Klacid Hp

Clarithromycin, pantoprazole, amoxicillin.

Each Klacid Hp (7 days) combination pack contains 14 tablets of Klacid containing clarithromycin 500 mg, 14 tablets of Controloc containing pantoprazole sodium sesquihydrate 45.1 mg equivalent to pantoprazole 40 mg, and 14 tablets of Ospamox containing amoxicillin 1 g.
Each Klacid Hp (14 days) combination pack contains 28 tablets of Klacid containing clarithromycin 500 mg, 28 tablets of Controloc containing pantoprazole sodium sesquihydrate 45.1 mg equivalent to pantoprazole 40 mg, and 28 tablets of Ospamox containing amoxicillin 1 g.

Pharmacology: Helicobacter pylori is a spiral, flagellated, gram-negative rod, primarily colonising the antrum of the stomach, it congregates at and around intercellular junctions. The natural habitat of H. pylori is the gastric mucosa, where the bacterium attaches itself via adhesion pedestals. H. pylori is associated with duodenal and gastric ulcer disease in about 95% and 70% of patients, respectively. H. pylori is the major factor in the development of gastritis and ulcers in such patients. Eradication of H. pylori is associated with reduced peptic ulcer recurrence. Eradication of H. pylori is therefore appropriate therapy in most patients with duodenal and gastric ulcer where the latter is not caused by nonsteroidal anti-inflammatory drug (NSAID) ingestion. Eradication of H. pylori was achieved in approximately 95% of patients following therapy with clarithromycin, pantoprazole and amoxicillin.
Klacid: Clarithromycin is active in vitro and in vivo against H. pylori. Clarithromycin exerts its antibacterial action by binding to the 50S ribosomal subunit of susceptible bacteria and suppresses protein synthesis. The 14-hydroxy metabolite of clarithromycin also has antimicrobial activity. The minimum inhibitory concentrations (MICs) of this metabolite are equal or 2-fold higher than the MICs of the parent compound.
Controloc: An irreversible proton pump inhibitor which has been developed for the treatment of acid-related gastrointestinal disorders. Pantoprazole reduces gastric acid secretion through inhibition of the proton pump on the gastric parietal cell. As a weak base, pantoprazole is highly ionised at low pH and readily accumulates in the highly acidic canalicular lumen of the stimulated parietal cell. In this acidic environment, pantoprazole is rapidly converted to the active species, a cationic cyclic sulfonamide which binds covalently to cysteine residues on the luminal (acidic) surface of H⁺K⁺-ATPase to form a mixed disulfide, thereby causing irreversible inhibition of gastric proton pump function. As H⁺K⁺-ATPase represents the final step in the secretory process, inhibition of this enzyme suppresses gastric acid secretion regardless of the primary stimulus.
Ospamox: Amoxicillin is a highly potent, broad-spectrum penicillin with a particularly rapid onset and a broad spectrum of action (active against both gram-positive and gram-negative microorganism). Like other penicillins, it acts by inhibiting cell wall synthesis.
Pharmacokinetics: A summary of the pharmacokinetic parameters for Klacid Hp are provided in the following table. For further information regarding pharmacokinetics of Klacid, Controloc or Ospamox, refer to full product information for the appropriate component. (See table.)

