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CBD Oil for Arthritis

Ongoing research shows evidence that cannabidiol (CBD) can have many benefits for those with arthritis. CBD products contain CBD extracts made from quality medical hemp plants that can be consumed or applied to individual parts of the body. Many people have heard about CBD products being used for arthritis and other chronic conditions. However, some may have questions about its effectiveness or how it works.

Arthritis can cause a variety of symptoms, including stiffness, pain, inflammation, and swelling. It can also cause reduced mobility, anxiety, and depression. Often, arthritis is only one of the ailments people deal with. This adds further stress and suffering in the process. These problems are leading many people to consider CBD as a safer therapeutic option. In this article, you will see some of the basics of CBD and arthritis. We will go over how CBD may help people with arthritis by relieving their symptoms.

Medical Marijuana’s Rich (and Long) History

Cannabis has long been used for medicinal and therapeutic purposes. These were often primary over the plant’s well-known capacity as a recreational substance. Medical marijuana seems to have been a primary use for the plant in many societies. It also seems there was never a clear-cut distinction between medical or therapeutic and recreational or social use. Thanks to current research, it is getting easier to understand how cannabis interacts with the body. Cannabinoids, compounds made by cannabis, do this both together and in isolation. This makes potential medical benefits far easier to understand.

Siberian burial mounds dating back to 3000 B.C. were found to contain charred cannabis seeds. This indicates that cannabis was in use thousands of years ago. Its presence in burial mounds shows that it had an important role in some ancient societies. Cannabis was a part of the medicinal, therapeutic, and social aspect of culture.

Cannabis has also been used in ancient Chinese therapies that originated thousands of years ago. Looking at cannabis through history, one finds that negative views of the flower only emerge over the last 500 years. Cannabis bans were rare until the 19th century and did not become commonplace until the 20th. Until then, for millions of people, cannabis was a part of life like any other homegrown crop.

Cannabis was also used widely for industrial purposes in the 18th century. Many American Founding Fathers grew hemp as a cash crop during the period. The first president of the United States, George Washington, grew hemp on his plantation at Mount Vernon. Cannabis only became illegal in the United States in 1937.

This means that cannabis remedies were available (though lesser-known) as little as a generation ago. While this can be shocking, it shows how cannabis was until very recently.

Unfortunately, many political factors led to the ban on cannabis in westernized countries. This controversial history in western cultures has made the study of cannabis’s benefits difficult over the last century. This explains why research on the potential uses for CBD is from more recent decades.

Sadly, current legislation in many countries continues to make the study of medical marijuana difficult. This is a fact that will only change with normalization and legalization of cannabis plants. Thankfully, more government leaders recognize the benefits of cannabis. This trend is due largely to a shift in public opinion. More people than ever believe that cannabis should be explored for its medical benefits.

What is CBD?

CBD is one of many beneficial cannabinoids derived from hemp plants. Hemp is classified as cannabis that contains extremely low amounts of tetrahydrocannabinol (THC). THC is the compound responsible for the “high” associated with cannabis. Certain products are put through special extraction processes. These remove the remaining trace amounts of THC. CBD oil is gathered from the flowers, leaves, and stalks of plants. CBD oil can be taken raw with carrier oils or infused into other products like topicals, edibles, and e-liquid. Because CBD oil is extremely low in THC, consumers can get the benefits of cannabinoids without any psychoactive effects. While THC can alter a consumer’s mental state or produce a “high” feeling, CBD has no such effect.

CBD products come in a variety of types with different concentrations of cannabinoids. Since cannabis has long had an unfortunate cultural stigma, some people still feel uncomfortable using medicinal and therapeutic cannabis products. Sadly, the history of anti-cannabis laws has cast an unwarranted shadow over medical marijuana products. Thankfully, this stigma continues to decline as people learn about cannabis’s potential benefits. This helps people to be more comfortable trying hemp-derived products.

CBD products are derived from hemp plants. These are cannabis strains bred specially to produce very low THC with high amounts of CBD and other cannabinoids.

As of the 2018 Farm Bill, the United States federal government has made a legal distinction between hemp and marijuana based on THC content. As long as a cannabis plant has no more than 0.3 percent THC, it is classified as hemp. This has made the clinical study of cannabinoids far easier. It also made hemp-derived remedies more widely available to the public.

CBD for Relief of Arthritis Symptoms

Many people use CBD products to relieve pain, inflammation, and other chronic symptoms. Emerging research shows that CBD can be useful for many people who suffer from pain, fatigue, and other chronic conditions. Arthritis is one of the most common chronic conditions in the United States and the leading cause of disability.

More than 50 million Americans suffer from arthritis every year. This number could be as high as 91 million when counting people who have arthritis but may not have been diagnosed. There are two types of arthritis that most commonly afflict Americans:

There is still much research that has to be done to understand how CBD affects arthritis and its precise applications in treatment. However, while CBD is yet being studied as a treatment for arthritis, the body of evidence in favor of this conclusion is growing. Studies conducted on animals show evidence that CBD has the potential to treat arthritis and relieve its symptoms. Other cannabinoids may help, too.

A 2014 review of clinical research concluded that CBD might be an effective treatment for OA. One 2016 study showed that topically applied CBD has an anti-inflammatory effect against arthritis. Another study done in 2017 showed further indications that CBD has the potential for treating OA.

Other cannabinoids show potential for bringing relief to those with arthritis. A 2006 study showed that a cannabis-derived oral spray, Sativex, relieved arthritis symptoms and pain.

Sativex is an oral spray that came from cannabis plants containing both CBD and THC. It is believed that both cannabinoids have the potential for therapeutic use, with the two possibly working in tandem as well. Another study conducted in 2011 showed that CBD helped improve symptoms of arthritis in rats. CBD altered how their nervous systems responded to painful sensations.

CBD Products for Chronic Pain Relief

Growing evidence shows that CBD could benefit people suffering from chronic pain. CBD may alter the brain’s natural response to pain signals, mitigating, or even eliminating painful sensations.

CBD and other cannabinoids attach to specially adapted receptors located in the brain and immune system. These cannabinoid receptors make up the body’s endocannabinoid system. There are two receptors in the endocannabinoid system, CB1 and CB2 receptors. CB1 receptors are mostly found in the brain. These interact with the body’s systems that regulate movement, thought, mood, coordination, appetite, and memory. THC, the psychoactive cannabinoid, interacts, especially with these receptors. This explains why using THC has such noticeable psychoactive effects.

Different receptors serve different purposes in the immune system. The specific roles of each are the subject of ongoing research. CB2 receptors help regulate pain and inflammation to support immune health. Current research indicates that CBD attaches itself to CB2 receptors once introduced into the body.

