Clarimicina Actions

• Actions of Clarimicina in details
• Clarimicina administration
• Clarimicina pharmacology
• Clarimicina reviews

Actions of Clarimicina in details

Pharmacology: Mechanism of Action: Clarimicina and other macrolides bind reversibly to the 50S subunit of the ribosome, resulting in blockage of the transpeptidation or translocation reactions, inhibition of protein synthesis, and hence inhibition of cell growth. Its action is predominantly bacteriostatic, but high concentrations are slowly bactericidal against the more sensitive strains. Because macrolides penetrate readily into white blood cells and macrophages, there has been some interest in their potential synergy with the host defense mechanism in vivo.

Microbiology: Clarimicina is reported to be more active than erythromycin against susceptible streptococci and staphylococci in vitro, as well as against some other species including Moraxella catarrhalis (Branhamella catarrhalis), Legionella spp, Chlamydia trachomatis and Ureaplasma urealyticum. Clarimicina is reported to be more active than erythromycin or azithromycin against some mycobacteria, including Mycobacterium avium complex and against M. leprae. It is reported to have some in vitro activity against the protozoan Toxoplasma gondii, and may have some activity against cryptosporidia. The major metabolite, 14-hydroxyclarithromycin, is also active, and may enhance the activity of Clarimicina in vivo, notably against Haemophilus influenzae.

Pharmacokinetics: Clarimicina is rapidly and well absorbed from the gastrointestinal tract after oral administration of Clarimicina tablets. The microbiologically active metabolite, 14-hydroxyclarithromycin, is formed by first-pass metabolism. Clarimicina may be given without regard to meals as food does not affect the extent of bioavailability of Clarimicina tablets. Food does slightly delay the onset of absorption of Clarimicina and formation of the 14-hydroxymetabolite.

The kinetics of orally administered modified-release Clarimicina have been studied in adult humans and compared with Clarimicina 250 and 500 mg immediate-release tablets. The extent of absorption was found to be equivalent when equal total daily doses were administered. The absolute bioavailability is approximately 50%.

Urinary excretion accounted for approximately 40% of the Clarimicina dose. Fecal elimination accounts for approximately 30%.

Clarimicina also penetrates the gastric mucus. Levels of Clarimicina in gastric mucus and gastric tissue are higher when Clarimicina is co-administered with omeprazole than when Clarimicina is administered alone.

How should I take Clarimicina?

Take Clarimicina only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

You may take Clarimicina with meals or milk or on an empty stomach. However, Clarimicina extended release tablets should be taken with food.

If you are using the extended-release tablets:

• Swallow the tablet whole. Do not break, crush, or chew it.
• While taking the extended-release form of Clarimicina, part of the tablet may pass into your stools. This is normal and is nothing to worry about.

Measure the oral liquid with a marked measuring spoon, syringe, or cup. The average household teaspoon may not hold the right amount of liquid. Shake the bottle of medicine well just before taking each dose.

If you are taking Clarimicina and zidovudine, these medicines should be taken at least 2 hours apart.

Keep using the medicine for the full time of treatment, even if you or your child begin to feel better after the first few doses. Your infection may not clear up if you stop using the medicine too soon.

Dosing

The dose of Clarimicina will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Clarimicina. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release tablets):
  • For bacterial infections:
    • Adults—1000 milligrams (mg) once a day for 7 to 14 days.
    • Children—Use and dose must be determined by your doctor.
  • For community-acquired pneumonia:
    • Adults—1000 milligrams (mg) once a day for 7 days.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage forms (suspension and tablets):
  • For bacterial infections:
    • Adults—250 to 500 milligrams (mg) every twelve hours for 7 to 14 days.
    • Children 6 months of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 7.5 milligrams (mg) per kilogram (kg) of body weight every twelve hours for 10 days.
    • Infants younger than 6 months of age—Use and dose must be determined by your doctor.
  • For community-acquired pneumonia:
    • Adults—250 milligrams (mg) every twelve hours for 7 to 14 days.
    • Children 6 months of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 7.5 milligrams (mg) per kilogram (kg) of body weight every twelve hours for 10 days.
    • Infants younger than 6 months of age—Use and dose must be determined by your doctor.
  • For prevention or treatment of Mycobacterium avium complex (MAC) infection:
    • Adults—500 milligrams (mg) two times a day.
    • Children 20 months of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 7.5 milligrams (mg) per kilogram (kg) of body weight, up to 500 mg, two times a day.
    • Children younger than 20 months of age—Use and dose must be determined by your doctor.
  • For treatment of ulcers associated with H. pylori:
    • Adults—500 milligrams (mg) two or three times a day for 10 or 14 days, in combination with omeprazole or ranitidine bismuth sulfate; 500 mg every twelve hours in combination with amoxicillin and lansoprazole for 10 or 14 days; or 500 mg every twelve hours in combination with amoxicillin and omeprazole for 10 days.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of Clarimicina, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Do not refrigerate or freeze the oral liquid. Throw away any unused mixed medicine after 14 days.

