Dabrafenib (oral)

As a cancer growth blocker, Dabrafenib stops melanomas which are caused by BRAF gene changes.

Overview:

Dabrafenib is a kinase inhibitor (often referred to as a cancer blocker). Some cancers are caused by a gene known as BRAF. This BRAF gene creates a protein which assists the division and growth of cancer cells. Dabrafenib functions by stopping cells from creating the BRAF proteins (or kinases), which results in the stopping or slowing down of cancer growth.

This medication is only suitable for patients who have a change in the BRAF gene. A doctor will perform a biopsy to test a piece of body tissue to ascertain whether the cancerous cells feature a change in BRAF cells, if this is the case the patient may be prescribed Dabrafenib to treat their condition. Dabrafenib is typically given to patients when cancer has spread or otherwise cannot be removed surgically.

Dabrafenib has been approved by the FDA for use in the treatment of mutation-positive advanced melanomas since 2013. It is often marketed under the name Tafinlar, and in some instances, healthcare professionals may use the name Tafinlar when referring to this generic medicine. It is administered orally and can be used as a standalone treatment or in conjunction with other anti-cancer agents.

Type of medicine:

• Kinase inhibitor

Conditions treated:

• Cancer

Side effects:

Dabrafenib can potentially cause unwanted side effects along with the desired effects. The most commonly reported side effects in patients undergoing treatment with this medicine include the following:

• nosebleeds
• bleeding gums
• prolonged bleeding from cuts
• bloody urine
• blurry vision
• difficulty breathing
• difficulty swallowing
• dry mouth
• dizziness
• black or tarry stools
• stomach pain
• skin rash
• increased hunger
• fruit-like breath odor
• ulceration of the skin
• inability to move
• unusual weakness or tiredness
• increased urination
• increased thirst
• vomiting
• sweating
• swelling of the extremities
• tingling in the feet or hands
• skin blisters
• rash
• nausea
• difficulty having a bowel movement
• general difficulty moving
• muscle aches
• sore throat
• coughing
• tallow eyes or skin
• thinning or the hair or general hair loss
• constipation
• indigestion

As the patient continues their treatment with Dabrafenib as prescribed, most (if not all) of these side effects should lessen. If side effects persist for a prolonged period or appear to get worse, the patient is advised to follow this up with their doctor as soon as possible. Doctors and healthcare providers may be able to suggest ways to alleviate common side effects which cause mild discomfort. For example, a sore throat could be alleviated with over the counter cough medicine or lozenges, and increased thirst can be combatted by regularly drinking large glasses of ice cold water.

Other side effects, which occur much less frequently, but often enough to warrant a mention, include the following: changes in vision or color perception, difficulty seeing at night (night blindness), acute eye pain, increased sensitivity of the eyes and/or watery eyes. Patients who experience any of these side effects are advised to contact their doctor or healthcare provider immediately.

Because Dabrafenib can potentially affect the eyesight, patients are advised to refrain from driving or operating heavy machinery until it has been observed that they do not experience substantial vision changes. This is because driving when impaired could put the patient or other road users at risk of injury or even death.

Not all side effects may have been reported. If a patient experiences any side effects not listed, they are advised to consult their doctor as soon as possible and to also report their findings to the FDA if they wish.

Dosage:

As with all medicines, it is imperative that the patient only takes Dabrafenib as prescribed by a qualified physician. This means that patients must avoid taking any more of this medication than advised – both in terms of dose size and frequency. In addition to this, patients must stop treatment with this medicine if a doctor advises them to, even if they still have a supply of the medicine remaining.

Dabrafenib should be taken at least one hour before a meal. Alternatively, it can be taken two hours after a meal. It should be taken at the same time every day with an approximate interval of 12 hours between each dose. Patients should swallow the Dabrafenib capsule whole, with a glass of water. Dabrafenib capsules should not be opened, chewed, crushed, broken or dissolved in liquid. Because of the instability of Dabrafenib, patients are also advised not to directly mix it with food.

