Busulfan (Tablets, Concentrate) Instructions for Use

ATC Code

L01AB01 (Busulfan)

Active Substance

Busulfan (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antitumor drug. Alkylating compound

Pharmacotherapeutic Group

Antineoplastic agents; alkylating compounds; alkyl sulfonates

Pharmacological Action

Antitumor agent with alkylating action. It has a cytostatic effect on myeloid cells. In relatively low doses, it selectively inhibits granulocytopoiesis.

Pharmacokinetics

After oral administration, it is completely absorbed from the gastrointestinal tract. It is rapidly metabolized in the liver. The half-life (T_1/2) is about 2.5 hours. It is excreted by the kidneys, almost entirely in the form of metabolites.

Indications

For the palliative treatment of chronic myeloid leukemia in the chronic phase of the disease. It can also be used for polycythemia vera, essential thrombocythemia, and myelofibrosis.

ICD codes

Dosage Regimen

Establish the dosage individually based on the specific disease, its stage, the patient’s hematopoietic status, and the prescribed anticancer therapy protocol.

For chronic myeloid leukemia, initiate treatment with a daily dose of 60 mcg/kg (0.06 mg/kg) of body weight or 1.8 mg/m². Alternatively, a daily dose of 4 mg to 12 mg may be used for the average adult.

Continue therapy until the white blood cell count falls to approximately 15,000-20,000/μL. Discontinue the drug immediately upon reaching this threshold.

Expect the white blood cell count to continue falling for up to two weeks after the last dose. Do not restart therapy until the leukocyte count has stabilized and begins to rise again.

For maintenance therapy, administer a daily dose of 0.5 mg to 2 mg to maintain a total leukocyte count within a desired range, typically between 5,000/μL and 20,000/μL.

Adjust the dosage for polycythemia vera and essential thrombocythemia. Administer 4 mg to 6 mg daily until the hematocrit is controlled, then reduce to a maintenance dose of 1 mg to 3 mg daily.

Keep the treatment courses for these indications as short as possible due to the drug’s carcinogenic potential, especially in younger patients.

For high-dose conditioning regimens prior to hematopoietic progenitor cell transplantation, use busulfan exactly as specified by the institutional protocol, which is typically based on body weight or body surface area and administered in divided doses.

Perform weekly monitoring of the peripheral blood picture during induction of remission. Conduct monitoring at least monthly during maintenance therapy.

Discontinue therapy immediately if the white blood cell count falls to 2000-2500/μL or the platelet count falls to 100,000/μL.

Administer the total daily dose as a single dose on an empty stomach. Swallow tablets whole; do not crush or chew.

Adverse Reactions

From the hematopoietic system: very often – dose-dependent bone marrow suppression, manifested by leukopenia and especially thrombocytopenia; rarely – aplastic anemia, usually after long-term use of standard doses, as well as when using high doses of busulfan.

From the nervous system: rarely – seizures when using high doses of busulfan; very rarely – severe myasthenia.

From the organ of vision: rarely – changes in the lens and cataract, which may be bilateral; thinning of the cornea (observed after bone marrow transplantation preceded by therapy with high doses of busulfan).

From the cardiovascular system: often – cardiac tamponade in patients with thalassemia receiving high doses of busulfan.

From the respiratory system: in some cases – interstitial pulmonary fibrosis.

From the digestive system: very often – nausea, vomiting, diarrhea, ulceration of the oral mucosa when using high doses of busulfan; rarely – dryness of the oral mucosa.

From the liver and biliary tract: very often – hyperbilirubinemia, jaundice, hepatic vein occlusion and centrilobular sinusoidal fibrosis with hepatocellular atrophy and necrosis when using high doses of busulfan; rarely – cholestatic jaundice and impaired liver function when using standard doses of busulfan, centrilobular sinusoidal fibrosis.

From the skin and subcutaneous tissues: often – alopecia during treatment with high doses of busulfan, hyperpigmentation; rarely – alopecia when using conventional doses of busulfan, skin reactions including urticaria, erythema multiforme, erythema nodosum, late cutaneous porphyria, allopurinol-type rash, as well as excessive dryness and brittleness of the skin with complete anhidrosis, cheilosis, Sjögren’s syndrome.

