Ranitidine

Pharmacological properties

Pharmacodynamic parameters. ranitidine - a pharmaceutically active ingredient of the drug - is an antagonist of H2 receptors. ranitidine competitively and reversibly blocks the action on the indicated receptors of parietal glandulocytes of histamine released by enterochromaffin-like cells of the stomach.

The effects of ranitidine:

• reduction in the volume of gastric juice;
• a decrease in the concentration of HCl in the gastric juice;
• decreased secretion of HCl (basal, nocturnal and stimulated);
• decreased pepsin secretion.

It is significant that ranitidine:

• does not affect the content of gastrin in the blood plasma and the production of mucus by the glands of the stomach;
• does not alter pancreatic secretion of bicarbonate or enzymes in response to stimulation with secretin and pancreosimine;
• no significant effect on CYP P450.

Pharmacokinetic parameters. After oral administration, they are rapidly absorbed regardless of the ingestion of food or antacids (bioavailability is about 50%). C_max in the blood, 440–545 ng / ml is achieved 2-3 hours after the administration of 150 mg of ranitidine. The volume of distribution is about 1.4 l / kg. Binding to plasma proteins on average - 15%.

Partially metabolized in the liver (to N- and S-oxides and desmethylranitidine). Renal clearance - approximately 410 ml / min (indicates active tubular excretion). T_½ is 2.5–3 hours (in case of impaired renal function, it increases to 4–5 hours)

The main route of excretion is with urine (about 30% of an orally administered dose is excreted unchanged). A small part is excreted in the feces.

It penetrates well through histohematological barriers (with the exception of the BBB). Significant amounts are excreted in breast milk.

In patients with cirrhosis of the liver in the stage of compensation, a small change in the pharmacokinetics of ranitidine does not have clinical significance.

There is a significant linear correlation between an orally administered dose (up to 300 mg) and the inhibitory effect of ranitidine on hydrochloric acid secretion. A plasma concentration of ranitidine of 50 ng / ml has a 50% inhibitory effect on stimulated HCl secretion.

After oral administration of 150 mg of ranitidine, its plasma concentration is higher than the EU₅₀ (36–94 ng / ml), persists for 8 hours. At the same time, after 12 hours the level of the drug in the blood plasma remains high enough to have a significant inhibitory effect on gastric secretion. In patients with a duodenal ulcer, oral administration of ranitidine at a dose of 150 mg every 12 hours significantly reduces the average 24-hour activity of hydrogen ions by 69% and nighttime hydrochloric acid secretion by 90%.

In addition, 300 mg of ranitidine when administered orally at night also effectively reduces the acidity of the gastric contents within 24 hours, as does the administration of 150 mg of ranitidine 2 times a day.

The results of long-term animal studies to study the toxic, carcinogenic and mutagenic effects of ranitidine suggest the absence of such in humans when the drug is administered in therapeutic doses.

Indications

• Peptic ulcer of the stomach and duodenum not associated with helicobacter pylori (including NSAID-induced), exacerbation phase; chronic gastritis (with increased acid production), stage of exacerbation; gastroesophageal reflux disease; reflux esophagitis; functional dyspepsia.

Application

Adults and children 12 years of age: per os, without chewing (drink with a small amount of water), regardless of food intake. in case of use 2 times a day, the drug is taken in the morning and in the evening. with a single use per day, the drug is taken at night.

• Peptic ulcer of the stomach and duodenum not associated with Helicobacter pylori (including NSAID-induced), exacerbation phase:

150 mg 2 times a day (or 300 mg 1 time per day), course - 4 weeks.In case of insufficient effective healing, the duration of therapy is increased by another 4 weeks.

• Prevention of NSAID-induced gastric and duodenal ulcers:

150 mg 2 times a day. Course - during the period of application of NSAIDs by the patient.

• Functional dyspepsia:

150 mg 2 times a day. Course - 2-3 weeks.

• Chronic gastritis (increased acid production), stage of exacerbation:

150 mg 2 times a day. Course - 2-4 weeks.

