Erlotinib is a medication that belongs to a class of drugs known as tyrosine kinase inhibitors (TKIs). It's primarily used in the treatment of certain types of cancer, particularly non-small cell lung cancer (NSCLC) and pancreatic cancer.

Erlotinib works by inhibiting the activity of the epidermal growth factor receptor (EGFR) tyrosine kinase, which is involved in promoting cell growth and division. In cancers like NSCLC and pancreatic cancer, there can be mutations or overexpression of EGFR that contribute to uncontrolled cell growth. Erlotinib helps to slow down the growth and spread of cancer cells by specifically targeting the EGFR pathway.

Erlotinib (Tarceva) is a Tyrosine kinase inhibitor that targets EGFR (epidermal growth factor receptors) mutated cancer cells.

Erlotinib (Tarceva) Uses:

• Metastatic Non-small cell lung cancer:
  • Used in the 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 by an approved test either as first-line, maintenance, or as second or greater line treatment after progression following at least 1 prior chemotherapy regimen.
  • Limitations of use:
    • Use in combination with platinum-depended chemotherapy is not recommended.
    • Safety and efficacy of treatment for metastatic NSCLC with EGFR mutations other than exon 19 deletion or exon 21 (L858R) substitution have not been established.
• Pancreatic cancer:
  • First-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer (in combination with gemcitabine)

Erlotinib (Tarceva) Dose in Adults

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

• The usual dose is one 150 mg tablet by mouth every day.
• They'll keep taking it until the cancer grows again or if they have bad side effects.

Erlotinib (Tarceva) Dose in the treatment of Pancreatic cancer:

• For treating pancreatic cancer, Erlotinib is taken as a 100 mg tablet once a day.
• It's taken along with another medicine called gemcitabine.
• The patient will keep taking it until the cancer gets worse or if the side effects become too much.

Erlotinib (Tarceva) Dosage adjustment for concomitant CYP inhibitors/inducers:

Strong CYP3A4 inhibitors:

• Try not to use them together with Erlotinib.
• If you must use them together and experience strong side effects, reduce the Erlotinib dose in steps of 50 mg. Do this once the side effects are back to normal or are mild.

Drugs that inhibit both CYP3A4 and CYP1A2 (like ciprofloxacin):

• Again, try not to use them together.
• If you have to and get strong side effects, reduce the Erlotinib dose in steps of 50 mg. Do this once the side effects are back to normal or are mild.

CYP3A4 inducers:

• Try not to use them at the same time as Erlotinib.
• If you must, increase the Erlotinib dose in steps of 50 mg every two weeks. You can go up to a maximum dose of 450 mg.
• When you stop taking the CYP3A4 inducer, go back to the regular starting dose of Erlotinib.

Moderate CYP1A2 inducers:

• Avoid using them with Erlotinib if you can.
• If you can't avoid it, increase the Erlotinib dose in steps of 50 mg every two weeks, but don't go over 300 mg. Watch closely for side effects.
• Once you stop the CYP1A2 inducer, go back to the regular Erlotinib dose for the specific medical condition you're treating.

Erlotinib (Tarceva) Dosage adjustment for concomitant smoking:

• It's best not to smoke while taking Erlotinib.
• If you do smoke, you might need a higher dose. Your doctor might increase it little by little, adding 50 mg every two weeks until you're taking no more than 300 mg.
• If you stop smoking, you should go back to the original dose of Erlotinib that was recommended for your health condition.

Use in Children:

Not indicated

Erlotinib (Tarceva) Pregnancy Risk Category: D

• Studies on animals showed that erlotinib might cause harm during pregnancy.
• The medicine can pass from a pregnant person to their unborn baby.
• We don't have a lot of information about its use during pregnancy in humans.
• Because of how erlotinib works, it could harm an unborn baby.
• It's advised that women who can get pregnant should use birth control while taking erlotinib and for at least 1 month after they stop taking it.

Use of Erlotinib (Tarceva), while breastfeeding

• We're not sure if erlotinib gets into breast milk.
• There's a chance that babies breastfed by someone taking erlotinib might experience serious side effects like skin problems, diarrhea, liver issues, lung issues, blood problems, and eye issues.
• Because of these risks, it's recommended that women who are breastfeeding should not take erlotinib. If they do, they shouldn't breastfeed while on the medication and for 2 weeks after they stop.

Erlotinib (Tarceva) Dose in Kidney Disease:

Starting Treatment with Kidney Problems:

• The maker of the drug doesn’t give special dosing instructions for people with kidney problems when they start treatment. This is because they haven't studied it in depth.
• Also, only a small amount of the medicine (less than 9%) goes out of the body through urine.

