Product Monograph - AG-Vitamine D Tablets

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TABLE OF CONTENTS

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RECENT MAJOR LABEL CHANGES ............................................................................................ 2

TABLE OF CONTENTS .............................................................................................................. 2

PART I: HEALTH PROFESSIONAL INFORMATION ...................................................................... 3

1. INDICATIONS .................................................................................................................. 3
2. CONTRAINDICATIONS ..................................................................................................... 3
4.
DOSAGE AND ADMINISTRATION ..................................................................................... 3
4.1 Dosing Consideration ............................................................................................................... 3
4.2 Recommended Dose and Dosage Adjustment ..................................................................... 3
4.5 Missed Dose .............................................................................................................................. 4
5. OVERDOSAGE ................................................................................................................. 4
6. DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ...................................... 4
7.
WARNINGS AND PRECAUTIONS ...................................................................................... 5
7.1 Special Populations ................................................................................................................... 6
7.1.1 Pregnant Women ................................................................................................................... 6
7.1.2 Breast-feeding ........................................................................................................................ 7
8. ADVERSE REACTIONS ...................................................................................................... 7
9. DRUG INTERACTIONS ...................................................................................................... 7
10.
CLINICAL PHARMACOLOGY .............................................................................................. 8
10.1 Mechanism of Action ............................................................................................................... 8
10.2 Pharmacodynamics .................................................................................................................. 9
10.3 Pharmacokinetics ...................................................................................................................... 9
11. STORAGE CONDITIONS ................................................................................................ 9
12. SPECIAL HANDLING INSTRUCTIONS .............................................................................. 9

PATIENT MEDICATION INFORMATION ................................................................................... 10

PART I: HEALTH PROFESSIONAL INFORMATION

1. INDICATIONS

AG-Vitamine D Tablets at 10 000 Units is indicated for:

the treatment of hypophosphatemic rickets (vitamin D – resistant rickets)
the treatment of hypoparathyroidism.

2. CONTRAINDICATIONS

Abnormal sensitivity to the toxic effect of vitamin D
Hypercalcemia and/or hypercalciuria
Hypersensitivity to vitamin D, any of its analogues and derivatives or to any ingredient in the formulation component of the container (see Dosage Form, Composition, and Packaging).
Hypervitaminosis D
Malabsorption syndrome
Nephrolithiasis (renal calculi)
Sarcoidosis
Severe renal impairment

4. DOSAGE AND ADMINISTRATION

4.1 Dosing Consideration

At the higher doses of Vitamin D used for active treatment, the range between therapeutic and toxic doses is narrow.

The dosage of vitamin D₃must be individualized with careful monitoring of serum-calcium levels. Readjust therapeutic dosage as soon as there is clinical improvement. Careful titration is necessary to avoid overdose. Dietary and other sources of vitamin D must be considered. Calcium intake should be adequate.

Blood calcium, phosphorus and urea determinations must be made every two weeks or more frequently if necessary.

The bones should be x-rayed every month until the condition is corrected and stabilized.

4.2 Recommended Dose and Dosage Adjustment

For the treatment of Vitamin D resistant rickets: 20,000 to 500,000 IU (0.5-12.5 mg) daily.

For the treatment of hypoparathyroidism: 50,000 to 200,000 IU (1.25 - 5 mg) daily. Calcium supplementation is also required.

The dosage of vitamin D depends on severity of the disease, as well as patient's response to treatment. The dosage and the frequency of administration has to be established individually by a physician.

Not all given recommended doses can be achieved with this product. When a higher daily dose of more than 100,000 IU (2.5 mg) is needed, it is recommended to use other Vitamin D products with higher strength.

4.5 Missed Dose

If a dose of this medication has been missed, it should be taken as soon as possible. However, if it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule. Do not take a double dose to make up for the missed dose.

5. OVERDOSAGE

Symptoms: Acute intoxication with Vitamin D₃(cholecalciferol) may cause hypervitaminosis D, manifested by hypercalcemia and its sequelae. Hypercalcemia is usually reversible, however, if metastatic calcification has occurred, severe renal or cardiac failure or even death may result (see WARNINGS AND PRECAUTIONS).

