1. Lower respiratory tract infections: such as bronchitis and pneumonia;
2. Upper respiratory tract infection: such as pharyngitis and sinusitis;
3. Mild and moderate infections of skin and soft tissues, such as folliculitis, cellulitis and erysipelas.
Specification 0.5g
dosage
Oral. The recommended dose for adults is one tablet (500 mg) once a day. Take it with meals. Do not crush or chew clarithromycin sustained-release tablets. /kloc-children over 0/2 are the same as adults. For children under 12, please use other varieties suitable for dosage form.
When the infection is serious, the dosage can be increased to 2 tablets per day 1 time (1000mg). The course of treatment is usually 7~ 14 days.
Clarithromycin sustained-release tablets are prohibited for patients with severe renal dysfunction (creatinine clearance rate < 30 ml/min). Clarithromycin tablets can be used in such patients. Patients with moderate renal function impairment (creatinine clearance rate 30~60ml/min) should be reduced by 50%, and the maximum dose is 500mg 1 tablet per day.
counteraction
Clarithromycin is well tolerated. It is reported that the temporary side effects of the central nervous system include dizziness, anxiety, insomnia, nightmares, tinnitus, interference, disorientation, hallucinations, mental disorders and personality disorders. A patient with bipolar disorder developed mental state change, paranoid behavior, hypokalemia and hypoxemia after taking 8g clarithromycin. There are also reports that the sense of smell has changed. It is usually associated with taste reversal. There have been cases of hearing loss after drug abuse, but they recovered after drug withdrawal. Other side effects include headache, joint pain, myalgia and allergic reactions, ranging from rubella, mild rash and angioedema to allergic reactions and rare Stevens-Johnson syndrome/toxic skin necrosis. Like other macrolides, there are few reports about the prolongation of Q-T interval after taking clarithromycin. Ventricular fibrillation and torsade de pointes ventricular tachycardia. It is reported that clarithromycin is similar to other macrolide antibiotics, and there will be abnormal liver function (generally reversible) after taking the medicine, including: changes in liver function and bile coagulation, with or without jaundice. Abnormal liver function can be very serious. However, there are few reports of liver failure. It is reported that taking a large dose of clarithromycin may cause gastrointestinal symptoms. The side effects associated with overdose should be gastric lavage and support measures. Like other macrolides, hemodialysis or peritoneal dialysis will not affect the blood concentration of clarithromycin. Other side effects include nausea, indigestion, diarrhea, vomiting, abdominal pain and paresthesia. There are also reports of stomatitis, glossitis, oral candidiasis and tongue discoloration. There are reports of leukopenia and thrombocytopenia in sporadic cases. There are few reports of patients with elevated serum creatinine, interstitial nephritis, renal failure, adenitis and convulsion after taking the medicine. Pseudomembranous laryngitis is rare during medication. Severity ranges from mild laryngitis to life-threatening. Hypoglycemia has been reported for a long time, some of which occurred when taken with oral hypoglycemic components or insulin.
It is reported that teeth discolored after clarithromycin treatment, but teeth discolored can generally be eliminated after professional tooth washing.
taboo
People who are allergic to macrolide antibiotics are prohibited. Because the dosage of clarithromycin sustained-release tablets cannot be reduced below 500mg per day, patients with creatinine clearance below 30ml/min are prohibited. Clarithromycin is forbidden to be used with the following drugs: astemizole, cisapride, pimozide and terfenadine.
Matters needing attention
It is reported that almost all antibiotics, including macrolides, may cause mild to life-threatening pseudomembranous colitis. Clarithromycin is excreted mainly through the liver. Therefore, care should be taken when using clarithromycin in patients with impaired liver function. Patients with moderate to severe renal impairment should also be careful when taking clarithromycin. Attention should also be paid to the possibility of cross-resistance between clarithromycin and other macrolides, lincomycin and clindamycin. The production of β -lactamase should not affect the activity of clarithromycin. Note: Most patients are resistant to neopenicillin I and clindamycin.
The safety of clarithromycin for pregnant and lactating women is not clear at 65,438+00. Pregnant women should use clarithromycin with caution, especially in the early pregnancy. Clarithromycin can be secreted from milk.
Children's medication/kloc-children over 0/2 years old, same as adults. /kloc-children under 0/2 years old, please use other varieties suitable for dosage forms.
