Bleomycin

Bleomycin is an antineoplastic agent belonging to the pharmacological class of antibiotics.

The FDA approved Bleomycin for treating squamous Cell Carcinoma, Hodgkin Disease, non-Hodgkin lymphoma, and Testicular Carcinoma.

Bleomycin poorly absorbs from the gastrointestinal tract but rapidly absorbs after parenteral, intraperitoneal, or intrapleural administration. It crosses the placenta, influences fetal exposure, has a volume of distribution of 22 L/m2, undergoes enzymatic degradation via bleomycin hydrolase, and is excreted via urine.

Bleomycin's most common side effects include fever, loss of appetite, loss of hair, weight loss, nausea, inflammation of the lungs (interstitial pneumonia), shortness of breath or cough.

Bleomycin is available as a powder for injection.

The molecule is available in India, the United States, Canada, China, countries within the European Union, Australia, Japan and South Korea.

Bleomycin is an antineoplastic agent belonging to the pharmacological class of antibiotics.

The current information suggests that Bleomycin primarily inhibits DNA synthesis, with some evidence suggesting a lesser degree of inhibition of RNA and protein synthesis, even though the precise mechanism of action of the drug is unknown. Bleomycin's ability to cleave DNA depends on metal ions and oxygen, as demonstrated by in vitro experiments. Bleomycin is thought to chelate metal ions, especially iron, creating a pseudoenzyme that combines with oxygen to generate free radicals called superoxide and hydroxide, which cleave DNA.

Peak plasma concentration reached around 30 minutes with intramuscular administration.

Bleomycin is available as powder for injection.

Powder for injection: To be administered parenterally by a health care professional as applicable.

The physician recommends taking this medication usually once or twice a week, with or without food.

Bleomycin is indicated in the following conditions:

Parenterally: Usually, Bleomycin is given as an injection powder. To make a solution for intravenous infusion, the drug is reconstituted using a sterile diluent, such as sterile water for injection. In a clinical setting, medical professionals administer the reconstituted solution intravenously (IV) or intramuscularly (IM). Proper handling and administration procedures- including aseptic techniques- are crucial to ensure the efficacy of the medication and reduce the risk of complications.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Bleomycin is available as a powder for injection.

0.5 to 0.25 units/kg (10 to 20 units/m2) IV/IM/SC for 1-2 weeks

Start the first dose by giving a test dose of 1-2 units of Bleomycin; monitor vital signs every 15 minutes; and wait at least one hour before giving the remaining dose. Provide the usual dosage schedule if there is no acute reaction observed.

0.25–0.5 units/kg (10–20 units/m2) IV/IM/SC every 1-2 weeks; after 50% response, decrease to the maintenance dose of 1 unit IV/IM every day or five units IV/IM every week.

0.25–0.5 unit/kg (10–20 unit/m2) IV/IM/SC for 1-2 weeks

If fluid accumulation persists, repeat the dose every few days (mixing in 50-100 mL or NS) and add lidocaine (100–200 mg) to ease local discomfort. 60 units in 50–100 mL as a single instillation.

Patients can actively manage side effects by altering their diet while receiving Bleomycin treatment. Include foods high in nutrients, like leafy greens, citrus fruits, fatty fish, berries, yoghurt, apples, peaches, broccoli, cauliflower, and beans. For the best possible treatment results, it is also imperative to refrain from smoking and drinking alcohol, as well as to avoid processed meats, fast food, fried foods, refined carbohydrates, and added sugars.

The dietary restriction should be individualized as per patient requirements.

Consume nutrient-rich foods; avoid smoking, alcohol, and processed meats.

The adverse reactions related to Bleomycin can be categorized as:

The clinically relevant drug interactions of Bleomycin are briefly summarized here.

