Storage:

Store unopened vial at CRT. Stable after initial reconstitution at room temperature for 7 days, up to 14 days if refrigerated. When further diluted to a concentration of 20 to 40 mcg/mL, it is stable at room temperature for 3 hours in D5W, 12 hours in NS, and 24 hours in sodium lactate ¹/₆ M.

Additive:

Manufacturer states that mitomycin (5 to 15 mg) and heparin (1,000 to 10,000 units) in 30 mL NS is stable at CRT for 48 hours. Other sources list dexamethasone (Decadron), heparin, hydrocortisone sodium succinate (Solu-Cortef).

Y-site:

Amifostine (Ethyol), bleomycin (Blenoxane), caspofungin (Cancidas), cisplatin (Platinol), cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), droperidol (Inapsine), fluorouracil (5-FU), furosemide (Lasix), granisetron (Kytril), heparin, leucovorin calcium, melphalan (Alkeran), methotrexate, metoclopramide (Reglan), ondansetron (Zofran), teniposide (Vumon), thiotepa, vinblastine, vincristine.

IV injection:

A single dose over 5 to 10 minutes.

Infusion:

Rate determined by amount and type of solution, typically 15 to 30 minutes.

Unlabeled uses:

Combination chemotherapy in anal, cervical, head and neck, metastatic breast, and non–small-cell lung cancers and in malignant mesothelioma.

Monitor:

Monitor WBC, RBC, platelet count, PT, bleeding time, differential, and hemoglobin before, during, and 7 to 10 weeks after therapy. ■ Monitor all patients, especially those nearing a cumulative dose of 60 mg, for unexplained anemia with fragmented cells on peripheral blood smear, thrombocytopenia, and decreased renal function; see Precautions. ■ Determine absolute patency of vein; use of an IV catheter is preferred because severe cellulitis and tissue necrosis will result from extravasation. If extravasation occurs, discontinue injection and use another vein. Elevate extremity and apply cold compresses to extravasated area. Delayed erythema with or without ulceration has occurred at or distant to the injection site. May occur weeks to months after mitomycin administration, even when no obvious evidence of extravasation was observed during administration. ■ May precipitate acute respiratory distress syndrome. Oxygen can be toxic to the lungs; monitor intake carefully and use only enough to provide adequate arterial saturation. ■ Monitor fluid balance; avoid overhydration. ■ Be alert for signs of bone marrow suppression or infection. ■ Monitor for thrombocytopenia (platelet count less than 50,000/mm³). Initiate precautions to prevent excessive bleeding (e.g., inspect IV sites, skin, and mucous membranes; use extreme care during invasive procedures; test urine, emesis, stool, and secretions for occult blood). ■ Prophylactic antibiotics may be indicated pending results of C/S in a febrile neutropenic patient. ■ Prophylactic antiemetics may reduce nausea and vomiting and increase patient comfort. ■ See Precautions and Drug/Lab Interactions.

Patient education:

Nonhormonal birth control recommended. ■ Report shortness of breath and IV site burning and stinging promptly. ■ See Appendix D, p. 1333.

Maternal/child:

Avoid pregnancy; may produce teratogenic effects on the fetus. ■ Information on safety in breast-feeding or in pediatric patients not available; discontinue breast-feeding.

Elderly:

Consider diminished hepatic function; monitor for early signs of toxicity.

Combination initial therapy for acute nonlymphocytic leukemia (ANLL) in adults:

Prostate cancer:

12 to 14 mg/M² as a short IV infusion once every 21 days. Used concurrently with steroids.

Multiple sclerosis (MS):

12 mg/M² as an infusion over 5 to 15 minutes. Repeat every 3 months. May be given for up to 2 years or until a cumulative dose of 140 mg/M² has been administered.

Filters:

No data available from manufacturer.

Storage:

Store unopened vial at RT (15° to 25° C [59° to 77° F]). Do not freeze. Diluted solution should be used immediately. After penetration of the stopper on a multidose vial, the undiluted mitoxantrone may be stored at RT for 7 days or refrigerated for up to 14 days. Do not freeze.

