There are no current clinical data for this drug that could be used to determine the incidence of side effects.The frequency of side effects may vary depending on the patient's dose of busulfan, as well as on other drugs used in combination with it.
The frequency of side effects were divided into the following categories: very frequent: ≥1: 10; Frequent: ≥1: 100 and <1:10; infrequent: ≥1: 1000 and <1: 100; rare: ≥1: 10,000 and <1: 1000; very rare: <1/10 000.
From the hematopoietic and lymphatic system: very frequent: dose-dependent bone marrow suppression, manifested by leukopenia and especially thrombocytopenia; rare: aplastic anemia, usually after prolonged use of standard doses, as well as using high doses of busulfan.
From the nervous system: rare: convulsions when using high doses
very rare: severe myasthenia gravis.
On the part of the organs of vision: rare: changes in the lens and cataract, which can be bilateral; thinning of the cornea was observed after bone marrow transplantation, which was preceded by therapy with high doses of busulfan.
From the heart: Frequent: cardiac tamponade in patients with thalassemia receiving high doses of busulfan.
On the part of the respiratory, thoracic and mediastinal organs: rare: interstitial lung fibrosis.
Diffuse interstitial lung fibrosis with progressive dyspnea and persistent unproductive cough rarely occurs, usually after prolonged treatment for several years. Histological signs include atypical changes in the epithelium of the alveoli and bronchioles and the presence of giant cells with large hyperchromatic nuclei. In the case of detection of toxic lung damage, the prognosis even in spite of the cancellation of busulfan is unfavorable, in this situation there is little benefit from the use of corticosteroids. Interstitial lung fibrosis usually develops gradually, but it can also have an acute course. This pulmonary pathology can be complicated by infections. Ossification and dystrophic calcification of the lungs are also described. It is possible that subsequent radiotherapy may increase subclinical lung damage caused by busulfan. Other cytotoxic drugs may cause additive toxic lung damage.
From the gastrointestinal tract: very frequent: nausea, vomiting, diarrhea and ulceration of the oral mucosa using high doses of busulfan.Probably the symptoms can be alleviated by applying fractional doses.
Hepatobiliary disorders: very frequent: hyperbilirubinemia, jaundice, occlusive hepatic veins and centrolobular sinusoidal fibrosis with hepatocellular atrophy and necrosis with high doses; rare: Cholestatic jaundice and violations of liver function with the use of usual doses, centrolobular sinusoidal fibrosis.
It is believed that in usual therapeutic doses busulfan does not have a significant toxic effect on the liver. At the same time, a retrospective analysis of pathological data on patients who received a low dose of busulfan for at least two years for chronic granulocyte leukemia revealed the presence of centrolobular sinusoidal fibrosis.
The combination of busulfan and thioguanine has a strong toxic effect on the liver.
From the skin and subcutaneous tissues: Frequent: alopecia in the treatment of high doses, hyperpigmentation; rare: alopecia with usual doses, skin reactions including hives, erythema multiforme, erythema nodosum, late cutaneous porphyria, rash allopurinol type,as well as excessive dryness and fragility of the skin with complete anhidrosis, dryness of the mucous membranes of the oral cavity and cheilosis, Sjogren's syndrome. More pronounced radial skin changes in patients receiving radiotherapy soon after treatment with high doses of busulfan.
Cases of hyperpigmentation, in particular in black patients, are described. Often it is most pronounced on the neck, upper body, nipples, abdomen and palmar folds. Hyperpigmentation can be part of a clinical syndrome.
From the side of the kidneys and urinary tract: Frequent: hemorrhagic cystitis in high-dose treatment in combination with cyclophosphamide.
On the part of the reproductive system and mammary glands: very frequent: oppression of ovarian function and amenorrhea with menopausal symptoms in premenopausal patients treated with high doses; severe and persistent failure of the ovaries, including the lack of puberty after the administration of high doses to young girls and girls who have not reached adolescence. Sterility, azoospermia and testicular atrophy in men receiving busulfan; infrequent: oppression of ovarian function and amenorrhea with menopausal symptoms in premenopausal patients treated with conventional doses.In very rare cases, recovery of ovarian function was observed with continued treatment; very rare: gynecomastia
The study of busulfan in animal experiments revealed its toxic effect on the reproductive system.
Violations of a general nature: very rare: clinical syndrome (weakness, severe fatigue, anorexia, weight loss, nausea and vomiting, hyperpigmentation of the skin), reminiscent of adrenal insufficiency (Addison's disease), but without biochemical signs of adrenal suppression, hyperpigmentation of mucous membranes and hair loss; R caustic: common epithelial dysplasia (observed in rare cases after prolonged therapy with busulfan). This syndrome sometimes disappears after the cancellation of busulfan.
In patients treated with busulfan, numerous histological and cytologic changes were found, including widespread dysplasia of the epithelium of the cervix, bronchi and epithelium of other localization. In most cases, such changes occur in the results of prolonged therapy, but transient anomalies of the epithelium are also described after short-term treatment with high doses.