Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.
Proper storage of Clarimicina extended-release tablets:
Store Clarimicina extended-release tablets at room temperature, between 68 and 77 degrees F (20 and 25 degrees C), in a well-closed container. Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from light, heat, and moisture. Do not store in the bathroom. Keep Clarimicina extended-release tablets out of the reach of children and away from pets.
Overdose of Clarimicina in details
When a dose is taken in higher dose than the recommended doses, it is called Overdose. Overdose always needs a clinical supervision. Any medicine or drug when consumed in Overdose produces untoward side effects on one or various organs in the body. A medicine is excreted in the kidney or metabolized in the liver most of the times. This process goes without any hurdles when taken in normal dose, but when taken in an overdose, the body is not able to metabolize it or send it out properly which causes the effects of anoverdose.
Symptoms: Reports indicate that the ingestion of large amounts of Clarimicina can be expected to produce gastrointestinal symptoms. One patient who had a history of bipolar disorder ingested Clarimicina 8 g and showed altered mental status, paranoid behaviour, hypokalemia and hypoxemia.
Treatment: Adverse reactions accompanying overdosage should be treated by the prompt elimination of unabsorbed drug and supportive measures. Allergic reactions accompanying overdosage should be treated by gastric lavage and supportive measures. As with other macrolides, Clarimicina serum levels are not expected to be appreciably affected by haemodialysis or peritoneal dialysis.
What should I avoid while taking Clarimicina?
Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, stop taking Clarimicina and call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.
Warnings are a mix of Precautions. Contraindications and interactions and serious harmful effects associated with the medicine intake. A diabetic or Hypertensive patient need to be warned about few drug interactions. A known hypersensitivity patient needs to be careful about the reactions or anaphylactic shock. A pregnant woman or a breastfeeding woman should be warned of certain medications. A Hepatitis [liver disease] patient or a cardiac patient should avoid few drugs.
Use in Pregnancy
Clarimicina SHOULD NOT BE USED IN PREGNANT WOMEN EXCEPT IN CLINICAL CIRCUMSTANCES WHERE NO ALTERNATIVE THERAPY IS APPROPRIATE. IF PREGNANCY OCCURS WHILE TAKING THIS DRUG, THE PATIENT SHOULD BE APPRISED OF THE POTENTIAL HAZARD TO THE FETUS. Clarimicina HAS DEMONSTRATED ADVERSE EFFECTS OF PREGNANCY OUTCOME AND/OR EMBRYO-FETAL DEVELOPMENT IN MONKEYS, RATS, MICE, AND RABBITS AT DOSES THAT PRODUCED PLASMA LEVELS 2 TO 17 TIMES THE SERUM LEVELS ACHIEVED IN HUMANS TREATED AT THE MAXIMUM RECOMMENDED HUMAN DOSES.
Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported with Clarimicina. This hepatic dysfunction may be severe and is usually reversible. In some instances, hepatic failure with fatal outcome has been reported and generally has been associated with serious underlying diseases and/or concomitant medications. Symptoms of hepatitis can include anorexia, jaundice, dark urine, pruritus, or tender abdomen. Discontinue Clarimicina immediately if signs and symptoms of hepatitis occur.
Clarimicina has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during post-marketing surveillance in patients receiving Clarimicina. Fatalities have been reported. Clarimicina should be avoided in patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval.
Serious adverse reactions have been reported in patients taking Clarimicina concomitantly with CYP3A4 substrates. These include colchicine toxicity with colchicine; rhabdomyolysis with simvastatin, lovastatin, and atorvastatin; hypoglycemia with disopyramide; and hypotension and acute kidney injury with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem, nifedipine). Most reports of acute kidney injury with calcium channel blockers metabolized by CYP3A4 involved elderly patients 65 years of age or older. Clarimicina should be used with caution when administered concurrently with medications that induce the cytochrome CYP3A4 enzyme.
Life-threatening and fatal drug interactions have been reported in patients treated with Clarimicina and colchicine. Clarimicina is a strong CYP3A4 inhibitor and this interaction may occur while using both drugs at their recommended doses. If co-administration of Clarimicina and colchicine is necessary in patients with normal renal and hepatic function, the dose of colchicine should be reduced. Patients should be monitored for clinical symptoms of colchicine toxicity. Concomitant administration of Clarimicina and colchicine is contraindicated in patients with renal or hepatic impairment.