CBD may even help the body produce cannabinoids that also attach to the receptors. The evidence seems to show that CBD changes the way the receptors respond to pain and other signals from the immune system. Because of this, CBD can help the endocannabinoid system reduce pain and inflammation. This includes those caused by arthritis. This gives CBD potential therapeutic uses for chronic pain management. Other cannabinoids, including CBC, CBN, and THC, may also have medical uses.

CBD has also been shown to have potential benefits for other chronic conditions, too. Sometimes, other chronic conditions can develop alongside or even independently of arthritis. Cannabinoids show potential to relieve pain for those with multiple sclerosis and at least some kinds of cancer.

Research also indicates that CBD can have positive effects on consumers with fibromyalgia pain. Generally, side effects are extremely mild, like drowsiness, dry mouth, or dizziness. They also tend to fade quickly.

Mental health also seems to improve for many people using CBD. Often, consumers see a reduction in anxiety and depression symptoms. Some researchers believe that CBD has the potential to treat multiple anxiety disorders. Cannabis products are currently not generally recommended for children. However, it is possible that CBD can help relieve anxiety in young children.

Other studies show that CBD is linked to reduced symptoms of depression. This is incredibly important for people suffering from arthritis symptoms.

According to the Arthritis Foundation, depression can be a big problem among those with arthritis. Often, it is 2-10 times as much as the general population. CBD has the potential as a treatment that relieves arthritis and it may also help with the associated mental health symptoms. This is wonderful news for people with arthritis.

How to Use CBD

CBD products for arthritis are offered in a wide variety of styles, application types, and concentrations. This gives consumers the flexibility to choose from powders, capsules, oils, creams, and gels. Consumers can take CBD orally using oils, tinctures, and sprays. They can also vaporize products in e-liquids and dry herb vaporizers (used for raw, high CBD hemp flower).

Consumers who have arthritis can especially benefit from topically applied creams and gels. CBD can be applied directly to uncomfortable, inflamed, swollen, or painful joints. This can give faster symptom relief than other ingestion methods. As well, CBD that is taken orally or through vaporizers is distributed evenly throughout the body. Creams and gels enable consumers to target problem areas for quicker, more effective symptom relief.

Before you decide to take any CBD products, make sure you consult with your physician. Your doctor should be kept aware of any supplements, dietary changes, or remedies you are considering. It is important for your health care that you keep your doctor abreast of any changes you make in this regard. Your doctor can help monitor for any interactions with medications or other adverse reactions. Side effects and adverse reactions from CBD products are rare. However, any new substance introduced to the body can cause unwanted reactions.

Potential Unwanted Side Effects of CBD for Arthritis

In the vast majority of cases, as also shown by smaller clinical studies, CBD is tolerated well by most consumers. However, no compound is without any risk whatsoever of adverse reactions or unwanted side effects. CBD can cause mild unwanted effects in a small percentage of consumers. Potential unwanted effects include:

CBD shows no evidence of causing physical dependence in consumers. This makes it a potentially wonderful alternative to more dangerous opioids used to treat chronic pain. Epidiolex is the CBD medication approved by the United States Food and Drug Administration (FDA) for seizures. Epidiolex successfully underwent clinical trials. Researchers found no evidence of physical dependence in patients because of the treatment.

CBD may interfere with cytochrome P450 complex, an enzyme used by the liver during the process of breaking down toxins. Potentially, though it is not yet established, CBD may exacerbate the risk of increased liver toxicity. Consumers who are already at risk should especially consult their doctors before using any CBD products. They should exercise caution in adding CBD to their supplement regimen.

CBD may also interact with prescription medications, over-the-counter medications, supplements, and dietary aids. People who take medications that have potential interactions with grapefruit should also be careful with CBD. There may be an increased potential for unwanted side effects. Rarely, CBD applied to the skin can cause irritation, so it should be applied to a small area when used for the first time.

Considerations Before Using CBD for Arthritis

CBD and medical marijuana are complex topics that are unfortunately made a bit more complex by the current laws in the United States. The 2018 Farm Bill removed all federal prohibition on the production, sale, and consumption of hemp-derived products. But not all states have legalized CBD and hemp products.

That means that cannabis products, including CBD products, are not yet legal in every state. In some states, only those prescribed with CBD products under a state medical marijuana program can legally possess and use them. Make sure to know your state’s regulations before making any purchases.

Make sure you check local and state laws before purchasing or using CBD products to ensure you are in compliance. Even if CBD and hemp are legal in your locality, high THC cannabis may still be partially or completely illegal. If traveling with hemp products, be sure to have the appropriate paperwork. This should show the product’s cannabinoid content and legality. This is especially true for raw flowers that could be mistaken for an illegal substance.

Currently, CBD is not approved for prescription treatment for arthritis by the FDA. The FDA has only approved CBD as a treatment for two rare kinds of epilepsy with severe symptoms, and it only gave this approval in June 2018. This means that the FDA has just begun to consider CBD as a treatment for diseases, and further approvals will take time.

The Effectiveness of CBD Compared to Current Treatments

CBD products could bring relief to people with arthritis pain and discomfort. CBD’s effects on the endocannabinoid system, and the brain and immune system’s CB2 receptors, are encouraging. Researchers continue to study CBD and other cannabinoids.

They hope to see how they interact with the immune systems of arthritis patients. More studies are needed before it can be said that CBD is an effective arthritis treatment. Even so, the current body of evidence continues to show that this is likely.

Many consumers wonder whether CBD can help with arthritis symptoms. They also want to know whether it is more effective or safer than treatments that are currently available. Medical experts are trying to find ways to reduce dependence on pain relievers.

This has led to much excitement surrounding CBD and other medical marijuana products. The products seem to show great effectiveness for symptom relief. They appear to be safe for the vast majority of consumers.

Current research shows that CBD is safe for most people. It can play an important role in reducing pain and inflammation caused by arthritis. Nevertheless, like with all other therapeutic substances, the effectiveness of CBD will vary from person to person. Many people report immediate or almost immediate symptom relief.

Others say that the full effects can take days to weeks to be felt. Consulting with your physician is an important step in figuring out the right CBD dosage. You should consider your medications, conditions, tolerance, and other factors. Combined with proper diet, regular exercise, and prescription medications, CBD could bring huge relief.

    Summary for UKPID


    Dr Alan Worsley Bsc(hons) PhD MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP

    This monograph has been produced by staff of a National Poisons
    Information Service Centre in the United Kingdom.  The work was
    commissioned and funded by the UK Departments of Health, and was
    designed as a source of detailed information for use by poisons
    information centres.

    Peer review group: Directors of the UK National Poisons Information



   Type of product

         For the treatment of ulcerative colitis.


         Sulphasalazine   tablets 500mg
                          suspension 250mg/5ml
                          Suppositories 500mg


         Probably not very toxic. A 33 year old adult took 10-15g and had
         no symptoms.


         Nausea and vomiting, dizziness, ataxia, drowsiness and dysuria.
         Urine and other body fluids may be coloured orange. Contact
         lenses may be stained.