Additive:

Y-site:

Allopurinol (Aloprim), amifostine (Ethyol), cladribine (Leustatin), etoposide (VePesid), etoposide phosphate (Etopophos), filgrastim (Neupogen), fludarabine (Fludara), gemcitabine (Gemzar), granisetron (Kytril), linezolid (Zyvox), melphalan (Alkeran), ondansetron (Zofran), oxaliplatin (Eloxatin), sargramostim (Leukine), teniposide (Vumon), thiotepa, vinorelbine (Navelbine).

IV injection:

A single dose of properly diluted medication over at least 3 to 5 minutes. Must be given through Y-tube or three-way stopcock of a free-flowing infusion of D5W or NS.

Intermittent infusion:

A single dose over 15 to 30 minutes.

Infusion:

Sometimes a single dose is given as a continuous infusion over 24 hours. Is combined with cytarabine.

Unlabeled uses:

Treatment of acute lymphocytic leukemia (ALL), breast cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphomas, myelodysplastic syndrome, pediatric acute leukemias, pediatric sarcoma, and part of a conditioning regimen for autologous hematopoietic stem cell transplantation (HSCT).

Monitor:

Obtain baseline CBC with differential and platelet count; repeat before each dose and if S/S of infection occur. ■ Complete a physical exam and ECG and obtain a complete history to assess for S/S of pre-existing cardiac disease. ■ In all patients, obtain an evaluation of left ventricular ejection fraction (LVEF) by echocardiogram or MUGA (multiple-gated acquisition) before therapy begins. ■ Evaluation of LVEF and assessment of cardiotoxicity by history, physical exam, and ECG should be repeated before each dose in MS patients. ■ Obtain repeat LVEF as indicated in all patients. ■ Mitoxantrone should not ordinarily be administered to MS patients who have received a cumulative dose equal to or greater than 140 mg/M² or to patients who experience a drop in LVEF to below the lower limit of normal or a clinically significant reduction in LVEF. MS patients should have an annual quantitative evaluation of LVEF after discontinuing mitoxantrone therapy to monitor for late-occurring cardiotoxicity. ■ Monitoring of liver function is indicated before and during therapy. ■ Because of rapid lysis of cancer cells, initiate hypouricemic therapy with allopurinol or similar agents before beginning treatment. Monitor uric acid levels, maintain hydration, and alkalinize urine if necessary. ■ Observe closely and frequently for all signs of bleeding or infection. ■ Prophylactic antibiotics may be indicated pending results of C/S in a febrile neutropenic patient. ■ Determine absolute patency of vein. Severe local tissue damage may occur with extravasation. Phlebitis at the infusion site has also been reported. Should extravasation or phlebitis occur, discontinue injection and use another vein. ■ Prophylactic antiemetics may reduce nausea and vomiting and increase patient comfort. ■ Monitor for thrombocytopenia (platelet count less than 50,000/mm³). Initiate precautions to prevent excessive bleeding (e.g., inspect IV sites, skin, and mucous membranes; use extreme care during invasive procedures; test urine, emesis, stool, and secretions for occult blood). ■ Monitor for S/S of acute leukemia (secondary leukemia); may include excessive bruising, bleeding, and recurrent infections. ■ See Precautions and Drug/Lab Interactions.

Patient education:

Nonhormonal birth control recommended; see Maternal/Child. ■ Blood and cardiac tests are imperative; keep all appointments. ■ Report IV site burning or stinging promptly. ■ Urine may turn blue-green for 24 hours following administration. Bluish discoloration of sclera may also occur. ■ Medication guide available; read before beginning treatment with mitoxantrone. ■ See Appendix D, p. 1333.

Maternal/child:

Category D: avoid pregnancy. May produce teratogenic effects on the fetus. Women with MS who are biologically capable of becoming pregnant should have a pregnancy test before each dose of mitoxantrone regardless of other methods of birth control used, including birth control pills. ■ Secreted in breast milk. Discontinue breast-feeding. ■ Safety for use in pediatric patients not established.

