What Is Pazopanib Accord and What Is It Used For?
Pazopanib Accord is a targeted anticancer medicine classified as a multi-tyrosine kinase inhibitor. It works by blocking the activity of several proteins (including VEGFR, PDGFR, and c-KIT) that are involved in the growth of new blood vessels and the proliferation of cancer cells, thereby starving tumors of their blood supply and inhibiting their growth.
Pazopanib Accord is prescribed for adults to treat two primary conditions. The first is advanced renal cell carcinoma (kidney cancer), particularly in patients whose disease has progressed or spread to other organs (metastatic disease). Renal cell carcinoma accounts for approximately 90% of all kidney cancers, and pazopanib has been a standard treatment option since its initial regulatory approval. The pivotal COMPARZ trial, published in the New England Journal of Medicine, established pazopanib as non-inferior to sunitinib in progression-free survival for first-line treatment of metastatic renal cell carcinoma.
The second approved indication is the treatment of certain forms of advanced soft tissue sarcoma (STS) in adults who have received prior chemotherapy or who are unsuitable for chemotherapy. Soft tissue sarcomas are rare cancers that develop in the supportive tissues of the body, including muscles, blood vessels, fat tissue, tendons, and tissues that surround and support internal organs. The PALETTE trial demonstrated that pazopanib significantly improved progression-free survival compared to placebo in patients with advanced non-adipocytic soft tissue sarcoma after prior chemotherapy.
The mechanism of action of pazopanib involves inhibiting angiogenesis — the process by which tumors develop new blood vessels to sustain their growth. By targeting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, and VEGFR-3), platelet-derived growth factor receptors (PDGFR-alpha and PDGFR-beta), and the stem cell factor receptor (c-KIT), pazopanib disrupts multiple signaling pathways critical to tumor vascularization and cell survival. This multi-targeted approach provides broad antitumor activity across different cancer types that depend on these growth pathways.
Pazopanib Accord is a generic formulation of pazopanib, manufactured by Accord Healthcare. It contains the same active ingredient in the same dosage form and strengths as the original reference product. Other generic formulations include Pazopanib Glenmark, Pazopanib Zentiva, and Pazopanib STADA. All of these products are therapeutically equivalent and have been approved by the European Medicines Agency (EMA) through rigorous bioequivalence studies.
What Should You Know Before Taking Pazopanib Accord?
Before starting treatment with Pazopanib Accord, your doctor will review your complete medical history and conduct baseline assessments of liver function, blood pressure, thyroid function, and cardiac status. Several conditions and situations require special caution or may make this medicine unsuitable for you.
Contraindications
You must not take Pazopanib Accord if you are allergic to pazopanib or any of the other ingredients in the tablets. An allergic reaction may include skin rash, itching, swelling of the face or throat, difficulty breathing, or dizziness. If you experience any signs of an allergic reaction, seek immediate medical attention. Your doctor will evaluate whether alternative treatment options are more appropriate for your situation.
Warnings and Precautions
Speak with your doctor before taking Pazopanib Accord if any of the following conditions apply to you. Your doctor will determine whether the benefits of treatment outweigh the risks and whether additional monitoring or dose adjustments are needed.
- Heart disease: Pazopanib can affect the heart's pumping ability, cause changes in heart rhythm (QT prolongation), and increase the risk of heart attack. Patients with pre-existing heart conditions require particularly close monitoring, including baseline and periodic echocardiograms and electrocardiograms.
- Liver disease: Pazopanib is metabolized by the liver and can cause hepatotoxicity, including potentially fatal liver failure. Liver function tests should be performed before starting treatment and at regular intervals throughout therapy. Patients with pre-existing liver impairment may require dose adjustment.
- History of blood clots or bleeding: Pazopanib increases the risk of both bleeding events and thromboembolic events (blood clots), including deep vein thrombosis, pulmonary embolism, and arterial thrombosis. Patients with a history of these conditions require careful risk-benefit assessment.
- Gastrointestinal problems: Patients with a history of gastrointestinal perforation (holes in the stomach or intestine) or fistula (abnormal connections between parts of the intestine) should inform their doctor, as pazopanib may increase the risk of these serious complications.
- Thyroid problems: Pazopanib can reduce thyroid hormone production (hypothyroidism). Thyroid function should be monitored before and during treatment. Patients who develop hypothyroidism may need thyroid hormone replacement therapy.
- Kidney problems: Renal function should be assessed before starting treatment. Patients with impaired kidney function require monitoring, as proteinuria (protein in the urine) is a known side effect of pazopanib.
- Previous lung collapse (pneumothorax): Patients with a history of pneumothorax should be closely monitored, as this condition has been reported in patients treated with pazopanib.
