Panitumumab - Uses, Side Effects, Dosage, Drug Warnings, and Precautions

Overview

In September 2006, the FDA granted Panitumumab its first approval for treating EGFR (epidermal growth factor receptor)-expressing metastatic colorectal cancer with disease progression despite earlier therapy. The European Medicines Agency (EMEA) and Health Canada both gave Panitumumab approval in 2007 and 2008, respectively, to treat refractory EGFR-expressing metastatic colorectal cancer in patients with non-mutated (wild-type) KRAS (Key Result Areas). It is an entirely human monoclonal antibody that targets the epidermal growth factor receptor. It is also the first monoclonal antibody to establish the use of KRAS as a prognostic biomarker.

Uses of Panitumumab

Panitumumab is used for treating metastatic colorectal cancer that expresses EGFR and is resistant to chemotherapy regimens containing Fluoropyrimidine, Oxaliplatin, and Irinotecan.

How Does Panitumumab Work?

Panitumumab functions by obstructing signals that instruct cancer cells to proliferate and divide. It adheres to a particular protein on the surface of some cancer cells known as the epidermal growth factor receptor (EGFR). Only bowel tumors that contain a healthy RAS gene respond to Panitumumab.

Dosage Forms

This medication is dispensed in single-use vials as a colorless, preservative-free, sterile solution.

The following forms are available -

• Each 5-milliliter single-use vial contains 100 milligrams of Panitumumab in 5 mL (20 mg/mL).

• Each 10 mL single-use vial contains 200 mg of Panitumumab in 10 mL (20 mg/mL).

• Each 20 mL single-use vial contains 400 mg of Panitumumab in 20 mL (20 mg/mL).

Dosage and Administration:

• This medication is administered intravenously with a dose of 6 mg/kg every 14 days via an intravenous infusion over 60 minutes (1000 mg) or 90 minutes (greater than 1000 mg).

• In mild infusion reactions, the infusion rate should be reduced by fifty percent.

• In cases of severe and debilitating reactions, this medication should be stopped immediately.

• Missed Dose: If patients miss an appointment, they should contact their healthcare professional to schedule the subsequent dose soon.

Use in Specific Populations:

1) Pregnancy

This medication should not be prescribed to pregnant women, as studies reveal its use can harm the developing fetus. Women expecting a pregnancy should also immediately stop this medication.

2) Lactating and Nursing Women

Studies reveal that traces of Panitumumab may not be passed on to the baby via lactation or nursing; however, IgG (immunoglobulin G) is excreted in human milk. Since these antibodies can be transferred to the lactating baby, based on the importance of the medication for lactating women, they should either stop breastfeeding or take it.

3) Geriatric Use

Studies show that there are no differences between younger and older adults in terms of the efficacy and safety of this medication. However, a thorough risk assessment should be made before prescribing Panitumumab to elderly patients.

4) Pediatric Use

Due to the limited availability of studies with individuals belonging to this population, an in-depth risk assessment should be made before prescribing Panitumumab to pediatric patients.

Warnings and Precautions:

1. Dermatologic Toxicity

Panitumumab is known to cause skin reactions. Hence, in the event of any skin reaction, this medication should be discontinued or withheld until symptoms resolve. Healthcare professionals should also monitor patients to prevent inflammatory and infectious skin reactions and their sequelae.

2. Photosensitivity

Patients should ensure that they limit sun exposure in all possible ways, as sunlight can exacerbate or, in some cases, precipitate skin reactions. Patients can use sunscreen and all physical barriers, such as sunglasses, wide-brimmed hats, etc.

3. Infusion Reactions

This medication is administered via intravenous routes. Infusion reactions are seen within the first 24 hours of administering or infusing the drug. In the event of any infusion reactions, the infusion should be stopped. The health care professionals should make an in-depth assessment, and based on the persistence and severity of the reaction, the medication can be readministered or discontinued permanently.

4. Increased Toxicity With Combination Chemotherapy

This medication should not be used with other drugs for chemotherapy, as studies have reported that its combination with other medications can result in increased toxicity.

5. Pulmonary Fibrosis

Several studies report that this medication can precipitate lung infections in specific individuals. Hence, in the event of any form of lung condition, such as interstitial lung disease, pneumonitis, or lung infiltrates, healthcare professionals should discontinue the use of Panitumamb in such patients with immediate effect.

