Clofazimine

Usage

Clofazimine is primarily used in combination with other anti-leprosy medications for the treatment of lepromatous leprosy, including dapsone-resistant lepromatous leprosy and lepromatous leprosy complicated by erythema nodosum leprosum. It is classified as a riminophenazine dye with antimycobacterial and anti-inflammatory properties. Its mechanism of action involves binding to bacterial DNA, inhibiting mycobacterial growth and replication. It also exhibits anti-inflammatory effects, likely by interfering with the production and release of inflammatory mediators.

Alternate Names

The drug is also recognized internationally as Clofazimine. A common brand name under which it is marketed is Lamprene.

How It Works

Pharmacodynamics: Clofazimine exerts its primary therapeutic effect by binding to the guanine bases of bacterial DNA, thereby disrupting DNA replication and leading to bacterial cell death. It also has anti-inflammatory effects, possibly by impairing the function of neutrophils and monocytes and reducing the release of TNF-alpha and other inflammatory mediators.

Pharmacokinetics:

• Absorption: Clofazimine is absorbed slowly and incompletely from the gastrointestinal tract. Absorption is enhanced when taken with food.
• Distribution: It is widely distributed throughout the body, accumulating in fatty tissues, including the liver, spleen, and skin. It also crosses the placenta and is present in breast milk.
• Metabolism: Clofazimine undergoes some hepatic metabolism, but the pathways are not fully elucidated.
• Elimination: The drug and its metabolites are primarily excreted in the feces, with a small amount eliminated in urine. The elimination half-life is quite long, ranging from several weeks to months, resulting in slow clearance from the body.

Dosage

Standard Dosage

Adults:

• Lepromatous Leprosy (Dapsone-sensitive): 100 mg daily in combination with rifampicin and dapsone, administered for at least 2 years.
• Lepromatous Leprosy (Dapsone-resistant): 100 mg daily in combination with one or more other anti-leprosy drugs for 3 years, followed by 100 mg daily as monotherapy.
• Erythema Nodosum Leprosum: 100-200 mg daily, in conjunction with other anti-leprosy drugs and steroids, for up to 3 months.

Children:

• Multibacillary Leprosy:
  • ≤10 years: Dose adjustment is necessary (e.g., 50 mg twice weekly + 100 mg once monthly, with rifampicin and dapsone).
  • 10-14 years: 50 mg every other day + 150 mg once monthly, with rifampicin and dapsone.

Special Cases:

• Elderly Patients: Dose adjustments may be needed based on organ function.
• Patients with Renal Impairment: Use caution in severe renal impairment.
• Patients with Hepatic Dysfunction: Use with caution; dose adjustment might be necessary.

Clinical Use Cases Clofazimine is not typically used in settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its principal indication is leprosy treatment.

Side Effects

Common Side Effects

• Skin discoloration (pink to brownish-black)
• Dry skin
• Gastrointestinal disturbances (nausea, vomiting, abdominal pain, diarrhea)
• Eye discoloration and dryness
• Discoloration of body fluids (sweat, tears, urine, feces)

Rare but Serious Side Effects

• QT prolongation
• Splenic infarction
• Bowel obstruction
• Gastrointestinal bleeding

Contraindications

• Hypersensitivity to clofazimine

Drug Interactions

• Drugs that prolong the QT interval
• Rifampin
• Hormonal contraceptives

Pregnancy and Breastfeeding

• Pregnancy: Clofazimine should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Effective contraception should be used during treatment and for at least 4 months afterward.
• Breastfeeding: Clofazimine is excreted in breast milk and may cause skin discoloration in infants. Breastfeeding should be avoided during treatment.

Drug Profile Summary

• Mechanism of Action: Binds to mycobacterial DNA, inhibiting growth and replication. Also exhibits anti-inflammatory effects.
• Side Effects: Skin discoloration, dry skin, gastrointestinal disturbances, eye discoloration, discoloration of body fluids. Rarely, QT prolongation, splenic infarction, bowel obstruction.
• Contraindications: Hypersensitivity.
• Drug Interactions: QT-prolonging drugs, rifampin, hormonal contraceptives.
• Pregnancy & Breastfeeding: Should generally be avoided.
• Dosage: Adults: 100-200 mg daily; Children: dose adjustment needed.
• Monitoring Parameters: Liver function tests, ECG, blood glucose, ESR.

Popular Combinations

• Dapsone and rifampicin for multibacillary leprosy.

Precautions

• General Precautions: Monitor for liver function, gastrointestinal issues, and QT prolongation.
• Specific Populations: Avoid or use with caution in pregnancy and breastfeeding; use with caution in hepatic impairment.
• Lifestyle Considerations: Advise patients about skin discoloration and the need for sun protection.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Clofazimine?

A: For adults with leprosy, the usual dose is 100 mg daily. For erythema nodosum leprosum, it can be increased to 100-200 mg daily. Children require dose adjustments based on age and weight.

Q2: What is the most common side effect of Clofazimine?

A: Skin discoloration (pink to brownish-black) is the most frequent side effect.

Q3: How long does the skin discoloration last after stopping Clofazimine?

A: The discoloration can persist for several months to years after discontinuation.

Q4: Does Clofazimine interact with other medications?

A: Yes, Clofazimine can interact with drugs that prolong the QT interval, rifampin, and hormonal contraceptives.

Q5: Can Clofazimine be used during pregnancy?

A: Clofazimine should be used during pregnancy only if the potential benefit clearly outweighs the potential risk to the fetus.

Q6: Is Clofazimine safe to use in patients with liver disease?

A: Use with caution in patients with hepatic impairment; dose adjustments may be necessary.

Q7: What are the signs of a serious adverse reaction to Clofazimine?

A: Severe abdominal pain, bloody stools, changes in heart rhythm, and signs of jaundice warrant immediate medical attention.

Q8: How does Clofazimine work against leprosy?

A: It binds to mycobacterial DNA, inhibiting bacterial growth and replication. It also has anti-inflammatory properties that help control the inflammatory reactions associated with leprosy.

Q9: Are there any dietary restrictions while taking Clofazimine?

A: It is recommended to take clofazimine with meals to enhance absorption and reduce gastrointestinal side effects.

Q10: Should patients taking Clofazimine take any precautions related to sun exposure?

A: Due to the risk of photosensitivity reactions, patients should avoid excessive sun exposure and use strong sunscreens.