Clarimicina administration

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

You may take Clarimicina tablets and oral suspension (liquid) with or without food.

Clarimicina extended-release tablets (Biaxin XL) should be taken with food.

Do not crush, chew, or break an extended-release tablet. Swallow it whole. Breaking the pill may cause too much of the drug to be released at one time.

Shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Take this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Clarimicina will not treat a viral infection such as the common cold or flu.

Store at room temperature away from moisture and heat. Do not keep the oral liquid in a refrigerator.

Clarimicina pharmacology

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Mechanism of Action

Clarimicina is a macrolide antimicrobial drug.

Pharmacokinetics

Absorption

Clarimicina Immediate-Release Tablets

The absolute bioavailability of 250 mg Clarimicina tablets was approximately 50%. For a single 500 mg dose of Clarimicina, food slightly delays the onset of Clarimicina absorption, increasing the peak time from approximately 2 to 2.5 hours. Food also increases the Clarimicina peak plasma concentration by about 24%, but does not affect the extent of Clarimicina bioavailability. Food does not affect the onset of formation of the active metabolite, 14-OH Clarimicina or its peak plasma concentration but does slightly decrease the extent of metabolite formation, indicated by an 11% decrease in area under the plasma concentration-time curve (AUC). Therefore, Clarimicina tablets may be given without regard to food. In non-fasting healthy human subjects (males and females), peak plasma concentrations were attained within 2 to 3 hours after oral dosing.

Clarimicina Extended-Release Tablets

Clarimicina extended-release tablets provide extended absorption of Clarimicina from the gastrointestinal tract after oral administration. Relative to an equal total daily dose of immediate-release Clarimicina tablets, Clarimicina extended-release tablets provide lower and later steady-state peak plasma concentrations but equivalent 24 hour AUCs for both Clarimicina and its microbiologically-active metabolite, 14-OH Clarimicina. While the extent of formation of 14-OH Clarimicina following administration of Clarimicina extended-release tablets (2 x 500 mg tablets once daily) is not affected by food, administration under fasting conditions is associated with approximately 30% lower Clarimicina AUC relative to administration with food. Therefore, Clarimicina extended-release tablets should be taken with food.

Figure 2: Steady-State Clarimicina Plasma Concentration-Time Profiles

Clarimicina for

Oral Suspension

When 250 mg doses of Clarimicina as Clarimicina suspension were administered to fasting healthy adult subjects, peak plasma concentrations were attained around 3 hours after dosing.

For adult patients, the bioavailability of 10 mL of the 125 mg/5 mL suspension or 10 mL of the 250 mg/5 mL suspension is similar to a 250 mg or 500 mg tablet, respectively.

In adults given 250 mg Clarimicina as suspension (n = 22), food appeared to decrease mean peak plasma Clarimicina concentrations from 1.2 (± 0.4) mcg/mL to 1.0 (± 0.4) mcg/mL and the extent of absorption from 7.2 (± 2.5) hr•mcg/mL to 6.5 (± 3.7) hr•mcg/mL.

Distribution

Clarimicina and the 14-OH Clarimicina metabolite distribute readily into body tissues and fluids. There are no data available on cerebrospinal fluid penetration. Because of high intracellular concentrations, tissue concentrations are higher than serum concentrations. Examples of tissue and serum concentrations are presented below.

Table 9. Tissue and Serum Concentrations of Clarimicina

Metabolism and Elimination

Clarimicina Immediate-Release Tablets

Steady-state peak plasma Clarimicina concentrations were attained within 3 days and were approximately 1 mcg/mL to 2 mcg/mL with a 250 mg dose administered every 12 hours and 3 mcg/mL to 4 mcg/mL with a 500 mg dose administered every 8 hours to 12 hours. The elimination half-life of Clarimicina was about 3 hours to 4 hours with 250 mg administered every 12 hours but increased to 5 hours to 7 hours with 500 mg administered every 8 hours to 12 hours. The nonlinearity of Clarimicina pharmacokinetics is slight at the recommended doses of 250 mg and 500 mg administered every 8 hours to 12 hours. With a 250 mg every 12 hours dosing, the principal metabolite, 14-OH Clarimicina, attains a peak steady-state concentration of about 0.6 mcg/mL and has an elimination half-life of 5 hours to 6 hours. With a 500 mg every 8 hours to 12 hours dosing, the peak steady-state concentration of 14-OH Clarimicina is slightly higher (up to 1 mcg/mL), and its elimination half-life is about 7 hours to 9 hours. With any of these dosing regimens, the steady-state concentration of this metabolite is generally attained within 3 days to 4 days.

