Clathinol® [Clarithromycin, lansoprazole, tinidazole]

Pharmacological properties

clarithromycin is a macrolide antibiotic that has antibacterial activity against many aerobic and anaerobic gram-positive and gram-negative microorganisms, including h. pylori. clarithromycin has an antibacterial effect by inhibiting protein synthesis by binding to the 50s subunit of the microbial cells ribosome membrane. minimum inhibitory concentration (mic 90) of clarithromycin and its active metabolite 14-hydroxyclarithromycin for h. pylori is 0.06 mcg / ml.

Lansoprazole blocks the final stage of hydrochloric acid formation. In the tubules of the parietal cells of the stomach is transformed into the active form - sulfenamide, irreversibly interacts with SH-groups H⁺-TO⁺-ATPase (proton pump). Reduces basal and stimulated (food, pentagastrin, insulin) secretion and secretion volume. Recovery activity H⁺-TO⁺-ATPase occurs with a half-period of 30–48 hours. The average daily pH of gastric juice rises to 2.9 (the percentage of time that pH 3 is stored is 47.6). After stopping the intake, the acid level remains below 50% basal for 39 hours, no ricocheted increase in secretion is noted. In patients with Zollinger-Ellison syndrome, it acts longer. It inhibits the production of pepsin (increases the level of pepsinogen in blood plasma). It has a gastroprotective effect: increased oxygenation of the mucous membrane, secretion of bicarbonates. It inhibits the growth of H. pylori (MPC is 0.78–6.25 mg / l), promotes the formation of specific immunoglobulins A. It reduces blood flow in the antrum of the stomach, pylorus and duodenal bulb by an average of 17%, and inhibits motor evacuation function of the stomach. Inhibition of secretion is accompanied by an increase in the number of nitrosobacteria and an increase in the concentration of nitrates in the gastric secretion. It increases the concentration of gastrin in blood plasma by 50-100%. Provides faster healing and a decrease in the severity of symptoms with duodenal ulcer. Effective in the treatment of gastric and duodenal ulcers resistant to N blockers₂receptors. The simultaneous use of clarithromycin and lansoprazole potentiates the pharmacokinetics of both drugs. The frequency of eradication of H. pylori increases significantly when tinidazole is included in this combination, which represents a group of nitroimidazoles with antimicrobial activity against anaerobic bacteria and protozoa, as well as against H. pylori. Due to its high lipophilicity, tinidazole easily penetrates into anaerobic microorganisms, where it is restored by nitroreductase and destroys the helical structure of DNA.

Thus, lansoprazole in combination with antibiotic therapy provides a quick reduction in the severity of symptoms and healing of ulcers. Clarithromycin and lansoprazole did not exhibit mutagenic properties in various tests.

Pharmacokinetics Clarithromycin, when taken orally, is rapidly and completely absorbed. Food slows down absorption, without significantly affecting bioavailability. After a single dose, 2 peaks of plasma concentration are recorded. The second peak is due to the ability to concentrate in the gallbladder, followed by a gradual or rapid release. In plasma it binds to proteins (more than 90%). About 20% of the dose taken is immediately oxidized in the liver with the formation of the main metabolite - 14-hydroxyclarithromycin. Biotransformation: catalyzed by enzymes of the cytochrome P450 system. It penetrates well into body fluids and tissues, forming concentrations 10 times higher than the level in blood plasma. T_½ when taken in a dose of 500 mg is 7–9 hours. Excreted in the urine unchanged up to 30%, the rest - in the form of metabolites.

Lansoprazole is rapidly absorbed with an absolute bioavailability of about 40%. The absorption of lansoprazole is not affected by food.Extensively metabolized in the liver. T_½ from blood plasma is 0.5-1 hours. About 80% of lansoprazole is excreted by the kidneys. After oral administration, the onset of the antisecretory effect of lansoprazole is observed after 1 hour. The duration of inhibition of the secretion of hydrochloric acid in the stomach is almost 24 hours. After repeated administration of the drug at a dose of 20 mg / day, the daily intragastric acidity decreases by 97%.

