Dabrafenib

Uses

What is Dabrafenib used for?

Dabrafenib may be used alone or in combination with another medication (trametinib) to treat a type of skin cancer (melanoma). It is also used with trametinib to treat a type of lung cancer (non-small cell lung cancer-NSCLC). Dabrafenib works by slowing the growth of cancer cells.

How should I take Dabrafenib?

Take this medication by mouth as directed by your doctor, usually twice daily about 12 hours apart. Take this medication on an empty stomach, at least 1 hour before or 2 hours after meals. Swallow the capsules whole. Do not open, crush, chew, or break the capsules.

The dosage is based on your medical condition and response to treatment.

Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of serious side effects will increase. Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the capsules.

How do I store Dabrafenib?

Dabrafenib is best stored at room temperature away from direct light and moisture. To prevent drug damage, you should not store Dabrafenib in the bathroom or the freezer. There may be different brands of Dabrafenib that may have different storage needs. It is important to always check the product package for instructions on storage, or ask your pharmacist. For safety, you should keep all medicines away from children and pets.

You should not flush Dabrafenib down the toilet or pour them into a drain unless instructed to do so. It is important to properly discard this product when it is expired or no longer needed. Consult your pharmacist for more details about how to safely discard your product.

Precautions & warnings

What should I know before using Dabrafenib?

Before taking dabrafenib, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: a certain enzyme deficiency (G6PD deficiency), liver disease, diabetes.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Dabrafenib is not recommended for use during pregnancy. It may harm an unborn baby. Discuss the risks and benefits with your doctor. It is important that men and women taking this medication use reliable forms of non-hormonal birth control (including condoms and/or diaphragms with spermicide) while taking this medication and for 2 weeks after treatment stops. Men and women taking dabrafenib, in combination with trametinib, should use reliable forms of non-hormonal birth control during treatment and for 4 months after stopping treatment. If you become pregnant, think you may be pregnant, or cause a pregnancy, tell your doctor right away.

Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the capsules.

It is unknown if this drug passes into breast milk. Because of the possible risk to the infant, breast-feeding is not recommended while using this drug and for 2 week after treatment.. Consult your doctor before breast-feeding.

Is it safe during pregnancy or breast-feeding?

There are no adequate studies in women for determining risk when using this Dabrafenib during pregnancy or while breastfeeding. Please always consult with your doctor to weigh the potential benefits and risks before taking Dabrafenib. Dabrafenib is pregnancy risk category N according to the US Food and Drug Administration (FDA).

FDA pregnancy risk category reference below:

• A=No risk,
• B=No risk in some studies,
• C=There may be some risk,
• D=Positive evidence of risk,
• X=Contraindicated,
• N=Unknown

Side effects

What side effects can occur from Dabrafenib?

Hair loss, thickening of the outer layers of the skin, headache, swelling/peeling of feet/hands, and joint/muscle/back pain may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Dabrafenib may rarely cause other cancers (including new skin cancer). Tell your doctor right away if you have symptoms such as: new wart, skin sore, change in size/color of a mole, skin bump that bleeds or does not heal, new lumps/growth, night sweats, unexplained/sudden weight loss.

This medication may rarely make your blood sugar rise, which can cause or worsen diabetes. Tell your doctor right away if you have symptoms of high blood sugar such as increased thirst/urination. If you already have diabetes, check your blood sugar regularly as directed and share the results with your doctor. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

In men, this medication can decrease sperm production, an effect that may lower male fertility. Consult your doctor for more details.

Tell your doctor right away if you have any serious side effects, including: easy bruising/bleeding, signs of heart failure (such as shortness of breath, swelling ankles/feet, unusual tiredness, unusual/sudden weight gain), signs of infection (such as fever, chills, persistent sore throat, cough), dizziness/fainting, signs of kidney problems (such as change in the amount of urine).

Get medical help right away if you have any very serious side effects, including: eye pain/swelling/redness, vision changes (such as blurred vision, sensitivity to light), fast/irregular heartbeat, signs of bleeding in the brain (such as severe headache, weakness on one side of the body, vision problems, slurred speech, seizures, or confusion), signs of stomach/intestinal bleeding (such as black/bloody stools, vomit that contains blood or looks like coffee grounds, or dizziness).

Dabrafenib can commonly cause a rash that is usually not serious. However, you may not be able to tell it apart from a rash that could be a sign of a severe reaction. Therefore, get medical help right away if you develop any rash.

Dabrafenib in combination with trametinib may rarely cause other serious side effects. Get medical help right away if you have any very serious side effects, including: sudden pain/swelling/redness (usually in the leg), chest pain, trouble breathing.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

Not everyone experiences these side effects. There may be some side effects not listed above. If you have any concerns about a side-effect, please consult your doctor or pharmacist.

Interactions

What drugs may interact with Dabrafenib?