Click on icon to see table/diagram/image

Klacid: Clarithromycin is rapidly and well absorbed from the gastrointestinal tract after oral administration of Klacid tablets. The microbiologically active metabolite 14-hydroxyclarithromycin is formed by first-pass metabolism. Klacid may be given without regard to meals as food does not affect the extent of bioavailability of Klacid tablets. Food does slightly delay the onset of absorption of clarithromycin and formation of the 14-hydroxy metabolite. The pharmacokinetics of clarithromycin are nonlinear; however, steady state is attained within 2 days of dosing. At 250 mg twice daily, 15-20% of unchanged drug is excreted in the urine. With 500 mg twice-daily dosing, urinary excretion is greater (approximately 36%). The 14-hydroxyclarithromycin is the major urinary metabolite and accounts for 10-15% of the dose. Most of the remainder of the dose is eliminated in the faeces, primarily via the bile; 5-10% of the parent drug is recovered from the faeces.
Klacid provides tissue concentrations that are several times higher than the circulating drug levels. Increased levels have been found in both tonsillar and lung tissue. Klacid also penetrates the gastric mucus. Levels of clarithromycin in gastric mucus and gastric tissue are higher when clarithromycin is co-administered with proton pump inhibitor than when clarithromycin is administered alone.
Controloc: Pantoprazole is subjected to low first-pass hepatic extraction, as reflected in an estimated absolute oral bioavailability of 77%. Concomitant intake of food has no influence on the bioavailability of pantoprazole. Plasma pantoprazole concentrations decline monophasically after oral administration with a mean plasma terminal elimination half-life of 0.9-1.9 hrs. Despite the short half-life of pantoprazole, inhibition of acid secretion, once accomplished, is long-lasting, persisting long after the drug has been cleared from the circulation. On repeated (7 days) oral administration, the pharmacokinetics of pantoprazole (20 and 40 mg/day) do not differ appreciably from those on single-dose administration suggesting that drug accumulation does not occur. In keeping with its high degree of plasma protein-binding (98%), pantoprazole has a relatively low apparent volume of distribution (mean 0.16 L/kg at steady state), suggesting limited tissue distribution. Pantoprazole is subject to extensive hepatic metabolism via cytochrome P-450 (CYP)-mediated oxidation followed by sulfate conjugation. Elimination is renal, with 80% of an oral dose being excreted as urinary metabolites, the remainder is excreted in the faeces which originates primarily from biliary secretion. The pharmacokinetics of pantoprazole do not appear to be modified to any clinically relevant extent by renal impairment. Haemodialysis does not appear to significantly influence the pharmacokinetics of pantoprazole or its main metabolite M2 in patients with renal disease or end-stage renal failure. The metabolism of pantoprazole is impaired in patients with hepatic dysfunction. However, C_max was only marginally elevated (50%), indicating that pantoprazole may be given without dosage adjustment to patients with hepatic impairment.
Ospamox: The absorption of amoxicillin is unaffected by meals. The drug is almost completely absorbed from the small intestine. Peak serum levels are reached within 1-2 hrs after ingestion. Amoxicillin readily distributes in body tissues and fluid including the sputum and purulent bronchial secretions. If liver function is intact, high biliary drug concentrations are reached. Amoxicillin is eliminated at a half-life of approximately 1-2 hrs. Elimination is predominantly renal. More than half of the oral dose is excreted with the urine in a therapeutically active form.

Treatment of peptic ulcer disease associated with Helicobacter pylori infection.

Recommended Dosage Regimen: Klacid 500 mg twice daily, Controloc 40 mg twice daily and Ospamox 1 g twice daily for 7 days. The combination therapy is implemented for 7 days in general and can be prolonged up to 2 weeks maximum.
Klacid: Klacid may be given without regard to meals as food does not affect the extent of bioavailability.
Controloc: Gastro-resistant tablets should not be chewed or crushed, and should be swallowed whole with water 1 hr before breakfast. In this H. pylori eradication therapy, the 2nd Controloc tablet should be taken before the evening meal.
Ospamox: Amoxicillin may be given without regard to meals as food does not affect the extent of absorption.

Klacid: Reports indicate that the ingestion of large amounts of clarithromycin can be expected to produce gastrointestinal symptoms. One patient who had a history of bipolar disorder ingested 8 g of clarithromycin and showed altered mental status, paranoid behaviour, hypokalemia and hypoxemia. Allergic reactions accompanying overdosage should be treated by gastric lavage and supportive measures. As with other macrolides, clarithromycin serum levels are not expected to be appreciably affected by hemodialysis or peritoneal dialysis.
Controloc: There are no known symptoms of overdosage in man. In the case of overdosage with clinical signs of intoxication, the usual rules of intoxication therapy apply.

Klacid: Patients with known hypersensitivity to macrolide antibiotic drugs. Clarithromycin and ergot derivatives should not be co-administered. Concomitant administration of clarithromycin and any of the following drugs is contraindicated: Cisapride, pimozide and terfenadine. Elevated cisapride, pimozide and terfenadine levels have been reported in patients receiving either of these drugs and clarithromycin concomitantly. This may result in QT prolongation and cardiac arrhythmias including ventricular fibrillation and torsade de pointes. Similar effects have been observed with concomitant administration of astemizole and other macrolides.
Controloc: Controloc should not be used in cases of known hypersensitivity to one of the constituents of Controloc or the combination partners. It must not be used in combination treatment for eradication of H. pylori patients with moderate to severe hepatic or renal dysfunction since currently, no data are available on the efficacy and safety of Controloc in combination treatment of these patients.
Ospamox: Known and suspected hypersensitivity to penicillins. Potential cross-allergy should be considered in patients with cephalosporin hypersensitivity. Because of the increased incidence of side effects (rashes), amoxicillin should not be administered to patients with mononucleosis and lymphatic leukemia. Severe gastrointestinal infections with persistent diarrhea or vomiting should not be treated with oral amoxicillin because of the risk of reduced absorption. Special caution should be exercised in patients with allergic diatheses or bronchial asthma and hay fever.