It was found that the simultaneous use of lansoprazole and clarithromycin favorably affects the pharmacokinetic properties of the latter. WITH_max 10% higher average C_min - 27% higher, and the average AUC - 15% more than when using clarithromycin alone. The concentration of clarithromycin in the tissues of the stomach and mucus also increased with its simultaneous administration with lansoprazole.

When taken orally, tinidazole is rapidly absorbed, the absorption rate is about 90%. Accumulates in blood, C_max achieved after 2 hours. Communication with plasma proteins - 10%. It easily penetrates into various tissues and body fluids, penetrates through the BBB. It undergoes biotransformation, the main metabolites are pharmacologically active hydroxylated substances (inhibit the growth of anaerobic microorganisms and can enhance the effect of tinidazole). Slowly excreted (including metabolites) by the kidneys (intense reabsorption in the renal tubules). T_½ in adults is 10-14 hours.

Indications

Gastric and duodenal ulcer, chronic gastritis associated with h. pylori.

Application

The decision on the treatment regimen, doses of the drugs and the timing of treatment should be made by the doctor. recommended dosage regimen and dosage: 1 strip containing 2 capsules of lansoprazole, 2 tablets of clarithromycin and 2 tablets of tinidazole, is designed for 1 day of treatment. In the morning, take 1 capsule of lansoprazole and 1 tablet of clarithromycin and tinidazole, in the evening they repeat the administration of drugs.

Mandatory additional intake of clarithromycin 250 mg 2 times a day.

The duration of complex therapy is 7 days.

Contraindications

Hypersensitivity to lansoprazole, clarithromycin or other macrolide antibiotics, tinidazole or other 5-nitroimidazole derivatives. simultaneous use of any of the following drugs: atazanavir; astemizole, cisapride, pimozide, terfenadine (this can lead to a lengthening of the q – t interval, the development of cardiac arrhythmias, including ventricular tachycardia and ventricular fibrillation, and paroxysmal tachycardia like pirouette (torsades de pointes)), ergotamine, dihydroergot ), lovastatin or simvastatin (due to the risk of rhabdomyolysis, treatment with these drugs must be stopped during treatment with clarithromycin). patients with a prolongation of the q – t interval or ventricular arrhythmias of the heart, including a history of paroxysmal tachycardia like pirouette (torsades de pointes). the simultaneous use of colchicine is contraindicated in patients with renal or hepatic insufficiency taking p-glycoprotein or a strong cyp 3a4 inhibitor (e.g. clarithromycin), patients with pathological changes in the blood or organic lesions of the nervous system.

Side effects

Clarithromycin

From the blood and lymphatic systems: leukopenia, neutropenia, thrombocythemia, eosinophilia, agranulocytosis, thrombocytopenia.

From the immune system: hypersensitivity, anaphylactic reactions, infection, vaginal infection.

Metabolic disorders: anorexia, decreased appetite, hypoglycemia.

Mental disorders: anxiety, nervousness, crying out, psychoses, confusion, depersonalization, depression, disorientation, hallucinations.

From the side of the central nervous system: loss of consciousness, dyskinesia, drowsiness, tremors, convulsions, loss of taste sensitivity, parosmia, anosmia, headache, anxiety, fear, insomnia, nightmares.

On the part of the hearing organ and labyrinth disorders: dizziness, hearing loss, ringing in the ears, hearing loss.

From the cardiovascular system: cardiac arrest; atrial fibrillation, lengthening of the Q – T interval; extrasystole, increased palpitations; ventricular tachycardia, including paroxysmal tachycardia of the pirouette type (torsades de pointes), vasodilation, hemorrhage.

From the respiratory system: asthma, nosebleeds, pulmonary embolism.

