Omeprotect 20Mg 14 Capsules ( Bottle)

Omeprotect 20 Mg 14 Gastrorresistant Capsules (Bottle)

ACTION AND MECHANISM

- Peptic antiulcer, H + / K + pump inhibitor. Omeprazole is a benzimidazole that acts as a specific, non-competitive and irreversible proton pump inhibitor (PPI) or ATPase H + / K +, located on the surface of the gastric parietal cell. The blocking of said proton pump prevents the production of gastric acid, both at baseline and before a stimulus, regardless of which one (acetylcholine, gastrin or histamine).

Omeprazole is a racemic mixture of two stereoisomers, S-omeprazole (esomeprazole, pharmacologically active) and R-omeprazole (no activity on acid production).

Omeprazole is a prodrug with a weak base nature, which after its absorption is distributed by the body, and especially in the light of the secretory canaliculi of the parietal cell. Here, and in the presence of an acid medium, it undergoes a non-enzymatic chemical reaction giving rise to the active form, a totally hydrophilic sulfonamido derivative, which tends to accumulate in the canaliculi and join the proton pump by means of disulfide bridges with cysteine ​​residues of the alpha-luminal chain.

Due to the formation of covalent bonds, the only way for the parietal cell to recover its secretory activity is the synthesis of new pumps, which is a great period of time and explains the long duration of the effects of PPIs, which can to last up to 4 days after the administration of a single dose, and despite its low t1 / 2.

The administration of an omeprazole dose of 20 mg resulted in a 70% reduction in acid secretion induced by 70% pentagastrin within 24 hours of administration.

The effects on acid production begin to appear after 2 h, although it may take up to 5 days to achieve maximum antiulcer activity. Its effects may be prolonged, and in some studies an inhibition of acid secretion of 26% (20 mg) and 48% (mg) has been observed 24 hours after administration.

PHARMACKINETICS

Oral, parenteral route:

Omeprazole is a prodrug, and after absorption and distribution to the parietal cell, it is transformed by a chemical reaction catalyzed in an acid medium in the active sulfonamido derivative.

- Absorption: it is absorbed quickly and almost completely in the small intestine, usually in about 3-6 hours, with a tmax of 1-2 hours. However, it undergoes an important hepatic first-pass metabolism, which reduces its bioavailability to 40%. This metabolism seems to be saturable, since after repeated doses the bioavailability is increased to 60%.

Food effect : they do not appear to significantly affect the absorption of omeprazole when administered as a modified release (gastro-resistant capsules). However, food may reduce and delay absorption, so it is generally recommended to take it on an empty stomach.

- Distribution: strong binding to plasma proteins (95-97%), especially albumin and acidic alpha-1 glycoprotein. Your Vd is 0.3 l / kg.

- Metabolism: extensive in the liver by CYP2C19, giving rise to the main metabolite, hydroxy-omeprazole. To a lesser extent, it also undergoes CYP3A4 metabolism, generating sulfone and omeprazole sulfide. None of these metabolites have appreciable activity.

Enzyme inducing / inhibiting capacity : it presents competitive inhibitory activity of CYP2C19 due to its high affinity for the enzyme. No inducing or inhibiting effects on other enzyme systems have been recorded.

- Excretion: in urine (77%) and feces (20%), mainly in the form of metabolites. The t1 / 2 is 0.5-1 h and the CLt is 500-600 ml / min.

Pharmacokinetics in special situations :

- Children: no significant differences in the pharmacokinetic parameters of children from 1 year have been observed, compared to adults. In children <6 months, lower CLt may occur due to liver immaturity.

- Elderly: patients> 75 years old could present a greater bioavailability and a lower elimination of omeprazole, as a consequence of lower liver metabolism. When administering a dose of 40 mg, a bioavailability of 76% and a CLt of 250 ml / min were recorded. However, dosage adjustments are not usually necessary.

- Renal impairment: no specific pharmacokinetic alterations have been recorded. In patients with moderate renal impairment (CLcr 30-60 ml / min), an accumulation of metabolites may occur, although these are not active. Omeprazole is not eliminated by hemodialysis.

- Hepatic impairment: an increase in bioavailability could occur due to the inhibition of the first hepatic passage, as well as an increase in t1 / 2 up to 3 h, while the CLt could be reduced to 70 ml / min. Despite this, omeprazole does not appear to accumulate after administration in single daily doses in these patients.

