Lomustine

Common side effects of lomustine include the following:

• nausea
• vomiting
• loss of appetite
• sores in the mouth and throat
• unusual tiredness or weakness
• pale skin
• fainting
• hair loss
• unsteady walk
• slurred speech

This is not a complete list of lomustine side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of lomustine, there are no specific foods that you must exclude from your diet when receiving this medication.

Usual Adult Dose for Brain/Intracranial Tumor:

As a single agent in previously untreated patients:
-130 mg/m2 orally as a single dose every 6 weeks

As a single agent in patients with compromised bone marrow function:
-100 mg/m2 orally as a single dose every 6 weeks

Comments:
-The dose should be adjusted accordingly when this drug is used in combination with other myelosuppressive drugs.
-All doses of this drug should be rounded to the nearest 10 mg by the prescriber.
-Only a single dose of this drug should be dispensed.

Uses:
As a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following:
-BRAIN TUMORS: both primary and metastatic tumors; in patients who have already received appropriate surgical and/or radiotherapeutic procedures.
-HODGKIN'S DISEASE: secondary therapy in combination with other approved drugs; in patients who relapse while being treated with primary therapy or who fail to respond to primary therapy.

Usual Adult Dose for Hodgkin's Disease:

As a single agent in previously untreated patients:
-130 mg/m2 orally as a single dose every 6 weeks

As a single agent in patients with compromised bone marrow function:
-100 mg/m2 orally as a single dose every 6 weeks

Comments:
-The dose should be adjusted accordingly when this drug is used in combination with other myelosuppressive drugs.
-All doses of this drug should be rounded to the nearest 10 mg by the prescriber.
-Only a single dose of this drug should be dispensed.

Uses:
As a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following:
-BRAIN TUMORS: both primary and metastatic tumors; in patients who have already received appropriate surgical and/or radiotherapeutic procedures.
-HODGKIN'S DISEASE: secondary therapy in combination with other approved drugs; in patients who relapse while being treated with primary therapy or who fail to respond to primary therapy.

Usual Pediatric Dose for Brain/Intracranial Tumor:

As a single agent in previously untreated patients:
-130 mg/m2 orally as a single dose every 6 weeks

As a single agent in patients with compromised bone marrow function:
-100 mg/m2 orally as a single dose every 6 weeks

Comments:
-The dose should be adjusted accordingly when this drug is used in combination with other myelosuppressive drugs.
-All doses of this drug should be rounded to the nearest 10 mg by the prescriber.
-Only a single dose of this drug should be dispensed.

Uses:
As a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following:
-BRAIN TUMORS: both primary and metastatic tumors; in patients who have already received appropriate surgical and/or radiotherapeutic procedures.
-HODGKIN'S DISEASE: secondary therapy in combination with other approved drugs; in patients who relapse while being treated with primary therapy or who fail to respond to primary therapy.

Usual Pediatric Dose for Hodgkin's Disease:

As a single agent in previously untreated patients:
-130 mg/m2 orally as a single dose every 6 weeks

As a single agent in patients with compromised bone marrow function:
-100 mg/m2 orally as a single dose every 6 weeks

Comments:
-The dose should be adjusted accordingly when this drug is used in combination with other myelosuppressive drugs.
-All doses of this drug should be rounded to the nearest 10 mg by the prescriber.
-Only a single dose of this drug should be dispensed.

Uses:
As a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following:
-BRAIN TUMORS: both primary and metastatic tumors; in patients who have already received appropriate surgical and/or radiotherapeutic procedures.
-HODGKIN'S DISEASE: secondary therapy in combination with other approved drugs; in patients who relapse while being treated with primary therapy or who fail to respond to primary therapy.

Other drugs may interact with lomustine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

• Alkylates DNA and RNA.a May inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.a Overall result is thought to be the inhibition of both DNA and RNA synthesis.b

• Risk of myelosuppression or pulmonary toxicity.a Importance of adherence to laboratory appointment schedules.a Notify clinician if fever, sore throat, or unusual bleeding or bruising occurs.a

• Importance of understanding there may be 2 or more different types and colors of capsules in the dispensed container.a

• Importance of understanding lomustine is administered as a single oral dose and will not be repeated for at least 6 weeks.a

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.a

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Importance of women avoiding pregnancy during therapy.a Advise pregnant women of risk to the fetus.a

• Importance of informing patients of other important precautionary information.a (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In the U.S.

• Ceenu
• Gleostine

Available Dosage Forms:

• Capsule

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Alkylating Agent

Chemical Class: Nitrosourea

Lomustine is used alone or in combination with other medicines to treat brain tumors, Hodgkin's disease, and other kinds of cancer. lomustine belongs to the group of medicines known as alkylating agents.

Lomustine interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by lomustine, other effects may occur. Some of these may be serious and must be reported to your doctor. Other effects (e.g., hair loss) may not be serious, but may cause concern. Some effects may not occur for months or years after the medicine is used.

