Riopan

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT RIOPAN (RIOPAN®)

Composition:

Active ingredient: magaldrate;

RIOPAN 800 mg
in sachet (10 mL) contains 800 mg of anhydrous magaldrate*;

RIOPAN 1600 mg
in sachet (10 mL) contains 1600 mg of anhydrous magaldrate*;

Excipients:
acacia (gum arabic), hypromellose, maltol, sodium cyclamate, simethicone emulsion 30%**, silver sulfate (E 174), chlorhexidine digluconate solution 20 %, cream flavor, caramel flavor, purified water.

* Used in the form of a 10 % magaldrate suspension.

Composition of the 10 % magaldrate suspension:
Anhydrous magaldrate, water, sodium hypochlorite.

** Composition of simethicone emulsion:
Simethicone, methylcellulose, sorbic acid, purified water.

Pharmaceutical form.
Oral suspension.

Main physicochemical characteristics:
White with a creamy tint, caramel-scented suspension.

Pharmacotherapeutic group.
Antacids. Combinations and complex compounds of aluminium, calcium and magnesium.

ATC code A02A D02.

Pharmacological properties.

Pharmacodynamics.

Magaldrate contains aluminium and magnesium hydroxides, maintaining gastric pH within the range of 3–5. 800 mg of magaldrate neutralizes approximately 18 to 25 mEq of hydrochloric acid.

Magaldrate simultaneously binds pepsin, bile acids, and lysolecithin, thereby reducing the aggressiveness of gastric acid. It forms a protective layer that shields the gastric mucosa from damage. Magaldrate does not affect gastric peristalsis and does not cause acid rebound.

Pharmacokinetics.

Absorption.

During the neutralization process in the gastrointestinal tract, small amounts of aluminium and magnesium ions are released.

A minor portion of cations is absorbed to a degree dependent on pH (see section "Interaction with other medicinal products and other forms of interactions").

Distribution.

Magnesium and aluminium ions are converted into poorly soluble phosphates, primarily during intestinal passage, and are excreted in feces. Absorbed aluminium ions bind to plasma proteins. Accumulation in bone, CNS, and other tissues may occur, particularly in case of impaired renal function and/or prolonged use of the drug at high doses, when the protein-binding capacity of plasma is exceeded. Rarely, a slight increase in serum aluminium levels has also been reported in patients with normal renal function.

Prolonged use of antacid agents containing aluminium and magnesium may lead to disturbances in phosphate and calcium balance.

Elimination.

Magaldrate is excreted via the gastrointestinal tract; a small amount of absorbed aluminium ions is eliminated by the kidneys.

Clinical characteristics.

Indications.

Symptomatic treatment of conditions requiring gastric acid binding: heartburn, acid regurgitation.

Contraindications.

Magaldrate must not be used in the presence of:

• hypersensitivity to the active substance or to any of the excipients;
• hypophosphatemia;
• myasthenia gravis (due to magnesium content).

Interaction with other medicinal products and other types of interactions.

Since antacids may impair the absorption of concomitant medications, an interval of 2 hours should be maintained between administration of magaldrate and other drugs.

In particular, a significant reduction in absorption of tetracyclines and quinolone derivatives (e.g., ciprofloxacin, ofloxacin, norfloxacin) has been observed when used concomitantly with antacids; therefore, the use of antacids is not recommended during therapy with these antibiotics. Furthermore, absorption of iron preparations, isoniazid, chlorpromazine, digoxin, and indomethacin may be somewhat reduced.

In addition, absorption of benzodiazepines, cheno- and ursodeoxycholic acid, and cimetidine may also be affected.

Concomitant use of magaldrate may lead to enhanced anticoagulant effect of coumarin derivatives.

Concomitant use of antacids containing aluminium and acidic beverages (fruit juice, wine, etc.) should be avoided, as they may increase intestinal absorption of aluminium salts. This also applies to effervescent tablets containing citric or tartaric acid.

Alkalinization of urine following administration of magnesium hydroxide may affect the elimination of certain drugs; increased excretion of salicylates has been observed.

There is a risk of reduced efficacy of calcium carbonate when used concomitantly with phosphate binders and famotidine in patients undergoing hemodialysis.

