How does it work?

Actonel combi is a combination pack consisting of tablets and granules. The tablets contain risedronate sodium, which is a type of medicine known as a bisphosphonate. Bisphosphonates are medicines that prevent the breakdown of bone. The granules contain calcium carbonate and colecalciferol (vitamin D3), both of which are essential for healthy bones.

Bone is not a static structure. It is continually shaped, reformed and rebuilt by cells called osteoblasts and osteoclasts. These cells continously deposit and remove calcium and phophorous, stored in a protein network that makes up the structure of the bone. Old bone is broken down by the osteoclasts and new bone is formed by the osteoblasts.

In women at the menopause, blood levels of the female hormone oestrogen start to decrease. One result of this is an increase in bone breakdown by the osteoclasts, which can lead to a loss of bone density. Bone loss is particularly rapid for the first ten years after the menopause and it may lead to the development of osteoporosis - a condition in which the bones become weak and brittle and break (fracture) more easily.

Risedronate is used to treat osteoporosis in women who have passed the menopause. It works by binding very tightly to the bone and preventing the calcium being removed by the osteoclasts. This helps keep the bones strong and less likely to break. In women who have passed the menopause, risedronate has been shown to reduce the risk of spinal and hip fractures.

Calcium is as essential mineral needed for many purposes in the body, including the formation of strong bones. Calcium requirements are raised in the years following the menopause, and when dietary intake of calcium is low. Calcium supplements have been shown to help prevent bone loss.

Colecalciferol, also known as vitamin D3, is an essential nutrient needed by the body for healthy bones. It is normally obtained primarily from sunlight acting on the skin, but is also consumed in the diet in oily fish and milk products. Vitamin D deficiency can develop as we get older, because our skin produces less vitamin D and we may also get less exposure to sunlight. It can also develop when there is a lack of the vitamin in the diet. Vitamin D is needed for calcium to be absorbed from the gut, and deficiency can lead to low calcium levels and subsequent weakening of bones. Vitamin D supplements correct vitamin D deficiency and improve calcium absorption from the gut.

What is it used for?

• Treatment of osteoporosis in women who have passed the menopause and also need to take supplements of calcium and vitamin D.

How do I take it?

• Actonel combi is taken as a seven day cycle. One Actonel tablet (containing risedronate 35mg) is taken on the first day, and then one sachet of calcium and vitamin D is taken once a day for the next six days. This cycle is then repeated each week.
• Your Actonel tablet should be taken once a week on the same day each week. It should be taken in the morning, at least 30 minutes before the first food, drink or medicine of the day.
• The Actonel tablet should be swallowed whole with a glass of plain water (at least 120ml, not mineral water) while you are sitting or standing in an upright position. Do not crush, chew or suck the tablet. You should not lie down for at least 30 minutes after taking the tablet.
• You should not eat or drink anything other than plain water for at least 30 minutes after taking the Actonel tablet. This is because food, some drinks (including mineral water) and some medicines can interfere with the absorption of the medicine from the gut and hence make it less effective.
• If you forget to take your weekly tablet, you should take it the day you remember, and then return to taking it once a week on your normal day. Never take two tablets on the same day. You may find it helpful to keep a reminder, eg on a calendar, of when you have taken your tablet and when your next dose is due.
• Your calcium and vitamin D3 granules should be taken once a day for the six days after taking your Actonel tablet. They should never be taken on the same day as your Actonel tablet. (If you take your Actonel tablet on the wrong day you should not take any granules on that day.) The granules should be mixed in a glass of water and the solution drunk immediately once it has stopped fizzing.
• The manufacturer states that you should not take the calcium and vitamin D3 granules at thesame time as foods containing high amounts of oxalic acid (eg spinachand rhubarb) or phytic acid (eg whole cereals).Take the granules at least two hours after eating suchfoods.
• If you forget to take a dose of calcium and vitamin D3 granules take it as soon as you remember. However, do not take two sachets in one day. Continue with the one sachet a day routine and discard any unused sachets at the end of the weekly cycle.

Warning!