6. Electrolyte Depletion and Monitoring

Healthcare professionals should monitor patients' electrolytes during and for eight weeks after the completion of Panitumumab therapy.

For Patients:

What Is Metastatic Colorectal Cancer?

Cancer that originates in the colon or rectum is known as colorectal cancer. This form of cancer has four stages, from stage 0, which represents extremely early cancer, to stage 4, which represents metastatic colorectal cancer. Colorectal cancer that has spread to other body parts, is called metastatic cancer. This indicates that it has progressed to local or distant areas, such as lymph nodes or other organs. Even though cancer can spread to any organ in the body, colorectal cancer most frequently metastasizes or spreads to the lining of the stomach and abdominal organs, the liver, and the lungs. Rarely is colon cancer that has spread to distant places treatable. Once cancer has spread, it might be challenging to inhibit its metastasis. However, some medicines can help manage symptoms and prevent or stop the spread of the malignancy. Treatments for colorectal cancer have improved due to ongoing developments.

What Are the Signs and Symptoms Associated With Colorectal Cancer?

Some various signs and symptoms are associated with metastatic colorectal cancer.

They can be categorized in the following manner -

1. Early warning signs and symptoms include

• Rectal bleeding.

• Anemia.

• Persistent abdominal pain.

• Sudden, unexplained weight loss.

• Frequent urgency to pass stools.

• Narrow stools.

2. Local symptoms of colorectal cancer include:

• Diarrhea.

• Constipation.

• Changes in bowel habits.

• Blood in stools.

• Abdominal bloating and discomfort.

• Abdominal cramps.

• Change in consistency of stool.

3. Systemic symptoms of colorectal cancer include:

• Nausea.

• Vomiting.

• Sudden, unexplained weight loss.

• Anemia.

• Jaundice.

• Fatigue.

What Is Panitumumab and How Does It Work?

Panitumumab is a drug that is used to treat colorectal cancer. It functions by obstructing signals that instruct cancer cells to proliferate and divide. It adheres to a particular protein on the surface of some cancer cells known as the epidermal growth factor receptor (EGFR). Only bowel tumors that contain a healthy RAS gene respond to Panitumumab.

Panitumumab is a medication that is administered intravenously, that is, via a drip in the vein. It can be given in the following manner -

• Via a Central Line - A central venous catheter is used to administer fluids, blood, medications, and nutrition to the patients. Usually, this line is much longer than regular intravenous catheters.

• Via a PICC Line - Otherwise known as the peripherally inserted central catheter, it provides healthcare professionals access to the large central veins near the heart. It is used to administer medications and liquid forms of nutrition.

• Via Portacath - A device that is used to deliver medications intravenously. It can also be used to draw blood.

This medication is administered at 6 mg/kg every 14 days as an intravenous infusion over 60 minutes (around 1000 mg) or 90 minutes (less than 1000 mg). Patients who miss an appointment or a scheduled dose should contact their healthcare professional to schedule the subsequent dose soon. The dosing of this medication is modified in the event of certain reactions.

The modifications are as follows -

• In the event of mild infusion reactions, the infusion rate should be reduced by fifty percent.

• In the event of severe and debilitating reactions, this medication should be stopped immediately.

Dietary instructions

Unless mentioned otherwise by the healthcare professional, patients can continue with their regular diet.

What Are the Side Effects of Panitumumab?

The use of this medication is associated with many side effects.

They include the following -

• Pimples.

• Itchy skin.

• Red, inflamed skin.

• Peeling of skin.

• Dry skin.

• Cracked skin.

• Swelling and inflammation around the nail beds in both fingernails and toenails.

• Dry mouth.

• Dry lips.

• Anxiety.

• Altered mental status.

• Confusion.

• Diarrhea.

• Decreased urination.

• Muscle cramps and spasms.

• Loosening of fingernails.

• Drowsiness.

• Nausea.

• Vomiting.

• Tingling in the hands and feet.

• Watery eyes.

• Unexplained fatigue.

• Sunken eyes.

• Unexplained and sudden weight loss and weight gain.

Studies have also reported severe side effects that necessitate immediate medical intervention.

If patients experience the following symptoms, they should rush to the hospital immediately -

• Difficulty in breathing.

• Difficulty in swallowing.

• Shortness of breath or breathlessness.

• Hoarseness of voice.

• Chest discomfort in the form of chest tightness and chest pain.

• Itchy skin.

• Skin rash.

• Hives.

