Diarrhoea grade 2 or higher was found in 24% of these patients, thrombocytopenia grade 3 or higher in 28%, and fatigue grade 2 or higher in 26%. Interactions
The drug has a low potential for interactions via cytochrome P450 (CYP) liver enzymes and transporter proteins. The only relevant finding in studies was a reduction of ixazomib blood levels when combined with the strong CYP3A4 inducer rifampicin. The Cmax was reduced by 54% and the area under the curve by 74% in this study. Pharmacology
Mechanism of action
At therapeutic concentrations, ixazomib selectively and reversibly inhibits the protein proteasome subunit beta type-5 (PSMB5) with a dissociation half-life of 18 minutes. This mechanism is the same as of bortezomib, which has a much longer dissociation half-life of 110 minutes; the related drug carfilzomib, by contrast, blocks PSMB5 irreversibly. Proteasome subunits beta type-1 and type-2 are only inhibited at high concentrations reached in cell culture models.PSMB5 is part of the 20S proteasome complex and has enzymatic activity similar to chymotrypsin. It induces apoptosis, a type of programmed cell death, in various cancer cell lines. A synergistic effect of ixazomib and lenalidomide has been found in a large number of myeloma cell lines. Pharmacokinetics
The medication is taken orally as a prodrug, ixazomib citrate, which is a boronic ester; this ester rapidly hydrolyzes under physiological conditions to its biologically active form, ixazomib, a boronic acid. Absolute bioavailability is 58%, and highest blood plasma concentrations of ixazomib are reached after one hour.
It is also used to treat bone and joint infections, particularly those caused by Staphylococcus aureus. Topical application of clindamycin phosphate can be used to treat mild to moderate acne. Acne
For the treatment of acne, in the long term, the combined use of topical clindamycin and benzoyl peroxide was similar to salicylic acid plus benzoyl peroxide. Topical clindamycin plus topical benzoyl peroxide is more effective than topical clindamycin alone. Susceptible bacteria
It is most effective against infections involving the following types of organisms:

Aerobic Gram-positive cocci, including some members of the Staphylococcus and Streptococcus (e.g. pneumococcus) genera, but not enterococci. Anaerobic, Gram-negative rod-shaped bacteria, including some Bacteroides, Fusobacterium, and Prevotella, although resistance is increasing in Bacteroides fragilis.Most aerobic Gram-negative bacteria (such as Pseudomonas, Legionella, Haemophilus influenzae and Moraxella) are resistant to clindamycin, as are the facultative anaerobic Enterobacteriaceae. A notable exception is Capnocytophaga canimorsus, for which clindamycin is a first-line drug of choice.The following represents MIC susceptibility data for a few medically significant pathogens. Staphylococcus aureus: 0.016 μg/ml - >256 μg/ml
Streptococcus pneumoniae: 0.002 μg/ml - >256 μg/ml
Streptococcus pyogenes: <0.015 μg/ml - >64 μg/ml

D-test
When testing a gram-positive culture for sensitivity to clindamycin, it is common to perform a "D-test" to determine if there is a sub-population of bacteria present with the phenotype known as iMLSB. This phenotype of bacteria are resistant to the macrolide-lincosamide-streptogramin B group of antibiotics, however, the resistance mechanism is only induced by the presence of 14-membered ring macrolides, such as erythromycin.