Gold Sodium Thiomalate - Indications, Warnings, Precautions, Adminstration, and Complications

Overview:

Gold sodium thiomalate helps to decrease inflammation or swelling in rheumatoid arthritis. It can be used to treat adult as well as juvenile rheumatoid disease. Gold sodium thiomalate does not repair damage to cartilage or bones that has occurred already.

Initially, the use of gold salts was a controversial treatment and was not accepted by the international community immediately. In 1929, studies supporting the use of this compound were published in France by Jacques Forestier. The use of gold salts showed successful treatment of Raoul Dufy's joint pain in 1940. Gold sodium thiomalate is one of only two gold compounds currently employed in modern medicine, along with an orally-administered gold salt, Auranofin.

What Are the Indications of Gold Sodium Thiomalate?

It is mainly used for treating moderate to severe rheumatoid arthritis and is administered once or twice weekly through intramuscular injection.

What Are the Warnings Before Starting Gold Sodium Thiomalate?

Before starting the treatment, the following must be monitored

• Hemoglobin.

• Erythrocyte.

• White blood cells.

• Differential and platelet counts (complete blood counts including platelet estimation must be done before every second injection throughout treatment).

• Urinalysis (urine should be analyzed for protein and sediment changes before administration of every injection).

In the case of purpura or ecchymosis at any time of the treatment, platelet count must be monitored immediately.

Danger signs of gold toxicity include

• Rapid reduction of hemoglobin.

• Eosinophilia above five percent.

• Leukopenia below 4000 WBC/mm³.

• Platelets decrease below 100,000/mm³.

• Hematuria.

• Albuminuria.

• Pruritus (itching).

• Stomatitis (inflammation and painful sores inside the mouth).

• Skin eruption.

• Persistent diarrhea.

The administration of further injections of Gold sodium thiomalate must be stopped until it is proved that these abnormalities are caused by conditions other than gold toxicity.

For Patients:

What Is Rheumatoid Arthritis?

Rheumatoid arthritis is an autoimmune disease, where the healthy cells in the body are attacked by their own immune system, causing inflammation or painful swelling in the affected body parts.

Rheumatoid arthritis usually attacks one joint, or many joints at once. The rheumatoid disease usually affects joints in the wrists, hands, and knees. In a joint with rheumatoid arthritis, the lining of the joint is inflamed and causes damage to joint tissue. This damage to the tissue can cause long-lasting or chronic pain, unsteadiness (lack of balance), and deformity. Rheumatic arthritis can also damage other tissues of the body and cause problems in the lungs, heart, and eyes.

Signs and symptoms of rheumatic arthritis include

• Pain and stiffness in more than one joint.

• The same symptoms are on both sides of the body like in both hands or both knees.

• Tenderness.

• Swelling in more than one joint.

• Weight loss.

• Fatigue or tiredness.

• Fever.

• Weakness.

Rheumatoid arthritis results from an immune response in which the body’s healthy cells are attacked by its immune system. The exact cause of rheumatoid arthritis is still unknown. However, some factors might increase the risk of developing the disease.

How Is Gold Sodium Thiomalate Used?

Gold sodium thiomalate is used in the form of an injection administered into a muscle. It is mainly given by a healthcare professional in a hospital. The healthcare team must inform the use of this medication in children. However, this medication can be prescribed for selected conditions, with certain precautions.

Overdosage:

If too much of this medication has been administered the poison control center or emergency room must be contacted immediately. This medicine must not be shared with others.

Does Gold Sodium Thiomalate Cause Allergy?

Certain studies have shown that Gold sodium thiosulfate might cause allergy. In the patch test with standard series, positive reactions were seen in around nine percent of 823 consecutive patients. No correlation was observed with other allergens in the standard series.

In a special study conducted on 38 patients, the following findings were obtained in patients with contact allergy to Gold sodium thiosulfate:

• Positive patch tests to the compound itself in dilute concentration.

• Positive patch tests to potassium dicyanoaurate.

• Negative patch tests Gold sodium thiomalate, sodium thiosulfate, and metallic gold.

• Positive intradermal tests to Gold sodium thiosulfate.

