like coffee grounds; nausea, heartburn, and/or indigestion, severe and continuing)
R{01}
R{02}
R{03}
Gastrointestinal bleeding without other signs and symptoms of ulcerative enterocolitis (bloody or black tarry stools)—occult blood in the stool has also been reported with auranofin
R{01}
U{10}
U{03}
Hematologic effects—may occur individually or in combination
Agranulocytosis (sore throat and fever with or without chills; sores, ulcers, or white spots on lips or in mouth)
R{01}
R{02}
R{03}
Anemia (unusual tiredness or weakness)
R{01}
U{02}
U{03}
Anemia, aplastic [anemia, hypoplastic; pancytopenia; red cell aplasia] (shortness of breath, troubled breathing, tightness in chest, and/or wheezing; sores, ulcers, or white spots on lips or in mouth; swollen and/or painful glands; unusual bleeding or bruising; unusual tiredness or weakness)
R{02}
R{02}
R{03}
Eosinophilia
 
L{01}
R{02}
R{03}
Leukopenia [neutropenia] (usually asymptomatic; rarely, fever or chills, cough or hoarseness, lower back or side pain, painful or difficult urination)
L{01}
R{02}
U{03}
Thrombocytopenia with or without purpura (usually asymptomatic; rarely, unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)
L{01}
R{02}
R{03}
Hepatotoxicity (dark urine, pale stools, and/or yellow eyes or skin)—cholestatic hepatitis and toxic hepatitis have both been reported
R{10}
R{02}
R{03}
Mucous membrane reactions
Gingivitis (redness, soreness, swelling, or bleeding of gums)
R{01}
M{02}
M{03}
Glossitis (irritation or soreness of tongue)
L{01}
M{02}
M{03}
Metallic taste —may indicate impending gingivitis, glossitis, or stomatitis
R{01}
M{02}
M{03}
Pharyngitis, tracheitis, or upper respiratory tract inflammation (irritation of nose, throat, and/or upper chest area, possibly with hoarseness and/or coughing)
U{10}
R{02}
U{10}
Stomatitis (ulcers, sores, or white spots in mouth or throat)—indicative of toxicity
M {01}(13%)
M{02}
M{03}
Vaginitis (irritation of vagina)
U{10}
R{02}
U{10}
Ocular effects
Conjunctivitis (redness, itching, or tearing of eyes; feeling of something in the eye)
M{01}
R{02}
R{03}
Corneal ulcers
 
U{01}
R{02}
R{03}
Iritis (eye pain, tearing, decreased vision)
U{01}
R{02}
R{03}
Pulmonary effects (coughing, shortness of breath)
Bronchitis [gold bronchitis], or
U{01}
R{02}
R{03}
Fibrosis, pulmonary , or
U{01}
R{02}
R{03}
Pneumonitis , interstitial
R{01}
R{02}
R{03}
Renal effects
Glomerulitis (pain in lower back or abdomen; bloody urine; difficulty in breathing; decreased urination; swelling of face and/or legs)
U{01}
R{02}
R{03}
Hematuria without other signs or symptoms of renal toxicity (bloody urine)—may be detected microscopically before bleeding is visually apparent
L{01}
R{02}
R{03}
Nephrotic syndrome (swelling of face, fingers, ankles, lower legs, and/or feet; cloudy urine)
U{01}
R{02}
R{03}
Proteinuria without other signs or symptoms of renal toxicity (cloudy urine)
M{01}
L{02}
L{03}
Medical attention needed only if continuing or bothersome
Allergic reaction
Nitritoid or allergic reaction, mild (dizziness, feeling faint, flushing or redness of face, increased sweating, nausea with or without vomiting, weakness)—may occur immediately after injection

 
R{02}
R{03}
Gastrointestinal effects
Abdominal or stomach cramps or pain, mild to moderate
M {01}(14%)
R{02}
R{03}
Bloated feeling, gas, or indigestion, mild to moderate
 
