Delayed-release capsules and for delayed release oral suspension
In which dosage forms and strengths this drug is available?
- The NEXIUM is available as the delayed release capsules in the strengths of 20mg and 40mg
- It is also available as for delayed release oral suspension form containing 2.5mg, 5 mg, 10mg, 20 mg and 40 mg of Nexium in the unit dose packaging. The Nexium is in the granular or powdered form in such a suspension.
Under which conditions Nexium should be used?
- Esomeprazole is commonly used for treating the conditions like GERD and erosive esophagitis. The treatment may last for 4 to 8 weeks until the symptoms of heartburn disappear.
- The patients on the continuous therapy with the painkillers called NSAIDS may tend to develop a type of gastric ulcer called as NSAID associated gastric ulcer. Esomeprazole can be administered for treating and preventing this type of gastric ulcer.
- It is also indicated as a combination therapy for the eradication and the removal of Helicobacter pylori (H.pylori). This is the major cause of the development of gastric and duodenal ulcer. A combination of three drugs i.e. Nexium plus clarithromycin plus amoxicillin is usually indicated for such condition.
- Nexium is also indicated for some of the other hyper secretory conditions such as Zollinger-Ellison Syndrome.
- In adults:
- GERD without Erosive Esophagitis: 20 mg per oral per day for 4 weeks; consider an additional 4 weeks of treatment if symptoms do not resolve completely in the first 4 weeks.
- GERD With Erosive Esophagitis: 20-40 mg orally per day for 4-8 weeks.
- Helicobacter Pylori Eradication: Combination therapy (with amoxicillin and clarithromycin) for eradication of H. pylori in patients with duodenal ulcers is 40 mg orally per day for 10 days, PLUS Amoxicillin 1000 mg per oral q12hours for 10 days, PLUs Clarithromycin 500 mg oral q12 hours for 10 days.
- NSAID-Induced Gastric Ulcer: 20 mg per oral (PO)/day for 4-8 weeks.
- Zollinger-Ellison Syndrome: 80 mg PO divided by 12hours (initial); adjust regimen to efficacy; up to 240 mg PO per day, OR 120 mg PO within 12 hours.
- In pediatrics:
- GERD without Erosive Esophagitis: <1 year: Safety and efficacy is not established. For 1-12 years: 10-20 mg PO /Day for up to 8 weeks. For >12 years: 20-40 mg PO per day for up to 8 weeks.
- GERD with Erosive Esophagitis (Healing) : <1 month: Safety and efficacy is not established. For 1 month to 1 year weighing 3.5 kg: 2.5 mg PO per day for up to 6 weeks. For >3.5-7.5 kg: 5 mg PO /Day for up to 6 weeks. For >7.5 kg: 10 mg PO /Day for up to 6 weeks. For 1-12 years and weighing <20 kg: 10 mg PO per day for 8 weeks. For ≥20 kg: 10-20 mg /day for 8 weeks. For >12 years: 20-40 mg PO /Day for 4-8 weeks. Maintenance dose: 20 mg PO q/day up to 6 months.
How should you take Nexium?
- Take Nexium exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than suggested.
- This medicine is usually given for 4 to 8 weeks only. Your doctor may recommend a second course of treatment if you need additional healing time.
- Take each dose with a full glass (8 ounces) of water.
- Nexium should be taken at least one hour before a meal.
- Do not crush or chew a delayed-release capsule. However to make swallowing easier, you may open the Nexium capsule and sprinkle the medicine into a spoonful of pudding or an apple sauce. Swallow right away without chewing. Do not save the mixture for later use.
- Nexium can be given through a nasogastric (NG) feeding tube. Open the capsule and sprinkle the medicine into a 60-milliliter syringe. Mix in 50 milliliters of water. Place the plunger into the syringe and shake the mixture well. Make sure there is no medicine granules stuck in the tip of the syringe. Attach the syringe to the NG tube and push the plunger down to empty the syringe into the tube. Then flush the tube with more water to wash the contents down.
- Take this medicine for the full prescribed length of time. Your symptoms may improve before the condition is fully treated.
- If you use Nexium for longer than 3 years, you could develop a vitamin B-12 deficiency. Talk to your doctor about how to manage this condition if you develop it.