• Gastroesophageal reflux disease:

- to alleviate the severity of symptoms: 150 mg 2 times a day. Course - 2 weeks (extend if necessary);

- prolonged therapy or in case of exacerbation: 150 mg 2 times a day (or 300 mg 1 time per day). The course is 8 weeks, (extend to 12 weeks, if necessary).

Patients with severe renal impairment (creatinine clearance 50 ml / min) are prescribed ranitidine at a dose of 150 mg / day.

Contraindications

• Individual hypersensitivity to the active substance of the drug or its other components; cirrhosis of the liver (complicated by hepatic encephalopathy); severe renal impairment; malignant neoplasms of the stomach.

Side effects

- a decrease in the number of leukocytes in peripheral blood (4⋅109 / l), a reversible decrease in the number of platelets (150⋅109 / l), agranulocytosis or a decrease in the content of all blood cells, in some cases, against the background of bone marrow hypo- or aplasia, neutropenia; usually reversible anemia (hemolytic immune or aplastic).

- Hypersensitivity reactions (including urticaria, Quinckes edema, anaphylactic shock, bronchospasm, exfoliative dermatitis, erythema multiforme exudative, Lyell, Stevens-Johnson syndromes), hyperthermia.

- Increased fatigue, confusion (reversible), drowsiness, agitation, insomnia, emotional lability, anxiety, anxiety, depression, irritability, nervousness, hallucinations, tinnitus, disorientation or confusion (mainly in elderly patients or patients with severe pathology )

- Headache, dizziness, involuntary movement disorders (reversible).

- Blurry of visual perception, disturbance of accommodation.

- Arterial hypotension, decreased heart rate (40 beats / min), increased heart rate (90 beats / min), asystole, AV block, vasculitis, chest pain, heart rhythm disturbances, extrasystole.

- Decreased appetite, nausea, vomiting, dry mouth, flatulence, constipation, diarrhea, abdominal pain, acute pancreatitis.

- Transient abnormalities in liver function tests (reversible), hepatitis (including anicteric forms).

- Hyperemia, itching, rash, dry skin, alopecia.

- Pain in the muscles, joints.

- Acute damage to the interstitial tissue of the kidneys, decreased renal function.

- Gynecomastia, amenorrhea, increased levels of prolactin in the blood, galactorrhea, reversible decrease in erectile function and / or sex drive.

special instructions

There is a likelihood of developing allergic reactions when taking ranitidine in case of an allergy in the patient to other β-antagonists of H2 receptors.

In patients with a decrease in immunological reactivity, in patients with acute porphyria (in history or at present), caution should be exercised when using ranitidine.

The dose should be reduced in case of development of confusion in elderly patients with hepatic or renal failure.

When taking ranitidine, a decrease in the severity of manifestations of malignant neoplasms of the stomach is possible.

When using ranitidine, there was an increased likelihood of community-acquired pneumonia in immunocompromised or elderly patients, patients with diabetes mellitus or people with chronic pulmonary pathology.

Ranitidine therapy should not be abruptly discontinued.

Patients with lactase deficiency, galactosemia, malabsorption of glucose and galactose should take into account the presence of lactose in the drug.

During pregnancy and lactation, the drug is not prescribed.

Since there is a likelihood of developing disorders of accommodation, dizziness and hallucinations, during the period of ranitidine, driving and working with other mechanisms are excluded.

Interactions

Taking ranitidine increases the absorption in the gastrointestinal tract of glipizide, midazolam and triazolam.

When combined with ranitidine, absorption in the gastrointestinal tract of gefitinib, itraconazole, ketoconazole, atazanavir is reduced.

The absorption of ranitidine in the gastrointestinal tract slows down while it is used with antacids (the proper interval is ≥1–2 hours).

Perhaps an increase in plasma levels of metoprolol with its combined use with ranitidine.

Prothrombin time may vary with the combined use of ranitidine with warfarin.

It is possible to increase the excretion time of procainamide and N-acetylprocainamide when combined with high doses of ranitidine.

The effectiveness of ranitidine decreases with smoking.

Overdose

In case of excessive use, an increase in the severity of adverse reactions is possible.

Storage conditions

At a temperature of ≤25 ° C in the original packaging.