How Genes Influence Co-Trimoxazole Allergy?

What Is Co-Trimoxazole?

Co-trimoxazole is a sulfonamide drug that is a combination of sulfamethoxazole and trimethoprim.

This drug is used to treat bacterial infections like pneumonia, bronchitis, urinary tract infections, and infection of the ears and intestines. Co-trimoxazole is also used to treat ‘traveler’s diarrhea.

Co-trimoxazole is also used to treat some fungal and parasitic infections.

This drug may be given orally or via intravenous (IV) infusion.

What Is Co-Trimoxazole Used For?

Co-trimoxazole is used for a variety of bacterial, fungal, and parasitic infections, including:

Acute otitis media (ear infection) caused by Streptococcus pneumoniae or Haemophilus influenzae
Gastrointestinal conditions like Traveler’s Diarrhea caused by E. coli, enteritis caused by Shigella flexneri or S. sonnei
Acute exasperation of chronic bronchitis
Treatment of UTIs caused by E.coli, Klebsiella, Enterobacter
Brucellosis
Cholera
Cyclospora infections
Listeria infections
Mycobacterium marinum infection as an alternative to minocycline
As an alternative to typhoid fever caused by Salmonella typhi

How Does Co-Trimoxazole Work?

Co-trimoxazole works by inhibiting the growth of bacteria, fungi, and parasites, thereby preventing the spread of the infection.

This drug is not effective against viruses and diseases caused by them.

How Long Does It Take For Co-Trimoxazole To Work?

The co-trimoxazle dose usually prescribed for adults is two tablets, twice a day.

Depending upon the infection, you may need to take co-trimoxazole for three to seven days.

The dosage and duration of co-trimoxazole in children depend upon their age, body weight, and the nature of the condition.

Side Effects Of Co-Trimoxazole

Despite its efficacy in treating several bacterial infections, co-trimoxazole is often preceded by simpler antibiotics due to its side effects in some people.

Common side effects observed with co-trimoxazole include

Nausea
Vomiting
Loss of appetite
Itching and rash
Sore throat
Chills
Fever
Cough

If you experience any side effects after taking co-trimoxazole, inform your doctor immediately.

Some severe side effects of co-trimoxazole that require immediate medical attention include:

Severe diarrhea that may occur with fever, stomach cramps
Shortness of breath
Unusual bruising and bleeding
Joint or muscle pain
Paleness
Red or purplish discolorations

Does Co-Trimoxazole Cause Liver Damage?

Trimethoprim in co-trimoxazole does not cause hepatic damage, but sulphamethoxazole is known to cause liver injury.

So, co-trimoxazole increases the risk of liver damage in some individuals.

Co-Trimoxazole: Interactions With Other Drugs

Co-trimoxazole interacts with several drugs, so you must always inform your doctor about all medications you are currently taking.

Some interactions of co-trimoxazole with other drugs include

Cyclic antidepressants

These are a class of drugs used to treat and manage major depressive disorder.

When co-trimoxazole is taken with cyclic antidepressants, there is a possible decrease in the latter's efficacy.

Cyclosporin

This drug is a calcineurin inhibitor and is used as an immunosuppressant drug to treat various diseases like rheumatoid arthritis and nephrotic syndrome and prevent rejection in transplant cases.

When cyclosporin is taken with co-trimoxazole, reversible nephrotoxicity has been reported in renal transplant patients.

Digoxin

This drug is used to treat cardiac conditions like irregular heart rhythm and heart failure.

Taking digoxin concomitantly with co-trimoxazole increases the concentration of digoxin in geriatric patients.

This may increase the side effects of the drug.

Diuretics

Diuretics or water pills are commonly used antihypertensive medications that increase urine production and enable sodium excretion.

Taking co-trimoxazole with diuretics (especially thiazides) raises the possibility of thrombocytopenia (a severe decrease in platelet count) and purpura.

This is usually observed in the geriatric population.

Oral hypoglycemics

These drugs are used in individuals with diabetes.

When oral hypoglycemics are taken with co-trimoxazole, the combination increases the risk for hypoglycemic complications in these individuals.

Indomethacin

This is an NSAID drug used to relieve moderate pain, tenderness, and swelling in joints caused by osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and other similar joint pains.

Taking indomethacin with co-trimoxazole may increase the sulfamethoxazole concentration and its side effects.

