Almagel® a

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALMAGEL® A (ALMAGEL® A)

Composition:

Active substances: aluminium hydroxide, magnesium hydroxide;

5 ml of suspension (1 measuring spoon) contains:

aluminium hydroxide gel 2.18 g calculated as aluminium oxide 218 mg;

magnesium hydroxide paste 350 mg calculated as magnesium oxide 75 mg;

benzocaine 109 mg;

10 ml (1 sachet) of suspension contains:

aluminium hydroxide gel 4.36 g calculated as aluminium oxide 436 mg;

magnesium hydroxide paste 700 mg calculated as magnesium oxide 150 mg;

benzocaine 218 mg;

Excipients: sorbitol (E 420), hydroxyethylcellulose, methylparahydroxybenzoate (E 218), propylparahydroxybenzoate (E 216), butylparahydroxybenzoate, sodium saccharin, lemon oil, ethanol 96%, purified water, hydrogen peroxide solution (30%), propylene glycol, macrogol 4000.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: white or almost white suspension. During storage, a layer of clear liquid may separate on the surface of the suspension. Homogeneity of the suspension is restored upon vigorous shaking of the container contents.

Pharmacotherapeutic group. Drugs for the treatment of acid-related disorders. Antacids. Aluminium compounds. Combinations.

ATC code A02A B10.

Pharmacological properties.

Pharmacodynamics.

Almagel® A is a balanced combination of aluminum hydroxide and magnesium hydroxide combined with sorbitol. The medicinal product exerts a moderate antacid effect when the recommended single and daily doses are used, lasting for 40–60 minutes after administration.

Aluminum hydroxide neutralizes excess hydrochloric acid secretion and reduces pepsin activity in the stomach by forming aluminum chloride. Under the alkaline conditions of the intestine, aluminum chloride is converted into alkaline aluminum salts, which are almost not absorbed and only slightly alter the concentration of aluminum salts in blood during prolonged use of Almagel® A. On the other hand, aluminum hydroxide has the ability to alter phosphate concentrations by binding phosphate ions in the intestine, thereby limiting their absorption.

Antacids containing aluminum, including Almagel® A, also exert a cytoprotective effect on the gastric mucosa, associated with the stimulation of prostaglandin synthesis. Thus, mucosal resistance is enhanced, protecting it from inflammatory-necrotic and erosive-hemorrhagic changes caused by irritant and ulcerogenic agents such as acetylsalicylic acid, nonsteroidal anti-inflammatory drugs, and ethanol.

Magnesium hydroxide also neutralizes hydrochloric acid in the stomach, converting into magnesium chloride, which exerts a mild laxative effect.

Benzocaine provides local analgesic action in the presence of pronounced pain syndrome.

Sorbitol exerts weak carminative, moderate cholagogue, and mild laxative effects. These effects counteract, in most patients, the tendency to constipation induced by aluminum hydroxide.

The medicinal product does not lead to the development of alkalosis or the formation of carbon dioxide (CO₂) in the stomach.

Pharmacokinetics.

Aluminum salts are minimally absorbed in the intestine. Magnesium ions are absorbed only by approximately 10%, and their blood concentration remains almost unchanged. Duration of action depends on gastric emptying rate. When administered on an empty stomach, the effect lasts 20–60 minutes; when administered one hour after a meal, antacid action may last up to 3 hours.

Benzocaine is absorbed in minimal amounts and practically does not exert systemic effects. Its local analgesic action begins 1–2 minutes after suspension administration.

Clinical characteristics.

Indications.

Short-term symptomatic treatment of inflammatory and erosive lesions accompanied by heartburn, discomfort, pain, nausea, and vomiting; in acute or chronic inflammatory processes or other disorders of the mucous membranes of the esophagus, stomach, or duodenum.

Contraindications.

The medicinal product should not be administered to children (due to the risk of developing methemoglobinemia), as well as to pregnant women and breastfeeding women, due to the presence of benzocaine.