Patients who miss a dose are advised to take the missed dose within six hours of the next scheduled dose. In the event that a dose is vomited or expelled, patients are advised not to take a replacement dose and to resume Dabrafenib administration with the next scheduled dose.

In some instances, patients will receive treatment with Dabrafenib in conjunction with another anti-cancer medication, such as Trametinib. In this case, the patient should consult their doctor in order to understand if any changes to dosing recommendations should be made prior to the initiation of combination treatment.

Usual adult dose for non-small cell lung cancer and/or metastatic melanoma:

Adults with this condition should receive 150mg of Dabrafenib orally, twice a day, either as monotherapy or in conjunction with another medicine such as Trametinib. The patient should continue with treatment at this level under their condition improves, or until unacceptable toxicity occurs.

Dose adjustments for patients living with other conditions:

Patients with liver or kidney conditions may require dose adjustments in order to ensure safety when undergoing treatment with Dabrafenib. Those with mild hepatic or renal impairment should not require any dose adjustments, however, those with moderate to severe hepatic or renal issues may require smaller doses, which should be decided upon by a doctor. Caution is advised when determining dosage for such patients, as an appropriate dose has yet to be formally established for safe use in those with liver or kidney disease.

Dose reductions:

As treatment progresses and the cancerous cells stop multiplying, the patient may no longer require doses of 150mg per day. These dose reductions can also be applied to patients who are unable to tolerate Dabrafenib at larger doses. A doctor will determine when dose reduction should occur, and will generally make reductions in the following increments:

• First reduction: 100mg per day, taken orally twice a day.
• Second reduction: 75mg per day, taken orally twice a day.
• Third reduction: 50mg per day, taken orally twice a day.

Patients who are unable to tolerate Dabrafenib at 50mg per day should discontinue use of the drug.

Dose adjustments are not recommended when Dabrafenib is used in conjunction with Trametinib, as the propensity for the following adverse reactions in increased: retinal pigment epithelial detachment (RPED), retinal vein occlusion, interstitial lung disease, pneumonia, and/or uncomplicated venous thromboembolism.

Patients who experience signs or symptoms of an overdose (difficulty breathing, extremely fast or slow heartbeat, seizures, unconsciousness, loss of coordination or flushed skin) may require immediate medical attention, and are advised to contact the local poison control center on 1800-222-1222, emergency services on 911 or to alternatively make their way to the local ER if it is in close enough proximity.

Interactions:

All drugs have the potential to interact with other medicines and chemicals within the human body. These interactions can change the effects of each medicine. In some instances, this can cause a medicine to become ineffective in treating the condition it was prescribed to alleviate. In other instances, interactions can cause potentially harmful or even fatal effects to occur. Because of these risks, it is imperative that patients keep a full, detailed list of all drugs they are currently taking. This list should include complementary medicines, over the counter remedies, herbal supplements and vitamins as well as prescribed medications.

Below is a partial list of some drugs known to have interacted negatively with Dabrafenib. Patients who are already taking one or more of these medicines should inform their doctor prior to beginning treatment with Dabrafenib:

