ADRIBLASTINA RAPID DISSOLUTION 50mg Injection/Powder for

What is ADRIBLASTINA RAPID DISSOLUTION 50mg

ADRIBLASTINA RAPID DISSOLUTION (doxorubicin HCl) is a lyophilised, red-orange powder presented in single-use 50 mg vials that are rapidly reconstituted to form an intravenous solution. It belongs to the anthracycline class of antineoplastic antibiotics and is a cornerstone drug in numerous solid-tumour and haematological chemotherapy protocols. Its broad antitumour spectrum includes breast carcinoma, lymphomas, sarcomas, paediatric malignancies, and many off-label indications in refractory disease. Each vial is typically dissolved with 25 mL of sterile water for injection to yield a 2 mg / mL solution, facilitating accurate dose titration and minimising preparation time in high-throughput oncology suites.

• Pharmacological classification: Cell-cycle nonspecific cytotoxic antibiotic (anthracycline).
• ATC code: L01DB01.
• Presentation: Sterile, preservative-free, rapid-dissolving lyophilisate for IV use only; do not administer intramuscularly, subcutaneously, or intrathecally.
• Colour & appearance: Fine brick-red cake; reconstituted solution is clear, red, and free of particulates.
• Excipient profile: Minimal—formulated without bacteriostatic agents to reduce hypersensitivity risk and ensure compatibility with infusion devices.
• Therapeutic intent: Curative, palliative, or adjuvant, depending on tumour type and stage.
• Cumulative dose limitation: 450–550 mg/m² (lifetime), above which the incidence of irreversible cardiomyopathy rises steeply.

How to use ADRIBLASTINA RAPID DISSOLUTION 50mg

Administration must take place in facilities equipped for cytotoxic handling and cardiopulmonary resuscitation, under the direct supervision of an oncologist or haemato-oncologist familiar with anthracycline therapy.

• Reconstitution:
  • Add exactly 25 mL sterile water for injection using a vented needle; swirl gently until complete dissolution (≈ 1 min).
  • Resulting concentration: 2 mg/mL; further dilute into 50–100 mL 0.9 % NaCl or 5 % dextrose for infusion.
  • Avoid vigorous shaking to minimise foaming and loss of potency.
• Route & rate:
  • Slow IV push over 3–5 min into a free-flowing infusion of isotonic saline, or
  • Short infusion (30–60 min) via side-arm tubing or central line to reduce venous irritation.
• Extravasation precautions: Confirm patency before and during injection; if infiltration is suspected, immediately cease, aspirate residual drug, and institute dexrazoxane or local cooling protocols.
• PPE & safe handling: Use chemotherapy-rated gloves, eye protection, and Class II BSC; dispose of waste via high-temperature incineration.
• Premedication/monitoring:
  • Baseline LVEF (ECHO or MUGA), full blood count, liver enzymes, bilirubin.
  • Anti-emetic regimen (5-HT₃ antagonist ± NK₁ antagonist, dexamethasone).
• Patient counselling: Expect red-orange urine for 24–48 h post-dose; report mouth ulcers, dyspnoea, or chest pain promptly.

Mode of Action ADRIBLASTINA RAPID DISSOLUTION 50mg

Doxorubicin exerts a multi-faceted cytotoxic effect that targets DNA integrity and cellular redox balance:

• Intercalation: Inserts rigid planar rings between DNA base pairs, disrupting helicase progression and transcriptional fidelity.
• Topoisomerase II inhibition: Stabilises the cleavable complex, locking double-strand breaks and preventing relegation, leading to lethal chromosomal fragmentation during S and G₂ phases.
• Free-radical generation: Semiquinone redox cycling in the presence of ferric ions produces hydroxyl and superoxide radicals, causing lipid peroxidation and protein oxidation—particularly hazardous to cardiomyocytes with low catalase reserves.
• Apoptosis induction: Up-regulates p53-mediated pro-apoptotic signalling (Bax, Fas) and down-regulates anti-apoptotic Bcl-2, tipping the balance toward programmed cell death.
• Immunomodulation: Increases tumour antigenicity and may enhance checkpoint-inhibitor efficacy by promoting immunogenic cell death (calreticulin exposure, HMGB1 release).
• Resistance mechanisms: P-gp efflux, topoisomerase IIα mutations, and enhanced glutathione peroxidase activity; understanding these is crucial to regimen design.

ADRIBLASTINA RAPID DISSOLUTION 50mg Interactions ADRIBLASTINA RAPID DISSOLUTION 50mg

Doxorubicin’s narrow therapeutic index necessitates meticulous review of concomitant therapies:

• Cytotoxics: Cyclophosphamide, ifosfamide, and platinum compounds amplify myelosuppression and mucositis; adjust scheduling or granulocyte-colony stimulating factor (G-CSF) support accordingly.
• Taxanes: Paclitaxel or docetaxel pre-administration increases doxorubicin AUC via P-gp inhibition—sequence taxane after doxorubicin to mitigate cardiotoxic synergy.
• HER2-targeted biologics: Trastuzumab, pertuzumab, or ado-trastuzumab emtansine steeply raise congestive heart-failure risk; maintain a 7-week washout or alternate non-anthracycline backbone when feasible.
• Radiotherapy: Concurrent mediastinal irradiation potentiates pericarditis and myocardial fibrosis; employ spacing or dose reduction.
• Live vaccines: Contra-indicated during and for ≥ 3 months post-therapy owing to prolonged immunosuppression.
• Antiretrovirals/azoles: Potent CYP3A4/P-gp inhibitors (ritonavir, ketoconazole) elevate serum doxorubicin—consider 30 % dose cut or therapeutic drug monitoring when available.
• Medical devices: Drug-eluting beaded embolics containing doxorubicin (TACE) may confound cumulative cardiotoxicity estimates; record all locoregional exposures.