- Pharmacogenetics: about 1-3% of the Caucasian population and 20% of the Asian population lack functional CYP2C19, considered slow metabolizers, compared to patients who have the isoenzyme and are considered fast metabolizers. In slow metabolizers, hepatic omeprazole metabolism is produced by CYP3A4. It has been observed that in these patients the cmax increases 3-5 times and the AUC 5-10 times, although no significant clinical repercussions have been recorded, and no specific dosage adjustments have been recommended.

INDICATIONS

- Short-term treatment of the symptoms of [GASTROESOPHAGIC REFLECTION], such as [GASTRIC HYPERACIDEZ] or acid regurgitation in adults.

POSOLOGY

"ORAL ADMINISTRATION"

- Adults:

* Gastric reflux: 20 mg / 24 h. 2-3 days of treatment are usually required to eliminate symptoms. Stop treatment when symptoms disappear, usually in about 7 days. Maximum treatment duration 14 days.

- Elderly: no dose adjustment required.

Missed dose : take as soon as possible, unless there is little time left for the next dose. In this case, skip the dose. Do not double the dose in the next administration.

POSOLOGY IN RENAL INSUFFICIENCY

It does not require dosage adjustment.

POSOLOGY IN HEPATIC INSUFFICIENCY

Usually a dose of 10-20 mg / 24 h is sufficient.

RULES FOR THE CORRECT ADMINISTRATION

- Gastro-resistant capsules: ingest whole with the help of half a glass of liquid. They should not be chewed, crushed or broken.

If the patient experiences difficulty swallowing the capsules, they can be opened and suctioned or suspended in half a glass of water without gas, fruit juice or soft foods such as yogurt or applesauce. The suspension with the granules should be drunk immediately or within 30 min. Then fill the glass halfway with water and hurry the contents. The granules should not be chewed or crushed.

Administration with food : preferably administered on an empty stomach, first thing in the morning.

CONTRAINDICATIONS

- Hypersensitivity to omeprazole, any other PPI, or any other component of the medication.

- Joint treatment with nelfinavir (see Interactions - Protease inhibitors).

PRECAUTIONS

- [LIVER FAILURE]. Hepatic impairment may increase exposure, due to a reduction in the effect of the first hepatic passage, and decrease elimination due to reduced metabolism. However, it has been proven that omeprazole does not tend to accumulate in these patients when administered once a day. It is advised to use with caution. Patients with liver failure may require a lower maintenance dose.

- [DIGESTIVE INFECTIONS]. The increase in gastric pH produced by antiulcer agents could favor colonization of the digestive system by certain pathogenic microorganisms, such as Salmonella, Campylobacter and even Clostridium difficile in hospitalized patients. It is recommended to make a differential diagnosis of [PSEUDOMEMBRANOSE COLITIS] in patients treated with an antiulcer in which severe diarrhea occurs.

- [DEFICIT OF CYANOCOBALAMINE]. The increase in pH produced by antiulcer drugs could decrease the absorption of cyanocobalamin, so it is recommended to take it into account in people with low deposits of this vitamin, such as in patients with [NUDE] or strict vegetarian diets without supplementation is this vitamin , or situations in which its absorption could be reduced, as in [CHRONIC ALCOHOLISM], [INTESTINAL MALABSORTION] or situations that could lead to malabsorption, such as [INTESTINAL INFLAMMATORY DISEASE] or major surgical processes of the digestive system.

- [HYPOMAGNESEMIA]. Treatment with PPI has been related to the occurrence of severe cases of hypomagnesemia, which could be associated with [HYPOCALCEMIA]. Its frequency has not been estimated, but it is considered rare. However, the great use of these drugs should be taken into account, so their clinical impact could be important. The majority of patients who presented hypomagnesemia were in long-term treatment (at least 3 months and essentially 1 year).

It is recommended to monitor magnesium levels at the beginning of treatment and periodically throughout it in patients on long-term treatment with PPI, on treatment with digoxin or with drugs that could lead to hypomagnesemia, such as diuretics.

In case of symptoms of hypomagnesemia, such as fatigue, dizziness, tetany, delirium, seizures or cardiac arrhythmia, magnesium levels will be determined. Hypomagnesemia responds to the elimination of PPI and the administration of magnesium supplements.

- [OSTEOPOROSIS]. The administration of PPI at high doses and for prolonged periods of time (> 1 year) has been associated with an increased risk of hip, wrist and vertebral fracture, especially in the elderly and with risk factors. It is therefore advised that women with osteoporosis receive adequate treatment and intake of calcium and vitamin D.

- [PNEUMONIA]. Treatment with PPI has been linked to cases of pneumonia, including community-acquired pneumonia (CAP), interstitial pneumonia or nosocomial pneumonia. The risk appears to be higher in patients who have just started treatment (especially <2 days), rather than long-term treatments.

