Aredia (pamidronate disodium)

What Is Aredia? 

AREDIA® is a bisphosphonate medication that prevents bone damage in multiple myeloma patients. Normally, our body has a delicate balance between cells that build bone (osteoblasts) and cells that break down bone (osteoclasts). For myeloma patients, signals sent by cancerous cells stimulate osteoclasts and disrupt this balance causing excess bone breakdown. 

Myeloma patients may experience various bone problems called skeletal-related events, or SREs, including  

• weak bones,
• lytic lesions (holes in the bones),
• and fractures.

In 2010, Lancet Oncology published the findings from a large, randomized, double-blind, phase III clinical trial by the Nordic Myeloma Study Group (NMSG), which compared Aredia given at 30 mg to the standard dose of 90 mg in patients with newly diagnosed multiple myeloma (NDMM). 

Given the toxicities associated with long-term bisphosphonate treatment, the aim of the NMSG study was to establish the lowest effective dose of Aredia. The study validated the efficacy of the reduced dose, concluding that “monthly infusion of Aredia 30 mg should be the recommended dose for prevention of bone disease” in myeloma patients. Ask your doctor if Aredia at 30 mg dose is appropriate for your individual case

Who Is a Candidate for Aredia? 

Aredia is indicated for treating osteolytic lesions in patients with multiple myeloma.

Aredia may not be recommended by your clinician if you have impaired kidney (renal) function or have a known allergy to bisphosphonates. You may also be unable to take Aredia if you are pregnant or breastfeeding.

There are other reasons you may not be a candidate for Aredia. Please see the package insert and discuss Aredia with your doctor for more information.

How Is Aredia Given? 

The typical dose of Aredia is 90 mg, given through an infusion into a vein. The infusion usually lasts 4 hours and is given every 3 to 4 weeks.

Your clinician may recommend taking calcium and Vitamin D supplements while taking Aredia. Your clinician will measure your vitamin D and calcium levels before treatment.

It is important to know that many side effects in patients taking Aredia also occurred in patients taking a placebo. In addition, many side effects seen in clinical trials are symptoms that can occur because of myeloma. Therefore, these side effects may not be caused by the medication.  

Toxicities associated with this medication are related to dosage, frequency of administration, and duration of infusion. Therefore, your doctor may recommend to reduce your dose and/or frequency of administration, and/or increasing the duration of infusion.

Aredia may cause severe side effects in some people. In a clinical trial of 392 patients, five patients experienced serious side effects related to Aredia:  

• worsening kidney function,
• respiratory distress,
• and an allergic reaction³

The kidney toxicity-related concern with the use of Aredia is an excess of a serum protein (albumin) in the urine, known as albuminuria or nephrotic syndrome, that has occurred predominantly if Aredia is given more frequently than monthly or at a dose higher than 90 mg. This side effect is usually reversible with dose and/or schedule adjustments or, in occasional severe cases, by discontinuing Aredia. Very rarely has irreversible damage occurred. Periodic monitoring (e.g., every 3 to 6 months) of urine protein levels with 24-hour urine collection is recommended to prevent any significant kidney damage.

The risk of kidney-related side effects may be increased if you are taking Aredia in combination with thalidomide.⁴ Your clinician will take bloodwork to monitor your creatinine (a measure of your kidney function) before and throughout treatment.  

In addition, your clinician will monitor your blood electrolyte levels (or minerals in your body) as Aredia may cause changes in these levels (for example, low phosphorus, potassium, magnesium, and calcium).

Like other bone-targeting medications, Aredia may cause osteonecrosis of the jaw (ONJ) or opening of areas of the jawbone. You will be advised to have a complete dental exam before starting treatment. ONJ may cause you to feel

• pain,
• numbness,
• unusual drainage,
• or swelling from your jaw, mouth, or teeth.

If you experience any of these symptoms while taking Aredia, it is important to contact your doctor.

For a complete list of side effects, please see the Aredia package insert and consult the additional resources below.

Other Possible Side Effects of Aredia

Be sure to discuss with your doctor the possible side effects of Aredia, including the following:

Osteonecrosis of the jaw

Osteonecrosis of the jaw (ONJ) is a problem that occurs in 3%–4% of patients with myeloma or other cancers who have been treated with either bisphosphonates or Xgeva. This condition is often preceded by inflammation or an infection in the mouth, and produces pain, swelling, and bone damage around the tooth sockets in the jaws. There is bone necrosis or loss of bone, which can lead to loose teeth, sharp edges of exposed bone, bone spurs, and the breaking loose of small bone spicules or dead bone. 

