SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Ergocalciferol Injection BP 300,000U

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Ergocalciferol BP 0.75% W/V For excipients see 6.1.

3    PHARMACEUTICAL FORM

Solution for Injection

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Intramuscular therapy with Ergocalciferol Injection is used in patients with gastrointestinal, liver or biliary disease associated with malabsorption of Vitamin D, resulting in hypophosphataemia, rickets, and osteomalacia.

4.2 Posology and method of administration

Route of Administration: IM injection

Adults, Children and Elderly:

Dosage should be individualised by the clinician for each patient. Serum and urinary calcium concentrations, phosphate and BUN should be monitored at regular intervals, initially weekly, in order to achieve optimum clinical response and to avoid hypercalcaemia.

Doses should not normally exceed 40,000 units/day (1.0mg/day) for adults and 10,000 units/day (0.25mg/day) for children.

Ergocalciferol Injection may be administered as a single dose or repeated daily, dependent upon clinical response and requirements. Calcium and phosphorous supplements should be administered where necessary.

4.3 Contraindications

Hypercalcaemia, evidence of vitamin D toxicity, hypervitaminosis D, decreased renal function, metastatic calcification.

4.4 Special warnings and precautions for use

Adequate dietary calcium is necessary for clinical response to Ergocalciferol therapy.

Caution should be used when the injectable forms are used in patients with vitamin D resistant rickets as the range between the toxic and therapeutic dosage is narrow.

Vitamin D should be administered with caution to infants and patients who may have an increased sensitivity to its effects. Use with care in patients with renal impairment, renal calculi or heart disease or arteriosclerosis who might be at increased risk of organ damage if hypercalcaemia were to occur.

Ergocalciferol is not recommended for use in hypoparathyroidism. In the event of hypoparathyroidism when Ergocalciferol is used, calcium, parathyroid hormone or dihydrotachysterol may be required.

Dosage should be individualised. Frequent serum and urinary calcium, phosphate and urea nitrogen determinations should be carried out. Adequate fluid intake should be maintained.

Should hyperglycaemia develop, Ergocalciferol should be discontinued immediately.

Because of the effect on serum calcium, Ergocalciferol should only be administered to patients with renal stones when potential benefits outweigh possible hazards.

4.5 Interaction with other medicinal products and other forms of interaction

Ergocalciferol and:-

i) Magnesium-containing antacids : hypermagnesaemia may develop in patients on chronic renal dialysis.

ii)    Digitalis glycosides : hypercalcaemia in patients on digitalis may precipitate cardiac arrhythmias.

iii)    Verapamil atrial fibrillation has recurred when supplemental calcium and Ergocalciferol have induced hypercalcaemia.

iv)    Anti-convulsants: vitamin D requirements may be increased in patients taking anti-convulsants (e.g. carbamazepine, phenobarbital, phenytoin and primidone).

v)    Thiazide diuretics : hypoparathyroid patients on Ergocalciferol may develop hypercalcaemia due to increased Ergocalciferol (although Ergocalciferol is not recommended for use in hypoparathyroidism).

4.6 Pregnancy and lactation

Pregnancy : There are no adequate data on the use of Ergocalciferol in pregnant women. Ergocalciferol Injection should not be used in pregnancy unless the potential benefit outweighs the potential hazards to the foetus.

Animal studies have shown foetal abnormalities associated with hypervitaminosis D. Calcifediol and calcitriol are teratogenic in animals when given in doses several times the human dose. The offspring of a woman administered 17-144 times the recommended dose of calcitriol during pregnancy manifested mild hypercalcaemia in the first 2 days of life, which returned to normal at day 3.

Lactation : Ergocalciferol is excreted in breast milk in limited amounts. In a mother given large doses of Ergocalciferol, 25-hydroxycholecalciferol appeared in the milk and caused hypercalcaemia in the child. Monitoring of the infants serum calcium is required in such cases. Ergocalciferol should not be administered to breast-feeding mothers.

4.7 Effects on ability to drive and use machines

Ergocalciferol may cause drowsiness and, if affected, patients should not drive or operate machinery.

4.8 Undesirable effects

Adverse events are generally associated with excessive intake of ergocalciferol leading to the development of hypercalcaemia. The symptoms of hypercalcaemia can include:

Early : weakness; headache; somnolence; nausea; vomiting; dry mouth; constipation; diarrhoea; abdominal pain; fatigue; muscle weakness or pain; bone pain; metallic taste.

Late : polyuria; polydipsia; anorexia; irritability; weight loss; nocturia; mild acidosis; reversible azotaemia; generalised vascular calcification; nephrocalcinosis; conjunctivitis (calcific); pancreatitis; photophobia; rhinorrhoea; pruritis; hyperthermia; decreased libido; elevated BUN; albuminuria; hypercholesterolaemia; elevated AST and ALT; ectopic calcification; hypertension; cardiac arrhythmias; overt psychosis (rare).

In clinical studies on hypoparathyroidism and pseudohypopathyroidism, hypercalcaemia was noted on at least one occasion in about 1 in 3 patients and hypercalciuria in about 1 in 7. Elevated serum creatinine levels were observed in about 1 in 6 patients (approximately one half of whom had normal levels at baseline).

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 product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme on the MHRA website (www.mhra.gov.uk/yellowcard).

4.9 Overdose

Administration to patients in excess of their daily requirement can cause hypercalcaemia (see Section 4.8 Undesirable Effects), hypercalciuria and hyperphosphataemia. Concomitant high intake of calcium and phosphate may lead to similar abnormalities.

Treatment of chronic overdose with resulting hypercalcaemia consists of immediate withdrawal of the vitamin, a low calcium diet and generous fluid intake. Severe cases may require hydration with intravenous saline together with symptomatic and supportive treatment as indicated by the patient’s clinical condition. Plasma calcium U & E’s should be monitored.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

ATC Code: A11C C01 - Vitamin D and analogues.

Ergocalciferol (vitamin D) is a fat soluble vitamin. In conjunction with parathyroid hormone and calcitonin, it regulates calcium haemostasis. Ergocalciferol metabolites promote active absorption of calcium and phosphorous by the small intestine, increase rate of excretion and resorption of minerals in bone and promote resorption of minerals in bone and promote resorption of phosphate by renal tubules.

Ergocalciferol deficiency leads to rickets in children and osteomalacia in adults. Ergocalciferol reverses symptoms of nutritional rickets or osteomalacia unless permanent deformities have occurred.

5.2 Pharmacokinetic properties

Distribution - Stored chiefly in the liver, ergocalciferol is also found in fat, muscle, skin and bones. In plasma, it is bound to alpha globulins and albumin.

Metabolism - There is a lag of 10 to 24 hours between administration of ergocalciferol and initiation of its action in the body. Maximal hypercalcaemic effects occur about 4 weeks after daily administration of a fixed dose and the duration of action can be > 2 months. Ergocalciferol is hydroxylated in the liver and further metabolism occurs in the kidney.

Excretion - The primary route of excretion of Ergocalciferol is in the bile. Additionally, some is excreted in the urine and faeces. There is also enterohepatic re-cycling.

5.3 Preclinical safety data

None stated.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Ethyl oleate

6.2    Incompatibilities

None stated.

6.3 Shelf life

36 months

6.4 Special precautions for storage

Store below 25°C Protect from light