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Gefitinib (Iressa) Tablets - Uses, Dose, Side effects, MOA, Brand Names

Gefitinib (Iressa) is a Tyrosine kinase inhibitor that is used to treat non-small cell lung cancer with mutated or overactive EGFR receptors.

Gefitinib (Iressa) Uses:

Non-small cell lung cancer:
- First-line treatment of metastatic non-small cell lung cancer (NSCLC) in tumors with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected in tumor or plasma specimen by an approved test.
Limitation of use:
- Safety and efficacy have not been established for patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution mutations.

Gefitinib (Iressa) Dose in Adults

Gefitinib (Iressa) Dose in the treatment of metastatic non-small cell lung cancer (NSCLC), with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations:

For people with a certain type of lung cancer called Non-Small Cell Lung Cancer (NSCLC) that has spread to other parts of the body, and who have specific changes in their cancer cells called EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, here's how the medicine is taken:

Take it by mouth (swallow it).
Take 250 milligrams (mg) all at once every day.
Keep taking it this way until either the cancer gets worse or the side effects become too severe.

Missed Doses:

If you forget to take a dose, it's okay.
But if it's less than 12 hours until your next scheduled dose, don't take the missed dose.
Just wait for the next scheduled dose.

Dosage adjustment for concomitant therapy:

Changing the Dose When Taking Other Medicines:

If you're taking a medicine that is a strong CYP3A4 inducer (a type of drug that affects how your body processes certain other drugs):

Increase your gefitinib dose to 500 mg once every day. But, only do this if you're not having bad side effects from gefitinib.
When you stop taking that strong CYP3A4 inducer, wait 7 days, then reduce the gefitinib dose back to the regular 250 mg once every day.

Use in Children:

Not indicated.

Gefitinib (Iressa) Pregnancy Risk Category: D

Tests on animals have shown that gefitinib can harm the baby if given to a pregnant mother.
Women who can become pregnant should use strong birth control methods during gefitinib treatment.
Keep using birth control for at least 2 weeks after stopping gefitinib.
It's crucial to avoid getting pregnant while on gefitinib to protect the baby.

Use of Gefitinib while breastfeeding

We don't know if gefitinib gets into breast milk.
Because it might harm a baby if it does, the maker of the medicine says women shouldn't breastfeed while taking gefitinib.

Gefitinib (Iressa) Dose in Kidney disease:

The manufacturer hasn't given any special dosage instructions for people with kidney problems.
Since only a tiny amount (less than 4%) of gefitinib and its breakdown products are removed from the body by the kidneys, it's probably not necessary to change the dose for people with kidney problems.
But, we don't have information on how safe it is for people with very low kidney function (those with a CrCl of 20 mL/minute or less).

Gefitinib (Iressa) Dose in Liver disease:

Starting Treatment with Existing Liver Problems:

The manufacturer hasn't given any special dosage instructions for people starting gefitinib with liver problems.
However, people with liver problems might have more of the drug in their system than others.

Adjusting Dosage if Liver Problems Develop While on Treatment:

If blood tests show your liver enzymes (ALT and/or AST) increase a lot (called grade 2 or higher):
- Stop taking gefitinib for up to 14 days.
- You can start taking it again once the liver problem gets better or is only mild (known as grade 1).
If you get severe liver problems while on gefitinib: Stop taking it forever.

Common Side Effects of Gefitinib (Iressa):

Central Nervous System:
- Insomnia
- Fatigue
Dermatologic:
- Dermatological Reaction
- Skin Rash
- Xeroderma
- Pruritus
- Paronychia
- Acne Vulgaris
- Alopecia
Gastrointestinal:
- Diarrhea
- Anorexia
- Nausea
- Decreased Appetite
- Vomiting
- Stomatitis
- Constipation
Genitourinary:
- Proteinuria
Hepatic:
- Increased Serum AST
- Increased Serum ALT
Neuromuscular & Skeletal:
- Weakness

Less Common Side Effects Of Gefitinib (Iressa):