Methotrexate

This drug is a chemotherapeutic agent and an immunosuppressant used to treat many autoimmune diseases and cancer.

Co-trimoxazole must be avoided in people with methotrexate as it increases the concentration of free methotrexate.

As a result, the efficacy of methotrexate is reduced.

Phenytoin

This drug is used in the treatment of epilepsy.

When phenytoin is taken with co-trimoxazole, the latter may inhibit the metabolism of phenytoin and increase its half-life, increasing the risk of its side effects.

Warfarin

Warfarin is a commonly used blood thinner.

Possible inhibition of warfarin metabolism and clearance may be seen when consumed with co-trimoxazole.

Warfarin dosage may need to be adjusted if it is taken with co-trimoxazole.

Can You Be Allergic To Co-Trimoxazole?

Individuals who are allergic to sulphonamides or trimethoprim can be allergic to co-trimoxazole.

Genetics Of Co-Trimoxazole Allergy

GCLC Gene and Co-Trimoxazole Allergy

rs761142 is a single nucleotide polymorphism or SNP in the glutamate-cysteine ligase catalytic subunit (GCLC) gene.

This SNP is associated with sulfamethoxazole-associated hypersensitivity in HIV/AIDS patients.

Individuals having the CC genotype have a greater risk of developing drug hypersensitivity when treated with sulphamethoxazole than those with the AA genotype.

In another study conducted, individuals having the minor G allele of rs761142 ad a greater risk of developing sulfamethoxazole hypersensitivity than those with the T allele.

Each minor G allele copy increased the risk of hypersensitivity by 1.9 fold.

HLA and Co-Trimoxazole Allergy

rs41554616 is an SNP located between HLA-B and MICA genes.

This SNP is associated with co-trimoxazole-induced severe cutaneous adverse reaction (SCAR).

HLA-B∗13:01 allele in the rs41554616 has been strongly linked to the development of SCAR in Asians.

Analyze Your Genetic Response to Co-Trimoxazole

Recommendations To Use Co-Trimoxazole

Drug Allergies

If you are allergic to co-trimoxazole, sulfonamides, or trimethoprim, you must inform your doctor before taking the drug.

Some common symptoms of allergy to co-trimoxazole include cough, shortness of breath, sore throat, fever, and other respiratory symptoms.

Megaloblastic Anemia (folate or G6PD deficiency)

Co-trimoxazole is not recommended in individuals with megaloblastic anemia due to folate deficiency.

People with G6PD deficiency may experience hemolysis when they take co-trimoxazole and must avoid the drug.

Children Below 2 Years of Age

Co-trimoxazole’s safety and efficacy have not been established in the pediatric population below two years of age.

So, it is not advisable to prescribe this drug to this age group.

Pregnant and Lactating Women

Sulfonamides are known to cause kernicterus in newborns, and so co-trimoxazole is contraindicated in pregnant women.

Since sulfamethoxazole and trimethoprim can pass into breast milk, co-trimoxazole is contraindicated in lactating and nursing women.

Geriatric Population

Co-trimoxazole is contraindicated in older adults, especially those with impaired hepatic or renal function.

These individuals may be at an increased risk for adverse reactions.

Summary

Co-trimoxazole is an antibacterial sulfonamide drug comprising sulfamethoxazole and trimethoprim.
Co-trimoxazole is used to treat a wide range of respiratory, gastrointestinal, and urinary tract infections.
Co-trimoxazole works by preventing the growth and spread of bacteria.
The dosage and duration of co-trimoxazole vary depending on age, condition, and weight (in children).
Though co-trimoxazole is a safe drug, it may cause side effects like nausea, vomiting, loss of appetite, and skin reactions in some people.
Co-trimoxazole interacts with drugs like cyclic antidepressants, cyclosporin, digoxin, warfarin, oral hypoglycemics, and diuretics.
Certain changes in genes like GCLC and HLA-B may increase the risk of hypersensitivity reactions to co-trimoxazole.
Inform your doctor about your medical history and your medications to avoid adverse reactions due to co-trimoxazole.
If you are pregnant, planning to conceive, or are nursing, avoid co-trimoxazole.
Co-trimoxazole is contraindicated in people with megaloblastic anemia, G6PD deficiency, and folate deficiency.

References

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