From the digestive tract: dyspepsia, esophagitis, gastroesophageal reflux disease, gastritis, proctalgia, bloating, constipation, dry mouth, belching, acute pancreatitis, discoloration of the tongue, discoloration of the teeth, candidiasis of the oral cavity, nausea, vomiting, change in taste , stomach pain, diarrhea, pseudomembranous colitis, stomatitis, glossitis, gastroenteritis.

From the hepatobiliary system: cholestasis, hepatitis, increased levels of AlAT, AsAT, GGT, liver failure, cholestatic jaundice, hepatocellular jaundice.

On the part of the skin and subcutaneous tissue: rash, hyperhidrosis, bullous dermatitis, pruritus, maculopapular rash, toxic epidermal necrolysis, drug-induced skin reaction accompanied by eosinophilia and systemic manifestations (DRESS), acne, cellulitis, Shenleyne’s disease, erythema, genogenitis, urticaria, Stevens-Johnson syndrome, anaphylactoid reactions.

From the musculoskeletal system and connective tissue: muscle spasms, musculoskeletal rigidity, myalgia, rhabdomyolysis (in some reports of rhabdomyolysis, clarithromycin was used simultaneously with statins, fibrates, colchicine or allopurinol), myopathy.

From the urinary system: increased creatinine, urea, renal failure, interstitial nephritis.

Common disorders: malaise, fever, asthenia, chest pain, chills, fatigue.

Laboratory studies: a change in the albumin-globulin ratio, an increase in the level of alkaline phosphatase, LDH in the blood, an increase in the international normalized ratio, an increase in prothrombin time, and a change in the color of urine. Paresthesia, arthralgia, angioedema have been reported. Very rarely, uveitis was reported primarily in patients who took rifabutin at the same time. Most cases were reversible. The development of colchicine toxicity (including death) has been reported with the combined use of clarithromycin and colchicine, especially in elderly patients, including against the background of renal failure.

Tinidazole

From the digestive tract: dyspeptic disorders, such as loss of appetite, nausea, sometimes vomiting, diarrhea, abdominal pain, anorexia, plaque on the tongue, glossitis, stomatitis.

From the nervous system and sensory organs: dizziness, headache, locomotor ataxia, dysarthria, paresthesia, hypesthesia, peripheral neuropathy, vertigo, impaired sensitivity, metallic taste in the mouth, hot flashes, fatigue, fever.

From the blood system and lymphatic system: transient leukopenia.

From the musculoskeletal system and connective tissue: convulsive reactions.

From the urinary system: staining of urine in a dark color.

On the part of the immune system: hypersensitivity reactions, urticaria, rash, itching (isolated cases), angioedema.

Alcohol. The simultaneous use of tinidazole and alcohol can lead to a disulfiram-like reaction, so this combination should be avoided.

Anticoagulants. Preparations with a similar chemical structure potentiate the effects of anticoagulants for oral administration. Prothrombin time indicators should often be monitored and, if necessary, the dose of the anticoagulant adjusted.

Lansoprazole

From the cardiovascular system: angina pectoris, arrhythmia, bradycardia, heart pain, cerebrovascular changes (stroke), hypertension, hypotension, migraine, myocardial infarction, palpitations, shock (circulatory failure), vasodilation, syncope, tachycardia.

From the blood and lymphatic systems: leukopenia, thrombocytopenia, eosinophilia, pancytopenia or agranulocytosis, aplastic anemia, hemolytic anemia, neutropenia, thrombotic and thrombocytopenic purpura.

From the nervous system: headache, infrequently - drowsiness, dizziness, hemiplegia, tremor, paresthesia.

Mental disorders: fear, depression, agitation, amnesia, agitation, apathy, hallucinations, hostility, nervousness, insomnia, impaired thinking, confusion.

From the respiratory system: asthma, bronchitis, severe cough, pharyngitis, rhinitis, hiccups, nosebleeds, pulmonary hemorrhage, pneumonia, inflammation or infection of the upper respiratory tract.

From the side of the organ of vision: eye pain, visual impairment, blurred vision, visual field defects.

From the side of the hearing organ: tinnitus, deafness, otitis media.

