4.1. Therapeutic indications

Renodyra is an alkalizing agent and indicated in adults for:

- The treatment of patients with kidney stones and hypocitraturia, or chronic calcium oxalate stones.

- The treatment and prevention of recurrent uric acid lithiasis with or without calcium lithiasis and cystine lithiasis.

- The treatment of renal tubular acidosis with calcium nephrolithiasis.

4.2. Posology and method of administration

Posology

In patients with severe hypocitraturia (urinary citrate <150 mg/day), therapy should be initiated at a dosage of 6480 mg (60 mEq) per day (6 tablets) divided into 3 intakes per day.

In patients with mild hypocitraturia (urinary citrate >150 mg/day), therapy should be initiated at a dosage of 3240 mg (30 mEq) per day (3 tablets) divided into 3 intakes per day.

If necessary, the dosage may be increased as long as the 10800 mg (100 mEq)/day limit is not exceeded.

Renal impairment

Renodyra is contraindicated in individuals with glomerular filtration rate (GFR) ≤44 mL/min/1.73m2 (see section 4.3). For individuals with a GFR between 45 and 59 mL/min/1.73m2 and plasma potassium levels in the normal ranges, regular monitoring of renal function parameters and blood potassium levels is recommended (see section 4.4).

Potassium citrate is contraindicated in patients with elevated plasma potassium levels (see section 4.3).

Hepatic impairment

Potassium citrate should be used with caution in patients with hepatic impairment (see section 4.4).

Paediatric population

The safety and efficacy of Renodyra in children have not been established. No data are available.

Method of administration

Renodyra is administered orally.

The tablets should be taken with meals or within 30 minutes after meals to avoid gastrointestinal reactions.

The tablets must be swallowed whole with enough liquid and should not be taken with alcohol, crushed, chewed or dissolved as this may result in the medicine being released too early.

The tablets should be taken in conjunction with a diet that avoids foods with high sodium content and avoids the use of table salts. Patients who take Renodyra modified-release tablets should increase their fluid intake.

It is recommended that 24-hour urinary citrate and urinary pH measurement is used to determine the adequacy of the initial dosage and to evaluate the effectiveness of any dosage change. In the case of a pH value which is higher or lower than the target range of 6.0 to 7.0, the daily dose should be adjusted in accordance with the needs of the patient. This is preferably done with the evening dose.

4.3. Contraindications

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

- Renal impairment (GFR ≤ 44 mL/min/1.73 m2)

- Active or persistent urinary tract infections

- Significant or complete obstruction of the urinary tract

- Hyperkalaemia

- Severe myocardial injury

- Uncontrolled diabetes mellitus

- Adrenal insufficiency

- Metabolic or respiratory alkalosis

- Active peptic ulcer

- Delayed gastric emptying

- Intestinal obstruction

4.4. Special warnings and precautions for use

Hyperkalaemia and cardiotoxicity

In patients with impaired mechanisms for excreting potassium, the administration of Renodyra may produce hyperkalaemia and cardiac arrest. Potentially fatal hyperkalaemia may develop rapidly and be asymptomatic.

Renodyra should be used with caution in case of combination with other products increasing plasma potassium or predisposing to cardiac arrest (see section 4.5).

Serum electrolytes (sodium, potassium, chloride and carbon dioxide), serum creatinine, and complete blood count should be monitored every four months.

Severe hepatic impairment

There is the potential for hyperkalaemia and citrate toxicity in severe hepatic impairment though the impact of oral potassium citrate in these patients has not been studied (see section 4.2).

Renal impairment

For individuals with a GFR between 45 and 59 mL/min/1.73m2 and plasma potassium levels in the normal ranges, regular monitoring of renal function parameters and blood potassium levels is recommended at starting dose, after new dose increase or in case of decreased GFR. Then frequency should be according to the physician's criteria, but at least twice a year.

Excipients

This medicinal product contains 390 mg potassium per tablet. To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.

4.5. Interaction with other medicinal products and other forms of interaction

Concomitant use should be avoided

Amphetamines

Alkalinizing agents may decrease the excretion of amphetamines. Management: Consider alternatives to using amphetamines and alkalinizing agents in combination. If these agents must be used together, patients should be monitored closely for excessive amphetamine effects. Modification of therapy should be considered.

Anticholinergic agents

May enhance the ulcerogenic effect of potassium citrate.

Potassium-sparing diuretics

(i.e., amiloride, eplerenone, spironolactone, triamterene)

Potassium salts may enhance the hyperkalaemic effect of potassium-sparing diuretics.

Management: This combination should only be used in cases of significant hypokalaemia, and only if serum potassium can be closely monitored. Modification of therapy should be considered.