Almagel® A is contraindicated in:

• hypersensitivity to any active and/or excipients contained in the medicinal product;
• increased sensitivity to anesthetics;
• chronic constipation;
• chronic diarrhea;
• severe abdominal pain of unknown origin, suspected acute appendicitis;
• Alzheimer's disease;
• severe forms of renal insufficiency (due to the risk of hypermagnesemia and aluminum intoxication);
• hypophosphatemia;
• pronounced patient exhaustion.

Interaction with other medicinal products and other types of interactions.

Reduced gastrointestinal absorption of medicinal products administered simultaneously with antacids may be observed. This may be related to the fact that the medicinal product alters gastric juice acidity, thereby affecting absorption, maximum plasma concentrations, bioavailability, and excretion of a large number of medicinal products when used concomitantly.

As a precautionary measure, an interval of at least 2 hours (4 hours for fluoroquinolones) should be maintained between administration of antacids and other medicinal products.

Almagel® A reduces the absorption of the following drugs: acetylsalicylic acid,
H2-histamine receptor blockers (cimetidine, ranitidine), antituberculosis agents [ethambutol, isoniazid (for oral administration)], mexiletine, lithium preparations, atenolol, metoprolol, propranolol, chloroquine, cyclines, diflunisal, digoxin, cefdinir, cefpodoxime, quinidine, bisphosphonates, fexofenadine, iron salts, vitamins, fluoroquinolones (e.g., ciprofloxacin), folic acid, sodium fluoride, glucocorticoids, except cortisol in replacement therapy (described for prednisolone and dexamethasone), indomethacin, ketoconazole (reduced gastrointestinal absorption of ketoconazole due to increased gastric pH), lansoprazole, lincosamides, phenothiazine neuroleptics, tetracycline antibiotics, sulpiride, penicillamine, phosphorus (supplements), thyroxine, sodium polystyrene sulfonate (reduced ability of the resin to bind potassium, which may lead to metabolic alkalosis in patients with renal insufficiency).

Whenever possible, the time interval between administration of Almagel® A and the above-mentioned drugs should exceed 2 hours. Reduced binding of these drugs is associated with the formation of insoluble complexes and/or alkalinization of gastric contents.

Caution should be exercised when using the product concomitantly with polystyrene sulfonate (kayexalate) due to the potential risk of reduced potassium-binding efficacy of the ion-exchange resin, development of metabolic alkalosis in patients with renal insufficiency (observed with aluminum hydroxide and magnesium hydroxide), and mechanical intestinal obstruction (observed with aluminum hydroxide).

When used concomitantly with enteric-coated tablets, increased gastric alkalinity may lead to premature dissolution of the coating and, consequently, cause irritation of the stomach and duodenum.

When used concomitantly with quinidine, plasma concentration of quinidine may increase, potentially leading to quinidine overdose.

Alkalinization of urine due to magnesium hydroxide administration may alter the excretion of certain drugs. In particular, renal excretion of salicylates increases when combined with salicylates.

In patients with renal insufficiency, combined administration with citrates may lead to elevated blood aluminum levels, particularly in patients with impaired renal function.

Almagel® A should not be used concomitantly with sulfonamides, as it contains benzocaine. Being a derivative of para-aminobenzoic acid, benzocaine acts as an antagonist of the antibacterial activity of sulfonamides, thereby reducing their therapeutic effect.

Effect on laboratory tests – see section "Special instructions for use".

Special precautions for use

The use of this medicinal product is not recommended in patients with metabolic alkalosis, liver cirrhosis, severe heart failure, ulcerative colitis, diverticulosis, colostomy, ileostomy (increased risk of water-electrolyte imbalance), acute hemorrhoids, or renal insufficiency.

Long-term use of antacids may mask symptoms of more serious conditions, such as gastrointestinal ulcers or cancer.

Patients should be advised to consult a physician in the following cases:

• Unintentional weight loss;
• Difficulty swallowing or persistent abdominal discomfort;
• New-onset digestive disturbances or changes in existing digestive symptoms;
• Renal insufficiency.