If Kidney Issues Happen During Treatment:

• Severe Kidney Issues (Grade 3/4):
  • Stop taking the drug and think about whether you should stop for good.
  • If you start the drug again after the kidney problems go away or get much better, take a lower dose. Reduce it by 50 mg.
• Kidney Failure because of Liver Problems or Being Too Dehydrated:
  • Stop taking the drug until your kidneys get better.
  • If you start the drug again, take a lower dose. Reduce it by 50 mg.

Erlotinib (Tarceva) Dose in Liver disease:

Starting Treatment with Liver Problems:

• If the bilirubin (a liver enzyme) is a bit high or the liver function is classed as Child-Pugh A, B, or C:
  • The drug's official instructions don't suggest a specific dose change, but you should be extra careful. Monitor the liver closely.
• If bilirubin is very high (more than 3 times the normal level):
  • Be extremely careful.
• Some studies suggest:
  • People with certain liver problems might start on a smaller dose (75 mg every day) and increase the dose if no problems come up.
  • One study said that people with moderate liver issues had similar experiences with the drug as those with normal liver function.

If Liver Problems Happen During Treatment:

• People with Normal Liver to Start:
  • If bilirubin goes over 3 times the normal level or other liver enzymes (transaminases) go over 5 times the normal level: Pause the medicine and think about whether you should stop for good.
  • If you start the drug again after the liver gets better, take a lower dose. Reduce it by 50 mg.
• People with Liver Problems or Blockages to Start:
  • If bilirubin doubles or transaminases go up by three times compared to the start: Pause the drug and consider if you should stop for good.
  • If you start the drug again after the liver gets better, take a lower dose. Reduce it by 50 mg.
• If there are severe liver problems and they don't get a lot better within 3 weeks: Stop the drug completely.

Common Side Effects of Erlotinib (Tarceva):

• Cardiovascular:
  • Chest Pain
• Central Nervous System:
  • Fatigue
• Dermatologic:
  • Skin Rash
  • Xeroderma
  • Acne Vulgaris
  • Pruritus
  • Paronychia
  • Alopeciaa
• Gastrointestinal:
  • Diarrhea
  • Anorexia
  • Abdominal Pain
  • Constipation
  • Nausea
  • Decreased Appetite
  • Vomiting
  • Mucositis
  • Stomatitis
• Genitourinary:
  • Urinary Tract Infection
• Hematologic & Oncologic:
  • Anemia
• Infection:
  • Increased Susceptibility To Infection
• Neuromuscular & Skeletal:
  • Back Pain
  • Arthralgia
  • Musculoskeletal Pain
  • Weakness
• Ophthalmic:
  • Conjunctivitis
  • Keratoconjunctivitis Sicca
• Respiratory:
  • Cough
  • Dyspnea
• Miscellaneous:
  • Fever

Less Common Side Effects Of Erlotinib (Tarceva):

• Cardiovascular:
  • Peripheral Edema
• Central Nervous System:
  • Pain
  • Headache
  • Anxiety
  • Voice Disorder
  • Dizziness
  • Insomnia
  • Neurotoxicity
  • Paresthesiaz
• Dermatologic:
  • Folliculitis
  • Nail Disease
  • Exfoliative Dermatitis
  • Palmar-Plantar Erythrodysesthesia
  • Bullous Dermatitis
  • Hypertrichosis
  • Skin Fissure
  • Acneiform Eruption
  • Erythema
  • Dermatitis
  • Erythematous Rash
• Endocrine & Metabolic:
  • Weight Loss
• Gastrointestinal:
  • Dyspepsia
  • Taste Disorder
  • Xerostomia
• Hematologic & Oncologic:
  • Leukopenia
  • Thrombocytopenia
  • Lymphocytopenia
• Hepatic:
  • Increased Serum ALT
  • Increased Gamma-Glutamyl Transferase
  • Hepatic Failure
  • Hyperbilirubinemia
• Neuromuscular & Skeletal:
  • Muscle Spasm
  • Musculoskeletal Chest Pain
  • Ostealgia
• Otic:
  • Tinnitus
• Renal:
  • Increased Serum Creatinine
  • Renal Failure,
• Respiratory:
  • Nasopharyngitis
  • Epistaxis
  • Pulmonary Fibrosis
  • Pulmonary Embolism
  • Respiratory Tract Infection
  • Pneumonitis

Adverse Reactions Reported With Combination Therapy:

Common Side Effects Of Erlotinib (Tarceva):