The above findings prove that Gold sodium thiosulfate is the second most common contact allergen after nickel sulfate. It is suggested that a positive skin test for Gold sodium thiosulfate represents gold allergy.

What Should Be Done in Case of a Missed Dose?

It is important that the patient should not miss the dose. Inform the healthcare team if the patient is unable to make it to an appointment.

Interactions:

This medication must not be taken with any of the following drugs:

• Dimercaprol.

• Penicillamine.

• Certain medications to treat cancer.

Other interactions are also possible. The patient must provide the healthcare provider with a list of all the herbs, medicines, non-prescription drugs, or dietary supplements that he/she is using. The doctor must also be if the patient smokes, drinks alcohol, or uses drugs.

What Precautions Must Be Taken While Taking Gold Sodium Thiomalate?

The patient must visit the healthcare provider for regular checks and assess the progress. The doctor might suggest laboratory tests during the course of the treatment. The patient must inform the doctor immediately if a rash is noticed while taking this medication. The patient must avoid exposure to sunlight while using this medication. The patient is also advised to use sunscreen and wear protective clothing.

What Are the Side Effects of Gold Sodium Thiomalate?

The side effects of Gold sodium thiomalate which require immediate attention include

• Allergic reactions like skin rash, itching, and swelling of the face, lips, or tongue.

• Changes in vision.

• Breathing problems.

• Irregular heartbeat.

• Fever and sore throat.

• Lightheaded.

• Hallucination, loss of contact with reality.

• Loss of appetite, nausea.

• Mouth sores.

• Metallic taste.

• Pain, numbness, and tingling in the hands or feet.

• Redness, blistering, or loosening of the skin.

• Stomach cramps.

• Difficulty in passing urine.

• Unusual bleeding or bruising.

• Fatigue.

• Yellowing of the eyes or skin.

Side effects that usually do not require immediate medical attention:

• Aches and pains.

• Diarrhea.

• Hair loss.

• Headache.

How Is Medicine Stored?

This medication is given in a hospital or clinic and will not be stored at home.

For Doctors:

Indications:

Gold sodium thiomalate is indicated for the treatment of certain patients with active rheumatoid arthritis including both adult and juvenile types. The medicine shows maximum benefits if administered in the early active stage.

In the later stages of the disease, cartilage, and bone are already damaged and Gold sodium thiomalate cannot repair damage caused by previously active diseases. It can only limit the progression of rheumatoid arthritis and prevent further damage to joints. Gold sodium thiomalate is usually used as a part of the therapy and not alone because it does not provide a complete treatment.

Clinical Pharmacology:

Gold sodium thiomalate is an aqueous solution (sterile). Gold sodium thiomalate is available as a solution for intramuscular injection of 50 mg of Gold sodium thiomalate per milliliter.

Composition:

• Gold sodium thiomalate is composed of the mono- and di-sodium salts of gold thiomalic acid.

• Benzyl alcohol (preservative): 0.5 percent.

• pH of the product: 5.8 to 6.5.

The exact mode of action of this medicine is still unknown. They predominantly act by suppressing the effect on the synovitis of active rheumatoid disease.

Administration:

• Gold sodium thiomalate is to be administered intramuscularly through an injection.

• It is usually administered intragluteal (injected into a muscle of the buttocks) with the patient lying down.

• The patient has to lie down for approximately ten minutes after the injection.

• Therapeutic effects of Gold sodium thiomalate occur slowly.

• Early improvement begins only after six to eight weeks of treatment and is limited to a reduction in morning stiffness. However beneficial effects may not be observed until after months of therapy.

• The material should not be used if it has darkened. Color should not exceed pale yellow.

• Parenteral drug products must be inspected visually for particulate matter and discoloration before administration.

What Is the Recommended Dosage of Gold Sodium Thiomalate?

For Adults:

The higher the dose of Gold sodium thiomalate, the higher the risk of gold toxicity. Selecting this medicine for treatment depends on the following factors:

• The physician's expertise in gold salt therapy.

• The patient's condition.

• The choice of alternative treatments.

• The availability of the patient for close regular administration and monitoring.

Weekly Injections:

• First injection - 10 mg.

• Second injection - 25 mg.

• Third and subsequent injections - 25 to 50 mg.

