Action and Spectrum

Actions and Spectrum:

It is a member of the class of medications known as diarylquinolines. It works by inhibiting the activity of an enzyme called ATP synthase, which is necessary for the bacteria that cause TB to produce energy. This leads to the death of the bacteria and helps to clear the infection. 

Bedaquiline is active against several species of Mycobacterium, including Mycobacterium tuberculosis, the bacterium that causes TB. It is typically used in combination with other medications as part of a regimen for the treatment of multidrug-resistant TB (MDR-TB). MDR-TB is a form of TB that is resistant to at least two of the most commonly used TB medications (isoniazid and rifampin). 

It is important to note that bedaquiline should only be used in an appropriate combination regimen to reduce the risk of developing resistance to the medication. The development of resistance to bedaquiline and other TB medications is a major concern in the treatment of TB, as it can make the disease more difficult to treat. 

Drug Interaction

Adverse Reaction

Frequency Defined  

>10%  

Adults  

Headache (28%)  

Nausea (38%)  

Chest pain (11%)  

Arthralgia (33%)  

Pediatrics  

Nausea (13%)  

Arthralgia (40%)  

Abdominal pain (13%)  

1-10%  

Adults  

Rash (8%)  

Anorexia (9%)  

Black Box Warning

Black Box Warnings:

The increased risk of death seen in the bedaquiline treatment group in the clinical trial suggests that bedaquiline may carry a higher risk of serious adverse events compared to placebo. 

QT prolongation is a condition in which the heart’s electrical activity is prolonged, which can lead to a potentially life-threatening arrhythmia called torsades de pointes. Bedaquiline has been associated with QT prolongation, and coadministration with other drugs that also prolong the QT interval may increase the risk of QT prolongation.

Therefore, it is important to carefully consider the potential risks and benefits of using bedaquiline, particularly in patients with certain medical conditions that may increase their risk of QT prolongation. 

Contraindication / Caution

Contraindication/Caution:

There are several contraindications and precautions to be aware of when using bedaquiline.

1. Contraindications are none
2. One of the main caution is the increased risk of death in the bedaquiline treatment group. It is also important to note that bedaquiline should only be used in an appropriate combination regimen to reduce the risk of developing resistance to the medication. 
3. Bedaquiline can cause hepatotoxicity, or liver damage, so it is important to monitor liver function tests (such as ALT, AST, alkaline phosphatase, and bilirubin) and symptoms of liver dysfunction (such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, and hepatomegaly) during treatment.
4. It is also important to avoid alcohol and other hepatotoxic drugs, especially in patients with hepatic impairment. 
5. Bedaquiline can also prolong the QT interval, which is a measure of the time it takes for the heart to contract and relax. It is important to obtain an ECG before starting treatment and at least 2, 12, and 24 weeks after starting treatment to monitor for QT prolongation.
6. It is also important to monitor electrolytes (such as potassium, calcium, and magnesium) and avoid coadministration with other drugs that can prolong the QT interval. There are also potential drug interactions to be aware of when using bedaquiline.
7. It is metabolized by CYP3A4, so it should be used with caution when coadministered with other medications that are metabolized by CYP3A4, such as strong CYP3A4 inducers (such as rifampin, rifapentine, rifabutin) or moderate CYP3A4 inducers (such as efavirenz).
8. Coadministration with strong CYP3A4 inhibitors should be avoided for more than 14 consecutive days, unless the benefit of treatment outweighs the risk.
9. There are limited data on the use of bedaquiline in HIV/MDR-TB coinfected patients, so caution should be exercised when using it in this population. 

Pregnancy / Lactation

Pregnancy warnings:     

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk is unknown  

Pregnancy Categories:         

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.    

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.   

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 available 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:

bedaquiline is an antimicrobial drug used to treat tuberculosis (TB). bedaquiline has been shown to be effective in treating multidrug-resistant TB, which is a form of TB that is resistant to traditional TB medications. It is typically used in combination with other TB medications to improve treatment outcomes. 

Pharmacodynamics: 

The pharmacodynamics of bedaquiline can be described as follows: 

1. Mode of action: Bedaquiline works by inhibiting the enzyme ATP synthase, which is responsible for synthesizing ATP (adenosine triphosphate), the primary source of energy for Mtb. This results in a reduction in the production of mycolic acids, leading to the death of the bacteria. 2.
2. Target population: Bedaquiline is used to treat patients with multidrug-resistant tuberculosis (MDR-TB) or extensively drug-resistant tuberculosis (XDR-TB), which are forms of TB that are resistant to multiple antibiotics. 3.
3. Drug interactions: Bedaquiline may interact with other drugs, such as rifampicin and isoniazid, which are also used to treat TB. This may increase the risk of side effects or reduce the effectiveness of the medication. 4.0
4. Side effects: Common side effects of bedaquiline include nausea, vomiting, abdominal pain, and loss of appetite. Other rare side effects may include liver damage, QT prolongation (a heart rhythm disorder), and psychosis. 

Pharmacokinetics: 

The pharmacokinetics of bedaquiline involves how the drug is absorbed, distributed, metabolized, and eliminated from the body. 

Absorption: Bedaquiline is well absorbed when taken orally, with peak plasma concentrations occurring within 1-2 hours of ingestion. It has a bioavailability of approximately 80%. 

Distribution: Bedaquiline is highly protein-bound >99.9% in the bloodstream, primarily to albumin. It has a volume of distribution of approximately 12 L/kg. 

Metabolism: Bedaquiline is metabolized in the liver by the cytochrome P450 (CYP) 3A4 enzyme. It has several active metabolites, including O-desmethylbedaquiline (M2) and N-desethylbedaquiline (M3). 

Elimination: Bedaquiline has a half-life of approximately 12-15 days and is eliminated primarily through the feces (60%) and urine (30%). It is not dialyzable. 

Adminstartion

Administration:

bedaquiline administered by directly observed therapy (DOT). DOT means that a healthcare provider or a designated observer is present to watch the patient take their medication and ensure that it is taken as directed. 

The instructions specify that the medication should be taken with food, and 100 mg tablets should be swallowed whole. For the 20 mg tablets, patients who can swallow them whole or divide them in half with food. For patients who cannot swallow the tablets whole, two methods are provided for preparing and administering the medication: 

Method 1: Disperse the tablets in a small amount of water, mix well until the tablets are completely dispersed, and then either consume the mixture as is or mix it with a beverage or soft food. Repeat this process as needed until the desired dose is reached, and then consume food immediately afterwards. 

Method 2: Crush the tablets and mix them with soft food, and then consume the mixture immediately. 

It is important to follow these instructions carefully to ensure that the medication is taken correctly and to maximize its effectiveness. If you have any questions or concerns about taking your medication, you should speak with your healthcare provider. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: bedaquiline 

Why do we use bedaquiline? 

bedaquiline is a Antitubercular Agents and is used to treat tuberculosis (TB). It is typically used in combination with other TB medications as part of a treatment regimen for TB that is resistant to other drugs. 

bedaquiline is a member of a class of drugs called diarylquinolines, which work by inhibiting the growth and replication of TB bacteria. It is usually given as an oral tablet that is taken once a day. 

bedaquiline is usually reserved for use in patients with TB that is resistant to other medications, as it can have serious side effects. Common side effects of bedaquiline include nausea, vomiting, abdominal pain, and dizziness. More serious side effects, such as liver damage and QT prolongation (a type of heart rhythm disturbance), can also occur.