Dosage of ADRIBLASTINA RAPID DISSOLUTION 50mg

Dosing must be individualised based on body-surface area (BSA), previous anthracycline exposure, organ function, and protocol.

• Single-agent: 60–75 mg/m² IV bolus every 21 days or 20 mg/m² on days 1–3 every 21 days.
• Combination regimens:
  • AC (Adriamycin + Cyclophosphamide): 60 mg/m² day 1 + cyclophosphamide 600 mg/m² day 1, q21d ×4.
  • CHOP (DLBCL): 50 mg/m² day 1 with cyclophosphamide, vincristine, prednisone ± rituximab.
  • MAP (osteosarcoma): 75 mg/m² divided over days 1–3 with high-dose methotrexate and cisplatin.
• Hepatic impairment: Reduce to 50 % (bilirubin 1.2–3 mg/dL) or 25 % (bilirubin > 3 mg/dL); modulate interval rather than fractionate dose when feasible.
• Renal impairment: No formal adjustment unless creatinine clearance < 30 mL/min; monitor for urate nephropathy in tumour lysis.
• Pediatric dosing: 25 mg/m² IV weekly or protocol-specific pulses; cumulative ceiling 300 mg/m² in children < 18 years.
• Supportive measures: Begin primary G-CSF prophylaxis if febrile-neutropenia risk ≥ 20 % or in elderly/comorbid patients.
• Lifetime cap: Include prior liposomal doxorubicin (factor 0.5 for equivalence) when tallying cumulative exposure.

Possible side effects of ADRIBLASTINA RAPID DISSOLUTION 50mg

Adverse events span acute infusion reactions to late-onset organ toxicities; rigorous monitoring is essential.

• Very common (> 1 in 10):
  • Myelosuppression: Grade 3–4 neutropenia (day 10–14 nadir), anaemia, thrombocytopenia.
  • Alopecia: Reversible, often complete, onset within 2–3 weeks.
  • Mucositis/stomatitis: Painful ulcers, dysphagia; institute prophylactic oral cryotherapy or palifermin where indicated.
  • Nausea/vomiting: Highly emetogenic (HEC) category without prophylaxis.
• Common (1 – 10 %):
  • Cardiotoxicity: Asymptomatic LVEF decline, acute arrhythmias, pericarditis-myocarditis syndrome.
  • Hyperpigmentation: Nail beds, skin folds; radiation-recall dermatitis.
  • Red/orange urine: Benign chromaturia up to 48 h.
• Uncommon (< 1 %):
  • Secondary AML/MDS: Alkylator-synergy risk, median latency 2–5 years.
  • Severe infusion reaction: Flushing, urticaria, bronchospasm.
• Rare: Extravasation necrosis (requires dexrazoxane), cardiomyopathy manifesting months–years later.
• Monitoring triggers: Febrile neutropenia > 38 °C, > Grade 2 mucositis, ≥ 10 % drop in LVEF, unexplained weight gain (possible heart failure).

ADRIBLASTINA RAPID DISSOLUTION 50mg Contraindications ADRIBLASTINA RAPID DISSOLUTION 50mg

• Absolute:
  • K–M or other severe hypersensitivity to doxorubicin or any anthracycline/anthracenedione.
  • Severe myocardial insufficiency, recent (< 6 months) myocardial infarction, uncontrolled arrhythmias.
  • Grade 4 myelosuppression or active sepsis.
  • Cumulative anthracycline dose > 550 mg/m² (or LVEF < 50 %).
  • Persistent severe hepatic impairment (bilirubin > 5 mg/dL) unresponsive to dose reduction.
  • Pregnancy (especially first trimester)—teratogenic and clastogenic.
  • Breast-feeding—rapid and extensive milk transfer.
  • Intrathecal or intramuscular administration (fatal).
• Relative:
  • Concurrent potent CYP3A4/P-gp inhibitors or radiotherapy to mediastinum.
  • Pre-existing renal dysfunction with tumour lysis risk.
  • Child-Pugh B cirrhosis—specialist dose tailoring mandatory.
• Special populations: Frail elderly > 70 years (evaluate geriatric assessment); infants < 6 months (limited data).

Storage of ADRIBLASTINA RAPID DISSOLUTION 50mg

• Unreconstituted vials:
  • Store at 2 – 8 °C (refrigerated) in original carton; excursions up to 25 °C for ≤ 7 days permitted.
  • Protect from light; anthracycline chromophores degrade under UV exposure.
  • Shelf-life: 24 months from manufacture if cold-chain maintained.
• Reconstituted solution (2 mg/mL):
  • Chemical/physical stability: 24 h at 2 – 8 °C or 6 h at < 25 °C in glass vials; discard unused portion.
  • Microbiological risk: prepare under ISO 5 laminar airflow; if aseptic conditions compromised, use immediately.
• Diluted infusion bags (0.5–4 mg/mL):
  • Stable 24 h at 2 – 8 °C in PVC or non-PVC bags; visually inspect for precipitation before administration.
• Transportation: Employ validated cool-chain containers with temperature logging.
• Disposal: Inactivate with 5 % sodium hypochlorite, then incinerate; follow local cytotoxic waste regulations.
• Spill management: Absorb with chemotherapy pads, decontaminate area with 3 % hydrogen peroxide, then rinse with water.