INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo ACTONEL® Once-a-Week
SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

ACTONEL® Once-a-Week
(film-coated tablets)

COMPOSITION:
One film-coated tablet contains risedronic acid equivalent to 35 mg risedronate sodium.

PHARMACOLOGICAL CLASSIFICATION:
A 3.2. Connective tissue medicines, non-hormonal preparations.

PHARMACOLOGICAL ACTION:
Pharmacodynamics:
Risedronate sodium is a pyridinyl bisphosphonate that binds to bone hydroxyapatite and inhibits osteoclast-mediated bone resorption, while bone formation is preserved. In preclinical studies, risedronate demonstrated potent anti-osteoclast and antiresorptive activity, dose-dependently. The activity of risedronate sodium was confirmed by bone marker measurements.
Pharmacokinetics:
Absorption: Absorption after an oral dose is relatively rapid (tmax ~1 hour) and occurs throughout the upper gastrointestinal tract. Absorption is independent of dose over the range studied (single dose study, 2.5 to 30 mg; multiple dose studies 2.5 to 5 mg daily and up to 50 mg dosed weekly). Mean oral bioavailability of the tablet is 0.63% and is decreased significantly when risedronate sodium is administered with food. Bioavailability was similar in men and women.
Distribution: Preclinical studies in rats and dogs dosed intravenously with single doses of [14C]-risedronate sodium, indicate that approximately 60% of the dose is distributed to bone. The remainder of the dose is excreted in the urine. The mean steady state volume of distribution is 6.3 L/kg in humans. Human plasma protein binding of the drug is about 24%.
Metabolism: There is no evidence of systemic metabolism of risedronate sodium.
Elimination: Approximately half of the absorbed dose is excreted in urine within 24 hours and 85% of an intravenous dose is recovered in the urine over 28 days. Mean renal clearance is 105 mL/min and mean total clearance is 122 mL/min, with the difference primarily reflecting non-renal clearance or clearance due to adsorption to bone. The renal clearance is not concentration dependent and there is a linear relationship between renal clearance and creatinine clearance.
Unabsorbed drug is eliminated unchanged in faeces. Once risedronate sodium is absorbed, the serum concentration-time profile is multi-phasic with an initial half-life of about 1.5 hours and a terminal exponential half-life of 480 hours.
Special populations: Elderly and patients with renal impairment (see Dosage and Directions for use).

INDICATIONS:
Treatment of osteoporosis in postmenopausal women, in combination with calcium 500-1000 mg per day. Additional administration of vitamin D should be considered when deficiency might be expected.

CONTRA-INDICATIONS:
Known hypersensitivity to any ingredient of this product.
Hypocalcaemia (see Side-effects and Special Precautions).
Pregnancy and lactation, as safety has not been established.
Advanced renal impairment: creatinine clearance <30 mL/min (see Special Precautions).

WARNINGS:
See Side-effects and Special Precautions.
Bisphosphonates may cause upper gastrointestinal disorders such as dysphagia, oesophagitis, oesophageal ulcer and gastric ulcer.
Bisphosphonates have been associated with oesophagitis and oesophageal ulcerations. Therefore, patients should pay attention to the dosing instructions (see Dosage and Directions for Use). Prescribers should emphasise the importance of the dosing instructions to patients who have a history of oesophageal disorders.
In order to facilitate delivery to the stomach and minimise the possibility of gastrointestinal adverse effects, patients should take Actonel while in an upright position (standing or sitting) with a full glass of plain water and should avoid lying down for 30 minutes after taking this medication.

