Can Amoxicillin/Clarithromycin/Omeprazole be used in combination

Can Amoxicillin/Clarithromycin/Omeprazole be used in combination

How does Amoxicillin work

Amoxicillin is a beta lactam class of antibiotic that is primarily used for the treatment of a variety of bacterial infections. Besides bacterial infections, the drug is also prescribed for skin and urinary tract infections, pneumonia, and strep throat. The drug is commonly available under generic name Amoxicillin and marketed under the various brand names such as Amoxil, Tycil, Trimox,  Amocla,  Actimoxi, Moxatag, Larotid  and Alphamox. The drug was first available in 1972 and was listed on the World Health Organization’s List of Essential Medicines. Amoxicillin chemically belongs to the Penicillins class of drugs and characterized by the presence of penam ring. The drug Amoxicillin is available in various forms such as capsule, tablets, oral solution and pediatric drops for oral uses. The recommended dose of Amoxicillin in adult is 500 mg thrice a day or 875 mg twice a day. However, the dose varies depending upon patient and diseased state.

How does Amoxicillin work

What is Clarithromycin

Clarithromycin is an antibiotic drug that belongs to macrolide class of antibiotics i.e. antibiotics that inhibit the growth of bacteria and fight with a broad spectrum of gram-positive bacteria. The drug is available under generic name Clarithromycin and brand names such as Biaxin, Biaxin XL, Biaxin XL-Pak. The drug Clarithromycin was developed in the year 1980 and later recognized and classified in World Health Organization’s List of Essential Medicines that are needed in a basic health system. The drug is chemically derived from Erythromycin and known as 6-O-methylerythromycin. It is generally prescribed to treat bacterial infections such as bronchitis (infection of the tubes leading to the lungs), pneumonia or lung infection, ear infection, skin infection, throat infection and sinuses infection. The drug is also used to treat cat scratch disease and other infections caused by bartonella, Cryptosporidiosis and as second line agent in the treatment of Toxoplasmosis and Lyme disease. The drug is also used as an alternative to treat strep throat and bacterial endocarditis in those who cannot take penicillin. The drug Clarithromycin is also used to treat disseminated Mycobacterium avium complex (MAC) infection, a condition that usually affects patients with HIV (Human Immunodeficiency Virus). Besides this, Clarithromycin is also used in combination with other drugs to treat H. pylori mediated stomach ulcer. The drug is available as delayed or extended release tablet that lasts for a long time or as liquid suspension form to be taken orally by mouth. The drug is recommended with a dosing schedule of 7 to 14 days, with or without food in every 12 hours i.e. twice a day. The length and duration of the drug vary depending upon patients and the disease status.

What is Clarithromycin

How does omeprazole work

Omeprazole is a proton pump inhibitor that acts through blocking gastric acid secretion. The drug was approved by FDA in September, 1989 and grouped in World Health Organization’s List of the essential medications required in a basic health system. Chemically, Omeprazole is a pro drug, which means normally it is biologically inactive agent that produces a drug only upon metabolization inside the body. The generic name of the drug is Omeprazole, Omeprazole/Sodium bicarbonate and is available under several brand names such as Prilosec, Omesec, Prilosec OTC, Zegerid, Zegerid OTC etc.  Chemically, Omeprazole belongs to a class of organic compounds known as sulfinylbenzimidazoles (containing a sulfinyl group attached at the position 2 of a benzimidazole moiety). Prescription Omeprazole is available as a delayed-release capsule (10, 20 and 40 mg), and packets of delayed-release granules (20 and 40 mg) for suspension, whereas nonprescription (over-the-counter) Omeprazole comes in the form of a delayed-release capsule or tablet (20 mg) to be taken by mouth. The dose of the drug depends upon the disease, age and weight. The active ingredient in the delayed-release capsule and delayed-release granule (oral suspension) are Omeprazole and Omeprazole magnesium respectively.

Can Omeprazole be taken with Amoxicillin

How Amoxicillin, Clarithromycin and Omeprazole work

Similar to penicillin and other beta lactam class of drugs Amoxicillin acts against susceptible bacteria during the stage of active multiplication. It acts on the bacteria through blocking or inhibiting the biosynthesis of cell wall mucopeptide (protein polysaccharide component of bacterial cell wall) during bacterial cell multiplication. In bacterial cell wall Amoxicillin interacts with penicillin-binding protein 1A (PBP-1A) and inactivate it through acylation.  PBP-1A enzyme is involved in crosslinking of two linear peptidoglycan strands or polymer chain. Inactivation of PBP-1 results in complete loss of development of cross-link formation and inhibition of cell wall biosynthesis that leads to the death of the bacteria. Amoxicillin is primarily used for the treatment of bacterial infections such as bronchitis, pneumonia, gonorrhoea etc. Besides, this the drug is also recommended to treat the infections of Salmonella and Chlamydia, Lyme disease, Streptococcal pharyngitis and Tonsillitis.