Elderly:

Specific age-related differences have not been identified; consider age-related organ impairment (e.g., bone marrow reserve, renal, hepatic) and possibility of increased sensitivity.

Post-marketing:

Secondary acute myelogenous leukemia (AML).

IV injection:

Manufacturer recommends an initial dose of 2 to 10 mg/70 kg of body weight. Repeat every 3 to 4 hours as necessary. Doses may range from 2 to 20 mg based on patient requirements and response. Titrate to achieve pain relief with lowest dose. Frequent, repeated doses (e.g., up to every 5 minutes if needed) in small-dose increments (e.g., 1 to 4 mg) may be associated with fewer side effects than the administration of larger, less frequent doses.

Cancer patients suffering with severe chronic pain often require higher doses because of increased tolerance (up to 150 mg/hr has been given). Very high doses (275 to 440 mg/hr) are occasionally used for short periods of time (hours to days) for extreme exacerbations of pain in these drug-tolerant individuals. 1 to 3 mg/kg over 15 to 20 minutes will induce unconsciousness.

Acute MI:

2 to 4 mg initially. May give additional doses of 2 to 8 mg at 5- to 15-minute intervals as needed (AHA guidelines).

Infusion:

1 mg/mL (range is 0.1 to 1 mg/mL) in NS or D5W per controlled infusion device (may be patient activated). Based on a 1 mg/mL dilution, an initial loading dose may be as high as 15 mg (15 mL). The continuous background infusion to provide a level of pain relief and maintain patency of the vein may range from 1 to 2.5 mg/hr (1 to 2.5 mL). Additional doses averaging 0.5 to 1.5 mg (0.5 to 1.5 mL) may be activated by the patient at selected intervals every 3 to 60 minutes (averaging 10 to 15 minutes). Additional boluses averaging 1 to 2 mg (1 to 2 mL) may be given by health care professionals (e.g., every 30 minutes prn). In selected cancer patients all of these doses may be considerably higher.

Open heart surgery:

0.5 to 3 mg/kg as the sole anesthetic or with an anesthetic agent. Cardiovascular function not depressed if oxygen is used and adequate ventilation maintained.

Dyspnea during end-of-life care (unlabeled):

2 to 5 mg IV every 5 to 10 minutes until relief. Patient-controlled anesthesia (PCA) is recommended in the inpatient setting. Higher doses may be needed for patients taking chronic opioids.

Analgesic:

Usual range is 0.05 to 0.1 mg/kg. Administer very slowly.

Postoperative analgesia:

0.01 to 0.04 mg/kg/hr (10 to 40 mcg/kg/hr).

Selected pediatric patients with severe chronic cancer pain:

0.025 to 2.6 mg/kg/hr (average 0.04 to 0.07 mg/kg/hr).

Selected pediatric patients with severe pain during sickle cell crisis:

0.025 to 2.6 mg/kg/hr (average 0.04 to 0.07 mg/kg/hr).

Analgesia/tetralogy (cyanotic) spells (unlabeled):

0.05 to 0.2 mg/kg/dose every 4 hours. Titrate to individual response. Another source suggests an IV injection of 0.05 to 0.1 mg/kg/dose every 4 to 8 hours or an IV infusion of 0.01 to 0.02 mg/kg/hr. Titrate to individual response.

Mechanical ventilation of neonates (unlabeled):

50 mcg/kg as an initial loading dose. Administer over 30 to 60 minutes. Follow with a continuous infusion of 10 to 30 mcg/kg/hr. Titrate to individual response.

Postoperative analgesia (unlabeled):

50 mcg/kg as an initial loading dose. Administer over 30 to 60 minutes. Follow with a continuous infusion of 15 mcg/kg/hr. Titrate to individual response.

IV injection:

May be given undiluted; however, further dilution with 5 mL of SWFI or NS for injection or other IV solutions to facilitate titration is appropriate. May be given through Y-tube or three-way stopcock of infusion set.

