Crutit 500mg S.C Antibiotice treats bacterial infections caused by sensitive bacteria (2 blisters x 10 tablets)

Pharmacokic

Clarithromycin is a semi -synthetic macrolid antibiotic. Clarithromycin often has a bactericidal effect on many gram -positive bacteria and some Gram -negative bacteria. The drug can have a high doses of bactericidal or very sensitive strains. Clarithromycin inhibits the synthesis of protein in sensitive bacteria by attaching the subunit of 50S ribosom, thus preventing the movement of aminocyl transfer-rna and inhibiting polypeptide synthesis. The effect of Clarithromycin is also the position of erythromycin, clindamycin, lincycin and chloramphenicol.

antibacterial spectrum:

In vitro, Clarithromycin have similar or stronger effect than erythromycin for bacteria sensitive to erythromycin and also have anti -micro -microbiological activity (such as the non -typical Mycobacteria, toxoplasma).

sensitive bacteria:

Gram -positive aerobic bacteria: Clarithromycin has a stronger printing effect than erythromycin for sensitive bacteria streptococci and staphylococci.

Clarithromycin also works on a few Gram -positive aerobic bacillus such as Listeria monocytogenes and some Corynebacterium.

Gram -negative aerobic bacteria: In vitro, Clarithromycin are active for some Gram -negative bacteria such as Neisseria Gonorrhoeae and Moraxella (Branhanmella) CatVhalis, Haemophilus Influenzae, H. Parainfluenzae, Pasteurella Multocida. Clarithromycin has a stronger printing effect than erythromycin with legionella spp., Campylobacter spp., Bordetella pertussis. Clarithromycin works with most Helicobacter pylori strains; The drug works on Helicobacter pylori stronger than other macrolids.

Clarithromycin works stronger than erythromycin and azithromycin for mycobacteria including complex mycobacterium avium and M. Leprae.

Other aerobic bacteria: Clarithromycin works with Mycoplasma Pneumonia, Ureaplasma Urealyticum, Chlamydia Trachomatis and some C. Pneumoniae strains.

Anaerobic bacteria: In vitro, Clarithromycin are active with most peptococcus strains, peptostreptoccus, clostridium perfringens, propionibacterium acnes, Prevotella spp strains., Bacteroides Fragilis.

Other bacteria sensitive to drugs include Toxoplasma Gondii, Gardnerella Vaginalis, Borrelia Burgdorferi and Cryptosporidis. The 14-hydroxy clarithromycin metabolism is active and can be in vitro in vitro with mother medicine to significantly increase the activity of clarithromycin clinically for Haemophilus Influenzae, Legionella spp ..

Drug resistance

Macrolid antibiotics are often associated with changes in the destination position associated with antibiotics, but the drug resistance is also due to the intensity of the bacterial antibiotic push. The resistance can be intermediaries or plasmid intermediaries. Macrolid -resistant bacteria produce an enzyme that makes adenin methylation remaining in RNA of ribosom and eventually inhibit antibiotics attached to ribosom.

Erythromycin resistant bacteria are usually resistant to all macrolides because these drugs stimulate methylase enzyme.The erythromycin resistance of streptococcus pneumoniae is usually cross -resistant to clarithromycin. The strains of penicillin -resistant bacteria are also highly resistant to clarithromycin and have been isolated Helicobacter pylori resistant. Due to the fast growing drug resistance with M. Avium when using clarithromycin, it is often recommended to use a combination of clarithromycin with another drug.

Most Enterococci such as Enterococcus Faecalis have both clarithromycin and erythromycin.

Anti -drugs have occurred with bacteria such as: Staphylococcus, anti -oxacilin, staphylococcus coagulase negative (S. Epidermidis), Enterobacteriaceae (Salmonella Enteridiis; Yersinia Enterocoliticica, Shigella and Vibrio SCP.

Dynamic pharmacokinetics

absorption

After taking Clarithromycin oral oral, well absorbed and quickly through the gastrointestinal tract, mainly in the rosary. Due to its chemical structure (6-o-methylerthromycin), Clarithromycin resistance is quite strong with the decomposition of stomach acid. Clarithromycin's peak blood concentration is 1 - 2 µg/ml, recorded in adults after oral use of 250 mg, 2 times daily. After oral oral 500 mg Clarithromycin 2 times daily, the peak concentration in plasma is 2.8 µg/ml.

After oral oral 250 mg Clarithromycin 2 times daily, the peak concentration of plasma of metabolites has an activity of 14-hydroxy is 0.6 µg/ml.

distribution

Clarithromycin penetrates well into different compartments of the body. The drug can quickly achieve the concentration of treatment greater than the minimum inhibitory concentration of common pathogenic microorganisms. Clarithromycin concentration in some tissues is several times higher than the concentration of circulation. Increased drug concentration is found in tissues in tonsils and lungs.

