Restanza

Uses

Restanza is a ketolide antibiotic with broad-spectrum activity against Gram-positive, Gram-negative, and atypical bacteria that may be useful for treating several conditions including community-acquired pneumonia, inhalation anthrax, plague, and tularemia.

Restanza currently has no FDA-approved indications; it was granted orphan drug designation for the prophylactic treatment of inhalation anthrax in 2007 and for the prophylactic treatment of both plague due to Yersinia pestis and tularemia due to Francisella tularensis in 2009.

Restanza is also used to associated treatment for these conditions: Plague caused by Yersinia pestis, Tularemia, Inhaled anthrax caused by Bacillus anthracis

How Restanza works

Respiratory tract infections can be caused by numerous strains of bacteria, requiring careful consideration of treatment and antibiotics effective against a broad spectrum of potential pathogens. Restanza, like other macrolide antibiotics, binds to the 23S rRNA of the 50S subunit of the bacterial ribosome. This binding, primarily mediated through regions II and V of the rRNA, occludes the peptide exit tunnel and inhibits bacterial protein synthesis. In addition, cethromycin is capable of binding to ribosomal intermediates during ribosome biogenesis, inhibiting the formation of functional 70S bacterial ribosomes. Due to the sequence and structural similarity of ribosomes between species, cethromycin displays broad-spectrum activity against diverse Gram-positive, Gram-negative, and atypical bacteria.

Toxicity

Toxicity information regarding cethromycin is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as diarrhea, nausea, vomiting, abdominal pain, and headaches. Symptomatic and supportive measures are recommended.

Food Interaction

Volume of Distribution

Restanza given in five 150 mg oral doses had an apparent volume of distribution at the terminal elimination phase of 1433 ± 843 L, and an apparent steady-state volume of distribution of 1453 ± 997 L. The corresponding values for a 300 mg dose was 761 ± 293 L and 769 ± 272 L. Restanza is known to accumulate in the epithelial lining fluid and alveolar cells, as well as within polymorphonuclear leukocytes.

Elimination Route

Restanza displays non-linear absorption kinetics. In healthy adults administered 150 mg cethromycin orally once daily for five doses, the calculated C_max, T_max, and AUC_0-24 values were 0.181 ± 0.084 μg/ml, 2.01 ± 1.30 hrs, and 0.902 ± 0.469 μg*h/ml, respectively. Similarly, the corresponding values for a 300 mg dose were 0.500 ± 0.168 μg/ml, 2.09 ± 0.03 hrs, and 3.067 ± 1.205 μg*h/ml, respectively.

In another study using a single oral dose of 150 mg cethromycin, the C_max was 318 ± 161 ng/ml, the T_max was 1.79 ± 0.50, the AUC_0-24 was 1596 ± 876 ng*h/ml, and the AUC_0-∞ was 1662 ± 907 ng*h/ml.

Half Life

Restanza given in five oral doses of 150 or 300 mg has a plasma half-life of 4.85 ± 1.10 and 4.94 ± 0.66 hrs, respectively. A single oral dose of 150 mg produced a measured half-life of 5.66 ± 0.77 hrs.

Clearance

Restanza clearance in patients receiving a once-daily oral dose of 300 mg is reported to be approximately 63 L/h.

Elimination Route

Restanza is primarily excreted by the biliary route, with 87.2% of an initial dose recovered in feces and only 7.0% in urine. Unchanged cethromycin accounted for 35.7% of the radioactivity recovered in feces and an N-desmethyl metabolite for 39.8%; the remaining radioactivity was approximately evenly divided between three minor metabolites and a group of uncharacterized additional products.

Innovators Monograph

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