- [LUTUS ERITEMATOSO CUTANEO SUBAGUDO] (LECS). PPIs have been linked to very rare cases of subacute cutaneous lupus erythematosus. In case of skin lesions, especially in areas exposed to the sun, accompanied by arthralgia, consider discontinuation of treatment. Patients with LECS for an PPI may experience this condition again if they receive a different PPI.

- Analytical interference. The increase in gastric pH induced by antiulcer agents may increase plasma gastrin levels (which usually return to baseline at 4 weeks after discontinuation of treatment) and chromogranin A (CgA).

CgA is a specific marker of neuroendocrine tumors, so antiulcer drugs may lead to false positives when this marker is used in diagnostic tests. Therefore, any antiulcer should be suspended at least 5 days before the determination of CgA. If CgA levels have not normalized in this period, the test should be repeated 14 days after the suspension of the antiulcer.

- Long term treatment. Antiulcer drugs eliminate symptoms related to acid diseases, which are common to those of malignant processes such as [CANCER DE ESTOMAGO] or [CANCER DE ESOFAGO]. Therefore, there is a risk of delaying the diagnosis of these processes.

It is recommended that patients receiving prolonged treatment, longer than one year, undergo regular monitoring, and be advised to notify the presence of other symptoms associated with these neoplasms, such as significant and unjustified weight loss, recurrent vomiting , dysphagia or vomiting in blood or feces. In case of suspicion of a serious digestive process, a differential diagnosis is recommended.

Patients who use omeprazole that does not require a medical prescription should inform their doctor and / or pharmacist if they have recurrent symptoms of indigestion or burning, are in continuous treatment for more than 4 weeks without getting relief from the symptoms or if their symptoms have changed or New symptoms have appeared, especially in> 55 years.

PRECAUTIONS RELATING TO EXCIPIENTS

- This medicine contains sucrose. Patients with hereditary [INTRODUCTION TO FRUCTOSE], glucose or galactose malabsorption, or sucrose-isomaltase insufficiency should not take this medication.

- This medicine contains sucrose. The administration of amounts greater than 5 g daily should be taken into account in patients with [DIABETES].

PATIENT ADVICE

- Do not stop treatment until directed by your doctor, even if the symptoms have disappeared. A premature suspension could cause symptoms to reappear.

- Tell your doctor about the medications you are taking.

- Tell your doctor and / or pharmacist if you have any of these symptoms:

* Intense and / or persistent diarrhea.

* Important and unjustified weight loss, frequent vomiting, difficulty swallowing or presence of blood in vomiting or feces.

* Unjustified tiredness, dizziness, muscle stiffness, seizures or cardiac arrhythmias.

* Appearance of skin lesions, especially in areas exposed to the sun, accompanied by joint pain.

* Symptoms of indigestion or heartburn frequently, despite treatment, especially if they are older than 55 years.

SPECIAL WARNINGS

- It is recommended to confirm the healing of ulcerations by endoscopy before stopping treatment.

- PPIs may mask the symptoms of digestive tumors of the esophagus or stomach. It is recommended to closely monitor patients treated with an PPI for prolonged periods, longer than 1 year. If the patient experiences symptoms such as significant and unjustified weight loss, frequent vomiting, dysphagia, hematemesis or mane, a differential diagnosis is recommended.

- In case of occurrence of severe and prolonged diarrhea, the possible infection with Clostridium difficile will be investigated.

- Treatment with PPI for a prolonged period has rarely resulted in severe conditions of hypomagnesemia, which could be associated with hypocalcemia. If the patient experiences symptoms such as asthenia, dizziness, tetany, seizures or cardiac arrhythmia, magnesium levels will be determined, and in case of hypomagnesemia the treatment will be suspended and a magnesium supplement will be administered.

- Antiulcer drugs may interfere with the diagnosis of neuroendocrine tumors, by increasing the levels of the specific marker chromogranin A (CgA), leading to false negatives. Suspend the antiulcer at least 5 days before the test, and if your levels had not normalized, repeat the test 14 days after the suspension.

- Monitoring:

* Magnesium levels at baseline and periodically in patients treated for long periods with omeprazole, treated with digoxin or with drugs that could lead to hypomagnesemia, such as diuretics.

INTERACTIONS

- Oral anticoagulants. Cases of increases in INR have been reported in patients treated with an anticoagulant and an PPI. It is recommended to use with caution, monitoring the INR.