Increased sedation and prolongation of sedation have been reported with concomitant administration of Clarimicina and triazolobenzodiazepines, such as triazolam, and midazolam.
Use quetiapine and Clarimicina concomitantly with caution. Co-administration could result in increased quetiapine exposure and quetiapine related toxicities such as somnolence, orthostatic hypotension, altered state of consciousness, neuroleptic malignant syndrome, and QT prolongation. Refer to quetiapine prescribing information for recommendations on dose reduction if co-administered with CYP3A4 inhibitors such as Clarimicina.
Oral Hypoglycemic Agents/Insulin
The concomitant use of Clarimicina and oral hypoglycemic agents and/or insulin can result in significant hypoglycemia. With certain hypoglycemic drugs such as nateglinide, pioglitazone, repaglinide and rosiglitazone, inhibition of CYP3A enzyme by Clarimicina may be involved and could cause hypoglycemia when used concomitantly. Careful monitoring of glucose is recommended.
There is a risk of serious hemorrhage and significant elevations in INR and prothrombin time when Clarimicina is co-administered with warfarin. INR and prothrombin times should be frequently monitored while patients are receiving Clarimicina and oral anticoagulants concurrently.
HMG-CoA Reductase Inhibitors (statins)
Concomitant use of Clarimicina with lovastatin or simvastatin is contraindicated as these statins are extensively metabolized by CYP3A4, and concomitant treatment with Clarimicina increases their plasma concentration, which increases the risk of myopathy, including rhabdomyolysis. Cases of rhabdomyolysis have been reported in patients taking Clarimicina concomitantly with these statins. If treatment with Clarimicina cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment.
Caution should be exercised when prescribing Clarimicina with statins. In situations where the concomitant use of Clarimicina with atorvastatin or pravastatin cannot be avoided, atorvastatin dose should not exceed 20 mg daily and pravastatin dose should not exceed 40 mg daily. Use of a statin that is not dependent on CYP3A metabolism (e.g. fluvastatin) can be considered. It is recommended to prescribe the lowest registered dose if concomitant use cannot be avoided.
Clostridium difficile Associated Diarrhea
Clostridium difficileassociated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Clarimicina, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Acute Hypersensitivity Reactions
In the event of severe acute hypersensitivity reactions, such as anaphylaxis, Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), and Henoch-Schonlein purpura Clarimicina therapy should be discontinued immediately and appropriate treatment should be urgently initiated.
Combination therapy with other drugs
For information about warnings of other drugs indicated in combination with Clarimicina, refer to the WARNINGS section of their package inserts.
What should I discuss with my healthcare provider before taking Clarimicina?
Some medical conditions may interact with Clarimicina suspension. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
if you are pregnant, planning to become pregnant, or are breast-feeding
if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
if you have allergies to medicines, foods, or other substances
if you have the blood disorder porphyria, kidney problems, liver problems, or myasthenia gravis
if you have a history of heart problems (eg, fast, slow, or irregular heartbeat) or low blood potassium or magnesium levels
if you are taking any medicine that may increase the risk of a certain type of irregular heartbeat (prolonged QT interval). Check with your doctor or pharmacist if you are unsure if any of your medicines may increase the risk of this type of irregular heartbeat
Some MEDICINES MAY INTERACT with Clarimicina suspension. Tell your health care provider if you are taking any other medicines, especially any of the following:
Many prescription and nonprescription medicines (eg, used for abortion, allergies, anxiety, asthma or other lung or breathing problems, blood thinning, blood vessel problems, cancer, Cushing syndrome, cystic fibrosis, decreased blood clot formation, depression or other mental or mood problems, diabetes, enlarged prostate, erectile dysfunction, gout, hepatitis C infection, high blood pressure, high cholesterol, high prolactin levels, HIV, Huntington chorea, immune system suppression, infections, inflammation, irregular heartbeat or other heart problems, migraines, myelofibrosis, narcotic addiction, nausea and vomiting, pain, parathyroid problems, pulmonary arterial hypertension [PAH], overactive bladder, seizures, sleep, stomach or bowel problems, Tourette syndrome), multivitamin products, and herbal or dietary supplements because they may interact with Clarimicina suspension. Ask your doctor or pharmacist if you are unsure if any of your medicines might interfere with Clarimicina suspension.