From the digestive tract: constipation, abdominal pain; diarrhea, nausea; dyspepsia, taste disorders; bad breath; dry mouth / thirst, dysphagia; cardiospasm; belching; vomiting, esophageal stenosis; esophageal ulcer; esophagitis, discoloration of feces; flatulence, polyps of the stomach; gastroenteritis, colitis, gastrointestinal bleeding, including rectal; vomiting with an admixture of blood (hemathemesis), increased or decreased appetite, anorexia, increased salivation; melena, stomatitis; glossitis, pancreatitis, tenesmus.

From the hepatobiliary system: jaundice, hepatitis, cholelithiasis.

From the endocrine system: diabetes mellitus, goiter, hyperglycemia / hypoglycemia, hypothyroidism.

On the part of the skin and subcutaneous tissues: often a rash, rarely itching, hives, purpura, angioedema, petechiae or hair loss, hyperhidrosis, acne, photosensitivity, very rarely, such severe generalized reactions as toxic epidermal necrolysis, Stevens-Johnson syndrome and polymorphic erythema.

From the musculoskeletal system and connective tissue: pain in the joints, muscles or bones, arthritis / arthralgia, myalgia.

From the urogenital system: interstitial nephritis, which can lead to renal failure, glucosuria, hematuria, albuminuria, kidney stones, urinary retention.

From the reproductive system: genitourinary disorders, impotence, decreased libido, enlarged mammary glands or gynecomastia, tenderness of the mammary glands, irregular menstruation.

Common disorders: anaphylactoid / anaphylactic reactions, anaphylactic shock, an increase in the abdomen, allergic reactions, asthenia, candidiasis, carcinoma, back pain, stiff neck, chest pain (not always specific), pelvic pain, facial flushing, speech disorders, swelling , chills, shortness of breath, fever, flu-like syndrome, infections (non-specific), weakness.

Laboratory studies: increase in the level of AcAT, AlAT, alkaline phosphatase, creatinine, globulins, gamma-glutamyl transpeptidase, increase / decrease in the level of leukocytes, violation of the albumin / globulin ratio, change in the number of red blood cells, hyperbilirubinemia, eosinophilia, hyperlipidemia, increase / decrease in electrolyte levels, increase / decrease in electrolytes, increase / decrease in electrolytes Cholesterol, a decrease in hemoglobin, an increase in the level of potassium, urea, salts in the urine, an increase in the level of glucocorticoids, LDL, an increase / decrease in platelets, an increase in the level of gastrin, a positive test for hidden blood, albuminuria, glucosuria, hematuria.

special instructions

Prolonged or repeated use of antibiotics can cause excessive growth of insensitive bacteria and fungi.if superinfection occurs, discontinue use of clarithromycin and begin appropriate therapy.

The use of any antimicrobial therapy, including clarithromycin, to treat H. pylory infection can lead to microbial resistance. In a small number of patients, H. pylory microorganisms may develop resistance to clarithromycin.

Caution should be used in patients with severe renal failure.

When clarithromycin was used, dysfunction of the liver, including elevated liver enzymes, and hepatocellular and / or cholestatic hepatitis with or without jaundice were reported. Impaired liver function can be severe and is usually reversible. In some cases, fatal liver failure has been reported, which is mainly associated with severe general illness and / or concomitant medication. Clarithromycin should be discontinued immediately if hepatitis symptoms and symptoms such as anorexia, jaundice, dark urine, itching, or abdominal pain occur.

The development of diarrhea from mild to fatal pseudomembranous colitis caused by Clostridium difficile has been reported with virtually all antibacterial drugs, including clarithromycin. You should always remember the possibility of developing diarrhea caused by Clostridium difficile in all patients with diarrhea after antibiotic use. In addition, it is necessary to carefully collect the anamnesis, since the development of diarrhea caused by Clostridium difficile was reported even 2 months after the use of antibacterial drugs.

An increase in symptoms of myasthenia gravis has been reported in patients taking clarithromycin.