Aluminium hydroxide may cause constipation, while magnesium salt overdose may lead to intestinal hypokinesia. High-dose administration of the medicinal product may cause or exacerbate mechanical or dynamic intestinal obstruction in high-risk patients, such as those with renal insufficiency or elderly individuals.

Aluminium hydroxide is absorbed in small amounts from the gastrointestinal tract; therefore, systemic effects are rarely observed in patients with normal renal function. Nevertheless, prolonged use at high doses in patients on a low-phosphate diet may lead to phosphate deficiency (due to binding of aluminium to phosphates), resulting in increased bone resorption, hypercalciuria, and risk of osteomalacia. Long-term treatment of patients at risk of phosphate deficiency should be conducted under medical supervision.

In patients with impaired renal function, plasma concentrations of aluminium and magnesium may increase. When treating patients with renal insufficiency or those undergoing chronic hemodialysis, the presence of aluminium and magnesium in the medicinal product must be taken into account (risk of encephalopathy, dementia, microcytic anemia, or worsening of dialysis-induced osteomalacia).

Aluminium hydroxide may be harmful in patients with porphyria undergoing hemodialysis, as aluminium has been shown to interfere with porphyrin metabolism. Prolonged use of the product (more than 7 days) is not recommended due to the presence of benzocaine (see section "Dosage and administration").

Long-term use in elderly patients may lead to progression of pre-existing bone and joint disorders, as well as progression of Alzheimer's disease.

During treatment with Almagel® A, consumption of alcohol and acidic substances (e.g., lemon juice, vinegar) should be avoided, as they may reduce the local anesthetic effect of benzocaine.

If signs of allergy to the medicinal product occur (rash, itching, facial swelling, breathing difficulties), the drug should be discontinued immediately and medical advice sought.

When using the suspension, numbness and anesthesia of the oral mucosa and tongue may occur. This phenomenon is transient, requires no therapeutic intervention, and should not concern the patient.

The product contains sorbitol, which is contraindicated in hereditary fructose intolerance.

Almagel® A contains parabens [excipients propylparahydroxybenzoate (E 216) and methylparahydroxybenzoate (E 218)], which may cause allergic reactions. These are usually delayed-type reactions. Immediate-type allergic reactions, including bronchospasm, are very rare.

The product contains 2.5% v/v ethanol (98.1 mg ethanol in a 5 ml dose, equivalent to 2.5 ml of beer or 1 ml of wine; 196.2 mg ethanol in a 10 ml dose, equivalent to 5 ml of beer or 2 ml of wine). Therefore, use of the product may adversely affect patients suffering from alcoholism, liver disease, central nervous system disorders, epilepsy, as well as during pregnancy and breastfeeding.

When concomitant treatment with other orally administered medicinal products is required, Almagel® A should be taken 2 hours (4 hours for fluoroquinolones) before or 2 hours after administration of the drugs mentioned in the section "Interaction with other medicinal products and other forms of interaction."

Effect on laboratory tests

Almagel® A may affect the results of certain laboratory and functional tests and examinations: it reduces gastric secretion when measuring its acidity; interferes with visualization tests for diverticula and bone scintigraphy using technetium (99mTc); moderately and temporarily increases plasma levels of gastrin, phosphorus, blood and urine pH.

Use during pregnancy or breastfeeding

Almagel® A should not be used during pregnancy or breastfeeding due to the presence of benzocaine.

Ability to influence reaction speed when driving or operating machinery

The small amount of ethanol in the medicinal product, when used at recommended doses, does not affect the ability to drive vehicles or operate machinery requiring high attention.

Method of Administration and Dosage

Almagel® A should be used for the treatment of adults.

Before administration, the suspension must be made homogeneous by thoroughly shaking the bottle or gently kneading the sachet. The medicinal product does not need to be diluted or taken with water. The required dose from the bottle should be measured using the dosing spoon provided in the package. When using the product in sachets, hold the sachet vertically, cut or tear off one of the corners at the marked place, and pour the contents through the opening into a spoon or directly into the oral cavity.

Doses

Administer 5–10 mL (1–2 dosing spoons) 3–4 times daily or 1 sachet 3–4 times daily, 10–15 minutes before meals.

