Nitib® (Nilotinib) — Second Generation BCR-ABL TKI for Chronic Myeloid Leukaemia

30-Fold Greater BCR-ABL Potency Than Imatinib — Faster and Deeper Molecular Responses With Treatment-Free Remission Potential

Nitib® (Nilotinib) is a second-generation, highly selective BCR-ABL tyrosine kinase inhibitor (TKI) used to treat Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) in chronic phase (CP) and accelerated phase (AP) — both as first-line therapy and in patients who have failed or are intolerant to prior therapy including Imatinib. Nilotinib was specifically engineered to overcome Imatinib resistance — with a binding affinity to BCR-ABL approximately 30 times greater than Imatinib, tighter binding that locks BCR-ABL in its inactive conformation, and activity against most Imatinib-resistant BCR-ABL mutations (with the notable exception of the T315I gatekeeper mutation).

Beyond overcoming Imatinib resistance, Nilotinib as first-line therapy achieves significantly higher and faster rates of major molecular response (MMR — ≥3-log BCR-ABL reduction) and deep molecular response (MR4, MR4.5 — ≥4-4.5-log BCR-ABL reduction) compared to Imatinib — making it the preferred choice for patients where achieving deep molecular response and eventual treatment-free remission (TFR) is the clinical goal.

A.K. Pharma is a trusted medicine distributor in Delhi supplying genuine Nitib (Nilotinib) to hospitals, haematology centres, oncology clinics, and pharmacies across India. Nitib contains Nilotinib — the same active ingredient as the originator Tasigna (Novartis) — available at accessible pricing for Indian patients.

What is Nitib (Nilotinib)?

Nitib contains Nilotinib — a synthetic aminopyrimidine derivative that acts as a highly selective, second-generation BCR-ABL tyrosine kinase inhibitor. In CML the Philadelphia chromosome — a translocation between chromosomes 9 and 22 (t(9;22)(q34;q11)) — creates the BCR-ABL fusion oncogene encoding a constitutively active tyrosine kinase that drives uncontrolled myeloid cell proliferation. Nilotinib inhibits this constitutively active BCR-ABL kinase — blocking the signalling cascade that drives CML leukaemogenesis.

Structural advantages over Imatinib:

• Nilotinib was rationally designed based on the crystal structure of Imatinib bound to ABL kinase — incorporating structural modifications to increase binding affinity and overcome steric clashes caused by resistance mutations
• Higher affinity binding to the ABL kinase inactive conformation — approximately 30-fold greater potency vs Imatinib
• More compact binding — overcomes steric hindrance from many resistance mutations
• Additional hydrophobic contacts with the ABL kinase domain — stabilising binding

BCR-ABL mutation coverage:

• Active against >40 Imatinib-resistant BCR-ABL mutations including E255K/V, Y253H, F359V/C, M244V, and most others
• Important exception: T315I gatekeeper mutation — not covered by Nilotinib (or Imatinib or Dasatinib) — requires Ponatinib or Asciminib
• Active against wild-type BCR-ABL with dramatically greater potency

Full prescribing information is available at the FDA label for Nilotinib.

Clinical Studies and Evidence

ENESTnd Trial (Nilotinib vs Imatinib — First-Line CML) Published in the New England Journal of Medicine (2010), the landmark ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials — Newly Diagnosed) trial was a Phase 3 randomised controlled trial of 846 patients with newly diagnosed Ph+ CML-CP — comparing Nilotinib 300mg twice daily and Nilotinib 400mg twice daily to Imatinib 400mg once daily. Key results at 5-year follow-up:

• MMR (Major Molecular Response — BCR-ABL ≤0.1%) at 12 months: Nilotinib 300mg 55.5% vs Imatinib 28.0% — significantly superior
• MR4.5 (BCR-ABL ≤0.0032%) at 5 years: Nilotinib 300mg 54% vs Imatinib 31% — dramatically higher rates of deep molecular response
• Progression to AP/BC: Nilotinib 300mg 0.7% vs Imatinib 4.2% — significantly fewer progressions to advanced phase
• Overall survival: Comparable between groups — both excellent
• Established Nilotinib 300mg twice daily as the preferred first-line TKI for patients where deep molecular response and TFR potential are clinical goals

ENESTnd 10-Year Long-Term Data Published in Leukemia (2020), 10-year follow-up from ENESTnd confirmed maintained superiority of Nilotinib over Imatinib for MMR and MR4.5 rates — with stable, low rates of transformation to advanced phase in Nilotinib-treated patients. The 10-year data also revealed the cardiovascular risk signal with long-term Nilotinib use — peripheral arterial occlusive disease (PAOD) at higher rates than Imatinib — requiring careful cardiovascular monitoring in long-term Nilotinib-treated patients.

