DRUG PRESENTATION: ZOLEDRONIC ACID (ACLASTA)

Presented by: CZARINA MAE F. CID

Zoledronic Acid (ACLASTA)

CLASS
Biphosphonates

First and only once-yearly medicine for osteoporosis MECHANISM OF ACTION

Aclasta

slows down bone resorption, allowing the bone-forming cells time to rebuild normal bone.

DOSING

In ready to use plastic bottles 5 mg doses in 100 mL aqueous solution Single dose should not exceed 5 mg Given once a year.

BONE

STRUCTURE

Compact (cortical) bone

The hard outer layer of bones is composed of compact bone tissue, so-called due to its minimal gaps and spaces. This tissue gives bones their smooth, white, and solid appearance, and accounts for 80% of the total bone mass of an adult skeleton. Filling the interior of the bone is the trabecular bone tissue (an open cell porous network also called cancellous or spongy bone), which is composed of a network of rod- and plate-like elements that make the overall organ lighter and allow room for blood vessels and marrow.

Trabecular (cancellous) bone

BONE

CELLULAR STRUCTURE
Osteoblasts

are mononucleate bone-forming cells which mineralizes to become bone. Osteocytes originate from osteoblasts that have migrated into and become trapped and surrounded by bone matrix that they themselves produce. They are mature bone cells. Osteoclasts are the cells responsible for bone resorption, thus they break down bone.

INDICATIONS & DOSING

INDICATION Prevention of postmenopausal osteoporosis in women Treatment of osteoporosis in men DOSING 5 mg IV infusion every 2 years 5 mg IV per year

Treatment of Pagets disease of bone

5 mg given as one-time IV infusion; rarely needs re-treatment within 5 years

5 mg IV per year 5 mg IV per year 5 mg IV per year

Treatment of glucocorticoid-induced osteoporosis Prevention of clinical fractures in patients after hip fracture Prevention of glucocorticoid-induced osteoporosis

Treatment of postmenopausal osteoporosis in women

5 mg IV per year

OSTEOPOROSIS

A disease where the bone mineral density (BMD) is reduced, bone microarchitecture deteriorates, and the amount and variety of proteins in bone is altered which leads to an increased risk of fracture Osteoporotic fractures are those that occur in situations where healthy people would not normally break a bone; aka. fragility fractures vertebral column, rib, hip and wrist

OSTEOPOROSIS

POST MENOPAUSAL OSTEOPOROSIS

Results

from a lack of estrogen (e.g. as a result of menopause) which increases bone resorption as well as decreases the deposition of new bone that normally takes place in weight-bearing bones.

OSTEOPOROSIS

Glucocortocoid-induced osteoporosis (GIOP)

PAGETS DISEASE

Aka osteitis deformans or osteodystrophia deformans Chronic disorder that can result in enlarged and misshapen bones. The excessive breakdown and formation of bone tissue causes affected bone to weaken, resulting in pain, misshapen bones, fractures, and arthritis in the joints near the affected bones. Typically is localized Of viral or genetic etiology No cure

CONTRAINDICATION

Aspirin-sensitive asthma Dental disease Kidney disease Hypocalcemia Allergic sensitivity to similar medicine Pregnant or trying to get pregnant Breast feeding Patients already receiving Zometa Malabsorption syndrome Bone cancer

DRUG INTERACTIONS
Medicines that can harm your kidneys Diuretics bumetanide and furosemide Certain antibiotics given by injection NSAIDs, medicines for pain and inflammation ibuprofen, naproxen Cancer medicine * Tell health care provider all medicines, herbs, non-prescription drugs and dietary supplements, * Smoking, drinking or illegal drugs

SIDE EFFECTS

Needs immediate intervention (Emergency):

Allergic

reactions: skin rash, itching or hives, swelling of the face, lips or tongue, breathing problems