Symptoms may not be obvious at first, or may include pain, swelling, numbness, a “heavy jaw” feeling, or loosening of a tooth.

• Before treatment with any bone-modifying agent such as Aredia, all myeloma patients should have a dental evaluation, preferably with an oral surgeon or dental oncologist familiar with ONJ. Careful monitoring and follow-up are required.
• Prevention can help avoid or reduce the scope of ONJ. Be sure to inform your dentist if you are receiving treatment with a BMA. Maintain excellent oral hygiene and visit your dentist regularly.
• If an infection is present, treatment with an antibiotic is recommended.The choice of antibiotic depends upon the type of infection that is documented. An oral rinse may be appropriate.
• If required, proceed with preventive dental care before starting treatment with a BMA.
• Management without surgery is recommended as a first step. Minor dental work to reduce sharp edges or remove injured tissue may be required. A protective mouth guard may be helpful.
• If possible, avoid tooth extraction and any elective jaw surgery. If dental surgery is required, interruption of BMA therapy is recommended. Current data indicate poor healing with continued BMA therapy in this setting.
• If problems persist or if healing is slow, consideration can be given to stopping bisphosphonate therapy for 2 to 4 months to facilitate recovery.
• Dentures can be worn, but may need adjustment. Dental implants appear to be contraindicated. Use of hyperbaric oxygen does not appear to be helpful.

Kidney dysfunction

All bisphosphonates are potentially toxic to the kidneys. Since myeloma itself can impact kidney function (through damage caused by myeloma light chain protein and/or by elevated blood calcium), the possibility of kidney-related side effects is of particular concern.

Before you begin treatment with a BMA such as Aredia, ask your doctor if the BMA in combination with other medications you are receiving may be more likely to have a negative impact on your kidney function. This includes myeloma therapies as well as nonsteroidal anti-inflammatory drugs (NSAIDs).

Fever

Pyrexia (medical term for fever) is defined as a temperature of 100.4°F (38°C) or higher. Fever may occur as an infusion-related reaction (IRR) associated with the use of bisphosphonates such as Aredia. The fever is usually mild; each treatment center has its own definition for “mild” temperature. You may experience a fever during your IV infusion or during the hours after, and the fever may last for several hours. Typically, fever occurs with the first or second infusion, and less frequently (if at all) with subsequent infusions. Patients who have severe recurrent fevers may not be able to tolerate IV bisphosphonates. As with other possible side effects, promptly report your fever to your doctor.

Vein irritation

With IV infusions of bisphosphonates, mild phlebitis (vein irritation) can occur at the site of the infusion. It is usually mild, and patients typically recover within 1 to 2 days. Careful monitoring is recommended during each infusion in order to avoid any leakage of medication around the vein.

A short infusion of saline at the end of the bisphosphonate infusion is recommended to clear the Aredia from the area and reduce the chance of phlebitis.

General aches and pains

These effects sometimes occur briefly, along with fever, with infused bisphosphonates. Back pain has been reported in patients who are receiving therapy with Xgeva. Ask your doctor if receiving medication before your infusions may be beneficial for you.

Combining Aredia with Myeloma Therapies

In general, BMAs can be safely combined with most myeloma therapies. Your doctor may decide not to give these therapies on or close to the same day as administration of intravenous treatment for myeloma. Caution about potential kidney toxicity with bisphosphonates has been discussed earlier on this webpage. Talk to your doctor to be sure that the BMA you are receiving is not being combined with another drug that can harm your kidneys.

Insurance coverage

In the U.S., the Centers for Medicare & Medicaid Services (CMS), a federal agency that administers the Medicare program, rei burse for bisphosphonate therapy. Most other insurance programs in the U.S. also reimburse for bisphosphonate therapy. Xgeva is significantly more expensive than generic Aredia or Zometa, so unless there are medical reasons why a patient cannot receive bisphosphonate therapy (e.g., kidney disease), there may be insurance issues with receiving reimbursement for Xgeva. If you experience any problems with insurance coverage or reimbursement, speak with your healthcare team.

Since hospitals and clinics set up contracts for one product versus another, it’s important to double-check which agent, from which source, is being administered to you. Some patients may experience a new side effect or be intolerant of the solution into which the active ingredients are added. If this happens to you, be sure to find out what drug you received and which
company manufactured it, and report your side effects to your doctor.

Additional information 

FDA package insert: Aredia

Efficacy of Pamidronate in Reducing Skeletal Events in Patients with Advanced Multiple Myeloma.