Klacid: Clarithromycin is principally excreted by the liver and kidney. Caution should be exercised in administering this antibiotic to patients with impaired hepatic or renal function. Prolonged or repeated use of clarithromycin may result in an overgrowth of nonsusceptible bacteria or fungi. If superinfection occurs, clarithromycin should be discontinued and appropriate therapy instituted. H. pylori organisms may develop resistance to clarithromycin in a small number of patients.
Controloc: Prior to treatment, the possibility of malignancy of gastric ulcer or malignant disease of the esophagus should be excluded as the treatment with pantoprazole may alleviate the symptoms of malignant ulcers and can thus delay diagnosis. To date there has been no experience with treatment in children.
Ospamox: Patients should be told about the potential occurrence of allergic reactions and instructed to report them. If allergic reactions occur, amoxicillin should be discontinued and the usual treatment with epinephrine, antihistamines and corticosteroids should be instituted. If maculopapular amoxicillin rashes develop, treatment should be confined to life-threatening conditions and patients should be carefully monitored. Adequate fluid intake and urine output are essential during treatment. Severe and persistent diarrhea should prompt suspicion of antibiotic-induced pseudomembranous colitis (blood-streaked, mucoid, watery diarrhea; dull diffuse or colicky abdominal pain, fever and occasional tenesmus) which may be life threatening. In pertinent cases, Ospamox should immediately be withdrawn and treatment specific for the offending organism (eg, oral vancomycin) should be instituted. Antiperistaltic drugs are contraindicated.
Use in pregnancy & lactation: Klacid: The safety of clarithromycin during pregnancy and breastfeeding of infants has not been established. Klacid should thus not be used during pregnancy or lactation unless the benefit is considered to outweigh the risk. Some animal studies have suggested an embryotoxic effect, but only at dose levels which are clearly toxic to mothers. Clarithromycin has been found in the milk of lactating animals and in human breast milk.
Controloc: Clinical experience in pregnant women is limited. There is no information on the excretion of pantoprazole into human breast milk. Controloc tablets should only be used when the benefit to the mother is considered greater than the potential risk to the fetus/baby.
Ospamox: There is no current evidence to suggest any embryotoxic, teratogenic or mutagenic effects of Ospamox during pregnancy. It should, however, be borne in mind that amoxicillin diffuses into breast milk.

Klacid: The safety of clarithromycin during pregnancy and breastfeeding of infants has not been established. Klacid should thus not be used during pregnancy or lactation unless the benefit is considered to outweigh the risk. Some animal studies have suggested an embryotoxic effect, but only at dose levels which are clearly toxic to mothers. Clarithromycin has been found in the milk of lactating animals and in human breast milk.
Controloc: Clinical experience in pregnant women is limited. There is no information on the excretion of pantoprazole into human breast milk. Controloc tablets should only be used when the benefit to the mother is considered greater than the potential risk to the fetus/baby.
Ospamox: There is no current evidence to suggest any embryotoxic, teratogenic or mutagenic effects of Ospamox during pregnancy. It should, however, be borne in mind that amoxicillin diffuses into breast milk.