Infusion:

Each 0.1 to 1 mg is usually diluted in 1 mL NS or D5W and administered via a controlled infusion device that may be patient activated (e.g., a narcotic syringe infuser system). Available in 60-mL ampules containing 1 to 2 mg/mL for direct transfer to syringe infuser systems. (Astramorph PF and Duramorph are preservative free and expensive; can be used IV, but are the only choice for epidural or intrathecal injection; see drug literature. Duramorph is NOT for use in continuous microinfusion devices. Infumorph is NOT for IV use.) Fluid restriction or high doses may require more concentrated solutions. Concentrations above 5 mg/mL are rarely exceeded. Available in vials containing 25 mg/mL, which must be further diluted before infusion. Also available in ADD-Vantage vials for use with ADD-Vantage infusion containers. Is sometimes added to larger amounts (500 mL to 1 L) of IV solution in selected situations and infused via a large volume-controlled infusion pump (requires close titration).

Storage:

Store at CRT. Protect from light and freezing.

Additive:

Alteplase (tPA, Activase), atracurium (Tracrium), dobutamine, fluconazole (Diflucan), furosemide (Lasix), ketamine (Ketalar), meropenem (Merrem IV), metoclopramide (Reglan), ondansetron (Zofran), succinylcholine, verapamil.

Y-site:

Acetaminophen (Ofirmev), acyclovir (Zovirax), allopurinol (Aloprim), amifostine (Ethyol), amikacin, aminophylline, amiodarone (Nexterone), ampicillin, ampicillin/sulbactam (Unasyn), anidulafungin (Eraxis), argatroban, atracurium (Tracrium), atropine, aztreonam (Azactam), bivalirudin (Angiomax), bumetanide, calcium chloride, caspofungin (Cancidas), cefazolin (Ancef), cefepime (Maxipime), cefotaxime (Claforan), cefotetan, cefoxitin (Mefoxin), ceftaroline (Teflaro), ceftazidime (Fortaz), ceftriaxone (Rocephin), cefuroxime (Zinacef), chloramphenicol (Chloromycetin), cisatracurium (Nimbex), cladribine (Leustatin), clindamycin (Cleocin), dexamethasone (Decadron), dexmedetomidine (Precedex), diazepam (Valium), digoxin (Lanoxin), diltiazem (Cardizem), diphenhydramine (Benadryl), dobutamine, docetaxel (Taxotere), dopamine, doripenem (Doribax), doxycycline, enalaprilat (Vasotec IV), epinephrine (Adrenalin), erythromycin (Erythrocin), esmolol (Brevibloc), etomidate (Amidate), etoposide phosphate (Etopophos), famotidine (Pepcid IV), fenoldopam (Corlopam), fentanyl, filgrastim (Neupogen), fluconazole (Diflucan), fludarabine (Fludara), foscarnet (Foscavir), furosemide (Lasix), gemcitabine (Gemzar), gentamicin, granisetron (Kytril), heparin, hetastarch in electrolytes (Hextend), hydrocortisone sodium succinate (Solu-Cortef), hydromorphone (Dilaudid), 6% hydroxyethyl starch (Voluven), insulin (regular), ketorolac (Toradol), labetalol, levofloxacin (Levaquin), lidocaine, linezolid (Zyvox), lorazepam (Ativan), magnesium sulfate, melphalan (Alkeran), meropenem (Merrem IV), methyldopate, methylprednisolone (Solu-Medrol), metoclopramide (Reglan), metoprolol (Lopressor), metronidazole (Flagyl IV), midazolam (Versed), milrinone (Primacor), nafcillin (Nallpen), nicardipine (Cardene IV), nitroglycerin IV, nitroprusside sodium, norepinephrine (Levophed), ondansetron (Zofran), oxacillin (Bactocill), oxaliplatin (Eloxatin), oxytocin (Pitocin), paclitaxel (Taxol), palonosetron (Aloxi), pancuronium, pantoprazole (Protonix IV), pemetrexed (Alimta), penicillin G potassium, phenobarbital (Luminal), piperacillin/tazobactam (Zosyn), potassium chloride (KCl), propofol (Diprivan), propranolol, ranitidine (Zantac), remifentanil (Ultiva), sodium bicarbonate, sulfamethoxazole/trimethoprim, tacrolimus (Prograf), teniposide (Vumon), thiotepa, ticarcillin/clavulanate (Timentin), tirofiban (Aggrastat), tobramycin, vancomycin, vecuronium, vinorelbine (Navelbine), warfarin (Coumadin), zidovudine (AZT, Retrovir).