If the single dose prescribed is 5 mL, it is recommended to use Almagel® A in bottles, as the dosing spoon included in this packaging allows accurate measurement of the required volume.

The duration of treatment with Almagel® A should not exceed 7 days. After this period, treatment may be continued with Almagel® as directed by a physician.

Renal Impairment. In cases of reduced kidney function, the daily dose should be reduced or the intervals between doses extended according to the severity of renal dysfunction.

Children.

The medicinal product should not be administered to children due to the risk of developing methemoglobinemia.

In young children, the use of magnesium hydroxide may cause hypermagnesemia, especially if renal function impairment or dehydration is present.

Overdose.

After single administration of large doses, no other overdose symptoms have been observed except constipation, flatulence, and a metallic taste in the mouth.

Prolonged use of Almagel® A in doses exceeding the recommended may lead to kidney stone formation (nephrocalcinosis), severe constipation, drowsiness, hypermagnesemia—despite the fact that the drug is poorly absorbed in the gastrointestinal tract. Prolonged use of Almagel® A may also cause phosphate deficiency. Symptoms of metabolic alkalosis may occur: mood changes and altered mental activity, numbness and muscle pain, nervousness and rapid fatigue, difficulty breathing, and unpleasant taste sensations. Other signs of intoxication may include decreased arterial pressure, nausea, vomiting, diminished reflexes, muscle weakness, neuromuscular paralysis, bradycardia, ECG abnormalities, hyp ventilation; in the most severe cases, respiratory paralysis, coma, renal failure, cardiac arrest, and anuria may occur.

Treatment. Measures should be taken to rapidly eliminate the drug from the body, such as gastric lavage (inducing vomiting, administration of activated charcoal).

Treatment of magnesium overdose: the effects of hypermagnesemia can be counteracted by intravenous administration of calcium gluconate, rehydration, and forced diuresis. Patients with renal impairment require hemodialysis or peritoneal dialysis.

Adverse Reactions

Adverse effects occur rarely when the drug is used at recommended doses.

Adverse effects are grouped by frequency according to the MedDRA classification. Frequency of adverse effects is defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); unknown (cannot be estimated from available data).

Gastrointestinal disorders:
Uncommon ‒ diarrhea, constipation (resolves after dose reduction);
Unknown ‒ abdominal pain, nausea, vomiting, stomach cramps, altered taste sensations.

Immune system disorders:
Unknown ‒ hypersensitivity reactions, including bronchospasm, skin rash, pruritus, urticaria, angioneurotic edema, and anaphylactic reactions.

Metabolic and nutritional disorders:
Very rare ‒ hypermagnesemia (with prolonged use of magnesium hydroxide in patients with impaired renal function);
Unknown ‒ hyperaluminemia, hypophosphatemia (reported after prolonged use of magnesium hydroxide in patients with impaired renal function). Prolonged use of aluminum and magnesium salts in high doses in patients with renal insufficiency or those on dialysis, as well as use of standard doses in patients with restricted phosphate intake, may lead to the development of encephalopathy, dementia, microcytic anemia, or may worsen dialysis-induced osteomalacia. Furthermore, due to the development of hypophosphatemia, such use may enhance bone resorption processes and lead to hypercalciuria, increasing the risk of osteomalacia.

If any adverse reactions occur, discontinue use of the medicinal product and consult a physician.

Shelf life. 2 years.

After first opening of the bottle, the suspension may be stored for up to 3 months under the specified storage conditions.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Do not freeze!

Keep out of reach of children!

Packaging.

170 ml of the preparation in a bottle, placed in a cardboard box together with a dosing spoon.

10 ml of the preparation in a sachet. 10 or 20 sachets per cardboard box.

Availability. Over-the-counter (without prescription).

Balkanpharma-Troyan AD / Balkanpharma-Troyan AD.

Manufacturer's location and address of its place of business.

Bulgaria, 5600 Troyan, 1 Krayrechna Str. / 1 Krayrechna Str., 5600 Troyan, Bulgaria.