Klacid: Clarithromycin is generally well tolerated. Adverse effects reported include nausea, dyspepsia, diarrhea, vomiting and abdominal pain. Stomatitis, glossitis and oral monilia have been reported. Other adverse effects include headache and allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis and rarely Stevens-Johnson syndrome. Taste perversion may occur. There have been reports of transient central nervous system side effects including anxiety, dizziness, insomnia, hallucinations, psychosis, bad dreams and confusion, however, a cause-and-effect relationship has not been established. There have been reports of hearing loss with clarithromycin which is reversible upon withdrawal of therapy. Pseudomembranous colitis has been reported rarely with clarithromycin and may range in severity from mild to life-threatening. As with other macrolides, hepatic dysfunction (which is usually reversible) including altered liver function tests, hepatitis and cholestasis with or without jaundice, has been reported. Dysfunction may be severe and very rarely fatal hepatic failure has been reported.
Controloc: Treatment with Controloc can occasionally lead to headache, gastrointestinal complaints eg, upper abdominal pain, diarrhea, constipation or flatulence and allergic reactions eg, pruritus, skin rash (in isolated cases also urticaria or angioedema).
There have been rare reports of nausea, dizziness or disturbances in vision (blurred vision). Peripheral edema, fever, depression or myalgia subsiding after termination of therapy were reported in individual cases.
Ospamox: Occasional transient adverse effects are mostly gastrointestinal (nausea and diarrhea). Owing to the better absorption of amoxicillin, they are, however less commonly seen than during ampicillin treatment. In patients developing diarrhea during treatment, pseudomembranous colitis should be considered (see Precautions). Rarely, hypersensitivity reactions eg, urticarial rashes, fever, joint pain, erythema multiforme, exfoliative dermatitis, angioneurotic edema and hematologic problems eg, thrombocytopenia, agranulocytosis, leukopenia and eosinophilia are seen. These usually run a mild course and generally subside within a few days. Like other penicillins, Ospamox may exceptionally cause severe systemic reactions (anaphylactic shock). Exfoliative dermatitis and erythema multiforme have been described in some cases. Like other penicillins, amoxicillin may cause headache, fatigue, glossitis, stomatitis, fever, joint pain, angioneurotic edema or interstitial nephritis. Minor transient elevations of serum transaminases (SGOT and SGPT) have occasionally been seen.

Klacid: Clarithromycin has been shown not to interact with oral contraceptives. As with other macrolide antibiotics, the use of clarithromycin in patients concurrently taking drugs metabolised by the cytochrome P-450 system (eg, warfarin, ergot alkaloids, triazolam, midazolam, disopyramide, lovastatin, phenytoin and cyclosporin) may be associated with elevations in serum levels of these other drugs. The administration of clarithromycin to patients who are receiving theophylline has been associated with an increase in serum theophylline levels and potential theophylline toxicity.
The use of clarithromycin in patients receiving warfarin may result in potentiation of the effects of warfarin. Prothrombin time should be frequently monitored in these patients. The effects of digoxin may be potentiated with concomitant administration of Klacid. Monitoring of serum digoxin levels should be considered. Clarithromycin may potentiate the effects of carbamazepine due to a reduction in the rate of excretion. Simultaneous oral administration of clarithromycin tablets and zidovudine to HIV-infected adult patients may result in decreased steady state of zidovudine by 1-2 hrs. No such reaction has been reported in children.
Controloc: Controloc may reduce the absorption of drugs whose bioavailability is pH-dependent (eg, ketoconazole). Pantoprazole is metabolized in the liver via the cytochrome P-450 enzyme system. An interaction of pantoprazole with other drugs or compounds which are metabolized using the same enzyme system cannot be excluded. No clinically significant interactions were, however, observed in specific tests with a number of such drugs or compounds eg, carbamazepine, caffeine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, metoprolol, nifedipine, phenprocoumon, phenytoin, theophylline, warfarin and an oral contraceptive. There were also no interactions with concomitantly administered antacids. Human kinetic interaction studies have been performed administering pantoprazole concomitantly with the respective antibiotics (clarithromycin, metronidazole, amoxicillin). No clinically relevant interactions were found.
Ospamox: Concomitant ingestion of allopurinol may promote the occurrence of skin rashes. The underlying mechanism is still poorly understood. As penicillins like amoxicillin only act on proliferating microorganisms, they should not be combined with bacteriostatic antibiotics eg, tetracyclines and chloramphenicol. If suggested by the outcome of susceptibility tests, combinations with other bactericidal antibiotics (cephalosporins, aminoglycoside) may be used. The concomitant administration of probenecid (eg, 0.5 g 4 times a day orally); contraindicated in children <2 years produces sustained and higher plasma level by suppressing renal elimination. Conversely, tissue distribution and diffusion of Ospamox may be reduced by probenecid. Like other antibiotics, aminopenicillin may rarely reduce the efficacy of oral contraceptives. Concomitant antacid intake reduces amoxicillin absorption. Non-enzymatic urinary glucose tests may be false positive. Urobilinogen tests may also be impaired.

Store below 30°C. Protect from light.
Shelf-Life: 36 months.

Antacids, Antireflux Agents & Antiulcerants

A02BD04 - pantoprazole, amoxicillin and clarithromycin ; Belongs to the class of various combinations for the eradication of Helicobacter pylori infection. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).