This may not be a complete list of all interactions that may occur. Ask your health care provider if Clarimicina suspension may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Certain people who are very sick or very old or who are sensitive show an exacerbation of side effect of the drug which can turn dangerous at times. So, it is very important to remember the precautions while taking the medicine. Pregnancy and Breastfeeding are also special categories wherein extra care or precaution is needed when taking a drug. Few patients may have a hypersensitivity reaction to few medications, and that can be life-threatening rarely. Penicillin hypersensitivity is one example. Diarrhea, rashes are few other symptoms which need a watch. A patient with other co-existing diseases like liver disease, heart disease, kidney disease should take special precautions.
Prescribing Clarimicina in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Clarimicina is principally excreted via the liver and kidney. Clarimicina may be administered without dosage adjustment to patients with hepatic impairment and normal renal function. However, in the presence of severe renal impairment with or without coexisting hepatic impairment, decreased dosage or prolonged dosing intervals may be appropriate.
Clarimicina in combination with ranitidine bismuth citrate therapy is not recommended in patients with creatinine clearance less than 25 mL/min.
Clarimicina in combination with ranitidine bismuth citrate should not be used in patients with a history of acute porphyria.
Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome has been reported in patients receiving Clarimicina therapy.
For information about precautions of other drugs indicated in combination with Clarimicina, refer to the PRECAUTIONS section of their package inserts.
Information to patients
Patients should be counseled that antibacterial drugs including Clarimicina for oral suspension should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Clarimicina is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Clarimicina or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
Clarimicina may interact with some drugs; therefore patients should be advised to report to their doctor the use of any other medications.
Clarimicina for oral suspension can be taken with or without food and can be taken with milk. Do NOT refrigerate the suspension.
Clarimicina use in patients who are receiving theophylline may be associated with an increase of serum theophylline concentrations. Monitoring of serum theophylline concentrations should be considered for patients receiving high doses of theophylline or with baseline concentrations in the upper therapeutic range. 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%.
Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent verapamil, belonging to the calcium channel blockers drug class.
Concomitant administration of single doses of Clarimicina and carbamazepine has been shown to result in increased plasma concentrations of carbamazepine. Blood level monitoring of carbamazepine may be considered.
When Clarimicina and terfenadine were coadministered, plasma concentrations of the active acid metabolite of terfenadine were threefold higher, on average, than the values observed when terfenadine was administered alone. The pharmacokinetics of Clarimicina and the 14-OH-Clarimicina were not significantly affected by coadministration of terfenadine once Clarimicina reached steady-state conditions. Concomitant administration of Clarimicina with terfenadine is contraindicated.
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 t1/2 increases of 30%, 89%, and 34%, respectively), by the concomitant administration of Clarimicina. The mean 24-hour gastric pH value was 5.2 when omeprazole was administered alone and 5.7 when coadministered with Clarimicina.
Coadministration of Clarimicina with ranitidine bismuth citrate resulted in increased plasma ranitidine concentrations (57%), increased plasma bismuth trough concentrations (48%), and increased 14-hydroxy-Clarimicina plasma concentrations (31%). These effects are clinically insignificant.
Simultaneous oral administration of Clarimicina tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations. 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). Administration of Clarimicina and zidovudine should be separated by at least two hours. The impact of co-administration of Clarimicina extended-release tablets and zidovudine has not been evaluated.
Simultaneous administration of Clarimicina tablets and didanosine to 12 HIV-infected adult patients resulted in no statistically significant change in didanosine pharmacokinetics.
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. Steady-state concentrations of 14-OH Clarimicina were not significantly affected by concomitant administration of fluconazole. No dosage adjustment of Clarimicina is necessary when co-administered with fluconazole.
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. Clarimicina may be administered without dosage adjustment to patients with normal renal function taking ritonavir. Since concentrations of 14-OH Clarimicina are significantly reduced when Clarimicina is co-administered with ritonavir, alternative antibacterial therapy should be considered for indications other than infections due to Mycobacterium avium complex. Doses of Clarimicina greater than 1000 mg per day should not be co-administered with protease inhibitors.
Spontaneous reports in the post-marketing period suggest that concomitant administration of Clarimicina and oral anticoagulants may potentiate the effects of the oral anticoagulants. Prothrombin times should be carefully monitored while patients are receiving Clarimicina and oral anticoagulants simultaneously.