Special precautions for use

Patients should consult a physician:

• if symptoms persist or only partially resolve and/or recur frequently. In such cases, appropriate evaluation should be performed to exclude any serious disorder;
• if they have been treated for dyspepsia or heartburn for two weeks or longer;
• if they suffer from weight loss, anemia, gastrointestinal bleeding, difficulty swallowing, persistent vomiting, or hematemesis, as symptoms of serious disorders may be masked or diagnosed with delay. In such cases, malignant neoplasms should be ruled out;
• if they have a history of gastric ulcer or gastrointestinal surgery;
• if they suffer from jaundice, impaired liver function, or any liver disease;
• if they suffer from any other serious illness affecting their general condition;
• if they are over 55 years of age and have new symptoms or recently changed symptoms.

Patients who suffer from recurrent episodes of dyspepsia or heartburn over a prolonged period should have regular medical check-ups. In particular, patients over 55 years of age who take over-the-counter medications for dyspepsia or heartburn on a daily basis should inform their physician or pharmacist.

Due to the risk of aluminium intoxication, hypermagnesemia, and hypophosphatemia (see section "Adverse reactions"), patients with severe renal impairment (creatinine clearance <30 mL/min), especially patients on dialysis, patients with Alzheimer's disease or other forms of dementia, as well as patients on a low-phosphate diet or with impaired bone metabolism, should be under medical supervision with regular monitoring of serum aluminium and magnesium levels if receiving long-term treatment with high doses.

Because of the risk of aluminium overload, prolonged use of the product should be avoided, or serum aluminium levels should be monitored regularly. Serum aluminium levels should not exceed 40 µg/L.

Since the product contains silver sulfate, the maximum duration of treatment with continuous use of the maximum daily dose of 6400 mg is limited to 1 year.

Riopan should not be used as a prophylactic or preventive agent.

Riopan is sucrose-free and can be used by patients with diabetes mellitus.

The product contains less than 1 mmol of sodium (23 mg) per 1 mL. Due to its low sodium content, it can be used in patients with high blood pressure.

As there are no studies on the safety and efficacy of the product in children and adolescents, use in children under 12 years of age is not recommended.

Use during pregnancy or breastfeeding

Aluminium compounds cross the placental barrier and are excreted in human breast milk. The benefit-risk balance should be carefully evaluated before use.

Pregnancy. Use should be short-term and at the lowest possible dose to avoid any aluminium burden to the unborn child.

Animal studies have shown reproductive toxicity. Human studies have shown aluminium accumulation in the bones of premature newborns (preterm delivery). With prolonged use, there is a potential risk of neurotoxicity.

Breastfeeding. Due to low intestinal absorption in both mother and infant, no risk to the newborn is expected.

Effect on ability to drive and use machines
Has no effect or has a negligible effect on the ability to drive and use machines.

Method of Administration and Dosage

For mild gastrointestinal complaints (e.g., heartburn, acid regurgitation), take 1 sachet (= 10 mL) of either 800 mg or 1600 mg as needed.

Since symptoms usually occur after meals or at night (when the body assumes a horizontal position), the usual dosage is 1 sachet (10 mL of either 800 mg or 1600 mg) four times daily, one hour after each main meal and at bedtime.

When using Riopan 800 mg, if acute symptoms occur between doses, the dosage may be increased up to 8 doses of 800 mg magaldrate per day.

In some cases, a single dose may suffice to relieve symptoms. Use may be discontinued as soon as symptoms resolve.

Maximum Daily Dose

The daily dose must not exceed 6400 mg of magaldrate (equivalent to 8 sachets of 10 mL Riopan 800 mg or 4 sachets of 10 mL Riopan 1600 mg).

Duration of Treatment

Magaldrate must not be taken for longer than 14 consecutive days. If symptoms do not resolve within this period, persist for more than 2 weeks, worsen, or if additional symptoms occur (see sections "Contraindications" and "Special Warnings and Precautions for Use"), a physician should be consulted. A diagnostic evaluation is required to exclude malignant neoplasms (see section "Special Warnings and Precautions for Use"). Treatment should be discontinued once symptoms have completely resolved.

