Omeprazole Healthkern 20 Mg 14 Gastro-resistant Capsules (jar)

Omeprazole Healthkern (20 Mg 14 Gastro-resistant Capsules)

Omeprazole

ACTION AND MECHANISM

- Peptic ulcer, H + / K + pump inhibitor. Omeprazole is a benzimidazole that acts as a specific, non-competitive and irreversible inhibitor of the proton pump (PPI) or H + / K + ATPase, located on the surface of the gastric parietal cell. The blockage of this proton pump prevents the production of gastric acid, both basal and in the event of a stimulus, regardless of which is (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 absorption is distributed throughout the body, especially in the lumen 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 sulfonamide derivative, which tends to accumulate in the canaliculi and bind to the proton pump through disulfide bridges with the cysteine ​​residues. of the alpha-luminal chain.

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

Administration of a 20 mg dose of omeprazole resulted in a 70% reduction in pentagastrin-induced acid secretion at 24 h after administration.

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

PHARMACOKINETICS

Omeprazole is a prodrug, and after its absorption and distribution to the parietal cell, it is transformed by an acid-catalyzed chemical reaction into the active sulfonamide derivative.

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

Effect of food : they do not appear to significantly affect the absorption of omeprazole when administered in modified release form (gastro-resistant capsules). However, food could reduce and delay absorption, so it is generally advisable to take it on an empty stomach.

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

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

Enzyme inducing / inhibiting capacity : it has competitive inhibitory activity of CYP2C19 due to its high affinity for the enzyme. Inductive or inhibitory effects on other enzyme systems have not 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 have been observed in the pharmacokinetic parameters of children from 1 year of age, compared to adults. In children <6 months, a lower CLt may occur due to liver immaturity.

- Elderly: patients> 75 years of age could present a higher bioavailability and a lower elimination of omeprazole, as a consequence of the lower hepatic 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 insufficiency: no specific pharmacokinetic alterations have been registered. In patients with moderate renal insufficiency (CLcr 30-60 ml / min), an accumulation of metabolites may occur, although these are not active. Omeprazole is not removed by hemodialysis.

- Hepatic failure: there could be an increase in bioavailability due to the inhibition of the first hepatic passage, as well as an increase in t1 / 2 up to 3 h, while 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: around 1-3% of the Caucasian population and 20% of the Asian population lack functional CYP2C19, which are considered poor metabolizers, compared to patients who have the isoenzyme and are considered rapid metabolizers. In poor metabolisers, the hepatic metabolism of omeprazole is by CYP3A4. It has been observed that in these patients the cmax increases 3-5 times and the AUC 5-10 times, although there have been no significant clinical repercussions, and no specific dosage adjustments have been recommended.

INDICATIONS

- Short-term treatment of the symptoms of [GASTROESOPHAGEAL REFLUX], such as [GASTRIC HYPERACIDITY] or acid regurgitation in adults.

POSOLOGY

"ORAL ADMINISTRATION"

- Adults:

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

- Children and adolescents <18 years: safety and efficacy have not been evaluated.

- Elderly: does not require dosage adjustment.

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

DOSAGE IN KIDNEY INSUFFICIENCY

It does not require dosage adjustment.

DOSAGE IN LIVER INSUFFICIENCY

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

RULES FOR CORRECT ADMINISTRATION

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

If the patient experiences difficulty swallowing the capsules, they can be opened and suctioned or suspended in half a glass of still water, fruit juice, or soft foods such as applesauce. The suspension with the granules should be drunk immediately or within 30 min. Then fill the glass halfway with water and drain the content. The granules should not be chewed or crushed.

Suspending the granules in milk or sparkling water is not recommended.

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

CONTRAINDICATIONS

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

- Co-treatment with nelfinavir (see Interactions - Protease Inhibitors).

PRECAUTIONS

- [LIVER FAILURE]. Hepatic failure could increase exposure, by reducing the hepatic first-pass effect, and decrease elimination by reducing metabolism. However, it has been found that omeprazole does not tend to accumulate in these patients when administered once a day. Use with caution is advised. Patients with impaired liver function may require a lower maintenance dose.

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

- [CYANOCOBALAMINE DEFICIT]. 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 [MALNUTRITION] or strict vegetarian diets without supplementation is this vitamin , or situations in which its absorption could be reduced, such as in [CHRONIC ALCOHOLISM], [INTESTINAL MALABSORPTION] or situations that could lead to malabsorption, such as [INFLAMMATORY INTESTINAL DISEASE] or major surgical processes of the digestive system.

- [HYPOMAGNESEMIA]. Treatment with PPIs has been associated with the development of severe cases of hypomagnesemia, which could be associated with [HYPOCALCEMIA]. Its frequency has not been estimated, but it is considered rare. However, the high use of these drugs must be taken into account, so their clinical impact could be significant. Most of the patients who presented hypomagnesemia were on long-term treatment (at least 3 months and mainly 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 PPIs, on treatment with digoxin or with drugs that could lead to hypomagnesemia, such as diuretics.

