Paznib

Name of Medicine: Paznib

Active Ingredient: Pazopanib

Chemical Formula: C21H23N7O2S

Inactive Ingredients: Magnesium stearate, povidone, microcrystalline cellulose, and sodium starch glycolate

Indication: Renal Cell Carcinoma (a type of Kidney Cancer)

Description: Paznib is a formulation of Pazopanib, an approved drug. It is administered orally with a glass of water.

What is Paznib?

Paznib is an anti-cancer medicine. It comprises pazopanib as its active salt composition. It belongs to the class of antineoplastic agents (drugs that hinder cancer cell growth). Paznib (Pazopanib) is considered a type of chemotherapy for cancer of the kidney. It is available in the form of tablets of strengths 200mg and 400mg.

Clinical Relevance

Paznib tablet is a prescription-based medicine. This drug is used in the treatment of patients diagnosed with a certain type of kidney cancer. It is effective specifically in treating renal cell carcinoma that has spread to nearby tissues, lymph nodes, or organs. Another indication of Pazopanib is advanced soft tissue sarcoma.

Clinical Pharmacology

Pharmacodynamics

Paznib is a synthetic indazolylpyrimidine with steady-state concentrations of more than 15 g/ml. This concentration is sufficient to see maximal inhibition of VEGFR2 phosphorylation as well as some anti-tumor effect (the concentration necessary to block receptors is 0.01 - 0.084 mol/L). In patients receiving treatment, there is a decrease in tumor blood flow, an increase in tumor apoptosis, prevention of tumor development, a decrease in tumor interstitial fluid pressure, and hypoxia in cancer cells.

Mechanism of Action

Paznib is a second-generation multitargeted tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors-1, -2, and -3, platelet-derived growth factor receptors-alpha, beta, and c-kit. These receptor targets are part of the angiogenesis pathway, which helps tumors survive and develop by facilitating the production of blood vessels.

Metabolism

CYP3A4 and, to a lesser extent, CYP1A2 and CYP2C8 metabolize it. Metabolites have a lower level of activity than pazopanib (10 to 20-fold less active). Three of its metabolites are found in the systemic environment and account for around 10% of plasma radioactivity.

Route of elimination

In cancer patients, it is primarily eliminated by feces (82.2%) and to a lesser extent through urine (4%). The majority of the dosage is excreted unaltered. Oxidative metabolites make up around 10% of the dose and are largely excreted in the stool.

Clinical Trials

Pazopanib showed a statistically and clinically significant increase in progression-free survival in patients with advanced/metastatic renal cell carcinoma in a randomized phase III study (VEG105192; NCT00334282) (mRCC). The final overall survival (OS) and safety results have been released.

The difference in ultimate OS between patients who received pazopanib and those who received placebo was not statistically significant (22.9 versus 20.5 months, respectively; hazard ratio [HR] = 0.91; 95 percent confidence interval [CI], 0.71–1.16; one-sided P =.224). The OS analysis was muddled by early and frequent crossover from placebo to pazopanib, as well as an extended period of crossover treatment. Pazopanib reduced mortality in IPCW studies (HR = 0.504; 95 percent CI, 0.315–0.762; two-sided P =.002). RPSFT analysis yielded similar, albeit non-significant, results (HR = 0.43; 95 percent CI, 0.215–1.388; two-sided P =.172). The cumulative exposure to pazopanib has grown by 30% since the prior cutoff. There were no new safety signals or changes in the type, frequency, or severity of adverse events in the pazopanib safety profile.

Drug Category

• Angiogenesis Inhibitors: These are unique cancer drugs that work by blocking the growth of blood vessels. Angiogenesis inhibitors block only those blood vessels that contribute to the growth of cancer cells in the body.
• Kinase Inhibitors: They are a group of pharmacologic agents that keep the cancerous cells from growing. Kinase inhibitors do so by interfering with the action of blood vessels responsible for tumor growth. 
• Antineoplastic Agents: Antineoplastic agents are drugs that are used to treat certain types of cancer. Anticancer agents function by identifying and killing malignant cells in the body.

Interactions

Drug-Disease Interaction

• Hepatic impairment: Certain patients with hepatic diseases may require dose adjustments after a few days. If the patient is suffering from mild disease, no modification of the dose is required. However, in moderate and severe cases, either dose must be reduced to 200 mg or the therapy can be discontinued.

