Miracid

Omeprazole.

Each capsule contains omeprazole 20 mg.

Pharmacodynamics: Mechanism of Action: Omeprazole is a selective and irreversible proton pump inhibitor. Omeprazole suppresses gastric acid secretion by specific inhibition of the hydrogen-potassium adenosine triphosphatase (H⁺, K⁺-ATPase) enzyme system found at the secretory surface of parietal cells. It inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen. The inhibitory effect is dose-related. Omeprazole inhibits both basal and stimulated acid secretion irrespective of the stimulus.
Pharmacokinetics: Omeprazole, the prototype drug of proton pump inhibitors (PPIs), is metabolized primarily by CYP2C19 to 5-hydroxyomeprazole. 5-hydroxyomeprazole is then transformed into 5-hydroxyomeprazole sulfone by CYP3A4.
Omeprazole is metabolized directly in part by CYP3A4 to omeprazole sulfone, then transformed into 5-hydroxyomeprazole sulfone by CYP2C19.
Absorption: T_max: delayed-release capsules: 30 minutes to 3.5 hours.
Bioavailability: 30% to 40%; Hepatic dysfunction ~100%; Asian: AUC increased upto fourfold compared to Caucasians.
Food effect: the rate, but not the extent, of absorption is affected by food.
Distribution: V_d: 0.34 to 0.37 L/kg.
Protein binding: 95% to 96%.
Metabolism: Hepatic, extensive first pass.
Excretion: Bile: 16% to 19%.
Fecal: 18% to 23%.
Renal: 70% to 77%; very little as unchanged drug.
Total body clearance: 500 to 600 mL/minute.
Elimination Half life: Adults: 0.5 to 1 hour.
Chronic liver disease: 3 hours.
Geriatric patient: 1 hour.

Duodenal ulcer; Duodenal ulcer associated with Helicobacter pylori. In combination with clarithromycin (dual therapy) or with amoxicillin and clarithromycin (triple therapy); Gastric ulcer; Gastroesophageal reflux disease (GERD); Pathologic GI hypersecretory conditions, e.g. Zollinger Ellison syndrome.

Recommended Doses: Duodenal ulcer: For the short-term treatment of active duodenal ulcer, the usual adult dosage of omeprazole is 20 mg once daily. Therapy should be continued until healing occurs, usually within 2-4 weeks; some patients may benefit from an additional 4 weeks of therapy. Occasionally, dosages up to 40 mg daily may be necessary in patients who have been poorly responsive to therapy with H₂-receptor antagonists.
Duodenal ulcer associated with Helicobacter pylori: When omeprazole is used in combination with clarithromycin (dual therapy) for the treatment of Helicobacter pylori infection in patients with active duodenal ulcer, the usual adult dosage of omeprazole is 40 mg once daily (in the morning) for 14 days. In patients who have an active ulcer present at the time anti-H. pylori therapy is initiated, an additional 14 days of therapy with omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief. When omeprazole is used in combination with clarithromycin and amoxicillin (triple therapy) for the treatment of H. pylori infection in patients with active duodenal ulcer, the usual adult dosage of omeprazole is 20 mg twice daily (morning and evening) for 10 days. In patients who have an active ulcer present at the time anti-H. pylori therapy is initiated, an additional 18 days of therapy with omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.
Gastric ulcer: For the short-term treatment of active benign gastric ulcer, the usual adult dosage of omeprazole is 40 mg once daily for 4-8 weeks.
Gastroesophageal reflux: For the short-term, symptomatic treatment of gastroesophageal reflux disease (GERD) without erosive esophageal lesions, the usual adult dosage of omeprazole is 20 mg once daily for 4 weeks.
For those with erosive esophagitis, the usual adult dosage of omeprazole is 20 mg once daily for 4-8 weeks. Occasionally, dosages up to 40 mg daily may be necessary in some patients. Therapy is continued until healing occurs, usually within 4-8 weeks; an additional 4 weeks therapy (up to 12 weeks for a single course) may contribute to healing and symptomatic improvement in some patients.
Pathologic GI hypersecretory conditions: For the treatment of pathologic GI hypersecretory conditions (e.g. Zollinger-Ellison syndrome), dosage of omeprazole should be individualized according to patient response and tolerance. The usual initial adult dosage is 60 mg once daily and therapy continued as long as clinically necessary. Daily dosages exceeding 80 mg should be administered in divided doses. A dosage up to 120 mg three times per day have been administered. Determination of gastric acid secretion during the hour prior to a dose may be useful in establishing optimum dosage.
Dosage in renal and hepatic impairment: Although pharmacokinetics may be altered in patients with renal impairment, dosage adjustment does not appear necessary in patients with such impairment. However, dosage adjustment should be considered in patients with hepatic impairment, particularly in such patients receiving long-term omeprazole therapy for maintenance or healing of erosive esophagitis. Some clinicians recommend that such patients with hepatic dysfunction receiving dosages exceeding 20 mg daily should be monitored closely for possible adverse effects.
Dosage in geriatric patients: Dosage adjustment solely on the basis of age generally is not required for geriatric patients especially when used short-term. However, since the bioavailability of omeprazole appears to be increased substantially in Asians, dosage adjustment should be considered in Asian patient especially when receiving long-term treatment for maintenance of healing of erosive esophagitis.
There is no evidence from omeprazole prescription safety database that Asians experience excess risk from omeprazole or that accumulation of omeprazole in the blood is harmful when used over a short period of time (e.g., 14 days of self-medication) in Asian patients.
Mode of Administration: Omeprazole should be taken before meal (most effective when given about 30 minutes prior to meals). Omeprazole usually is administered once daily in the morning. Patients should be advised that the capsules must be swallowed intact and not opened, chewed or crushed.

