Lancid Kit, a set of tablets and capsules 56 pcs.

How to take, the dosage

Ingestion. Take 500 mg (1 tablet) of clarithromycin, 1000 mg of amoxicillin (2 capsules), and 30 mg of lansoprazole (1 capsule), twice daily, morning and evening before meals.

The tablets and capsules must not be crushed or chewed, they should be swallowed whole. The duration of treatment is 7 days; if necessary, it may be increased up to 14 days.

Each blister of Lancid® Kit contains two tablets of clarithromycin (500 mg), four capsules of amoxicillin (500 mg) and two capsules of lansoprazole (30 mg) and is designed for one day of treatment. One package contains 7 blisters and is designed for one course of treatment.

Interaction

Clarithromycin

The co-administration of clarithromycin and drugs that are primarily metabolized by CYP3A isoenzymes may result in increased concentrations, which may increase or prolong both therapeutic and adverse effects. Co-administration with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, alprazolam, midazolam, triazolam is contraindicated.

. Use with caution with carbamazepine, cilostazol, cyclosporine, disopyramide, lovastatin, methylprednisolone, omeprazole, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, vinblastine, phenytoin, theophylline and valproic acid (metabolized through other cytochrome P450 isoenzymes). Correction of the dose of drugs and monitoring of plasma concentrations is necessary.

Clarithromycin may decrease clearance of triazolam and thus increase its pharmacological effects with development of drowsiness and confusion.

For benzodiazepines whose excretion is not dependent on CYP3A4 isoenzymes (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely.

There have been reports of increased plasma concentrations of digoxin in patients receiving digoxin and clarithromycin concomitantly. Plasma digoxin concentrations should be monitored continuously to avoid digoxin intoxication and potentially fatal arrhythmias.

The concomitant use with ergotamine and dihydroergotamine (ergot derivatives) may lead to acute ergotamine intoxication manifesting as severe peripheral vasospasm, ischemia of the extremities and other tissues, including the central nervous system, and perverse sensitivity.

In concomitant administration of clarithromycin with HMG-CoA reductase inhibitors lovastatin and simvastatin, rare cases of rhabdomyolysis have been described.

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine (cytochrome P450 inducers) decrease the plasma concentration of clarithromycin and impair its therapeutic effect, and at the same time increase the concentration of 14(R)-hydroxyclarithromycin.

The co-administration of fluconazole 200 mg and clarithromycin 1 g/day may increase equilibrium concentration and AUC of clarithromycin by 33% and 18%, respectively. No clarithromycin dose adjustment is required.

Possible cross-resistance between clarithromycin and other macrolide antibiotics and lincomycin and clindamycin should be noted.

The concomitant administration of clarithromycin and zidovudine in adult HIV-infected patients may result in lower equilibrium levels of zidovudine. Doses of clarithromycin and zidovudine should be adjusted.

The concomitant administration of clarithromycin and ritonavir, atazanavir or other protease inhibitors increases plasma concentrations of both clarithromycin, which should then not be prescribed in doses over 1 g/day, and the protease inhibitor.

When clarithromycin and itraconazole are coadministered, both drugs may have increased plasma concentrations. Patients taking itraconazole and clarithromycin concomitantly should be monitored closely due to possible intensification or prolongation of pharmacological effects of these drugs.

Concomitant administration of clarithromycin (1 g/day) and saquinavir (soft gelatin capsules, 1200 mg 3 times daily) may increase AUC and equilibrium concentration of saquinavir by 177 and 187%, respectively, and clarithromycin by 40%. No dose adjustments are required when these two drugs are co-administered for a limited time in the doses/drug forms indicated above. Since coadministration of colchicine, which is a substrate for CYP3A and P-glycoprotein, and clarithromycin, as well as other macrolide inhibitors of CYP3A and P-glycoprotein, may lead to increased effects of colchicine, patients should be closely monitored to detect symptoms of toxic effects of colchicine. When using clarithromycin with tolterodine in patients with low CYP2D6 isoenzyme activity, a dose reduction of tolterodine in the presence of clarithromycin (CYP3A isoenzyme inhibitor) may be required.

