Arsenox

Arsenox is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

The response rate of other acute myelogenous leukemia subtypes to Arsenox has not been examined.

Arsenox injection is used to treat a type of leukemia (cancer of the blood cells) called acute promyelocytic leukemia (APL) in patients who have not responded to other medication regimens. It may also be used to treat other kinds of cancer, as determined by your doctor.

Arsenox belongs to the general group of medicines called antineoplastics. It interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by Arsenox, other unwanted effects will also occur. Some of these may be serious and must be reported to your doctor.

Before you begin treatment with Arsenox, you and your doctor should talk about the benefit of Arsenox as well as the risks of using it.

Arsenox is to be given only by or under the immediate supervision of your doctor.

Usual Adult Dose for Acute Promyelocytic Leukemia

Induction Treatment Schedule: 0.15 mg/kg intravenously daily until bone marrow remission. Total induction dose should not exceed 60 doses.

Arsenox should be administered intravenously over 1-2 hours. The infusion duration may be extended up to 4 hours if acute vasomotor reactions are observed. (A central venous catheter is not required.)

Consolidation Treatment Schedule: Consolidation treatment should begin 3 to 6 weeks after completion of induction therapy. Arsenox should be administered intravenously at a dose of 0.15 mg/kg daily for 25 doses over a period up to 5 weeks.

Renal Dose Adjustments

Exposure of Arsenox may be higher in patients with severe renal impairment. Patients with severe renal impairment (creatinine clearance less than 30 mL/min) should be closely monitored for toxicity and dose reduction may be warranted.

Liver Dose Adjustments

Since limited data are available across all hepatic impairment groups, caution is advised in the use of Arsenox in patients with hepatic impairment. Patients with severe hepatic impairment (Child-Pugh class C) should be closely monitored for toxicity.

Precautions

Prior to initiating therapy with Arsenox, a 12 lead ECG should be performed and serum electrolytes (potassium, calcium, and magnesium) and creatinine should be assessed; preexisting electrolyte abnormalities should be corrected and, if possible, drugs that are known to prolong the QT interval should be discontinued. For QTc greater than 500 msec, corrective measures should be completed and the QTc reassessed with serial ECGs prior to considering using Arsenox. During therapy with Arsenox, potassium concentrations should be kept above 4 mEq/L and magnesium concentrations should be kept above 1.8 mg/dL. Patients who reach an absolute QT interval value > 500 msec should be reassessed and immediate action should be taken to correct concomitant risk factors, if any, while the risk/benefit of continuing versus suspending Arsenox therapy should be considered. If syncope, rapid or irregular heartbeat develops, the patient should be hospitalized for monitoring, serum electrolytes should be assessed, Arsenox therapy should be temporarily discontinued until the QTc interval regresses to below 460 msec, electrolyte abnormalities are corrected, and the syncope and irregular heartbeat cease. There are no data on the effect of Arsenox on the QTc interval during the infusion.

Electrolyte, hematologic and coagulation profiles should be monitored at least twice weekly, and more frequently for clinically unstable patients during the induction phase and at least weekly during the consolidation phase. ECGs should be obtained weekly, and more frequently for clinically unstable patients, during induction and consolidation.

Dialysis

The use of Arsenox in patients on dialysis has not been studied.

Other Comments

Arsenox should be diluted with 100 to 250 mL of 5% dextrose injection or 0.9% sodium chloride injection immediately after withdrawal from the ampule. Do not mix Arsenox with other medications.

See also:
What is the most important information I should know about Arsenox?

Call your doctor at once if you have a serious side effect such as sharp chest pain, wheezing, rapid breathing, feeling short of breath, dry cough, feeling weak or tired, dizziness, fainting, fast or pounding heartbeat, fever, or swelling in your ankles or feet.

Do not use Arsenox without telling your doctor if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

Before receiving Arsenox, tell your doctor if you have congestive heart failure, a heart rhythm disorder, an electrolyte imbalance, high blood pressure, a history of "Long QT syndrome," liver disease, or kidney disease.

There are many other drugs that can interact with Arsenox. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

To be sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested on a regular basis. You must remain under the care of a doctor while you are using Arsenox. Do not miss any follow-up appointments.

Use Arsenox as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Arsenox is usually administered as an injection at your doctor's office, hospital, or clinic.
• Do not use Arsenox if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Arsenox, contact your doctor immediately.

Ask your health care provider any questions you may have about how to use Arsenox.

