solithromycin

Action and Spectrum

Actions and spectrum: 

solithromycin is a broad-spectrum antibiotic that belongs to the ketolide class. It works by inhibiting bacterial protein synthesis, thereby preventing the growth, and spread of susceptible bacteria.

It exhibits activity against both Gram-positive and Gram-negative bacteria, including pathogens commonly associated with respiratory tract infections such as Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae. solithromycin has also demonstrated efficacy against atypical pathogens and some strains of multi-drug resistant bacteria. 

Drug Interaction

Adverse Reaction

None

Black Box Warning

Black Box Warning: 

There are no specific black box warnings associated with solithromycin 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: solithromycin should not be used in individuals who have a known hypersensitivity or allergic reaction to solithromycin or any of its components. 
• Severe hepatic impairment: solithromycin is contraindicated in patients with severe hepatic impairment as it may exacerbate the condition and lead to further liver damage. 
• Myasthenia gravis: solithromycin should be avoided in individuals with myasthenia gravis, a neuromuscular disorder, as it may worsen muscle weakness and respiratory function. 
• Co-administration with certain medications: solithromycin should not be used in combination with certain medications that may increase the risk of QT prolongation or Torsades de Pointes, a potentially life-threatening heart rhythm disorder.

Caution: 

• QT Prolongation: solithromycin has been associated with QT interval prolongation, which may lead to a potentially life-threatening arrhythmia called Torsades de Pointes.  
• Drug Interactions: solithromycin may interact with other medications, including certain antibiotics, antifungal agents, and drugs metabolized by the liver enzymes CYP3A4 or CYP3A5. Caution should be exercised when co-administering solithromycin with other medications, and dose adjustments may be necessary. 
• Pregnancy and Lactation: The safety of solithromycin during pregnancy and lactation has not been established. It is not known whether solithromycin is excreted in human breast milk, so caution is advised when administering to breastfeeding women.

Comorbidities: 

• Hepatic Impairment: Patients with pre-existing liver disease or impaired liver function may require caution when using solithromycin, as the medication can potentially cause hepatotoxicity (liver toxicity). 
• Renal Impairment: solithromycin is primarily metabolized in the liver, and no dose adjustment is necessary for patients with renal impairment. However, caution should still be exercised, and individualized dosing may be required based on the severity of renal dysfunction. 
• Cardiovascular Disease: solithromycin has been associated with QT interval prolongation, which can lead to an increased risk of arrhythmias, including Torsades de Pointes. Therefore, patients with a history of QT prolongation, congenital long QT syndrome, or other significant cardiovascular diseases may require caution and close monitoring during treatment. 

Pregnancy / Lactation

Pregnancy consideration: N/A 

Lactation: N/A  

Pregnancy category: 

• 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 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: 

• Inhibition of Protein Synthesis: solithromycin binds to the 50S subunit of ribosome, inhibiting the proteins synthesis necessary for bacterial growth and replication. It specifically targets the peptidyl transferase center, disrupting the peptide bonds formation between amino acids during protein synthesis. 
• Bacteriostatic and Bactericidal Activity: solithromycin exhibits both bacteriostatic (inhibiting bacterial growth) and bactericidal (killing bacteria) activity, depending on the specific bacterial strain and its susceptibility to the drug. 
• Anti-inflammatory Effects: solithromycin has been shown to possess anti-inflammatory properties beyond its antibacterial effects. It can inhibit inflammatory mediators’ production, such as chemokines and cytokines, which contribute to the pathogenesis of respiratory infections. 
• Extended Half-Life: solithromycin has an extended half-life compared to other macrolide antibiotics, allowing for once-daily dosing. This prolonged exposure to the drug enhances its effectiveness and convenience in clinical practice.

Pharmacodynamics: 

• Antibacterial Activity: solithromycin exhibits potent antibacterial activity against a wide range of pathogens, including Gram-positive and Gram-negative bacteria. It is effective against common respiratory pathogens, atypical bacteria like Mycoplasma pneumoniae and Chlamydia pneumoniae. solithromycin acts by inhibiting bacterial protein synthesis, leading to the inhibition of bacterial growth, and killing the bacteria. 
• Time-Dependent Killing: The antibacterial activity of solithromycin is time-dependent, meaning that it requires a certain concentration of the drug to be maintained over a specific period to effectively kill the bacteria. This property influences the dosing regimen and ensures that adequate drug levels are maintained in the body for optimal efficacy. 
• Concentration-Dependent Effects: Although solithromycin exhibits time-dependent killing, higher drug concentrations have also been associated with increased bacterial killing activity. This concentration-dependent effect may contribute to its broad spectrum of activity and effectiveness against resistant strains of bacteria. 
• Post-Antibiotic Effect: solithromycin has demonstrated a prolonged post-antibiotic effect. This property further contributes to its efficacy and allows for less frequent dosing. 

Pharmacokinetics: 

Absorption 

• solithromycin is available in oral formulations, such as tablets and suspensions. 
• It is well-absorbed from the gastrointestinal tract after oral administration. 

Distribution 

• solithromycin has a high volume of distribution, indicating extensive tissue distribution. 
• It is distributed to various tissues, including respiratory tract tissues, where it exerts its antibacterial effects. 
• solithromycin crosses the blood-brain barrier, allowing it to target infections in the central nervous system. 

Metabolism 

• solithromycin undergoes hepatic metabolism primarily via cytochrome P450 (CYP) enzymes, particularly CYP3A4. 
• It is metabolized to an active metabolite, N-acetyl-solithromycin, which contributes to the overall antibacterial activity of the drug. 

Elimination and excretion 

• solithromycin and its metabolites are primarily excreted in the feces and to a lesser in the urine. 
• The elimination half-life of solithromycin is 20 to 24 hours. 

Adminstartion

Administration: 

solithromycin is typically administered orally in the form of tablets or suspensions. 

• Oral Tablets: administer the tablet whole with a full glass of water. It is generally taken one time a day, with or without the food.  
• Oral Suspension: Shake the suspension well before each use. Use the provided measuring device or syringe to measure the correct dose. Administer the suspension orally according to the prescribed dosage and frequency. It is often taken once daily, with or without food. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: solithromycin 

Pronounced: (soh-lih-throh-MY-sin)  

Why do we use solithromycin? 

solithromycin, received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA). The CRL indicated that the approval of the New Drug Applications (NDAs) for oral and intravenous solithromycin was pending until the FDA obtained additional clinical safety information and satisfactory resolution of manufacturing facility inspection deficiencies.

• Community-Acquired Pneumonia (CAP): solithromycin is approved for the treatment of community-acquired pneumonia in adults. It is effective against common respiratory pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Legionella pneumophila. 
• Acute Bacterial Exacerbations of Chronic Bronchitis (ABECB): solithromycin is also used to treat acute bacterial exacerbations of chronic bronchitis. It helps in reducing inflammation and clearing the infection in the airways. 
• Uncomplicated Genital Infections: solithromycin may be used to treat uncomplicated genital infections caused by certain bacteria, such as Chlamydia trachomatis and Neisseria gonorrhoeae.