Clarithromycin is a semisynthetic macrolide antibiotic that was originally derived from Erythromycin. The drug acts against a wide range of bacteria including gram-positive (Staphylococcus aureus, S. pneumoniae, and S. pyogenes) and gram-negative aerobic bacteria (Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis), many anaerobic bacteria, and some Mycobacteria. The drug also shows significant activity against other organisms including Mycoplasma, Toxoplasma, Ureaplasma, Chlamydia, and Borrelia. Clarithromycin is usually bacteriostatic antibiotic that means it stops bacteria from reproducing, while not necessarily killing them otherwise. However, depending upon the organism and concentration, Clarithromycin may also show bactericidal effects. Chemically, Clarithromycin belongs to the class of organic compounds known as macrolides and analogues, which are characterized by a lactone ring of at least twelve members.  Clarithromycin acts in a manner similar to that of its parent compound Erythromycin. Clarithromycin, is first metabolized into active compound 14-OH Clarithromycin, which works synergistically with the parent compound. Clarithromycin active metabolites inhibit bacterial protein synthesis through its interaction with bacterial 50S ribosomal subunit. Within 50S ribosomal subunit, Clarithromycin specifically and reversibly binds with domain V of 23S ribosomal RNA. This results in inhibition or blocking of aminoacyl t-RNA translocation and ultimately polypeptide synthesis. Besides this, it has also been suggested that Clarithromycin also acts and inhibits microsomal CYP3A4 isozyme and P-glycoprotein.

The Omeprazole drug is a benzimidazole, which is a selective and irreversible proton pump inhibitor. The proton pumps are integral membrane proteins that are capable of moving protons across a biological membrane. In stomach, proton pumps (such as hydrogen-potassium (H+/ K+) ATPase enzyme system) are present at the secretory surface of parietal cells in the stomach and involved in pronounced and long-lasting production of gastric acid or gastric juice. The gastric acid is composed of hydrochloric acid (HCl), potassium chloride (KCl) and sodium chloride (NaCl). Omeprazole results in the suppression of gastric acid secretion by formation of a stable disulfide bond with the sulfhydryl group of the hydrogen-potassium (H+/ K+) ATPase enzyme system, thus inhibiting the final step in the acid production i.e., transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen. Due to its mode of action the Omeprazole is generally prescribed to be taken atleast one hour before meals. The drug (prescription) is prescribed either alone or in combination with other medications in therapy of acid-induced inflammation, gastroesophageal reflux disease (GERD), stomach and duodenum ulcers, erosive esophagitis, Zollinger-Ellison Syndrome (gastrin-producing tumour), and heartburn.

Can Amoxicillin, Clarithromycin and Omeprazole be taken together in combination

Yes, Amoxicillin, Clarithromycin and Omeprazole medications can be used in combination. Amoxicillin (penicillin antibiotic) and Clarithromycin (macrolide antibiotic) are antibiotics that act against a broad spectrum of bacteria, where as Omeprazole acts as a proton pump inhibitor thus reduces the formation of gastric juice. Amoxicillin, Clarithromycin, and Omeprazole are together used in combination as a triple therapy to treat gastric or stomach ulcer caused by infection with Helicobacter pylori (H. pylori). In triple therapy, Omeprazole inhibits transport of hydrogen ions into the gastric lumen and suppresses gastric acid secretion, while Amoxicillin and Clarithromycin interrupt the bacterial cell wall and protein synthesis, thus causing weakening of the bacterial cell wall and cell lysis, as well as inhibition of bacterial reproduction. Amoxicillin shows several advantages over other antibiotics such as high tolerability and digestibility, lack of resistance to H.pylori and potent activity and efficacy in eradicating H.pylori. Each dosing regimen contains 4 pills (3 capsules and 1 tablet). Amoxicillin, Clarithromycin, and Omeprazole dosing schedule consists of an initial dose of 1000 mg Amoxicillin, 500 mg Clarithromycin and 20 mg Omeprazole, twice a day (12 h interval) in the morning and evening before eating a meal. The triple combination is available under brand name Omeclamox-Pak, which contains all three Amoxicillin, Clarithromycin and Omeprazole in prescribed dose. The triple therapy is usually recommended for a period of 10 days, however in case of an active gastric ulcer an additional dosing for 18 days of Omeprazole 20 mg once a day is also recommended. The pill or tablet should not be crushed or chewed rather it is recommended to swallow pill/tablet as a whole.