It is allocated by a liver and kidneys. Caution should be exercised when using the drug in patients with impaired liver function, moderate or severe renal impairment.

In the case of severe acute hypersensitivity reactions, such as anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, Shenlein-Genoch disease, clarithromycin therapy should be stopped immediately and appropriate treatment should be started.

Tinidazole causes dark urine. During treatment, the use of alcoholic beverages is prohibited due to the possible development of a disulfiram-like reaction (abdominal cramps, nausea, vomiting).

The drug is recommended for patients who have not previously used drugs of the nitroimidazole group.

Capsules of lansoprazole contain sugar, which should be considered for patients with diabetes mellitus.

Use during pregnancy and lactation. Clathinol is contraindicated during pregnancy and lactation.

Children. Not used in pediatric practice.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. The use of the drug does not affect the ability to drive vehicles or work with potentially dangerous mechanisms, as well as to engage in activities that require quick response and coordination of actions. However, taking into account possible side effects, caution should be exercised in the treatment with clatinol.

Interactions

Clarithromycin

Clarithromycin does not interact with oral contraceptives. The use of the following drugs is strictly contraindicated due to the possible development of severe consequences of the interaction.

Cisapride, pimozide and terfenadine. With their simultaneous use with clarithromycin, an increase in their plasma level was noted, which can cause an extension of the Q – T interval and the appearance of arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsade de pointes. Similar effects were noted with the combined use of astemizole and other macrolides.

Ergotamine / dihydroergotamine. The simultaneous use of clarithromycin and ergotamine or dihydroergotamine was associated with the appearance of signs of acute ergotism, which was characterized by vasospasm and ischemia of the limbs and other tissues, including the central nervous system.

The effect of other drugs on the pharmacokinetics of clarithromycin. Drugs that induce CYP 3A (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, St. Johns wort preparations) can induce the metabolism of clarithromycin. This can lead to subtherapeutic levels of clarithromycin and a decrease in its effectiveness. In addition, it may be necessary to monitor plasma concentrations of the CYP 3A inducer, which may be increased due to inhibition of CYP 3A by clarithromycin (see also the instructions for use of the corresponding CYP 3A4 inducer). The simultaneous use of rifabutin and clarithromycin led to an increase in rifabutin and a decrease in plasma clarithromycin levels with a simultaneous increase in the risk of uveitis.

The effect of the following drugs on the concentration of clarithromycin in the blood is known or is expected, therefore, a dose change or the use of alternative therapy may be required.

Powerful cytochrome P450 enzyme inducers, such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentin, can accelerate the metabolism of clarithromycin, reducing its concentration in blood plasma, but increasing the concentration of 14-OH-clarithromycin, a microbiologically active metabolite. Since the microbiological activity of clarithromycin and 14-OH-clarithromycin is different in relation to different bacteria, the expected therapeutic effect may not be achieved with the combined use of clarithromycin and inducers of cytochrome P450 enzymes. The action of clarithromycin was attenuated by etravirine, however, the concentrations of the active metabolite of 14-OH-clarithromycin increased. Since 14-OH-clarithromycin exhibits reduced activity against Mycobacterium avium complex, the total activity against this pathogen may change.

The equilibrium concentrations of the active metabolite of 14-OH-clarithromycin did not significantly change while using fluconazole. Clarithromycin dose adjustment is not required.

The use of ritonavir and clarithromycin led to a significant inhibition of the metabolism of clarithromycin. WITH_max clarithromycin increased by 31%, C_min - by 182% and AUC - by 77%. Complete suppression of the formation of 14-OH-clarithromycin was noted. Due to the large therapeutic window, dose reduction of clarithromycin in patients with normal renal function is not required. However, in patients with renal failure, dose adjustment is necessary: ​​for patients with creatinine clearance of 30-60 ml / min, the dose of clarithromycin must be reduced by 50%. In patients with severe renal failure (creatinine clearance of 30 ml / min), the dose of clarithromycin must be reduced by 75%. Doses of clarithromycin in excess of 1 g / day should not be used with ritonavir. The same dose adjustment should be performed in patients with impaired renal function when using ritonavir as a pharmacokinetic enhancer along with other HIV protease inhibitors, including atazanavir and saquinavir.