ENESTcmr Trial (Nilotinib Switch in Imatinib-Treated Patients) Published in Blood (2012), ENESTcmr demonstrated that switching to Nilotinib in Imatinib-treated patients who had achieved complete cytogenetic response but not MMR significantly improved the rate of MR4.5 deep molecular response — enabling more patients to achieve the deep response required for TFR attempts.

ENESTfreedom Trial (Treatment-Free Remission With Nilotinib) Published in Leukemia (2016), ENESTfreedom demonstrated that 51.6% of patients who achieved sustained deep molecular response (MR4.5) on Nilotinib first-line therapy and discontinued treatment remained in treatment-free remission at 48 weeks — establishing TFR as an achievable clinical goal in appropriately selected Nilotinib-treated patients. This represented a paradigm shift in CML management — making treatment-free remission a realistic goal for many patients.

ENESTnd Imatinib-Resistant/Intolerant CML Multiple Phase 2 trials demonstrated Nilotinib 400mg twice daily achieved major cytogenetic response (MCyR) in 59% and CCyR in 44% of Imatinib-resistant CML-CP patients — with MMR in 29% — establishing Nilotinib as highly effective second-line therapy after Imatinib failure.

Available Strengths

Nitib is available in the following strengths:

Critical — Must be taken on empty stomach: Like Abiraterone, food dramatically increases Nilotinib absorption — taking with food can increase plasma exposure by 82% (high-fat meal) to 112% (low-fat meal), causing toxic blood levels. Nilotinib must be taken on an empty stomach — no food for at least 2 hours before and 1 hour after each dose. This is the single most critical patient counselling point for Nilotinib therapy.

Indications — What Nitib is Used For

Newly Diagnosed Ph+ CML in Chronic Phase (First-Line):

• Adults with newly diagnosed Ph+ CML-CP where achieving deep molecular response and treatment-free remission potential is the clinical goal
• Nilotinib 300mg twice daily — FDA approved dose for first-line CML-CP

Ph+ CML Resistant to or Intolerant of Prior Therapy:

• Adults with Ph+ CML-CP or CML-AP resistant to or intolerant of prior TKI therapy including Imatinib
• Nilotinib 400mg twice daily — FDA approved dose for resistant/intolerant CML

For detailed indication information refer to MedlinePlus Nilotinib.

Key Benefits of Nitib

Superior MMR and Deep Molecular Response Rates vs Imatinib ENESTnd demonstrates Nilotinib achieves MMR in 55.5% vs 28.0% of patients at 12 months — and MR4.5 in 54% vs 31% at 5 years. These higher rates of deep molecular response are directly relevant to achieving treatment-free remission — the ultimate goal of modern CML management.

Treatment-Free Remission (TFR) — Potentially Stopping Treatment The ENESTfreedom trial demonstrates that patients who achieve sustained MR4.5 on Nilotinib first-line therapy have a 51.6% probability of remaining in TFR after stopping treatment — making Nilotinib the preferred first-line TKI for patients who prioritise eventual treatment discontinuation. Imatinib achieves lower MR4.5 rates — reducing TFR candidacy.

Significantly Fewer Progressions to Advanced Phase ENESTnd demonstrates 0.7% vs 4.2% progression to advanced phase with Nilotinib vs Imatinib — dramatically reducing the risk of disease transformation to accelerated or blast phase — the most serious complication of CML management.

Overcomes Most Imatinib Resistance Mutations Nilotinib is active against >40 BCR-ABL mutations that cause Imatinib resistance — providing a highly effective salvage option for patients who develop Imatinib-resistant disease (except T315I).

30-Fold Greater BCR-ABL Potency Superior BCR-ABL inhibition translates to faster and deeper molecular responses — achieving MMR faster than Imatinib, enabling earlier assessment of TFR candidacy.

Over 15 Years of Post-Marketing Experience Extensive long-term real-world and clinical trial experience provides comprehensive safety characterisation — enabling informed monitoring and management decisions in clinical practice.

