Plenachol D3 20 000 IU Capsules

Summary of Product Characteristics Updated 15-Oct-2019 | Auden Mckenzie (Pharma Division) Ltd (a subsidiary of Actavis PLC)

1. Name of the medicinal product

Plenachol D3 20 000 IU Capsules

Colecalciferol 20000 IU Capsules

2. Qualitative and quantitative composition

Each capsule contains 20 000 IU colecalciferol (equivalent to 0.5 mg vitamin D3).

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Capsule, hard

Hard white capsules containing a clear, slightly yellowish oily liquid.

4. Clinical particulars
4.1 Therapeutic indications

The prevention and treatment of vitamin D deficiency.

4.2 Posology and method of administration

Posology:

Paediatric population:

▪ Prevention of vitamin D deficiency 12-18 years: 20 000 IU (1 capsule) every 6 weeks

▪ Treatment of vitamin D deficiency 12-18 years: 20 000 IU (1 capsule) once every 2 weeks for 6 weeks (followed by maintenance therapy equivalent to 400-1000 IU/day, such as 1 capsule per month)

Adults:

▪ Prevention of vitamin D deficiency: 20 000 IU/month (1 capsule), higher doses may be required in certain situations, see below

▪ Treatment of vitamin D deficiency: 40 000 IU/week (2 capsules) for 7 weeks, followed by maintenance therapy (equivalent to 1400-2000 IU/day, such as 2-3 capsules per month, may be required. Follow-up 25(OH)D measurements should be made approximately three to four months after initiating maintenance therapy to confirm that the target level has been achieved)

Certain populations are at high risk of vitamin D deficiency, and may require higher doses and monitoring of serum 25(OH)D:

Institutionalised or hospitalised individuals

Dark skinned individuals

Individuals with limited effective sun exposure due to protective clothing or consistent use of sun screens

Obese individuals

Patients being evaluated for osteoporosis

Use of certain concomitant medications (e.g., anticonvulsant medications, glucocorticoids)

Patients with malabsorption, including inflammatory bowel disease and coeliac disease

Those recently treated for vitamin D deficiency, and requiring maintenance therapy.

This medicine should not be given to children under 12 years due to the risk of choking.

Method of administration:

Oral - The capsules should be swallowed whole with water.

Patients should be advised to take this medicine preferably with a meal (see section 5.2 Pharmacokinetic properties - “Absorption”).

4.3 Contraindications

▪ Hypersensitivity to colecalciferol or to any of the excipients listed in section 6.1.

▪ Hypercalcaemia and/or hypercalciuria.

▪ Nephrolithiasis, or patients who are susceptible to form calcium-containing renal calculi (kidney stone).

▪ Severe renal impairment.

▪ This medicine must not be used in children (under 12 years) due to their inability to swallow capsules and/or the potential risk of choking.

▪ Hypervitaminosis D.

4.4 Special warnings and precautions for use

Vitamin D should be used with caution in patients with impairment of renal function and the effect on calcium and phosphate levels should be monitored. The risk of soft tissue calcification should be taken into account.

Caution is required in patients receiving treatment for cardiovascular disease (see section 4.5 Interaction with other medicinal products and other forms of interaction - cardiac glycosides including digitalis).

This medicine should be prescribed with caution in patients with sarcoidosis, due to a possible increase in the metabolism of vitamin D in its active form. In these patients the serum and urinary calcium levels should be monitored.

Allowances should be made for the total dose of vitamin D in cases associated with treatments already containing vitamin D, foods enriched with vitamin D, cases using milk enriched with vitamin D, and the patient's level of sun exposure.

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.

Oral administration of high-dose vitamin D (500,000 IU by single annual bolus) was reported to result in an increased risk of fractures in elderly subjects, with the greatest increase occurring during the first 3 months after dosing.

Treatment with vitamin D can unmask previously undiagnosed primary hyperparathyroidism. Adjusted serum calcium levels should be checked 1 month after completing the loading regimen or after starting vitamin D supplementation in case primary hyperparathyroidism has been unmasked.

Furthermore, certain groups may be at an increased risk of hypercalaemia with this treatment regimen and they should be monitored by measuring adjusted serum calcium levels.

Paediatric population

This medicine must not be used in children (under 12 years) due to their inability to swallow capsules and/or the potential risk of choking.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant use of anticonvulsants (such as phenytoin) or barbiturates (and possibly other drugs that induce hepatic enzymes) may reduce the effect of vitamin D3 by metabolic inactivation.

In cases of treatment with thiazide diuretics, which decrease urinary elimination of calcium, monitoring of serum calcium concentration is recommended.

Concomitant use of glucocorticoids can decrease the effect of vitamin D.

In cases of treatment with drugs containing digitalis and other cardiac glycosides, the administration of vitamin D may increase the risk of digitalis toxicity (arrhythmia). Strict medical supervision is needed, together with serum calcium concentration and electrocardiographic monitoring if necessary.

Simultaneous treatment with ion exchange resin such as cholestyramine, colestipol hydrochloride, orlistat or laxative such as paraffin oil may reduce the gastrointestinal absorption of vitamin D.