The effect of clarithromycin on the pharmacokinetics of other drugs

Antiarrhythmic drugs. There are post-marketing reports on the development of ventricular tachycardia of the pirouette type that arose with the simultaneous use of clarithromycin with quinidine or disopyramide. It is recommended to conduct ECG monitoring for the timely detection of lengthening of the Q – T interval. During clarithromycin therapy, the concentration of these drugs in the blood plasma should be monitored.

The combined use of clarithromycin and CYP 3A inhibitors or drugs, mainly metabolized by CYP 3A, can lead to an increase in the concentration of the latter in blood plasma, which, in turn, can enhance or prolong its therapeutic effect and increase the risk of adverse reactions. Caution should be exercised when clarithromycin is used in patients receiving drug therapy with CYP 3A substrates, especially if the CYP 3A substrate has a narrow therapeutic range (e.g. carbamazepine) and / or is extensively metabolized by this enzyme.

Dose adjustment and, if possible, careful monitoring of plasma concentrations of the drug metabolized by CYP 3A may be required in patients who are simultaneously using clarithromycin.

There is a likelihood of increasing plasma concentrations of PDE inhibitors (sildenafil, tadalafil and vardenafil) when combined with clarithromycin, which may require a reduction in the dose of PDE inhibitors. A dose reduction of tolterodine may be required when it is used with clarithromycin.

Triazolbenzodiazepines (alprazolam, midazolam, triazolam). The combined use of oral midazolam and clarithromycin should be avoided. When using midazolam with clarithromycin, careful monitoring of the patients condition should be carried out for timely dose adjustment. The same rules should be followed when using other benzodiazepines metabolized by CYP 3A, including triazolam and alprazolam. For benzodiazepines, the elimination of which is independent of CYP 3A (temazepam, nitrazepam, lorazepam), the development of a clinically significant interaction with clarithromycin is unlikely. There are post-marketing reports of drug interactions and the development of side effects from the central nervous system (such as drowsiness and confusion) with the combined use of clarithromycin and midazolam. The condition of the patient should be monitored, given the possibility of increasing the severity of pharmacological effects from the central nervous system.

Other types of interactions. Colchicine is a substrate of CYP 3A and P-glycoprotein (Prg). It is known that clarithromycin and other macrolides are able to suppress CYP 3A and Pgp. With the simultaneous use of clarithromycin and colchicine, inhibition of Pgp and CYP 3A by clarithromycin can lead to increased exposure to colchicine. It is necessary to monitor the condition of patients to identify clinical symptoms of colchicine toxicity. During post-marketing observation, an increase in the concentration of digoxin in the blood plasma of patients taking clarithromycin simultaneously with digoxin was reported. Some patients have developed signs of digitalis toxicity, including fatal arrhythmias. The concentration of digoxin in the blood plasma of patients should be carefully monitored when it is used with clarithromycin. The simultaneous use of clarithromycin immediate-release tablets and zidovudine in HIV-infected patients can cause a decrease in equilibrium plasma concentrations of zidovudine. This can be avoided by observing the interval between doses of clarithromycin and zidovudine. Such an interaction with the use of a suspension of clarithromycin and zidovudine or dideoxinazine in children has not been reported.

Spontaneous or published reports of the interaction of CYP 3A inhibitors, including clarithromycin, with drugs that are not considered substrates of CYP 3A (phenytoin and valproate) have been received. It is recommended to determine the level of these drugs in blood plasma while prescribing them with clarithromycin. An increase in their plasma level has been reported.

A bilateral drug interaction between clarithromycin and atazanavir, itraconazole, saquinavir is also possible.

The development of arterial hypotension, bradyarrhythmias and lactic acidosis has been reported with the simultaneous use of clarithromycin and verapamil.