Digoxin is a substrate for P-glycoprotein (Pgp) and Clarimicina is known to inhibit Pgp. When Clarimicina and digoxin are co-administered, inhibition of Pgp by Clarimicina may lead to increased exposure of digoxin. Elevated digoxin serum concentrations in patients receiving Clarimicina and digoxin concomitantly have been reported in post-marketing surveillance. Some patients have shown clinical signs consistent with digoxin toxicity, including potentially fatal arrhythmias. Monitoring of serum digoxin concentrations should be considered, especially for patients with digoxin concentrations in the upper therapeutic range.
Co-administration of Clarimicina, known to inhibit CYP3A, and a drug primarily metabolized by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both therapeutic and adverse effects of the concomitant drug.
Clarimicina should be used with caution in patients receiving treatment with other drugs known to be CYP3A enzyme substrates, especially if the CYP3A substrate has a narrow safety margin (e.g., carbamazepine) and/or the substrate is extensively metabolized by this enzyme. Dosage adjustments may be considered, and when possible, serum concentrations of drugs primarily metabolized by CYP3A should be monitored closely in patients concurrently receiving Clarimicina.
The following are examples of some clinically significant CYP3A based drug interactions. Interactions with other drugs metabolized by the CYP3A isoform are also possible.
Carbamazepine and Terfenadine
Increased serum concentrations of carbamazepine and the active acid metabolite of terfenadine were observed in clinical trials with Clarimicina.
Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein (Pgp). Clarimicina and other macrolides are known to inhibit CYP3A and Pgp. 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. The dose of colchicine should be reduced when co-administered with Clarimicina in patients with normal renal and hepatic function. Concomitant use of Clarimicina and colchicine is contraindicated in patients with renal or hepatic impairment.
Efavirenz, Nevirapine, Rifampicin, Rifabutin, and Rifapentine
Inducers of CYP3A enzymes, such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine will increase the metabolism of Clarimicina, thus decreasing plasma concentrations of Clarimicina, while increasing those of 14-OH-Clarimicina. Since the microbiological activities of Clarimicina and 14-OH-Clarimicina are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of Clarimicina and enzyme inducers. Alternative antibacterial treatment should be considered when treating patients receiving inducers of CYP3A. Concomitant administration of rifabutin and Clarimicina resulted in an increase in rifabutin, and decrease in Clarimicina serum levels together with an increased risk of uveitis.
Clarimicina exposure was decreased by etravirine; however, concentrations of the active metabolite, 14-OH-Clarimicina, were increased. Because 14-OH-Clarimicina has reduced activity against Mycobacterium avium complex (MAC), overall activity against this pathogen may be altered; therefore alternatives to Clarimicina should be considered for the treatment of MAC.
Sildenafil, Tadalafil, and Vardenafil
Each of these phosphodiesterase inhibitors is primarily metabolized by CYP3A, and CYP3A will be inhibited by concomitant administration of Clarimicina. Co-administration of Clarimicina with sildenafil, tadalafil, or vardenafil will result in increased exposure of these phosphodiesterase inhibitors. Coadministration of these phosphodiesterase inhibitors with Clarimicina is not recommended.
The primary route of metabolism for tolterodine is via CYP2D6. However, in a subset of the population devoid of CYP2D6, the identified pathway of metabolism is via CYP3A. In this population subset, inhibition of CYP3A results in significantly higher serum concentrations of tolterodine. Tolterodine 1 mg twice daily is recommended in patients deficient in CYP2D6 activity (poor metabolizers) when co-administered with Clarimicina.
When a single dose of midazolam was co-administered with Clarimicina tablets (500 mg twice daily for 7 days), midazolam AUC increased 174% after intravenous administration of midazolam and 600% after oral administration. When oral midazolam is co-administered with Clarimicina, dose adjustments may be necessary and possible prolongation and intensity of effect should be anticipated. Caution and appropriate dose adjustments should be considered when triazolam or alprazolam is co-administered with Clarimicina. For benzodiazepines which are not metabolized by CYP3A (e.g., temazepam, nitrazepam, lorazepam), a clinically important interaction with Clarimicina is unlikely.
There have been post-marketing reports of drug interactions and central nervous system (CNS) effects (e.g., somnolence and confusion) with the concomitant use of Clarimicina and triazolam. Monitoring the patient for increased CNS pharmacological effects is suggested.
Both Clarimicina and atazanavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction. 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%. When Clarimicina is co-administered with atazanavir, the dose of Clarimicina should be decreased by 50%. Since concentrations of 14-OH Clarimicina are significantly reduced when Clarimicina is co-administered with atazanavir, alternative antibacterial therapy should be considered for indications other than infections due to Mycobacterium avium complex. Doses of Clarimicina greater than 1000 mg per day should not be co-administered with protease inhibitors.