Method of Administration

The medicinal product is intended for oral use.

Riopan oral suspension may be taken undiluted or mixed with liquid.

Before administration, the Riopan sachet should be shaken well, then opened along the indicated line. The contents should be squeezed directly into the mouth and swallowed.

Patients with Renal or Hepatic Impairment

Patients with impaired renal or hepatic function should use the medicinal product only after prior consultation with a physician (see section "Special Warnings and Precautions for Use").

Children

As safety and efficacy of the medicinal product in children and adolescents have not been established, its use is not recommended in children under 12 years of age.

Overdose

Symptoms

Overdose with aluminium salts is primarily possible in patients with chronic severe renal impairment and may present with symptoms such as encephalopathy, seizures, and dementia.

Treatment

In case of overdose, treatment should be symptomatic and include general supportive measures.

Adverse Reactions

Undesirable effects are classified by frequency of occurrence into the following categories: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), and not known (cannot be estimated from available data).

From the nervous system:

Not known: neurotoxicity, encephalopathy**.

From the gastrointestinal tract:

Common: soft stools and increased frequency of defecation.

Very rare: diarrhea (especially at high doses).

Not known: nausea; vomiting, constipation, abdominal pain.

Metabolism and nutrition disorders:

Very rare: in patients with renal insufficiency (creatinine clearance < 30 mL/min), particularly in patients undergoing dialysis, and with prolonged use, aluminum and magnesium intoxication may occur, which can manifest as hypermagnesemia with cardiac and central nervous system adverse effects*.

Not known: manifestations of aluminum and magnesium intoxication may also include hypophosphatemia.

*Patients undergoing hemodialysis should be monitored for elevated serum aluminum levels.

**In patients with renal insufficiency or with prolonged use of high doses of the drug, increased levels of aluminum and magnesium in the blood may occur, leading to accumulation of aluminum, primarily in nervous and bone tissues, and to phosphate deficiency.

In patients with renal insufficiency and with prolonged high-dose use, toxicity of aluminum and magnesium may occur.

Manifestations include: hypermagnesemia (symptoms include, for example, skin flushing, thirst, hypotension, drowsiness, loss of tendon reflexes due to neuromuscular blockade, weakness, respiratory depression, cardiac arrhythmias, coma, and cardiac arrest).

The following adverse reactions have also been reported with the use of drugs containing aluminum hydroxide and/or magnesium hydroxide:

Dysgeusia (chalky taste sensation); nausea; vomiting; aluminum and/or magnesium intoxication, most frequently in patients with renal insufficiency.

Dementia, worsening of Alzheimer's disease.

Osteomalacia, osteoporosis.

Due to the formation of intestinal complexes of excreted magnesium and sodium ions with phosphate and calcium, prolonged use of high doses over many years may lead to osteopenic bone changes such as rickets, due to reduced absorption of calcium and phosphate.

Hypersensitivity reactions, including pruritus, urticaria, angioedema, and anaphylactic reactions, bronchospasm.

Reduction in phosphorus content in the body may occur even with the use of normal doses of the drug in patients whose diet is low in phosphorus.

Enhanced resorption processes in bone tissue, hypercalciuria.

In patients with renal insufficiency, prolonged use of high doses of aluminum and magnesium salts may lead to the development of encephalopathy, microcytic anemia, or may worsen dialysis-induced osteomalacia. Prolonged use or high-dose intake may cause phosphorus deficiency syndrome (loss of appetite, muscle weakness, weight loss).

Aluminum hydroxide may be hazardous for porphyria patients undergoing hemodialysis.

Shelf life:
3 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions:
Store at a temperature not exceeding 25°C. Do not freeze!

Keep out of reach of children!

Packaging:
10 mL in sachets. 10, 20, or 50 sachets per cardboard box.

Prescription status:
Over-the-counter.

Manufacturer:
Takeda GmbH, Germany / Takeda GmbH, Germany.

Manufacturer's address and place of business:
Robert-Bosch-Strasse 8, 78224 Singen, Germany / Robert-Bosch-Strasse 8, 78224 Singen, Germany.