After a 250 mg tablet every 12 hours, approximately 20% of the dose is excreted in the urine as Clarimicina, while after a 500 mg tablet every 12 hours, the urinary excretion of Clarimicina is somewhat greater, approximately 30%. In comparison, after an oral dose of 250 mg (125 mg/5 mL) suspension every 12 hours, approximately 40% is excreted in urine as Clarimicina. The renal clearance of Clarimicina is, however, relatively independent of the dose size and approximates the normal glomerular filtration rate. The major metabolite found in urine is 14-OH Clarimicina, which accounts for an additional 10% to 15% of the dose with either a 250 mg or a 500 mg tablet administered every 12 hours.

Clarimicina Extended-Release Tablets

In healthy human subjects, steady-state peak plasma Clarimicina concentrations of approximately 2 mcg/mL to 3 mcg/mL were achieved about 5 hours to 8 hours after oral administration of 1,000 mg Clarimicina extended-release tablets once daily; for 14-OH Clarimicina, steady-state peak plasma concentrations of approximately 0.8 mcg/mL were attained about 6 hours to 9 hours after dosing. Steady-state peak plasma Clarimicina concentrations of approximately 1 mcg/mL to 2 mcg/mL were achieved about 5 hours to 6 hours after oral administration of a single 500 mg Clarimicina extended-release tablets once daily; for 14-OH Clarimicina, steady-state peak plasma concentrations of approximately 0.6 mcg/mL were attained about 6 hours after dosing.

Steady-state peak plasma concentrations were attained in 2 days to 3 days and were approximately 2 mcg/mL for Clarimicina and 0.7 mcg/mL for 14-OH Clarimicina when 250 mg doses of the Clarimicina suspension were administered every 12 hours. Elimination half-life of Clarimicina (3 hours to 4 hours) and that of 14-OH Clarimicina (5 hours to 7 hours) were similar to those observed at steady state following administration of equivalent doses of Clarimicina tablets.

Specific Populations for Clarimicina Tablets, Clarimicina Extended-Release Tablets, and Clarimicina for

Oral Suspension Formulations

Clarimicina for

Oral Suspension in Pediatric Patients

Clarimicina penetrates into the middle ear fluid of pediatric patients with secretory otitis media.

Table 10. Middle Ear Fluid and Serum Concentrations of Clarimicina and 14-OH- Clarimicina in Pediatric Patients

When pediatric patients (n = 10) were administered a single oral dose of 7.5 mg/kg Clarimicina as an oral suspension, food increased mean peak plasma Clarimicina concentrations from 3.6 (±1.5) mcg/mL to 4.6 (± 2.8) mcg/mL and the extent of absorption from 10.0 (± 5.5) hr•mcg/mL to 14.2 (± 9.4) hr•mcg/mL.

In pediatric patients requiring antibacterial therapy, administration of 7.5 mg/kg every 12 hours of Clarimicina as an oral suspension generally resulted in steady-state peak plasma concentrations of 3 mcg/mL to 7 mcg/mL for Clarimicina and 1 mcg/mL to 2 mcg/mL for 14-OH Clarimicina.

In HIV-infected pediatric patients taking 15 mg/kg of Clarimicina as an oral suspension every 12 hours, steady-state Clarimicina peak concentrations generally ranged from 6 mcg/mL to 15 mcg/mL.

HIV Infection

Steady-state concentrations of Clarimicina and 14-OH Clarimicina observed following administration of 500 mg doses of Clarimicina every 12 hours to adult patients with HIV infection were similar to those observed in healthy volunteers. In adult HIV-infected patients taking 500 mg or 1,000 mg doses of Clarimicina every 12 hours, steady-state Clarimicina Cmax values ranged from 2 mcg/mL to 4 mcg/mL and 5 mcg/mL to 10 mcg/mL, respectively.