    1. Empty the stomach if more than 10 tablets ingested.

    2. Liberal fluids.

    3. Other measures are indicated by patients' clinical condition.


    ABPI Data Sheet Compendium. Datapharm publications Limited 1996-1997

    British National Formulary. Number 32 (september 1996). British
    medical Association and Royal Pharmaceutical Society.

    Dollery C. Therapeutic Drugs. (Pt 2). Churchill Livingstone (1994).



    Brand Name


   Generic Name


Chemical group/family

         treatment of chronic diarrhoea
         BNF 1.4

  Reference number1

         (CAS) 599-79-1


         Pharmacia & Upjohn Ltd,
         7 Windermere Rd
         West Wickham,
         BR4 9AN

         01908 661101


         sulphasalzine 500mg tablets
         pack size 100,
         sulphasalazine enteric coated 500mg tablets
         pack size 100,
         sulphasalazine suspension 250mg/5ml
         pack size 500ml,
         sulphasalazine suppositories 500mg
         pack size 10 & 50,
         sulphasalazine retention enema 3g in 100ml
         pack size 7x 100ml.

   Physicochemical properties (Dollery)3

         2-Hydroxy-4'-(2-pyridylsulphamoyl)azobenzene-3-carboxylic acid

    Molecular Weight

         2.4, 8.3, 11.0

         in water            insoluble
         in alcohol          1 in 2900

    octanol/water partition coefficient



    Induction and maintenance of remision in ulcerative colitis; active
    Crohn's disease; rheumatoid arthritis.

   Therapeutic Dosage (BNF)6

    Adults (by mouth)

    Acute attack 1-2 g 4 times daily until remission occurs, reducing to
    maintenance dose of 500mg 4 times daily.

   Child (by mouth)

    Over 2 years, acute attack 40-60mg/kg daily, maintenance dose 20-
    30mg/kg daily.

    Adults (by rectum)

    In suppositories, alone or in conjunction with oral treatment 0.5-1g
    morning and night after bowel movement. As an enema, 3g at night,
    retained for at least 1hr.


    Salicylate and sulphonamide hypersensitivity. CHILD under 2 years of


    History of allergy; hepatic and renal disease; G6PD deficiency; slow
    acetylator status; risk of haematological and hepatic toxicity
    (differential white cell, red cell and platelet counts initially and
    at monthly intervals for first 3 months, liver function tests at
    monthly intervals for first 3 months; upper gastro-intestinal side
    effects common over 4g daily; pregnancy and breast feeding; porphyria.

    Pharmacokinetics (Dollery)3

         Oral absorption               20-30%
         Presystemic metabolism        70-80%
         Plasma half-life
         range                         3-11hr
         mean                          6hr

         Plasma half-life
         range                         6-17hr
         mean                          10hr

         Plasma half-life
         (acetyl-5-aminosalicylic acid)
         range                         4-10hr
         mean                          7hr

         Volume of distribution        -
         Plasma protein binding        95-99%


         None available

    Adverse effects (data sheet)

    Overall about 75% of adverse drug reactions occur within 3 months of
    starting therapy and over 90% by 6 months. Some undesirable effects
    are dose dependant and symptoms can often be alleviated by reduction
    of the dose. Since sulphasalazine is metabolised to sulphapyridine and
    5-aminosalicylic acid, side effects of sulphonamides and salicylates
    may occur. Patients with slow acetylator status are more likely to
    experience adverse effects due to sulphapyridine. The most commonly
    encountered reactions are nausea, headache, rash, loss of apetite and
    raised temperature.
    The folowing adverese reactions have been reported:

     Haematological: Potentially fatal leucopaenia, neutropaenia,
    agranulocytosis, aplastic anaemia and thrombocytopaenia. Leucopaenia,
    which is normally mild and transient, may occur in up to 1.5% of
    patients and agranulocytosis in up to 1 in 700 patients during the
    second month of therapy.
    Heinz body anaemia, methaemaglobinaemia, hypoprothrombinaemia,
    haemolytic anaemia, megaloblastic anaemia.

     Hypersensitivity reactions: Generalised skin eruptions, Stevens-
    Johnson syndrome, exfoliative dermatitis, epidermal necrolysis,
    pruritis, urticaria, photosensitisation, anaphylaxis, serum sickness,
    drug fever, periorbital oedema, conjunctival and scleral injection,
    arthralgia, allergic myocarditis, polyarteritis nodosa, LE-phenomenon
    and lung complications with dyspnoea, fever, cough, eosinophilia,
    fibrosing alveolitis.

     Gastro-intestinal reactions: Stomatitis, parotitis, pancreatitis,

     CNS Reactions: Vertigo, tinnitus, peripheral neuropathy, ataxia,
    convulsions, insomnia, mental depression, aseptic meningitis and

     Fertility: Oligospermia, reversible on discontinuance of drug.

     Renal reactions: Crystallurai, haematuria, proteinuria and nephrotic
    syndrome. An acute attack may be precipitated in patients with


    Long term clinical usage and experimental studies have failed to
    reveal any teratogenic or icteric hazards.
    No increase in congenital defects or newborn toxicity has bee observed
    from its use in pregnancy. However, three reports, involving five
    infants (two stillborn), have described congenital malformations after
    exposure to this drug. It cannot be determined whether the observed
    defects were related to the therapy, the disease, or a combination of
    these or other factors.
    Sulphasalazine and its metabolite, sulphapyridine, readily cross the
    placenta to the fetal circulation. Fetal concentrations are
    approximately the same as maternal concentrations.
    Placental transfer of 5-amoinosalicylic acid is limited since only
    negligible amounts are absorbed from the caecum and colon and these
    are rapidly excreted in the urine.

   Breast Milk

    Sulphapyridine (metabolite of sulphasalazine) is excreted into breast
    milk. Milk concentrations were approximately 40-60% of maternal serum
    levels. One of the infant's urine contained 3-4 microg/ml of drug,
    representing about 30-40% of the total dose excreted in the milk.


    Sulphasalazine      Interaction with ampicillin. Reduction in the
                        release of 5-ASA due to disturbance of gut flora.
                        Interaction with cholestyramine. Cholestyramine
                        has been shown to bind to sulphasalazine in the
                        gut, thereby reducing activity.
                        Interaction with digoxin. serum digoxin levels can
                        be reduced by the concurrent use of
                        Interaction with ferrous sulphate. Sulphasalazine
                        and iron appear to bind together in the gut,
                        thereby reducing activity.
                        Interaction with folic acid. Sulphasalazine can
                        reduce the absorption of folic acid.
                        Interaction with iron preparations. Sulphasalazine
                        and iron appear to bind together in the gut,
                        thereby reducing activity.
                        Interaction with rifampicin. Reduction in the
                        release of 5-ASA due to disturbance of gut flora.
                        Interaction with talinolol. Sulphasalazine
                        markedley reduced the absorption of talinolol.