Clarithromycin also passes through the mucous membrane of the stomach.

At the concentration of treatment, about 80% clarithromycin is attached to plasma proteins.

Seruming time in serum of metabolites is active 14- (R) -Hydroxy is in the range of 5-6 hours.

transformation

Clarithromycin is rapidly metabolized and high in the liver. The metabolism is mainly related to reducing alkyl, oxidation and hydroxy at a fixed position C14.

Elimination

After using Clarithromycin oral, radioactive isotope, 70-80% of radioactive activity is found in the feces. About 20-30% are eliminated in the urine in the form of unchanged. This ratio will increase when the dose increases. If the patient has renal failure and is not reduced, the concentration of medication in the blood will increase.

For patients with stomach -duodenal ulcer due to H. Pylori infection, can use 1 tablet/time -time crutit tablet 2 times daily with amoxicillin 1000 mg, 2 times daily and Omeprazol 20 mg, 2 times daily.

Patients with renal failure

Maximum recommendations must be reduced corresponding to the degree of renal failure. In patients with renal impairment with creatinine clearance

Treatment time:

The treatment period with Crutit film tablets depends on the patient's clinical condition, and must follow the doctor's instructions.

There have been reports from after -sales data on drug interactions and effects on the central nervous system (CNS) (for example, fattening and confusion) when using Clarithromycin and Triazolam. Recommended monitoring of increased pharmacological effects on central nervous systems in patients.

young children

Clinical trials with clarithromycin chaos for children have been conducted on children from 6 months to 12 years old. Therefore, children under 12 years of age should use clarithromycin for children.

frequency, type and severity of unwanted effects in young children are similar to adults.

Patients with immunodeficiency

In patients with AIDS and other immunodeficiency patients when used with clarithromycin higher doses in prolonged time to treat Mycobacterial infection, it is difficult to distinguish unwanted effects caused by clarithromycin with existing signs of immunodeficiency syndrome in humans (HIV) or other diseases on available disease.

Instructions on how to handle ADR:

Notify the physician the unwanted effects when using the drug.

Contraindicated to use Clarithromycin in patients with a history of the QT period (congenital or have been recorded in a period of QT) or ventricular arrhythmia, including vertices.

Do not simultaneously use Clarithromycin with HMG-CoA Reductase inhibitors (Statin) are strongly metabolized by CYP3A4 (Lovastatin or Simvastatin), due to increased risk of muscle pain, including muscle pattern.

Contraindicated drugs for patients with hypokalemia (due to the risk of prolonged QT time).

Do not take the drug in patients with severe liver failure accompanied by renal failure.

As well as other powerful CYP3A4 inhibitors, do not take the drug for patients being treated with Colchicin.

Be cautious when using

need to be very careful when taking the drug for patients in the following cases:

Doctors must not prescribe Clarithromycin for pregnant women without careful consideration of the benefits and risks of drug use, especially in the first 3 months of pregnancy.

Be cautious when taking drugs in patients with severe renal impairment.

Clarithromycin is excreted mainly through the liver, so be cautious when taking the drug in patients with liver failure. Also be cautious when using clarithromycin for patients with medium and severe renal failure.

There have been reports that patients with life -threatening liver failure, possibly because some of these patients have had liver diseases before or use other toxic drugs to the liver. Patients should stop treatment and consult a doctor if the signs and symptoms of liver disease appear, such as anorexia, jaundice, dark urine, itching, or soft belly.

There has been a report that patients with fake colitis with almost all antibiotics, including macrolids, the severity of mild to life -threatening disease. There has been a report on patients with diarrhea related to Clostridium difficile (CDAD) with almost all antibiotics including Clarithromycin, and the diverse severity of mild diarrhea to life -threatening colitis. Treatment with antibiotics changes the bacteria system in the intestinal tract, which can lead to excessive growth of C. Difficile. CDAD must be considered for all patients with diarrhea after taking antibiotics. Carefully review the patient's medication history is necessary because the patient has a CDAD more than 2 months after taking antibiotics. Therefore, it is necessary to consider stopping treatment with clarithromycin with any indications. Patients must be performed with bacterial tests and fully treated. Avoid using peristalsis inhibitors.

There have been reports from after -sales data about colchicin poisoning when using clarithromycin and colchicin simultaneously, especially in the elderly, some also appear in patients with renal failure. There have been some deaths in these patients.

Contrain to clarithromycin and colchicin simultaneously.

Be cautious when taking the drug simultaneously with triazolobenzodiazepin, such as triazolam, Midazolam.

