Dlune-D3™ SG

4.4 Special Warnings and Precautions for use

• Use with caution in patients with sarcoidosis; monitor serum and urinary calcium.
• During long-term therapy, monitor serum calcium and renal function (serum creatinine).
• Closer monitoring is required in elderly patients, and in those receiving cardiac glycosides, diuretics, or with a history of renal calculi.
• In case of hypercalciuria or renal impairment, reduce the dose or discontinue treatment.
• Use cautiously in renal impairment; monitor calcium and phosphate levels and consider the risk of soft tissue/ectopic calcification.
• In severe renal insufficiency, cholecalciferol may not be adequately metabolized; alternative forms of vitamin D may be required.
• Consider the total vitamin D and calcium intake when co-prescribing other vitamin D or calcium-containing products; additional supplementation should be under medical supervision with serum calcium monitoring.
• Use with caution in patients with cardiac disease (e.g., arteriosclerosis) and hyperlipidemia.
• Medical supervision is recommended in children.

4.5 Drug Interactions

• Thiazide diuretics may reduce urinary calcium excretion and increase the risk of hypercalcaemia; serum calcium should be monitored.
• Phenytoin and barbiturates may reduce the effect of vitamin D by increasing its metabolism.
• Concomitant use with vitamin D analogues is not recommended due to additive effects and increased risk of toxicity.
• Excessive vitamin D may cause hypercalcaemia, increasing the risk of digitalis toxicity and serious arrhythmias; ECG and serum calcium monitoring is advised.
• Glucocorticoids may reduce the effect of vitamin D by increasing its metabolism and decreasing calcium absorption.
• Cholestyramine, ion-exchange resins, and paraffin oil may reduce gastrointestinal absorption of vitamin D; a maximum possible dosing interval is recommended.
• Concomitant use may reduce the absorption and efficacy of ketoconazole.
• Rifampicin may decrease the effect of vitamin D3 by increasing its metabolism.

4.6 Use in special populations

Pregnancy: The product should be used during pregnancy only in case of a vitamin D deficiency. It is not recommended during pregnancy in patients without a vitamin D deficiency. Studies in animals have shown reproductive toxicity of high doses of vitamin D. There are no indications that vitamin D at therapeutic doses is teratogenic in humans.
Overdose of vitamin D has been associated with teratogenic effects in animals.

Lactation: Vitamin D can be used during breast feeding. Vitamin D3 passes into breast milk. This should be considered while giving additional vitamin D to the child.

Hepatic Insufficiency: The intestinal absorption of cholecalciferol may be markedly impaired; conversion to calcifediol may also be reduced significantly, with the requirement of high doses. Agents not requiring hepatic hydroxylation (e.g. calcitriol, alphacalcidol) are preferred.

Renal Insufficiency: Although only small amounts of a vitamin D dose are recovered in the urine, metabolic conversion to calcitriol is impaired and higher doses are generally required in most conditions. Agents not requiring hepatic hydroxylation (e.g., Calcitriol, alphacalcidol) are preferred.

4.7 Effects on Ability to Drive and Use Machines

Dlune-D3 Softgel capsules have no influence on the ability to drive and use machines.

4.8 Undesirable Effects

• Side effects may include arrhythmias, confusion, dry mouth, headache, lethargy, metallic taste, muscle/bone pain, sluggishness, nausea, vomiting, constipation, loss of appetite, increased thirst/urination, and mental/mood changes.
• Rare: pruritus, rash, urticaria, serious allergic reactions (rash, itching/swelling of face/tongue/throat, dizziness, trouble breathing).
• Prolonged use may lead to hypercalcemia, hypercalciuria, and hyperphosphatemia.

Symptoms of Hypercalcemia:Constipation, nausea, decreased appetite, abdominal pain, peptic ulcers, kidney stones, flank pain, frequent urination, confusion, dementia, memory loss, depression, bone pain, fractures, spinal curvature, loss of height.

Symptoms of Hypercalciuria:Dysuria, abdominal pain, irritability, urinary frequency/urgency, change in urine appearance, colic, daytime incontinence, recurrent UTIs, vesicourethral reflux.

Symptoms of Hyperphosphatemia:Altered mental status, delirium, obtundation, coma, seizures, muscle cramps/tetany, neuromuscular hyperexcitability, paresthesias.

Reporting of Suspected Adverse Reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zorvia.com

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

The most serious consequence of acute or chronic overdose is hypercalcaemia due to vitamin D toxicity. Symptoms may include nausea, vomiting, polyuria, anorexia, weakness, apathy, thirst and constipation. Chronic overdoses can lead to vascular and organ calcification as a result of hypercalcaemia.

Symptoms: Acute or chronic overdose of vitamin D can cause hypercalcaemia. Symptoms of hypercalcemia are tiredness, psychiatric symptoms (e.g., euphoria, dazedness, disturbed consciousness), symptoms (e.g., euphoria, dazedness, disturbed consciousness), nausea, vomiting, lack of appetite, weight loss, thirst, polyuria, formation of renal calculi, nephrocalcinosis, extraosseous calcification and kidney failure, changes in ECG, arrhythmias, and pancreatitis. In isolated cases their course has been described as fatal.