Central Nervous System:
- Hypoesthesia
- Peripheral Sensory Neuropathy
- Peripheral Neuropathy
Dermatologic:
- Nail Disease
- Acneiform Eruption
Endocrine & Metabolic:
- Dehydration
Gastrointestinal:
- Xerostomia
Genitourinary:
- Cystitis
Hematologic & Oncologic:
- Anemia
- Pulmonary Hemorrhage
- Hemorrhage
- Neutropenia
- Leukopenia
- Thrombocytopenia
Hepatic:
- Increased Serum Bilirubin
Neuromuscular & Skeletal:
- Myalgia
- Arthralgia
Ophthalmic:
- Eye Disease
Renal:
- Increased Serum Creatinine
Respiratory:
- Cough
- Interstitial Pulmonary Disease
Miscellaneous:
- Fever

Contraindications to Gefitinib (Iressa):

In the US: The manufacturer hasn't listed any specific conditions or situations where you shouldn't take gefitinib.
In Canada: Don't take gefitinib if you're allergic to it or any part of the pill.

Warnings and precautions

Gefitinib and Skin Problems:

A lot of people (almost half) taking gefitinib get skin reactions.
Some people can have severe skin reactions. This includes peeling skin, blisters, and conditions like toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, and bullous dermatitis.
If you get severe skin issues like big blisters or peeling skin while on gefitinib, stop the medicine or take a break from it.

Gefitinib and Stomach Issues:

About one-third of people taking gefitinib have diarrhea. Some cases can be severe (grade 3 or 4).
If you get diarrhea, your doctor will help manage it. Drink enough fluids to avoid dehydration.
If your diarrhea is severe or doesn't go away, you might need to stop gefitinib for a little while (up to 14 days).
Rarely, there have been cases of holes forming in the stomach or intestines. If this happens, you'll need to stop taking the medicine.
Other stomach-related problems like feeling sick (nausea), throwing up (vomiting), eating less (decreased appetite), and mouth sores (stomatitis) can also happen while taking gefitinib.

Gefitinib and Liver Problems:

Gefitinib can raise liver enzyme levels, like ALT, AST, and bilirubin. Some of these increases can be pretty severe.
Very rarely, people taking gefitinib have had deadly liver problems.
To keep an eye on the liver, doctors will check liver tests from time to time.
If the liver starts to work poorly while on gefitinib, the medicine might be paused. If liver problems get really bad, gefitinib will need to be stopped for good.

Gefitinib and Eye Problems:

Some people taking gefitinib experience eye issues. This includes problems like inflamed eyes (keratitis), scratched corneas (corneal erosion), weird eyelash growth, pink eye (conjunctivitis), eyelid inflammation (blepharitis), and dry eyes. Some of these can be quite severe.
If you've had recent eye surgery or wear contact lenses, you might be at a higher risk of getting these eye problems.
If you're taking gefitinib and start having symptoms like increased tearing, blurry vision, eye pain, a red eye, or sensitivity to light, tell your doctor right away.
If someone has signs of a severe eye condition called keratitis, they should see an eye specialist immediately.
If eye problems get worse or are severe, you might need to pause or even stop taking gefitinib.

Gefitinib and Lung Problems:

Rarely, gefitinib can cause lung issues. This includes a condition called Interstitial Lung Disease (ILD) and other similar lung problems. Some of these problems can be very serious or even deadly.
If someone taking gefitinib starts having breathing problems (like shortness of breath), a cough, or a fever, they should tell their doctor right away.
If the doctor thinks it's ILD, they'll stop the gefitinib. If tests confirm it's ILD, the patient will need to stop taking gefitinib forever.

Gefitinib and Liver Problems:

People with liver problems due to cirrhosis might have more gefitinib in their system than others, whether their liver problem is mild, moderate, or severe.
Interestingly, in a study of patients with liver cancer spread (metastases), those with moderate liver problems had about the same amount of gefitinib in their system as those without liver problems.
If someone has moderate or severe liver problems and is taking gefitinib, they need to be watched closely for any side effects or issues.