- Clopidogrel. High-dose omeprazole may decrease the effect of clopidogrel, by inhibiting the transformation to its active metabolite, mediated by CYP2C19 (although there may be some other mechanism since clopidogrel has several metabolic pathways). It is recommended to avoid the association between omeprazole and clopidogrel. Pantoprazole, and to a lesser extent lansoprazole and rabeprazole, could be safer alternatives.

- Disulfiram. A case of catatonic reaction has been described when combined with omeprazole.

- Drugs with pH dependent absorption. The increase in pH produced by antiulcer agents could modify the absorption of certain medications, by favoring or reducing their dissolution in the aqueous medium of gastric contents. In this way an increase in the absorption of digoxin has been observed, as well as a reduction in that of azolic antifungals (itraconazole, ketoconazole, posaconazole), mycophenolate mofetil, rilpivirine, vitamin B12 and tyrosine kinase inhibitors (dasatinib, erlotinib, gefitinib, lapatinib, nilotinib, pazopanib).

The occurrence of digoxin toxicity is rare, but due to its serious effects caution is advised in elderly patients treated with high doses. It is recommended to monitor the plasma levels of digoxin.

- Enzyme inducers / inhibitors. Omeprazole is metabolized by CYP2C19 and to a lesser extent by CYP3A4, so that its plasma levels could be modified by potent inhibitors (fluconazole, fluvoxamine, ticlopidine) or inducers (rifampicin) of both isoenzymes. There are also certain risks with drugs that affect a single isoenzyme, especially CYP2C19, which is the majority. A dosage adjustment is not considered necessary, since the effect would be as observed in slow metabolizers, but it could be more important in case of severe liver failure and long-term treatment.

- Protease inhibitors (IP). PPIs could alter the plasma levels of certain IPs, either by increasing the pH or by inhibiting CYP2C19.

Major reductions in plasma levels of nelfinavir and atazanavir have been described. Co-administration with nelfinavir is contraindicated, and it is not advised to combine with atazanavir. If it is not possible to avoid this association, it is recommended to increase the dose of atazanavir from 300 to 400 mg, although this increase in dose did not completely counteract the effect on the plasma levels of atazanavir, so the response in the patient should be evaluated.

An increase in saquinavir levels of up to double has been reported.

Finally, no significant pharmacokinetic alterations have been observed when combined with amprenavir, darunavir, fosamprenavir, lopinavir or tipranavir.

- Methotrexate. PPIs could increase serum methotrexate levels.

- CYP2C19 substrates. Omeprazole is a moderate CYP2C19 inhibitor, so it could increase plasma levels of drugs that are metabolized by this system, such as certain tricyclic antidepressants (clomipramine, imipramine), cilostazol, citalopram, diazepam, phenytoin, voriconazole or warfarin. It may be necessary to reduce the doses of these drugs, especially in case of treatments on demand with PPI.

In the case of phenytoin and warfarin, it would also be advisable to monitor your plasma levels when starting and ending a treatment with omeprazole.

- Tacrolimus. An increase in serum tacrolimus levels has been reported when administered with omeprazole.

No pharmacological interactions were found when associating antacids, beta-blockers (metoprolol, propranolol) domperidone, fluoroquinolones or theophylline.

PREGNANCY

Safety in animals : Omeprazole did not give rise to teratogenicity when administered in rats or pregnant rabbits at doses 345 and 172 DMRH, although an increase in fetal mortality was recorded.

Safety in humans : the gestational safety of PPIs (including lansoprazole, omeprazole and pantoprazole) has been evaluated in several clinical trials and meta-analyzes, and no teratogenic effects or embryotoxicity have been found, although they cannot be completely ruled out, especially in the case of rare or delayed onset fetal adverse reactions. However, and depending on the information obtained in animal studies, the risk would not be very high.

Omeprazole crosses the placenta. It is recommended to use with caution, restricting its use to situations in which there are no safer therapeutic alternatives, and the benefits outweigh the possible risks.

Effects on fertility : no specific studies have been conducted on its effects on fertility.

LACTATION

Animal safety : administration to lactating rats (35-345 MDRH) was associated with a reduction in the weight gain of the offspring.

Safety in humans : omeprazole is excreted in breast milk, reaching levels of 7% of the maternal cp. The consequences that it could have for the infant are unknown, although it must be taken into account that PPIs are labile drugs at acidic pH, which is why they are administered orally as gastro-resistant forms. Is recomended to suspend the lactancy or evy the administration.

CHILDREN

Omeprazole has been used orally for the treatment of reflux esophagitis and the symptomatic treatment of esophagitis in children from 1 year of age and at least 10 kg in weight, as well as for the eradication of H. pylori in children and adolescents From 4 years.