    No specific data on sulphasalazine poisoning are available.

    Case report

    A 23 yr old man ingested 50 x 500mg sulphasalazine tablets. He
    developed a headache and felt dizzy. He was treated with Gastric
    lavage, activated charcoal with sorbitol and I/V dextrose with sodium
    bicarbonate. He survived with few ill effects7.


    Range of toxicity (Poisindex)

    Since many of the adverse effects appear to be hypersensitivity
    reactions, there is no specific toxic dose. The incidence of the
    adverse effects appears to increase with increased sulphonamide
    The majority of the 5-aminosalicylic acid (80%) is excreted in the
    stool8. Thus toxicity due to salicylate is likely to occur only at
    high levels of sulphasalazine ingestion. There are no data available
    on the toxicity of 5-aminosalicylic acid.

    Fatal level
    Not Known

Toxicity of Sulphasalazine?

    If toxic levels of aspirin are achieved in adults by an approximate
    consumption of 5 to 30g, then toxicity may similarly be achieved with
    salicylate by taking 3.8 to 22.8g (allowing for changes in atomic
    mass). If Toxic levels of salicylate are then compared to
    5-aminosalicylic acid , toxic levels could be achieved by ingestion of
    4.22 to 25.5g of 5ASA.
    The equivalent proportion of sulphasalazine needed to be taken to
    cause toxic levels of toxicity as described above would be within the
    range 11.1 to 66.66g. However the majority of sulphasalazine excreted
    in the stool is approximately 80%. Therefore ingestion of 55.5g to
    333.3g of sulphasalazine would be required in order to achieve toxic
    levels of salicylate.
    [This calculation is an approximation]





    Adverse reactions to sulphonamides involve nearly every organ system;
    often in multiple fashion and in varying degree. Although there is a
    difference as to the frequency of toxic effects between short acting
    and long acting, there is considerable overlap. Many of the adverse
    effects appear to be hypersensitivity reactions, the incidence of
    which is dose related.


    Transient myopia, conjunctivitis and keratitis may occur in
    association with hypersensitivity reaction.


    Nausea and vomiting are likely to occur.


    Hypersensitivity reactions to sulphonamides may produce hepatic


    Haematological effects are uncommon, but sveral have been reported.
    These include acute haemolytic anaemia, agranulocytosis,
    thrombocytopaenia, aplastic anaemia and methaemoglobinaemia


    1. Administer activated charcoal within 1-2 hours of ingestion.
    2. Treatment is symptomatic and supportive.
    3. Hypotension- administer IV fluids.
    4. Monitor renal function.

    NPIS Newcastle

    Dr Alan Worsley Bsc(hons) PhD MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP

    This monograph was produced by the staff of the Newcastle Centre of
    the National Poisons Information Service in the United Kingdom. The
    work was commissioned and funded by the UK Departments of Health, and
    was designed as a source of detailed information for use by poisons
    information centres.

    Peer review was undertaken by the Directors of the UK National Poisons
    Information Service.

    Last updated September 1997


    1. Martindale: the Extra Pharmacopoeia. 30th edition. Pharmaceutical
    Press (1993)
    2. ABPI Data Sheet Compendium. Datapharm Publications Ltd (1995-6)
    3. Therapeutic Drugs. Dollery C (Ed). Churchill Livingstone (1991)
    4. Briggs GG et al. Drugs in pregnancy and lactation. Williams and
    Wilkins Ltd (1993)
    5. British National Formulary. No 32 (Sept 1996).
    6. Medical Toxicology. 2nd Edition. Ellenhorn MJ (Ed) Elsevier 1992.
    7. Minocha A, Dean HA & Mayle JE. Acute sulphasalazine overdose. Clin
    Toxicol (1991);29:543-551
    8. Hanngren A, Hansson E, Svartz N, Ullberg S. Distribution of studies
    of salicylazosulphapyridine part I. Acta Medica Scandinavia (1963);

Summary for UKPID




    Kathryn Pughe, BSc (Hons) MRPharmS


    National Poisons Information Service (Newcastle Centre)

    Regional Drug & Therapeutics Centre

    Wolfson Building

    Claremont Place

    Newcastle upon Tyne

    NE1 4LP


    This monograph has been produced by staff of a National Poisons

    Information Service Centre in the United Kingdom.  The work was

    commissioned and funded by the UK Departments of Health, and was

    designed as a source of detailed information for use by poisons

    information centres.


    Peer review group: Directors of the UK National Poisons Information






         Generic             Auranofin

         Proprietary         Ridaura


         Generic             Sodium aurothiomalate

         Proprietary         Myocrisin

         Synonyms            Gold sodium thiomalate,

                             Sodium aurothiosuccinate


    Chemical Group/Family


         Drugs suppressing rheumatic disease

         BNF 10.1.3


    Reference Number


         Na aurothiomalate

         CAS 12244-57-4 (xNa, anhydrous)

         CAS 39377-38-3 (2Na monohydrate)



         CAS 34031-32-8


         Product licence numbers:

         Myocrisin:     10 mg inj 0012/5114

                        20 mg inj 0012/5113

                        50 mg inj 0012/5006

         Ridaura:       0002/0082




         Myocrisin:     Rhone-Poulenc Rorer Ltd

                        RPR House

                        52 St Leonards Road


                        East Sussex

                        BN21 3YG


                        Tel: 01323 417125

                        Fax: 01323 534086


         Ridaura:       Bencard

                        Welwyn Garden City


                        AL7 1EY


                        Tel: 0800 616482

                        Fax: 0181 913 4560




         Myocrisin      Pale yellow solution

                        0.5ml amps in boxes of 10 x 10 mg

                        0.5ml amps in boxes of 10 x 20 mg

                        0.5ml amps in boxes of 10 x 50 mg


         Ridaura        Pale yellow, film coated square tablets

                        3 mg tabs in containers of 60


    Physico-Chemical Properties


    Chemical structure

         Myocrisin      C4H3AuNa2O4S

                        Disodium salt of (aurothio)succinic acid


         Auranofin      C20H34AuO9PS


                        S-tri-ethylphosphine gold


    Physical state at room temperature

         Aurothiomalate      Fine, pale yellow powder with a slight odour

         Auranofin           Fine white powder


    Molecular weight


         (Hexomer)           2500 in 0.5M NaCl

         (Monomer)           390.1

         Auranofin           678.5



         thiomalate          3.2

         carboxyl            4.2

         Auranofin           -



         Aurothiomalate      in alcohol insoluble

                             in water       very soluble

         Auranofin           in alcohol 1 in 27

                             in water       1 in 5900






         Sodium aurothiomalate - active progressive rheumatoid arthritis,

         and progressive juvenile chronic arthritis.


         Auranofin - active progressive rheumatoid arthritis when NSAIDs

         inadequate alone.