The co-administration of clarithromycin with verapamil may result in decreased blood pressure, bradyarrhythmia and lactic acidosis.

The use of etravirine decreases the concentration of clarithromycin but increases the concentration of the active metabolite 14(R)-hydroxyclarithromycin.

When clarithromycin and oral hypoglycemic agents and/or insulin are coadministered, severe hypoglycemia may occur. Concomitant use of clarithromycin and some glucose-lowering drugs such as nateglinide, pioglitazone, repaglinide and rosiglitazone may result in inhibition of CYP3A isoenzyme by clarithromycin, which may lead to hypoglycemia. Close monitoring of glucose concentration is recommended.

Amoxicillin

Antacids, glucosamine, laxatives, aminoglycosides, food slow down and decrease absorption of amoxicillin; ascorbic acid increases absorption.

Probenecid reduces excretion of amoxicillin by the kidneys and increases the concentration of amoxicillin in bile and plasma. Bactericidal antibiotics (including aminoglycosides, cephalosporins, vancomycin, rifampicin) – synergistic effect; bacteriostatic drugs (macrolides, chloramphenecol, lincosamides, tetracyclines, sulfonamides) – antagonistic.

When taking amoxicillin in combination with metronidazole, nausea, vomiting, anorexia, diarrhea, constipation, epigastric pain, digestive disorders, in rare cases jaundice, interstitial nephritis, hematopoiesis disorders are observed.

Amoxicillin increases the effectiveness of indirect anticoagulants (by inhibiting intestinal microflora, reduces the synthesis of vitamin K and prothrombin index), which leads to prolongation of blood clotting time. If necessary, adjust the dose of indirect anticoagulants. Concomitant use of amoxicillin and allopurinol increases the risk of skin rash.

Amoxicillin decreases clearance and increases toxicity of methotrexate, probably due to competitive inhibition of renal tubular secretion of methotrexate by amoxicillin. In patients receiving amoxicillin and methotrexate concomitantly, plasma concentrations of the latter should be carefully monitored. Increased absorption time of digoxin during amoxicillin therapy is possible. If necessary, the dose of digoxin shall be adjusted.

Diuretics, allopurinol, oxyphenbutazone, phenylbutazone, nonsteroidal anti-inflammatory drugs and other drugs that block tubular secretion increase the plasma concentration of amoxicillin.

Amoxicillin decreases plasma concentrations of estrogens and progesterones, which can lead to loss of contraceptive effect of oral contraceptives. During treatment with amoxicillin, additional non-hormonal methods of contraception should be used.

Lansoprazole

Lansoprazole slows the elimination of drugs that are metabolized in the liver by microsomal oxidation (including diazepam, phenytoin, indirect anticoagulants).

Decreases the clearance of theophylline by 10%.

Inhibits pH-dependent absorption of drugs belonging to the weak acid groups and accelerates absorption of drugs belonging to the base groups.

Inhibits absorption of ketoconazole, itraconazole, ampicillin, iron salts, digoxin.

Lansoprazole slows absorption of cyanocobalamin.

Compatible with ibuprofen, indomethacin, diazepam, propranololol, warfarin, oral contraceptives, phenytoin, prednisolone. Sucralfate decreases bioavailability of lansoprazole by 30%, therefore it is necessary to observe an interval between the intake of these drugs of 30-40 minutes.

Antacids should be prescribed 1 hour before or 1-2 hours after taking lansoprazole, because they slow down and decrease its absorption.

In volunteers who received 60 mg of lansoprazole and 400 mg of atazanavir concomitantly per day, there was a 90% reduction in AUC and Cmax of the latter. Lansoprazole should not be administered concomitantly with atazanavir.

Ritonavir (a CYP2C19 substrate and inhibitor) may variably affect the AUC of lansoprazole (increase or decrease). If concomitant therapy is necessary, monitoring of therapeutic and possible side effects and adjusting the dose of lansoprazole is recommended.

The simultaneous use of lansoprazole and tacrolimus (substrate of CYP3A4 isoenzyme and P-glycoprotein) leads to increased plasma concentration of the latter (up to 81%). Plasma concentrations of tacrolimus should be monitored when concomitantly administered with lansoprazole.

