Gastrosam

Uses

• LRTIs for example, acute and chronic bronchitis and pneumonia.
• URTIs for example, sinusitis and pharyngitis.
• Community-acquired pneumonia, atypical pneumonia
• Skin and soft tissue infection
• Adjunct in the treatment of duodenal ulcers to eradicate of H. pylori

Lansoprazole is used for:

• Short term treatment of active duodenal ulcer
• Maintenance of healed duodenal ulcers
• Short term treatment of active benign gastric ulcers
• Short term treatment of active erosive esophagitis
• Maintenance of healing of erosive esophagitis
• Pathological hypersecretory conditions including Zollinger- Ellison Syndrome
• H. pylori eradication to reduce the risk of duodenal ulcer recurrence

Gastrosam is also used to associated treatment for these conditions: Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB), Acute maxillary sinusitis, Bacterial Infections, Bartonellosis, Community Acquired Pneumonia (CAP), Duodenal ulcer caused by helicobacter pylori, Infective Endocarditis, Lyme Disease, Mycobacterial Infections, Otitis Media (OM), Pertussis, Streptococcal Pharyngitis, Streptococcal tonsillitis, Uncomplicated skin and subcutaneous tissue bacterial infectionsGastro-esophageal Reflux Disease (GERD), Gastrointestinal Bleeding, Helicobacter Pylori Infection, Peptic Ulcer Disease, Hypersecretory conditions

How Gastrosam works

Clarithromycin is first metabolized to 14-OH clarithromycin, which is active and works synergistically with its parent compound. Like other macrolides, it then penetrates bacteria cell wall and reversibly binds to domain V of the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome, blocking translocation of aminoacyl transfer-RNA and polypeptide synthesis. Clarithromycin also inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump.

As a PPI, lansoprazole is a prodrug and requires protonation via an acidic environment to become activated. Once protonated, lansoprazole is able to react with cysteine residues, specifically Cys813 and Cys321, on parietal H+,K+-ATPase resulting in stable disulfides. PPI's in general are able to provide prolonged inhibition of acid secretion due to their ability to bind covalently to their targets.

Dosage

Gastrosam dosage

Clarithromycin may be given with or without meals.

Adults (12 years or above):

250 mg twice daily for 7 days. Dose may be increased to 500 mg twice daily for up to 14 days in pneumonia or severe infections.

Combination therapy for H. pylori infection:

Clarithromycin 500 mg (two 250 mg tablets or one 500 mg tablet) twice daily in combination with Amoxicillin 1000 mg twice daily and Omeprazole 20 mg twice daily should be continued for 10 days.

Children:

The usual recommended daily dosage is 15 mg/kg in 2 divided doses for 10 days.

Approximate Calculation of dose:

1. For 9kg body weight 2.5ml 12 hourly for 10 days

2. For 17kg body weight 5ml 12 hourly for 10 days

3. For 25kg body weight 7.5ml 12 hourly for 10 days

4. For 33kg body weight 10ml 12 hourly for 10 days

Direction for reconstitution of suspension:

Shake the bottle to loosen granules. Add 35 ml of boiled and cooled water with the help of the supplied cup, to the dry granules of the bottle. For ease of preparation, add water to the bottle in two proportions. Shake well after each addition until all the granules is in suspension.

Note: Shake the suspension well before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place, preferably in refrigerator.

Benign gastric ulcer: 30 mg daily in the morning for 8 weeks.

Duodenal ulcer: 30 mg daily in the morning for 4 weeks; maintenance 15 mg.

NSAID-associated duodenal or gastric ulcer: 15-30 mg daily for 4 weeks, followed by a further 4 weeks if not fully healed.

Zollinger-Ellison syndrome (and other hypersecretory conditions): Initially 60 mg once daily adjusted according to response; daily doses of 120 mg or more is given in two divided doses.

Gastroesophageal reflux disease: 30 mg daily in the morning for 4 weeks, followed by a further 4 weeks if not fully healed; maintenance 15-30 mg daily.

Acid-related dyspepsia: 15-30 mg daily in the morning for 2-4 weeks.

This may be given with or without meals.

The usual duration of treatment is 6 to 14 days.

Children older than 12 years: As for adults.

Eradication of H. pylori in patients with duodenal ulcers: Adults: The usual duration of treatment is 6 to 14 days.

45 ml of water is to be added to the granules in the bottle and shaken to yield 70 ml of reconstituted suspension. The concentration of clarithromycin in the reconstituted suspension is 125 mg per 5 ml.

Side Effects

The most frequently reported events in adults taking Clarithromycin were diarrhoea (3%), nausea (3%), abnormal taste (3%), dyspepsia (2%), abdominal pain/discomfort (2%), headache (2%) and oral monilia.

Severe or irreversible adverse effects: The possible induction of carcinoid tumors by profound acid suppression, and a rise in serum gastrin may occur. There is a rise in serum gastrin levels in the first 3 months of treatment, which are then maintained though at a lower level than those found in pernicious anaemia. Long term treatment with a proton pump inhibitor in patients with Helicobacter pylori infection may accelerate the development of atrophic gastritis.