Treatment: If a massive dose has been ingested ventricular emptying may be considered, together with the administration of carbon. Sunlight and further administration of vitamin D or calcium should be avoided. Rehydration and treatment with diuretics, e.g. furosemide to ensure adequate diuresis. In hypercalcemia biphosphonates or calcitonin and corticosteroids may be given. The treatment is directed to symptoms.

5.0 Pharmacological Properties

5.1 Mechanism of action

The mechanism of action of 1,25(OH)₂D (calcitriol) is mediated by the interaction of calcitriol with the vitamin D receptor (VDR). Calcitriol binds to cytosolic VDRs within target cells, and the receptor-hormone complex translocates to the nucleus and interacts with DNA to modify gene transcription. The VDR belongs to the steroid and thyroid hormone receptor supergene family. Calcitriol also exerts nongenomic effects that may require the presence of a functional VDR.

5.2 Pharmacodynamic properties

Vitamin D₃ is converted to 25-hydroxyvitamin D₃ in the liver. Conversion to the active calcium-mobilizing hormone 1,25-dihydroxyvitamin D₃ (calcitriol) in the kidney is stimulated by both parathyroid hormone and hypophosphatemia. The principal action of 1,25-dihydroxyvitamin D₃ is to increase intestinal absorption of both calcium and phosphate as well as regulate serum calcium, renal calcium and phosphate excretion, bone formation and bone resorption. Vitamin D is required for normal bone formation. Vitamin D insufficiency develops when both sunlight exposure and dietary intake are inadequate. Insufficiency is associated with negative calcium balance, increased parathyroid hormone levels, bone loss, and increased risk of skeletal fracture. In severe cases, deficiency results in more severe hyperparathyroidism, hypophosphatemia, proximal muscle weakness, bone pain and osteomalacia.

5.3 Pharmacokinetic properties

Absorption: Vitamin D substances are well absorbed from the gastrointestinal tract. The presence of bile is essential for adequate intestinal absorption; absorption may be decreased in patients with decreased fat absorption.

Distribution:Vitamin D and its metabolites circulate in the blood, bound to a specific alpha-globulin. Vitamin D can be stored in adipose and muscle tissue for long periods of time. It is slowly released from such storage sites and from the skin where it is formed in the presence of sunlight or ultraviolet light. Cholecalciferol has a slow onset and a long duration of action.

Metabolism: Cholecalciferol is converted in the liver by hydroxylation to the active form 25-hydroxycholecalciferol. It is then further converted in the kidneys to 1,25-dihydroxycholecalciferol. 1,25-dihydroxycholecalciferol is the metabolite responsible for increasing calcium absorption. Vitamin D that is not metabolized is stored in adipose and muscle tissues.

Excretion: Vitamin D compounds and their metabolites are excreted mainly in the bile and faeces, with only small amounts appearing in the urine. There is some enterohepatic recycling but it is considered to have a negligible contribution to vitamin D status. Certain vitamin D substances may be distributed into breast milk.

6.0 Nonclinical Properties

6.1 Animal Toxicology or Pharmacology

Vitamin D is well known and is a widely used material and has been used in clinical practice for many years. As such, toxicity is only likely to occur in chronic overdosage where hypercalcaemia could result.

Cholecalciferol has been shown to be teratogenic in high doses in animals (4–15 times the human dose). Offspring from pregnant rabbits treated with high doses of vitamin D had lesions anatomically similar to those of supravalvular aortic stenosis and offspring not showing such changes show vasculotoxicity similar to that of adults following acute vitamin D toxicity.

7.0 Description

Dlune-D3 Softgel capsule contains cholecalciferol (Vitamin D3). Vitamin D3 is essential for the proper growth and development of the body. It is synthesized within the body after exposure to sunlight and is essential for many important functions of the human body. Vitamin D3 in Dlune-D3 also increases the calcium absorption from the intestines.

• Chemical name: (1S,3Z)-3-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidencyclohexan-1-ol
• Chemical formula: C₂₇H₄₄O

Molecular weight: 384.6

8. Pharmaceutical particulars

8.1 Incompatibilities

Not specified

8.2 Shelf-Life

Refer on pack

8.3 Packaging Information

1 X 4 softgel capsules

8.4 Storage and Handling Instructions

• Store below 25°C
• Protect from direct sunlight
• Keep out of reach of children
• SHAKE WELL BEFORE USE
• FOR PAEDIATRIC USE ONLY

9.0 Patient Counselling Information

Take exactly as directed by your doctor or on the label. Do not increase the dosage or take for longer than is recommended.

Instruct patients on the following points when administering the drug. Inform the patient not to take Cholecalciferol if they have 

• allergic to vitamin D or any of the other ingredients of this medicine
• high levels of vitamin D in your blood
• kidney stones or serious kidney problems 
• high levels of calcium in your blood and/or urine

Remind patients to inform their healthcare provider immediately before taking Cholecalciferol if they have 

• problems with kidneys 
• sarcoidosis
• they are already taking other medicines or supplements containing vitamin D.