This dose is continued until there is a major clinical improvement or toxicity is noticed up to a cumulative dose of one gram.

If clinical improvement is seen before a cumulative dose of one gram has been administered, the dose can be reduced or the interval between injections is increased. A maintenance dose of 25 to 50 mg every other week for 2 to 20 weeks is recommended. If the clinical course is stable, injections of 25 to 50 mg can be administered every third and subsequently every fourth week. However, some patients may require maintenance doses at intervals of one to three weeks.

If no improvement is observed during the initial therapy of a cumulative dose of one gram, the following possibilities should be considered:

• Gold sodium thiomalate is discontinued as the patient is considered unresponsive.

• The Gold sodium thiomalate dosage can be increased by 10 mg increments every one to four weeks, not exceeding 100 mg in a single injection.

• A 25 to 50 mg of Gold sodium thiomalate may be continued for ten additional weeks (approximately).

Gold sodium thiomalate therapy must be stopped immediately if no significant improvement or if toxicity is observed.

Dosage for Juvenile Rheumatoid Arthritis:

The pediatric dosage of Gold sodium thiomalate is proportional to the adult dosage and calculated based on the weight.

After the test dosage of 10 mg, the dosage for children is one milligram per kilogram of body weight, not exceeding 50 mg for a single injection. The guidelines for administration to adults are also recommended for pediatric patients.

Concomitant Drug Therapy:

Gold salts should not be used simultaneously with Penicillamine. The safety of this medication if administered along with cytotoxic drugs has not been established. Medicines like salicylates, other nonsteroidal anti-inflammatory drugs (NSAIDs), or systemic corticosteroids may be continued along with Gold sodium thiomalate.

If improvement is seen, analgesic and anti-inflammatory drugs may be discontinued gradually as symptoms reduce.

Storage:

• The injections are stored at 20° to 25° Celsius (68° to 77° Fahrenheit).

• It has to be kept away from light.

• The container is stored in a carton until the contents have been consumed.

How Is Medicine Supplied?

Injection Gold sodium thiomalate consists of a light yellow or yellow solution (depending on potency).

It is supplied as follows:

• Gold sodium thiomalate - 50 mg per mL, 1 mL in 2 mL vials (partially filled) in packages of 6.

• Gold sodium thiomalate - 50 mg per mL, 10 mL vials.

Adverse Effects:

The adverse reactions usually develop during the initial phase of the therapy:

1. Cutaneous Reactions: The most common reaction is dermatitis. Pruritus usually develops before dermatitis becomes apparent, and therefore must be considered a warning signal of a cutaneous reaction. In severe cases, the cutaneous reaction can cause generalized exfoliative dermatitis leading to alopecia and nail shedding. Gold dermatitis can aggravate by exposure to sunlight.

2. Mucous Membrane Reactions: The second most common adverse reaction is stomatitis. Diffuse glossitis or gingivitis may also occur. A metallic taste first develops that can be considered a warning signal.

3. Renal Reactions: Gold may also lead to kidney toxicity and produce nephrotic syndrome or glomerulitis with hematuria. The renal reactions are usually mild and can be avoided if recognized early. The toxicity can become severe and chronic if treatment is continued after the onset of the reaction. Therefore, urinalysis must be performed before every injection, and the treatment should be stopped if proteinuria or hematuria is identified.

4. Hematologic Reactions: Gold toxicity might lead to granulocytopenia; thrombocytopenia, with or without purpura; eosinophilia, and hypoplastic and aplastic anemia; have all been reported.

5. Allergic Reactions: Fainting, flushing, dizziness, and sweating are the most commonly observed. Other symptoms include nausea, malaise, vomiting, headache, and weakness.

Less common effects but more severe adverse effects include

• Anaphylactic shock.

• Syncope.

• Bradycardia.

• Thickening of the tongue.

• Difficulty in swallowing and breathing.

• Angioneurotic edema.

These effects usually occur immediately after injection or as late as ten minutes after the injection. If these side effects may be seen during the course of the treatment, treatment with Gold sodium thiomalate should be stopped.

Miscellaneous Reactions:

Gastrointestinal reactions may also occur, including

• Nausea.