Its use is not recommended in other indications or at ages other than those established in the approved indications.

ELDERLY

No specific problems have been described in the elderly that require a dose adjustment.

EFFECTS ON DRIVING

It does not appear to have significant effects. It is rare for dizziness to appear, and rarely blurred vision and vertigo.

ADVERSE REACTIONS

The adverse reactions of omeprazole appear to be dose-independent. The most frequent are digestive in nature, as well as headache.

In the trials performed, the safety profile in children was similar to that recorded in adult patients. There are no long-term safety data in children, nor about the effects on growth.

Adverse reactions are described according to each frequency range, being considered very frequent (> 10%), frequent (1-10%), rare (0.1-1%), rare (0.01-0.1%) , very rare (<0.01%) or of unknown frequency (cannot be estimated from the available data).

- Digestive: frequent [NAUSEAS] and [VOMITES], [ABDOMINAL PAIN], [CONDEMNATION], [DIARRHEA], [FLATULENCE]; rare [MOUTH DRYING], [STOMATITIS], [CANDIDIASIS]; unknown frequency [PANCREATITIS].

- Hepatic: uncommon [INCREASE OF TRANSAMINASES]; rare [HEPATITIS] with or without [ICTERICIA]; very rare [HEPATIC INSUFFICIENCY], [HEPATIC ENCEPHALOPATHY] in patients with previous liver disease; unknown frequency [COLESTASIS].

- Cardiovascular: frequency unknown [ARTERIAL HYPERTENSION], [PALPITATIONS], [CHEST ANGINA], [RAYNAUD SYNDROME].

- Neurological / psychological: frequent [CEFALEA]; uncommon [MAREO], [PARESTHESIA], [SOMNOLENCE], [INSOMNIUM]; rare [NERVIOSISM], [CONFUSION], [DEPRESSION], [DISGEUSIA]; very rare [ALUCINATIONS], [AGGRESSIVE]; unknown frequency [ATAXIA].

- Respiratory: frequent [TOS], [RESPIRATORY INFECTION]; rare [BRONCHIAL SPASM]; unknown frequency [PNEUMONIA].

- Genitourinary: rare [INTERSTICIAL NEFRITIS]; very rare [GYNECOMASTIA]; frequency unknown [GALACTORREA], [SERICA CREATININE INCREASE].

- Dermatological: infrequent [DERMATITIS], [PRURITE], [EXANTEMATIC ERUPTIONS], [URTICARY]; rare [ALOPECIA], [PHOTOSENSITIVITY REACTIONS]; very rare [MULTIFORM ERYTHEMA], [TOXIC EPIDERMIC NECROLYSIS], [STEVENS-JOHNSON SYNDROME]; unknown frequency [ANGIOEDEMA]; frequency unknown [LUTUS ERITEMATOSO CUTANEO SUBAGUDO].

- Allergic: rare [HYPERSENSITIVITY REACTIONS], with [FEVER], [ANGIOEDEMA] or [ANAFILAXIA], and [ERYTHEMATE LUPUS].

- Osteomuscular: frequent [BACK PAIN]; uncommon [HIP FRACTURE], [VERTEBRAL FRACTURE] or wrist; rare [OSTEOMUSCULAR PAIN], [MIALGIA]; very rare [MIASTENIA]; unknown frequency [RABDOMIOLISIS].

- Ophthalmological: rare [VISION DELETE]; unknown frequency [OPTICAL NEURITIS], [OPTICAL NEUROPATHY].

- Otics: uncommon [VERTIGO].

- Hematologic: rare [LEUCOPENIA], [TROMBOCITOPENIA]; very rare [AGRANULOCITOSIS], [PANCITOPENIA]; frequency unknown [NEUTROPENIA], [HEMOLITIC ANEMIA] or [MEGALOBLASTIC ANEMIA].

- Metabolic: rare [HYPONATREMIA]; frequency unknown [HYPOMAGNESEMIA], [HYPERCALCEMIA], [HYPOGLUCEMIA], [HYPOPOTHEMEMIA], [CYANOCOBALAMINE DEFICIT], [WEIGHT INCREASE].

Hypomagnesemia may occur with [ASTENIA], [MAREO], [TETANIA], [DELIRIO], [CONVULSIONS] or [CARDIAC ARRITMIA] among others. In case of occurrence of symptoms, magnesium levels will be determined. Hypomagnesemia responds to the elimination of PPI and the administration of magnesium supplements.

- Gen