    Therapeutic Dosage


          Sodium aurothiomalate


         By deep im injection only.

         Adults: Initial test dose of 10 mg in first week followed by

         weekly doses of 50 mg until signs of remission occur. With full

         remission, the interval between injections should be

         progressively increased to 3, 4 and then, after 18-24 months, to

         6 weeks. If after reaching a total dose of 1g, excluding the test

         dose, no major improvement has occurred and the patient has not

         shown any signs of gold toxicity, six 100 mg injections may be

         administered at weekly intervals. If no signs of remission occur

         after this time, consider alternative treatments.


         Children: Weekly doses of 1mg/kg up to maximum weekly dose of 50

mg This dose may be preceded by a smaller test dose of 1/10th or

         1/5th of the full dose for 2-3 weeks. Continue weekly doses until

         signs of remission appear then increase intervals to 2 weeks.

         With full remission increase interval to 3 then 4 weeks. I f no

         signs of remission after 20 weeks, consider alternative

         treatments. Treatment should be continued for 6 months. Expect

         response at 300-500 mg level. If patients respond, maintenance

         therapy should be continued with the dosage administered over the

         previous 2-4 weeks for 1-5 years.




         Adults: Starting dose 3 mg twice daily, then 6 mg as single daily

         dose if well tolerated. Continue for minimum of 3-6 months to

         assess response. Increase to 3 mg three times a day if response

         inadequate after 6 months, if still inadequate after a further 3

         months, then discontinue


         Child: Not recommended




          Sodium aurothiomalate


         Severe renal and hepatic disease; history of blood disorders or

         bone marrow aplasia; exfoliative dermatitis; systemic lupus

         erythematosus; necrotising enterocolitis; pulmonary fibrosis;

         pregnancy and breastfeeding; porphyria.




         Not for use in patients with a history of gold-induced disorders

         as for sodium aurothiomalate.














         Aurothiomalate      Intramuscular absorption 100%, not orally


         Auranofin           Oral absorption 13-33%




         Aurothiomalate      Volume of distribution - 0.1Lkg-1

         Auranofin           Volume of distribution - NIF




         Aurothiomalate      No presystemic metabolism, 95% plasma protein


         Auranofin           No presystemic metabolism, 60% plasma protein





         Aurothiomalate      70% excreted in urine, 30% in faeces

         Auranofin           85% excreted in faeces, 15% in urine



         Aurothiomalate      Initial 5.5 days; terminal 250 days

         Auranofin           17-25 days (plasma); total body 70 days


    Special Populations




    The safety of gold salts in pregnancy has not been established. Gold

    salts should not be used in women of child-bearing potential, unless

    the benefits outweigh the possible risks, as clinical experience is



    Gold is teratogenic in rats and rabbits at high doses which produce

    maternal toxicity, increased frequencies of skeletal, CNS and other

    malformations were seen.


    There are no controlled studies of gold administration     during

    human pregnancy. Placental passage of gold salts has been documented

    in clinical reports.


    The frequency of malformations was not increased in a study of 119

    children born to women who had been treated with gold compounds during

    the first trimester of pregnancy. 26 patients in this series received

    gold treatment throughout pregnancy, 2 minor anomalies were seen but a

    causal association with gold has not been established.


    Hepatic disease


    Use with caution in patients with any degree of hepatic dysfunction.

    Intrahepatic cholestasis with eosinophilia may be seen after gold

    injections. The condition is self-limiting, and liver function tests

    return to normal within about 3 months.


    Renal disease


    Use with caution in patients with any degree of renal impairment.




    Monitor with extra caution due to decreased renal function




    Avoid if breastfeeding as significant amounts of gold excreted.






    Acute overdose is usually the result of administration errors with IM

    injections, and until 1984 therapeutic gold drugs were only available

    parenterally. Most toxic data are based on therapeutic toxicity.




    There is a high incidence of adverse reactions when gold salts are

    used for rheumatoid arthritis, incidence is between 5-50% (Eyring &

    Engleman, 1963; Davis & Hughes, 1974). The rate of serious reactions

    is approximately 3-5%. Anaphylactoid effects may occur after any

    course of therapy, usually within the first 10 minutes of



    Problems with therapeutic use include mouth ulcers, skin reactions,,

    proteinuria, blood disorders (sometimes sudden onset and fatal).

    Rarely colitis, peripheral neuritis, pulmonary fibrosis,

    hepatotoxicity with cholestatic jaundice and alopecia can also occur.

    Diarrhoea and other gastrointestinal symptoms are associated with

    auranofin use.


    Proteinuria occurs in 2-20% of patients treated with injected gold and

    may be sufficiently severe to cause nephrotic syndrome in 10-30% of

    those affected. Proteinuria usually resolves on stopping treatment.


    Gold lung is a rare toxic side effect of gold therapy that may begin

    after administration of 300-1000 mg total gold dose. Dyspnoea appears

    suddenly over a period of 2-10 days. Chest x-rays show diffuse

    bilateral pulmonary shading (Gortenuti et al 1985), and a moderate

    eosinophilia may be present. The prognosis is good after withdrawal of

    treatment (McFadden et al 1989), although impairment of lung function

    may be permanent (Cohen 1988).


    Patients treated with gold salts should be asked to report immediately

    the appearance of pruritis, metallic taste, sore throat or tongue,

    buccal ulceration or easy bruising, purpura, epistaxis, bleeding gums,

    menorrhagia or diarrhoea.




    Increased risk of toxicity with other nephrotoxic and myelosuppressive







    No deaths have been recorded. Adults have been given up to 500 mg (10

    times the therapeutic dose ) in a single dose with variable

    consequences. One patient took 27 mg auranofin daily for 10 days and

    developed an encephalopathy and peripheral neuropathy. The patient

    made a gradual recovery after auranofin was discontinued





    Effects would be expected to be extensions of toxic therapeutic





    Most of the reported cases of overdose have not developed  features.

    Early features of acute overdose have included a generalized skin

    rash, which settled within a few hours, and oedema of the eyelids in

    one case, and ventricular tachycardia in another. Acute renal failure

    is a potential problem but has not been reported. Abnormal LFTs with

    elevation of ALT and alkaline phosphatase were reported 3 weeks post-

    overdose in one case.




    Observation and supportive measures are probably all that are

    required. There is some doubt as to whether toxic reactions seen are

    due to direct effects of gold, or an indirect effect through the

    immune system.




    Overdose with oral gold salts is not commonly seen and it is not known

    if activated charcoal is effective in minimizing drug absorption in

    such cases. Metallic gold is poorly adsorbed by activated charcoal.


    Supportive care


    D-Penicillamine has been used to treat skin reactions (Davis 1969)

    and thrombocytopenia (Bluhm et al 1962) in   cases where BAL and

    corticosteroids showed initial but not sustained results. It should be

    avoided in penicillin-allergic patients. Monitoring for proteinuria

    should be performed.


