lomustine

LOMUSTINE

Complete information including dosage, side effects, interactions and pregnancy & breast feeding warnings for patient and professional use.

Overview and uses

Lomustine is an alkylating agent belonging to Nitrosoureas used for the treatment of cancer. Nitrosoureas are highly lipid soluble compounds with a wide range of anti-tumor activity.

Indication (uses)

  • Brain Tumors

Lomustine is indicated for the treatment of patients with primary and metastatic brain tumors following appropriate surgical and/or radiotherapeutic procedures.

  • Hodgkin’s Lymphoma

Lomustine is indicated as a component of combination chemotherapy for the treatment of patients with Hodgkin’s lymphoma whose disease has progressed following initial chemotherapy.

Pharmacological classification

Alkylating agent (Nitrosoureas) used for the treatment of cancer.

Brand names

CeeNU, Gleostine

Dosage form

  • Gleostine capsules are available in four strengths, distinguishable by the color of the capsules:
    • 100 mg capsules (green/green)
    • 40 mg capsules (white/green)
    • 10 mg capsules (white/white)
    • 5 mg capsules (yellow/yellow)

Mechanism of action

Lomustine alkylates DNA and RNA. It may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.

Dosage

Dispense only one dose for each treatment cycle. Do not dispense the entire container.

Recommended dose

Recommended dose for Lomustine in adult and pediatric patients is 130 mg/m2 of the body surface area, taken as a single oral dose taken every 6 weeks.

  • Doses should be rounded to nearest 5 mg.
  • Lomustine should be given as a single oral dose and should not be repeated for at least 6 weeks.
  • In patients with compromised bone marrow function, the dose should be reduced to 100 mg/m2 of the body surface area, every 6 weeks.
  • Reduce the dose of Lomustine accordingly when used with other myelosuppressive agents.

Dose modifications

  • Perform weekly complete blood counts and withhold each subsequent dose for more than 6 weeks if needed until platelet counts recover to 100,000/mm3 or greater and leukocytes recover to 4000/mm3 or greater
    • Leukocytes (/mm3) ≥ 4000 & Platelets (/mm3) ≥ 100,000
      • No dose adjustment required.
    • Leukocytes (/mm3) 3000 – 3999 & Platelets (/mm3) 75,000 – 99,999
      • No dose adjustment required.
    • Leukocytes (/mm3) 2000 – 2999 & Platelets (/mm3) 25,000 – 74,999
      • Reduce the dose of Lomustine by 70%.
    • Leukocytes (/mm3) < 2000 & Platelets (/mm3) < 25,000
      • Reduce the dose of Lomustine by 50%.

Renal dose adjustments

  • Data not available. Dose adjustments may be required.

Hepatic dose adjustments

  • Data not available. Dose adjustments may be required.

Geriatric dose adjustments

  • Data not available. Dose adjustments may be required.

Pediatric use

  • Data not available. Dose adjustments may be required.

Overdosage

  • No specific antidote is known.
  • Symptoms of Overdosage includes
    • Severe Myelosuppression.
    • Abdominal pain
    • Diarrhea
    • Vomitting
    • Anorexia
    • Lethargy
    • Dizziness
    • Abnormal hepatic function.
    • Cough
    • Shortness of breath.
  • Treatment of overdosage involves
    • General supportive measures.

Side effects or adverse effects

  • Delayed Myelosuppression
    • Lomustine causes myelosuppression that can result in fatal infections and bleeding.
    • Myelosuppression from Lomustine is delayed, dose-related, and cumulative. It usually occurs 4 to 6 weeks after drug administration and persists for 1 to 2 weeks.
    • Thrombocytopenia is generally more severe than leukopenia.
    • Cumulative myelosuppression from Lomustine is manifested by greater severity and longer duration of cytopenias.
    • Monitor blood counts for at least 6 weeks after each dose. Do not give Lomustine more frequently than every 6 weeks. Adjust dose based on nadir blood counts from prior dose.
  • Pulmonary toxicity
    • Pulmonary toxicity characterized by pulmonary infiltrates and/or fibrosis occurs with Lomustine.
    • Patients with a baseline below 70% of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLCO) are at increased risk.
    • The onset of pulmonary toxicity occurs after an interval of 6 months or longer from the start of therapy, with cumulative doses of Lomustine usually greater than 1100 mg/m2.
    • Obtain baseline pulmonary function tests prior to initiating treatment and repeat frequently during treatment.
    • Permanently discontinue Lomustine in patients diagnosed with pulmonary fibrosis.
  • Secondary malignancies
    • Acute leukemia is associated with long term use.
    • Myelodysplasia is associated with long term use.
  • Hepatotoxicity
    • Hepatic toxicity, manifested by increased levels of transaminases, alkaline phosphatase, and bilirubin occurs with Lomustine.
    • Monitor liver function.
  • Bone marrow depression
    • Bone marrow depression is the most serious side effect/toxicity. It is also a limiting factor for the dose. Infections and bleeding are the common complications.
    • Bone marrow depression results in granulocytopenia, agranulocytosis, thrombocytopenia and aplastic anemia.
    • Consult your doctor as soon as possible if you observe any of the below-mentioned symptoms:
      • Sore throat
      • Chills
      • Sudden fever
      • Weakness in limbs
      • Mouth ulcers
      • Bleeding gums
      • Sore mouth
      • Fast heart rate
      • Low blood pressure
      • Sore gums
      • Skin abscesses
      • Rapid breathing
      • Rapid progression of infection of any organ
      • Rapid progression of Septicemia
    • Gastrointestinal side effects
      • Nausea and vomiting are commonly observed with anticancer medicines.
      • Mucositis – painful inflammation and ulceration of mucus membrane lining the digestive tract.
      • Diarrhea, shredding of mucosa and hemorrhage due to decreased rate of renewal of gastrointestinal mucosa lining.
    • Skin
      • Alopecia or hair loss.
      • Dermatitis
    • Oral side effects
      • Breaches during chewing.
      • Depression of immunity due to a reduction in the number of WBCs largely increases the risk of oral infections.
      • Bleeding gums
      • Rapid progression of dental caries.
    • Gonadal side effects
      • Infertility due to Oligozoospermia in males.
      • Impotence in males.
      • Loss or reduces sex drive.
      • Inhibition of ovulation in females
      • Amenorrhea in females.
      • Damage to germinal cells may lead to mutagenesis.
    • Lymphoreticular tissue
      • Lymphocytopenia (reduced number of lymphocytes)
      • Inhibition of lymphocyte function.
      • Suppression of immunity due to bone marrow depression and reduced lymphocyte function highly increases the risk of opportunistic infections like:
        • Candida and other infections causing deep mycosis.
        • Cytomegalo virus
        • Herpes zoster
        • Pneumocystis jiroveci
        • Toxoplasma
      • Fetal side effects
        • Use of anti-cancer medicines in pregnant women may cause fetal damage leading to:
          • Fetal death
          • Abortion
          • Teratogenesis
        • Renal side effects
          • Progressive renal failure with a decrease in kidney size occurs with Lomustine.
          • Monitor renal function.
        • Hyperuricemia
          • An elevated level of uric acid is common in leukemia and bulky lymphomas.
        • Please note: The side effects mentioned above are from the reported cases. However, side effects are not limited to above-mentioned conditions and symptoms. Consult your doctor as soon as possible if you feel or observe any symptoms that you relate to your treatment.