Be cautious when using Clarithromycin simultaneously with other toxic drugs in other ears, especially with aminoglycosides. Monitor the listening and vestibular function during and after treatment.

extends the range of qt

Do not use Clarithromycin at a dose greater than 1g/ day simultaneously with ritonavir.

Consider adjusting the same dose in patients with Ritonavir to enhance pharmacokinetics when used simultaneously with other HIV protease inhibitors including Atazanavir and Saquinavir.

The effect of clarithromycin on other drugs

CYP3A interactions

Simultaneous use Clarithromycin is known to inhibit CYP3A and drugs metabolized mainly through CYP3A can lead to increased concentration and thus increases or prolongs both the effectiveness of treatment as well as the unwanted effects of these drugs. Caution must be used when using Clarithromycin for patients being treated simultaneously with drugs that are the substrate of the CYP3A enzyme, especially if this substrate has a narrow safety range (eg carbamazepine) and/ or substances that are strongly metabolized by this enzyme.

Can consider adjusting the dose if possible. The serum concentration of the drugs must be closely monitored mainly converted mainly by CYP3A when used simultaneously with Clarithromycin.

The following drugs or groups of drugs are known to be metabolized by the same iszymy CYP3A: Alprazolam, Astemizol, Carbamazepin, Cilostazol, Cisaprid, Cyclosporin, Disopyramid, Alcaloids spurs, Lovastatin, Methylprednisolon, Midazol, Omeprazol, anti -drugs Oral coagulation (eg Warfarin), non -typical sedatives (eg Quetiapin), Pimozid, Quinidin, Rifabutin, Sildenafil, Simvastatin, Sirolimus, Tacrolimus, Terfenadin, Triazolam and Vinblastin. But this list is still incomplete. Interactive drugs by similar mechanisms through other iszymes in the Cytochrom P450 system include phenytoin, theophylin and valproot.

anti -arrhyths

There have been reports from after -sales data, patients who are twisted when using clarithromycin and quinidine or disopyramid. Must monitor the extension of the QT distance on the electrocardiogram when using Clarithromycin simultaneously with these drugs. Serum concentration must be monitored for quinidine and disopyramid during treatment with clarithromycin.

There have been reports from after -sales data patients with hypoglycemia when using clarithromycin and disopyramid simultaneously. Therefore, blood sugar concentration must be monitored while simultaneous use Clarithromycin and disopyramid.

Oral hypoglycemic drugs/insulin

With some hypoglycemic drugs such as nateganid and repaglinid, the inhibition of CYP3A enzyme by Clarithromycin may be affected and causing hypoglycemia when used simultaneously.

Recommended monitoring of tight blood sugar levels.

omeprazol

Clarithromycin (500 mg every 8 hours) when used simultaneously with omeprazol (40 mg per day) in healthy adults has increased the concentration in the stable state of omeprazol (CMAX increased by 30%, AUC0-24 increased by 89%, and T1/2 up 34%). The average pH value after 24 hours when used separately Omeprazol is 5.2 and when used simultaneously with clarithromycin is 5.7.

Sildenafil, Tadalafil, and Vardenafil

These phosphodiesterase inhibitors are metabolized, at least in part by CYP3A, and CYP3A can be inhibited when used simultaneously with clarithromycin. Simultaneous use Clarithromycin with Sildenafil, Tadalafil or Vardenafil will most likely increase exposure to phosphodiesterase inhibitors. Consider reducing the dose of Sildenafil, Tadalafil and Vardenafil when using Clarithromycin simultaneously.

Theophylin, carbamazepin

According to the results of clinical studies show that when concurrent, theophylin or carbamazepin with clarithromycin will increase the concentration of the periodic period of these drugs, although the increase is small but still have statistical thoughts (p

Tolterodin

Tolterodin is metabolized mainly through the ISOform 2D6 of Cytochrom P450 (CYP2D6). However, in subjects without CYP2D6, the metabolism is done through CYP3A. In these people, CYP3A inhibitors will significantly increase the serum concentration of Tolterodin. It may be necessary to reduce the tolterodine dose if there are CYP3A inhibitors, such as clarithromycin in poor metabolic people through CYP2D6.

triazolobenzodiazepin (for example alprazolam, midazolam, triazolam)

When using simazolam simultaneously with clarithromycin tablets (500 mg 2 times daily), Midazolam's AUC AUC increases 2.7 times after using Midazolam intravenous tract and 7 times after oral use. Must Midazolam and Clarithromycin must be used. If concurrently using intravenous midazolam with clarithromycin, the patient must be closely monitored to adjust the dose. Similarly, be careful when using other benzodiazepines that are metabolized through CYP3A, including triazolam and alprazolam.

With benzodiazepin, excretion does not depend on CYP3A (Temazepam, Nitrazepam, Lorazepam), it is difficult to occur clinical interactions with clarithromycin.