Overdose: In limited overdose cases clinical effects have consisted of mild tachycardia, flushing, somnolence, confusion, headache, blurred vision, abdominal pain, nausea, vomiting dry mouth, and moderate leukocytosis.
Treatment: Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting.

Omeprazole is contraindicated in patients with known hypersensitivity to the drug, esomeprazole or other substituted benzimidazoles (e.g. lansoprazole, pantoprazole, rabeprazole) or any ingredient in the formulation.
Concurrent use of omeprazole and rilpivirine is contraindicated.

1) Patients should be advised to consult their clinician before using omeprazole if: They are taking warfarin, an antifungal agent (e.g. ketoconazole), diazepam or digoxin.
They have heartburn that has persisted for more than 3 months or heartburn in conjunction with lightheadedness, sweating or dizziness.
They are experiencing chest or shoulder pain with lightheadedness, shortness of breath, sweating or pain spreading to arm, neck or shoulders.
They have frequent chest pain, unexplained weight loss, nausea and vomiting, stomach pain or frequent wheezing (especially with heartburn).
2) Patients should discontinue taking omeprazole and consult their clinician if heartburn persists or worsens after 14 days of therapy or a course of treatment is needed more frequently than every 4 months.
3) Patients with difficulty or pain with swallowing, vomiting with blood or bloody or blackened stools should not use omeprazole; such manifestations should be reported promptly to a clinician.

Pregnancy: Omeprazole cross the placenta in animals and humans. Because there are no adequate and controlled studies using omeprazole in pregnant women and because studies to date in animals and pregnant women cannot rule out the possibility of harm, the drug should be used during pregnancy only when the potential benefits justify the possible risk to the fetus.
Lactation: Omeprazole is distributed into human milk. Because of the potential for serious adverse reactions to omeprazole in nursing infants and because of the potential for tumorigenicity shown in animal studies, a decision should be made whether to discontinue nursing or the drug taking account the importance of the drug to the women.

The most frequent adverse effects associated with omeprazole therapy involve the GI tract (e.g. diarrhea, nausea, constipation, abdominal pain, vomiting, flatulence) and the CNS (e.g. headache, dizziness).
GI Effects: diarrhea, nausea, constipation, abdominal pain, vomiting, flatulence, acid regurgitation, dysphagia, abdominal swelling, anorexia, irritable colon, fecal discoloration, pancreatitis (sometimes fatal), esophageal candidiasis, mucosal atrophy of the tongue, taste perversion, dry mouth and stomatitis have been reported during postmarketing surveillance.
Nervous System Effects: Headache and dizziness are the most common side effects. Psychic and sleep disturbances, including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, tremors, apathy, somnolence, anxiety and dream abnormalities have been reported during postmarketing surveillance.
Musculoskeletal Effects: Back pain has been reported in about 1% of patients receiving omeprazole. Other musculoskeletal effects have been reported during postmarketing surveillance; a causal relationship to the drug was not established in many cases. Such effects include muscle cramps, myalgia, muscle weakness, joint pain and leg pain. Limited observational data suggest that long-term use of proton-pump inhibitors, particularly high doses, may increase the risk of hip fracture in patients older than 50 years of age.
Hepatic Effects: Mild and rarely, marked increases in serum ALT (SGPT), AST (SGOT), γ-glutamyltransferase (GGT, γ-glutamyltranspeptidase, GGTP) alkaline phosphatase and bilirubin concentrations have been reported during postmarketing surveillance.
Dermatologic and Sensitivity Reactions: Rash has been reported during postmarketing surveillance; rarely, severe generalized reactions such as toxic epidermal necrolysis (TEN) (some fatal), Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis and lichenoid eruptions have been reported. Other adverse dermatologic effects reported during postmarketing surveillance include skin inflammation, urticaria, purpura and/or petechiae (some case with rechallenge), angioedema, pruritus, photosensitivity, alopecia, dry skin and hyperhidrosis. Hypersensitivity reaction, including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis and urticaria, have been reported.
Hematologic Effects: Agranulocytosis (occasionally fatal) has been reported rarely with omeprazole therapy but a causal relationship to the drug is uncertain. Other adverse hematologic effects reported during postmarketing surveillance include pancytopenia, thrombocytopenia, neutropenia, leukopenia, anemia and leukocytosis.
Genitourinary Effects: Acute interstitial nephritis, urinary tract infection, microscopic pyuria, urinary frequency, elevated serum creatinine concentration, proteinuria, hematuria, glycosuria, testicular pain and gynecomastia have been reported during postmarketing surveillance.
Cardiovascular Effects: Chest pain, angina pectoris, tachycardia, bradycardia, palpitation, elevated blood pressure and peripheral edema have been reported during postmarketing surveillance.
Ocular Effects: Blurred vision, ocular irritation, dry eye syndrome, optic atrophy, anterior ischemic optic neuropathy, optic neuritis and double vision have been reported during postmarketing surveillance. In many cases a causal relationship has not been established.
Respiratory Effects: Upper respiratory tract infections and cough have occurred in 1.9 and 1.1% respectively, of patients receiving omeprazole. Administration of gastric acid suppressants (e.g. PPIs, H2-receptor antagonists) has been associated with an increased risk for developing community-acquired pneumonia (CAP). Some clinicians state that gastric acid suppressants should be used in patients in whom CAP may be severe (e.g., those with asthma COPD, immunocompromised patients, pediatric or geriatric individuals) only when clearly needed and the lowest effective dose should be employed.

