PATIENT INFORMATION LEAFLET

DISEON 0.25 mcg soft capsules, 1 mcg soft capsules, 2 mcg/ml oral drops, solution

Alfacalcidol
PHARMACOTHERAPEUTIC CATEGORY
Vitamin D and analogues.
THERAPEUTIC INDICATIONS
Renal osteodystrophy in dialysis or non-dialysis patients. Hypoparathyroidism. Rickets and
D-resistant or D-dependent osteomalacia (pseudo-deficiency). Rickets and osteomalacia due to
renal disturbances in vitamin D metabolism. Postmenopausal osteoporosis.
CONTRAINDICATIONS

Hypersensitivity to the active substance or to any of the excipients.
States of hypercalcemia.
Vitamin D toxicity/proven hypervitaminosis D.

PRECAUTIONS FOR USE
Since overdose of Diseon may cause hypercalcemia and, in some cases, hypercalciuria, serum calcium levels should be measured at least twice weekly during the dose adjustment phase. Once the optimal daily dose has been established, monthly monitoring of serum calcium is sufficient, although calcium levels should still be checked promptly if symptoms suggestive of toxicity occur.
A similar monitoring is recommended for infants who are breastfed by mothers receiving pharmacological doses of 1-alpha-hydroxycalciferol.
During treatment with 1-alpha-hydroxycalciferol, plasma phosphate concentrations must be monitored to reduce the risk of ectopic calcifications.
A decrease in alkaline phosphatase levels usually precedes the onset of hypercalcemia and may serve as an early warning sign. If hypercalcemia develops, the drug and any concomitant calcium supplementation should be temporarily discontinued until serum calcium levels rapidly return to normal.
Treatment can then be resumed at a lower dosage. Since Diseon affects phosphate transport in the intestine, kidney, and bone, concomitant administration of phosphate-binding agents should be adjusted according to serum phosphate levels (normal range: 2–5 mg/100 ml).
Vitamin D supplementation in the diet may be harmful in individuals who already receive adequate amounts through diet and sun exposure, as the difference between therapeutic and toxic concentrations is relatively small.
Since 1-alpha-hydroxycalciferol is the most potent form of vitamin D, a higher risk of toxicity might reasonably be expected.
INTERACTIONS
Inform your doctor or pharmacist if you have recently taken any other medicines, including those without a prescription.
Vitamin D or its analogues
Pharmacological doses of vitamin D or its analogues must not be administered during treatment with 1-alpha-hydroxycalciferol due to the possibility of additive effects and increased risk of hypercalcemia.
Warfarin
Animal studies have suggested a possible potentiation of warfarin's effect when co-administered with calciferol. Although similar evidence is lacking with 1-alpha-OHD, caution is advised when these two drugs are used together.
Digitalis
Hypercalcemia in patients taking digitalis-containing preparations may worsen cardiac arrhythmia. Patients receiving digitalis concurrently with 1-alpha-hydroxycalciferol must be closely monitored.
Antiepileptics
Some antiepileptic drugs may increase the requirements for 1-alpha-hydroxycalciferol (e.g., carbamazepine, phenobarbital, phenytoin, and primidone).
Cholestyramine, colestipol, sucralfate, aluminum-based antacids
The absorption of 1-alpha-hydroxycalciferol may be impaired by concomitant use of bile acid sequestrants (cholestyramine, colestipol), sucralfate, or aluminum-based antacids.
Magnesium-containing antacids and laxatives
Caution should be exercised when using magnesium-containing antacids or laxatives in patients taking 1-alpha-hydroxycalciferol, especially in those undergoing chronic renal dialysis. Hyper-magnesemia may occur.
Calcium or phosphate preparations or thiazide diuretics
The risk of hypercalcemia is increased in patients taking calcium- or phosphate-containing preparations or thiazide diuretics concomitantly with 1-alpha-hydroxycalciferol. In such cases, plasma calcium concentrations should be monitored.
Rifampicin and isoniazid
Rifampicin and isoniazid may reduce the efficacy of vitamin D.
Corticosteroids
Corticosteroids may counteract the effect of vitamin D.
SPECIAL WARNINGS
DISEON should be used with caution in infants, who may have increased sensitivity to its effects, and in patients with impaired renal function, kidney stones, or heart disease, who are at greater risk of organ damage if hypercalcemia occurs.
Overdose of any form of vitamin D may lead to severe manifestations.
Hypercalcemia caused by excessive doses of vitamin D or its metabolites may require emergency treatment. Chronic hypercalcemia may lead to generalized vascular calcifications, nephrocalcinosis, and calcification of other soft tissues. Therefore, it is essential to ensure that the product of serum calcium and phosphate levels (Ca × P) does not exceed 70. Radiographic examination of anatomical regions prone to calcification may be useful for early diagnosis.
Fertility, pregnancy and lactation.
Consult your doctor or pharmacist before taking any medicine.
During pregnancy and breastfeeding, this product should be administered only after careful assessment of the risk-benefit ratio.
Effects on ability to drive and use machines
Diseon does not affect or affects negligibly the ability to drive vehicles or operate machinery.
Important information about certain excipients
DISEON soft capsules and DISEON oral drops, solution contain small amounts of ethanol (alcohol), less than 100 mg per dose.
DISEON soft capsules and DISEON oral drops, solution contain sorbitol. If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking this medicine.