• Unexplained fever.

• A sudden episode of chills.

• Dizziness.

• Fainting spells.

• Vision problems such as diminished or blurred vision.

• Nausea.

Storage

• This medication is dispensed in single-use vials, and they should be stored in their original packaging until use, under refrigeration, ensuring that the temperatures range between two and eight degrees Celsius ( 36 to 46 degrees Fahrenheit). This medication should never be frozen.

• This medication should be kept away from direct sunlight.

• The vials of Panitumumab do not contain preservatives. Hence any unused portion remaining in the vial must be discarded.

• The diluted infusion solution of this medication should be used within six hours of its preparation, provided it is stored at room temperature. However, if it is stored at two to eight degrees Celsius (36 to 46 degrees Fahrenheit), it should be used within 24 hours of dilution.

• This medication should be discarded per the local guidelines and medical regulatory bodies. If not expired, unneeded medicines can also be returned to the pharmacist.

Overdose

• Studies report that an overdose can occur when the recommended therapeutic dose is doubled, at about 12mg/kg. It can result in diarrhea, dehydration, fatigue, and skin toxicity.

• Skin reactions and toxicities that belong to grade three and higher necessitate the permanent discontinuation of the drug, provided the toxicity does not reduce to a lower level within a month.

• Suppose the toxicity level reduces to a lower grade, for example, grade two; in that case, the healthcare professional should focus on symptomatic treatment while a maximum of two doses of Panitumumab.

• When the Panitumumab therapy is started again, it should begin with half the percentage of the initial dose.

• If toxicities recur after the infusion, the drug should be permanently discontinued, and other treatment options should be considered.

Contraindications

Patients of the following groups should not use Panitumumab -

• Pregnant women.

• Nursing or breastfeeding women.

• Individuals with a history of allergies to this drug.

• Individuals who elicit signs of allergies after using the drug.

• Individuals with lung disease can exacerbate with the use of Panitumumab.

What Should Be Informed to the Healthcare Provider Before Using Panitumumab?

Before starting the infusions, patients should inform their healthcare professionals of the following things -

1. Individuals having a history of allergy to this medication should inform their healthcare professional about the history. Usually, healthcare professionals avoid prescribing this medication to such individuals or modify the dose to a lower concentration.

2. Patients should share their medical history and inform the physician of all the prescription and non-prescription medications they might be taking.

3. Patients should also share their medical history, especially in the case of the following conditions -

• Heart conditions.

• Eye disorders.

• Kidney diseases.

• Skin and nail conditions.

• Lung diseases.

What Precautions Should Patients Take After Starting the Infusions of Panitumumab?

After starting the infusions, patients should be wary of the following things -

1. Panitumumab is known to cause skin reactions ranging from mild to severe. A few skin conditions may be so extreme that they can lead to infections and death.

Patients should immediately contact the physician if any of the following signs and symptoms are elicited-

• Pimples.

• Itchy skin.

• Red, inflamed skin.

• Peeling of skin.

• Dry skin.

• Cracked skin.

• Swelling and inflammation around the nail beds in both fingernails and toenails.

2. Panitumumab may also cause severe or life-threatening reactions in specific individuals. Hence, both patients and doctors should closely monitor all signs and symptoms.

When any of the following symptoms are experienced, patients should stop taking the medication and immediately rush to the hospital without any delay -

• Difficulty in breathing.

• Difficulty in swallowing.

• Shortness of breath or breathlessness.

• Hoarseness of voice.

• Chest discomfort in the form of chest tightness and chest pain.

• Itchy skin.

• Skin rash.

• Hives.

• Unexplained fever.

• A sudden episode of chills.

• Dizziness.

• Fainting spells.

• Vision problems such as diminished or blurred vision.

• Nausea.

If such symptoms and a severe reaction occur, the healthcare professional should stop the medication and focus on treating the debilitating symptoms.

3. Both men and women that receive the infusions should use adequate contraception during and after the last dose of Panitumumab.

For Doctors:

Indications

Panitumumab is used for treating metastatic colorectal cancer that expresses EGFR and is resistant to chemotherapy regimens containing Fluoropyrimidine, Oxaliplatin, and Irinotecan.

Contraindications

This medication is contraindicated in individuals that belong to the following groups -

• Pregnant women.

• Nursing or breastfeeding women.

• Individuals with a history of allergies to this drug.

• Individuals who elicit signs of allergies after using the drug.

