This is the last blog post in the series of posts focused on the G6PD gene and G6PD deficiency. If interested, the previous blog posts were the following:
In this final post, I will explain the critical examples of hematological and rheumatological G6PD gene-related drug labeling. Over time I will try to update this post and cover all other G6PD-related drug labelings, as hematological and rheumatological G6PD gene-related drug labelings are not the only ones in the case of the G6PD gene.
The G6PD gene-related drug labelings presented here are all listed under the FDA’s list of Pharmacogenomic Biomarkers in Drug Labeling.
What is Drug Labelling? According to FDA, human prescription drug labeling contains a summary of the essential scientific information needed for the safe and effective use of the drug. Also, it includes the Prescribing Information, FDA-approved patient labeling (Medication Guides, Patient Package Inserts, and/or Instructions for Use), and/or carton and container labeling. According to Wikipedia, Drug labeling is a written, printed, or graphic matter on any drug or its containers or accompanying such a drug. Drug labels seek to identify drug contents and to state specific instructions or warnings for administration, storage, and disposal.
It is important to underline that FDA labeling and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines recommend that G6PD testing be undertaken in high-risk populations before prescribing drugs known to cause acute hemolytic anemia (AHA). This test involves full gene sequencing of all exons and intron/exon boundaries of the G6PD gene [citation].
According to FDA, 40 drugs have the G6PD gene-related drug labeling. As previously mentioned, I will start with hematological and rheumatological drugs with the G6PD gene-related drug labeling.
There are two hematological and two rheumatological drugs that have the G6PD gene-related drug labeling. The two hematological drugs are Succimer and Methylene Blue, and the two rheumatological are Probenecid and Pegloticase.
What Type of Drug Is Succimer? When Is Succimer Indicated To Be Taken?
Succimer is a mercapto-carboxylic acid heavy metal chelator used to treat heavy metal poisoning. It is distributed under the brand name Chemet.
What is a metal chelator? Metal chelators are administered into the bloodstream, and once in the bloodstream, they bind to metals. By doing this, chelators accumulate all the heavy metals into a chemical compound that can filter through the kidneys and finally release in urine.
What Is the Relation Between Succimer and G6PD Deficiency?
Dimercaptosuccinic acid (DMSA), which is another name for Succimer, has been approved by the FDA for the treatment of lead toxicity in children. The population that can take Succimer is large. The risk of hemolytic anemia for G6PD deficient persons who take DMSA is not well described [citation].
Do We Have To Do a Genetic Test for the G6PD Deficiency if One Would Have To Take Succimer and Why?
As explained above, dimercaprol treatment requires great caution as it has been reported for dimercaprol induces hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, and those at high risk for hemolysis should be screened before therapy of dimercaprol (succimer is derivative of dimercaprol) [citation]. Therefore, testing for G6PD deficiency should be performed before Succimer's prescription [citation].
What Type of Drug Is Methylene Blue? When Is Methylene Blue Indicated To Be Taken?
What is methemoglobinemia? Methemoglobinemia is a condition characterized by increased quantities of methemoglobin in the blood. Methemoglobin is a form of hemoglobin in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal hemoglobin. What this means, in practice, is useless as an oxygen carrier which further means that methemoglobin cannot bind oxygen, which means it cannot carry oxygen to tissues, further causing varying degrees of cyanosis. Methemoglobinemia can be induced by specific drugs and chemicals, but it is also hereditary.
What Is the Relation Between Methylene Blue and G6PD Deficiency?
Methylene Blue should not be used in patients with G6PD deficiency [citation] because it exacerbates oxidative stress in red blood cells with G6PD deficiency, inducing hemolysis [citation]. Patients with glucose-6-phosphate dehydrogenase deficiency may not reduce Methylene Blue to its active form in vivo, and therefore it may not be effective in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
The G6PD-deficient individuals produce insufficient NADPH to efficiently reduce methylene blue to leucomethylene blue, which is necessary to activate the NADPH-dependent methemoglobin reductase system [citation]. Therefore, using Methylene Blue to treat patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may result in severe hemolysis and severe anemia. Therefore, Methylene Blue is contraindicated for patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Do We Have To Do a Genetic Test for the G6PD Deficiency if One Would Have To Take Methylene Blue and Why?
Any G6PD deficiency must be detected or documented before methylene blue administration. Again to underline, methylene blue is not the ideal mode of treatment in G6PD-deficient patients because it can increase hemolysis in patients [citation].
What Type of Drug Is Probenecid?
Probenecid is uricosuric, and its primary role is lowering high levels of uric acids in the blood.
When Is Probenecid Indicated To Be Taken?
Probenecid is used in the treatment of chronic gout or gouty arthritis. These conditions are caused by too much uric acid in the blood. Probenecid works by removing the extra uric acid from the body.
What Is the Relation Between Probenecid and G6PD Deficiency?
Probenecid is classified as ''probably safe'' in G6PD patients [citation], marked with ''possible risk for hemolysis'' [citation], also confirmed by the website g6pd.org related to G6PD Deficiency Association [citation]. Also, several case studies show a relationship between Probenecid and hemolytic anemia [citation] [citation], so patients should avoid oxidative drugs [citation].
Do We Have To Do a Genetic Test for the G6PD Deficiency if One Would Have To Take Probenecid and Why?
What Type of Drug Is Pegloticase?
Pegloticase is a recombinant urate oxidase conjugated to polyethylene glycol (PEG) that is approved for the management of chronic refractory gout after the failure of conventional urate-lowering therapies (ULTs) (i.e., allopurinol, febuxostat or probenecid) [citation].
When Is Pegloticase Indicated To Be Taken?
Pegloticase is prescribed for treating chronic refractory gout after the failure of conventional urate-lowering therapies such as allopurinol, febuxostat, or probenecid [citation].
What Is the Relation Between Pegloticase and G6PD Deficiency?
It is reported that Pegloticase triggers hemolysis and methemoglobinemia in patients with G6PD deficiency [citation]. Also, critical to mentation that patients of African, Mediterranean (including Southern European and Middle Eastern), and Southern Asian ancestry are at increased risk for G6PD deficiency.
Do We Have To Do a Genetic Test for the G6PD Deficiency if One Would Have To Take Pegloticase and Why?
The G6PD deficiency screening is recommended before Pegloticase prescription because of a predisposition for hemolysis due to oxid ative stress [citation]. Also, it is important to explain to patients that G6PD deficiency is more frequently found in individuals of African, Mediterranean, or Southern Asian ancestry and that they may be tested to determine if they have G6PD deficiency unless already known.