Hepatic Impairment

The steady-state concentrations of Clarimicina in subjects with impaired hepatic function did not differ from those in normal subjects; however, the 14-OH Clarimicina concentrations were lower in the hepatically impaired subjects. The decreased formation of 14-OH Clarimicina was at least partially offset by an increase in renal clearance of Clarimicina in the subjects with impaired hepatic function when compared to healthy subjects.

Renal Impairment

The pharmacokinetics of Clarimicina was also altered in subjects with impaired renal function.

Drug Interactions

Fluconazole

Following administration of fluconazole 200 mg daily and Clarimicina 500 mg twice daily to 21 healthy volunteers, the steady-state Clarimicina Cmin and AUC increased 33% and 18%, respectively. Clarimicina exposures were increased and steady-state concentrations of 14-OH Clarimicina were not significantly affected by concomitant administration of fluconazole.

Colchicine

When a single dose of colchicine 0.6 mg was administered with Clarimicina 250 mg BID for 7 days, the colchicine Cmax increased 197% and the AUC0-∞ increased 239% compared to administration of colchicine alone.

Atazanavir

Following administration of Clarimicina (500 mg twice daily) with atazanavir (400 mg once daily), the Clarimicina AUC increased 94%, the 14-OH Clarimicina AUC decreased 70% and the atazanavir AUC increased 28%.

Ritonavir

Concomitant administration of Clarimicina and ritonavir (n = 22) resulted in a 77% increase in Clarimicina AUC and a 100% decrease in the AUC of 14-OH Clarimicina.

Saquinavir

Following administration of Clarimicina (500 mg bid) and saquinavir (soft gelatin capsules, 1200 mg tid) to 12 healthy volunteers, the steady-state saquinavir AUC and Cmax increased 177% and 187% respectively compared to administration of saquinavir alone. Clarimicina AUC and Cmax increased 45% and 39% respectively, whereas the 14–OH Clarimicina AUC and Cmax decreased 24% and 34% respectively, compared to administration with Clarimicina alone.

Didanosine

Simultaneous administration of Clarimicina tablets and didanosine to 12 HIV-infected adult patients resulted in no statistically significant change in didanosine pharmacokinetics.

Zidovudine

Following administration of Clarimicina 500 mg tablets twice daily with zidovudine 100 mg every 4 hours, the steady-state zidovudine AUC decreased 12% compared to administration of zidovudine alone (n=4). Individual values ranged from a decrease of 34% to an increase of 14%. When Clarimicina tablets were administered two to four hours prior to zidovudine, the steady- state zidovudine Cmax increased 100% whereas the AUC was unaffected (n=24).

Omeprazole

Clarimicina 500 mg every 8 hours was given in combination with omeprazole 40 mg daily to healthy adult subjects. The steady-state plasma concentrations of omeprazole were increased (Cmax, AUC0-24, and t½ increases of 30%, 89%, and 34%, respectively), by the concomitant administration of Clarimicina.

The plasma levels of Clarimicina and 14–OH Clarimicina were increased by the concomitant administration of omeprazole. For Clarimicina, the mean Cmax was 10% greater, the mean Cmin was 27% greater, and the mean AUC0-8 was 15% greater when Clarimicina was administered with omeprazole than when Clarimicina was administered alone. Similar results were seen for 14–OH Clarimicina, the mean Cmax was 45% greater, the mean Cmin was 57% greater, and the mean AUC0-8 was 45% greater. Clarimicina concentrations in the gastric tissue and mucus were also increased by concomitant administration of omeprazole.

Theophylline

In two studies in which theophylline was administered with Clarimicina (a theophylline sustained-release formulation was dosed at either 6.5 mg/kg or 12 mg/kg together with 250 or 500 mg q12h Clarimicina), the steady-state levels of Cmax, Cmin, and the area under the serum concentration time curve (AUC) of theophylline increased about 20%.

Midazolam

When a single dose of midazolam was coadministered with Clarimicina tablets (500 mg twice daily for 7 days), midazolam AUC increased 174% after intravenous administration of midazolam and 600% after oral administration.

For information about other drugs indicated in combination with Clarimicina, refer to their full prescribing information, CLINICAL PHARMACOLOGY section.

Microbiology

Mechanism of Action

Clarimicina exerts its antibacterial action by binding to the 50S ribosomal subunit of susceptible bacteria resulting in inhibition of protein synthesis.

Resistance

The major routes of resistance are modification of the 23S rRNA in the 50S ribosomal subunit to insensitivity or drug efflux pumps. Beta-lactamase production should have no effect on Clarimicina activity.

Most isolates of methicillin-resistant and oxacillin-resistant staphylococci are resistant to Clarimicina.