M{01}
U{02}
U{03}
Constipation
 
L{04}
U{10}
U{10}
Decrease or loss of appetite
 
M{01}
R{02}
R{03}
Diarrhea or loose stools
M {01}(47%)
R §{02}
R §{03}
Loss of or other change in taste sense
 
L{01}
U{02}
U{03}
Nausea with or without vomiting, mild to moderate
 
M{01} (10%)
R §{02}
R §{03}
Joint pain—may occur for 1 or 2 days after injection

L{02}
L{03}
* Differences in frequency of occurrence may reflect either lack of clinical-use data or actual pharmacologic distinctions among agents (although their pharmacologic similarity suggests that side effects occurring with one may occur with the others).
For auranofin: M=3–9%; L=1–3%; R=<1%; U=unknown; unless otherwise specified.
For aurothioglucose and gold sodium thiomalate (actual percentages not available): M=more frequent; F=less frequent; R=rare; U=unknown.
 Has not been reported with auranofin.
 May occur during therapy or up to several months after cessation of therapy.
§  If severe, may indicate overdose (parenteral dosage forms only).




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

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

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to gold, other heavy metals, or sesame products

Pregnancy—Studies in humans have not been done, but gold compounds have caused teratogenic and fetotoxic effects in animal studies





Breast-feeding—Use is not recommended because of potential adverse effects in the nursing infant; aurothioglucose and gold sodium thiomalate are excreted in human breast milk; it is not known whether auranofin is excreted in human breast milk





Dental—Risk of adverse effects such as infection, delayed healing, and gingival bleeding associated with blood dyscrasias, as well as gold compound–induced gingivitis, glossitis, and/or stomatitis
Other medications, especially penicillamine
Other medical problems, especially serious adverse effects to prior gold therapy, blood dyscrasias (especially hemorrhagic or caused by sensitivity to a medication), severe debilitation, Sjögren's syndrome, systemic lupus erythematosus, eczema, or urticaria

Proper use of this medication
Compliance with therapy; symptomatic relief may not occur until after three to six months of continuous use

» Proper dosing

For auranofin (oral dosage form) only
» Not taking more medication than amount prescribed

Missed dose: If dosing schedule is



• Once a day: Taking as soon as possible; not taking if not remembered until next day; not doubling doses


• More than once a day: Taking as soon as possible; not taking if almost time for next dose; not doubling doses


» Proper storage

Precautions while using this medication
Possibility of phototoxicity

For oral dosage form only
Regular visits to physician to check progress during therapy; blood and urine tests may be required to detect possible adverse effects

For parenteral dosage forms only
Possibility of nitritoid reactions immediately following injection

Possibility of joint pain occurring for 1 or 2 days after injection


Side/adverse effects
Signs and symptoms of potential side effects, especially allergic reactions, blood dyscrasias, central nervous system or neurologic effects, cutaneous or dermatologic effects, difficulty in swallowing, fever, ulcerative enterocolitis, gastrointestinal bleeding, hepatotoxicity, mucous membrane reactions, ocular effects, pulmonary effects, and renal effects

Possibility of side effects occurring up to many months after discontinuation of medication


General Dosing Information
Concurrent therapy with salicylates or other nonsteroidal anti-inflammatory drugs or glucocorticoids is necessary, especially during the first few months of gold therapy, to provide symptomatic relief.{02}

Following mild adverse reactions, therapy should be discontinued temporarily. After the reactions have cleared, therapy may be resumed using a reduced dosage schedule.{02}{03}

Therapy should not be reinstituted after severe or idiosyncratic reactions.

