Action and Spectrum

Actions and Spectrum:  

clofazimine is an antibiotic medication used to treat various bacterial infections such as leprosy, tuberculosis, and Mycobacterium avium complex (MAC) infections. Its mechanism of action involves binding to bacterial DNA and altering its structure, thereby inhibiting bacterial replication. Additionally, clofazimine also has immunomodulatory properties, which may contribute to its effectiveness in treating certain infections. 

The spectrum of activity of clofazimine is primarily limited to mycobacteria, including Mycobacterium leprae (the causative agent of leprosy), Mycobacterium tuberculosis (the causative agent of tuberculosis), and MAC. It has also been used in the treatment of other infections, such as some fungal infections and certain types of diarrhea caused by bacteria such as Vibrio cholerae. 

Drug Interaction

Adverse Reaction

Frequency defined  

Adults 

>10% 

Ichthyosis and dry skin (8-28%) 

Gastrointestinal: Abdominal and epigastric pain, diarrhea, nausea, vomiting, GI intolerance (40%-50%) 

Skin discoloration (75-100%)  

1-10% 

Increased blood glucose levels (>1%) 

Ocular symptoms such as conjunctival and corneal pigmentation due to crystal deposits, dryness, burning, itching, and irritation (>1%) 

Discoloration of urine, feces, sputum, and sweat (>1%)Increased ESR (erythrocyte sedimentation rate)  

Rash and itching in (1-5%)   

<1% 

Nervous: Dizziness, drowsiness, fatigue, headache, giddiness, neuralgia, taste disorder 

Ocular: Diminished vision 

Skin: Phototoxicity, erythroderma, acneiform eruptions, monilial cheilosis 

Psychiatric: Depression secondary to skin discoloration  

Gastrointestinal: Bowel obstruction, GI bleeding, anorexia, constipation, weight loss, hepatitis, jaundice, eosinophilic enteritis, enlarged liver 

Ocular: Addition of maculopathy (bull’s eye retinopathy) 

Body fluid discoloration and other skin reactions 

Other: Splenic infarction, thromboembolism, anemia, cystitis, bone pain, edema, fever, lymphadenopathy, vascular pain 

Black Box Warning

Black Box Warning:  

clofazimine carries a black box warning due to the risk of skin discoloration. Prolonged use of clofazimine can cause the skin to turn brown or purple. This discoloration can be permanent and may affect any part of the body, including the eyes. Patients taking clofazimine should be monitored regularly for signs of skin discoloration, and if it occurs, the medication should be discontinued.

Additionally, clofazimine can cause gastrointestinal disturbances and should be used with caution in patients with a history of gastrointestinal disease. Finally, clofazimine has been associated with an increased risk of QT prolongation, which can lead to potentially life-threatening arrhythmias. Therefore, it should be used with caution in patients with a history of arrhythmias or other cardiac disorders, and electrocardiogram (ECG) monitoring may be necessary. 

Contraindication / Caution

Contraindication/Caution:   

clofazimine is contraindicated in patients who have a history of hypersensitivity or an allergic reaction to the medication or any of its components. It should not be used in patients who have shown previous intolerance or allergic reactions to clofazimine or any other similar medications. 

clofazimine is also contraindicated in patients with severe liver or kidney disease, as well as in patients with a history of depression, psychiatric illness, or psychosis.  

Additionally, clofazimine should not be used during pregnancy, as it can cause harm to the developing fetus. It is also not recommended for use during breastfeeding, as it can be excreted in breast milk and potentially harm the infant. 

Overall, clofazimine should only be used under the guidance and supervision of a healthcare provider, and patients should inform their provider of any medical conditions, allergies, or medications they are currently taking before starting treatment with clofazimine. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

<b>Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:

clofazimine has a gradual bactericidal impact on Mycobacterium leprae (Hansen’s bacillus), restrains the growth of mycobacteria, and has a higher affinity to bond with mycobacterial DNA. 

Pharmacodynamics: 

clofazimine is an antimycobacterial drug that is used primarily in the treatment of leprosy. The pharmacodynamics of clofazimine involves several mechanisms, including: 

Inhibition of Mycobacterial DNA Synthesis: clofazimine is believed to inhibit the synthesis of DNA in Mycobacterium leprae by binding to bacterial DNA and interfering with replication. 

Generation of Reactive Oxygen Species (ROS):   

clofazimine is known to generate reactive oxygen species (ROS) that can damage bacterial membranes and lead to bacterial death. 

Modulation of Host Immune Response:   

clofazimine is thought to modulate the host immune response by altering the production of cytokines and chemokines.  

MOA:  

Binding to DNA: clofazimine binds to bacterial DNA and disrupts the replication process, leading to the inhibition of bacterial growth.  

Membrane Disruption: clofazimine also can disrupt the bacterial cell membrane, leading to leakage of essential cellular components and eventual cell death.  

Generation of Reactive Oxygen Species (ROS): clofazimine generates reactive oxygen species (ROS) that can cause oxidative damage to the bacterial cells, leading to their death.  

Modulation of Host Immune Response: clofazimine has immunomodulatory effects, which means it can alter the immune response of the host to the bacterial infection. It has been shown to reduce the production of pro-inflammatory cytokines, leading to a decrease in inflammation and tissue damage caused by the infection.  

Pharmacokinetics:  

Absorption: 

clofazimine is absorbed orally with a bioavailability of approximately 60-70%. The absorption of clofazimine is enhanced when taken with food or acidic beverages, such as orange juice.  

Distribution:  

clofazimine is distributed throughout the body and has a high affinity for adipose tissue. The drug is known to accumulate in the liver, spleen, and lymph nodes, as well as the skin and mucous membranes.  

Metabolism: 

clofazimine is metabolized primarily in the liver by the cytochrome P450 system, specifically the CYP3A4 and CYP2C19 enzymes. The primary metabolite is desmethyleneclofazimine, which is less active than the parent drug.  

Elimination and excretion: 

clofazimine and its metabolites are primarily eliminated via the feces, with only a small percentage eliminated in the urine. The elimination half-life of clofazimine is approximately 70 days, indicating that the drug has a long residence time in the body. 

Adminstartion

Administration:  

Dosage: The dose of clofazimine can vary depending on the condition being treated, the age and weight of the patient, and other factors. The usual dose for leprosy is 50-100 mg per day, taken orally in one or two divided doses.  

Form: clofazimine is available in capsule form, which should be swallowed whole with water. Do not crush or chew the capsules.  

Timing: clofazimine can be taken with or without food, but it is best to take it at the same time each day to maintain consistent blood levels.  

Duration: The length of treatment with clofazimine can vary depending on the condition being treated. For leprosy, treatment may last for several months to several years. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: clofazimine 

Why do we use clofazimine?  

clofazimine is an antibiotic medication that is used to treat several different types of bacterial infections, such as leprosy and Mycobacterium avium complex (MAC) infection. 

clofazimine works by binding to the bacterial DNA and altering its structure, which disrupts the bacteria’s ability to replicate and grow. This leads to the death of the bacteria and helps to clear the infection. 

In addition to its antibiotic properties, clofazimine also has some anti-inflammatory properties, which may help to reduce the inflammation associated with certain infections. 

Overall, clofazimine is an important medication for the treatment of certain bacterial infections, particularly those that are resistant to other antibiotics. However, it should only be used under the guidance of a healthcare provider, as it can have potential side effects and interactions with other medications.