• It is very important that the instructions for taking the Actonel tablets are followed completely. This is because when the medicine is taken by mouth it can cause irritation and ulceration of the foodpipe (oesophagus). Following the instructions above minimises this risk. If you are unclear about anything ask your pharmacist for advice.
• If you experience any signs of irritation to your foodpipe during treatment with this medicine, for example new or worsening problems with swallowing, pain on swallowing, pain behind your breastbone, or heartburn, you should stop taking these tablets and inform your doctor.
• If you have mild to moderately decreased kidney function, raised levels of calcium in your urine (hypercalciuria) or a history of kidney stones, your kidney function and the amount of calcium in your blood and urine should be regularly monitored while you are taking this medicine.
• The class of medicines that risedronate belongs to (bisphosphonates) has been associated with a rare condition called osteonecrosis of the jaw. The majority of cases of this condition have been in cancer patients treated with bisphosphonates by injection into a vein, and many of these people were also having treatment with chemotherapy or corticosteroids. However, the condition has also been seen in people taking bisphosphonates by mouth. The risk may also be increased by poor oral hygiene, dental problems such as gum disease or poorly fitting dentures, teeth extractions, oral surgery and smoking. For this reason, you should have a dental examination and, if necessary, appropriate preventive dentistry, before you start treatment with this medicine. Discuss this with your doctor. It is important to look after your mouth and teeth as much as possible while you are taking this medicine. You should have regular check-ups with your dentist and get advice straight away if you have any problems with your mouth or teeth. When you see a dentist during treatment, make sure they know you are taking this medicine. Invasive dental procedures such as tooth extraction or surgery should be avoided if possible.
• Some people being treated with bisphosphonates (mainly people having long-term treatment for osteoporosis) have experienced an unusual fracture of their thigh bone. For this reason it is important to let your doctor know if you get any pain in your thighs, hips or groin while you are having treatment with this medicine. These symptoms could be an early indication of a possible fracture.

Use with caution in

• People with conditions that cause difficulty swallowing or delayed passage of food through the foodpipe (oesophagus), eg narrowing or obstruction of the foodpipe.
• People who cannot stand or sit upright for at least 30 minutes.
• People with active disorders of the upper part of the digestive system, such as difficulty swallowing, disorders affecting the foodpipe (eg reflux disease), ulcers, inflammation of the lining of the stomach (gastritis), inflammation of the small intestine (duodenitis).
• Disorders of the parathyroid gland (gland that produces hormones responsible for regulating calcium metabolism).
• Sarcoidosis.
• Vitamin D deficiency.
• Decreased kidney function.

Not to be used in

• Children and adolescents.
• Severely decreased kidney function.
• People with low levels of calcium in their blood (hypocalcaemia).
• People with high levels of calcium in their blood (hypercalcaemia).
• People with high levels of calcium in their urine (hypercalciuria).
• Diseases or conditions that can cause increased levels of calcium in the blood or urine, such as prolonged immobility.
• People with high amounts of vitamin D in their blood (hypervitaminosis D).
• Kidney stones (nephrolithiasis).
• Pregnancy.
• Breastfeeding.
• Actonel once a week tablets contain lactose and are not suitable for people with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
• The calcium and vitamin D3 granules contain sucrose and are not suitable for people with fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.
• The calcium and vitamin D3 granules also contain soya-bean oil and are not suitable for people with allergy to peanuts or soya.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy orbreastfeeding. However, other medicines may be safely used in pregnancy orbreastfeeding providing the benefits to the mother outweigh the risks to theunborn baby. Always inform your doctor if you are pregnant or planning apregnancy, before using any medicine.

• This medicine has not been studied in pregnant women, hence its safety has not been established. It should not be used during pregnancy.
• It is not known if this medicine passes into breast milk. It should not be used by breastfeeding mothers.

Side effects

Medicines and their possible side effects can affect individualpeople in different ways. The following are some of the side effects that areknown to be associated with this medicine. Just because a side effect is statedhere does not mean that all people using this medicine will experience thator any side effect.