For treatment of adverse effects
Recommended treatment may include

   • Discontinuing the medication promptly.{02}{03}
   • Administering appropriate therapy, such as topical adrenocorticoids, soothing lotions, or local anesthetics, for relief of mild to moderately severe skin or mucous membrane reactions.{02}{03}
   • Administering systemic glucocorticoids (i.e., 10 to 40 mg of prednisone daily in divided doses) for severe or generalized dermatitis or stomatitis.{02}{03}
   • Administering high doses of glucocorticoids (i.e., 40 to 100 mg of prednisone daily in divided doses) if required for severe pulmonary or other complications.{02}{03} If symptoms do not improve with high-dose glucocorticoid treatment, or if significant glucocorticoid-induced adverse effects develop, use of a chelating agent such as dimercaprol (BAL) to enhance gold excretion may be considered.{02}{03} However, the efficacy of BAL has not been established. Also, caution in use of BAL is recommended because of its toxicity.{02}{03}
   • Administering other supportive treatment as required for specific complications.{01}{02}{03}

AURANOFIN

Summary of Differences


Pharmacology/pharmacokinetics:
Protein-binding—Less extensive than with parenteral gold formulations.

Onset of action—Usually 3 to 4 months, but up to 6 months in some patients.



Precautions:


Patient monitoring—
Hepatic and renal function tests also recommended.




Side/adverse effects:
Nitritoid reactions and temporary joint pain that sometimes occur following injections have not been reported.

Lower incidence of mucous membrane reactions (other than stomatitis) than with injectible gold formulations.

Higher incidence of gastrointestinal irritation (e.g., cramping, indigestion, constipation, diarrhea, nausea) than with injectible gold products.



Additional Dosing Information
See also General Dosing Information.

Diarrhea occurring during auranofin therapy may respond to a reduction in dosage.{01}


Oral Dosage Forms

AURANOFIN CAPSULES

Usual adult dose
Oral, 6 mg once a day or 3 mg twice a day.{01}

Note: Initiation of therapy with doses higher than 6 mg per day is associated with an increased incidence of diarrhea and is not recommended.{01}
If an adequate response has not been achieved after six months, the daily dose may be increased to 9 mg, administered in three divided doses.{01} If an adequate response has not been achieved after three months of treatment at the higher dose, therapy should be discontinued.{01}


Usual adult prescribing limits
9 mg per day.{01}

Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


3 mg (Rx) [Ridaura (lactose)]
{01}
Canada—


3 mg (Rx) [Ridaura (lactose)]
{04}
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.


AUROTHIOGLUCOSE

Summary of Differences


Pharmacology/pharmacokinetics:
Protein-binding—More extensive than with auranofin.

Onset of action—Usually 6 to 8 weeks.



Side/adverse effects:
May cause nitritoid reactions and temporary joint pain after an injection.

Higher incidence of mucous membrane reactions (other than stomatitis) than with auranofin.

Lower incidence of gastrointestinal irritation (e.g., cramping, indigestion, constipation, diarrhea, nausea) than with auranofin.



Additional Dosing Information
See also General Dosing Information.

Aurothioglucose is for intramuscular injection only. Injections should be administered deeply into the upper outer quadrant of the gluteal region, using an 18-gauge, 11/2-inch (2-inch for obese patients) needle.{02}

Before withdrawing the dose, the vial should be thoroughly shaken to obtain a uniform suspension.{02}

The needle and syringe used to withdraw the dose from the vial must be dry.{02}

To facilitate withdrawing the suspension from the vial, the vial may be heated by immersing in warm water.{02}


Parenteral Dosage Forms

STERILE AUROTHIOGLUCOSE SUSPENSION USP

Usual adult and adolescent dose
Initial
Intramuscular, 10 mg the first week, 25 mg the second and third weeks, then 25 to 50 mg once a week until a total dose of 800 mg to 1 gram has been given.{02}{07}

Maintenance
Intramuscular, 25 to 50 mg every two weeks for two to twenty weeks, then 25 to 50 mg every three to four weeks.{02}{07}


Usual adult prescribing limits
Up to 50 mg per week.{02}

Usual pediatric dose
Children up to 6 years of age—Dosage has not been established.

Children 6 to 12 years of age—Intramuscular, 2.5 mg the first week, 6.25 mg the second and third weeks, then 12.5 mg every week until a total dose of 200 to 250 mg has been given; thereafter, 6.25 to 12.5 mg every three to four weeks.{02}

Strength(s) usually available
U.S.—


50 mg per mL (Rx) [Solganal (propylparaben)]
{02}
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Auxiliary labeling:
   • Shake well.