How Nitib Works

CML Pathogenesis: The Philadelphia chromosome translocation (t(9;22)) fuses the BCR gene on chromosome 22 to the ABL1 tyrosine kinase gene on chromosome 9 — creating the BCR-ABL1 fusion oncogene. BCR-ABL protein is a constitutively active tyrosine kinase — unlike normal ABL which is tightly regulated, BCR-ABL is always switched on — continuously phosphorylating downstream substrates that drive:

• Uncontrolled myeloid progenitor cell proliferation
• Suppression of apoptosis — cancer cell survival
• Impaired differentiation — accumulation of immature myeloid cells
• Genomic instability — risk of additional mutations causing progression to blast phase

Nilotinib’s Mechanism:

Step 1 — ABL Kinase Domain Binding: Nilotinib binds with high affinity to the ATP-binding site of the BCR-ABL kinase domain — competing with ATP (the substrate whose γ-phosphate is transferred to target proteins). Critically, Nilotinib stabilises BCR-ABL in its inactive (DFG-out) conformation — a conformation less accessible to resistance mutations that affect the active site.

Step 2 — Tyrosine Kinase Inhibition: By occupying the ATP-binding site, Nilotinib prevents ATP from binding → BCR-ABL cannot phosphorylate downstream substrates → signalling cascades driving proliferation and survival are blocked.

Step 3 — Downstream Signalling Blockade: Key downstream pathways blocked include:

• RAS/MAPK pathway — proliferation
• PI3K/AKT pathway — survival and anti-apoptosis
• STAT5 pathway — survival and differentiation block
• SRC kinase pathway — adhesion and migration

Step 4 — Induction of Apoptosis: Loss of survival signalling → BCR-ABL-dependent leukaemic progenitor cells undergo apoptosis (programmed cell death) → progressive reduction in leukaemic clone — reflected in declining BCR-ABL PCR values on molecular monitoring.

Why Empty Stomach is Critical: Nilotinib is a BCS Class II compound — poorly water-soluble but highly permeable. Food — particularly fat — increases gastric acid secretion and prolongs gastric emptying, dramatically increasing Nilotinib dissolution and absorption. This food effect is non-linear and unpredictable — making consistent fasted-state administration essential for reliable, controlled drug exposure.

For detailed mechanism overview refer to ELN (European LeukemiaNet) CML Recommendations 2020 and NCCN CML Guidelines.

Molecular Monitoring — The Foundation of CML Management

CML treatment response is monitored by quantitative PCR measuring BCR-ABL1 transcript levels in peripheral blood — standardised on the International Scale (IS):

ELN Milestone Monitoring Schedule for Nitib:

• Baseline: BCR-ABL PCR + cytogenetics + mutation analysis
• Month 3: BCR-ABL PCR — should be ≤10% IS (warning if >10%, failure if >10% with Imatinib reference)
• Month 6: BCR-ABL PCR — should be <1% IS
• Month 12: BCR-ABL PCR — should be ≤0.1% IS (MMR)
• Every 3 months thereafter: BCR-ABL PCR

Treatment-Free Remission (TFR) Criteria:

• Sustained MR4.5 or deeper for ≥2 years on Nilotinib first-line
• Requires monthly PCR monitoring for first year after stopping
• Molecular relapse (BCR-ABL detectable on 2 occasions or loss of MMR) → restart Nilotinib promptly — all patients regain response

Dosage and Administration

First-Line CML-CP:

• 300mg orally twice daily — 12 hours apart
• On an empty stomach — no food for 2 hours before and 1 hour after each dose
• Swallow capsules whole — do not open, crush, dissolve, or chew

Resistant/Intolerant CML-CP and CML-AP:

• 400mg orally twice daily — 12 hours apart
• On an empty stomach — same restriction

Dose Modifications:

• QTc prolongation — withhold if QTc >480ms; assess and correct electrolytes; restart at reduced dose once resolved
• Haematological toxicity (ANC <1.0×10⁹/L or platelets <50×10⁹/L) — withhold; restart when counts recover
• Non-haematological toxicity — dose reduce per SmPC guidance

Monitoring Schedule:

• ECG (QTc) — at baseline, 7 days after initiation, and periodically. Do not initiate if QTc >450ms at baseline
• Electrolytes (potassium, magnesium) — at baseline and periodically; correct hypokalaemia and hypomagnesaemia before starting — both prolong QT
• CBC — every 2 weeks for first 2 months, then monthly
• LFTs — at baseline then monthly
• Lipase and amylase — at baseline then monthly
• BCR-ABL PCR — every 3 months — molecular monitoring is the cornerstone of CML management
• Cardiovascular assessment — ankle-brachial index at baseline; monitor for signs of PAOD (claudication, cold extremities) — peripheral arterial occlusive disease risk is elevated with long-term Nilotinib

Full dosing guidelines available at Drugs.com Nilotinib Dosage.