IV injection:

15 mg or fraction thereof over 4 to 5 minutes.

Infusion:

Initial loading dose, basal rate (continuous rate of infusion), patient selfadministered dose and interval, additional boluses permitted, and total dose for 1 hour should be ordered by physician. Administer initial dose and boluses at rate for IV injection. For continuous infusion and self-administered dose and interval, note range of mL/hr under Usual Dose.

Unlabeled uses:

Treatment of dyspnea in end-of-life care. ■ Control of pain during mechanical ventilation in neonates. ■ Control of postoperative pain in neonates.

Monitor:

Oxygen, controlled respiratory equipment, and naloxone must always be available. ■ Observe patient frequently to continuously based on amount of dose and monitor vital signs. ■ Assess baseline pain, then assess pain with vital signs and/or more frequently if needed. Reassess after administration of morphine and adjust dose or interval as required. ■ Keep patient supine; orthostatic hypotension and fainting may occur; less likely with continuous low doses, but observe closely during ambulation. ■ Uncontrolled pain causes sleep deprivation, decreases pain threshold, and increases pain. When pain is finally controlled, expect the patient to sleep more until recovery from sleep deprivation. ■ Adhere to prescribed bowel care regimen to avoid constipation and/or impaction. Maintain adequate hydration. ■ See Drug/Lab Interactions.

Patient education:

Avoid alcohol or other CNS depressants (e.g., barbiturates, benzodiazepines [e.g., diazepam (Valium)]). ■ May cause blurred vision, dizziness, or drowsiness; use caution in tasks that require alertness. ■ Request assistance with ambulation. ■ May be habit forming.

Maternal/child:

Category C: safety for use in pregnancy or breast-feeding not established. Benefits must outweigh risks. ■ May reduce strength, duration, and frequency of uterine contractions during labor and delivery. ■ See Contraindications. ■ Pediatric patients may be more sensitive to effects, especially respiratory depressant effects. ■ May cause paradoxical excitation. ■ May cause respiratory depression in the neonate when given during labor and delivery. Have naloxone and resuscitative equipment available. ■ Infants born to mothers who have been taking morphine chronically may exhibit withdrawal symptoms.

Elderly:

See Dose Adjustments and Precautions. ■ May be more sensitive to effects (e.g., respiratory depression, constipation, urinary retention). ■ Lower doses may provide effective analgesia. ■ Consider age-related organ impairment.

Average dose:

Anxiety, bradycardia, confusion, constipation, decreased libido in men and women, delayed absorption of oral medications, depression of cough reflex, dizziness, drowsiness/sedation, euphoria, histamine-related reactions (e.g., local tissue irritation, pruritus, urticaria, wheals), hypersensitivity reactions, hypothermia, increased intracranial pressure, interference with thermal regulation, menstrual irregularities (including amenorrhea), nausea, neonatal apnea, oliguria, orthostatic hypotension, physical or psychological dependence, reduced male potency, respiratory depression (slight), skeletal muscle rigidity, tremors, urinary retention, vomiting. Side effects associated with histamine and constipation may be more common with morphine than with most other narcotic analgesics.

Higher doses:

CNS excitation (convulsions), respiratory depression (severe).

Overdose:

Anaphylaxis, cardiac arrest, Cheyne-Stokes respiration, circulatory collapse, coma, excitation, hypotension (severe), inverted T-wave on ECG, myocardial depression (severe), pinpoint pupils, respiratory depression or arrest, tachycardia, death.