Concomitant use requires monitoring

ACE inhibitors

May enhance the hyperkalaemic effect of potassium salts.

Aliskiren

Potassium salts may enhance the hyperkalaemic effect of aliskiren.

Alpha-/beta-agonists (indirect-acting)

Alkalinizing agents may increase the serum concentration of alpha-/beta-agonists (indirect-acting).

Aluminium hydroxide

Citric acid derivatives may increase the absorption of aluminium hydroxide.

Amantadine

Alkalinizing agents may increase the serum concentration of amantadine.

Angiotensin II receptor blockers

Potassium salts may enhance the hyperkalaemic effect of angiotensin II receptor blockers.

Beta-blockers

May enhance the hyperkalaemic effect of potassium salts.

Digoxin

May enhance the hyperkalaemic effect of potassium salts.

Drospirenone-containing products

May enhance the hyperkalaemic effect of potassium salts.

Finerenone

Potassium salts may enhance the hyperkalaemic effect of finerenone.

Heparin (incl. low-molecular weight)

May enhance the hyperkalaemic effect of potassium salts.

Mecamylamine

Alkalinizing agents may increase the serum concentration of mecamylamine.

Memantine

Alkalinizing agents may increase the serum concentration of memantine.

Nicorandil

May enhance the hyperkalaemic effect of potassium salts.

Nonsteroidal anti-inflammatory agents (NSAIDs) (e.g., indomethacin)

May enhance the hyperkalaemic effect of potassium salts.

Quinine

Alkalinizing agents may increase the serum concentration of quinine.

Interaction with alcohol

Taking Renodyra with alcohol can lead to a loss of the modified-release effect (see section 4.2).

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of Renodyra in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).

Renodyra should only be used during pregnancy if the expected benefits outweigh the potential risks. Although during pregnancy and more so during labour, there is more risk associated to a potentially severe acidosis and hypokalaemia in dRTA patients than to alkali treatment, in women with problem pregnancies there might be an increased risk to develop hyperkalaemia when potassium intake is high.

Breast-feeding

Potassium is excreted in human milk, but at therapeutic doses of Renodyra no effects on the breastfed newborns/infants are anticipated.

Renodyra can be used during breast-feeding.

Fertility

Potassium citrate is not known to affect fertility.

4.7. Effects on ability to drive and use machines

Renodyra has no influence on the ability to drive and use machines.

4.8. Undesirable effects

The most common adverse reaction relates to the formulation and potassium products causing gastro-intestinal upset including nausea, vomiting, diarrhoea, abdominal pain and discomfort, and can potentially lead to gastro-intestinal ulceration, bleeding, perforation and/or obstruction.

Adverse reactions are listed according to MedDRA organ classes and frequency. Frequencies are defined as: 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), not known (cannot be estimated from the available data).

System organ class/frequency

MedDRA preferred term

Gastrointestinal disorders

Very common

Abdominal pain, nausea

Common

Abdominal pain upper, diarrhoea, dyspepsia, dysphagia, oesophagitis, vomiting, gaseousness (bloating, belching, flatulence)

Not known

Gastrointestinal mucosal damage, gastrointestinal bleeding or obstruction

Metabolism and nutrition disorders

Not known

Hyperkalaemia

Skin

Common

Rash

In patients with rapid gastrointestinal transit time, the tablet wax matrix may be present in their faeces.

Description of selected adverse reactions

Ingestion of potassium citrate may induce hyperkalaemia.

Severe hyperkalaemia may lead to muscle weakness/paralysis and cardiac conduction abnormalities (e.g., heart block, ventricular arrhythmias, asystole). Patients with cardiovascular disease e.g., heart failure, cardiac arrhythmias, may be more susceptible to life-threatening cardiac effects associated with hyper/hypokalaemia and, therefore, potassium citrate should be used with caution (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal products. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms

Overdosage of Renodyra can cause hyperkalaemia. Disturbances caused by hyperkalaemia are mainly neuromuscular and cardiovascular.

Neuromuscular disturbances include depression, mental confusion, paraesthesia, muscle weakness and sometimes flaccid paralysis of the extremities, which can be progressive.

Cardiovascular disturbances include bradycardia, low blood pressure, which may in some cases be serious, leading to cardiac arrhythmias, cardiac arrest and sudden death.

Treatment

In case of overdose, administration of potassium should be stopped. Depending on the severity of hyperkalaemia, treatment may include rapid acting therapies to treat hyperkalaemia (calcium and insulin with glucose) and measures to remove potassium from the body (haemodialysis, gastrointestinal potassium binders, or diuretics). Patients should be ECG monitored.