• Vomiting.

• Anorexia.

• Abdominal cramps.

• Diarrhea.

• Ulcerative enterocolitis can be severe or even fatal.

What Are the Complications Related to Gold Sodium Thiomalate?:

Central nervous system complications include hallucinations, confusion, and seizures. These signs and symptoms subside upon discontinuation of gold therapy. Peripheral neuropathy, with or without, sensorimotor effects (Guillain-Barré syndrome), fasciculations, and elevated spinal fluid protein are seen.

Jaundice, hepatitis, gold bronchitis, pulmonary injury including hair loss, and fever have also been documented.

How to Manage the Adverse Reactions?

Treatment with Gold sodium thiomalate must be stopped immediately when toxic reactions occur.

Minor complications include:

• Localized dermatitis.

• Mild stomatitis.

• Slight proteinuria.

The adverse reactions generally require no other treatment and resolve spontaneously by suspending Gold sodium thiomalate.

The exact duration of corticosteroid treatment varies depending upon the response of the individual patient. If adverse effects are unusually severe or progressive therapy might be required for many months.

High doses of systemic corticosteroids like Prednisone 40 to 100 mg daily in divided doses are administered for severe renal, pulmonary, hematologic, and enterocolitis complications. The reactions on the skin and mucous membranes can be managed with topical corticosteroids, oral antihistamines, and soothing or anesthetic lotions. Systemic corticosteroids can be administered for providing symptomatic relief in the case of dermatitis or stomatitis.

A chelating agent may be given for enhancing gold excretion, in patients where the complications cannot be improved with high-dose corticosteroid treatment, or in patients where significant steroid-related adverse reactions develop.

Dimercaprol can be administered successfully. However, patients must be monitored carefully as numerous unwanted reactions may occur. Corticosteroids can be used along with the chelating agent.

Gold sodium thiomalate can be administered after mild reactions have resolved, by using a reduced dosage. The initial test dose of 5 mg Gold sodium thiomalate is tolerated well with progressively larger doses. A 5 to 10 mg dosage might be given at weekly to monthly intervals until a dosage of 25 to 50 mg is reached.

What Precautions Should Be Taken For Gold Sodium Thiomalate?

Gold salts must not be used along with Penicillamine. Gold sodium thiomalate must be used cautiously in patients with the following issues:

• Allergy or hypersensitivity to medications.

• A history of blood dyscrasias like granulocytopenia or anemia.

• History of kidney or liver disease.

• Hypertension.

• Skin rash.

• Decreased cerebral or cardiovascular circulation.

• Diabetes mellitus or congestive heart failure must be controlled before initiating gold therapy.

Pregnancy

Gold sodium thiomalate is teratogenic during the organogenetic period in rabbits and rats when given in doses 140 and 175 times the usual human dose, respectively. Hydrocephalus and microphthalmia were the abnormalities observed in rats when Gold sodium thiomalate at a dosage of 25 mg/kg/day from day 6 to day 15 of gestation was administered subcutaneously.

In rabbits, limb abnormalities and gastroschisis were reported when Gold sodium thiomalate was administered subcutaneously at doses of 20 to 45 mg/kg/day from day 6 to day 18 of gestation. No adequate studies have been performed on pregnant women. Gold sodium thiomalate must be during pregnancy only after calculating the risk and benefits.

Nursing Mothers

The presence of gold has been reported in the milk of nursing mothers. In addition, gold has been found to be present in the serum and red blood cells of a nursing infant. Because of the above findings and the potential for severe adverse reactions in nursing infants from Gold sodium thiomalate, a careful decision must be made whether to stop nursing or the drug. The persistence of gold in the mother due to slow excretion even after therapy is discontinued must also be considered.

Carcinogenicity

Renal adenomas have been documented in long-term toxicity data of rats receiving Gold sodium thiomalate at high dosage levels approximately 2 to 42 times the usual human dose. No studies have been reported on renal adenomas in men in association with the use of Gold sodium thiomalate.

Contraindications:

• Severe debilitation.

• Systemic lupus erythematosus.

• Hypersensitivity to any component of this medicine.

• Severe toxicity due to previous exposure to gold or other heavy metals.