This medication may decrease the effectiveness of hormonal birth control such as pills, patch, or ring. This could cause pregnancy. Discuss with your doctor or pharmacist if you should use additional reliable birth control methods while using this medication. Also tell your doctor if you have any new spotting or breakthrough bleeding, because these may be signs that your birth control is not working well.

Other medications can affect the removal of dabrafenib from your body, which may affect how dabrafenib works. Examples include azole antifungals (such as itraconazole, ketoconazole), gemfibrozil, macrolide antibiotics (such as clarithromycin, erythromycin), nefazodone, St. John’s wort, drugs used to treat seizures (such as phenobarbital, phenytoin), among others.

This medication can speed up the removal of other medications from your body, which may affect how they work. Examples include midazolam, warfarin, among others.

Dabrafenib may interact with other drugs that you are currently taking, which can change how your drug works or increase your risk for serious side effects. To avoid any potential drug interactions, you should keep a list of all the drugs you are using (including prescription drugs, nonprescription drugs and herbal products) and share it with your doctor and pharmacist. For your safety, do not start, stop, or change the dosage of any drugs without your doctor’s approval.

Does food or alcohol interact with Dabrafenib?

Dabrafenib may interact with food or alcohol by altering the way the drug works or increase the risk for serious side effects. Please discuss with your doctor or pharmacist any potential food or alcohol interactions before using this drug.

What health conditions may interact with Dabrafenib?

Dabrafenib may interact with your health condition. This interaction may worsen your health condition or alter the way the drug works. It is important to always let your doctor and pharmacist know all the health conditions you currently have.

Dosage

The information provided is not a substitute for any medical advice. You should ALWAYS consult with your doctor or pharmacist before using this Dabrafenib.

What is the dose of Dabrafenib for an adult?

Usual Adult Dose for Non-Small Cell Lung Cancer

150 mg orally twice a day, either used as monotherapy or in combination with trametinib.

Duration of Therapy: Until disease progression or unacceptable toxicity occurs.

Comments: Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to treatment initiation with FDA-approved tests: http://www.fda.gov/CompanionDiagnostics.

Uses: Treatment of:

-BRAF V600E Mutation-Positive Unresectable or Metastatic Melanoma as a single agent.

-BRAF V600E OR V600K Mutation-Positive Unresectable or Metastatic Melanoma in combination with trametinib.

-BRAF V600E Mutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC) in combination with trametinib.

Usual Adult Dose for Melanoma – Metastatic

150 mg orally twice a day, either used as monotherapy or in combination with trametinib.

Duration of Therapy: Until disease progression or unacceptable toxicity occurs.

Comments: Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to treatment initiation with FDA-approved tests.

Uses: Treatment of:

-BRAF V600E Mutation-Positive Unresectable or Metastatic Melanoma as a single agent.

-BRAF V600E OR V600K Mutation-Positive Unresectable or Metastatic Melanoma in combination with trametinib.

-BRAF V600E Mutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC) in combination with trametinib.

Renal Dose Adjustments

-Mild to Moderate Renal Impairment: No adjustment recommended.

-Severe Renal Impairment: Dose adjustment(s) may be required; however, an appropriate dose has not been established. Caution is recommended.

Liver Dose Adjustments

-Mild Hepatic Impairment: No adjustment recommended.

-Moderate to Severe Hepatic Impairment: Dose adjustment(s) may be required; however, an appropriate dose has not been established. Caution is recommended.

Dose Adjustments

First dose reduction: 100 mg orally twice daily

Second dose reduction: 75 mg orally twice daily

Third dose reduction: 50 mg orally twice daily

If unable to tolerate 50 mg twice daily: Discontinue dabrafenib

For New Primary Cutaneous Malignancies that develop: No dose modifications are recommended.

For New Primary Non-Cutaneous Malignancies: Permanently discontinue in patients who develop RAS mutation-positive non-cutaneous malignancies.

Fever 101.3F to 104F:

-Withhold dabrafenib until adverse reaction resolves, then resume at same dose or at a reduced level.

-NEW PRIMARY CUTANEOUS MALIGNANCIES: No adjustment recommended.

-NEW PRIMARY NON-CUTANEOUS MALIGNANCIES: Permanently discontinue treatment in patients who develop RAS mutation-positive non-cutaneous malignancies.

DOSE REDUCTIONS FOR ADVERSE REACTIONS:

-First Dose Reduction: 100 mg twice a day

-Second Dose Reduction: 75 mg twice a day

-Third Dose Reduction: 50 mg twice a day

-Subsequent Modification: Permanently discontinue treatment if unable to tolerate 50 mg twice a day.

CARDIAC:

-Symptomatic Congestive Heart Failure; Absolute Decrease in Left Ventricular Ejection Fraction [LVEF] of Greater Than 20% from Baseline that is Below Lower Level of Normal [LLN]): Withhold treatment, then resume at same dose upon recovery of cardiac function.