In the event of symptoms of hypomagnesemia, such as fatigue, dizziness, tetany, delirium, seizures or cardiac arrhythmia, magnesium levels should be determined. Hypomagnesemia responds to removal of PPI and magnesium supplementation.

- [OSTEOPOROSIS]. Administration of PPIs 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. Therefore, it is recommended that women with osteoporosis receive treatment and an adequate supply of calcium and vitamin D.

- [PNEUMONIA]. Treatment with PPIs has been associated with 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 a treatment (especially <2 days), rather than in long-term treatments.

- [SUB-ACUTE CUTANEOUS LUPUS ERYTHEMATOSUS] (LECS). PPIs have been associated with very rare cases of subacute cutaneous lupus erythematosus. In case of appearance of skin lesions, especially in areas exposed to the sun, accompanied by arthralgia, consider interrupting the treatment. Patients with LECS from a PPI may re-experience this condition if they receive a different PPI.

- Analytical interferences. The increase in gastric pH induced by antiulcer drugs can increase plasma levels of gastrin (which usually return to baseline level 4 weeks after stopping treatment) and chromogranin A (CgA).

CgA is a specific marker for neuroendocrine tumors, so antiulcer drugs could lead to false positives when this marker is used in diagnostic tests. Therefore, any antiulcer must be discontinued for at least 5 days before the determination of CgA. If the 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 the symptoms related to acid diseases, which are common to those of malignant processes such as [STOMACH CANCER] or [ESOPHAGUS CANCER]. Therefore, there is a risk of delaying the diagnosis of these processes.

It is recommended that patients who receive prolonged treatment, greater than one year, are subjected to regular surveillance, and that they are warned to report the presence of other symptoms associated with these neoplasms, such as significant and unjustified weight loss, recurrent vomiting , dysphagia or vomiting in blood or stool. In case of suspicion of a serious digestive process, a differential diagnosis is recommended.

Patients using omeprazole that do not require a prescription should inform their doctor and / or pharmacist if they have recurrent symptoms of indigestion or burning, are on continuous treatment for more than 4 weeks without getting relief from 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 [FRUCTOSE INTOLERANCE], glucose or galactose malabsorption, or sucrase-isomaltase insufficiency should not take this medicine.

ADVICE TO THE PATIENT

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

- Advise 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.

* Significant and unjustified weight loss, frequent vomiting, difficulty swallowing or presence of blood in vomit or stool.

* Unexcused 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 you are over 55 years old.

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. Close monitoring of patients treated with a PPI for prolonged periods of more than 1 year is recommended. If the patient experiences symptoms such as significant and unwarranted weight loss, frequent vomiting, dysphagia, hematemesis, or melena, a differential diagnosis is recommended.

- In the event of severe and prolonged diarrhea, a possible Clostridium difficile infection will be investigated.

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

- Antiulcer drugs could interfere in 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 its levels have 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 described in patients treated with an anticoagulant and a PPI. It is recommended to use with caution, monitoring the INR.

- Clopidogrel. Omeprazole at high doses could decrease the effect of clopidogrel, by inhibiting the transformation to its active metabolite, mediated by CYP2C19 (although there could 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 combining with omeprazole.

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

Digoxin toxicity is rare, but due to its serious effects, caution is advised in elderly patients treated with high doses. Monitoring of plasma levels of digoxin is recommended.

- Enzyme inducers / inhibitors. Omeprazole is metabolized by CYP2C19 and to a lesser extent by CYP3A4, so 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. No dosage adjustment is considered necessary, as the effect would be as seen in poor metabolisers, but could be more important in severe hepatic impairment and long-term treatment.

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

Significant reductions in plasma levels of nelfinavir and atazanavir have been reported. Co-administration with nelfinavir is contraindicated, and combination with atazanavir is not recommended. 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 dose increase did not completely offset the effect on plasma levels of atazanavir, so the response in the patient should be evaluated.

An increase in saquinavir levels of up to two times has been described.

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

- Methotrexate. PPIs could increase serum levels of methotrexate.

- CYP2C19 substrates. Omeprazole is a moderate inhibitor of CYP2C19, so it could increase the 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 the case of on-demand treatments with PPIs.

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

- Tacrolimus. Increased serum levels of tacrolimus have been reported when administered with omeprazole.

No drug interactions have been found when combining antacids, beta-blockers (metoprolol, propranolol), domperidone, fluoroquinolones or theophylline.

PREGNANCY

Safety in animals : omeprazole did not cause teratogenicity when administered to pregnant rats or rabbits at doses of 345 and 172 MRHD, 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 or embryotoxic effects have been found, although they cannot be completely ruled out, especially in the case of Rare or delayed-onset fetal adverse reactions. However, and based 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 : There have been no specific studies on its effects on fertility.