    Adults: 15-40mg/kg/day orally; max 250-500 mg four times a day before



    Children: 20-30mg/kg/day orally once or twice daily before meals.


    Immunosuppressives such as cyclophosphamide have also been used to

    control toxic reactions. A dose of 100 mg daily for 6 months was used

    until platelets stabilised at 100,000 per cubic mm, and then the dose

    was reduced to 75mg daily (Kozloff et al 1979).




    Haematology, liver and renal functions should be monitored.


    Gold urine levels during treatment vary      considerably. There seems

    to be no correlation between blood gold levels and toxicity or

    therapeutic effect. In a summary of 20 cases of toxicity, the

    cumulative toxic dose was from 230 mg to 10g of gold salt.




    Some patients have been given dimercaprol (BAL) to chelate the

    gold but there is no evidence that it is of value.


    The dose of BAL is individualized. A common dosage schedule is 3-5

    mg/kg/dose every 4 hours by deep IM injection for the first 2 days,

    then 2.5-3/mg/kg/dose IM every 6 hours for 2 days, then 2.5-3 mg/kg IM

    every 12 hours for 7 days.






    N-acetylcysteine (NAC) has been used to remove / redistribute gold and

    reduce haematological reactions (Godfrey et al 1982). Lorber et al

    (1973) demonstrated in vitro and in vivo chelation of gold by NAC,

    with up to a 54% increase over normal excretion in subjects tested.


    Dose: 2-9g in 100ml dextrose 5% or 0.45% sodium chloride iv over 2-6

    hours. Total dose per therapy ranged from 13 to 153g.


    D-Penicillamine was shown to enhance the urinary excretion of gold

    when tested in 9 patients (Erying & Engleman 1963).




    Haematology, liver and renal functions should be monitored.


    Management controversies 


    Use of dimercaprol: Patients with high gold levels not given

    dimercaprol do not appear to have had an adverse outcome, but there is

    insufficient data to make categoric statements. Chelation reduces the

    amount of circulating gold, but it is nearly impossible to remove all

    the gold from the system.






Auranofin overdose (27 mg/day for 10 days) has resulted in

    peripheral neuropathy and encephalopathy, which resolved upon drug

    withdrawal (Ridaura Prod Info, 1985).




  1. Pik et al (1985) reported two acute overdose cases in which

    patients received 1000 mg and 500 mg of intramuscular aurothioglucose,

    respectively. Both patients were asymptomatic and recovered

    uneventfully without treatment. One patient, however, developed

    microhaematuria and granular casts without proteinuria which resolved

    spontaneously within four weeks.


  1. A 53 year old male was accidentally injected with an im dose of 450

    mg sodium aurothiomalate. Palpebral oedema and a cutaneous generalized

    rash were observed within 30 minutes. The gold blood levels reached

    29.7mg/L without significant toxicity. The patient was treated with

    BAL and recovered (Barelli et al 1987).


  1. A 32 year old patient developed ventricular tachycardia 3 hours

    after im injection of 500 mg of aurothiomalate (Sharf et al 1976).




    Kathryn Pughe, BSc (Hons) MRPharmS


    National Poisons Information Service (Newcastle Centre)

    Regional Drug & Therapeutics Centre

    Wolfson Building

    Claremont Place

    Newcastle upon Tyne

    NE1 4LP



    This monograph was produced by the staff of the Newcastle Centre of

    the National Poisons Information Service in the United Kingdom. The

    work was commissioned and funded by the UK Departments of Health, and

    was designed as a source of detailed information for use by poisons

    information centres.


    Peer review was undertaken by the Directors of the UK National Poisons

    Information Service.


    Last updated March 1997






  1.   ABPI Compendium of Data Sheets and Summaries of Product

         Characteristics. Datapharm Publications Ltd. 1996-97.


  1.   AHFS Drug Information. McEvoy GK (Ed.) 1997.


  1.   British National Formulary. Number 32 (September 1996). British

         Medical Association and Royal Pharmaceutical Society.


  1.   Dollery C. Therapeutic Drugs. Churchill Livingstone. 1991.


  1.   Ellenhorn MJ. Ellenhorn's Medical Toxicology: Diagnosis and

         Treatment of Human Poisoning. 2nd Edition. Williams & Wilkins.



  1.   Martindale : The Extra Pharmacopoeia. 31st Edition. Reynolds JEF

         (Ed.) Pharmaceutical Press. 1996.




  1.   Barrelli A, Calimici A, Pala F. Gold salts acute poisoning: a

         case report. Vet Hum Toxicol 1987; 29(suppl 2): 108-110.


  1.   Bluhm GB, Sigler JW, Ensign DC et al. D-penicillamine therapy of

         thrombocytopenia secondary to chrysotherapy: a case report.

         Arthritis Rheum 1962; 5: 638.


  1.   Cohen MAH. Adverse reactions to gold compounds. Adverse Drug

         React Acute Poison Rev 1988; 4: 163-178.


  1.   Davis CM. D-penicillamine for the treatment for the treatment of

         gold dermatitis. Am J Med 1969; 46: 472-477.


  1.   Davis P & Hughes GRV. Significance of eosinophilia during gold

         therapy. Arthritis Rheum 1974; 17: 964-967.


  1.   Erying EJ & Engleman EP. Interaction of gold and penicillamine.

         Arthritis Rheum 1963; 6: 216-223.


  1.   Godfrey NF, Peter A, Simon TM et al. IV N-acetylcysteine

         treatment of hematologic reactions to chrysotherpay. J Rheum

         1982; 9: 519-526.


  1.   Gortenuti G, Parrinello A, Vicentini D. Diffuse pulmonary changes

         caused by gold salt therapy. Report of a case. Diagn Imag Clin

         Med 1985; 54: 298-303.


  1.   Kozloff M, Votaw M & Penner JA. Gold-induced thrombocytopenia

         responsive to cyclophosphamide. South Med J 1979; 72: 1490-1491.


  1. Lorber A, Baumgartner WA, Bovy RA et al. Clinical application for

         heavy metal complexing potential of N-acetylcysteine. J Clin

         Pharmacol 1973; 13: 332-336.


  1. McFadden RG, Traher LJ, Thompson JM. Gold-naproxen pneumonitis. A

         toxic drug reaction? Chest 1989; 96: 216-218.


  1. Pik A, Cohen N, Yona E et al. Should gold overdose be invariably

         treated? J Rheumatol 1985; 12: 1174-1175.


  1. Rubinstein I et al. Aurothioglucose overdosage in five patients

         with rheumatoid arthritis. Clin Rheumatol 1987; 6: 583-587.


  1. Sharf J, Nahir M, Nirenberg L. Ventricular tachycardia caused by

         gold overdose. Arthritis Rheum 1976; 19: 137-138.