Lansoprazole

Atazanavir. Lansoprazole, like other proton pump inhibitors, reduces the concentration of atazanavir (an HIV protease inhibitor), the absorption of which depends on gastric acidity, and therefore can affect the therapeutic effect of atazanavir and the development of resistance to HIV infection. The simultaneous use of atazanavir and lansoprazole is contraindicated.

Medicines that are metabolized by the cytochrome P450 system. Lansoprazole may increase plasma concentrations of drugs metabolized by CYP 3A4 (warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisolone, diazepam, clarithromycin, or terfenadine).

Medicines that suppress CYP 2C19 (fluvoxamine). Fluvoxamine leads to a significant increase (4 times) in the concentration of lansoprazole in blood plasma. With simultaneous use, dose adjustment of lansoprazole is necessary.

Medicines inducing CYP 2C19 and CYP 3A4 (rifampicin, St. Johns wort grass). Inductors CYP 2C19 and CYP 3A4 can significantly reduce the concentration of lansoprazole in blood plasma. With simultaneous use, dose adjustment of lansoprazole is necessary.

Medicines, the absorption of which is important pH value. Lansoprazole causes prolonged inhibition of gastric secretion, therefore, it is theoretically possible to influence lansoprazole on the bioavailability of drugs for which, when absorbed, the pH value is important (itraconazole, ampicillin esters).

Amoxicillin. Clinical manifestations of the interaction of lansoprazole with amoxicillin were not observed.

Sucralfate and antacids may decrease the bioavailability of lansoprazole, so lansoprazole must be taken at least 1 hour after the use of these drugs.

NSAIDs. No clinically significant interaction was found between lansoprazole and NSAIDs.

Theophylline. With the simultaneous use of lansoprazole with theophylline (CYP 1A2, CYP 3A), a moderate increase (10%) in theophylline clearance is noted, but the clinical significance of their interaction is unlikely. However, in order to maintain clinically effective concentrations of theophylline, individual patients require dose adjustment of theophylline at the beginning or upon termination of treatment with lansoprazole.

Warfarin. Lansoprazole does not affect the pharmacokinetics of warfarin and prothrombin time. An increase in the international normalized ratio and prothrombin time can lead to bleeding and even death.

Digoxin. With the simultaneous use of digoxin and lansoprazole, an increase in the level of digoxin in the blood plasma is noted.

Tacrolimus. With the simultaneous use of lansoprazole and tacrolimus, the concentration of tacrolimus in blood plasma may increase, especially in patients who underwent transplantation.

Tinidazole

Tinidazole is compatible with sulfanilamides and antibiotics (aminoglycosides, erythromycin, rifampicin, cephalosporins); not recommended with ethionamide. Phenobarbital accelerates inactivation in the liver. Enhances the effect of indirect anticoagulants (to reduce the risk of bleeding, it is recommended to reduce the dose of the latter by 50%).

Alcohol. The simultaneous use of tinidazole and alcohol can lead to a disulfiram-like reaction, so this combination should be avoided.

Anticoagulants. Preparations with a similar chemical structure potentiate the effects of anticoagulants for oral administration. Prothrombin time parameters should often be monitored and, if necessary, the dose of the anticoagulant adjusted.

Overdose

Lansoprazole

Symptoms: not described (a single dose of 600 mg was not accompanied by clinical manifestations of an overdose).

Treatment: if an overdose is suspected, supportive and symptomatic therapy is recommended. Hemodialysis is ineffective.

Clarithromycin

Symptoms: possible reactions from the gastrointestinal tract (nausea, vomiting, diarrhea).

Treatment: immediate gastric lavage and symptomatic treatment are necessary. Hemodialysis and dialysis do not lead to a significant change in the level of clarithromycin in the blood.

Tinidazole

Cases of overdose are not described.

There is no specific antidote. Tinidazole is excreted during hemodialysis.

Storage conditions

In a dry, dark place at a temperature of no higher than 30 ° C.