The concomitant administration of fluvoxamine (CYP2C19 isoenzyme inhibitor) and lansoprazole leads to a fourfold increase in plasma concentrations of the latter.

Rifampicin and St. John’s wort (induces CYP2C19 and CYP3A4 isoenzymes) can significantly decrease plasma concentrations of lansoprazole.

Special Instructions

Before starting therapy, malignancy must be ruled out (especially with gastric ulcers), because treatment, by masking symptoms, can delay a correct diagnosis.

Clarithromycin

Long-term antibiotic use may lead to colonies with increased numbers of insensitive bacteria and fungi. Appropriate therapy should be prescribed if superinfection occurs.

Hepatic dysfunction (increased plasma hepatic enzyme concentrations, hepatocellular and/or cholestatic hepatitis with or without jaundice) has been reported with clarithromycin. Liver dysfunction can be severe, but is usually reversible. There are cases of hepatic failure with fatal outcome, mainly associated with the presence of serious comorbidities and/or concomitant use of other drugs. In case of signs and symptoms of hepatitis, such as anorexia. jaundice, darkened urine, abdominal pain on palpation, clarithromycin therapy should be stopped immediately.

In the presence of chronic liver disease, regular monitoring of plasma enzymes is necessary.

In treatment with virtually all antibacterials, including clarithromycin, there have been cases of pseudomembranous colitis, which can range in severity from mild to life-threatening.

Antibiotic drugs can change the normal gut microflora, which can lead to growth of Clostridium difficile. Pseudomembranous colitis caused by Clostridium difficile should be suspected in all patients who experience diarrhea after using antibiotics. After a course of antibiotic therapy, careful medical follow-up of the patient is necessary. Cases of pseudomembranous colitis have been described 2 months after antibiotic treatment.

Clarithromycin should be used with caution in patients with coronary heart disease (CHD), severe heart failure, hypomagnesemia, severe bradycardia (less than 50 bpm), and concomitant use with class IA (quinidine, procainamide) and class III (dofetilide, amiodarone, sotalol) antiarrhythmic drugs. In these conditions and when concomitant administration of clarithromycin with these drugs, regular monitoring of electrocardiogram for QT interval prolongation should be performed.

Cross-resistance to clarithromycin and other macrolide antibiotics and to lincomycin and clindamycin may develop.

In case of acute hypersensitivity reactions such as anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), Schoenlein-Henoch purpura, clarithromycin should be stopped immediately and appropriate therapy initiated.

A worsening of symptoms of myasthenia gravis has been reported in patients taking clarithromycin.

In case of co-administration with warfarin or other indirect anticoagulants, the INR and prothrombin time should be monitored.

Amoxicillin

Before starting amoxicillin administration, a detailed history should be taken regarding previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. Serious, and sometimes fatal, hypersensitivity reactions (anaphylactic reactions) to penicillins have been described. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins. In case of allergic reactions, amoxicillin should be discontinued and therapy with antibiotic of other group should be started. In severe hypersensitivity reactions, appropriate measures should be taken immediately. Epinephrine, oxygen therapy, intravenous glucocorticosteroids, and airway support, including intubation, may also be required.

The use of amoxicillin should be withheld if infectious mononucleosis is suspected, since in patients with this disease amoxicillin may cause a rash of the skin, making diagnosis difficult.

Long-term treatment with amoxicillin sometimes leads to overgrowth of insensitive microorganisms.

When using amoxicillin, it is recommended to periodically assess the function of the kidneys, liver and hematopoiesis. Amoxicillin should be used with caution in patients with liver dysfunction. Monitoring of liver function should be carried out on a regular basis. In patients with impaired renal function the dose of amoxicillin should be reduced according to the degree of impairment.

Amoxicillin may provoke nonspecific binding of immunoglobulins and albumin to the red blood cell membrane, which may cause false positive reaction in Coombs test.

In patients with decreased diuresis, crystalluria is very rare. Adequate fluid intake and maintenance of adequate diuresis are extremely important during therapy with amoxicillin.

