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Overview

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Name

Pazopanib Hydrochloride

Precaution

Before starting treatment with **Pazopanib Hydrochloride**, it is essential that patients consult their healthcare provider. Some key precautions include: - **Liver Function**: Pazopanib can cause **liver toxicity**, so it is important to monitor **liver enzymes** (such as **ALT** and **AST**) before starting therapy and periodically during treatment. If there is significant liver enzyme elevation, the medication may need to be discontinued. - **Hypertension**: Pazopanib can lead to **high blood pressure** (hypertension). Blood pressure should be monitored regularly, and hypertension should be managed appropriately. If hypertension is not controlled, Pazopanib should be discontinued. - **Bleeding Risk**: Pazopanib increases the risk of **bleeding** events, including **gastrointestinal bleeding** and **hemorrhage**, particularly in patients with tumors in areas prone to bleeding. Patients should be monitored closely for any signs of bleeding. - **Gastrointestinal Perforation**: There is a risk of **gastrointestinal perforation** (holes in the digestive tract), which is a serious side effect. Patients with a history of gastrointestinal problems should be monitored carefully. - **Wound Healing**: Pazopanib can interfere with the body's ability to heal wounds. It should be discontinued at least **7 days before any planned surgery**, and it should not be resumed until the wound has healed. - **Pregnancy and Breastfeeding**: Pazopanib is classified as **Pregnancy Category D** due to potential harm to the fetus. It should be avoided during pregnancy unless absolutely necessary. It is also not recommended during breastfeeding, as it is unknown if it is excreted in breast milk.

Indication

Pazopanib Hydrochloride is primarily used to treat specific types of cancers, including: - **Renal Cell Carcinoma (RCC)**: Pazopanib is approved for the treatment of **advanced renal cell carcinoma** (a type of kidney cancer). It is used in patients who are not candidates for surgery or who have metastatic RCC. - **Soft Tissue Sarcoma**: Pazopanib is also indicated for the treatment of **advanced soft tissue sarcoma** in patients who have previously received chemotherapy. It works by inhibiting tumor growth and reducing the spread of cancer cells. - **Ovarian Cancer**: In combination with other agents, Pazopanib is used to treat **advanced ovarian cancer** (although this may vary based on the specific clinical setting). - **Other Malignancies**: Pazopanib is also under investigation in various clinical trials for its effectiveness against other cancer types, particularly in **solid tumors**.

Contra indication

Pazopanib is contraindicated in the following situations: - **Hypersensitivity**: It should not be used by patients who have known **allergies** or **hypersensitivity** to Pazopanib or any of its components. - **Severe Liver Dysfunction**: Pazopanib is contraindicated in patients with **severe hepatic impairment** (Child-Pugh Class C) due to the risk of exacerbating liver dysfunction. - **Pregnancy**: Due to its potential teratogenic effects, Pazopanib should not be used during pregnancy unless the potential benefits outweigh the risks. It should be avoided in breastfeeding women as well. - **Severe Cardiovascular Disease**: Pazopanib is contraindicated in patients with a history of **severe cardiovascular disease**, including **recent heart attacks** or **uncontrolled heart failure**, due to the potential for cardiovascular complications such as **heart failure** and **arrhythmias**.

Side Effect

Pazopanib can cause both common and serious side effects. Patients should monitor for the following: - **Common Side Effects**: - **Fatigue** or weakness - **Diarrhea** - **Nausea** or vomiting - **Hypertension** (elevated blood pressure) - **Loss of appetite** - **Hair color changes** (e.g., graying or lightening of hair) - **Serious Side Effects**: - **Liver Toxicity**: Symptoms include yellowing of the skin or eyes (**jaundice**), dark urine, and severe abdominal pain. Liver function tests should be regularly monitored. - **Cardiovascular Issues**: Pazopanib can cause serious heart problems, including **heart failure**, **arrhythmias**, and **prolonged QT interval**. Patients should seek medical attention if they experience chest pain, shortness of breath, or palpitations. - **Hemorrhage**: Increased risk of bleeding (e.g., **gastrointestinal bleeding**, **hemorrhagic stroke**) is a concern. Watch for signs such as **bruising**, **coughing up blood**, or **black, tarry stools**. - **Gastrointestinal Perforation**: Symptoms such as **severe abdominal pain**, **fever**, or **vomiting** may indicate a perforation. - **Wound Healing Complications**: Pazopanib may interfere with the healing of wounds, so it is advised to stop treatment 7 days before surgery and avoid resuming until the wound is fully healed.