Drug-Drug Interactions

• CYP3A4 Inhibitors: Drugs like ritonavir, ketoconazole, and clarithromycin must not be administered concomitantly with Paznib (Pazopanib) tablets. These are the strong inhibitors of  CYP3A4 that can increase pazopanib concentrations. Dose reduction may be required if these drugs can’t be avoided.
• CYP3A4 Inducers: Drugs like rifampin must not be administered concomitantly with Paznib (Pazopanib) tablets. These are the strong inducers of  CYP3A4 that can decrease pazopanib concentrations. Dose adjustments may be required if these drugs can’t be avoided.

Dosage and Administration

Recommended Dose: Paznib (Pazopanib) is available as tablets of two strengths: 200 mg and 400 mg. The recommended dose to start the therapy is 800 mg. The dose must be administered at least 2 hours after or 1 hour before food. It is advisable to not crush or chew the tablets due to the chance of increased absorption rate. 

Overdosage: An overdose on Paznib (Pazopanib) therapy can lead to severe events including heart failure and death. It is important to know the right amount of dose. If overdose symptoms occur, seek your doctor’s help immediately. 

Dose Adjustments: Certain patients with hepatic diseases may require dose adjustments after a few days. If the patient is suffering from mild disease, no modification of the dose is required. However, in moderate and severe cases, either dose must be reduced to 200 mg or the therapy can be discontinued.

Adverse Reactions

While receiving Paznib (Pazopanib) tablets, patients may develop certain adverse effects. They must be monitored thoroughly for severe events. In case of unmanageable conditions, dose adjustments or discontinuation of the medicine may be required.

Gastrointestinal effects like stomach pain, indigestion, diarrhea, black-colored stools, dark urine, nausea, vomiting, tenderness while touching the abdomen, and pelvis pain may occur in some individuals receiving Paznib therapy. 

Moderate side effects may occur including painful urination, muscle weakness, high blood pressure, difficulty in breathing, unusual sweating, dizziness, fainting, swelling in the legs or arms, decreased alertness, severe back pain.

Severe events such as vertigo, sleeplessness, anxiety, sadness, palpitations, myocardial infarction (lack of blood flow to your heart muscle), angina pectoris (chest pain or discomfort), and cardiomegaly (an enlarged heart) can be experienced.

Allergic reactions like skin rash, itching, redness on the skin, abdominal pain, irritation, back or joint pain, seizures, breathing problems, vision changes, and drowsiness may also be experienced by some individuals getting Paznib therapy.

Warnings and Precautions

• Pediatrics: The safety and effectiveness of Paznib (Pazopanib) tablets have not been established in pediatric patients.
• Geriatrics: No overall differences in the effectiveness of this drug have been noted during the clinical trials. Though patients aged above 60 years may be more vulnerable to adverse events.
• Pregnant women: At a dose of 3 mg/kg/day (roughly 0.1 times the human clinical exposure based on AUC), pazopanib caused teratogenic effects in pregnant rats, including cardiovascular malformations (retro esophageal subclavian artery, missing innominate artery, changes in the aortic arch) and incomplete or absent ossification.
• Nursing mothers: This medication is not known to be excreted in human milk. Because many drugs are excreted in human milk and because Pazopanib can cause major adverse reactions in nursing infants, a choice may be made to stop breastfeeding.
• Hepatic impairment: Certain patients with hepatic diseases may require dose adjustments after a few days. If the patient is suffering from mild disease, no modification of the dose is required. However, in moderate and severe liver problems, either dose must be reduced to 200 mg or the therapy can be discontinued.
• Surgery: If you have a scheduled surgery during the treatment period of Paznib (Pazopanib) tablets, make sure to contact your doctor regarding the potential benefits and risks. 
• Severe allergic reactions: During Paznib (Pazopanib) therapy, some patients may experience serious allergic reactions like abdominal pain, irritation, back or joint pain, and redness on the skin. Contact your doctor if the condition gets unmanageable.

Packaging and Storage

Paznib (Pazopanib) is available in the form of tablets of strengths 200 mg and 400 mg for oral administration only. Paznib tablets must be stored at 68°F to 77°F (20°C to 25°C). Keep anti-cancer drugs away from children and pets. Protect the medicines from direct heat, light, and moisture. Store Paznib (Pazopanib) tablets in the same bottle.