• Abiraterone
• Acarbose
• Acetaminophen/Aluminum Hydroxide/Aspirin/Caffeine/Magnesium Hydroxide
• Acetaminophen/Caffeine/Chlorpheniramine/Hydrocodone/Phenylephrine
• Acetaminophen/Caffeine/Dihydrocodeine
• Acetaminophen/Hydrocodone
• Acetaminophen/Oxycodone
• Acetohexamide
• Albendazole
• Alfentanil
• Alfuzosin
• Alginic Acid/Aluminum Hydroxide/Magnesium Carbonate
• Alginic Acid/Aluminum Hydroxide/Magnesium Trisilicate
• Aliskiren/Amlodipine
• Aliskiren/Amlodipine/Hydrochlorothiazide
• Aliskiren/Valsartan
• Allopurinol/Lesinurad
• Alogliptin
• Alogliptin/Metformin
• Alogliptin/Pioglitazone
• Alprazolam
• Aluminum Carbonate
• Aluminum Hydroxide
• Baclofen/Flurbiprofen/Lidocaine Topical
• Bazedoxifene/Conjugated Estrogens
• Belladonna/Caffeine/Ergotamine/Pentobarbital
• Belladonna/Ergotamine/Phenobarbital
• Bepridil
• Betamethasone
• Bexarotene
• Bisacodyl/Polyethylene Glycol 3350/Potassium Chloride/Sodium Bicarbonate/Sodium Chloride
• Boceprevir
• Bortezomib
• Bosentan
• Bosutinib
• Brigatinib
• Brompheniramine/Dihydrocodeine/Phenylephrine
• Brompheniramine/Dihydrocodeine/Pseudoephedrine
• Brompheniramine/Hydrocodone/Phenylephrine
• Brompheniramine/Hydrocodone/Pseudoephedrine
• Bupivacaine/Fentanyl
• Bupivacaine/Lidocaine/Triamcinolone
• Buprenorphine
• Buprenorphine/Naloxone
• Bupropion
• Bupropion/Naltrexone
• Buspirone
• Busulfan
• Butorphanol
• Cabazitaxel
• Cabozantinib
• Caffeine/Ergotamine
• Caffeine/Pheniramine/Phenylephrine/Sodium Citrate/Sodium Salicylate
• Calcium Acetate/Magnesium Carbonate
• Calcium Carbonate
• Calcium Carbonate/Famotidine/Magnesium Hydroxide
• Calcium Carbonate/Fluoride
• Calcium Carbonate/Magnesium Carbonate
• Calcium Carbonate/Magnesium Chloride
• Calcium Carbonate/Magnesium Hydroxide
• Calcium Carbonate/Magnesium Hydroxide/Simethicone
• Calcium Carbonate/Melatonin/Pyridoxine
• Calcium Carbonate/Psyllium
• Calcium Carbonate/Risedronate
• Calcium Carbonate/Simethicone
• Calcium/Ferrous Fumarate/Vitamin D
• Calcium/Vitamin D
• Canagliflozin/Metformin
• Carbamazepine
• Carbinoxamine/Hydrocodone/Phenylephrine
• Carbinoxamine/Hydrocodone/Pseudoephedrine
• Cariprazine
• Dapagliflozin/Metformin
• Dapagliflozin/Saxagliptin
• Dapsone
• Darifenacin
• Darunavir
• Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
• Dasatinib
• Deflazacort
• Dehydroepiandrosterone
• Delavirdine
• Deoxycholic Acid
• Desogestrel/Ethinyl Estradiol
• Dexamethasone
• Dexamethasone/Lidocaine
• Dexbrompheniramine/Hydrocodone/Phenylephrine
• Dexchlorpheniramine/Hydrocodone/Phenylephrine
• Dextromethorphan/Quinidine
• Diazepam
• Diclofenac
• Diclofenac/Misoprostol
• Dienogest/Estradiol
• Diethylstilbestrol
• Dihydrocodeine/Guaifenesin
• Dihydrocodeine/Guaifenesin/Phenylephrine
• Dihydrocodeine/Guaifenesin/Pseudoephedrine
• Dihydrocodeine/Phenylephrine
• Dihydrocodeine/Phenylephrine/Pyrilamine
• Dihydroergotamine
• Dihydroxyaluminum Sodium Carbonate
• Diltiazem
• Diltiazem/Enalapril
• Diphenhydramine/Hydrocodone/Phenylephrine
• Diphenhydramine/Ibuprofen
• Diphenhydramine/Naproxen
• Disopyramide
• Docetaxel
• Donepezil
• Donepezil/Memantine
• Doxorubicin
• Doxorubicin Liposomal
• Dronedarone
• Droperidol/Fentanyl
• Drospirenone/Estradiol
• Drospirenone/Ethinyl Estradiol
• Drospirenone/Ethinyl Estradiol/Levomefolate Calcium