DISEON soft capsules contain peanut oil. Do not use if you are allergic to peanuts or soy.
DISEON oral drops, solution contain polyoxylated hydrogenated castor oil. It may cause gastrointestinal disturbances and diarrhea.
DISEON oral drops, solution contain methyl parahydroxybenzoate. It may cause allergic reactions (including delayed reactions).
Doping warning
For individuals engaged in sports activities, the use of medicinal products containing ethyl alcohol may result in positive doping tests, depending on the blood alcohol concentration limits set by certain sports federations.
DOSAGE, METHOD AND DURATION OF ADMINISTRATION
Recommended initial dosage for all indications:
Adults and adolescents over 20 kg body weight: 1 mcg daily.
Children under 20 kg body weight: 0.05 mcg/kg/day
The dose may subsequently be adjusted according to response, depending on individual needs and patient weight.
The product is available as soft capsules (0.25 mcg and 1 mcg) and oral drops (each drop corresponds to 0.05 micrograms of 1-alpha-hydroxycalciferol).
OVERDOSE
Excessive intake of vitamin D leads to the development of hypercalcemia. Symptoms of overdose include anorexia, fatigue, nausea and vomiting, constipation or diarrhea, polyuria, nocturia, sweating, headache, thirst, drowsiness, and dizziness. Sensitivity to vitamin D varies considerably; infants and children are generally more susceptible to its toxic effects. If toxicity occurs, vitamin D must be discontinued.
In acute overdose, early treatment with gastric lavage and/or administration of mineral oils may reduce absorption and promote fecal elimination.
In cases of severe hypercalcemia due to accidental overdose, after temporarily suspending the drug, diuretics together with intravenous fluids or corticosteroids may be administered.
In case of accidental ingestion/overdose of an excessive dose of Diseon, contact a doctor immediately or go to the nearest hospital.
If you have any doubts about using this medicine, consult your doctor or pharmacist.
UNDESIRABLE EFFECTS
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The frequencies of adverse reactions are classified according to the following convention: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000), very rare (<1/10,000), not known (frequency cannot be estimated from available data).
Immune system disorders
Not known: Hypersensitivity
Metabolism and nutrition disorders
Common: Hypercalcemia*, hypercalciuria
Rare: Hyperphosphatemia
*Effects associated with hypercalcemia include hypercalciuria, ectopic calcifications, renal and cardiovascular damage, weakness, headache, drowsiness, nausea, vomiting, dry mouth, constipation, bone and muscle pain. In later stages, urinary disturbances, conjunctivitis (due to calcification), photophobia, pancreatitis, rhinorrhea, pruritus, hyperthermia, decreased libido, albuminuria, hypercholesterolemia, increased SGOT and SGPT, ectopic calcifications, hypertension, cardiac arrhythmias, and rarely psychosis. Since the half-life of calcitriol is short, normalization of any hypercalcemia occurs within a few days after discontinuation of Diseon treatment, and more rapidly than during therapy with vitamin D or its metabolites.
Reporting of adverse reactions.
If you experience any adverse reaction, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report adverse reactions directly via the website: http://www.agenziafarmaco.gov.it/it/responsabili . By reporting adverse reactions, you can help provide more information on the safety of this medicine.
EXPIRY DATE AND STORAGE
Expiry date: see the date printed on the packaging.
The expiry date refers to the product stored unopened and correctly stored.
Warning: do not use the medicine after the expiry date stated on the packaging.
Capsules
Store below 25°C.
Oral drops
Store at a temperature not exceeding 25°C in the original container protected from light.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
COMPOSITION
DISEON 0.25 microgram soft capsules
Each capsule contains:
Active substance:
1-alpha-hydroxycalciferol mcg 0.25
Excipients:
Ethyl alcohol absolute, anhydrous citric acid, propyl gallate, d,l-alpha-tocopherol, peanut oil.
Capsule shell composition: gelatin, glycerol 85%, sorbitol special solution (Anidrisorb 85/70), iron oxide red (E172), black ink.
DISEON 1 microgram soft capsules
Each capsule contains:
Active substance:
1-alpha-hydroxycalciferol mcg 1
Excipients:
Ethyl alcohol absolute, anhydrous citric acid, propyl gallate, d,l-alpha-tocopherol, peanut oil.
Capsule shell composition: gelatin, glycerol 85%, sorbitol special solution (Anidrisorb 85/70), iron oxide yellow (E172), titanium dioxide (E171), black ink.
DISEON 2 micrograms/ml oral drops, solution
Each ml (40 drops) contains:
Active substance:
1-alpha-hydroxycalciferol mcg 2
Excipients:
Polyoxylated hydrogenated castor oil, anhydrous citric acid, sodium citrate dihydrate, d,l-alpha-tocopherol, methyl parahydroxybenzoate, ethyl alcohol, sorbitol 70% non-crystallizable solution, purified water q.s.
Each drop contains 0.05 mcg of 1-alpha-hydroxycalciferol.
PHARMACEUTICAL FORM AND CONTENT
Soft capsules: carton containing 30 capsules of 0.25 mcg or 1 mcg
Oral drops, solution: 10 ml bottle
MARKETING AUTHORISATION HOLDER:
THERAMEX IRELAND LIMITED,
3RD FLOOR, KILMORE HOUSE, PARK LANE, SPENCER DOCK, DUBLIN 1, D01 YE64,
IRELAND.
MANUFACTURER
Soft capsules
Teva Pharma B.V. – Swensweg, 5 – 2031 GA Haarlem (Netherlands)
Oral drops, solution
Istituto Biochimico Nazionale Savio S.r.l. - Via del Mare, 36 - Pomezia (Rome)