• Cardiovascular:
  • Edema
  • Thrombosis
• Central Nervous System:
  • Fatigue
  • Anxiety
  • Depression
  • Dizziness
  • Headachez
• Dermatologic:
  • Skin Rash
  • Alopecia
• Gastrointestinal:
  • Nausea
  • Anorexia
  • Flatulence
  • Diarrhea
  • Abdominal Pain
  • Vomiting
  • Weight Loss
  • Stomatitis
  • Dyspepsia
• Hepatic:
  • Increased Serum ALT
  • Increased Serum AST
  • Hyperbilirubinemia
• Infection:
  • Increased Susceptibility To Infection
• Neuromuscular & Skeletal:
  • Ostealgia
  • Rigors
  • Myalgia
  • Neuropathy
• Respiratory:
  • Dyspnea
  • Cough
• Miscellaneous:
  • Fever

Less Common Side Effects Of Erlotinib (Tarceva):

• Cardiovascular:
  • Cardiac Arrhythmia
  • Syncope
  • Deep Vein Thrombosis
  • Cerebrovascular Accident
  • Myocardial Infarction
• Gastrointestinal:
  • Intestinal Obstruction
  • Pancreatitis
• Hematologic & Oncologic:
  • Hemolytic Anemia
  • Microangiopathic Hemolytic Anemia With Thrombocytopenia
• Renal:
  • Renal Insufficiency
  • Renal Failure
• Respiratory:
  • Interstitial Pulmonary Disease

Contraindications to Erlotinib (Tarceva):

• In the U.S.: There are no specific reasons listed by the manufacturer that say you shouldn't take erlotinib.
• In Canada: Don't take erlotinib if you're allergic to it or any of its ingredients.

Warnings and precautions

Cardiovascular events

• There have been reports of strokes, heart attacks, and reduced blood flow to the heart while using Erlotinib.
• Some of these events have been deadly.

Dermatologic toxicities:

• Skin issues like blisters, peeling, and rashes, which can be serious, even leading to conditions like Stevens-Johnson syndrome or toxic epidermal necrolysis, have been seen, and some have been fatal.
• A rash that looks like acne often appears on the face, upper chest, and back.
• Rashes might relate to how well the treatment is working and how long someone lives.
• Milder rashes can be managed with lotions, topical antibiotics, or creams. In severe cases, doctors might use oral antibiotics or systemic corticosteroids.
• Stay away from the sun, and if skin reactions are bad, the treatment dose might be reduced or temporarily stopped. For severe skin problems, the treatment might have to be stopped altogether.

Perforation of the gastrointestinal (GI),

• There have been reports of holes forming in the stomach or intestines (called GI perforation). Some of these have been deadly.
• The risk of this happening goes up if you're also taking medicines that affect blood vessels, steroids, NSAIDs, certain types of chemotherapy, or if you have a history of stomach ulcers or weak spots in the colon.
• If this severe issue happens while on Erlotinib, stop the treatment permanently.

Hematologic effects

• A rare blood condition, where red blood cells break down and there's a decrease in platelets (which help with clotting), has been seen in people taking Erlotinib combined with another drug called gemcitabine.

Hemorrhage

• There have been cases of increased bleeding, including some that were deadly, when people took Erlotinib with warfarin (a blood thinner).
• If taking both, it's important to closely check the blood's clotting ability using tests like prothrombin time and INR.

Hepatotoxicity

• Some people have experienced severe liver problems, including liver failure and a syndrome affecting both the liver and kidneys. Some of these cases were deadly.
• This risk seems higher in people who already have liver problems, but it has also been seen in those with normal liver function.
• Regularly check liver health using specific tests.
• People with any liver concerns should be checked even more often, especially if their liver issues come from a large number of cancer cells in the liver.
• If there are changes in liver health, the Erlotinib dose might need to be lowered, paused, or fully stopped.
• Be very careful with Erlotinib if the bilirubin (a marker of liver function) is more than 3 times the normal level.
• If you don't have liver problems to start with but your bilirubin goes over 3 times the normal level, or another liver test goes over 5 times the normal, pause the drug.
• If you had liver problems or blockages at the start and the bilirubin doubles or another liver test triples from the starting value, pause the drug.

Ocular toxicities:

• Some people have had serious eye problems like holes or ulcers in the cornea (the clear front part of the eye).
• Other issues include dry eyes, unusual eyelash growth, or inflammation of the cornea.
• These conditions can raise the risk of holes or ulcers in the cornea.
• If someone has eye pain or any new or worsening eye issues while taking Erlotinib, they should pause or stop the medicine.
• It's a good idea to have an eye check-up before starting Erlotinib. Then, check for any eye problems 4 to 8 weeks after starting the medicine.

Toxicity in the lungs:

• There have been rare but sometimes deadly cases of lung problems with Erlotinib. This includes a condition where lung tissue becomes damaged and scarred, known as interstitial lung disease (ILD).
• Symptoms can include difficulty breathing, lung inflammation, and scarring, among others.
• These symptoms can start anywhere from 5 days to over 9 months after starting the medicine, with an average time of about 39 days.
• If someone has new or worsening lung symptoms like shortness of breath, coughing, or fever without a clear reason, they should pause Erlotinib.
• If ILD is confirmed, Erlotinib should be stopped for good.

