Actamax 35mg Tablets

ACTAMAX 35 mg is indicated in the treatment of osteoporosis in postmenopausal women, in combination with calcium 500 u2013 1000 mg per day. Additional administration of vitamin D should be considered, when vitamin D deficiency is expected. Treatment of primary osteoporosis in males.

Posology

Adults: Take one 35 mg tablet orally, once a week on the same day each week.

Special populations

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 u2265 30 ml/min. There is no clinical data in patients with severe renal impairment (creatinine clearance < 30 ml/min) (see section 4.3).

Paediatric population

Safety and efficacy of ACTAMAX 35 mg have not been established in children and growing adolescents.

Method of administration

ACTAMAX 35 mg must be taken at least 30 minutes before the first food, liquid or any other medicine of the day other than water, at least two hours before or after food or liquid at any other time of the day and at least 30 minutes before going to bed. ACTAMAX 35 mg should not be taken at bedtime or before getting up in the morning. The tablets must be swallowed whole and not sucked or chewed.

Food, beverages and medicines containing calcium, magnesium, iron and aluminium may interfere with the absorption of ACTAMAX 35 mg and should not be taken at the same time. Patients should take ACTAMAX 35 mg while in an upright position with a glass of plain water (u2265 120 ml) to aid delivery to the stomach. Patients should not lie down for 30 minutes after taking the tablet (see section 4.4).

Missed dose

One ACTAMAX 35 mg tablet should be taken on the day that the tablet is remembered if a dose is missed. 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.

• Hypersensitivity to risedronate or to any of the ingredients of ACTAMAX 35 mg.
• Hypocalcaemia (see sections 4.4 and 4.8).
• Advanced renal impairment: creatinine clearance < 30 ml/min (see section 4.4).
• Pregnancy and lactation (see section 4.6).

Efficacy of bisphosphonates including ACTAMAX 35 mg in the treatment of osteoporosis is related to the presence of low bone mineral density and/or prevalent fracture. High age or clinical risk factors for fracture alone are not sufficient reasons to initiate treatment of osteoporosis with a bisphosphonate such as ACTAMAX 35 mg. The evidence to support efficacy of bisphosphonates including ACTAMAX 35 mg in the very elderly (>80 years) is limited.

u2022 ACTAMAX may cause upper gastrointestinal disorders such as dysphagia, oesophagitis, oesophageal ulcer and gastric ulcer, and should be used with caution in patients with a history of upper gastrointestinal disorders.

Caution should be taken:

• in patients who have a history of oesophageal disorders which delay oesophageal transit or emptying e.g. stricture or achalasia
• in patients who are unable to stay in the upright position for at least 30 minutes after taking the tablet
• if ACTAMAX 35 mg is given to patients with active or recent oesophageal or upper gastrointestinal problems (including known Barrett's oesophagus).

u2022 Prescribers should emphasize the importance of the dosing instructions in patients who have a history of these disorders and be alert to any signs and symptoms of possible oesophageal reaction. The patients should be instructed to seek timely medical attention if they develop symptoms of oesophageal irritation such as dysphagia, pain on swallowing, retrosternal pain or new/worsened heartburn (see section 4.8).

u2022 ACTAMAX 35 mg should be taken while in an upright position (standing or sitting) with a full glass of water. Patients should not lie down for 30 minutes after taking ACTAMAX 35 mg and should not take ACTAMAX at bedtime, or before getting up for the day, in order to minimise the possibility of gastrointestinal adverse effects (see section 4.2).

u2022 Foods, drinks and medicines containing calcium, magnesium, iron and aluminium may interfere with the absorption of ACTAMAX and should not be taken at the same time (see section 4.5). Therefore, to achieve the benefits of ACTAMAX 35 mg, the tablets should be taken at least 30 minutes before the first food, drink or any other medicine of the day, other than water. Failing this, ACTAMAX 35 mg should be taken two hours either before or after the intake of food or liquid.

u2022 Hypocalcaemia and other disturbances of bone and mineral metabolism should be effectively treated before ACTAMAX 35 mg therapy is initiated. Asymptomatic, decreases in serum calcium and phosphorus levels have been observed. Adequate intake of calcium and vitamin D is important. Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.

u2022 The patient should be informed to pay particular attention to the dosing instructions as clinical benefits may be compromised by failure to take ACTAMAX 35 mg according to instructions.

u2022 ACTAMAX 35 mg is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml/min) (see section 4.3).

u2022 Osteonecrosis of the jaw, frequently associated with tooth extraction and/or local infection (including osteomyelitis), has been reported. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates such as ACTAMAX 35 mg.

u2022 A dental examination with appropriate preventive dentistry should be considered prior to treatment with ACTAMAX 35 mg in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene).

u2022 While on treatment, these patients should avoid invasive dental procedures if possible. For patients who developed osteonecrosis of the jaw while on ACTAMAX 35 mg therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of ACTAMAX 35 mg treatment reduces the risk of osteonecrosis of the jaw. Clinical judgement of the treating medical practitioner should guide the management plan of each patient based on individual benefit/risk assessment.

u2022 Osteonecrosis of the external auditory canal has been reported with bisphosphonates such as ACTAMAX 35 mg, mainly in association with long term therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving ACTAMAX 35 mg who present with ear symptoms including chronic ear infections.