The elderly drug researchers conducted an experiment to evaluate and compare the safety and pharmacokinetics of clarithromycin tablets with healthy elderly male and female subjects and healthy young adult male subjects. Compared with the young group, the plasma concentrations of drugs and circulating system 14- hydroxyl metabolism in the elderly group and the mother were higher and eliminated slowly. However, there was no difference between the two groups when the renal clearance rate was related to the creatinine clearance rate. Therefore, the disposal of clarithromycin in vivo is related to renal function.
The data show that clarithromycin is mainly metabolized by cytochrome P450 isoenzyme, which is an important mechanism that determines the interaction of many drugs. Under this mechanism, the metabolism of other drugs used with clarithromycin is inhibited. As a result, the drug concentration in serum increased. It is known or suspected that some or one of the following drugs are metabolized by the same CYP3A isoenzyme: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporine, propyramide, ergot alkaloid, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (such as warfarin) and aspirin. Zoran and vinblastine. Other drugs that interact with other isoenzymes in cytochrome P450 system are phenytoin, theophylline and sodium valproate.
Clinical studies showed that when theophylline or amidine was combined with clarithromycin, the circulating concentration increased slightly, but it was statistically significant (P≤0.05). When clarithromycin is combined with HMG-CoA reductase inhibitors (such as lovastatin and simvastatin), there are few reports of rhabdomyolysis. The combination of cisapride and clarithromycin will increase the blood concentration of cisapride in patients, leading to prolonged Q-T interval and arrhythmia, such as.
Macrolides can change the metabolism of terfenadine and increase its plasma concentration, accompanied by arrhythmia, such as prolonged Q-T interval, ventricular tachycardia, ventricular fibrillation and peak torsion (see contraindications). The study of 14 healthy volunteers found that the combination of clarithromycin and terfenadine could increase the plasma concentration of acidic metabolites of terfenadine by 2-3 times, which led to the prolongation of Q-T interval, but it did not.
A similar reaction was observed when astemizole was administered simultaneously with other macrolides. It has been reported after the market that when danclarithromycin is combined with quinidine or propyramide, there is a peak phenomenon. When Dancla mycin is used for treatment, the blood concentration of these drugs should be monitored. Interaction with other drugs will lead to an increase in the blood concentration of digoxin, so monitoring the blood concentration should be considered.
Interaction with antiretroviral drugs: Oral administration of clarithromycin tablets and zidovudine at the same time in adults infected with HIV will lead to a decrease in the steady-state plasma concentration of zidovudine, because clarithromycin seems to interfere with the absorption of zidovudine at the same time. So far, the above interaction has not occurred in pediatric patients infected with HIV. There is no similar study on the interaction between clarithromycin sustained-release tablets and zidovudine.
Pharmacokinetic studies showed that the combination of ritonavir (200mg, once every 8 hours) and clarithromycin (500mg, once every 65±438±02h hours) could significantly inhibit clarithromycin metabolites, and the Cmax, Cmin and AUC of clarithromycin increased by 365 438 0%, 65 438 082% and 77, respectively. The formation of 14-(R) hydroxyclarithromycin was obviously inhibited. Because of the large therapeutic window of clarithromycin, it is not necessary to reduce the dose when the patient's renal function is normal, but the dose of clarithromycin should be adjusted as follows: for patients with ClCR of 30~60ml/min, the dose of clarithromycin should be reduced by 50%. That is, the maximum daily dose is 1 clarithromycin sustained-release tablets. Patients with severely impaired renal function (ClCR less than 30ml/min) should not use clarithromycin sustained-release tablets because this product cannot reduce the dose. Clarithromycin tablets can be used in this population. When the daily dose of clarithromycin is greater than 1g, it should not be combined with ritonavir.
The side effects caused by excessive drug therapy should be eliminated in time and supportive treatment should be taken. Like other macrolides, hemodialysis or peritoneal dialysis can not reduce the blood concentration of clarithromycin.
Pharmacology and toxicology
Pharmacological action: Clarithromycin is a macrolide antibiotic. Its antibacterial effect is similar to erythromycin. Its mechanism of action is to inhibit the protein synthesis of microorganisms by binding to the 50S subunit on the ribosome of microorganisms. The product is effective against aerobic and anaerobic gram-positive and negative microorganisms in vitro. In addition, it is also effective for most Mycobacterium avium complex (MAC) microorganisms. Animal experiments in vitro and clinical infection treatment have confirmed that this product is active against the following microorganisms: aerobic gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes; Aerobic gram-negative microorganisms: Haemophilus influenzae, Legionella pneumophila and Moraxella catarrhalis.