Before you begin treatment with lomustine, you and your doctor should talk about the good lomustine will do as well as the risks of using it.

lomustine is available only with your doctor's prescription.

Along with their needed effects, medicines like lomustine can sometimes cause unwanted effects such as blood problems, loss of hair, and other side effects; these are described below. Also, because of the way these medicines act on the body, there is a chance that they might cause other unwanted effects that may not occur until months or years after the medicine is used. These delayed effects may include certain types of cancer, such as leukemia. Discuss these possible effects with your doctor.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bleeding gums
• chest pain
• shortness of breath
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness

• Awkwardness
• black, tarry stools
• blood in the urine or stools
• confusion
• cough or hoarseness
• decrease in urination
• fever or chills
• lower back or side pain
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• slurred speech
• swelling of the feet or lower legs
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness

• Abdominal or stomach pain or tenderness
• bone pain
• change in frequency of urination or amount of urine
• clay colored stools
• dark urine
• decreased appetite
• dizziness
• drowsiness
• dry mouth
• headache
• increased blood pressure
• increased thirst
• itching
• loss of appetite
• nausea or vomiting
• skin rash
• weight gain
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Darkening of the skin
• diarrhea

• Blurred vision
• changes in patterns and rhythms of speech
• confusion about identity, place, and time
• decreased vision
• eye pain
• hair loss or thinning of the hair
• shakiness and unsteady walk
• swelling or inflammation of the mouth
• trouble with speaking
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• It is used to treat a type of brain tumor.
• It is used to treat a type of lymphoma.
• It may be given to you for other reasons. Talk with the doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Lomustine (CCNU) is one of the nitrosoureas used in the treatment of certain neoplastic diseases. It is 1-(2-chloro-ethyl)-3-cyclohexyl-1-nitrosourea. It is a yellow powder with the empirical formula of C9H16ClN3O2 and a molecular weight of 233.71. Lomustine is soluble in 10% ethanol (0.05 mg per mL) and in absolute alcohol (70 mg per mL). Lomustine is relatively insoluble in water (<0.05 mg per mL).

It is relatively un-ionized at a physiological pH.

Inactive ingredients in Lomustine Capsules are magnesium stearate and mannitol.

The structural formula is:

Lomustine is available in 10 mg, 40 mg, and 100 mg capsules for oral administration.

Lomustine Capsules are available in individual bottles of 5 capsules each.

Stability

Lomustine Capsules are stable for the lot life indicated on package labeling when stored in well-closed containers at 25°C (77°F); excursions permitted to 15°C–30°C (59°F–86°F) [see USP Controlled Room Temperature]. Avoid excessive heat (over 40°C, 104°F).

Directions to the Pharmacist

Confirm the total dose prescribed by the physician can be obtained by determining the appropriate combination of capsule strengths. Only the appropriate number of Lomustine capsules required for the administration of a single dose should be dispensed.

In order to provide the proper dose of Lomustine, patients should be aware that the prescribed dose may be made up of 2 or more different strengths and colors of capsules and that each strength must be dispensed separately. Inform patients that Lomustine is taken as a single oral dose and will not be repeated for at least 6 weeks. Daily use of the recommended dose may lead to toxicities and fatal outcomes.

Caution should be exercised when handling Lomustine Capsules. Procedures for proper handling and disposal of anticancer drugs should be utilized. Several guidelines on this subject have been published.1-4 To minimize the risk of dermal exposure, always wear impervious gloves when handling bottles containing Lomustine Capsules. Lomustine Capsules should not be broken. Personnel should avoid exposure to broken capsules. If contact occurs, wash immediately and thoroughly. More information is available in the references listed below.

• Antineoplastic Agent, Alkylating Agent
• Antineoplastic Agent, Alkylating Agent (Nitrosourea)

Note: Dispense only enough capsules for a single dose; do not dispense more than one dose at a time (ISMP 2014). Repeat courses should only be administered after adequate recovery of leukocytes to >4,000/mm3 and platelets to >100,000/mm3. Doses should be rounded to the nearest 5 mg. Lomustine is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting.

Brain tumors: Manufacturer’s labeling: Oral: 130 mg/m2 as a single dose once every 6 weeks; reduce dose to 100 mg/m2 as a single dose once every 6 weeks in patients with compromised bone marrow function (dosage reductions may be recommended for combination chemotherapy regimens).

Anaplastic oligodendroglioma: PCV regimen (off-label combination): Oral: 130 mg/m2 on day 1 every 6 weeks for up to 4 cycles prior to radiation therapy (in combination with procarbazine and vincristine) (Cairncross 2013; Cairncross 2006).

Astrocytoma, high grade: POC regimen (off-label dosing): Adults ≤21 years: Oral: 100 mg/m2 on day 1 every 6 weeks for 8 cycles (in combination with vincristine and prednisone) (Finlay 1995).