Increased frequency and severity of lung toxicity when combined with prior or ongoing chest radiation therapy. Combined with vinca alkaloids, it may cause a syndrome similar to Morbus Raynaud's ischaemia, which can cause the body's peripheral tissues (fingers, toes, tip of the nose) to necrotize. It might lessen phenytoin's absorption. Agranulocytosis risk is higher when using clozapine.

Increased pulmonary toxicity when using oxygen, cisplatin, or brentuximab is potentially fatal.

The common side effects of Bleomycin include:

Fever

Hair loss

Weight loss

Hyperkeratosis: an excessive skin thickening

Loss of appetite

Stomatitis, or inflammation of the mouth's mucous lining

Low blood platelets

Nail discoloration

Breathing difficulties

Interstitial pneumonitis (inflammatory changes in the lungs)

A lung disease called pulmonary fibrosis is brought on by an increase in the connective tissue that forms between the alveoli.

Nausea and vomiting

Inflammatory redness of the skin

Itching

Striae (stretch marks)

Blistering

Hyperpigmentation (increased pigment formation)

Tenderness and swelling of the fingertips

Pulmonary fibrosis

Rigors

Pregnancy Category D (FDA): Use in cases where no safer medication is available and life is in danger. Positive evidence of prenatal risk in humans.

Pregnant women who receive therapy may experience harm to their fetus; however, there have been no studies conducted on this population.

Patients who use injections while pregnant or who become pregnant while taking this medication should be informed of the possible risks to the developing fetus.

Pregnant women should be advised against getting pregnant while receiving therapy.

1.6 times the recommended human dose per millimetre (m2) was administered intraperitoneally to rats on days 6 to 15 of gestation, resulting in skeletal malformations, shortened innominate arteries, and hydrometers. This has been demonstrated to be teratogenic in rats.

In rabbits, intravenous doses of 1.2 mg/kg/day (approx 2.4 times the recommended human dose on a unit/m2 basis) administered on gestation days 6 to 18 result in abortion but do not cause teratogenic effects.

Although it is unknown if the medication is eliminated in human milk, it is advised that women undergoing bleomycin therapy stop nursing their babies because many medicines are excreted in it and because there is a risk of severe adverse reactions.

As per the FDA, Bleomycin is not recommended in paediatric populations.

CrCl > 50 mL/min: No need to change the dosage

CrCl 40–50 mL/min: 70% of the standard dosage

CrCl 30–40 mL/min: 60% of the standard dosage

CrCl 20–30 mL/min: 55% of the standard dosage

CrCl 10–20 mL/min: 45% of the standard dosage

CrCl 5–10 mL/min: 40% of the standard dosage

Not required to adjust the dosage.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Bleomycin.

Overconsumption of Bleomycin could lead to hypotension, fever, rapid pulse and general symptoms of shock.

Overdosing on Bleomycin doesn't have a specific antidote. It's crucial to stop taking the medication immediately if an overdose occurs. The use of supportive and symptomatic measures is recommended. Treat respiratory complications with a broad-spectrum antibiotic and a corticosteroid. For patients with severe myelosuppression, hospitalization is advised to manage mucositis, administer antimicrobials, and receive platelet transfusions. Hemopoietic growth factors (GM-CSF, G-CSF) could be taken into consideration.

There has been evidence of antitumor activity for the antibiotic bleomycin. Bleomycin inhibits explicitly deoxyribonucleic acid (DNA) synthesis. The level of cross-linking induced by mitomycin is correlated with the guanine and cytosine content. The drug at high concentrations also inhibits cellular RNA and protein synthesis. It has been demonstrated that Bleomycin inhibits the proliferation of B cells, T cells, and macrophages and affects antigen presentation, interferon-gamma secretion, TNFa, and IL-2. Besides Bleomycin, which has significant effects in the G2 and M phases, all antibiotic antitumor drugs are nonspecific to the cell cycle.

The initial half-life of an intravenous (IV) bolus is 0.5 hours, while the terminal half-life is 4 hours. An IV infusion has a 1.3-hour initial half-life and a 9-hour terminal half-life.