Other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae, Mycobacterium, Mycobacterium avium complex (MAC) (including Mycobacterium avium and Mycobacterium avium intracellulare). In vitro tests show that this product is effective against Listeria monocytogenes. Staphylococcus (groups C, F and G); Bordetella pertussis; Propionibacterium acne is active. Bacteria resistant to other macrolide antibiotics are also resistant to this product. The microorganism producing β -lactamase is ineffective for this product. Most methicillin-resistant and oxacillin-resistant staphylococcus are also resistant to this product. Toxicological study on genotoxicity: The genotoxicity test results of standard combination show that this product has no mutagenic effect.
Reproductive toxicity: When the dose of this product in rats and rabbits is 265,438+0 and 4 times of the maximum recommended clinical dose (calculated by body surface area), it has no harm to animal fertility and fetus. The dose of CD-65,438+0 in mice is 65,438+000 mg/kg (calculated by body surface area, 8 times the maximum recommended dose for human use). Fetal weight loss, incomplete ossification and developmental retardation occurred. When rats took this product at a dose of 1000mg/kg two weeks before mating, during the whole mating period and during the whole pregnancy, the degree of ossification was also reduced. At present, there is no sufficiently strict controlled study on pregnant women, so we should weigh the advantages and disadvantages before deciding on the use of this product. It is not clear whether the product is secreted by human milk, but the milk of rodents and other large animals can be secreted.
Carcinogenicity: No research results show that this product is potentially carcinogenic to animals.
Pharmacokinetics The pharmacokinetic comparison of clarithromycin sustained-release tablets with 250mg and 500mg clarithromycin tablets showed that the absorption degree was the same under the same total daily dose. The absolute bioavailability of clarithromycin sustained-release tablets (compared with intravenous injection) is close to 50%. After repeated administration, the metabolic tendency of any species has not accumulated and changed.
In vitro: The results of in vitro study showed that the average binding rate of plasma protein was 70% at the concentration of 0.45~4.5mg/kg/ person. When the concentration reaches 45.0mg/ml, the binding rate drops to 465,438+0%, which means that the binding site may be saturated, but this only happens when the concentration is much higher than the effective concentration of therapeutic drugs. The pharmacokinetic behavior of clarithromycin is not linear. For patients who eat, 500 mg clarithromycin is given every day. The peak stable plasma concentrations of clarithromycin and 14- hydroxycclarithromycin were 1.3 and 0.48mg/ml respectively. When the daily dose increased to 1000mg, the steady-state values were 2.4mg/ml and 0.67mg/ml respectively. The elimination half-lives of parent drug (clarithromycin) and metabolite are about 5.3 hours and 7.7 hours, respectively. The half-life of clarithromycin is obviously prolonged. About 40% of clarithromycin is excreted in urine and 30% in feces. Clarithromycin and its 14- hydroxy metabolite are easily distributed in tissues and body fluids. Limited data obtained from a few patients showed that clarithromycin did not reach the effective concentration in cerebrospinal fluid (CSF) after oral administration. The CSF drug concentration of patients with normal blood-brain barrier is only 1~2% of serum concentration). The concentration of drugs in tissues is usually several times higher than that in serum. A study on patients with hepatic insufficiency compared a group of healthy subjects with a group of patients with hepatic insufficiency, taking clarithromycin tablets 250mg twice a day two days ago and 250mg once a day on the third day. Results There was no significant difference in the steady-state plasma concentration and systemic clearance rate of clarithromycin between the two groups. On the contrary, the concentration of 14- hydroxyclarithromycin in patients with hepatic insufficiency was significantly lower. The decrease of metabolic clearance rate of parent compound 14- hydroxylation was partially offset by the increase of renal clearance rate of parent drug. Therefore, subjects with abnormal liver function and healthy subjects have the same steady-state plasma concentration of maternal drugs. These results show that patients with moderate or severe liver dysfunction and normal renal function do not need to adjust the dose. Researchers with renal insufficiency conducted an experiment to evaluate and compare the pharmacokinetics of 500mg clarithromycin tablets after repeated oral administration in subjects with normal renal function and decreased renal function. Results: The plasma concentration, half-life, Cmax and Cmin of clarithromycin and its 14- hydroxy metabolite were higher in patients with renal insufficiency, while the AUC was higher, while the excretion of clindamycin and urine was lower. The more serious the renal function damage, the more significant the difference (see contraindication usage and dosage).