Rennie® with orange flavor

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT RENNIE® WITH ORANGE FLAVOR

Composition:

Active substances: calcium carbonate, heavy magnesium carbonate;

1 tablet contains 680 mg of calcium carbonate (272 mg of elemental calcium) and 80 mg of heavy magnesium carbonate;

Excipients: sucrose, pregelatinized corn starch, potato starch, talc, magnesium stearate, light mineral oil, sodium saccharin, orange flavoring.

Pharmaceutical form. Chewable tablets.

Main physicochemical characteristics: cream-white, square-shaped tablets with concave surfaces, embossed with the word "RENNIE" on both sides, with an orange odor.

Pharmacotherapeutic group. Antacids, other combinations. ATC code A02AX.

Pharmacological Properties

Pharmacodynamics

Rennie® with orange flavor is a combination of two antacids – calcium carbonate and magnesium carbonate – which exert a local effect by neutralizing gastric acid, independent of systemic absorption. Calcium carbonate has a prolonged and strong neutralizing activity. This effect is enhanced by magnesium carbonate, which also has potent neutralizing activity.

The total acid-neutralizing capacity of the drug in vitro is 16 mEq H+ (titration to the endpoint pH of 2.5).

In vitro acid neutralization studies (artificial stomach model) have shown that Rennie® with orange flavor increases gastric pH from 1.5–2 to 3 within 40 seconds, and a pH of 4 can be reached within 1 minute 13 seconds. The maximum pH level achieved in the model was 5.24.

Pharmacokinetics

In the stomach, calcium carbonate and magnesium carbonate react with gastric juice to form water and soluble mineral salts.

CaCO3 + 2HCl → CaCl2 + H2O + CO2

MgCO3 + 2HCl → MgCl2 + H2O + CO2

Calcium and magnesium may be absorbed in the form of their soluble salts. The extent of absorption of calcium and magnesium from these compounds depends on the dose of the drug. Maximum absorption levels are 10% for calcium and 15–20% for magnesium. In healthy volunteers, a small amount of absorbed calcium and magnesium is excreted by the kidneys. In case of impaired renal function, plasma concentrations of calcium and magnesium may increase. During intestinal digestion, insoluble compounds are formed from the soluble salts and are eliminated in feces.

Preclinical studies of Rennie® products have not been conducted. Available preclinical data on calcium carbonate and magnesium carbonate (repeated-dose toxicity, genotoxicity and/or carcinogenic potential, reproductive toxicity data in rodents), described in scientific literature, do not provide any additional information beyond that contained in other sections of the instructions.

Clinical characteristics.

Indications.

For adults and children aged 15 years and older, to relieve symptoms associated with increased gastric acidity (e.g., heartburn, gastroesophageal reflux) leading to digestive disturbances and dyspepsia.

Contraindications.

• Hypersensitivity to the components of the drug;
• hypercalcemia and/or conditions leading to hypercalcemia;
• nephrolithiasis caused by deposition of calcium-containing stones;
• severe renal impairment (creatinine clearance below 30 mL/min);
• hypophosphatemia.

Interaction with other medicinal products and other forms of interaction.

Other medicinal products are recommended to be taken 1–2 hours before or after taking Rennie® with orange flavor.

Since reduced gastrointestinal absorption of certain concomitantly administered drugs has been observed, as a precautionary measure, a 2-hour interval should be maintained between taking Rennie® with orange flavor and acetylsalicylic acid, estramustine, H2-antisecretory antihistamines, atenolol, metoprolol or propranolol, chloroquine, diflunisal, digoxin, bisphosphonates, fexofenadine, glucocorticoids (prednisolone and dexamethasone, except hydrocortisone used in replacement therapy), indomethacin, ketoconazole, phenothiazine neuroleptics, penicillamine, thyroid hormones (thyroxine), ethambutol, isoniazid, lansoprazole, sulpiride, and tetracyclines.

Changes in gastric acidity, for example during treatment with antacids, may impair the rate and extent of absorption of other medicinal products taken concomitantly. When Rennie® with orange flavor is used concomitantly with antibiotics (tetracyclines, quinolones, lincosamides) and cardiac glycosides (digoxin), bisphosphonates, dolutegravir (the antacid should be administered either 2 hours after or 6 hours before dolutegravir), phosphorus compounds, strontium and zinc, levothyroxine, and eltrombopag, the absorption of these agents is reduced.

Thiazide diuretics reduce urinary excretion of calcium and increase its serum levels. Due to the increased risk of hypercalcemia when thiazide diuretics are used concomitantly, serum calcium levels should be monitored regularly.

Calcium salts reduce the absorption of fluorides and iron-containing preparations; also, calcium and magnesium salts may interfere with phosphate absorption.

It should be noted that concomitant use may lead to enhanced renal excretion of salicylates due to urinary alkalinization.

Sodium sulfonate – a cation-exchange resin: the resin's ability to bind potassium is reduced, leading to a risk of developing metabolic alkalosis in renal impairment.