- Aneurysm or arterial dissection: Patients with a history of aneurysm (enlargement and weakening of a blood vessel wall) or arterial dissection (tearing of a blood vessel wall) should inform their doctor, as VEGF pathway inhibitors may increase the risk of these events.
Children and Adolescents
Pazopanib Accord is not recommended for use in patients under 18 years of age. The safety and efficacy of pazopanib have not been established in the pediatric population. For safety reasons, pazopanib must not be given to children younger than 2 years. Pediatric oncology patients should be treated according to established pediatric protocols under specialist supervision.
Pregnancy, Breastfeeding, and Fertility
Pazopanib Accord is not recommended during pregnancy. Based on its mechanism of action and preclinical data, pazopanib may cause harm to a developing fetus by disrupting blood vessel formation, which is essential for normal embryonic and fetal development. The effects of pazopanib during human pregnancy have not been studied in controlled trials, but the potential for teratogenicity and embryo-fetal toxicity is a recognized concern with all VEGF pathway inhibitors.
Women of childbearing potential must use effective contraception during treatment and for at least 2 weeks after the last dose. If pregnancy occurs during treatment, the patient should inform her doctor immediately for reassessment of the treatment plan. Men (including those who have had a vasectomy) whose partner is or could become pregnant must use condoms during treatment and for at least 2 weeks after the last dose.
Breastfeeding should be avoided during pazopanib treatment, as it is not known whether the active substance or its metabolites pass into breast milk. Given the potential for serious adverse effects in nursing infants, a decision should be made to either discontinue breastfeeding or discontinue treatment, taking into account the importance of the medicine to the mother.
Fertility may be affected by pazopanib treatment in both men and women. Patients who wish to preserve fertility should discuss options such as sperm banking or oocyte cryopreservation with their healthcare provider before starting treatment.
Driving and Operating Machinery
Pazopanib Accord may cause side effects such as dizziness, fatigue, weakness, and blurred vision that can impair your ability to drive or operate machinery safely. If you experience any of these symptoms, avoid driving or using machines until the symptoms have resolved. Each patient is responsible for assessing their own fitness to drive based on their individual response to the medicine.
How Does Pazopanib Accord Interact with Other Drugs?
Pazopanib Accord has clinically significant interactions with several drug classes. As pazopanib is primarily metabolized by the cytochrome P450 enzyme CYP3A4, drugs that strongly inhibit or induce this enzyme can substantially alter pazopanib blood levels, potentially reducing efficacy or increasing toxicity.
Always inform your doctor or pharmacist about all medicines you are currently taking, have recently taken, or might take, including over-the-counter medicines, herbal remedies, and nutritional supplements. Your doctor may need to adjust your pazopanib dose or choose an alternative medication to avoid dangerous interactions.
Major Interactions
| Drug/Class | Category | Effect | Clinical Recommendation |
|---|---|---|---|
| Ketoconazole, Itraconazole, Voriconazole | Strong CYP3A4 inhibitors | Significantly increases pazopanib levels | Avoid concomitant use; consider alternative antifungal agents |
| Clarithromycin, Telithromycin | Strong CYP3A4 inhibitors | Significantly increases pazopanib levels | Avoid; use azithromycin as an alternative if possible |
| Atazanavir, Indinavir, Nelfinavir, Ritonavir, Saquinavir | HIV protease inhibitors (CYP3A4 inhibitors) | Significantly increases pazopanib levels | Avoid concomitant use; consult HIV specialist for alternatives |
| Rifampicin | Strong CYP3A4 inducer | Significantly decreases pazopanib levels | Avoid; substantially reduces anticancer efficacy |
| Nefazodone | Strong CYP3A4 inhibitor | Significantly increases pazopanib levels | Avoid; use alternative antidepressant |
Other Important Interactions
| Drug/Class | Category | Effect | Clinical Recommendation |
|---|---|---|---|
| Simvastatin (and other statins) | HMG-CoA reductase inhibitors | Increased risk of statin-related side effects (myopathy, rhabdomyolysis) | Monitor closely; consider dose reduction or alternative lipid-lowering agent |
| Proton pump inhibitors (e.g., omeprazole) | Acid-reducing agents | May reduce pazopanib absorption | Avoid if possible; consult your doctor for alternatives |
| H2-receptor antagonists (e.g., ranitidine) | Acid-reducing agents | May reduce pazopanib absorption | Take pazopanib at least 2 hours before or 10 hours after the H2 blocker |
| Antacids (e.g., aluminum/magnesium hydroxide) | Acid-neutralizing agents | May reduce pazopanib absorption due to raised gastric pH | Separate administration by at least 2 hours |
What Is the Correct Dosage of Pazopanib Accord?
The standard recommended dose of Pazopanib Accord is 800 mg taken once daily. The tablets must be taken on an empty stomach — at least two hours after a meal or one hour before a meal — as food significantly increases absorption and may lead to higher, potentially toxic, blood levels.