There have been reports from after -sales data about drug interactions and unwanted effects in the central nervous system (CNS) (for example, confused and confused) when using Clarithromycin and Triazolam. Suggestions for monitoring on increasing pharmacological effects on the central nervous system in patients.

Other drug interactions

aminoglycosides

Be cautious when using clarithromycin with toxic drugs, especially with aminoglycosides.

colchicin

Colchicin is a substrate for both CYP3A and shipping proteins, p-glycoprotein (PGP).

Clarithromycin and other macrolids are known to inhibit CYP3A and PGP. When using clarithromycin and colchicin simultaneously, PGP and/or CYP3A inhibitors by clarithromycin may increase exposure to colchicin.

digoxin

Digoxin is considered the substrate of shipping proteins, p-glycoprotein (PGP).

Clarithromycin is known as PGP inhibition. When using clarithromycin and digoxin simultaneously, PGP inhibitors by clarithromycin may increase exposure to digoxin. There have been reports from after -sales data, patients with increased serum digoxin concentration when using clarithromycin and digoxin simultaneously. The clinical symptoms have been recorded with Digoxin in some patients, which may include life -threatening arrhythmia.

Closely monitor serum digoxin concentration when patients use Digoxin with clarithromycin.

zidovudin

Simultaneous use of Clarithromycin and Zidovudin tablets for adults infected with HIV can reduce the concentration in the stable state of zidovudin. Because clarithromycin affects the absorption of zidovudin when taken simultaneously oral, this drug interact is largely avoided by taking these two drugs 4 hours apart. This interaction does not seem to appear in HIV -infected patients and are simultaneously using clarithromycin with zidovudin or dideoxyinosin. This interaction is less likely to occur if Clarithromycin intravenously.

Phenytoin and Valproat

There have been individual reports on interactions between CYP3A inhibitors, including clarithromycin with drugs that are considered not metabolized by CYP3A (for example, Phenytoin and Valproat). It is recommended to determine the serum concentration of these drugs when used simultaneously with clarithromycin. There have been reports in serum increased.

2 -way drug interactions

Atazanavir

both Clarithromycin and Atazanavir are the substrate, as well as the inhibitor of CYP3A. There have been evidence of two -way drug interaction. Simultaneous use Clarithromycin (500 mg, 2 times daily) with Atazanavir (400 mg, once a day) increases 2 times exposure to clarithromycin and decreases 70% of exposure to 14-oh-clarithromycin, and also increases 28% AUC of Atazanavir. Because clarithromycin has a wide window, it is not necessary to reduce the dose in patients with normal kidney function. For patients with average renal function (creatinine clearance from 30-60 ml/minute), a 50% discount of clarithromycin should be reduced. Patients with creatinine clearance

Do not simultaneously use clarithromycin larger than 1000 mg daily with protease inhibitors.

Calcium channel blockers

Should be cautious when using Clarithromycin with calcium channel blockers metabolized by CYP3A4 (for example, Verapamil, Amlodipin, Diltiazem) due to the risk of lowering blood pressure. This interaction can cause the plasma concentration of clarithromycin as well as calcium channel blockers. Patients have been recorded with hypotension, slow heart rate and lactic acidosis in patients with simultaneous use of Clarithromycin and Verapamil.

iTraconazole

both Clarithromycin and Itraconazole are the substrates and CYP3A inhibitors, which lead to two -way drug interaction. Clarithromycin may increase the plasma concentration of otraconazole, while iTraconazole may also increase the concentration of clarithromycin. Closely monitor signs or symptoms of increased or prolonged pharmacological effects on patients when using ITRACONAZOL and Clarithromycin simultaneously.

saquinavir

both Clarithromycin and Saquinavir are the substrates and CYP3A inhibitors, which lead to two -way drug interaction. Concomitance Clarithromycin (500 mg, 2 times daily) and Saquinavir (soft gelatin capsule, 1200 mg 3 times daily) in 12 healthy volunteers have increased 177% of AUC value and 187% CMAX value in equilibrium state compared to those who only use Saquinavir. Clarithromycin's AUC and CMAX value increased by about 40% compared to only clarithromycin. It is not necessary to adjust the dose of these two drugs when used simultaneously in a short time in the doses/formulas that have been studied. The results obtained from drug interactive studies using soft gelatin capsules may not be enough to represent the effects obtained when using hard gelatin capsules Saquinavir. The results obtained from drug interactive research when using SAQIINAVIR may not be enough to represent the effects obtained when using the combination form of Saquinavir/Ritonavir. When used simultaneously Saquinavir with Ritonavir, it is necessary to consider the possible effects of Ritonavir on Clarithromycin.

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