Patients with cholangitis or cholecystitis can be treated with antibiotics only if the disease is mild and there is no cholestasis. During therapy with amoxicillin it is necessary to remember about possible development of superinfection (usually caused by bacteria of Pseudomonas spp. or Candida fungi). In this case the therapy with amoxicillin should be discontinued and/or appropriate treatment should be prescribed.

In case of persistent severe diarrhea pseudomembranous colitis caused by antibiotics should be suspected, which may be life-threatening for the patient (watery stool with a mixture of blood and mucus; blunt widespread or colic-like abdominal pain; fever, sometimes tenesmus). In such cases, amoxicillin should be immediately discontinued and treatment specific to the pathogen, such as vancomycin, should be prescribed. At the same time, agents that reduce gastrointestinal peristalsis are contraindicated. Excretion of amoxicillin leads to its high content in the urine, which may lead to false-positive results in the determination of glucose in the urine (e.g., Benedict test, Feling test). In this case it is recommended to use glucose oxidase method to determine the concentration of glucose in urine.

When concomitant use of amoxicillin with anticoagulants is necessary, prothrombin time or INR should be carefully monitored when prescribing or withdrawing amoxicillin.

When concomitant use of estrogen-containing oral contraceptives and amoxicillin, other or additional methods of contraception should be used if possible.

Particular caution is recommended in patients with allergic diathesis or bronchial asthma, history of gastrointestinal diseases (in particular, colitis caused by antibiotic treatment).

In case of long-term use of amoxicillin, nystatin, levorin or other antifungal drugs should be prescribed simultaneously.

Alcohol consumption is not recommended during treatment.

Lansoprazole

The co-administration of proton pump inhibitors and clopidogrel is recommended to be avoided. Co-administration increases the risk of recurrent myocardial infarction, hospitalization for heart attack or unstable angina, stroke, and repeat revascularization. Patients should be closely monitored if co-prescribing is absolutely necessary.

The co-administration of proton pump inhibitors and antiretroviral drugs in HIV-infected patients should be avoided. If coadministration with atazanavir/ritonavir is necessary, a 12-hour interval between administration of lansoprazole and these drugs is recommended, and the dose of lansoprazole 30 mg should not be exceeded.

When co-administered with antiretrovirals (indinavir, nelfinavir, atazanavir) as well as ketoconazole, itraconazole, posaconazole, cefpodoxime, cefuroxime and ampicillin, their effectiveness and appearance of resistance should be monitored.

The co-administration of imatinib may increase the risk of adverse reactions (potential interaction via CYP3A4), especially in those with a history of severe allergic reactions.

Because of the increased risk of myotoxicity, patients taking atorvastatin, lovastatin or simvastatin should be closely monitored during concomitant use of lansoprazole.

In patients taking warfarin concomitantly, prothrombin time and MHO should be monitored.

Long-term use of proton pump inhibitors increases the risk of infection (including Salmonella, Campylobacter, Clostridium difficile). The benefit of upper gastrointestinal bleeding prophylaxis must be weighed against the potential risk of ventilator-associated pneumonia.

Long-term use of proton pump inhibitors increases the risk of fractures in menopausal women.

Alcoholic beverages should be avoided during treatment.

Pharmacogenetic factor. The effectiveness of the drug depends on the genetic polymorphism of CYP2C19. In patients belonging to “slow metabolizers” (PM-type) the efficacy is higher and eradication of Helicobacte rpylori is significantly more frequent compared to “fast metabolizers” (homEM-type), even against clarithromycin resistance.

“Withdrawal syndrome” or “acid ricochet” is not characteristic of lansoprazole if the duration of use recommendations are followed.

Impact on ability to operate machinery and motor transport

At the time of treatment it is necessary to exercise caution while driving motor transport and engaging in other potentially dangerous activities requiring increased concentration and rapid psychomotor reactions, because the drug may cause weakness, drowsiness and dizziness.

.