Pregnancy Category ID

4

Mode of Action

Pazopanib is a **tyrosine kinase inhibitor** that works by blocking the activity of several **receptor tyrosine kinases** involved in tumor cell growth and angiogenesis (formation of new blood vessels). Specifically, Pazopanib inhibits: - **VEGFR (Vascular Endothelial Growth Factor Receptor)**: Reducing angiogenesis, which is essential for tumor growth and metastasis. - **PDGFR (Platelet-Derived Growth Factor Receptor)**: Inhibiting this receptor decreases the growth of tumor cells. - **c-Kit**: This receptor is involved in the growth of several cancers, and its inhibition by Pazopanib reduces cancer cell proliferation. - **FGFR (Fibroblast Growth Factor Receptor)**: Blocking this receptor further reduces the ability of tumors to grow and spread. Through these mechanisms, Pazopanib reduces blood flow to tumors, inhibits cancer cell growth, and helps to shrink or stabilize tumors.

Interaction

Pazopanib interacts with several drugs, which can affect its efficacy or safety: - **CYP3A4 Inhibitors/Inducers**: Pazopanib is metabolized by the **CYP3A4 enzyme**, so drugs that affect this enzyme can alter Pazopanib levels. **CYP3A4 inhibitors** (e.g., **ketoconazole**, **ritonavir**) may increase Pazopanib levels, while **CYP3A4 inducers** (e.g., **rifampin**, **carbamazepine**) may decrease its levels. - **Anticoagulants**: Pazopanib may increase the risk of **bleeding** when used with **anticoagulants** (e.g., **warfarin**). Regular monitoring of blood coagulation is recommended if these drugs are used together. - **Chemotherapy**: Pazopanib may be used in combination with other chemotherapy agents; however, the combination can increase the risk of **toxicity** and **myelosuppression**. Close monitoring is required when used in combination with other cytotoxic drugs. - **Antihypertensive Drugs**: Pazopanib may cause **hypertension**, and patients using **antihypertensive medications** may need to adjust their dosage to manage blood pressure effectively. - **Gastric Acid Suppressants**: Since Pazopanib is absorbed in the stomach, **gastric acid suppressants** (e.g., **proton pump inhibitors**, **H2 blockers**) may interfere with its absorption and reduce its effectiveness.

Pregnancy Category Note

Information not available

Adult Dose

The typical dose of **Pazopanib Hydrochloride** for adults is **800 mg** taken orally once daily. It should be taken on an empty stomach, at least **1 hour before** or **2 hours after** meals. If a dose is missed, it should not be taken if the next dose is due in less than 12 hours. The dosage may need adjustment if there are issues related to liver function, blood pressure, or significant side effects. In such cases, dose reductions or discontinuation may be necessary.

Child Dose

Pazopanib has not been studied extensively in pediatric populations. Therefore, its use is not recommended in children, and the safety and efficacy have not been established for this age group. Pediatric patients should not be treated with Pazopanib unless in the context of a clinical trial or under special circumstances, and only with approval from an oncologist or pediatric specialist. Always consult a healthcare provider for guidance regarding the use of Pazopanib in specific situations, particularly for individuals with coexisting health conditions.

Renal Dose

In patients with **mild to moderate renal impairment** (creatinine clearance of 30–80 mL/min), no dose adjustment is needed. However, Pazopanib should be used cautiously in patients with severe renal impairment (creatinine clearance <30 mL/min). Close monitoring of renal function is required, and the dose may need to be reduced based on individual responses.

Administration

Information not available