• Dutasteride/Tamsulosin
• Dyphylline/Ephedrine/Guaifenesin/Phenobarbital
• Efavirenz
• Efavirenz/Emtricitabine/Tenofovir
• Elbasvir/Grazoprevir
• Eliglustat
• Elvitegravir
• Empagliflozin/Linagliptin
• Empagliflozin/Metformin
• Emtricitabine/Lopinavir/Ritonavir/Tenofovir
• Emtricitabine/Nelfinavir/Tenofovir
• Enalapril/Felodipine
• Enzalutamide
• Ephedrine/Phenobarbital/Potassium Iodide/Theophylline
• Ephedrine/Phenobarbital/Theophylline
• Epinephrine/Lidocaine
• Eplerenone
• Ergonovine
• Ergotamine
• Erlotinib
• Erythromycin
• Erythromycin/Sulfisoxazole
• Escitalopram
• Esomeprazole/Naproxen
• Estazolam
• Esterified Estrogens
• Esterified Estrogens/Methyltestosterone
• Estradiol
• Estradiol Topical
• Estradiol/Levonorgestrel
• Estradiol/Medroxyprogesterone
• Estradiol/Norethindrone
• Estradiol/Norethindrone Topical
• Estradiol/Norgestimate
• Etonogestrel
• Etoposide
• Etravirine
• Everolimus
• Exemestane
• Exenatide
• Ezetimibe/Simvastatin
• Famotidine
• Famotidine/Ibuprofen
• Glipizide
• Glipizide/Metformin
• Glyburide
• Glyburide/Metformin
• Granisetron
• Guaifenesin/Hydrocodone
• Guaifenesin/Hydrocodone/Pheniramine/Phenylephrine/Phenylpropanolamine
• Guaifenesin/Hydrocodone/Pheniramine/Phenylpropanolamine/Pyrilamine
• Guaifenesin/Hydrocodone/Phenylephrine
• Guaifenesin/Hydrocodone/Pseudoephedrine
• Guanfacine
• Halofantrine
• Haloperidol
• Halothane
• Homatropine/Hydrocodone
• Hydrochlorothiazide/Irbesartan
• Hydrochlorothiazide/Losartan
• Hydrochlorothiazide/Propranolol
• Hydrochlorothiazide/Valsartan
• Hydrocodone
• Hydrocodone/Ibuprofen
• Hydrocodone/Pheniramine/Phenylephrine/Phenylpropanolamine/Pyrilamine
• Hydrocodone/Phenylephrine
• Indinavir
• Indomethacin
• Insulin
• Ketamine
• Ketoconazole
• Lansoprazole/Naproxen
• Lapatinib
• Lesinurad
• Letrozole
• Letrozole/Ribociclib
• Leuprolide/Norethindrone
• Levobupivacaine
• Levomethadyl Acetate
• Levonorgestrel
• Lidocaine
• Lidocaine/Oxytetracycline
• Lidocaine/Potassium Chloride
• Lidocaine/Sodium Bicarbonate
• Linagliptin
• Linagliptin/Metformin
• Liraglutide
• Lomitapide
• Lopinavir/Ritonavir
• Losartan
• Lovastatin
• Lovastatin/Niacin
• Lurasidone
• Magaldrate
• Magaldrate/Simethicone
• Magnesium Carbonate
• Magnesium Hydroxide
• Magnesium Hydroxide/Mineral Oil
• Magnesium Oxide
• Maraviroc
• Medroxyprogesterone
• Mefenamic Acid
• Mefloquine
• Megestrol
• Meloxicam
• Mephenytoin
• Mestranol/Norethindrone
• Metformin
• Methysergide Maleate
• Mibefradil
• Midazolam
• Midostaurin
• Mifepristone
• Miglitol
• Mirabegron
• Mirtazapine
• Mitotane
• Modafinil
• Montelukast
• Naloxegol
• Naloxone/Oxycodone
• Naltrexone/Oxycodone
• Naproxen
• Naproxen/Pseudoephedrine
• Naproxen/Sumatriptan
• Nateglinide
• Nebivolol/Valsartan
• Nefazodone
• Nelfinavir
• Neratinib
• Ombitasvir/Paritaprevir/Ritonavir
• Omeprazole/Sodium Bicarbonate
• Ondansetron
• Osimertinib
• Oxybutynin
• Oxycodone
• Paclitaxel
• Paclitaxel Protein-Bound
• Palbociclib
• Panobinostat
• Paricalcitol
• Pazopanib
• Prednisolone
• Prednisone
• Primidone
• Progesterone
• Progesterone Topical
• Propofol
• Ranitidine
• Ranitidine Bismuth Citrate
• Ranolazine
• Red Yeast Rice
• Regorafenib
• Repaglinide
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Rivaroxaban
• Roflumilast