Contraindications

• high sensitivity to any drug component (main ingredient and/or excipients), macrolides, penicillins, cephalosporins, carbapenems;
• Simultaneous administration of clarithromycin with the following drugs: astemizole, cisapride, pimozide, terfenadine; with ergot alkaloids such as ergotamine, dihydroergotamine; with oral midazolam;
• concomitant administration of clarithromycin with colchicine in patients with impaired hepatic and renal function;
• patients with a history of QT interval prolongation,
• patients with a history of QT interval prolongation,
• ventricular arrhythmias or pirouette-type ventricular tachycardia;
• patients with hypokalemia (risk of QT interval prolongation);
• patients with severe hepatic impairment concurrent with renal impairment;
• in porphyria;
• when breastfeeding and pregnant;
• patients with atopic dermatitis, bronchial asthma, pollinosis, infectious mononucleosis, lympholeukemia, liver failure, GI diseases in the history (especially colitis associated with antibiotic use),
• children under 18 years of age;
• in the presence of sucrose/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption.

.

Side effects

Clarithromycin

Infectious and parasitic diseases: infrequent – candidiasis, gastroenteritis, development of superinfection (with prolonged or repeated use of clarithromycin), vaginal infections; frequency unknown – pseudomembranous colitis, rye, erythrasis.

Blood and lymphatic system disorders: infrequent – leukopenia, neutropenia, thrombocythemia, eosinophilia; frequency unknown – agranulocytosis, thrombocytopenia.

Immune system disorders: infrequent hypersensitivity; frequency unknown – anaphylactic reactions.

Metabolic and nutritional disorders: infrequent anorexia, decreased appetite; frequency unknown – hypoglycemia (including concomitant use of hypoglycemic drugs).

Psychiatric disorders: frequent – insomnia; infrequent – anxiety, nervousness; frequency unknown – psychosis, confusion, depersonalization, depression, disorientation, hallucinations, “nightmare” dreams, mania.

Nervous system disorders: frequently – change in taste (dysgeusia), headache; infrequently – dizziness, loss of consciousness, somnolence, tremor; frequency unknown – seizures, loss of taste sensation, olfactory disorders, loss of sense of smell, paresthesias.

Hearing and labyrinth disorders: infrequent – vertigo, hearing disorders, tinnitus, tinnitus; frequency unknown – hearing loss (resolving after discontinuation of the drug).

Chronic disorders: infrequent – prolongation of QT interval on electrocardiogram, palpitations; frequency unknown – ventricular tachycardia such as “pirouette”, ventricular tachycardia, ventricular flutter and fibrillation.

Vascular disorders: frequency unknown – unusual bleeding, hemorrhage.

Respiratory system, thorax and mediastinum disorders: infrequent – nasal bleeding.

Gastrointestinal disorders: frequent – diarrhea, vomiting, dyspepsia, nausea, abdominal pain; infrequent – gastroesophageal reflux disease, gastritis, proctalgia, stomatitis, glossitis, bloating, constipation, dry mouth, belching, flatulence; frequency unknown – acute pancreatitis, discoloration of tongue and teeth.

Hepatic and biliary tract disorders: frequently – atypical liver function test; infrequent – cholestasis, hepatitis, increased ALT activity, increased AST activity, increased GGT activity; frequently unknown – liver failure, hepatocellular jaundice.

Skin and subcutaneous tissue disorders: frequent – rash, increased sweating; infrequent – itching, urticaria, patchy-papular rash; frequency unknown – malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome), drug rash with eosinophilia and systemic manifestations, acne, Schoenlein-Henoch purpura.

Muscular and connective tissue disorders: infrequent – muscle spasm, myalgia; frequency unknown – rhabdomyolysis, myopathy, increased symptoms of myasthenia gravis.

Renal and urinary tract disorders: very rare – renal failure, interstitial nephritis.

General disorders and disorders at the site of administration: infrequent – malaise, fever, asthenia, chest pain, chills, weakness.

Laboratory parameters: infrequent – increased alkaline phosphatase activity, increased blood LDH activity; very rare – hypercreatinemia; frequency unknown – increased international normalized ratio (MHO), increased prothrombin time, changes in urine color, increased bilirubin concentration.