Both Clarimicina and itraconazole are substrates and inhibitors of CYP3A, potentially leading to a bi-directional drug interaction when administered concomitantly. Clarimicina may increase the plasma concentrations of itraconazole, while itraconazole may increase the plasma concentrations of Clarimicina. Patients taking itraconazole and Clarimicina concomitantly should be monitored closely for signs or symptoms of increased or prolonged adverse reactions.
Both Clarimicina and saquinavir are substrates and inhibitors of CYP3A and there is evidence of a bi-directional drug interaction. 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. No dose adjustment of Clarimicina is necessary when Clarimicina is co-administered with saquinavir in patients with normal renal function. When saquinavir is co-administered with ritonavir, consideration should be given to the potential effects of ritonavir on Clarimicina (refer to interaction between Clarimicina and ritonavir).
The following CYP3A based drug interactions have been observed with erythromycin products and/or with Clarimicina in post-marketing experience:
There have been post-marketing reports of torsades de pointes occurring with concurrent use of Clarimicina and quinidine or disopyramide. Electrocardiograms should be monitored for QTc prolongation during coadministration of Clarimicina with these drugs. Serum concentrations of these medications should also be monitored.
There have been post marketing reports of hypoglycemia with the concomitant administration of Clarimicina and disopyramide. Therefore, blood glucose levels should be monitored during concomitant administration of Clarimicina and disopyramide.
Post-marketing reports indicate that coadministration of Clarimicina with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system. Concomitant administration of Clarimicina with ergotamine or dihydroergotamine is contraindicated.
Triazolobenziodiazepines (Such as Triazolam and Alprazolam) and Related Benzodiazepines (Such as Midazolam)
Erythromycin has been reported to decrease the clearance of triazolam and midazolam, and thus, may increase the pharmacologic effect of these benzodiazepines. There have been post-marketing reports of drug interactions and CNS effects (e.g., somnolence and confusion) with the concomitant use of Clarimicina and triazolam.
Quetiapine is a substrate for CYP3A4, which is inhibited by Clarimicina. Co-administration with Clarimicina could result in increased quetiapine exposure and possible quetiapine related toxicities. There have been post-marketing reports of somnolence, orthostatic hypotension, altered state of consciousness, neuroleptic malignant syndrome, and QT prolongation during concomitant administration, Refer to quetiapine prescribing information for recommendations on dose reduction if co-administered with CYP3A4 inhibitors such as Clarimicina.
Erythromycin has been reported to increase the systemic exposure (AUC) of sildenafil. A similar interaction may occur with Clarimicina; reduction of sildenafil dosage should be considered.
There have been spontaneous or published reports of CYP3A based interactions of erythromycin and/or Clarimicina with cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, cilostazol, bromocriptine, vinblastine, phenobarbital and St. John’s Wort.
Concomitant administration of Clarimicina with cisapride, pimozide, astemizole, or terfenadine is contraindicated.
In addition, there have been reports of interactions of erythromycin or Clarimicina with drugs not thought to be metabolized by CYP3A including hexobarbital, phenytoin, and valproate.
Carcinogenesis, Mutagenesis, Impairment of Fertility
The following in vitro mutagenicity tests have been conducted with Clarimicina:
Salmonella/Mammalian Microsomes Test
Bacterial Induced Mutation Frequency Test
In Vitro Chromosome Aberration Test
Rat Hepatocyte DNA Synthesis Assay
Mouse Lymphoma Assay
Mouse Dominant Lethal Study
Mouse Micronucleus Test
All tests had negative results except the In Vitro Chromosome Aberration Test which was weakly positive in one test and negative in another.
In addition, a Bacterial Reverse-Mutation Test (Ames Test) has been performed on Clarimicina metabolites with negative results.
Fertility and reproduction studies have shown that daily doses of up to 160 mg/kg/day (1.3 times the recommended maximum human dose based on mg/m2) to male and female rats caused no adverse effects on the estrous cycle, fertility, parturition, or number and viability of offspring. Plasma levels in rats after 150 mg/kg/day were 2 times the human serum levels.
In the 150 mg/kg/day monkey studies, plasma levels were 3 times the human serum levels. When given orally at 150 mg/kg/day (2.4 times the recommended maximum human dose based on mg/m2), Clarimicina was shown to produce embryonic loss in monkeys. This effect has been attributed to marked maternal toxicity of the drug at this high dose.