Common (affect between 1 in 10 and 1 in 100 people)

• Disturbances of the gut such as diarrhoea, constipation, nausea, indigestion or abdominal pain.
• Headache.
• Pain in joints, muscles or bones (musculoskeletal pain).

Uncommon (affect between 1 in 100 and 1 in 1000 people)

• Difficulty or pain when swallowing (dysphagia).
• Inflammation of the stomach (gastritis).
• Inflammation of the food pipe (oesophagitis).
• Ulceration of the food pipe.
• Inflammation of the small intestine (duodenitis).
• Inflammation of the coloured part of the eye (iritis).
• High level of calcium in the blood or urine (hypercalcaemia or hypercalciuria).

Rare (affect between 1 in 1000 and 1 in 10,000 people)

• Inflammation of the tongue (glossitis).

Unknown frequency (reported since the medicine has been on the market)

• Skin reactions, eg rash (including severe allergic skin reactions).
• Hair loss.
• Eye inflammation (uveitis).
• Osteonecrosis of the jaw (see warning section above).
• Unusual fractures of the thigh bone (see warning section above).

The side effects listed above may not include all of the sideeffects reported by the medicine'smanufacturer. For moreinformation about any other possible risks associated with this medicine,please read the information provided with the medicine or consult your doctoror pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to make sure that the combination is safe.

Other medicines may interfere with the absorption of risedronate from the gut and could therefore make the medicine lesseffective. For this reason, you should not take other medicines by mouth at the same time as or for at least 30 minutes after taking your Actonel tablet. This is particularly important for the medicines listed below:

• antacids (indigestion remedies)
• calcium supplements
• iron supplements
• laxatives containing magnesium
• mineral supplements
• multivitamins containing minerals such as calcium, iron, magnesium or zinc
• zinc supplements.

There may an increased chance of the amount of calcium in the blood falling too low if aminoglycoside antibiotics such as gentamicin are used in combination with risedronate.

There may be an increased risk of side effects on the digestive system if non-steroidal anti-inflammatory drugs such as ibuprofen or diclofenac are taken in combination with risedronate. You should ask your doctor or pharmacist for advice before taking this type of painkiller.

You should not take any other calcium or vitamin D supplements (including those found in multivitamins) in combination with Actonel combi, unless specifically prescribed by your doctor.

Thiazide diuretics, such as bendroflumethiazide, reduce the amount of calcium excreted in the urine, and this can increase the amount of calcium in the blood. If you are taking a thiazide diuretic in combination with this medicine you should have regular blood tests to monitor the level of calcium in your blood.

People taking digoxin or other cardiac glycosides may have an increased risk of abnormal heart rhythms if they experience abnormally high blood calcium levels while taking this medicine.

Calcium carbonate may reduce the absorption of tetracycline antibiotics (eg tetracycline, minocycline, doxycycline) and quinolone antibiotics (eg ciprofloxacin, norfloxacin, nalidixic acid) from the gut and could make them less effective. If you are prescribed a course of one of these types of antibiotics it is recommended that you take the antibiotic at least two hours before or four to six hours after taking the calcium and vitamin D3 granules. Ask your pharmacist for further advice.

Calcium salts may also reduce the absorption from the gut of the following medicines:

• eltrombopag
• iron supplements such as ferrous sulphate
• levothyroxine
• sodium fluoride
• strontium ranelate
• zinc.

To avoid the calcium stopping these medicines from being adequately absorbed, the calcium and vitamin D3 granules should be separated from these medicines by at least three hours.

The following medicines may decrease the absorption of vitamin D from the gut and should not be taken at the same time of day as the granules:

• orlistat
• colestyramine
• colestipol.

Other medicines containing the same active ingredients

There are currently no other medicines available in the UK that contain this combination of risedronate sodium, calcium carbonate and colecalciferol. However, the ingredients are available separately.

Actonel once a week, Actonel 30mg tablets and Actonel 5mg tabletsall contain risedronate sodium.

Adcal D3, Cacit D3, Calceos, Calcichew D3and Calcichew D3 forteall contain calcium carbonate and colecalciferol.