Treatment: Treatment of acute or chronic intoxication includes withdrawal of the Vitamin D₃and any calcium supplements, maintenance of low-calcium diet, administration of oral IV fluids and, if needed, corticosteroids or calciuric diuretics, such as furosemide and ethacrymic acid, to decrease serum calcium concentrations. Peritoneal or hemodialysis with calcium free dialysate will help remove calcium.

If acute ingestion is recent, gastric lavage or emesis may minimize further absorption. If the drug has already passed through the stomach, administration of mineral oil may promote faecal elimination.

Hypercalcemia is usually reversible, however, if metastatic calcification has occurred, severe renal or cardiac failure or even death may result.

For management of a suspected drug overdose, contact your regional poison control centre.

6. DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING

Table – Dosage Forms, Strengths, Composition and Packaging

Route of Administration	Dosage Form / Strength/Composition	Non-medicinal Ingredients
Oral	Tablets, 10 000 Units	sodium ascorbate, all-rac-α-tocopherol, modified starch, sucrose, medium chain triglycerides, colloidal silicon dioxide, microcrystalline cellulose, polacrilin potassium, croscarmellose sodium, silica colloidal anhydrous, magnesium stearate, hypromellose, diethyl phthalate, ethyl cellulose, talc, titanium dioxide, polydextrose, maltodextrin and may contain traces of methylene chloride and isopropyl alcohol.

Description

AG-Vitamine D Tablets is a white to off-white coloured, round, biconvex, film coated tablet, scored on one side and embossed with "D" on other side, and contains 10 000 Units (0.25 mg) of Vitamin D3 (Cholecalciferol).

Available in HDPE bottles of 60, 250, 500 tablets and blister pack of 10 (1x10) tablets and 100 (10 x 10) tablets.

7. WARNINGS AND PRECAUTIONS

General

Chronic or acute administration of excessive doses may lead to hypervitaminosis D, manifested by hypercalcemia and its sequelae.

The therapeutic index of Vitamin D products is narrow, and there is great interindividual variation in the dose that will lead to chronic toxicity. Daily doses of cholecalciferol ranging from 50,000 to 100,000 IU (1.25 to 2.5 mg) in adults and 1000 IU (25 mcg) in children may result in hypervitaminosis. Other Vitamin D products with shorter duration of action may have a lower propensity to accumulate and to cause hypercalcemia.

Cardiovascular

Caution is required for patients receiving treatment for cardiovascular disease. (See DRUG INTERACTIONS)

Endocrine and Metabolism

Hypercalcemia

Early symptoms of hypercalcemia may include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, vertigo, tinnitus, ataxia and hypotonia.

Later and possibly more serious manifestation include nephrocalcinosis, renal dysfunction, osteoporosis in adults, impaired growth in children, anemia, metastatic calcification, pancreatitis, generalized vascular calcification and seizures. Extreme hypercalcaemia may result in coma and death.

Immune

AG-Vitamine D Tablets should not be prescribed in patients with sarcoidosis, as there is increased conversion of vitamin D to its active metabolite. (See CONTRAINDICATIONS). High doses of Vitamin D can induce hypercalcemia and hypercalcuria. Serum and urinary calcium levels should be monitored.

Monitoring and Laboratory Tests:

Periodic monitoring of serum calcium, phosphate, magnesium, and alkaline phosphatase is recommended for patients taking Vitamin D3. Serum calcium should be maintained in the range of 2.25-2.5 mmol/L and not allowed to exceed 2.75 mmol/L.

The best indicator of vitamin D status is 25-hydroxyvitamin D or 25(OH)D serum concentration, as this level reflects total vitamin D exposure (from skin synthesis, food and supplements). However, there is no clinical benefit in monitoring vitamin D levels unless a clinical condition, such as malabsorption syndromes, chronic renal or liver failure, unexplained bone pain, unusual fractures, and other evidence of metabolic bone disorders, predisposes the patient to vitamin D deficiency. Other clinical situations where vitamin D testing is indicated include hypo- or hypercalcemia/hyperphosphatemia, hypo-or hyperparathyroidism, unexplained increases in serum alkaline phosphatase or patients with symptoms suggesting hypervitaminosis D. Testing for vitamin D levels may also be indicated when a patient is on medications that affect vitamin D metabolism or absorption (see Table 1)

Renal

AG-Vitamine D Tablets should not be used in patients with severe renal impairment and should be used with caution in patients with mild and moderate impairment of renal function. (See CONTRAINDICATIONS). The effect on calcium and phosphate levels should be monitored. The risk of soft tissue calcification should be taken into account.

