Rennie® sugar-free

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT RENNIE® SUGAR FREE (RENNIE® SUGAR FREE)

Composition:

Active substances: calcium carbonate and heavy magnesium carbonate;

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

Excipients: sorbitol (E 420), pregelatinized corn starch, potato starch, talc, magnesium stearate, light mineral oil, peppermint flavor, sodium saccharin.

Pharmaceutical form. Chewable tablets with peppermint flavor.

Main physicochemical properties: white to creamy white square tablets with concave surfaces, embossed with the word "RENNIE" on both sides, and having a minty odor.

Pharmacotherapeutic group. Drugs for the treatment of acid-related disorders. Antacids in combination with other agents.

ATC code A02AX.

Pharmacological Properties

Pharmacodynamics

Rennie® sugar-free is a combination of two antacids: calcium carbonate and magnesium carbonate, which act locally by neutralizing gastric acid independently of systemic absorption. Calcium carbonate has a prolonged and strong neutralizing activity. This effect is enhanced by magnesium carbonate, which also has potent acid-neutralizing activity.

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

In vitro acid neutralization studies (artificial stomach model) have shown that Rennie® sugar-free 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 and 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 eliminated in feces.

Preclinical studies with Rennie® medicinal 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 contain additional information beyond that already presented in other sections of the medicinal product’s instructions for medical use.

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.

This medicinal product is contraindicated in the following cases:

• Hypersensitivity to the active substances or to any of the excipients;
• Hypercalcemia and/or conditions predisposing to hypercalcemia;
• Nephrolithiasis caused by 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 should be administered 1–2 hours before or after taking Rennie® Sugar Free.

Since reduced gastrointestinal absorption of certain concomitantly administered drugs may occur, as a precautionary measure, a 2-hour interval should be maintained between administration of Rennie® Sugar Free and acetylsalicylic acid, estramustine, H2-antagonist antihistamines, atenolol, metoprolol or propranolol, chloroquine, diflunisal, digoxin, bisphosphonates, fexofenadine, glucocorticoids (prednisolone and dexamethasone, except hydrocortisone in replacement therapy), indomethacin, ketoconazole, phenothiazine neuroleptics, penicillamine, thyroid hormones (thyroxine), ethambutol, isoniazid, lansoprazole, sulpiride, and cyclines.

Changes in gastric acidity, such as those occurring during antacid treatment, may impair the rate and extent of absorption of other drugs when taken simultaneously. When Rennie® Sugar Free 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), compounds containing phosphorus, strontium, or 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. Additionally, 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 polystyrene sulfonate – a cation-exchange resin: the ability of the resin to bind potassium is reduced, which may lead to a risk of metabolic alkalosis in renal impairment.

Special precautions for use

The treatment course with the sugar-free Rennie® preparation should not exceed 10 days. If symptoms do not disappear, partially persist, or worsen after 10 days of treatment, a physician should be consulted for examination and reassessment of the treatment regimen.

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 in high doses may lead to adverse reactions such as hypercalcemia, hypermagnesemia, and milk-alkali syndrome, especially in patients with renal insufficiency. The product should not be taken simultaneously with large amounts of milk or dairy products. Prolonged use of sugar-free Rennie® may increase the risk of kidney stone formation. When using 4 to 5 tablets per day, the treatment course should be short, and treatment should be discontinued immediately after symptoms resolve. One tablet of sugar-free Rennie® contains less than 1 mmol (23 mg) of sodium, i.e., it can be considered essentially sodium-free.

Medical advice should be sought in case of: weight loss, swallowing difficulties, or persistent discomfort in the stomach, signs of digestive disorders—especially if they are newly occurring 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 cases of 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.

One tablet of sugar-free Rennie® contains 400 mg of sorbitol; therefore, this preparation should not be used by patients with hereditary fructose intolerance.

Patients with diabetes mellitus. One tablet of sugar-free Rennie® contains 400 mg of sorbitol and saccharin; therefore, the medicinal product can be used by patients with diabetes mellitus.

Use during pregnancy or breastfeeding.

Pregnancy

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

To date, in clinical practice, no specific congenital defects or fetotoxic effects have been observed with the use of calcium carbonate and magnesium carbonate at recommended doses. However, there is insufficient clinical experience during pregnancy with this combination to fully exclude all risks.

It should be considered that magnesium salts may cause diarrhea, and prolonged use of high doses of calcium may increase the risk of hypercalcemia with calcinosis of various organs, including the kidneys. Sugar-free Rennie® should be used during pregnancy only if clearly necessary.

It should also be noted 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 sugar-free Rennie® should not be exceeded, use should be limited to one week, and during treatment, continuous consumption of milk (1 liter contains up to 1.2 g of elemental calcium) and dairy products should be avoided to prevent calcium excess, 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 sugar-free Rennie® are used, no effect on newborns/infants who are breastfed is expected.

Breastfeeding is possible while using this medicinal product, provided it is used according to the 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.

Dosage and Administration.

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

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

The dose may be increased for a short period 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, whose clinical manifestations may include 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 (with magnesium-containing antacids) or hypercalcemia and alkalosis manifested by gastrointestinal symptoms and muscle weakness.

Gastrointestinal disorders.

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

Musculoskeletal and connective tissue disorders.

Muscle weakness may occur.

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

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

Reporting of adverse reactions after marketing authorization 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 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 °C.

Keep out of reach and sight of children.

Packaging.

6 tablets in a blister; 2 or 4 blisters in a cardboard box.

12 tablets in a perforated blister; 1 or 2 blisters in a cardboard box.

Availability.

Over-the-counter (without prescription).

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.