DOSAGE AND DIRECTIONS FOR USE:
Dosage:
Adults: The recommended dose is one 35 mg tablet orally, once a week. The tablet should be taken on the same day each week.
Foods, drinks (other than plain water) and drugs containing polyvalent cations (such as calcium, magnesium, iron and aluminium) may interfere with the absorption of Actonel and should not be taken at the same time. Therefore, Actonel should be taken either, at least 30 minutes before the first food or drink of the day or, at least two hours away from food or drink at any other time of the day and at least 30 minutes before going to bed.
Patients should be instructed that if a dose is missed, one Actonel Once-a-Week 35 mg tablet should be taken on the day that the tablet is remembered. Patients should then return to taking one tablet once a week on the day the tablet is normally taken. Two tablets should not be taken on the same day.
The tablets must be swallowed whole and not sucked or chewed.
Patients should take Actonel while in an upright position with a glass of plain water (>120 mL) to aid delivery to the stomach. Patients should not lie down for 30 minutes after taking the tablet (see Special Precautions).
Elderly: No dosage adjustment is necessary since bioavailability and disposition were similar in elderly (>60 years of age) compared to younger subjects.
Renal impairment: No dosage adjustment is necessary in patients with creatinine clearance >30 mL/min. There is no clinical data in patients with severe renal impairment (creatinine clearance <30 mL/min), so no dosage recommendation can be made for this population.
Children: Safety and efficacy of Actonel have not been established in children and growing adolescents.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Common side effects (1% to 10%):
Body as a whole:
Pain
Digestive system:
Dyspepsia, nausea, abdominal pain, constipation, diarrhoea, GI disorders
Musculoskeletal system:
Musculoskeletal pain, arthralgia, bone pain
Nervous system:
Headache
Uncommon side effects (0.1% to 1%):
Digestive system:
Oesophagitis, oesophageal ulcer, gastritis, dysphagia, duodenitis, glossitis, oesophageal stricture
Other:
Rash
Uncommon cases of iritis have been reported.
Laboratory findings: decreases in serum calcium and phosphate levels have been observed.
Abnormal liver function tests have been reported (see Special Precautions).
Special Precautions:
Foods, drinks (other than plain water) and drugs containing polyvalent cations (such as calcium, magnesium, iron and aluminium) may interfere with the absorption of Actonel and should not be taken at the same time. Therefore, to achieve the proven benefits of Actonel, patients should take the tablet either, at least 30 minutes before the first food or drink of the day or, at least two hours away from food or drink at any other time of the day.
Hypocalcaemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Actonel therapy. Asymptomatic, small decreases in serum calcium and phosphorus levels have been observed in some patients. Adequate intake of calcium and vitamin D is important.
Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.
Actonel should be used with caution in patients with a history of upper gastrointestinal disorders.
The patient should be informed to pay particular attention to the dosing instructions as clinical benefits may be compromised by failure to take the medicine according to instructions.
Actonel is not recommended in patients with severe renal impairment (creatinine clearance <30 mL/min).
Interaction with other medicaments and other forms of interaction:
In the Actonel Phase III osteoporosis studies with daily dosing, aspirin or NSAID use was reported in 32% and 48% of patients, respectively. In the Phase III once a week study, aspirin or NSAID use was reported by 57% and 40% of patients, respectively.
If considered appropriate, Actonel may be used concomitantly with Hormone Replacement Therapy.
Concomitant ingestion of medications containing polyvalent cations (e.g. calcium, magnesium, iron and aluminium) will interfere with the absorption of Actonel (see Special Precautions),
Actonel is not systemically metabolised, does not induce cytochrome P450 enzymes and has low protein binding.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
No specific information is available on the treatment of acute overdose with Actonel.
Decreases in serum calcium following substantial overdose may be expected in some patients. Signs and symptoms of hypocalcaemia may also occur in some of these patients.
Milk or antacids containing magnesium, calcium or aluminium should be given to bind Actonel and reduce absorption of the drug. In cases of substantial overdose, gastric lavage may be considered to remove unabsorbed drug.

IDENTIFICATION:
Oval, light-orange film-coated tablets with RSN on one side and 35 mg on the other.

PRESENTATION:
Packed in aluminium-backed, clear PVC blisters in cartons of 4 tablets.

STORAGE INSTRUCTIONS:
Store below 25°C.
Keep out of reach of children.

REGISTRATION NUMBER:
37/3.2/0129

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Aventis Pharma (Pty) Ltd
2 Bond Street
Midrand
1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
7 February 2003

New addition to this site: February 2004
Source: Community Pharmacy

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