Adults
Standard Dosing — Renal Cell Carcinoma & Soft Tissue Sarcoma
Dose: 800 mg once daily (taken as 2 x 400 mg tablets or 4 x 200 mg tablets)
Timing: Take on an empty stomach, at least 2 hours after a meal or 1 hour before a meal
Administration: Swallow tablets whole with water. Do not crush, break, or chew
Maximum dose: 800 mg per day
Duration: Continue for as long as your doctor recommends, typically until disease progression or unacceptable toxicity
Take Pazopanib Accord at approximately the same time each day to maintain consistent blood levels. For example, you may take it two hours after breakfast or one hour before lunch. Your doctor may reduce the dose in 200 mg increments (to 600 mg, 400 mg, or as needed) if you experience side effects that require dose modification. The dose should not be increased above 800 mg per day.
Patients with moderate hepatic impairment may require a reduced starting dose of 200 mg once daily. Pazopanib is not recommended for patients with severe hepatic impairment due to insufficient data and the risk of hepatotoxicity. Your doctor will perform liver function tests before starting therapy and regularly throughout your treatment course.
Children and Adolescents
Pediatric Use
Pazopanib Accord is not recommended for patients under 18 years of age. Safety and efficacy have not been established in the pediatric population. Pazopanib must not be administered to children younger than 2 years of age for safety reasons.
Elderly Patients
No specific dose adjustment is required for elderly patients based on age alone. However, elderly patients may be more susceptible to certain side effects, particularly hepatotoxicity, hypertension, and cardiac events. More frequent monitoring of liver function, blood pressure, and cardiac status is recommended. Dose adjustments should be made based on individual tolerability and organ function rather than age.
Missed Dose
If you miss a dose, do not take a double dose to make up for it. Simply take your next dose at the usual scheduled time. Missing a single dose is unlikely to significantly affect the overall efficacy of your treatment, but consistent daily dosing is important for maintaining therapeutic drug levels. If you frequently forget doses, discuss strategies with your pharmacist or doctor to help you remember.
Overdose
If you take more Pazopanib Accord than prescribed, or if a child accidentally swallows the medicine, contact your doctor, hospital emergency department, or poison control center immediately. There is no specific antidote for pazopanib overdose. Treatment is supportive and may include monitoring of blood pressure, liver function, and cardiac rhythm. Show the medication packaging or leaflet to the healthcare provider if possible. Doses above 800 mg have been associated with increased toxicity, particularly hepatotoxicity and hypertension.
What Are the Side Effects of Pazopanib Accord?
Like all medicines, Pazopanib Accord can cause side effects, although not everybody gets them. Some side effects can be serious and require immediate medical attention. Your healthcare team will monitor you closely for potential complications throughout your treatment.
Potentially Serious Side Effects Requiring Immediate Medical Attention
The following serious side effects have been reported with pazopanib. If you experience any of these, stop taking the medicine and seek emergency medical care immediately:
- Posterior reversible leukoencephalopathy syndrome (RPLS): A rare but potentially life-threatening brain condition causing speech problems, vision changes, seizures, confusion, and high blood pressure.
- Hypertensive crisis: Sudden and severe blood pressure elevation causing severe chest pain, headache, blurred vision, confusion, nausea, shortness of breath, seizures, or fainting.
- Cardiac events: Heart failure, heart attack, or abnormal heart rhythm (QT prolongation) causing irregular heartbeat, chest pain, swelling of the legs, or sudden loss of consciousness.
- Stroke: Numbness or weakness on one side of the body, difficulty speaking, sudden headache, or dizziness.
- Severe hemorrhage: Bleeding in the gastrointestinal tract, lungs, kidneys, or brain, presenting as blood in stool, urine, or sputum, or unexplained abdominal pain.
- Gastrointestinal perforation or fistula: Severe abdominal pain, nausea, vomiting, fever, or discharge of bloody or foul-smelling fluid from the abdomen.
- Hepatotoxicity: Yellowing of skin or eyes (jaundice), dark urine, fatigue, nausea, right-sided abdominal pain, easy bruising.
- Thromboembolic events: Blood clots in legs (deep vein thrombosis) or lungs (pulmonary embolism) causing chest pain, shortness of breath, leg swelling or pain.
- Tumor lysis syndrome: A rapid breakdown of cancer cells causing irregular heartbeat, seizures, confusion, muscle cramps, and decreased urine output.