Gefitinib: Drug Interaction

Risk Factor C (Monitor therapy)
Ajmaline	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Aprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CloBAZam	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Cobicistat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
CYP2D6 Inhibitors (Moderate)	May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).
CYP3A4 Inhibitors (Strong)	May increase the serum concentration of Gefitinib.
Darunavir	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Duvelisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Imatinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Lumefantrine	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Panobinostat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Peginterferon Alfa-2b	May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Perhexiline	CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
QuiNINE	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Vinorelbine	Gefitinib may enhance the neutropenic effect of Vinorelbine.
Vitamin K Antagonists (eg, warfarin)	Gefitinib may enhance the anticoagulant effect of Vitamin K Antagonists.
Risk Factor D (Consider therapy modification)
Abiraterone Acetate	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity.
Antacids	May decrease the serum concentration of Gefitinib. Management: Administer gefitinib at least 6 hours before or after administration of an antacid, and closely monitor clinical response to gefitinib.
Asunaprevir	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
CYP2D6 Inhibitors (Strong)	May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Strong)	May decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Dacomitinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index.
Enzalutamide	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring.
Histamine H2 Receptor Antagonists	May decrease the serum concentration of Gefitinib. Management: Administer gefitinib at least 6 hours before or after administration of a histamine H2-antagonist, and closely monitor clinical response to gefitinib.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.
Mitotane	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.
Pitolisant	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant.
Proton Pump Inhibitors	May decrease the serum concentration of Gefitinib. Management: Avoid use of proton pump inhibitors (PPIs) with gefitinib when possible. If required, administer gefitinib 12 hours after administration of the PPI or 12 hours before the next dose of the PPI.
St John's Wort	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Risk Factor X (Avoid combination)
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Monitoring parameters:

Before Starting Treatment:

EGFR Mutation: Check if the cancer cells or blood have a specific change (mutation) in the EGFR gene.

Regular Checks:

Liver Health:
- Check ALT, AST, and bilirubin levels in the beginning and then from time to time.
Blood Clotting (if also taking warfarin):
- Measure INR or prothrombin time to see how fast the blood clots.

Signs to Watch Out For:

Skin Issues: Look for rashes or skin reactions.
Stomach Issues: Be alert for signs of holes in the stomach or intestines.
Eye Problems: Watch out for any eye discomfort or vision changes.
Lung Issues: Pay attention to any breathing difficulties or coughing.

Special Groups:

CYP2D6 Poor Metabolizers: Some people process gefitinib differently; watch them closely for side effects.
Liver Issues: People with liver problems should be monitored extra carefully for side effects.

Always Check:

Adherence: Make sure the patient is taking the medicine as prescribed.

How to administer Gefitinib (Iressa)?

Regular Use:

You can take the tablet with or without eating food.

For Those Who Can't Swallow Pills:

Put the tablet in 120 to 240 mL (about half to a full cup) of water.
Stir it around for about 15 minutes.
Drink the mixture right away. If needed, it can be given through a nose-to-stomach tube.
To make sure you get all the medicine, rinse the container with another 120 to 240 mL of water.
Drink this rinse water or give it through the tube.

Mechanism of action of Gefitinib (Iressa):

Type of Drug: Gefitinib is a kind of medicine called a "tyrosine kinase inhibitor" (TKI).
Target: It focuses on a protein called "epidermal growth factor receptor" (EGFR). EGFR is found on the surface of normal and cancer cells. It's important for making cells grow and multiply.
How It Works: Gefitinib blocks the activity of EGFR by stopping it from getting "phosphorylated" (adding a chemical tag). This prevents signals from going further and makes it hard for cells to grow because they depend on these signals.
Effects: By doing this, gefitinib slows down the growth of cancer cells that rely on EGFR for their growth.
Different Types of EGFR: Gefitinib works especially well on cancer cells with specific types of mutations in the EGFR gene. These mutations are called "exon 19 deletion" and "exon 21 (L858R) substitution." The drug has a stronger bond to cells with these mutations than to normal EGFR.

Remember, gefitinib's goal is to stop cancer cells from growing by targeting a protein that's important for their growth.

Distribution:

Gefitinib spreads out in the body and takes up about 1400 liters of space.

Binding to Proteins:

90% of the drug attaches to proteins in the blood. It mainly binds to proteins named "albumin" and "alpha-acid glycoprotein."

Changing in the Body (Metabolism):

The liver changes most of gefitinib, especially by a system called "CYP3A4." A smaller part is changed by "CYP2D6." These changes create different substances (metabolites).

Getting into the Blood (Bioavailability):