Amoxicillin

Infectious and parasitic diseases: infrequent – development of superinfection, oral candidiasis, vaginal candidiasis.

Blood and lymphatic system disorders: rarely – eosinophilia, hemolytic anemia; very rarely – leukopenia, neutropenia, grayulocytopenia, thrombocytopenia, pancytopenia, anemia, myelosuppression, agranulocytosis, reversible increase of prothrombin time and bleeding time.

Immune system disorders: rarely – laryngeal edema, serum sickness, allergic purpura, anaphylactic reaction.

Nervous system disorders: infrequent – headache; rare – agitation, anxiety, insomnia, ataxia, confusion, hyperkinesia, altered behavior, depression, peripheral neuropathy, dizziness, seizures (in patients with renal disorders, epilepsy or meningitis).

Gastrointestinal disorders: frequently – nausea, loss of appetite, vomiting, flatulence, soft stools, diarrhea, oral mucosa rash, dry mouth, distortion of taste perception; rarely – darkening of tooth enamel; very rarely – pseudomembranous colitis, black “hairy” tongue.

Hepatic and biliary tract disorders: infrequent – reversible increase in “hepatic” transaminase activity; rare – hepatitis, cholestatic jaundice.

Skin and subcutaneous tissue disorders: frequent – skin rashes, itching, urticaria; rarely – angioedema (Quincke’s edema), polymorphic exudative erythema, acute generalized exanthematous pustulosis, toxic epidermal necrolysis (Lyell’s syndrome), malignant exudative erythema (Stevens-Johnson syndrome), bullous and exfoliative dermatitis.

Repnal disorders: rarely – acute interstitial nephritis, crystalluria.

General disorders and disorders at the site of administration: rarely – drug fever.

Lansoprazole

Blood and lymphatic system disorders: infrequent – thrombocytopenia, eosinophilia, leukopenia; rare – anemia; very rare – agranulocytosis, pancytopenia.

Immune system disorders: very rare – anaphylactic shock.

Disorders of metabolism and nutrition: rare – anorexia; frequency unknown – hypomagnesemia.

Psychiatric disorders: infrequent – depression; rare – insomnia, hallucinations, confusion.

Nervous system disorders: often – headache, dizziness; rarely – anxiety, vertigo and paresthesia, somnolence, tremor.

Visual organ disorders: rare – visual disturbances.

Gastrointestinal disorders: frequently – nausea, diarrhea, abdominal pain, constipation, vomiting, flatulence, dry mouth or throat; rarely – glossitis, oesophageal candidiasis, pancreatitis, violation of sense of taste; very rarely – colitis, stomatitis.

Liver and biliary tract disorders: often – increased activity of “hepatic” transaminases; rarely – hepatitis, jaundice; very rarely – hyperbilirubinemia.

Respiratory system: rarely – cough, pharyngitis, rhinitis, upper respiratory tract infection, flu-like syndrome.

Skin and subcutaneous tissue disorders: common – urticaria, itching, rash; rarely – petechiae, purpura, alopecia, angioedema (Quincke’s edema), erythema multiforme, photosensitization; very rare – malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome).

Muscular and connective tissue disorders: infrequent – arthralgia, myalgia, fracture of the hip, wrist or spine.

Repnal and urinary tract disorders: rarely – interstitial nephritis.

Gender and mammary gland disorders: rarely – gynecomastia, impotence.

General disorders and disorders at the site of administration: often – weakness; infrequently – edema; rarely – fever, increased sweating.

Laboratory measures: very rarely – increase in cholesterol and triglycerides, hyponatremia.

.

Overdose

Clarithromycin

Symptoms: abdominal pain, nausea, vomiting, diarrhea, possible headache, confusion.

Treatment: gastric lavage, supportive therapy. Not removed by hemo- or peritoneal dialysis.

Amoxicillin

Symptoms: nausea, vomiting, diarrhea, water-electrolyte imbalance (as a consequence of vomiting and diarrhea), crystalluria.

Treatment: gastric lavage, activated charcoal, saline laxatives, drugs to maintain water-electrolyte balance; hemodialysis.

.