Renal impairment

• Some people have had serious kidney problems, including complete kidney failure, while on Erlotinib. Some of these cases were deadly.
• These kidney problems can be because of existing liver issues or due to severe dehydration.
• People with or at risk of kidney problems should be cautious when taking Erlotinib.
• It's essential to monitor for dehydration and regularly check kidney function and salt levels in the blood, especially if someone is at risk of dehydration.
• If severe kidney problems occur, pause Erlotinib until things get better.

NSCLC

• Some people with NSCLC might respond better to Erlotinib. This is often seen in:
  • People who have never smoked.
  • Those with EGFR mutations.
  • People of Asian descent.
• Specific EGFR mutations, mainly changes in exon 19 and exon 21 (L858R), seem to make Erlotinib more effective.
• However, Erlotinib might not be the best choice for people with NSCLC who have K-ras mutations. They likely won't benefit much from the drug. Studies have shown these mutations might even make the treatment less effective.
• There's a test called the "cobas EGFR mutation test" that can detect these specific EGFR mutations to help decide on NSCLC treatment.

Erlotinib: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Liver Checks:

• Regularly check liver function (transaminases, bilirubin, and alkaline phosphatase).
• Test more often if liver function gets worse.

Kidney Checks:

• Regular kidney function tests.
• Check salt levels in the blood, especially for those at risk of dehydration.

Blood Clotting (for those on warfarin):

• Regularly check prothrombin time and INR.

Lung Cancer (NSCLC) Checks:

• See if there's an EGFR mutation (important for treatment decisions).
• Use the "cobas EGFR mutation test" for first-line treatment decisions.
• Know the smoking status of the patient.

Eye Checks:

• Consider an eye exam at the start.
• Recheck for any eye issues 4 to 8 weeks after starting treatment.

Other Monitoring:

• Keep an eye on hydration levels.
• Watch for symptoms of lung issues, skin problems, and eye issues.

How to administer Erlotinib (Tarceva)?

On an Empty Stomach:

• Take it at least 1 hour before eating or 2 hours after eating.

With Stomach Medications:

• If possible, avoid taking it with medicines that reduce stomach acid, like proton pump inhibitors.
• If taking with an H2-receptor antagonist (like ranitidine):
  • Take Erlotinib 10 hours after the H2 antagonist and at least 2 hours before the next H2 antagonist dose.
• If needing an antacid, take it several hours apart from Erlotinib.

If You Can't Swallow Tablets:

• Dissolve the tablet in 100 mL of water.
• It can be taken by mouth or a feeding tube (silicone-based).
• Rinse the container with 40 mL of water and take that too to ensure the full dose.
• Take it right after preparing.
• If needed, you can also make an oral suspension (see instructions for making it, if available).

Mechanism of action of Erlotinib (Tarceva):

• Erlotinib acts like a "blocker" for a specific part of cells called HER1/EGFR, which is involved in cell growth.
• By blocking this, it stops a chain reaction inside cells that can lead to cell growth and division.
• This means it can help stop or slow down the growth of cancer cells.
• Erlotinib works especially well on certain mutations (changes) in EGFR, specifically exon 19 deletion or exon 21 L858R mutations, better than on regular, unchanged EGFR.

In short, Erlotinib blocks specific signals that can let cancer cells grow and divide.

Absorption:

• Taken by mouth, about 60% is absorbed on an empty stomach.
• Food boosts this to almost 100%.

Distribution:

• Spreads through a volume of 232 liters in the body.

Protein Binding:

• 93% binds to proteins in the blood, mainly to albumin and alpha-acid glycoprotein.

Metabolism (How the Body Breaks it Down):

• Mostly in the liver.
• Mainly by CYP3A4 and to a smaller extent by CYP1A1, CYP1A2, and CYP1C.

Bioavailability (Amount that Reaches the Bloodstream):

• Almost 100% with food.
• About 60% without food.

Half-life (Time for Half to Leave the System):

• 36.2 hours.

Time to Peak Level in Blood:

• 4 hours after taking it.

Excretion (How It Leaves the Body):

• Mostly as broken-down products.
• 83% through feces (only 1% unchanged).
• 8% through urine (less than 1% unchanged).

International Brand Names of Erlotinib:

• Tarceva
• Etopul
• Lungitinib
• Orlicert
• Tarcenib
• APO-Erlotinib
• PMS-Erlotinib
• TEVA-Erlotinib
• Birlotib
• Erlocip-E
• Erlonib
• Erlonix
• Erlotaz

Erlotinib Brand Names in Pakistan: