What is Clarithromycin?
Clarithromycin is the name of an antibiotic drug belonging to the macrolide family.
discovery
Clathromycin was developed by researchers at the Japanese pharmaceutical company Taisho Pharmaceutical in the 1970s. The discovery of clarithromycin was the result of research aimed at the development of an improved version of the progenitor of the macrolides, erythromycin; the latter, in fact, has various disadvantages, such as different side effects - such as nausea and stomach pains - and acid instability in the digestive tract. The pharmaceutical company requested authorization for clarithromycin in 1980 and after about ten years released the medicinal product under the registered name of Clarith ®. However, a few years earlier, in 1985, Taisho became a partner of the US pharmaceutical company Abbott Laboratories. In 1991, almost simultaneously with the launch of the drug in Japan, Abbott Laboratories launched the same specialty in the United States under the registered name of Biaxin ®. Clartithromycin became a generic drug in 2004 in Europe and the United States in 2005, so it can now be found as generic under the name of the molecule itself, ie clarithromycin, or under many fancy names, such as Macladin ®, Klacid ®, Soriclar ®, Veclam ®, Winclar ® etc.
Spectrum of action and Uses
The action spectrum of clarithromycin is the same as that of erythromycin, with the only difference that it is also active against Mycobacterium leprae and Mycobacterium avium .
Clarotromycin is a widely used antibiotic because it has a very broad spectrum of action, similar to that of penicillin; it can therefore be used in cases where beta-lactam antibiotics are not suitable.
Clarithromycin is used to treat diseases with bacterial etiology, such as various forms of tonsillitis, laryngitis, pharyngitis, chronic bronchitis, acute sinusitis, pneumonia and skin infections; clarithromycin is also one of the main drugs used in triple therapy to eradicate Helicobacter pylori.
Clarithromycin acts by binding to the 50S ribosomal bacterial unit, thus interfering with the protein synthesis of the pathogen: this involves stopping growth and multiplying the microbe, with regression of bacterial infection.
Clarithromycin: chemical structure
Posology and method of use
In the treatment of eradication of Helicobacter pylori through triple therapy, it is recommended to take 1500 mg of clarithromycin per day, divided into 3 daily administrations of 500 mg each, for a standard period of fourteen days.
For the treatment of sinusitis 1000 mg / day of clarithromycin are used, taken in two single administrations: one every 12 hours. The recommended treatment duration is two weeks.
To treat patients suffering from bronchitis it is recommended to use 500 mg of clarithromycin every 12 hours, for a period varying from seven to fourteen days. The recommended starting dose for patients with bronchitis caused by H. parainfluenzae is 500 mg of clarithromycin every 12 hours, for one week, while for patients with bronchitis caused by M.catarrhali or S.pneumaniae the recommended starting dose is 250 mg every 12 hours, for 7/14 days based on the individual pharmacological response.
The dose used for bacterial endocarditis prophylaxis is 500 mg of clarithromycin, to be administered one hour before surgery.
In the treatment of Legionella Pneumonia the recommended clarithromycin dose varies from 500 to 1000 mg / day, to be taken in two daily administrations, one every 12 hours, for about two weeks, depending on the severity of the infection.
In the treatment of skin infections or soft tissue infections, the recommended clarithromycin dose varies from 500 to 1000 mg / day, to be divided into two daily administrations for 7/14 days; both the dose and duration of treatment vary depending on the severity of the infection.
The recommended dose in the treatment of non-gonococcal urethritis ranges from 500 to 1000 mg of clarithromycin per day, to be divided into two daily administrations, one every 12 hours; the duration of the treatment can in this case vary from 3 to 7 days, always in relation to the nature and severity of the infection.
In the treatment of toxoplasmosis the recommended clarithromycin dose is 2000 mg / day, divided into two daily administrations, one every 12 hours. The recommended duration of treatment varies from 3 to 6 weeks, depending on the severity of the infection and the individual pharmacological response. It is recommended - after the conclusion of the treatment - a long lasting therapy with an appropriate drug.
In the treatment of otitis media and pharyngitis the recommended clarithromycin dose normally varies from 500 to 1000 mg / day, to be divided into two administrations, one every 12 hours. In cases where the bacterium Haemophilus influenzae is considered to be involved it is strongly recommended to use a dose of clarithromycin of 1000 mg / day. The recommended treatment duration is 10 to 14 days.
Also in the treatment of pneumonia (pneumonia) the recommended dose of clarithromycin varies from 500 to 1000 mg / day, taken in two administrations, one every 12 hours, with the recommendation to go up to 1000 mg / day if you have the etiological suspicion of Haemophilus influenzae. The recommended duration of treatment varies from 7 to 14 days when it comes to pneumonia from pneumococcus, and from 14 to 21 days for all other pathogens.
Contraindications and warnings
Clarithromycin is a potent inhibitor, and also a substrate, of the cytochrome P450 metabolizing enzyme system; in particular, clarithromycin inhibits the cytoromial isoenzyme CYP3A4. The cytochromial isoenzyme CYP3A4 is the enzyme of the cytochrome P450 family most represented in the intestine. The CYP3A subfamily contributes to the metabolism of about half of the drugs used by humans and represents about 30% of all cytochrome P450 isoenzymes.
