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Rifampicin Toxicity - Side Effects, Toxicity, and Diagnosis

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Rifampicin toxicity occurs when the drug's concentration in the blood exceeds the normal range. Read the article to know more about it.

Medically reviewed by

Dr. Penchilaprasad Kandikattu

Published At June 13, 2023
Reviewed AtMay 16, 2024

Introduction

A macrocyclic antibiotic with significant action against mycobacteria, Rifampin (also known as Rifampicin) is frequently used in combination with other medications to treat tuberculosis (TB). Nowadays, a two-month co-administration of four medications (Isoniazid, Rifampicin, Ethambutol, and Pyrazinamide) is advised for treating pulmonary tuberculosis. This is followed by a four-month maintenance phase involving only the administration of Isoniazid and Rifampicin (WHO, 2019). This treatment plan has an 85 % success rate. Nonetheless, the most recent data on treatment outcomes show that 15 % of TB infections are still being treated unsuccessfully (WHO, 2019).

The disruption or premature termination of the first-line treatment approach, the latter of which is attributed to the rather severe side effects brought on by the consumption of these drugs, are two other factors that can be blamed for this occurrence. Other causes include metabolic variation. The side effects of Rifampin are acute liver damage that can be severe and even fatal, as well as temporary and asymptomatic rises in blood aminotransferase and bilirubin levels. A better understanding of the underlying toxicity of Rifampicin helps to lower the rate of failure of TB treatment and the subsequent development of more efficient, less toxic TB therapy procedures.

What Is Rifampicin?

A strain of Streptomyces mediterranei, a species that was first isolated in Italy in 1957 from a soil sample taken in France, is used to ferment Rifampicin, a semi-synthetic derivative of the antibiotics Rifamycin. Rifampicin is a complex macrocyclic antibiotic against several bacteria. It inhibits the growth of M. tuberculosis most prominently and several atypical mycobacterial species. Rimactane and Rifadin, as well as other generic names for Rifampin, are available in 150 mg and 300 mg capsules. There are other pediatric formulations and powdered parenteral preparations available. Adults should take 600 mg (around 10 mg/kg) daily for tuberculosis treatment, and children should take 10 to 20 mg/kg, but no more than 600 mg daily.

Rifampicin is used in the following disease:

What Are the Side Effects of Rifampicin?

The following are the side effects of Rifampicin:

  • Rash.

  • Fever.

  • Flu-like symptoms.

  • Gastrointestinal upset.

  • Discoloration of urine and sweat.

  • Hypersensitivity, shock, shortness of breath, acute

  • Hemolytic anemia.

  • Renal failure (nephrotoxicity).

  • Chills.

  • Nausea and vomiting.

  • Arthralgia.

  • Diarrhea.

  • Peripheral neuritis.

  • Decreased vision.

  • Affects eyelids and conjunctiva.

  • Irritation of the eyes, which manifests transiently as lacrimation.

  • Hyperemia.

  • Edema.

  • Ocular pain.

What Is Rifampicin Toxicity?

The level of Rifampicin toxicity depends on the duration of therapy, dose, and individual patient factors, including age, liver function, and concomitant medications. Rifampicin toxicity can affect multiple organs, including the liver, kidneys, nervous system, and blood. Rifampicin overdose results in signs and symptoms that are progressions of adverse responses, including reddish-orange discoloration of the skin and bodily fluids. Upon oral delivery, they began to manifest between 0.5 and 4 hours later and continued for an average of 28 hours (range 1 to 72 hours).

Rifampicin overdose has led to hepatotoxicity. Alcohol intake with Rifampicin increases the risk of hepatotoxicity. Rifampicin toxicity can affect the central nervous system, liver, and kidney.

The following are the Rifampicin toxicity:

  • Hepatotoxicity: Liver toxicity is the most common manifestation of Rifampicin toxicity. Rifampicin-induced liver injury can range from mild elevations in liver enzymes to severe hepatitis (inflammation of the liver) and liver failure. The mechanism of Rifampicin-induced liver injury is unclear, but it is thought to be due to oxidative stress, immune-mediated reactions, or idiosyncratic drug reactions. The risk of liver injury is higher in patients with pre-existing liver disease, alcohol abuse, and concomitant medications that affect liver function. The patients (10 % to 20 %) receiving long-term Rifampicin therapy experience mild, temporary increases in serum aminotransferase levels. These abnormalities does not depend on the dose. Rifampin's effects on serum bilirubin levels are peculiar and paradoxical. In the majority of patients, total and indirect serum bilirubin levels rise during the first few days of rifampin therapy. However, after a few weeks of beginning treatment, Rifampin therapy might be linked to a noticeable rise in both direct and total bilirubin levels without any signs of liver damage. Rifampicin can cause liver cirrhosis.

  • Central Nervous System Toxicity: Nervous system toxicity is a rare but potentially serious adverse effect of Rifampicin. Rifampicin-induced nervous system toxicity can manifest as confusion, dizziness, headache, and seizures. The exact mechanism of nervous system toxicity is unknown, but it may be related to the drug's ability to penetrate the blood-brain barrier. An overdose of Rifampicin can interfere with impulse transmission. It can cause neuronal damage.

  • Hematological Effects: Rifampicin can also cause a reduction in the number of blood cells, leading to anemia, thrombocytopenia, and leukopenia. The risk of blood cell toxicity is higher in patients with pre-existing blood disorders and those receiving long-term Rifampicin therapy.

  • Multi-organ Toxicity: Studies have shown that an overdose of Rifampicin can cause multi-organ (liver, kidney, and brain) metabolome variation. Rifampicin toxicity interference with bile salts or bile production. The variation in the metabolite of the various organ causes disruption in ion regulation and membrane structure.

How Is Rifampicin Toxicity Diagnosed?

If patients who are receiving Rifampicin suffers from rashes, shortness of breath, and other illness, then they should consult their doctors. Liver function tests and kidney function tests should be performed regularly, especially in patients with pre-existing liver or kidney disease. Patients should be advised to report any symptoms of nervous system toxicity promptly. Blood cell counts should be monitored regularly, especially in patients receiving long-term Rifampicin therapy.

The following are the ways to diagnose Rifampicin toxicity:

  • Liver Function Test - Liver enzyme values may be elevated, they are not always predictive of clinical hepatitis and may return to normal or continued therapy with Rifampicin. The level of aminotransferases and alanine may be increased in the case of toxicity.

  • Complete Blood Count - The complete blood count has elevated levels of platelets and prothrombin time.

  • Urine Test - The color of the urine and chemical composition of urine helps to diagnose the toxicity.

Conclusion

Rifampicin is a highly effective antibiotic medication used to treat various bacterial infections. However, like any other medication, it can cause unwanted side effects, including toxicity. Rifampicin toxicity affects multiple organs, including the liver, kidneys, nervous system, and blood. Healthcare providers should carefully monitor patients receiving Rifampicin to minimize the risk of toxicity. Patients should also be advised to report any symptoms of toxicity promptly to their healthcare provider.

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Dr. Penchilaprasad Kandikattu
Dr. Penchilaprasad Kandikattu

Internal Medicine

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tuberculosis
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