Gastric acid secretion decreased by PPIs can influence the absorption of other drugs (e.g., resulting in increased digoxin and decreased ketoconazole and itraconazole absorption). Drug solubility may be reduced at neutral pH compared with acidic conditions. PPIs have been demonstrated to reduce the bioavailability of many clinically relevant drugs by 50% or more compared with the control values. Other important drug interactions are connected to hepatic CYP-mediated oxidative metabolism. PPIs may alter drug metabolism by induction or inhibition of the cytochrome P450 enzymes. This is an important consideration in patients taking medication with a narrow therapeutic window (diazepam, phenytoin and warfarin).
Omeprazole inhibits its own CYP2C19-mediated metabolism, but it is also able to affect the degradation of other drugs metabolized through the CYP2C19 isoenzyme.
Other CYP isoenzymes besides CYP2C19 are also involved in the interactions related to the metabolism of omeprazole. Coadministration of ketoconazole inhibits the omeprazole-omeprazole sulfone transformation. This interaction is exerted through the inhibition of the CYP3A4 isoenzyme, involved in the metabolism of both ketoconazole and omeprazole. If the activity of CYP2C19 is decreased or inhibited (in poor metabolizers or owing to environmental factors), the CYP3A4-mediated pathway becomes the main, alternative pathway of the elimination of PPIs.
Metabolism/Transport Effects: Substrate of CYP2A6 (minor), CYP2C19 (major), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (minor);
Note: Assignment of major/minor substrate status based on clinically relevant drug interaction potential;
Inhibits CYP1A2 (weak), CYP2C19 (moderate), CYP2C9 (moderate), CYP2D6 (weak), CYP3A4 (weak);
Induces CYP1A2 (weak/moderate).
Avoid Concomitant Use: Avoid concomitant use of omeprazole with any of the following: Clopidogrel; Dasatinib; Delavirdine; Erlotinib; Nelfinavir; Pimozide; Ponatinib; Posaconazole; Rifampin; Rilpivirine; Risedronate; St John's Wort.
Increased Effect/Toxicity: Omeprazole may increase the levels/effects of: amphetamines; aripiprazole; benzodiazepines (metabolized by oxidation); carvedilol; cilostazol; citalopram; clozapine; cyclosporine (systemic); CYP2C19 substrates; CYP2C9 substrates; dexmethylphenidate; escitalopram; fosphenytoin; lomitapide; methotrexate; methylphenidate; phenytoin; pimozine; raltegravir; risedronate; saquinavir; tacrolimus (systemic); vitamin K antagonists; voriconazole; alprazolam; carbamazepine; clobazam; clorazepate; diazepam; digoxin; disulfiram; fluvastatin; midazolam; triazolam; armodafinil.
The levels/effects of omeprazole may be increased by: fluconazole; ketoconazole (systemic); voriconazole.
Decreased Effect: Omeprazole may decrease the levels/effects of: atazanavir; ampicillin; bisphosphonate derivatives; bosutinib; cefditoren; clopidogrel; clozapine; dabigatran etexilate; dasatinib; delavirdine; erlotinib; gefitinib; indinavir; iron salts; itraconazole; ketoconazole (systemic); mesalamine; multivitamins/minerals (with A,D,E,K, folate, iron); mycophenolate; nelfinavir; nilotinib; ponatinib; posaconazole; rilpivirine; risedronate; vismodegib; bendamustine.
The level/effects of omeprazole may be decreased by: CYP2C19 inducers (strong); peginterferon alfa-2b; rifampin; St John's Wort; tipranavir.
Ethanol/Nutrition/Herb Interactions: Ethanol: Avoid ethanol (may cause gastric mucosal irritation).
Food: Food delays absorption.
Herb/Nutraceutical: Avoid use of St John's Wort; ginkgo biloba; cranberry (may decrease efficacy of omeprazole).

Store below 30°C.

Antacids, Antireflux Agents & Antiulcerants

A02BC01 - omeprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).

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