Symptomatic adverse effect: Dose dependent diarrhoea occurs with an incidence of about 4% at 30 mg per day, rising to 8% at 60 mg per day. Headache occurs in 2-3% of treated patients

Toxicity

Symptoms of toxicity include diarrhea, nausea, abnormal taste, dyspepsia, and abdominal discomfort. Transient hearing loss with high doses has been observed. Pseudomembraneous colitis has been reported with clarithromycin use. Allergic reactions ranging from urticaria and mild skin eruptions to rare cases of anaphylaxis and Stevens-Johnson syndrome have also occurred. Rare cases of severe hepatic dysfunctions also have been reported. Hepatic failure is usually reversible, but fatalities have been reported. Clarithromycin may also cause tooth decolouration which may be removed by dental cleaning. Fetal abnormalities, such as cardiovascular defects, cleft palate and fetal growth retardation, have been observed in animals. Clarithromycin may cause QT prolongation.

The most commonly reported adverse events occurring more frequently in lansoprazole treated patients compared to placebo include abdominal pain, constipation, diarrhea, and nausea. There is a case report of toxic epidermal necrolysis (TEN), which is a rare but very serious cutaneous reaction, caused by lansoprazole. The previously healthy patient presented with symptoms of TEN 15 days after starting lansoprazole to manage peptic disease. Although the use of PPI's is rarely associated with TEN, causation should be considered if a patient presents with TEN shortly after newly commencing a PPI.

In a single case report, a patient ingested 600 mg of lansoprazole and did not experience any adverse effects or symptoms of overdose. Overall, lansoprazole is well tolerated with relatively few adverse effects.

Lansoprazole is classified as Pregnancy Category B. Although there are animal studies that suggest lansoprazole does not cause harm to the fetus, there is still a paucity of human data. Hence, lansoprazole should only be administered to pregnant women if other options with more safety data have been exhausted.

It is unknown if lansoprazole is excreted in human breast milk. It is worth mentioning that lansoprazole has been used safely in infants, and is therefore likely safe to use during breastfeeding.

Precaution

Caution should be taken in administering this antibiotic to patients with impaired hepatic and 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.

Pharmaceutical precaution

Clarithromycin tablet should be stored in a cool and dry place and away from sunlight.

Gastric malignancy should be ruled out. Hepatic impairment. Pregnancy and lactation.

Interaction

Concomitant use of Clarithromycin who are receiving Theophylline may be associated with an increase in serum Theophylline concentrations. Clarithromycin may alter the metabolism of Terfenadine. The effects of digoxin may be potentiated with concomitant administration of Clarithromycin. Clarithromycin resulted in decrease in serum levels of Rifabutin, followed by an increased risk of uveitis.

Lansoprazole appears to be a selective inhibitor of the cytochrome P-450 monooxygenase system; there may be an effect on hepatic clearance, but there have been no reports to date of clinically relevant interactions. There is some uncertainty over the effect of Lansoprazole on the oral combined contraceptive pill. Further assessment is currently underway. Physiological changes similar to those found with Omeprazole are likely to take place because of the reduction in gastric acid, which is likely to influence the bacterial colonization of the stomach and duodenum and also vitamin B12 absorption.

Volume of Distribution

The apparent volume of distribution of lansoprazole is 0.4 L/kg.

Elimination Route

Clarithromycin is well-absorbed, acid stable and may be taken with food.

The oral bioavailability of lansoprazole is reported to be 80-90% and the peak plasma concentration(Cmax) is achieved about 1.7 hours after oral dosing. Food reduces the absorption of lansoprazole (both Cmax and AUC are reduced by 50-70%); therefore, patients should be instructed to take lansoprazole before meals.

Half Life

3-4 hours

One source reports the half life of lansoprazole to be 0.9 - 1.6 hours, while another source cites 0.9 - 2.1 hours. The general consensus is that lansoprazole has a short half life and is approximately 2 hours or less. These numbers may be misleading since it suggests that lansoprazole has a short duration of action when in practice, lansoprazole can effectively inhibit acid secretion for ~24 hours due to it's mechanism of action.

Clearance

The reported clearance of lansoprazole is 400-650 mL/min.

Elimination Route

After a 250 mg tablet every 12 hours, approximately 20% of the dose is excreted in the urine as clarithromycin, while after a 500 mg tablet every 12 hours, the urinary excretion of clarithromycin is somewhat greater, approximately 30%.

A reported 14-23% of a lansoprazole is eliminated in the urine with this percentage range including both conjugated and unconjugated hydroxylated metabolites.

Pregnancy & Breastfeeding use

Clarithromycin is not recommended for pregnant women. Breast milk from mothers receiving Clarithromycin should not be given to infants until treatment is completed. Clarithromycin may be used in neonates and children in appropriate doses.

Lansoprazole should be avoided in pregnancy unless there are compelling reasons.

Contraindication

Hypersensitive to Clarithromycin, Erythromycin or any of the macrolide antibiotics. Patients receiving terfenadine who have pre-existing cardiac abnormalities or electrolyte disturbances.

Lansoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation.

Special Warning

Clarithromycin may be used in neonates and children in appropriate doses.

Neonates:There is no relevant human data. The drug is not recommended for use with neonates.

Children: The youngest person to have received Lansoprazole in clinical trials was 13 years old.

The Elderly: No problems have been encoun- tered in clinical use and there has been no increase in adverse drug reaction in the elderly.

Acute Overdose

Signs & Symptoms : Ingestion of large amounts of Clarithromycin can be expected to produce gastrointestinal symptoms. Symptoms of overdose may largely correspond to the profile of side effects.

Management: There is no specific antidote on overdose. Serum levels of Clarithromycin can not be reduced by haemodialysis or peritoneal dialysis.

Storage Condition

Store in a cool and dry place, protected from light.

Store at 25° C.

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