There is no clear evidence for causation between vitamin D supplementation and renal stones, but the risk is plausible, especially in the context of concomitant calcium supplementation. The need for additional calcium supplementation should be considered for individual patients. Calcium supplements should be given under close medical supervision.

During treatment, the serum and urinary calcium levels should be monitored and the kidney function checked by measurement of serum creatinine. These checks are particularly important in concomitant treatment with diuretics. In the case of hypercalcaemia or signs of impaired kidney function, the dose must be reduced or treatment interrupted. It is recommended to reduce the dose or to interrupt treatment if the urinary calcium level exceeds 7.5 mmol/24 hours (300 mg/24 hours).

Vitamin D must be used with particular caution in patients with disturbed urinary excretion of calcium and phosphate, in treatment with benzothiadiazine derivatives. Plasma and urinary calcium levels should be monitored in these patients.

7.1 Special Populations

7.1.1 Pregnant Women

The recommended daily dose of Vitamin D in pregnant women in Canada is 600 IU (15 mcg) daily. Studies have shown safe use of Vitamin D at doses up to 4000 IU (100 mcg) daily during pregnancy although studies in animals have shown reproductive toxicity. Avoid the use of vitamin D in excess of the recommended dietary allowance during pregnancy unless potential benefits outweigh the possible adverse effects. Hypercalcemia during pregnancy may also lead to suppression of parathyroid hormone release in the neonate, resulting in hypocalcemia, tetany and seizures.

Severe deficiency of vitamin D during pregnancy can result in maternal osteomalacia and lead to significant morbidity in both mother and fetus.

7.1.2 Breast-feeding

The recommended daily dose of Vitamin D in nursing women is 600 IU (15 mcg). Vitamin D and its metabolites are excreted in breast milk. However, Vitamin D may be deficient in maternal milk; therefore, breastfed infants may require supplementation. Use of excessive amounts of Vitamin D in nursing mothers may result in hypercalcemia in infants. A daily dose of 4,000 IU (100 mcg) should not be exceeded. When prescribing additional vitamin D to a breast-fed child the practitioner should consider the dose of any additional vitamin D given to the mother.

8. ADVERSE REACTIONS

Vitamin D₃(cholecalciferol) is generally well tolerated in doses that do not exceed the recommended daily intake. Chronic excessive dosing can lead to toxicity (see precautions). Possible side effects include symptoms of hypercalcaemia and hypercalciuria (see WARNINGS AND PRECAUTIONS). Rare cases of pruritus, rash and urticarial have been reported.

9. DRUG INTERACTIONS

Table 1: Drug-Drug Interactions

Interacting Drug	Effect	Clinical Comment
Antacids (aluminum- containing)	Increased intestinal absorption of aluminum may lead to increased aluminum levels.	Avoid this combination if possible.
Antacids (magnesium- containing)	Hypermagnesemia may develop when these agents are used concurrently with vitamin D.	Monitor magnesium levels particularly in patients with chronic renal failure.
Anticonvulsants (e.g., phenytoin, phenobarbital, carbamazepine)	Strong CYP3A4 inducers can reduce vitamin D levels, potentially causing vitamin D deficiency.	Consider prophylactic vitamin D supplementation. Monitor serum 25(OH)D every 2 years; supplement with vitamin D if necessary
Cholestyramine, colestipol	Intestinal absorption of vitamin D may be impaired.	Patients should be advised to allow as much time as possible between the ingestion of these drugs and vitamin D.
Danazol	Danazol may increase the hypercalcemic response to vitamin D.	Monitor serum calcium levels.