Warnings:

Patients are advised to inform their doctors of any allergies they have, along with the symptoms they experience due to these allergies (such as wheezing, coughing, swelling of the face/lips/tongue, shortness of breath, rashes or hives). This is because Dabrafenib may contain active or inactive ingredients which could cause allergic reactions in certain patients.

Sometimes this medicine is prescribed in conjunction with Trametinib. Before taking either medication, patients should familiarize themselves with the potential side effects they may experience. Some side effects can be serious and even require medical treatment.

Dabrafenib can increase the propensity for some patients to get certain forms of cancer. Patients are advised to discuss these risks with their doctor and to have their skin checked on a regular basis. If a patient notices any changes to the skin, such as a new bump, wart or sore, or if they develop lumps which bleed and do not heal, they should contact their healthcare provider immediately.

Dabrafenib can potentially raise blood sugar. Patients with diabetes or other conditions related to blood sugar levels are advised to consult their doctor prior to taking this medicine. A doctor may prescribe another treatment to alleviate blood sugar level issues. Patients should regularly have their blood sugar checked while undergoing treatment with this medicine, even if they feel fine and have no symptoms of diabetes.

Geriatric patients may be more susceptible to the effects of this medicine, and could therefore also experience increased side effects. In these instances, a doctor may recommend adjusting the dose of the medicine to more tolerable levels.

Dabrafenib can potentially affect fertility, leading to a patient not being able to reproduce. Patients are advised to donate sperm or eggs prior to using this medicine. Dabrafenib may also affect how the hormonal birth control works – patients are therefore advised to use condoms while using this medicine, and for at least two weeks after treatment with Dabrafenib has ceased.

Very bad eye problems can occur as a result of Dabrafenib use. These problems can lead to total loss of sight. Patients who experience flashes of light or “floaters” should contact their doctor immediately, as this is a sign of retinal detachment.

Storage:

Dabrafenib should be stored at room temperature, in the packaging, it was shipped in. The manufacturer advises that it should be kept away from light, heat and moisture, making it unsuitable for storage in a bathroom. Instead, Dabrafenib should be kept in a locked, dedicated medicine cabinet if possible, out of reach of children and pets.

Patients who have unused or expired medicines should check with their pharmacist to find out the best way to dispose of them. Dabrafenib should not be poured down a drain or toilet. It should be disposed of in accordance with state law. Most pharmacies offer “take back” schemes where they will dispose of or recycle unwanted medicines. Patients are advised to use this method.

Summary:

While Dabrafenib is a greatly beneficial medicine, it also poses a risk to patients who do not communicate effectively with their doctors. As a treatment designed to stop cancer cells from replicating, Dabrafenib functions very well – particularly when the patient is unable to undergo surgery, or if the cancer is situated in an area too risky to perform an operation on. However, it can also cause side effects which impede the patient’s day-to-day functioning. For this reason, it is important for patients to be up-front about their medical history, in order to rule out any potentially harmful effects cause be interactions.

When taken correctly, Dabrafenib helps patients to defeat cancer. To achieve this, patient and doctor must work together to find the most appropriate dose size and frequency of use.