• Individuals with lung disease can exacerbate with the use of Panitumumab.

Dosage Forms and Strengths:

• 100 mg Panitumumab in 5 mL (20 mg/mL) single-use vial.

• 200 mg Panitumumab in 10 mL (20 mg/mL) single-use vial.

• 400 mg Panitumumab in 20 mL (20 mg/mL) single-use vial.

The solution for infusion should be prepared under aseptic conditions in the following way -

• Before administering, the medications should be inspected for discoloration, contamination, and forms of particulate matter.

• Ideally, it should be a colorless solution. Occasionally it may contain small amounts of visible translucent-to-white, proteinaceous, amorphous particulates of Panitumumab. These particles can be easily removed via filtration. If any such particles are seen, the vials should not be shaken. Discolored vials should be discarded as they are contaminated.

• A small amount of the medication, required for the dose of 6mg/kg, should be withdrawn and diluted to achieve a total volume of 100 mL with 0.9 % sodium chloride injection, USP.

• The doses above 1000 mg require a dilution to 150 mL with 0.9 percent sodium chloride injection, USP.

• Physicians should ensure the final concentration is at most 10mg/mL.

• The diluted solution should be mixed via gentle inversion.

Drug Administration

• This medication should be administered using a low-protein-binding 0.2 μm or 0.22 μm in-line filter.

• Healthcare professionals should never forget that the infusion of Panitumumab should always be administered via an infusion pump.

• They should flush the line before and after administering the infusion with 0.9 percent sodium chloride injection, USP, so the infusion does not mix with other drug products or intravenous solutions.

• The infusion should not be administered as an infusion or mixed with other medications. A peripheral intravenous line or indwelling intravenous catheter should administer the infusion over 60 minutes.

• However, doses higher than 1000 mg should always be infused over 90 minutes.

• The diluted infusion of Panitumumab should be used within six hours of preparation, provided it is stored at room temperature. However, storing it between two and eight degrees Celsius can be used within 24 hours of dilution.

• Any remnants in the vial should be discarded.

• Measures should be taken to ensure this medication is not administered as an intravenous push or bolus.

Pharmacology:

Mechanism of Action

Panitumumab, which binds specifically to the human epidermal growth factor receptor (EGFR), is a recombinant human IgG2 kappa monoclonal antibody. The type I receptor tyrosine kinase subfamily includes the transmembrane glycoprotein known as EGFR. The overexpression of EGFR has been seen in many human malignancies, including those of the colon and rectum, even though it is expressed in normal cells.

When the EGFR interacts with its typical ligands, several intracellular proteins are phosphorylated and activated, which controls the transcription of genes involved in cellular growth, survival, motility, and proliferation. The wild-type KRAS gene is activated by signal transduction through EGFR, but the KRAS gene can become activated somatically by mutation within a cancer cell.

Half-Life of Panitumumab

After administering a single dose, Panitumumab has an approximate half-life of seven and a half days.

Adverse Effects

The adverse effects of Panitumumab include the following -

• Pimples.

• Pruritis.

• Red, inflamed skin.

• Peeling of skin.

• Dry skin.

• Cracked skin.

• Swelling and inflammation around the nail beds in both fingernails and toenails.

• Xerostomia.

• Dry lips.

• Anxiety.

• Altered mental status.

• Confusion.

• Diarrhea.

• Decreased urination.

• Muscle cramps and spasms.

• Loosening of fingernails.

• Drowsiness.

• Nausea.

• Vomiting.

• Tingling in the hands and feet.

• Watery eyes.

• Unexplained fatigue.

• Sunken eyes.

• Unexplained and sudden weight loss and weight gain.

• Difficulty in breathing.

• Difficulty in swallowing.

• Dyspnea.

• Hoarseness of voice.

• Chest discomfort in the form of chest tightness and chest pain.

• Hives.

• Unexplained fever.

• A sudden episode of chills.

• Dizziness.

• Fainting spells.

• Vision problems such as diminished or blurred vision.

Pharmacokinetics -

• Absorption: This drug is administered intravenously, and hence has a faster absorption rate than other drugs which are administered via oral routes.

• Metabolism: Metabolism studies have not been conducted with this drug.

• Distribution: Studies have not been done in humans, and have only been done on monkeys. However, the studies that have been done on monkeys have shown inconsistent results.

• Elimination: Studies reveal that most metabolites are excreted via urine.