CCNSB Capsules

Name: CCNSB Capsules

Description

CCNSBTM (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. CCNSB is soluble in 10% ethanol (0.05 mg per mL) and in absolute alcohol (70 mg per mL). CCNSB is relatively insoluble in water (<0.05 mg per mL).

It is relatively un-ionized at a physiological pH.

Inactive ingredients in CCNSB Capsules are magnesium stearate and mannitol.

The structural formula is:

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

Precautions

General

In all instances where the use of CCNSB is considered for chemotherapy, the physician must evaluate the need and usefulness of the drug against the risks of toxic effects or adverse reactions. Most such adverse reactions are reversible if detected early. When such effects or reactions do occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken according to the clinical judgment of the physician. Reinstitution of CCNSB therapy should be carried out with caution and with adequate consideration of the further need for the drug and alertness as to possible recurrence of toxicity.

Information for Patients

Provide patients with the following information and instructions:

  1. In order to provide the proper dose of CCNSB, the dose may be made up of 2 or more different strengths and colors of capsules. Each strength must be dispensed separately by the pharmacist.
  2. CCNSB is given 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.
  3. Patients may experience nausea and vomiting that usually last less than 24 hours. Patients may also experience loss of appetite that may last for several days.
  4. Instruct patients to contact their physician if they develop any of the following reactions: fever, chills, sore throat, unusual bleeding or bruising, shortness of breath, dry cough, swelling of feet or lower legs, mental confusion, or yellowing of eyes and skin.
  5. Instruct patients to wear impervious (rubber or latex) gloves when handling CCNSB Capsules.

Laboratory Tests

Due to delayed bone marrow suppression, blood counts should be monitored weekly for at least 6 weeks after a dose.

Baseline pulmonary function studies should be conducted along with frequent pulmonary function tests during treatment. Patients with a baseline below 70% of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLCO) are particularly at risk.

Since CCNSB may cause liver dysfunction, it is recommended that liver function tests be monitored periodically.

Renal function tests should also be monitored periodically.

Carcinogenesis, Mutagenesis, Impairment of Fertility

CCNSB is carcinogenic in rats and mice, producing a marked increase in tumor incidence in doses approximating those employed clinically. Nitrosourea therapy does have carcinogenic potential in humans (see ADVERSE REACTIONS). CCNSB also affects fertility in male rats at doses somewhat higher than the human dose.

Pregnancy

Pregnancy Category D

See WARNINGS.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from CCNSB, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

See ADVERSE REACTIONS: Pulmonary Toxicity and DOSAGE AND ADMINISTRATION.

Geriatric Use

No data from clinical studies of CCNSB are available for patients 65 years of age and over to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Lomustine and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored.

Overdosage

Accidental overdose with lomustine has been reported, including fatal cases. 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 for CCNSB overdosage. In case of overdose, appropriate supportive measures should be taken.

Dosage and administration

The recommended dose of CCNSB in adult and pediatric patients as a single agent in previously untreated patients is 130 mg/m2 as a single oral dose every 6 weeks (see PRECAUTIONS: Information for Patients and HOW SUPPLIED: Directions to the Pharmacist). In individuals with compromised bone marrow function, the dose should be reduced to 100 mg/m2 every 6 weeks. When CCNSB is used in combination with other myelosuppressive drugs, the doses should be adjusted accordingly. All doses of CCNSB must be rounded to the nearest 10 mg by the prescriber (see HOW SUPPLIED).

Doses subsequent to the initial dose should be adjusted according to the hematologic response of the patient to the preceding dose. The following schedule is suggested as a guide to dosage adjustment:

Nadir After Prior Dose Percentage of Prior Dose
to be Given
Leukocytes (/mm3) Platelets (/mm3)
≥4000 ≥100,000 100%
3000–3999 75,000–99,999 100%
2000–2999 25,000–74,999 70%
<2000 <25,000 50%

A repeat course of CCNSB should not be given until circulating blood elements have returned to acceptable levels (platelets above 100,000/mm3; leukocytes above 4000/mm3), and this is usually in 6 weeks. Adequate number of neutrophils should be present on a peripheral blood smear. Blood counts should be monitored weekly and repeat courses should not be given before 6 weeks because the hematologic toxicity is delayed and cumulative.

Principal Display Panel - 10 mg Bottle Label

NDC 58181-3030-5 5 CAPSULES

NEXTSOURCE

Biotechnology

CCNSB™

(lomustine) Capsules Rx only

10 mg per capsule

Caution: DO NOT DISPENSE ENTIRE

CONTAINER.

Dispense only enough capsules for one dose.

Lomustine Pregnancy Warnings

Animal studies have revealed evidence of embryotoxicity and teratogenicity at dose levels equivalent to the human dose; and fertility impairment in males at doses somewhat higher than the human dose. This drug should be regarded as a potential mutagen. There are no controlled data in human pregnancy. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

UK: Use of this drug is contraindicated in pregnant patients. US: Use should be avoided during pregnancy as this drug can cause fetal harm based on animal studies. AU: Use should be avoided during pregnancy unless the expected benefit outweighs any potential risk. AU TGA pregnancy category: D US FDA pregnancy category: D Comments: -Female patients of childbearing potential should be advised to avoid becoming pregnant while taking this drug, and should be apprised of the potential hazard to the fetus if pregnancy occurs during treatment. -All patients should be advised to use effective contraception during treatment and for 6 months after therapy. (UK) -Male patients should be informed about the possibility of irreversible infertility caused by this drug; advised not to father children during treatment and for 6 months after treatment cessation; and to seek advice regarding sperm conservation prior to treatment initiation. (UK)

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