Use: Labeled Indications

Acute promyelocytic leukemia (newly diagnosed) (low-risk disease): Treatment of newly diagnosed low-risk acute promyelocytic leukemia (APL), in combination with tretinoin, in adults whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression

Acute promyelocytic leukemia (relapsed or refractory): Remission induction and consolidation treatment of APL in patients who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression

Off Label Uses

Acute promyelocytic leukemia (newly diagnosed) (including intermediate- or high-risk disease)

Data from a randomized, multicenter, phase III study support the use of Arsenox (in combination with tretinoin) in the management of intermediate-risk acute promyelocytic leukemia (APL). These studies also included patients with newly diagnosed low-risk APL, which is a labeled indication.

See also:
What other drugs will affect Arsenox?

Drugs That Can Prolong the QT/QTc Interval

Concomitant use of these drugs and Arsenox may increase the risk of serious QT/QTc interval prolongation. Discontinue or replace with an alternative drug that does not prolong the QT/QTc interval while patient is using Arsenox. Monitor ECGs more frequently in patients when it is not feasible to avoid concomitant use.

Drugs That Can Lead to Electrolyte Abnormalities

Electrolyte abnormalities increase the risk of serious QT/QTc interval prolongation. Avoid concomitant administration of drugs that can lead to electrolyte abnormalities. Monitor electrolytes more frequently in patients who must receive concomitant use of these drugs and Arsenox.

See also:
What are the possible side effects of Arsenox?

Applies to Arsenox: intravenous solution

As well as its needed effects, Arsenox (the active ingredient contained in Arsenox) may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking Arsenox, check with your doctor or nurse immediately:

More common:

• Chills
• convulsions (seizures)
• cough
• decreased urine output
• dry mouth
• eye pain
• general feeling of illness
• headache
• increased thirst
• irregular heartbeat
• loss of appetite
• mood changes
• muscle pain or cramps
• nausea or vomiting
• numbness or tingling in hands, feet, or lips
• sore throat
• trouble breathing
• unusual tiredness or weakness

• Abdominal or stomach cramps
• black, tarry stools
• bluish lips or skin
• blurred vision
• chest pain
• dizziness or lightheadedness
• fever
• flushed, dry skin
• fruit-like breath odor
• increased hunger
• increased urine output
• irregular or pounding heartbeat or pulse
• painful or difficult urination
• sores, ulcers, or white spots on the lips or in the mouth
• stomachache
• sweating
• swollen glands
• unexplained weight loss
• unusual bleeding or bruising
• unusual weight gain

• Anxiety
• behavior changes similar to drunkenness
• bleeding
• blood in the urine or stools
• bluish fingernails, palms, or nailbeds
• bruising
• cloudy urine
• cold sweats
• cool pale skin
• drowsiness
• headache
• large hives or rash
• persistent bleeding or oozing from puncture sites, mouth, or nose
• severe nausea
• shakiness
• sore mouth or tongue
• swelling of the eyelids, lips, or face
• vomiting of blood or material that looks like coffee grounds
• white patches in the mouth or on the tongue

If any of the following symptoms of overdose occur while taking Arsenox, get emergency help immediately:

Symptoms of overdose:

• Confusion
• convulsions (seizures)
• muscle weakness, severe

Minor Side Effects

Some Arsenox side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common:

• Diarrhea

• Acid or sour stomach
• back pain
• belching
• bloating or swelling of the face, hands, lower legs, or feet
• bone pain
• constipation
• flushing
• heartburn
• heavy non-menstrual vaginal bleeding
• indigestion
• injection site pain, redness, or swelling
• itching
• itchy, red skin
• joint or muscle pain
• limb pain
• loss of appetite
• mental depression
• neck pain
• nosebleeds
• pale skin
• shivering chills
• trouble sleeping or getting to sleep
• weight gain

• Agitation
• blisters inside the mouth
• coughing or spitting up blood
• earache
• eye dryness, redness, or pain
• loss of bowel or bladder control
• night sweats
• rapid, shallow breathing
• ringing in the ears
• small red or purple spots on skin
• swelling of the abdominal or stomach area
• swelling or puffiness of the face or eyelids
• swollen, painful, or tender lymph glands in the neck, armpit, or groin

Arsenox is a chemotheraputic agent of idiopathic function used to treat leukemia that is unresponsive to first line agents. It is suspected that arsenic trisulfide induces cancer cells to undergo apoptosis. Due to the toxic nature of arsenic, this drug carries significant health risks. The enzyme thioredoxin reductase has recently been identified as a target for Arsenox.