Treatment-Free Remission — Who Is Eligible?

TFR with Nilotinib is appropriate for carefully selected patients meeting all of the following:

• First-line Nilotinib therapy — not salvage
• Sustained MR4.5 (BCR-ABL ≤0.0032% IS) for ≥2 years
• Reliable access to monthly BCR-ABL PCR monitoring — mandatory
• Understanding of and willingness to restart Nilotinib immediately if molecular relapse occurs
• Discussion with treating haematologist — TFR is not appropriate for all patients

Patients who relapse after TFR restart Nilotinib and virtually all regain molecular response — TFR discontinuation is safe when guidelines are followed.

Who Should Use Nitib

Nitib is prescribed for:

• Adults with newly diagnosed Ph+ CML-CP where deep molecular response and TFR potential are treatment goals
• Adults with Ph+ CML-CP or CML-AP resistant to or intolerant of prior Imatinib or other TKI therapy
• Patients with Imatinib-resistant BCR-ABL mutations (except T315I) — mutation testing mandatory before second-line TKI selection
• Patients where superior MMR rates and lower progression risk justify Nilotinib’s cardiovascular monitoring requirements

Nitib is prescribed by haematologists and oncologists specialising in leukaemia management. A.K. Pharma supplies Nitib to hospitals, haematology centres, and pharmacies across Delhi and India.

Possible Side Effects

Common side effects include rash (36%), nausea (22%), headache (21%), fatigue (18%), pruritus (15%), constipation (12%), diarrhoea (11%), vomiting (10%), and musculoskeletal pain.

Serious side effects include:

QT Prolongation and Sudden Death: Nilotinib prolongs the QT interval — risk of potentially fatal ventricular arrhythmias (Torsades de Pointes) — Black Box Warning. Do not use with other QT-prolonging drugs. Correct hypokalaemia and hypomagnesaemia before starting. ECG monitoring is mandatory.

Peripheral Arterial Occlusive Disease (PAOD): Long-term Nilotinib therapy — particularly at 400mg twice daily — is associated with increased risk of PAOD including claudication, critical limb ischaemia, and coronary artery disease. Monitor with ankle-brachial index at baseline and annually. Discontinue if PAOD develops.

Hepatotoxicity: Elevated liver enzymes in up to 10% of patients. Monthly LFT monitoring required. Dose reduce or discontinue for significant elevation.

Pancreatitis: Lipase and amylase elevation — monitor monthly. Suspend if clinical pancreatitis develops.

Haematological toxicity: Neutropenia and thrombocytopenia — particularly in first 2 months. CBC monitoring every 2 weeks initially.

Full side effect information available at FDA Nilotinib Safety Information.

Precautions

• QT prolongation — Black Box Warning — ECG at baseline, 7 days post-initiation, periodically; do not initiate if QTc >450ms; correct electrolytes before starting; avoid concomitant QT-prolonging medicines
• Sudden death — Black Box Warning — Sudden deaths occurred in clinical trials — likely QT-related; emphasises importance of QT monitoring
• Empty stomach requirement — mandatory — food dramatically increases absorption and toxicity
• T315I mutation — test for BCR-ABL mutations before second-line use; T315I is not covered by Nilotinib
• Cardiovascular risk — PAOD — assess cardiovascular risk factors at baseline; monitor throughout; consider switching to Imatinib or alternative TKI in patients with established cardiovascular disease
• Strong CYP3A4 inhibitors — avoid; significantly increase Nilotinib plasma levels (ketoconazole, clarithromycin, ritonavir)
• Strong CYP3A4 inducers — avoid; significantly reduce Nilotinib levels (rifampicin, phenytoin, carbamazepine, St John’s Wort)
• Hepatic impairment — dose reduce in moderate-severe hepatic impairment
• Pregnancy — teratogenic; effective contraception required; discontinue breastfeeding
• Refer to ELN CML Recommendations for complete management context

Storage and Handling

• Store at room temperature below 30°C
• Keep in original packaging — protect from moisture and light
• Keep out of reach of children
• Do not open or crush capsules

As a responsible medicine distributor in Delhi, A.K. Pharma stores all haematology medicines including Nitib under manufacturer-recommended conditions ensuring product integrity for every supply.