Special precautions for use

If symptoms do not disappear, partially persist, or worsen within 10 days of treatment, a medical examination should be performed to determine their cause and reassess the treatment regimen. The duration of treatment with Rennie® should not exceed 10 days. Adverse reactions have been observed when used concomitantly with thiazide diuretics (see section "Interaction with other medicinal products and other forms of interaction"). Prolonged use of the medicinal product at high doses may lead to adverse reactions such as hypercalcemia, hypermagnesemia, and milk-alkali syndrome, particularly in patients with renal insufficiency. The product should not be taken simultaneously with large amounts of milk or dairy products. Prolonged use of Rennie® may increase the risk of kidney stone formation. When using 4 to 5 tablets per day, treatment should be short-term and discontinued immediately after symptoms resolve.

Patients should consult a physician in case of: weight loss, difficulty swallowing, persistent discomfort in the stomach, or signs of digestive disturbances, especially if these symptoms are new or have changed in character, as well as in case of renal insufficiency (calcium and magnesium levels should be monitored).

Calcium carbonate and magnesium carbonate should not be used in patients with hypercalciuria. This medicinal product should be used with caution in patients with impaired renal function. If calcium carbonate and magnesium carbonate must be administered to such patients, plasma levels of calcium, phosphorus, and magnesium should be monitored regularly.

Patients with hereditary conditions associated with fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not use this product, as it contains 475 mg of sucrose. This should also be considered in patients with diabetes mellitus.

Use during pregnancy or breastfeeding

Pregnancy

Animal studies have not shown any direct or indirect harmful effects on reproductive function.

To date, in clinical practice, no specific congenital malformations or fetotoxic effects have been observed with the use of calcium carbonate and magnesium carbonate at recommended doses. However, there are insufficient data on pregnancy outcomes following use of this combination to exclude all potential risks.

It should be noted that magnesium salts may cause diarrhea, and prolonged use of high doses of calcium may increase the risk of hypercalcemia with calcinosis in various organs, including the kidneys. Rennie® with orange flavor should be used during pregnancy only if clearly needed.

It should also be considered that during pregnancy or breastfeeding, calcium carbonate and magnesium carbonate provide a significant amount of calcium in addition to dietary intake.

To prevent calcium overload, the maximum recommended daily dose of Rennie® with orange flavor should not be exceeded, use should be limited to 1 week, and continuous consumption of milk (1 liter contains up to 1.2 g of elemental calcium) and dairy products should be avoided during treatment to prevent excess calcium intake, which may lead to the so-called milk-alkali syndrome (Burnett's syndrome)—a rare but serious condition requiring medical intervention.

Lactation

Calcium and magnesium are excreted in breast milk; however, when therapeutic doses of Rennie® with orange flavor are used, no effect on newborns or infants who are breastfed is expected.

Breastfeeding is possible while using this medicinal product, provided the product is used according to instructions; however, prolonged use of high doses should be avoided.

Fertility

There is no information on the effect of the product on fertility.

Ability to affect reaction speed when driving or operating machinery

No effect.

Ability to affect reaction speed when driving or operating machinery

No effect.

Dosage and Administration.

For oral use in adults and children aged 15 years and older.

1–2 chewable tablets as a single dose should be sucked or chewed one hour after meals, or when heartburn or pain occurs, or before bedtime.

The dose may be temporarily increased to up to 5 tablets per day.

The duration of treatment should not exceed 10 days (see section "Special Warnings and Precautions for Use").

Children.

Do not use in children under 15 years of age.

Overdose.

Prolonged use of high doses of calcium carbonate and magnesium carbonate, especially in patients with renal insufficiency, may lead to hypermagnesemia, hypercalcemia, and alkalosis, manifested by gastrointestinal symptoms (nausea, vomiting, diarrhea or constipation) and muscle weakness. In such cases, the drug should be discontinued and adequate fluid intake ensured. In severe cases of overdose (e.g., Burnett's syndrome), additional rehydration measures (infusion) may be required.

Adverse Reactions.

Immune system disorders.

Very rarely, hypersensitivity reactions have been reported, manifesting as rash, pruritus, urticaria, angioedema, dyspnea, and anaphylaxis.

Metabolism and nutrition disorders.

In patients, especially those with impaired renal function, prolonged use of high doses may lead to hypermagnesemia (when using magnesium-containing antacids) or hypercalcemia and alkalosis, manifested by gastrointestinal symptoms and muscle weakness. There is also a risk of kidney stone formation and development of renal failure.

Gastrointestinal disorders.

Nausea, vomiting, gastric discomfort, constipation, and diarrhea may occur.

Musculoskeletal and connective tissue disorders.

Muscle weakness is possible.

Adverse effects observed only in milk-alkali syndrome (Burnett's syndrome):

• Gastrointestinal disorders (ageusia);
• General disorders (calcinosis and asthenia);
• Nervous system disorders (headache);
• Renal and urinary disorders (azotemia).

Reporting of adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 ºC.

Keep out of reach of children.

Packaging.

6 tablets in blisters made of PVC and aluminum, 2 or 4 blisters in a cardboard box; or 12 tablets in perforated PVC and aluminum blisters, 1 or 2 blisters in a cardboard box.

Prescription status.

Over-the-counter.

Manufacturer.

Delpharm Gaillard /

Delpharm Gaillard

Manufacturer's address and place of business.

33 rue de l’Industrie, 74240, Gaillard, France /
33 rue de l’Industrie, 74240, Gaillard, France