Clarithromycin increases the plasma concentration of ergot alkaloids (ergotamine, ergotin, etc.) precisely due to the metabolic inhibition of the drug mediated by the cytochromial isoenzyme CYP3A4, thus increasing the risk of ischemic events and ergotism, which in some documented cases have had a serious outcome.
Clarithromycin could increase the plasma levels of some antiarrhythmics, such as amiodarone and quinidine, thus also increasing their toxic effects.
Particular attention is recommended in the treatment of patients who use antidepressants. Indeed, clarithromycin could increase - due to pharmacometabolic inhibition - the plasma levels of some antidepressants such as fluoxetine, imipramine, sertraline, amitriptyline and mirtazapine. In fact, in some patients treated with fluoxetine, the appearance of delirium and psychosis was noted after administration of clarithromycin. These effects have been attributed to the accumulation of fluoxetine due to the inhibition of its metabolism by joint intake of clarithromycin.
Also the plasma concentration of some antiepileptics, such as carbamazepine, phenytoin or felbamate, could increase following the administration of clarithromycin, again due to the aforementioned mechanism of pharmacometabolic inhibition. Concomitant administration of carbamazepine and clarithromycin has been studied in several clinical cases and the interaction between them is clinically significant. For example, it has been shown that in patients treated with 600 mg / day of carmbamazepine, excessive somnolence accompanied by vertigo occurred after administration of 400 mg / day of clarithromycin. Analyzing the plasma concentrations of carbamazepine following clarithromycin administration, a doubling of the antiepileptic concentration compared to normal was seen. Discontinuation of clarithromycin administration reported carbamazepine plasma levels within 5 days, and undesirable effects also disappeared after normalization of plasma levels.
Clarithromycin may increase plasma concentrations of some antipsychotics such as haloperidol, clozapine, quetiapine, risperidone and pimozide. In fact, in a pharmacometabolic interaction study between clarithromycin and pimozide, it was noted that in patients receiving clarithromycin after the administration of a single dose of pimozide the plasma level of the latter had risen by 39% compared to the norm. Since the interaction between clarithromycin and pimozide may also increase the risk of ventricular arrhythmias, it is advised not to use these drugs at the same time.
Concurrent administration of clarithromycin and calcium antagonists such as verapamil, nifedipine and diltiazem leads to an increase in plasma levels due to pharmacometabolic inhibition. Furthermore, clarithromycin and verapamil are both inhibitors of P-glycoprotein; not surprisingly, the simultaneous administration of these two drugs has led to the manifestation of hypotension and bradycardia, which is why it is advised to be especially careful when these drugs must be administered simultaneously.
Clarithromycin may increase the plasma concentration of many other drugs, among which the most important are the anticoagulant Warfarin, the 5-phosphodiesterase inhibitors (sildenafil, the active ingredient of Viagr, tadalafil and vardenafil, the active ingredient of Levitra), l cyclosporine immunosuppressant, the antiarrhythmic digoxin etc.
Clarithromycin is metabolised by the liver, so care must be taken in administering the drug to patients with impaired liver function. Furthermore, clarithromycin, like all macrolide antibiotics, may worsen myasthenia gravis, therefore it is recommended to administer it with care in patients with this disease.
Pregnancy and breastfeeding
Clarithromycin is believed to be unsuitable for use in pregnancy. Several animal studies have indeed shown that during use during pregnancy adverse effects on the fetus occurred, such as the incidence of cardiovascular abnormalities and palate cracking; however, it should be emphasized that in these studies the doses used were 2 to 17 times greater than the plasma levels reached during treatment in humans. In fact, another multi-field study conducted on about 150 pregnant women - being treated with clarithromycin - has not shown any effects on the fetus or pregnancy. In another study, however, about 120 pregnant women underwent clarithromycin treatment during the first six months of gestation; it was observed that the incidence of major or minor congenital malformations remained the same as the standard one, while the incidence of spontaneous abortion was greater than normal; the authors of the study believe that this data is the result of other factors that were not included in their study. At the base of these studies, as a precautionary measure the manufacturers of the drug advise against the use of clarithromycin during pregnancy, except in cases where there are no other possibilities of treatment; in these circumstances the possibility of damage to the fetus must be taken into consideration.
In several studies on mothers who used clarithromycin during lactation it was found that the latter is excreted in breast milk. Based on this study it was calculated that the newborn receives about 2% of the dose taken by the mother; in about 12% of breast-fed children, undesirable effects such as loss of appetite, drowsiness and diarrhea occurred. Therefore, during lactation it is recommended to use clarithromycin only when the benefits to the mother outweigh the potential risks to the baby.
Side and unwanted effects
The most commonly observed undesirable effects during clarithromycin administration involve the gastrointestinal tract: diarrhea, nausea, dyspepsia, abdominal pain, stomatitis, glossitis, reversible discoloration of the tongue and changes in taste. In the second analysis we can mention the side effects related to the central nervous system, such as headache and migraines. As regards the hepatic system, an increase in transaminases has been noted, which tend to normalize after the end of treatment; furthermore, very rare cases of hepatic failure with severe outcome have been reported in patients with pre-existing liver failure. Other minor side effects due to incidence affect the cardiovascular system and include palpitations, arrhythmia, ventricular tachycardia and prolongation of the QTc interval. Finally we can mention the dermatological and systemic side effects of clarithromycin, such as erythema, skin rash, edema, urticaria, Stevens-Johnson syndrome and pancreatitis.