From the urinary system: hemorrhagic cystitis during treatment with high doses of busulfan in combination with cyclophosphamide.

From the reproductive system and mammary gland: very often – suppression of ovarian function and amenorrhea with menopausal symptoms in premenopausal patients during treatment with high doses of busulfan; severe and persistent ovarian failure, including lack of sexual maturity after administration of high doses to young girls and girls who have not reached adolescence; sterility, azoospermia and testicular atrophy in men; infrequently – suppression of ovarian function and amenorrhea with menopausal symptoms in premenopausal patients during treatment with standard doses of busulfan; very rarely – gynecomastia.

Other: very rarely – a clinical syndrome (weakness, feeling of fatigue, anorexia, weight loss, nausea, vomiting, skin hyperpigmentation) resembling adrenal insufficiency (Addison’s disease), but without biochemical signs of adrenal suppression, hyperpigmentation of mucous membranes and hair loss; rarely – widespread epithelial dysplasia (observed in rare cases after long-term therapy with busulfan).

Contraindications

Hypersensitivity to busulfan, previously identified resistance to busulfan; pregnancy, breastfeeding period.

Special caution should be exercised when using busulfan for the treatment of polycythemia vera and essential thrombocythemia, taking into account the carcinogenic properties of busulfan. For these diseases, the use of Busulfan is not recommended in young patients or in the absence of symptoms. If busulfan administration is necessary, the courses of therapy should be as short as possible.

Use in Pregnancy and Lactation

Busulfan is contraindicated during pregnancy. If it is necessary to use during lactation, breastfeeding should be discontinued.

Women of childbearing age during busulfan administration should use reliable methods of contraception.

Use in Hepatic Impairment

Can be used according to indications.

Use in Renal Impairment

Can be used according to indications.

Pediatric Use

Can be used in children according to indications in age-appropriate recommended doses.

Geriatric Use

Can be used according to indications.

Special Precautions

Busulfan is a cytotoxic drug that should be used only under the supervision of physicians experienced in the use of such agents.

Its use is not recommended in patients with chickenpox (including recently contracted or after contact with sick individuals), with herpes zoster, other acute infectious diseases, gout or nephrolithiasis (including in the medical history).

Use with caution in patients with a history of seizures, traumatic brain injury; while taking drugs that increase the risk of seizures; in patients who have previously received cytotoxic antitumor agents or radiation therapy.

Vaccination of patients and their family members should not be carried out while taking busulfan.

A thorough monitoring of the peripheral blood picture should be performed once a week during the induction of remission and at least once every 4 weeks during maintenance therapy. The use of busulfan should be discontinued if the white blood cell count drops to 2000-2500/µL or the platelet count drops to 100,000/µL.

During the use of busulfan, periodic monitoring of liver transaminase activity and alkaline phosphatase, as well as plasma bilirubin levels, should be performed.

In patients with hyperuricemia and/or hyperuricouria, correction of these disorders is required before starting treatment with busulfan.

In children, Busulfan is used in very rare cases for strict indications.

Experimental studies have established the carcinogenic and mutagenic effects of busulfan.

Drug Interactions

With simultaneous use with other drugs that have myelodepressive properties, it is possible to enhance the toxic effect of busulfan on hematopoiesis.

With simultaneous use of uricosuric anti-gout agents, the risk of developing nephropathy associated with increased uric acid formation may increase, so the preferred drug for preventing or eliminating hyperuricemia associated with busulfan therapy is allopurinol.

The combination of busulfan with other pneumotoxic cytotoxic drugs may enhance the toxic effect on lung tissue.

Prescribing phenytoin to patients taking high doses of busulfan may lead to a decrease in the effect of the latter.

Concomitant use of busulfan with itraconazole and metronidazole may reduce the clearance of busulfan.

During combined therapy with busulfan and cyclophosphamide, an increase in the clearance of busulfan and cyclophosphamide, respectively, is possible.

The combination of busulfan and thioguanine has a strong toxic effect on the liver.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.