Warnings & Precautions

  • Lomustine can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 2 weeks after the final dose.

Contraindications

  • None.

Pregnancy & breast feeding warnings

  • Pregnancy
    • Category D, which means 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.
  • Nursing
    • It is not known whether Lomustine is excreted in human breast milk or not.
    • Since many drugs are excreted in milk and because of the potential for side effects in nursing infants, a decision should be made whether to discontinue drug or to discontinue nursing.

Interactions

Drug – drug interactions

  • Concomitant use of Lomustine with following drugs/medicines should be strictly avoided.
    • Leflunomide as it increases the risk of infections.
    • Adalimumab as it increases the risk of infections.
    • Teriflunomide as it increases the risk of infections.
    • Certolizumab as it increases the risk of infections.
    • Clozapine as it may lower the WBC count.
    • Cimetidine may increase the suppressive effect of Lomustine on bone marrow function.
    • Tofacitinib as it increases the risk of infections.
    • Deferiprone as it may lower the WBC count.
    • Etanercept as it increases the risk of infections.
    • Fingolimod as it increases the risk of infections.
    • Golimumab as it increases the risk of infections.
    • Infliximab as it increases the risk of infections.
    • Thalidomide may increase the risk of dangerous blood clots.
    • Lomitapide may cause liver problems and concomitant use with Lomustine may increase that risk.
    • Mipomersen may cause liver problems and concomitant use with Lomustine may increase that risk.
    • Nalidixic acid as the combination may cause unusual bruising or bleeding, nausea, stomach pain, unusual weakness, low fever and loss of appetite.
    • Natalizumab as it increases the risk of infections.
    • Thiotepa may increase the blood levels of Lomustine.
    • Brentuximab may cause liver problems and concomitant use with Lomustine may increase that risk.
    • Doxorubicin may increase the side effects of Lomustine, especially on bone marrow function.
    • Aldesleukin may increase the side effects of Lomustine, especially on bone marrow function.
    • Alefacept as it increases the risk of infections.
    • Alemtuzumab as it increases the risk of infections.
    • Azathioprine as it increases the risk of infections.
    • Bedaquiline may cause liver problems and concomitant use with Lomustine may increase that risk.
    • Bendamustine may increase the side effects of Lomustine, especially on bone marrow function.
    • Carmustine may increase the side effects of Lomustine, especially on bone marrow function.
    • Busulfan may increase the side effects of Lomustine, especially on bone marrow function.
    • Naltrexone may cause liver problems and concomitant use with Lomustine may increase that risk.
    • Bleomycin may increase the side effects of Lomustine, especially on bone marrow function.
    • Canakinumab as it increases the risk of infections.
    • Cisplatin may increase the side effects of Lomustine, especially on bone marrow function.
    • Cladribine as it increases the risk of infections.
    • Capecitabine may increase the side effects of Lomustine, especially on bone marrow function.
    • Carboplatin may increase the side effects of Lomustine, especially on bone marrow function.
    • Daunorubicin may increase the side effects of Lomustine, especially on bone marrow function.
    • Cyclophosphamide may increase the side effects of Lomustine, especially on bone marrow function.
    • Ganciclovir may increase the side effects of Lomustine, especially on bone marrow function.
    • Dacarbazine may increase the side effects of Lomustine, especially on bone marrow function.
    • Decitabine may increase the side effects of Lomustine, especially on bone marrow function.
    • Dactinomycin may increase the side effects of Lomustine, especially on bone marrow function.
    • Roflumilast as it increases the risk of infections.

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Reference

By |2017-12-20T13:13:38+00:00August 10th, 2017|medicines|0 Comments

About the Author:

B. Pharm (K.L.E. society's S.V.V. Patil College of Pharmacy, Bengaluru) M. Pharm (Maharishi Arvind Institute of Pharmacy, Jaipur)

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