Digoxin	Vitamin D or any analogues should be used with caution in patients taking digoxin. Hypercalcemia (which may result from concomitant use) may enhance the arrhythmogenic effects of digoxin.	Strict medical supervision is required. Monitor serum calcium levels.
Efavirenz	Increased metabolism of vitamin D via CYP24A induction leads to a deficiency state.	Consider prophylactic vitamin D supplementation.
Mineral oil	Intestinal absorption of vitamin D may be impaired.	Patients should be advised to allow as much time as possible between the ingestion of these drugs.
Orlistat	Intestinal absorption of vitamin D may be impaired.	Patients should be advised to allow as much time as possible between the ingestion of these drugs.
Sevelamer	Sevelamer may decrease the serum concentration of orally administered vitamin D.	Monitor serum 25(OH)D levels and adjust vitamin D or analogue dose if necessary.
Sucralfate	Increased intestinal absorption of aluminum from sucralfate may lead to increased aluminum levels.	Avoid this combination if possible.
Thiazide diuretics	Increased risk of hypercalcemia and associated calcium toxicity. Thiazides decrease renal excretion of calcium and increase calcium release from bone. Thiazides may also enhance the effect of parathyroid hormone and vitamin D on release of calcium from bone.	Monitor serum calcium levels with concomitant therapy.

Different Vitamin D products should not be administered concurrently.

10. CLINICAL PHARMACOLOGY

10.1 Mechanism of Action

Vitamin D is a fat-soluble vitamin that helps regulate serum calcium and phosphorous concentrations by enhancing the efficiency of the small intestine to absorb these minerals from the diet. Vitamin D has two main forms: cholecalciferol (Vitamin D₃), and ergocalciferol (Vitamin D₂).

One microgram (mcg) is equivalent to 40 IU of vitamin D activity. Vitamin D is essential for the absorption and utilization of calcium and phosphate and aids in the mobilization of bone calcium and maintenance of serum calcium concentrations.

10.2 Pharmacodynamics

In humans, cholecalciferol (vitamin D₃) is synthesized in the skin, from 7-dehydrocholesterol, on exposure to ultraviolet radiation, and obtained from the diet from fish liver oils and salt water fish. In the absence of adequate sunlight exposure, vitamin D₃is an essential dietary nutrient.

Cholecalciferol is a prohormone with several active metabolites that act as hormones. It is metabolised by the liver to form 25-hydroxycholecalciferol (calcifediol), which is then converted in the kidneys to the active 1,25-dihydroxyvitamin D₃(calcitriol).

In its biologically active form, vitamin D₃stimulates intestinal calcium absorption, incorporation of calcium into the osteoid, and release of calcium from bone tissue. In the small intestine, it promotes rapid and delayed calcium uptake. The passive and active transport of phosphate is also stimulated. In the kidney, it inhibits the excretion of calcium and phosphate by promoting tubular resorption. The production of parathyroid hormone (PTH) in the parathyroids is inhibited directly by the biologically active form of vitamin D₃. PTH secretion is inhibited further by the increased calcium uptake in the small intestine under the influence of biologically active vitamin D₃.

10.3 Pharmacokinetics

Vitamin D from nutritional sources and synthetic Vitamin D products are readily absorbed from the small intestine in the presence of dietary lipids and bile acids. Cholecalciferol is metabolised by the microsomal enzyme vitamin D-25-hydroxylase to form 25-hydroxycolecalciferol (25(OH)D3, calcidiol), the primary storage form of vitamin D₃. 25(OH)D3 undergoes a secondary hydroxylation within the kidney to form the predominant active metabolite 1,25-hydroxycolecalciferol (1,25(OH)2D3, calcitriol). The conversion to calcitriol is regulated by its own concentration, PTH, and serum concentrations of calcium and phosphate. The metabolites circulate in the blood bound to a specific α-globin. Vitamin D and its metabolites are excreted mainly in the bile and faeces.

11. STORAGE CONDITIONS

Blister: Store between 15-30^⁰C. Protect from light.

Bottle: Store between 15-30^⁰C, in a well closed container. Protect from light and moisture.

12. SPECIAL HANDLING INSTRUCTIONS

Do not use if safety seal is broken.

Keep out of reach and sight of children.

Rx or OTC	Prescription (Rx)?
DIN	02498944
Schedule(s)	PRESCRIPTION
Active ingredient(s)	Vitamin D3 10000 UNIT
Dosage form(s)	Tablet
Route(s) of administration	Oral
Drug class (WHO ATC)	A Alimentary tract and metabolism drugs A11 Vitamins A11C Vitamin A and D, incl. combinations of the two A11CC Vitamin D and analogues A11CC05 Colecalciferol
Company	ANGITA PHARMA INC.
Current status	Marketed
Current status date	August 28, 2025

AG-Vitamine D Tablets Product Monograph