    Computer databases:


  1.   Poisindex System(R), Micromedex inc., Denver Colorado, Edition

         Expires 31/3/97.


  1.   Reprotox System(R), Micromedex inc., Denver Colorado, Edition

         Expires 31/3/97.


  1.   TOXBASE, National Poisons Information Service, 1997.




VOL.: 26 (1981) (p. 47)


  1. Summary of Data Reported and Evaluation

5.1 Experimental data

Azathioprine was tested by intraperitoneal, subcutaneous and/or intramuscular administration in mice and by oral and intraperitoneal administration in rats. Suggestive evidence was obtained for the induction of lymphomas after intraperitoneal, subcutaneous or intramuscular injection in mice and for ear-duct carcinomas in rats after oral administration. Because of limitations in design and reporting, however, the results were considered to be inconclusive.

Studies in which azathioprine was tested in combination with other agents were inadequate for evaluation.


Azathioprine is embryolethal at doses nontoxic to the mother and can induce a variety of severe teratogenic effects in several animal species. It is mutagenic in bacteria and yeast in vitro and in Drosophila melanogaster and mice in vivo. At high concentrations, the drug is clastogenic to human lymphocytes in vitro.


5.2 Human data

Azathioprine has been widely used since the 1970s to prevent rejection following organ transplantation. It is also used to treat a variety of autoimmune diseases.

Use of azathioprine during pregnancy may reduce birth weight significantly. The data were insufficient to evaluate the teratogenic potential of this drug to humans. Azathioprine produces chromosomal abnormalities and increases in sister chromatid exchanges in the peripheral lymphocytes of non-cancer patients. No data were available to evaluate the mutagenic potential of this drug to humans.


There is evidence that azathioprine, often combined with prednisone, is associated with an increased incidence of non-Hodgkin's lymphoma, squamous-cell cancers of the skin, hepato-biliary carcinomas, mesenchymal tumours, and perhaps certain other rare neoplasms. The risk of non-Hodgkin's lymphoma is higher in organ transplant recipients; the presence of the graft may make some contribution to this increased incidence.


5.3 Evaluation

There is limited evidence for the carcinogenicity of azathioprine in mice and rats. There is sufficient evidence that azathioprine is carcinogenic in humans.

For definition of the italicized terms, see Preamble Evaluation.


Subsequent evaluation: Suppl. 7 (1987)


Last updated: 8 April 1998

See Also:

        Azathioprine (IARC Summary & Evaluation, Supplement 7, 1987)

        Azathioprine (PIM 053)


(Group 1)

For definition of Groups, see Preamble Evaluation.


Supplement 7: (1987) (p. 119)


CAS No.: 446-86-6

Chem. Abstr. Name: 1H-Purine, 6-[(1-methyl-4-nitro-1H-imidazol-5-yl)thio]-


A. Evidence for carcinogenicity to humans (sufficient)


Two large prospective epidemiological studies have shown that renal transplant patients, who usually receive azathioprine as an immunosuppressant, become at high risk for non-Hodgkin's lymphoma, squamous-cell cancers of the skin, hepatobiliary carcinomas and mesenchymal tumours. While this is true for each of the various etiological entities resulting in the need for a transplant, these patients also have in common heavy exposure to foreign antigens [ref: 1]. Other patients who have received azathioprine as an immunosuppressant, including those with rheumatoid arthritis, systemic lupus and other 'collagen' disorders, inflammatory bowel disease and certain skin and renal diseases, have also been studied: the same array of malignancies was found to be in excess, although to a lesser extent [ref: 1,2]. For these patients, however, the picture is still not completely clear, because patients with rheumatoid arthritis constituted the largest category in the latter study [ref: 2], and some [ref: 3], but not all studies [ref: 4], have found that this disease conveys a risk for non-Hodgkin's lymphoma in the absence of treatment.


B. Evidence for carcinogenicity to animals (limited)


Suggestive evidence was obtained that lymphomas were induced in mice after intraperitoneal, subcutaneous or intramuscular injection of azathioprine, and that thymic lymphomas and squamous-cell carcinomas of the ear duct were induced in rats after oral administration, but there were limitations in the design and reporting of these studies [ref: 1,5].


C. Other relevant data


There are conflicting reports of effects on the incidence of chromosomal aberrations in lymphocytes and bone-marrow cells of patients treated with azathioprine. In one study, the incidence of sister chromatid exchanges in lymphocytes of treated patients was not increased [ref: 6].


In animals treated in vivo, azathioprine induced dominant lethal mutations in mice; chromosomal aberrations in rabbit lymphocytes and Chinese hamster bone-marrow cells, and micronuclei in mice, rats and hamsters; it did not induce sister chromatid exchanges in Chinese hamster bone-marrow cells. Azathioprine induced chromosomal aberrations but not sister chromatid exchanges in human lymphocytes in vitro. It induced chromosomal aberrations in Drosophila and was weakly mutagenic to fungi and was mutagenic to bacteria [ref: 6].


Overall evaluation


Azathioprine is carcinogenic to humans (Group 1).


For definition of the italicized terms, see Preamble Evaluation.


Also see previous evaluation: Vol. 26 (1981)




  1. IARC Monographs, 26, 47-78, 1981


  1. Kinlen, L.J. (1985) Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment. Am. J. Med., 78 (Suppl. 1A), 44-49


  1. Isomäki, H.A., Hakulinen, T. & Joutsenlahti, U. (1978) Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis. J. chron. Dis., 31, 691-696


  1. Fries, J.F., Bloch, D., Spitz, P. & Mitchell, D.M. (1985) Cancer in rheumatoid arthritis: a prospective long-term study of mortality. Am. J. Med., 78 (Suppl. 1A), 56-59


  1. Cohen, S.M., Erturk, E., Skibba, J.L. & Bryan, G.T. (1983) Azathioprine induction of lymphomas and squamous cell carcinomas in rats. Cancer Res., 43, 2768-2772


  1. IARC Monographs, Suppl. 6, 86-88, 1987










BW 57322









NSC 39084

Last updated: 6 February 1998

See Also:

        Azathioprine (IARC Summary & Evaluation, Volume 26, 1981)

        Azathioprine (PIM 053)

INTOX Home Page


    Summary for UKPID



    Dr Alan Worsley Bsc(hons) PhD MRPharmS


    National Poisons Information Service (Newcastle Centre)

    Regional Drug & Therapeutics Centre

    Wolfson Building

    Claremont Place

    Newcastle upon Tyne

    NE1 4LP


    This monograph has been produced by staff of a National Poisons

    Information Service Centre in the United Kingdom.  The work was

    commissioned and funded by the UK Departments of Health, and was

    designed as a source of detailed information for use by poisons

    information centres.