- Call your doctor if your symptoms do not improve or if they get worse while you are taking this medicine.
- Nexium can cause unusual results with certain medical tests, and you may need to stop using the medicine for a short time before a test. Tell any doctor who treats you that you are using this medicine.
- Store at room temperature away from moisture and heat.
Under what circumstances this drug should not be used?
- It is contraindicated in the patients exhibiting any sort of hypersensitivity to any of the components of the formulation or to the active ingredient. It is also contraindicated in those patients who are allergic to the substituted benzimidazoles. The chief complaints associated with the hypersensitivity are anaphylactic shock, urticarial, bronchospasm, anaphylaxis, and acute nephritis.
- This drug shows interaction with clopidogrel, a prodrug which inhibits the platelet aggregation. The mechanism by which the clopidogrel is converted into its active metabolite is hampered by the presence of some other drugs such as esomeprazole. So esomeprazole should not be used with this drug.
Therapy with Nexium should be monitored closely and with caution for the following conditions.
- The condition of concurrent gastric malignancy
- Condition of Atrophic gastritis
- Condition of acute interstitial nephritis
- Deficiency of Vitamin B-12
- Diarrhea associated with Clostridium difficile
- It should be used with great caution in the patients with bone fractures as it increases the incidence of osteoporosis.
- Treatment for more than three months with this drug may lead to a condition called as hypo-magnesemia.
- Acute interstitial nephritis has been reported in patients taking proton pump inhibitors.
- Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin.
What adverse effects this drug can cause?
The most frequently occurring adverse drug reactions include:
- Pain in the abdomen
- Dryness of the mouth
The less frequent adverse drug reactions may include
- Flu like symptoms
Cardiovascular related adverse effects include
Gastrointestinal related adverse reactions include
- Stool and bowel irregularities
- Epigastric pain
- Gastrointestinal pain
- Ulcerative stomatitis
Hematological adverse reactions include
- Epistaxis (nose bleeds)
Hepatic adverse reactions include
- Impaired liver functions i.e. increased SGOT and SGPT levels
Nervous system effects include
- Sleep disorder
Respiratory adverse effects include
- Aggravation of asthma
Other observed effects are glycosuria, tinnitus, goiter, conjunctivitis, polyuria, and dysuria and vitamin B-12 deficiency.
What kind of drug-interactions can it cause?
Esomeprazole shows interactions with many other drugs such as:
- Anti-retrovial drugs
- It can interact with the antiretroviral drugs such as atazanavir and nelfinavir and decrease the plasma level concentration of these drugs leading to the development of the resistance to the therapy. So its use with these agents is contraindicated.
- It may decrease the absorption of certain other drugs like
- Iron salts
- Mycophenolate mofetil (MMF)
- It can also increase the absorption of certain other drugs such as digoxin.
- Interaction with a drug clopidogrel results in its decreased platelet inhibition activity
- Concomitant administration of this drug with cilostazol increases its plasma contrations therefore dose adjustment is necessary.
- Other drugs that need the dose adjustment while co-administering are voriconazole, rifampin and tacrolimus.
- When administered with methotrexate it increases the plasma level of methotrexate and no adverse effect is observed.
Something about Nexium Pharmacology: What is its mode of action?
The drug esomeprazole belongs to a class of drugs known as proton pump inhibitors. It acts by inhibiting H+/K+ ATPase pump in the parietal cells of the gastric mucosa. This inhibition leads to a decrease in the secretion of gastric acid from the stomach. Esomeprazole blocks the final step of the acid production thus reducing the acidity of the stomach.
How the absorption of Nexium takes place?
Both NEXIUM delayed release capsules and for delayed release oral suspension contain bioequivalent ingredient esomeprazole magnesium. It is present in the granular form and is enteric-coated. The maximum peak plasma levels are attained in an approximate time (tmax.) of 1.5 hours. The maximum peak plasma concentration (Cmax.) of the drug is dose dependent i.e. it increases in the direct proportion with the dose.
- When the dose is increased from 20 mg to 40 mg the area under the plasma level time curve (AUC) is increased three times.
- The systemic bioavailability with a single dose of 40 mg of Nexium is 64% and 90% after the repeated daily single dose administration.
- It is observed that the AUC after the administration of 40 mg of Nexium as a single dose is decreased significantly after the intake of the food when compared to the fasting conditions.