Glioblastoma, recurrent:

PCV regimen (off-label dosing): Oral: 110 mg/m2 on day 1 every 6 weeks for 7 cycles (in combination with procarbazine and vincristine) (Levin 2000).

Single-agent therapy: Oral: 100 to 130 mg/m2 every 6 weeks until disease progression or unacceptable toxicity (Wick 2010).

Medulloblastoma (off-label dosing): Adults ≤21 years: Oral: 75 mg/m2 once every 6 weeks for 8 cycles (in combination with cisplatin and vincristine) (Packer 2006; Packer 1999).

Hodgkin lymphoma: Manufacturer’s labeling: Oral: 130 mg/m2 as a single dose once every 6 weeks; reduce dose to 100 mg/m2 as a single dose once every 6 weeks in patients with compromised bone marrow function (dosage reductions may be recommended for combination chemotherapy regimens). Note: The use of lomustine in the management of Hodgkin lymphoma is limited due to efficacy of other chemotherapy agents/regimens.

Note: Dispense only enough capsules for a single dose; do not dispense more than one dose at a time (ISMP 2014). Repeat courses should only be administered after adequate recovery of leukocytes to >4,000/mm3 and platelets to >100,000/mm3. Doses should be rounded to the nearest 5 mg. Lomustine is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011).

Brain tumors: Manufacturer’s labeling: Oral: 130 mg/m2 as a single dose once every 6 weeks; reduce dose to 100 mg/m2 as a single dose once every 6 weeks in patients with compromised bone marrow function (dosage reductions may be recommended for combination chemotherapy regimens)

Astrocytoma, high grade: POC regimen (off-label dosing): Children ≥18 months and Adolescents: Oral: 100 mg/m2 on day 1 every 6 weeks for 8 cycles (in combination with vincristine and prednisone) (Finlay 1995)

Medulloblastoma (off-label dosing): Children ≥3 years and Adolescents: Oral: 75 mg/m2 once every 6 weeks for 8 cycles (in combination with cisplatin and vincristine) (Packer 2006; Packer 1999)

Hodgkin lymphoma: Manufacturer’s labeling: Oral: 130 mg/m2 as a single dose once every 6 weeks; reduce dose to 100 mg/m2 as a single dose once every 6 weeks in patients with compromised bone marrow function (dosage reductions may be recommended for combination chemotherapy regimens). Note: The use of lomustine in the management of Hodgkin lymphoma is limited due to efficacy of other chemotherapy agents/regimens.

Store at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Avoid temperatures over 40°C (104°F).

As a single agent in previously untreated patients:
-130 mg/m2 orally as a single dose every 6 weeks

As a single agent in patients with compromised bone marrow function:
-100 mg/m2 orally as a single dose every 6 weeks

Comments:
-The dose should be adjusted accordingly when this drug is used in combination with other myelosuppressive drugs.
-All doses of this drug should be rounded to the nearest 10 mg by the prescriber.
-Only a single dose of this drug should be dispensed.

Uses:
As a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following:
-BRAIN TUMORS: both primary and metastatic tumors; in patients who have already received appropriate surgical and/or radiotherapeutic procedures.
-HODGKIN'S DISEASE: secondary therapy in combination with other approved drugs; in patients who relapse while being treated with primary therapy or who fail to respond to primary therapy.

Dose adjustments may be required; however, no specific guidelines have been provided in the manufacturer product information.

Administration Advice:
-Administering of this drug on an empty stomach may reduce the incidence of nausea and vomiting.
-Rubber or latex gloves should be worn when handling containers and capsules of this drug.
-Areas that come into contact with broken capsules should be washed immediately and thoroughly with soap and water.
-Handling and disposal of this drug should be performed in a manner consistent with safe procedures for cytotoxic agents.

Storage Requirements:
-Store below 25C/77F; avoid excessive heat (over 40C/104F).
-Store in the original container to protect from light and moisture.

General:
-In order to provide the proper dose of this drug, the prescribed dose may be made up of 2 or more different strengths and colors of capsules; only the appropriate number of drug capsules required for a single dose should be dispensed and different capsule strengths should be dispensed separately.
-Cross resistance with other nitrosoureas is usual (cross resistance between this drug and carmustine has occurred), but cross resistance with conventional alkylating agents is unusual.
-Overdosage: Accidental overdose has been associated with bone marrow suppression, abdominal pain, diarrhea, vomiting, anorexia, lethargy, dizziness, abnormal hepatic function, cough, and shortness of breath. No proven antidotes have been established; treat overdosage immediately with gastric lavage and appropriate supportive measures.

Monitoring:
-Hematological: Blood counts (prior to treatment, then weekly for 6 weeks after a dose)
-Hepatic: Liver function tests (periodically)
-Renal: Kidney function tests (periodically)
-Respiratory: Pulmonary function tests (prior to and frequently during treatment)