Pazopanib is a targeted therapy medicine for certain cancers. It is marketed as Votrient and Paznib among others. The drug is indicated for the treatment of patients with advanced renal cell cancer (kidney cancer). It is also prescribed to treat metastatic soft tissue sarcoma in some patients prior to chemotherapy. It is available as tablets of strengths 200 mg and 400 mg for oral administration.

FDA Approval History:

For advanced renal cell cancer: Oct 19, 2009

For advanced soft tissue sarcoma: Apr 26, 2012

Uses

Pazopanib is a tyrosine kinase inhibitor that targets multiple proteins that feed cancer cells. The drug is indicated for use in patients with:

• Renal cell carcinoma: Advanced tumors that begin in the tissues that line the kidney.
• Soft tissue sarcoma: Tumors that begin in muscle, nerves, blood vessels, tendons, or any other soft tissue.

This drug belongs to the class of antineoplastic agents. It is a second-generation small-molecule inhibitor of many tyrosine kinases. Initially, Pazopanib was developed by a multinational pharmaceutical company, GlaxoSmithKline. It works by starving the tumor cells. The medicine is expected to stop blood flow to the tumor. This may lead to cancer cell death (apoptosis) eventually.

Working

Like other multitargeted tyrosine kinase inhibitors, Pazopanib works against elements that help cancer cells grow. In medical terms, those elements are known as growth factor receptors.

STEP-1
Growth Factor Receptors: These receptors include Vascular endothelial growth factor receptors (VEGFR-1, -2, and -3), Platelet-derived growth factor receptors (PDGFR-α and -β), Fibroblast growth factor receptors (FGFR-1 and -3), and Stem cell factor receptor (c-Kit).

STEP-2
Pazopanib Enters: Pazopanib inhibits multiple kinases. It interferes with ligand-induced autophosphorylation of VEGFR-2, Kit, and PDGFR-β receptors. In vivo, it inhibited the growth of some human tumor xenografts in mice.

STEP-3
Cell Death: It reduces tumor blood flow, increases tumor apoptosis (programmed cell death), reduces tumor interstitial fluid pressure, and inhibits tumor growth.

Side Effects

Alongside the expected effects, Pazopanib may show certain unwanted reactions. The oncologist may prescribe some drugs to counter the side effects. Note that experiencing any side effects for too long requires medical attention.

Bladder-related issues

• Blood in the urine
• Frequent urination
• Pain in the pelvis
• Dark urine

More common side effects

• Chills
• Pale eyes
• Nervousness
• Chest pain
• Constipation
• Dry skin
• Swollen glands
• Weight gain
• Blurred vision
• Hair loss
• Loss of appetite

Less common side effects

• Confusion
• Fainting
• Sweating
• Bloody nose
• Bleeding from the rectum
• Trouble speaking
• Irregular heart rate

Side effects specific to females

• Irregular vaginal bleeding
• Vaginal discharge
• Increased menstrual flow

Warnings & Precautions

• Pregnancy
  Pazopanib is not indicated for use in pregnant females. Its administration may result in fetal harm to the unborn baby. If the patient gets pregnant during Pazopanib therapy, she must be informed about the potential risks.
• Breastfeeding
  It is not known whether Pazopanib is excreted into breast milk or not. On the safer side, the oncologists ask the patient to discontinue breastfeeding.
• Pediatric Use
  Experts aren’t sure about the safety and efficacy of Pazopanib in pediatric patients.
• Geriatric Use
  When Pazopanib was administered to older patients, experts didn’t observe any major differences. Though not considering the greater sensitivity of geriatric patients remains irrelevant.
• Renal Impairment
  Patients with renal impairment may require dose adjustments. If a case of severe renal dysfunction exists, the use of Pazopanib must be avoided.
• Hepatic Impairment
  Patients with severe hepatic impairment may not be prescribed this drug. Cases like mild to moderate liver diseases may require dose modifications.
• Hemorrhagic Events
  Pazopanib has not been studied for use in patients with gastrointestinal hemorrhage. Experts advise that this drug must not be used if such a condition has occurred in the recent past.
• Cardiac Dysfunction
  As per the trial results of pazopanib, 0.6% of enrolled patients were diagnosed with cardiac dysfunction. Thus, period evaluation of heart function becomes necessary.
• Gastrointestinal Perforation
  During the clinical trials, 0.9% of patients administering Pazopanib experienced gastrointestinal perforation. For the same reason, signs of such a condition must not be ignored.
• Infection
  Oncologists recommend discontinuation of Pazopanib if signs of a severe infection occur. In moderate cases, anti-infective therapy may be prescribed.

Interactions

Your doctor may ask you to list the medicines you already take and diseases you have or ever had. This is because of the fact that some medicines or diseases may interact with Pazopanib.

Interaction with medicines: Medicines that may interfere with Pazopanib’s working are abrocitinib, citalopram, bedaquiline, eltrombopag, efavirenz, hydroxychloroquine, and itraconazole. Patients may require dose adjustments if any of these drugs can’t be avoided. Though there are other drugs also that may have an effect on Pazopanib.

Interaction with diseases: Since disease interactions affect the medicine's working, doctors ask for the patient's medical history. Pazopanib may not be indicated or require dose changes in the following conditions:

• CV disease
• Hypothyroidism
• Bleeding
• Liver dysfunction
• QT prolongation
• Thromboembolic disorders
• Hypertension
• GI perforation
• Lung dysfunction
• Proteinuria

Interaction with food and alcohol: Consumption of grapefruit during Pazopanib therapy may cause side effects. Grapefruit does so by increasing the blood levels of the drug. Taking this medicine with food may also lead to higher blood levels. Thus, it is advised to take Pazopanib on an empty stomach.

To eliminate the risk of interactions, oncologists may recommend certain dose modifications.

Overdose

The recommended dosage of Pazopanib is 800 mg orally once daily on an empty stomach. Though this remains relevant only till unacceptable toxicity or disease progression. The dose must be reduced for patients with liver disease. Note that this drug is not recommended for use in patients with severe hepatic impairment.

In case of an overdose, the patient may experience serious side effects. There is no proven antidote to manage this condition. Treatment of overdosage involves only general supportive therapies.

NOTE: This article is not intended to be a substitute for any prescription or medical advice. Pazopanib is a prescription-based drug that must not be consumed/sold otherwise.