Side Effects by Frequency
Very Common
May affect more than 1 in 10 patients
- High blood pressure (hypertension)
- Diarrhea
- Nausea and vomiting
- Abdominal pain
- Decreased appetite and weight loss
- Taste changes or loss of taste
- Mouth sores (stomatitis)
- Headache
- Tumor-related pain
- Fatigue, weakness, and lack of energy
- Hair color changes or hair loss (alopecia)
- Decreased skin pigmentation
- Skin rash (possibly with peeling)
- Hand-foot syndrome (redness and swelling of palms or soles)
- Elevated liver enzymes (in blood tests)
- Decreased albumin, platelets, or white blood cells (in blood tests)
- Protein in urine (proteinuria)
Common
May affect up to 1 in 10 patients
- Indigestion, bloating, and flatulence
- Nosebleeds (epistaxis)
- Dry mouth
- Infections
- Drowsiness or insomnia
- Chest pain and shortness of breath
- Heart failure and slow heart rate
- Blood clots (thromboembolic events)
- Bleeding in the mouth, rectum, or lungs
- Dizziness and blurred vision
- Hot flushes and chills
- Edema (swelling due to fluid retention)
- Tingling, weakness, or numbness in extremities
- Skin rash, redness, itching, dry skin
- Nail disorders
- Excessive sweating and dehydration
- Muscle, joint, and tendon pain; muscle cramps
- Hoarseness, shortness of breath, cough
- Coughing up blood (hemoptysis)
- Hiccups
- Pneumothorax (lung collapse)
- Hypothyroidism and abnormal liver function (in blood tests)
Uncommon
May affect up to 1 in 100 patients
- Stroke and transient ischemic attack (TIA)
- Heart attack (myocardial infarction) and cardiac ischemia
- Thrombotic microangiopathy (TMA)
- Increased red blood cell count (polycythemia)
- Pulmonary embolism
- Severe gastrointestinal hemorrhage
- QT prolongation (heart rhythm disorder)
- Gastrointestinal perforation or fistula
- Hypertensive crisis
- Pancreatitis (inflammation of the pancreas)
- Hepatitis, liver dysfunction, or jaundice
- Peritonitis (inflammation of the abdominal lining)
- Severe or irregular menstruation
- Increased sensitivity to sunlight (photosensitivity)
- Non-healing skin ulcers
Rare
May affect up to 1 in 1,000 patients
- Pneumonitis (inflammation of the lungs)
- Aneurysm and arterial dissection (weakening or tearing of blood vessel walls)
- Posterior reversible leukoencephalopathy syndrome (RPLS)
If you experience any side effect that becomes severe or bothersome, or if you notice any side effects not listed here, please inform your doctor or pharmacist. Reporting of suspected adverse reactions after authorization is important, as it allows continued monitoring of the benefit-risk balance of the medicine.
How Should You Store Pazopanib Accord?
Store Pazopanib Accord at room temperature with no special storage conditions required. Keep out of sight and reach of children at all times. Do not use after the expiry date printed on the blister pack, bottle, and carton after "EXP."
The expiry date refers to the last day of the stated month. Once expired, medicines may no longer be safe or effective and should be disposed of properly. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist about how to dispose of medicines no longer in use — these measures help protect the environment and prevent accidental exposure.
Pazopanib Accord tablets are available in PVC/PE/PVDC/aluminum blister packs or white HDPE bottles with child-resistant PP closures. Keep the tablets in the original packaging to protect them from moisture and light. If stored in a bottle, ensure the cap is firmly closed after each use. Do not transfer tablets to other containers.
What Does Pazopanib Accord Contain?
Pazopanib Accord contains pazopanib (as hydrochloride) as its active ingredient, available in 200 mg and 400 mg film-coated tablets with distinct appearances for easy identification.
200 mg Film-Coated Tablets
Each 200 mg tablet contains pazopanib hydrochloride equivalent to 200 mg of pazopanib. The tablets are capsule-shaped, pink, film-coated, and embossed with "200" on one side, measuring approximately 14.3 mm × 5.7 mm. The inactive ingredients include: microcrystalline cellulose (E460), sodium starch glycolate (type A), povidone (E1201), and magnesium stearate (E470b) in the tablet core. The film coating (Opadry 13B540026 Pink) contains hypromellos (E464), titanium dioxide (E171), macrogol (E1521), red iron oxide (E172), and polysorbate 80 (E433).
400 mg Film-Coated Tablets
Each 400 mg tablet contains pazopanib hydrochloride equivalent to 400 mg of pazopanib. The tablets are capsule-shaped, white, film-coated, and embossed with "400" on one side, measuring approximately 18.0 mm × 7.1 mm. The inactive ingredients are the same as the 200 mg tablets, except the film coating (Opadry 13B58802 White) does not contain red iron oxide.
Available Pack Sizes
Pazopanib Accord is available in blister packs containing 10, 30, 60, or 90 tablets; perforated unit-dose blisters containing 10×1, 30×1, 60×1, or 90×1 tablets; or white HDPE bottles containing 30, 60, or 90 tablets. Not all pack sizes may be marketed in your country. The marketing authorization holder is Accord Healthcare B.V., Utrecht, Netherlands.