Atypical fractures of the femur

u2022 Atypical, low energy fractures of the subtrochanteric and proximal femoral shaft have been reported with long-term use (usually longer than 3 years) in bisphosphonate-treated patients. Some were stress fractures (also reported as insufficiency fractures) occurring in the absence of apparent trauma. Some patientu2019s experienced prodromal pain in the affected area, often associated with imaging features of stress fracture, weeks to months before a fracture occurred. Approximately one third of these fractures were bilateral; therefore, the contralateral femur should be examined in patients who have sustained a femoral shaft stress fracture and receive appropriate orthopaedic care. Poor healing of these fractures has been reported.

u2022 ACTAMAX 35 mg treatment should be stopped in patients with stress fractures and they should receive appropriate orthopaedic care.

u2022 During therapy with ACTAMAX 35 mg, patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.

Information on excipients of ACTAMAX

ACTAMAX 35 mg contains lactose. Patients with the rare hereditary conditions of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency or glucose-galactose malabsorption should not take ACTAMAX 35 mg. ACTAMAX 35 mg contains lactose which may have an effect on the glycaemic control of patients with diabetes mellitus.

• Concomitant use of medicines containing calcium, magnesium, iron and aluminium, including antacids, mineral supplements and some osmotic laxatives may interfere with the absorption of ACTAMAX 35 mg (see section 4.4).
• ACTAMAX 35 mg and concurrent use with aspirin and NSAID medicine may increase gastrointestinal irritation.
• ACTAMAX 35 mg may be used concomitantly with Hormone Replacement Therapy.
• There may be additive hypocalcaemic effects with aminoglycosides.
• ACTAMAX 35 mg is not systemically metabolised, does not induce cytochrome P450 enzymes and has low protein binding.

The safety of ACTAMAX 35 mg in pregnancy and breastfeeding has not been established and use of ACTAMAX 35 mg is contraindicated (see section 4.3).

ACTAMAX 35 mg has no or negligible influence on the ability to drive and use machinery.

a) Tabulated summary of adverse reactions

System Organ Class

Frequency

Side effects

Blood and lymphatic system disorders

Less frequent

Frequency unknown

Anaemia, thrombocytopenia, leukopenia

Eosinophilia, neutropenia

Immune system disorders

Frequent

Frequency unknown

Hypersensitivity reactions

Anaphylactic reaction, skin reactions including angioedema

Metabolism and nutrition disorders

Less frequent

Hypocalcaemia, hypophosphatemia

Psychiatric disorders

Frequency unknown

Insomnia, somnolence

Nervous system disorders

Frequent

Headache

Eye disorders

Frequent

Less frequent

Dry eye, sore eye, conjunctivitis

Iritis, scleritis, episcleritis, uveitis, non-specific conjunctivitis, abnormal vision, blurred vision

Gastrointestinal disorders

Frequent

Less frequent

Frequency unknown

Dyspepsia, nausea, vomiting, abdominal pain, constipation, diarrhoea, gastrointestinal disorders

Oesophagitis, oesophageal ulcer, gastritis, dysphagia, duodenitis, glossitis, oesophageal stricture, peptic ulceration

Flatulence, gastric haemorrhage, eructation, odynophagia

Hepato-biliary disorders

Frequent

Frequency unknown

Abnormal liver function tests

Serious hepatic disorders

Skin and subcutaneous tissue disorders

Less frequent

Frequency unknown

Generalised rash and bullous skin reactions, urticaria, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis and leukocytoclastic vasculitis, hair loss

Hyperhidrosis

Musculoskeletal, connective tissue and bone disorders

Frequent

Less frequent

Musculoskeletal pain, arthralgia, bone pain, atypical femoral fractures, myalgia

Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction), osteonecrosis of the jaw and ear canal

Reproductive system and breast disorders

Frequency unknown

Decreased libido

General disorders and administrative site conditions

Frequent

Less frequent

Frequency unknown

Pain

Fever, chills, fatigue, malaise

Acute mountain sickness, pyrexia

Investigations

Less frequent

Frequency unknown

Oesophageal cancer

Decreases in serum calcium and phosphate levels

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Signs and symptoms

Although overdose with risedronate has not been reported, decreases in serum calcium would be expected to occur with substantial overdose. Signs and symptoms of hypocalcaemia may also occur in some of these patients.

Management of overdose

Standard procedures for treatment of hypocalcaemia are to be followed. Milk or antacids containing magnesium, calcium or aluminium should be given to bind ACTAMAX 35 mg and reduce absorption of risedronate. In cases of substantial overdose, gastric lavage may be considered to remove unabsorbed medicine.