Summary of Product Characteristics (SmPC) - Ergocalciferol injection BP 300 000 units
1 NAME OF THE MEDICINAL PRODUCT
Ergocalciferol 300,000 IU solution for injection
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ampoule of 1 ml solution for injection contains 300,000 IU of ergocalciferol.
For the full list of excipients, see section 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
Posology
Adults and Elderly
Ergocalciferol Injection is typically administered as a single dose of 300,000 IU every 3-6 months.
Paediatric population
In children 1-12 years, a bolus dose 300,000IU ergocalciferol is generally given in 2 divided doses.
However, for all age groups dosage should be individualised by the clinician for each patient dependent upon clinical response and requirements.
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.
Calcium and phosphorous supplements should be administered where necessary.
4.3 Contraindications
Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.
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 Fertility, pregnancy and lactation
Pregnancy
There are no or limited amount of data from 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.
Breast-feeding
Ergocalciferol is excreted in human milk in limited amounts and effects have been shown in infants of treated women. 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.
Fertility
None stated.
4.7 Effects on ability to drive and use machines
Ergocalciferol may cause drowsiness and can affect the ability to drive and use machines. 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 following convention has been used for the classification of frequency: 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 | Adverse event | |
| Frequency | ||
| Metabolism and nutrition disorders | Hypercalcaemia * | Very common |
| Hypercholesterolaemia† | Not known | |
| Muscle weakness§ | Not known | |
| Muscle pain§ | Not known | |
| Mild acidosis† | Not known | |
| Polydipsia† | Not known | |
| Anorexia† | Not known | |
| Psychiatric disorders | Overt psychosis† | Rare |
| Somnolence§ | Not known | |
| Nervous system disorders | Headache§ | Not known |
| Endocrine disorders | Hypoparathyroidism* pseudohypopathyroidism* | Very common |
| Eye disorders | Conjunctivitis (calcific) | Not known |
| Photophobia | Not known | |
| Cardiac disorders | Cardiac arrhythmias | Not known |
| Rebal disorders | Elevated serum creatinine levels* | Very common |
| Vascular disorders | Generalised vascular calcification† | Not known |
| Hypertension† | Not known | |
| Respiratory, thoracic and mediastinal disorders | Rhinorrhoea† | Not known |
| Gastrointestinal disorders | Pancreatitis† | Not known |
| Nausea§ | Not known | |
| Vomiting§ | Not known | |
| Dry mouth§ | Not known | |
| Constipation§ | Not known | |
| Diarrhoea§ | Not known | |
| Abdominal pain§ | Not known | |
Skin and subcutaneous tissue disorders | Pruritus† | Not known |
| Musculoskeletal and connective tissue disorders | Bone pain§ | Not known |
| Ectopic calcification† | Not known | |
| Renal and urinary disorders | Polyuria† | Not known |
| Nocturia† | Not known | |
| Nephrocalcinosis† | Not known | |
| Albuminuria† | Not known | |
| Reversible azotemia† | Not known | |
| Reproductive system and breast disorders | Decreased libido† | Not known |
System Organ Class | Adverse event | |
| Frequency | ||
| General disorders and administration site conditions | Hyperthermia† | Not known |
| Fatigue§ | Not known | |
| Irritability† | Not known | |
| Weakness§ | Not known | |
| Investigations | Elevated AST † | Not known |
| Elevated ALT† | Not known | |
| Elevated BUN† | Not known | |
| Weight loss† | Not known | |
| Surgical and medical procedures | Metallic taste§ | Not known |
*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).
§ Possible early symptoms of hypercalcaemia
†Possible late symptoms of hypercalcaemia
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
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
Symptoms
Administration to patients in excess of their daily requirement can cause hypercalcaemia (see section 4.8), hypercalciuria and hyperphosphataemia. Concomitant high intake of calcium and phosphate may lead to similar abnormalities.
Management
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
Pharmacotherapeutic group: Vitamin D and analogues, ATC Code: A11CC01
Mechanism of action and Pharmacodynamic effects
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.
Biotransformation
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.
Elimination
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.
Keep the ampoules in the outer carton in order to protect from light.
6.5 Nature and contents of container
1ml clear, one-point cut (OPC) glass Type 1 Ph Eur ampoules packed in cartons of 5 or 10 ampoules. Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Plastic syringes should not be used to administer Ergocalciferol 300,000 IU solution for injection.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
RPH Pharmaceuticals AB
Box 603
101 32 Stockholm
Sweden
8 MARKETING AUTHORISATION NUMBER(S)
PL 36301/0008
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
04/04/2006
10 DATE OF REVISION OF THE TEXT
09/12/2022