Can Amoxicillin, Clarithromycin and Omeprazole be taken together in combination

Clinical research and current scenario of Amxicillin/Clarithromycin/Omeprazole triple therapy

  • Double blind, multicentre United States trials have revealed that 10 days of twice-daily triple therapy with Amoxicillin, Clarithromycin and Omeprazole achieves per-protocol Helicobacter pylori eradication rates of approximately 80% to 90% in duodenal ulcer disease.
  • Similarly in China, one-week triple therapy of Amoxicillin, Clarithromycin and Omeprazole showed significant efficacy for the eradication of pylori infection. This therapeutic regimen suggested a low cost, good compliance and mild adverse events that offer a good choice for the treatment of peptic ulcers associated with H. pylori infection.
  • In children and adolescents, triple combination therapy with Amoxicillin, Clarithromycin and Omeprazole have shown a moderate efficacy. The data had shown that 10 days therapy achieves a better eradication rate (73%) than 7 days course (50%) to treat pylori infection.
  • It has been observed that addition of vitamin C along with Amoxicillin, Clarithromycin and Omeprazole 7 day therapy can reduce the dosage of Clarithromycin with higher eradication efficiency in pylori infection.
  • In a pilot study, it has been observed that a four-day, twice daily, quadruple therapy with Amoxicillin, Clarithromycin, Tinidazole and Omeprazole showed acceptably high cure rate of peptic ulcers associated with pylori infection.
  • Another pilot study performed in Japanese population has shown the efficacy and safety of Helicobacter pylori eradication therapy with Amoxicillin, Omeprazole and high and low dosage of Clarithromycin. In this study it has been demonstrated that triple-therapy regimen with Clarithromycin 400 mg/day was as effective as that with Clarithromycin 800 mg/day.
  • Currently, Amoxicillin is also used as triple therapy forHelicobacter pylori infection and duodenal ulcer disease in combination with Clarithromycin and Lansoprazole.

Amoxicillin Clarithromycin Omeprazole side effects

Safety and precautions while taking Omeprazole-Amoxicillin combination

  • The usual dosing of the drug in combination may vary depending upon the efficiency and side effects of the drug in a particular individual. Therefore, it is advisable to discuss all the health related issues with your doctor before taking Clarithromycin in combination with Amoxicillin and Omeprazole.
  • Do not use the medicine if you are hypersensitive or allergic (e.g., anaphylaxis or Stevens-Johnson syndrome) to Amoxicillin or any other penicillin antibiotic (such as Ampicillin, Dicloxacillin and Oxacillin) or to any macrolide antibiotic (e.g., erythromycin) or substituted benzimidazoles or to any ingredient of the drug formulation.
  • The Clarithromycin, Omeprazole and Amoxicillin may interact with other drugs. Therefore, care should be taken when you are taking any prescription or non-prescription medicines and herbal or vitamin supplements. It is advisable that you do not start, stop or change or take any medicine unless you have discussed with your doctor or professional consult.
  • It has been observed that Omeprazole may cause a serious type of allergic reaction when used in combination with antibiotics. In case of allergic hypersensitive reactions such as itching, trouble breathing or swallowing, or any swelling of your hands, face, or mouth, it is advisable to call your doctor right away.
  • The triple combination is not recommended if you have infectious mononucleosis or any previous kidney or liver problems, or low blood potassium or magnesium level, certain types of irregular heartbeat such as ventricular arrhythmias,  long QT syndrome and QT prolongation.
  • Before taking Clarithromycin- Omeprazole-Amoxicillin, tell your doctor about your medical history if you have kidney disease, liver disease, asthma, mononucleosis (also called “mono”), a bleeding or blood clotting disorder, or any type of allergy, hay fever or hives. Do not stop taking Amoxicillin until you do not finish the prescription. If you do not follow the prescription or stop taking aAmoxicillin too early, it may lead to the development of antibiotic resistance in bacteria.
  • The use of Clarithromycin and Amoxicillin may sometimes increase the risk of Clostridium difficile-associateddiarrhea (CDAD). If you experience symptom of diarrhea that does not seem to improve seek immediate medical attention.
  • Antibiotic therapy of Amoxicillin and Clarithromycin in the absence of suspected bacterial infection and discontinuation of therapy before time or too early increases the risk of the development of drug-resistant bacteria.
  • It has been observed that colitis is occasionally caused by taking antibiotics (antibiotic associated colitis). Antibiotic therapy is usually associated with reduced gut microbial flora, permits overgrowth of some of the harmful bacteria over normal gut flora. Clostridium difficile is one of such bacterial species that flourish well under antibiotic therapy. Its toxin is supposed to be a primary cause of antibiotic-associated colitis. Thus, antibiotic therapy with Amoxicillin and other broad-spectrum antibiotics agents should be managed cautiously in patients with a history of gastrointestinal diseases, particularly colitis.

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