PYREXIA:

-Fever of 101.3 to 104 Degrees Fahrenheit: Withhold treatment until fever resolves, then resume at same or lower dose level.

-Fever Higher Than 104 Degrees Fahrenheit; Fever Complicated by Rigors, Hypotension, Dehydration, or Renal Failure: Withhold treatment until fever resolves, then resume at lower dose level OR permanently discontinue treatment.

SKIN TOXICITY (Intolerable Grade 2, Grade 3, or Grade 4): Withhold treatment for up to 3 weeks

-If Improved: Resume at lower dose.

-If Not Improved: Permanently discontinue treatment.

UVEITIS (Severe OR Mild/Moderate that Does Not Respond to Ocular Therapy): Withhold treatment for up to 6 weeks.

-If Improved to Grade 0 to 1: Resume at same or lower dose level.

-If Not Improved: Permanently discontinue treatment.

OTHER ADVERSE REACTIONS:

INTOLERABLE GRADE 2; ANY GRADE 3: Withhold treatment.

-If Improved to Grade 0 to 1: Resume at lower dose level.

-If Not Improved: Permanently discontinue treatment.

FIRST OCCURRENCE OF ANY GRADE 4: Withhold treatment until improvement to Grade 0 to 1, then resume at lower dose level OR permanently discontinue treatment.

RECURRENT GRADE 4: Permanently discontinue treatment.

Comments:

-Dose adjustments are NOT recommended for this drug when it is administered in combination with trametinib for the following adverse reactions: retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED), interstitial lung disease (ILD)/pneumonitis, and uncomplicated venous thromboembolism.

-Consult the manufacturer product information for trametinib dosing recommendations.

Other Comments

Administration Advice:

-Direct patients to take this drug at least 1 hour before or 2 hours after a meal, and at similar times every day with an interval of approximately 12 hours between doses.

-Instruct patients to swallow drug capsules whole with water, and not to open, crush, chew, or break capsules.

-Warn patients not to mix capsule contents with food or liquids due to the chemical instability of this drug.

-Advise patients not to take a missed dose within 6 hours of the next scheduled dose.

-In the event of a vomited dose, counsel patients not to retake that dose and to resume dosing with the next scheduled dose.

-Consult the manufacturer product information for trametinib dosing recommendations prior to initiation of combination treatment with this drug.

Storage Requirements:

-Store at 25 degrees Celsius (77 degrees Fahrenheit); excursions are permitted from 15 to 30 degrees (59 to 86 Fahrenheit).

General:

-This drug is not indicated for treatment of wild-type BRAF melanoma or wild-type BRAF NSCLC.

-The safety and efficacy of using this drug in combination with trametinib has not been evaluated in patients with BRAF V600 mutation-positive melanoma with brain metastases.

Monitoring:

-CARDIOVASCULAR: LVEF by echocardiogram or multigated acquisition scan (before initiation of this drug with trametinib, 1 month after initiation of this drug, and then at 2- to 3-month intervals during treatment); blood pressure (baseline and during treatment); thrombosis signs and symptoms

-HEPATIC: Liver function (every 4 weeks for 6 months after treatment initiation of this drug with trametinib and thereafter as clinically indicated)

-OCULAR: Uveitis signs and symptoms (routinely during treatment)

-ONCOLOGIC: Cutaneous malignancies: Skin exam (prior to treatment initiation, monthly to every 2 months during treatment, and for up to 6 months following treatment discontinuation or until initiation of another antineoplastic therapy), head and neck exam with visual inspection of oral mucosa and lymph node palpation (prior to treatment initiation and every 3 months during treatment or as clinically appropriate), chest/abdomen CT scan (prior to treatment initiation and every 6 months during treatment or as clinically appropriate), secondary/recurrent malignancies (for up to 6 months following treatment discontinuation or until initiation of another antineoplastic therapy); Non-cutaneous malignancies: Anal exams and pelvic exams for women (before and at the end of treatment or when clinically indicated), CBC (as clinically indicated)

-RENAL: Serum creatinine, renal function (routinely during treatment, especially during and following severe pyrexia)

What is the dose of Dabrafenib for a child?

The dosage has not been established in pediatric patients. It may be unsafe for your child. It is always important to fully understand the safety of the drug before using. Please consult with your doctor or pharmacist for more information.

How is Dabrafenib available?

Dabrafenib is available in the following dosage forms and strengths:

• Oral capsule.

What should I do in case of an emergency or overdose?

In case of an emergency or an overdose, call your local emergency services or go to your nearest emergency room.

What should I do if I miss a dose?

If you miss a dose of Dabrafenib, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and take your regular dose as scheduled. Do not take a double dose.