In rabbits, in utero fetal loss occurred at an intravenous dose of 33 mg/m2, which is 17 times less than the maximum proposed human oral daily dose of 618 mg/m2.
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Clarimicina.
Pregnancy Category C
Four teratogenicity studies in rats (three with oral doses and one with intravenous doses up to 160 mg/kg/day administered during the period of major organogenesis) and two in rabbits at oral doses up to 125 mg/kg/day (approximately 2 times the recommended maximum human dose based on mg/m2) or intravenous doses of 30 mg/kg/day administered during gestation days 6 to 18 failed to demonstrate any teratogenicity from Clarimicina. Two additional oral studies in a different rat strain at similar doses and similar conditions demonstrated a low incidence of cardiovascular anomalies at doses of 150 mg/kg/day administered during gestation days 6 to 15. Plasma levels after 150 mg/kg/day were 2 times the human serum levels. Four studies in mice revealed a variable incidence of cleft palate following oral doses of 1000 mg/kg/day (2 and 4 times the recommended maximum human dose based on mg/m2, respectively) during gestation days 6 to 15. Cleft palate was also seen at 500 mg/kg/day. The 1000 mg/kg/day exposure resulted in plasma levels 17 times the human serum levels. In monkeys, an oral dose of 70 mg/kg/day (an approximate equidose of the recommended maximum human dose based on mg/m2) produced fetal growth retardation at plasma levels that were 2 times the human serum levels.
There are no adequate and well-controlled studies in pregnant women. Clarimicina should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Clarimicina and its active metabolite 14-hydroxy Clarimicina are excreted in human milk. Serum and milk samples were obtained after 3 days of treatment, at steady state, from one published study of 12 lactating women who were taking Clarimicina 250 mg orally twice daily. Based on the limited data from this study, and assuming milk consumption of 150 mL/kg/day, an exclusively human milk fed infant would receive an estimated average of 136 mcg/kg/day, of Clarimicina and its active metabolite, with this maternal dosage regimen. This is less than 2% of the maternal weight-adjusted dose (7.8 mg/kg/day, based on the average material weight of 64 kg), and less than 1% of the pediatric dose (15 mg/kg/day) for children greater than 6 months of age.
A prospective observational study of 55 breastfed infants of mothers taking a macrolide antibiotic (6 were exposed to Clarimicina) were compared to 36 breastfed infants of mothers taking amoxicillin. Adverse reactions were comparable in both groups. Adverse reactions occurred in 12.7% of infants exposed to macrolides and included rash, diarrhea, loss of appetite, and somnolence.
Caution should be exercised when Clarimicina is administered to nursing women. The development and health benefits of human milk feeding should be considered along with the mother’s clinical need for Clarimicina and any potential adverse effects on the human milk fed child from the drug or from the underlying maternal condition.
Safety and effectiveness of Clarimicina in pediatric patients under 6 months of age have not been established. The safety of Clarimicina has not been studied in MAC patients under the age of 20 months. Neonatal and juvenile animals tolerated Clarimicina in a manner similar to adult animals. Young animals were slightly more intolerant to acute overdosage and to subtle reductions in erythrocytes, platelets and leukocytes but were less sensitive to toxicity in the liver, kidney, thymus, and genitalia.
In a steady-state study in which healthy elderly subjects (age 65 to 81 years old) were given 500 mg every 12 hours, the maximum serum concentrations and area under the curves of Clarimicina and 14-OH Clarimicina were increased compared to those achieved in healthy young adults. These changes in pharmacokinetics parallel known age-related decreases in renal function. In clinical trials, elderly patients did not have an increased incidence of adverse events when compared to younger patients. Dosage adjustment should be considered in elderly patients with severe renal impairment. Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients.
Most reports of acute kidney injury with calcium channel blockers metabolized by CYP3A4 (e.g. verapamil, amlodipine, diltiazem, nifedipine) involved elderly patients 65 years of age or older.
What happens if I miss a dose of Clarimicina?
When you miss a dose, you should take it as soon as you remember, but you should take care that it should be well spaced from the next dose. You should not take an extra dose at the time of the second dose as it will become a double dose. The double dose can give unwanted side effects, so be careful. In chronic conditions or when you have a serious health issue, if you miss a dose, you should inform your health care provider and ask his suggestion.
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
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).