Drug information of Dacomitinib

Dacomitinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which has activity against EGFR/HER1, HER2, and HER4, as well as some EGFR-activating mutations (exon 19 deletion or exon 21 L858R substitution mutation). Dacomitinib also has activity against DDR1, EPHA6, LCK, DDR2, and MNK1 (in vitro).

Distribution

V_ss: 1,889 L

Metabolism

Hepatic, primarily via oxidation and glutathione conjugation; CYP2D6 is involved in the formation of O-desmethyl dacomitinib (active), and CYP3A4 contributes to the formation of minor oxidative metabolites

Excretion

Feces: 79% (20% as parent drug); Urine: 3% (<1% as parent drug)

Time to Peak

~6 hours (range: 2 to 24 hours)

Half-Life Elimination

70 hours

Protein Binding

~98%

Labeled Indications

Non-small cell lung cancer, metastatic: First-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an approved test.

45 mg orally once a day until disease progression or unacceptable toxicity

Missed doses: If a dose is missed or vomited, do not make up the missed/vomited dose; administer the next dose as scheduled.

Side effects requiring immediate medical attention

Along with its needed effects, dacomitinib may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to dacomitinib or any component of the formulation.

Check with your doctor immediately if any of the following side effects occur while taking dacomitinib:

More common:

Blistering, crusting, irritation, itching, or reddening of the skin

body aches or pain

chest pain

chills

cough

cracked lips

cracked, dry, or scaly skin

deep cracks, grooves, or lines in the skin

diarrhea

difficulty in swallowing

ear congestion

fever

headache

itching, skin rash

loosening of the fingernails

loss of voice

nasal congestion

redness or soreness around the fingernails

redness, swelling, or pain of the skin

runny nose

scaling of the skin on the hands and feet

sneezing

sore throat sores, ulcers, or white spots on the lips, tongue, or inside the mouth

swelling

tightness in the chest

tingling of the hands and feet

trouble breathing

ulceration of the skin

unusual tiredness or weakness

Less common:

Confusion

decreased urination

dizziness

dry mouth

fainting

fever

increase in heart rate

lightheadedness

loss of heat from the body

rapid breathing

sunken eyes

thirst

wrinkled skin

Side effects not requiring immediate medical attention

Some side effects of dacomitinib may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common:

Burning, dry, or itching eyes

change in taste

constipation

decreased appetite

decreased weight

discharge, excessive tearing

hair loss or thinning of hair

increased hair growth on the forehead, back, arms, and legs

lack or loss of strength

loss of taste

nausea

redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid

trouble sleeping

vomiting

Less common:

Eye redness, irritation, or pain

You may need to have a negative pregnancy test before starting this treatment.

Do not use dacomitinib if you are pregnant. It could harm the unborn baby. Use effective birth control to prevent pregnancy while you are using dacomitinib and for at least 17 days after your last dose.

Do not breast-feed while using this medicine, and for at least 17 days after your last dose.

Tell your doctor if you have ever had:

• frequent diarrhea; or
• breathing problems (other than lung cancer).

Your doctor will perform a special test to make sure you have the correct tumor type to be treated with dacomitinib.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

Take the medicine at the same time each day, with or without food.

If you vomit shortly after taking dacomitinib, do not take another dose. Wait until your next scheduled dose time to take the medicine again.

Drink plenty of liquids while you are taking dacomitinib.

Dacomitinib can cause severe diarrhea, which can be life-threatening if it leads to dehydration or infection.

If you have diarrhea while taking dacomitinib: Call your doctor right away. You may need to start taking anti-diarrhea medicine such as loperamide (Imodium) to quickly treat diarrhea.

Store at room temperature away from moisture and heat.

Dacomitinib can cause skin reactions. Use a skin moisturizer and avoid sunlight or tanning beds. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Use is not recommended.

US FDA pregnancy category: Not assigned.

Comments:

-Advise females of reproductive potential to use effective contraception during therapy and for at least 17 days after the final dose.

-If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.

-Verify negative pregnancy status in females of reproductive potential prior to initiating therapy.