Manufacturer Information

Nitib (Nilotinib) contains the same active ingredient as the originator Tasigna — developed by Novartis AG. Nilotinib received FDA approval in October 2007 for resistant/intolerant CML and in June 2010 for newly diagnosed CML-CP. A.K. Pharma supplies only genuine Nitib sourced from authorised distributors.

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Frequently Asked Questions

Q. What is Nitib used for? Nitib (Nilotinib) is used to treat Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) — both as first-line therapy in newly diagnosed CML-CP and in patients whose CML is resistant to or intolerant of prior TKI therapy including Imatinib. More information available at MedlinePlus.

Q. What is the generic name of Nitib? The generic name of Nitib is Nilotinib. It is a second-generation BCR-ABL tyrosine kinase inhibitor containing the same active ingredient as the originator Tasigna.

Q. How is Nilotinib different from Imatinib? Nilotinib is a second-generation BCR-ABL TKI with approximately 30-fold greater potency than Imatinib. The ENESTnd trial demonstrates Nilotinib achieves significantly higher MMR and MR4.5 rates and fewer progressions to advanced phase compared to Imatinib — making it the preferred first-line choice when deep molecular response and treatment-free remission are the clinical goals.

Q. Why must Nitib be taken on an empty stomach? Food dramatically increases Nilotinib absorption — a high-fat meal increases plasma exposure by up to 112%. This unpredictable food effect can cause toxic drug levels. Nilotinib must be taken on a completely empty stomach — at least 2 hours after and 1 hour before food — this is mandatory and non-negotiable for safe treatment.

Q. What is treatment-free remission and can it be achieved with Nilotinib? Treatment-free remission (TFR) means stopping CML treatment while maintaining molecular response — effectively being in remission without taking medicine. The ENESTfreedom trial demonstrates 51.6% of appropriately selected patients who achieve sustained MR4.5 on Nilotinib first-line therapy can stop treatment and remain in TFR at 48 weeks. Patients who relapse restart Nilotinib and virtually all regain response.

Q. What is the T315I mutation and why is it important? T315I is a BCR-ABL gatekeeper mutation that confers resistance to Nilotinib, Imatinib, and Dasatinib. Before using Nilotinib as second-line therapy, BCR-ABL mutation testing is mandatory to identify T315I — which requires different therapy (Ponatinib or Asciminib). A.K. Pharma recommends mutation testing before second-line TKI selection.

Q. Is Nitib available in India? Nitib can be supplied to hospitals, haematology centres, and pharmacies across India through licensed pharmaceutical distributors. Contact A.K. Pharma — medicine distributor in Delhi — for availability and pricing.

Q. What is the price of Nitib in India? Nitib price in India varies by strength and pack size. Contact A.K. Pharma at 011 4172 6999 or WhatsApp +91 9810034827 for current pricing and bulk supply rates.

Q. How to order Nitib from A.K. Pharma? You can request a quote directly from this page, call us at 011 4172 6999, or WhatsApp us at +91 9810034827 with your requirements and we will respond promptly.

Q. Does A.K. Pharma supply Nitib in bulk? Yes. A.K. Pharma supplies Nitib in bulk to haematology centres, oncology clinics, hospitals, and pharmacies across Delhi and India. Contact us for bulk pricing and availability.

Why Order Nitib from A.K. Pharma?

• Licensed medicine distributor in Delhi with all required drug licenses
• 100% genuine Nitib sourced from authorised distributors
• Both 150mg and 200mg capsule strengths available
• Available alongside companion haematology medicines — Venclexta, Acabrunat, Azadine — simplifying procurement
• Bulk supply available for hospitals and haematology centres
• Prompt response to all quote requests
• Serving haematologists and oncologists across Delhi NCR and India

Contact A.K. Pharma for Nitib Supply 📍 E-2/257A, 2nd Floor, Shastri Nagar, New Delhi 110052 📞 011 4172 6999 📱 WhatsApp: +91 9810034827 🌐 akpharma.in