    Peer review group: Directors of the UK National Poisons Information


    PENICILLAMINE (Distamine)




    Type of product


    For the treatment of severe rheumatoid arthritis and cystinuria




    Penicillamine 50, 125 and 250mg


    Fatal Dose


    Not Known- A 52 year old male presented at hospital 8 hours after

    ingesting 3.1g. Symptoms included vomiting, dehydaration, abdominal

    pain and tachycardia.




    Nausea and vomiting, abdominal pain, hyperpyrexia, thrombocytopaenia,

    neutropaenia, proteinuria, haematuria and tachycardia




    Empty the stomach if >500mg ingested, maintain a good diuresis.

    Monitor renal function and treat failure conventionally. Supportive




    There are no specific antidotes


    Elimination techniques


    No data available




    ABPI Data Sheet Compendium. Datapharm publications Limited 1996-1997


    British National Formulary. Number 32 (September 1996). British

    Medical Associiation and Royal Pharmaceutical Society.


    Dollery C, Therapeutic Drugs. (Pt 2), Churchill Livingstone. 1994




    Brand Name




    Generic Name




    Chemical Group/family



         BNF 10.13


    Reference number


         CAS-52-67-5 (penicillamine)

         CAS-2219-30-9 (hydrochloride)




         Eli Lilly & Co Ltd,

         Dextra Court,

         Chapel Hill,

         Basingstoke, Hants.

         RG21 5SY

         Tel: 01256 315000




         Penicillamine 50mg, 125 mg, 250 mg tablets.


    Physicochemical properties:(Dollery)3




    Molecular weight



    pKa (COOH, NH, SH)

         1.8, 7.9, 10.5



         in alcohol         1 in 530

         in water           1 in 9

         octanol/water partition coefficient   -






    Penicillamine is indicated in Wilson's disease, cystinuria, rheumatoid

    arthritis, juvenile chronic polyarthritis, palindromic rheumatism,

    sero-negative polyarthritis, progressive systemic sclerosis, chronic

    active hepatitis.


    Therapeutic Dosage (BNF)2




    Severe active rheumatoid arthritis, 500-750 mg daily maintenance (max

    1.5g daily)

    Wilson's disease, 1.5-2.0g daily in divided doses.

    Cystinuria, 1-3g daily in divided doses (adjusted to maintain urinary

    cysteine below 200mg/litre.

    Chronic active hepatitis.




    Severe active rheumatoid arthritis15-20mg/kg maintenance.

    Wilson's disease, up to 20mg/kg daily in divided doses.

    Cystinuria, minimum dose to maintain urinary cysteine below





    hypersensitivity (except in life threatening situations) systemic

    lupus erythematosus.


    Pharmacokinetics  (Dollery)3


         Oral absorption 40%

         presystemic metabolism -

         plasma half life

         mean 1-6h

         volume of distribution 0.8litre/kg

         plasma protein binding up to 85%




         No specific data available


    Adverse effects (Data Sheet)1


    Nausea, anorexia, fever and rash may occur early in therapy.

    Thrombocytopenia occurs commonly and neutropenia less often.

    Proteinuria occurs in 30% of patients and is dose related. Haematuria

    is rare.

    Haemolytic anaemia, nephrotic syndrome.




    Penicillamine crosses the placenta to the fetus and has been

    administered during pregnancy for the treatment of rheumatoid

    arthritis, cystinuria and Wilson's disease4. Conflicting reports

    suggest that penicillamine should either be stopped during

    pregnancy5, or be continued during pregnancy with the treatment of

    Wilson's disease, but discontinued in the treatment of rheumatoid



    The use of penicillamine has been observed in approximately 100

    pregnancies. Eight anomalies were observed, of which 5 cases were

    cutis laxa. The later three cases were not thought to be related to

    penicillamine, because they did not conclude connective tissue



    Breast Milk


    There are no reports that describe the use of penicillamine during

    lactation or if the drug is excreted in milk have been located.

    Authors of one review recomend avoiding penicillamine during



    Interactions (BNF)2


    Antacids: reduced absorption of penicillamine

    Iron: reduced absorption of penicillamine

    Zinc:reduced absorption of penicillamine




    Limited specific data of penicillamine poisoning are available.


    A 52 year old male presented at hospital 8 hours after ingesting 3.1 g

    penicillamine. Symptoms included, vomiting, dehydration, abdominal

    pain and tachycardia.


    Side effects reported at therapeutic dosage include:


    Initially nausea, anorexia, fever and skin reactions; taste loss

    (mineral supplements not recommended); blood disorders including

    thrombocytopaenia, agranulocytosis and aplastic anaemia; proteinuria,

    rarely haematuria (withdraw immediately); haemolytic anaemia,

    nephrotic syndrome, lupus erythematosus-like syndrome, myasthenia

    Gravis-like syndrome, pemphigus, Goodpasture's syndrome, and

    Stevens-Johnson syndrome also reported; in non-rheumatoid conditions

    rheumatoid arthritis-like syndrome also reported; late rashes (reduce

    dose or withdraw treatment).




    No specific details available




    If ingestion is within 2 hours, 50-100grams (adults) or 25-50 grams

    (children) of oral activated charcoal may be administered. Lactulose

    (20ml) should be given to prevent constipation. There is no data to

    indicate whether or not this is effective in penicillamine poisoning.


    Supportive care


    General supportive care should be given




    As no data are available on penicillamine poisoning vital signs should

    be monitored-pulse, blood pressure, respiration.




    There are no specific antidotes


    Elimination techniques


    No data available




    No data is available on penicilllamine poisoning, but routine

    investigations including renal function tests, urinalysis and

    electrolytes could be carried out.


    Case Data


    Other Toxicological Data

         No data available


    Ecotoxicological Data

         No data available


    Hazard Warnngs

         No data available


    Waste disposal data

         No data available




    Dr Alan Worsley Bsc(hons) PhD MRPharmS


    National Poisons Information Service (Newcastle Centre)

    Regional Drug & Therapeutics Centre

    Wolfson Building

    Claremont Place

    Newcastle upon Tyne

    NE1 4LP



    This monograph was produced by the staff of the Newcastle Centre of

    the National Poisons Information Service in the United Kingdom. The

    work was commissioned and funded by the UK Departments of Health, and

    was designed as a source of detailed information for use by poisons

    information centres.


    Peer review was undertaken by the Directors of the UK National Poisons

    Information Service.


    Last updated January 1997




  1. ABPI Data Sheet Compendium. Datapharm Publications Limited. 1996-



  1. British National Formulary. Number 32 (september 1996). British

    Medical Association and Royal Pharmaceutical Society.


  1. Dollery C. Therapeutic Drugs. (Suppl 2), Churchill Livingstone.



  1. Crawhall JC et al . BMJ (1967);2:216-8


  1. Ostensen M et Husby G. Scand J Rheumatol. (1985);14:1-7


  1. Miehle W. Z Rhematol (1988);47(suppl 1):20-3


  1. Gal P et Ravenel SD. J Clin Dysmorphol (1984);2:9-12