So, Nexium should be taken at least an hour prior to meals.
How this drug is distributed?
This drug is majorly bound to plasma proteins almost 97%. The apparent volume of distribution (Vd) at the steady state concentration is observed to be approx. 16 Liters.
Metabolism of Nexium
Esomeprazole is metabolized by the Cytochrome P450 (CYP) enzyme system. The major site for its metabolism is liver. The resultant metabolites do not have any secretion blocking activity. CYP2C19 is the major enzyme that is chiefly responsible for its metabolism. Both S- and R- isomeric forms are metabolized by liver at different rates. Therefore, the S- isomeric form has a high concentration in the plasma compared to the R- isomer.
How this drug is eliminated out of the body?
The elimination half-life of esomeprazole is 1 to 1.5 hours approximately. Almost 80% of the drug metabolites are excreted out of the body through urine whereas only 1% of the drug is excreted in the unchanged form. The remaining inactive metabolites are excreted through the feces.
What is the pharmacokinetics for special populations?
- For the geriatric patients a slight increase in the AUC and Cmax is observed but the condition does not warrant for any dose adjustment.
- The values for AUC and Cmax were found to be slightly higher approx. 13% in females than in males. Dose adjustment is not considered to be necessary.
- Similarly, the pharmacokinetic data after administration of esomeprazole to the patients having renal impairment shows no significant difference to that of the healthy human volunteers.
Can this drug be used in the specific populations?
- During pregnancy: it is a pregnancy category C There are no adequate and well-controlled studies with NEXIUM in pregnant women. NEXIUM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- In nursing women: Esomeprazole is likely to be present in human milk. Caution should be exercised when Nexium is administered to a nursing woman.
- In pediatrics: the safety and effectiveness of NEXIUM have not been established in patients less than 1 month of age.
- In geriatrics: no major differences in responses occur between the elderly and younger patients.
Toxicology of Nexium:
- The carcinogenic potential of NEXIUM was assessed using studies of omeprazole, of which esomeprazole is an enantiomer.
- omeprazole at daily doses of 1.7, 3.4, 13.8, 44, and 140.8 mg/kg/day (about 0.4 to 34 times the human dose of 40 mg/day expressed on a body surface area basis) was found to produce gastric ECL cell carcinoids in a dose-related manner in both male and female rats; the incidence of this effect was markedly higher in female rats, which had higher blood levels of omeprazole.
- Although no influence was discovered on reproductive organs of the animals, and no injurious effects were seen on the fertility of the rats.
What should you tell your doctor before taking this medication?
- You should not use Nexium if you are allergic to esomeprazole or to similar medicines such as lansoprazole (Prevacid), omeprazole (Prilosec, Zegerid), pantoprazole (Protonix), or rabeprazole (AcipHex).
- Heartburn is often confused with the first symptoms of a heart attack. Seek emergency medical attention if you have chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, and a general ill feeling.
- Taking a proton pump inhibitor such as Nexium may increase your risk of bone fracture in the hip, wrist, or spine. This effect has occurred mostly in people who have taken the medicine long term or at high doses, and in those who are of age 50 and older.
To make sure Nexium is safe for you, tell your doctor if you have:
- severe liver disease;
- low bone mineral density (osteopenia); or
- low levels of magnesium in your blood.
- It is not known whether Nexium will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.
- It is not known whether esomeprazole passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.
What are the storage requirements for Nexium?
It should be stored at room temperature 250C (770F).
What are the ingredients in NEXIUM?
Active ingredient: esomeprazole magnesium trihydrate
Inactive ingredients in NEXIUM Delayed-Release Capsules (including the capsule shells): glyceryl monostearate 40-55, hydroxypropyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer type C, polysorbate 80, sugar spheres, talc, triethyl citrate, gelatin, FD&C Blue #1, FD&C Red #40, D&C Red #28, titanium dioxide, shellac, ethyl alcohol, isopropyl alcohol, n-butyl alcohol, propylene glycol, sodium hydroxide, polyvinyl pyrrolidone, and D&C Yellow #10.
Inactive granules in NEXIUM for Delayed-Release Oral Suspension: dextrose, xanthan gum, crospovidone, citric acid, iron oxide, and hydroxypropyl cellulose.