LACTATION

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

Human safety : omeprazole is excreted in human milk, reaching levels of 7% of the mother's CP. The consequences for the infant are unknown, although it must be borne in mind that PPIs are acid-pH labile drugs, which is why they are administered orally as gastro-resistant forms. Is recomended to suspend the lactancy or evy the administration.

SENIORS

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

EFFECTS ON DRIVING

It does not appear to present significant effects. Dizziness is rare, and blurred vision and vertigo are rare.

ADVERSE REACTIONS

Omeprazole adverse reactions appear to be dose-independent. The most frequent are digestive in nature, as well as headaches.

In the trials carried out, the safety profile in children was similar to that in adult patients. There are no long-term safety data in children, or on the effects on growth.

Adverse reactions are described according to each frequency range, being considered very common (> 10%), common (1-10%), uncommon (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 [VOMITING], [ABDOMINAL PAIN], [CONSTIPATION], [DIARRHEA], [FLATULENCE]; rare [DRYNESS OF MOUTH], [STOMATITIS], [CANDIDIASIS]; frequency unknown [PANCREATITIS].

- Hepatic: infrequent [INCREASED TRANSAMINASES]; rare [HEPATITIS] with or without [JAUNDICE]; very rare [HEPATIC FAILURE], [HEPATIC ENCEPHALOPATHY] in patients with previous liver disease; frequency unknown [CHOLESTASIS].

- Cardiovascular: frequency unknown [ARTERIAL HYPERTENSION], [PALPITATIONS], [ANGINA PECTORIS], [RAYNAUD'S SYNDROME].

- Neurological / psychological: frequent [HEADACHE]; uncommon [DIZZINESS], [PARESTHESIA], [Drowsiness], [INSOMNIA]; rare [NERVIOSISM], [CONFUSION], [DEPRESSION], [DYSGEUSIA]; very rare [HALLUCINATIONS], [AGGRESSIVENESS]; unknown frequency [ATAXIA].

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

- Genitourinary: rare [INTERSTICIAL NEFRITIS]; very rare [GYNECOMASTY]; frequency unknown [GALACTORRHEA], [INCREASED SERIAL CREATININE].

- Dermatological: infrequent [DERMATITIS], [PRURITO], [EXANTEMATIC ERUPTIONS], [URTICARIA]; rare [ALOPECIA], [PHOTOSENSITIVITY REACTIONS]; very rare [ERYTHEMA MULTIFORME], [TOXIC EPIDERMAL NECROLYSIS], [STEVENS-JOHNSON SYNDROME]; unknown frequency [ANGIOEDEMA]; frequency unknown [LUPUS ERYTHEMATOSUS CUTANEO SUBACUDO].

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

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

- Ophthalmological: rare [BLURRED VISION]; frequency unknown [OPTIC NEURITIS], [OPTIC NEUROPATHY].

- Optic: infrequent [VERTIGO].

- Hematological: rare [LEUCOPENIA], [THROMBOCYTOPENIA]; very rare [AGRANULOCYTOSIS], [PANCITOPENIA]; frequency unknown [NEUTROPENIA], [HEMOLYTIC ANEMIA] or [MEGALOBLASTIC ANEMIA].

- Metabolic: rare [HYPONATREMIA]; frequency unknown [HYPOMAGNESEMIA], [HYPERCALCEMIA], [HYPOGLYCAEMIA], [HYPOPOTASEMIA], [CYANOCOBALAMINE DEFICIT], [WEIGHT GAIN].

Hypomagnesemia can occur with [ASTENIA], [DIZZINESS], [TETANIA], [DELUSION], [SEIZURES] or [HEART ARRHYTHMIA] among others. In the event of symptoms, magnesium levels will be determined. Hypomagnesemia responds to removal of PPI and magnesium supplementation.

- General: frequent [ASTENIA], [FEVER]; infrequent [GENERAL DISASTER], [EDEMA MALEOLAR]; rare [HYPERHYDROSIS].

OVERDOSE

Symptoms : single doses of up to 2,400 mg, equivalent to 120 MRHD, have been administered. No serious or irreversible adverse reactions have been described, and in most cases the patients presented symptoms such as nausea and vomiting, abdominal pain, diarrhea, dizziness, headache, depression, apathy or confusion.

Measures to be taken :

- Antidote: there is no specific antidote.

- General measures of elimination: administer activated charcoal in case of very serious poisoning, although it is not usually necessary. It is not expected to be easily dialyzable due to its high plasma protein binding.

- Monitoring: clinical status of the patient.

- Treatment: symptomatic.

Omeprazole Healthkern 20 Mg 14 Gastro-resistant Capsules