Serious side-effects:
Urinating

less than usual or not at all Muscle spasms, numb or tingly feeling (especially around your mouth) Severe joint, bone, or muscle pain Jaw burning, cramping or pain OSTEONECROSIS Fainting

HYPOCALCEMIA

Less than 2.1 mmol/L or 9 mg/dl or an ionized calcium level of less than 1.1 mmol/L or 4.5 mg/Dl
Normal

serum calcium: 2.2-2.6 mmol/L (910.5 mg/dL) Normal ionized calcium:1.1-1.4 mmol/L (4.55.6 mg/dL)

HYPOCALCEMIA

"CATS go numb Petechiae Oral, perioral and acral paresthesias, tingling or 'pins and needles' sensation in and around the mouth and lips, and in the extremities of the hands and feet Carpopedal and generalized tetany Latent tetany

Trousseau sign of latent tetany Chvostek's sign

Tendon reflexes are hyperactive Life threatening complications

Laryngospasm Cardiac arrhythmias Intermittent QT prolongation; puts the patient at high risk of torsades de pointes

ECG changes include:

OSTEONECROSIS OF THE JAW (ONJ)

severe bone disease that affects the maxilla and the mandible. Signs / symptoms: The definitive symptom of ONJ is the exposure of mandibular or maxillary bone through lesions in the gingiva that do not heal.
Pain inflammation

of the surrounding soft tissue secondary infection or drainage may or may not be present.

SIDE EFFECTS

Do not usually require medical attention (report if it continues):

Bone, Fever

joint or muscle pain

Irritation

at IV site Loss of appetite Nausea and vomiting Stomach upset Feeling of fatigue

OVERDOSE

Signs and Symptoms

Numbness

or tingling in your hands and feet Muscle stiffness Spasms in the muscles of your face Uneven heartbeats Wheezing or trouble breathing.

PRE-INFUSION CONSIDERATIONS

Dental exam for preventive tooth and gum care Correct disturbances of mineral metabolism - Calcium and vitamin D

Ensure calcium is in normal range: 2.0-2.6mmol/L Vitamin D supplementation:

If patient is not on Vitamin D, administer 2 x 1.25mg calciferol during the week before infusion Instruct patients to continue taking Vitamin D supplements (calciferol 1.25mg per month)

Confirm creatinine clearance is 35 mL/min. Do not infuse Aclasta in patients with creatinine clearance of <35 mL/min On the day of the infusion, it is important to drink at least 500 mL (2 cups) of fluids before and after the treatment.

DURING THE INFUSION

Infuse over no less than 15 minutes over a constant infusion rate Infuse at a slower rate in elderly patients Flushing is recommended Must be given in a separate, vented IV line. Do not mix with other medication and must not come in contact with any calcium- or divalent cation-containing solution

POST INFUSION

In patients at risk for renal failure, consider interim monitoring of renal function All patients should be instructed on the importance of calcium and vitamin D supplementation.

Paget's disease: patient should also receive 1500 mg of elemental calcium and 800 IU vitamin D daily, especially during the 2 weeks after the injection of zoledronic acid. It is strongly advised that patients with Pagets disease receive adequate supplemental calcium corresponding to at least 500 mg elemental calcium twice a day and vitamin D, this should be ensured during the initial 10 days following Aclasta administrationn

Transient postdose symptoms (fever, myalgia, flu-like symptoms, headache and arthralgia) occur within 3 days of infusion and most resolved within 3 days of onset - Paracetamol or ibuprofen given up to 3 days after Aclasta Adequate calcium and vitamin D intake prior to Aclasta therapy in patients with preexisting hypocalcaemia, and for 10 days following Aclasta in patients with Paget's disease of the bone

STORAGE AND STABILITY

Keep unopened vial below 30C. Opened vials should be used immediately. Unused, opened vials can be stored up to 24hrs at 2-8 C Discard any unused contents of the vial after infusion. Alcasta must reach room temperature prior to infusion if refrigerated.

THANK YOU!