The cytotoxic agent actinomycin and imidazole antifungal agents interfere with vitamin D activity by inhibiting the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by the kidney enzyme, 25-hydroxyvitamin D-1-hydroxylase.

4.6 Fertility, pregnancy and lactation

In pregnancy and lactation the high strength formulation is not recommended and a low strength formulation should be used.

Pregnancy

There are no or limited amount of data from the use of cholecalciferol in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3 Preclinical safety data). The recommended daily intake for pregnant women is 400 IU, however, in women who are considered to be vitamin D deficient a higher dose may be required. During pregnancy women should follow the advice of their medical practitioner as their requirements may vary depending on the severity of their disease and their response to treatment vitamin D and its metabolites are excreted in breast milk.

Breast-feeding

Vitamin D can be prescribed while the patient is breast-feeding if necessary. This supplementation does not replace the administration of vitamin D in the neonate.

Overdose in infants induced by nursing mothers has not been observed, however, 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

Fertility

There is no data regarding treatment with vitamin D3 and its effects on fertility.

4.7 Effects on ability to drive and use machines

There are no data on the effects of this medicine on the ability to drive. However, an effect on this ability is unlikely.

4.8 Undesirable effects

The frequency of the undesirable effects listed below is defined using the following convention: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000).

Metabolism and nutrition disorders

Uncommon: Hypercalcaemia and hypercalciuria

Skin and subcutaneous disorders

Rare: pruritus, rash, and urticaria.

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 the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Discontinue this medicine when calcaemia exceeds 10.6 mg/dl (2.65 mmol/l) or if the calciuria exceeds 300 mg/24 hours in adults or 4-6 mg/kg/day in children. An overdose manifests as hypercalcaemia and hypercalciuria, the symptoms of which include the following: nausea, vomiting, thirst, constipation, polyuria, polydipsia and dehydration.

Chronic overdosage may lead to vascular and organ calcification, as a result of hypercalcaemia.

Treatment in cases of overdose

Discontinue administration of this medicine and initiate rehydration.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Colecalciferol (vitamin D and analogues)

ATC code: A11C C05

Mechanism of action

In its biologically active form vitamin D stimulates 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 additionally by the increased calcium uptake in the small intestine under the influence of biologically active vitamin D.

5.2 Pharmacokinetic properties

The pharmacokinetics of vitamin D is well known.

Absorption

Vitamin D is well absorbed from the gastro-intestinal tract in the presence of bile, so the administration with the major meal of the day might therefore facilitate the absorption of vitamin D.

Distribution and biotransformation

It is hydroxylated in the liver to form 25-hydroxy-cholecalciferol and then undergoes further hydroxylation in the kidney to form the active metabolite 1, 25-dihydroxy-cholecalciferol (calcitriol).

Elimination

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.

Characteristics in Specific Groups of Subjects or Patients

A 57% lower metabolic clearance rate is reported in subjects with renal impairment as compared with that of healthy volunteers.

Decreased absorption and increased elimination of vitamin D occurs in subjects with malabsorption.

Obese subjects are less able to maintain vitamin D levels with sun exposure, and are likely to require larger oral doses of vitamin D to replace deficits.

5.3 Preclinical safety data

Pre-clinical studies conducted in various animal species have demonstrated that toxic effects occur in animals at doses much higher than those required for therapeutic use in humans.

In toxicity studies at repeated doses, the effects most commonly reported were increased calciuria and decreased phosphaturia and proteinuria.

Hypercalcaemia has been reported in high doses. In a state of prolonged hypercalcaemia, histological alterations (calcification) were more frequently borne by the kidneys, heart, aorta, testes, thymus and intestinal mucosa.

Colecalciferol has been shown to be teratogenic at high doses in animals.

At doses equivalent to those used therapeutically, colecalciferol has no teratogenic activity.

Colecalciferol has no potential mutagenic or carcinogenic activity.

6. Pharmaceutical particulars
6.1 List of excipients

Medium-chain triglycerides

Butylhydroxyanisole

Colloidal anhydrous silica

Hypromellose

Capsule Shell:

Hypromellose

Titanium dioxide (E171)

6.2 Incompatibilities

None applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Store this medicinal product in the original package in order to protect from light.

6.5 Nature and contents of container

PVC/PVdC foiled aluminium blister.

Pack sizes: 4, 10 & 20

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Any unused product should be disposed of in accordance with local requirements.

7. Marketing authorisation holder

Accord Healthcare Limited

Sage House

319 Pinner Road

North Harrow

Middlesex

HA1 4HF

United Kingdom

8. Marketing authorisation number(s)

PL 20075/0672

9. Date of first authorisation/renewal of the authorisation

06/10/2014

10. Date of revision of the text

02/07/2019

Company Contact Details
Auden Mckenzie (Pharma Division) Ltd (a subsidiary of Actavis PLC)
Address

Mckenzie House, Bury Street, Ruislip, Middlesex, HA4 7TL

Telephone

+44 (0)1895 627 480

Fax

+44 (0)895 627421

Medical Information Direct Line

+44(0) 1271 385257

Stock Availability

0800 373573

WWW

www.accord-healthcare.co.uk

Telephone

+44 (0)1895 627420

Medical Information Direct Line

+44 (0)1271 385 257

Medical Information e-mail