GOLD SODIUM THIOMALATE

Summary of Differences


Pharmacology/pharmacokinetics:
Protein-binding—More extensive than with auranofin.

Onset of action—Usually 6 to 8 weeks.



Side/adverse effects:
May cause nitritoid reactions and temporary joint pain after an injection.

Higher incidence of mucous membrane reactions (other than stomatitis) than with auranofin.

Lower incidence of gastrointestinal irritation (e.g., cramping, indigestion, constipation, diarrhea, nausea) than with auranofin.



Additional Dosing Information
See also General Dosing Information.

Gold sodium thiomalate should be administered only by intramuscular injection{03}, preferably intragluteally.

To reinstitute therapy following mild adverse reactions, an initial dose of 5 mg is given. If the medication is well tolerated, the dose may be increased in 5- to 10-mg increments at weekly to monthly intervals until a dose of 25 to 50 mg is reached.{03}

Maintenance treatment at intervals of 1 to 3 weeks may be required for some patients.{03}


Parenteral Dosage Forms

GOLD SODIUM THIOMALATE INJECTION USP

Usual adult and adolescent dose
Initial
Intramuscular, 10 mg the first week, 25 mg the second week, then 25 to 50 mg once a week until the desired therapeutic response is obtained or until toxicity occurs, up to a total dose of 1 gram.{03}

Maintenance
Intramuscular, 25 to 50 mg every two weeks for two to twenty weeks, then 25 to 50 mg every three or four weeks.{03}


Usual pediatric dose
Intramuscular, 10 mg the first week, then 1 mg per kg of body weight, not to exceed 50 mg per dose.{03} See Usual adult and adolescent dose for recommended spacing of doses.

Strength(s) usually available
U.S.—


10 mg per mL (Rx)[Generic]
{09}

25 mg per mL (Rx) [Myochrysine (benzyl alcohol)][Generic]
{08}

50 mg per mL (Rx) [Myochrysine (benzyl alcohol)][Generic]
{03}
Canada—


10 mg per mL (Rx) [Myochrysine]
{12}

25 mg per mL (Rx) [Myochrysine]
{12}

50 mg per mL (Rx) [Myochrysine]
{12}
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Stability:
Do not use if solution has darkened to more than a pale yellow.{03}



Revised: 12/21/1999



References
  1. Auranofin (Ridaura). In PDR Physicians' desk reference. 53rd ed. 1999. Montvale, NJ: Medical Economics Data; 1999. p. 903-4.
  1. Aurothioglucose (Solganal). In PDR Physicians' desk reference. 53rd ed. 1999. Montvale, NJ: Medical Economics Data 1999. p. 2884-6.
  1. Gold sodium thiomalate (Myochrisine). In: PDR Physicians' desk reference. 53rd ed. 1999. Montvale, NJ: Medical Economics Data; 1999. p. 1846-8
  1. Auranofin (Ridaura, Smith, Kline & French). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmaceutical Association; 1998. p. 1456-7.
  1. Gilman AG, Rall TW, Nies AS, Taylor P, editors. Goodman and Gilman's the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990. p. 671.
  1. Panel consensus, Gold Compounds (Systemic) monograph revision of 84.
  1. Panel consensus, Gold Compounds (Systemic) monograph revision of 85.
  1. Gold sodium thiomalate package insert (Myochrysine, Merck—US), Rev 11/82, Rec 12/82.
  1. Gold sodium thiomalate (Quad—US) Rev 3/88, Rec 11/88
  1. Panel consensus, Gold Compounds (Systemic) monograph revision of 89.
  1. Panel consensus, Gold Compounds (Systemic) monograph revision of 86.
  1. Gold sodium thiomalate (Myochrisine, Merck). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmaceutical Association; 1998. p. 1061-2.
  1. Fleeger CA, editor. USAN 1994 and the USP dictionary of names. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1993. p. 62, 314.
Hide
(web1)