If H. pylori is not eradicated after treatment with Clarimicina-containing combination regimens, patients may develop Clarimicina resistance in H. pylori isolates. Therefore, for patients who fail therapy, Clarimicina susceptibility testing should be done, if possible. Patients with Clarimicina-resistant H. pylori should not be treated with any of the following: omeprazole/Clarimicina dual therapy; omeprazole/Clarimicina/amoxicillin triple therapy; lansoprazole/Clarimicina/amoxicillin triple therapy; or other regimens which include Clarimicina as the sole antibacterial agent.

Antimicrobial Activity

Clarimicina has been shown to be active against most of the isolates of the following microorganisms both in vitro and in clinical infections.

Gram-Positive Bacteria

• Staphylococcus aureus
• Streptococcus pneumoniae
• Streptococcus pyogenes

Gram-Negative Bacteria

• Haemophilus influenzae
• Haemophilus parainfluenzae
• Moraxella catarrhalis

Other Microorganisms

• Chlamydophila pneumoniae
• Helicobacter pylori
• Mycobacterium avium complex (MAC) consisting of M. avium and M. intracellulare
• Mycoplasma pneumoniae

At least 90 percent of the microorganisms listed below exhibit in vitro minimum inhibitory concentrations (MICs) less than or equal to the Clarimicina susceptible MIC breakpoint for organisms of similar type to those shown in Table 11. However, the efficacy of Clarimicina in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

Gram-Positive Bacteria

• Streptococcus agalactiae
• Streptococci (Groups C, F, G)
• Viridans group streptococci

Gram-Negative Bacteria

• Legionella pneumophila
• Pasteurella multocida

Anaerobic Bacteria

• Clostridium perfringens
• Peptococcus niger
• Prevotella melaninogenica
• Propionibacterium acnes

Susceptibility Testing Methods (Excluding Mycobacteria and Helicobacter)

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antimicrobial drug for treatment.

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method1,2 (broth and/or agar). The MIC values should be interpreted according to the criteria provided in Table 11.

Diffusion Techniques

Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method.2,3 This procedure uses paper disks impregnated with 15 mcg of Clarimicina to test the susceptibility of bacteria to Clarimicina. The disk diffusion interpretive criteria are provided in Table 11.

Susceptibility Testing for Mycobacterium avium Complex (MAC)

The reference methodology for susceptibility testing of Mycobacterium avium complex (MAC) is broth dilution (either microdilution or macrodilution method).4 For broth microdilution testing, cation-adjusted Mueller-Hinton broth (CAMHB) supplemented with 5% OADC is recommended. Transparent colonies should be used for the inoculum, if present. Susceptibility testing at either pH 6.8 or pH 7.4 is acceptable, provided that interpretation is done based on the culture conditions employed. Microdilution trays are incubated at 35 ºC to 37 ºC in ambient air and examined after seven days. Trays should be incubated and read again at 10 to 14 days, if growth is poor on initial inspection.

Susceptibility Testing for Helicobacter pylori

The reference methodology for susceptibility testing of H. pylori is agar dilution MICs.5 One to three microliters of an inoculum equivalent to a No. 2 McFarland standard (1 x 107-1 x 108 CFU/mL for H. pylori) are inoculated directly onto freshly prepared antimicrobial containing Mueller-Hinton agar plates with 5% aged defibrinated sheep blood (> 2 weeks old). The agar dilution plates are incubated at 35°C in a microaerobic environment produced by a gas generating system suitable for Campylobacter species. After 3 days of incubation, the MICs are recorded as the lowest concentration of antimicrobial agent required to inhibit growth of the organism. The Clarimicina MIC values should be interpreted according to the criteria in Table 11.

Table 11. Susceptibility Test Interpretive Criteria for Clarimicina

A report of Susceptible (S) indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the site of infection. A report of Intermediate (I) indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant (R) indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the infection site; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory control bacteria to monitor and ensure the accuracy and precision of supplies and reagents in the assay, and the techniques of the individual performing the test.1 to 5 Standard Clarimicina powder should provide the following range of MIC values as noted in Table 12. For the diffusion technique using the 15 mcg disk, the criteria in Table 12 should be achieved.

Table 12. Acceptable Quality Control Ranges for Clarimicina

References

1. DailyMed. "CLARITHROMYCIN: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
2. NCIt. "Clarithromycin: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
3. EPA DSStox. "Clarithromycin: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).

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Information checked by Dr. Sachin Kumar, MD Pharmacology