Actiq

Common Side Effects of Fentanyl

The most common side effects of fentanyl are:

• Nausea, vomiting, constipation, and diarrhea
• Drowsiness and dizziness
• Insomnia
• Increased sweating
• Fatigue
• Feeling cold
• Anorexia
• Headache

Less common side effects, which may be severe, include such things as:

• Depression
• Abnormally slow heart action
• Muscle spasms and tremors
• Fluid retention and swelling of tissues in the lower limbs
• Abdominal pain
• Anxiety, confusion, and hallucinations
• Urinary problems
• Tingling sensations

Rare Side Effects of Fentanyl

Rare side effects from using fentanyl have also been reported, including:

• Euphoria
• Sexual and erectile dysfunction (ED)
• Eczema and other skin disorders
• Reduced sense of touch
• Flu-like symptoms

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of fentanyl in children younger than 18 years of age for the Abstral®, Fentora®, Onsolis®, and Subsys® brands, and in children younger than 16 years of age for the Actiq® brand. Safety and efficacy have not been established in these age groups.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of fentanyl in the elderly. However, elderly patients may be more sensitive to the effects of narcotic analgesics than younger adults and are more likely to have age-related lung or kidney problems, which may require caution and an adjustment in the dose for patients receiving fentanyl in order to avoid serious side effects.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Mifepristone
• Nalmefene
• Naltrexone
• Safinamide

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acepromazine
• Alefacept
• Alfentanil
• Almotriptan
• Alprazolam
• Amineptine
• Amiodarone
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Anileridine
• Aripiprazole
• Asenapine
• Baclofen
• Benperidol
• Benzphetamine
• Blinatumomab
• Boceprevir
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Buspirone
• Butabarbital
• Butorphanol
• Carbamazepine
• Carbinoxamine
• Cariprazine
• Carisoprodol
• Carphenazine
• Ceritinib
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Cyclobenzaprine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Droperidol
• Duloxetine
• Eletriptan
• Eluxadoline
• Enflurane
• Enzalutamide
• Escitalopram
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Flibanserin
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Furazolidone
• Golimumab
• Granisetron
• Guselkumab
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Idelalisib
• Imipramine
• Indinavir
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ketamine
• Ketobemidone
• Ketoconazole
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Lumacaftor
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Midazolam
• Milnacipran
• Mirtazapine
• Mitotane
• Moclobemide
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Naratriptan
• Nefazodone
• Nelfinavir
• Netupitant
• Nialamide
• Nicardipine
• Nicomorphine
• Nifedipine
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Oxymorphone
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pazopanib
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Phenytoin
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Pitolisant
• Posaconazole
• Prazepam
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Ranolazine
• Rasagiline
• Remifentanil
• Remoxipride
• Ribociclib
• Rifampin
• Ritonavir
• Rizatriptan
• Saquinavir
• Secobarbital
• Secukinumab
• Selegiline
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John's Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Telaprevir
• Telithromycin
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Vilazodone
• Voriconazole
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol
• Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, or history of or
• Brain tumor, history of or
• Breathing problems (eg, asthma, apnea) or
• Chronic obstructive pulmonary disease (COPD) or
• Cor pulmonale (serious heart condition) or
• Depression, history of or
• Drug dependence, especially narcotic abuse, history of or
• Head injury, history of or
• Mental health problems, history of—Use with caution. May cause side effects to become worse.

• Bradyarrhythmia (slow heart rhythm) or
• Hypotension (low blood pressure) or
• Pancreatitis (inflammation of the pancreas)—Use with caution. May make these conditions worse.

• Diabetes—Use the Actiq® brand with caution. There are 2 grams of sugar in each unit.

• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Stomach or bowel blockage (including paralytic ileus), known or suspected—Should not be used in patients with these conditions.

This section provides information on the proper use of a number of products that contain fentanyl. It may not be specific to Actiq. Please read with care.

Use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.

The Abstral®, Actiq®, Fentora®, Onsolis®, and Subsys® products are only available under a restricted distribution program. You will have to read and sign papers that explain how the medicine is used when you pick up your prescription.

This medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions. Ask your pharmacist for the Medication Guide if you do not have one.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

Keep the medicine in the original blister package. Open the package right before use.

Abstral® tablets:

• Place the tablet under the tongue until it dissolves. Do not chew, suck, or swallow the tablet.
• Do not eat or drink anything until the tablet has dissolved. If your mouth is dry, use water to rinse the mouth before you place the tablet under the tongue.

Actiq® lozenges:

• Place the lozenge in the mouth between the cheek and lower gum. Using the handle, move the lozenge from one side to the other every now and then.
• Suck the medicine for 15 minutes and do not chew it.

Fentora® buccal tablets:

• Peel the blister back to remove the tablet. Do not push the tablet through the blister as this may damage the tablet.
• Place the tablet between the upper cheek and gum, above a back molar, until it dissolves. Do not chew, suck, or swallow the tablet.
• If the tablet does not dissolve completely after 30 minutes, you may swallow it with a glass of water.

Onsolis® buccal film:

• Use your tongue to wet the side of your cheek or rinse your mouth with water in the area where you will place the film.
• Do not cut or tear the film. Hold the film on a clean, dry finger with the pink side facing up.
• Press the film against your cheek and hold it there for 5 seconds.
• Leave the film in place until it dissolves and do not touch or move the film. Do not chew or swallow the film.
• If you must use more than one film, place the second film on the other side of your mouth.
• Do not eat any food until the film dissolves. You may drink water or other liquids after 5 minutes.

Subsys® sublingual spray:

• Carefully spray the medicine under your tongue.
• Hold the medicine under your tongue for 30 to 60 seconds. Do not rinse your mouth and do not spit out any medicine.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For cancer pain:
  • For buccal dosage form (film):
    • Adults—At first, one 200 microgram (mcg) film for each pain episode. Your doctor may adjust your dose as needed. However, the maximum number of pain episodes that can be treated each day is 4.
    • Children—Use and dose must be determined by your doctor.
  • For buccal dosage form (tablets):
    • Adults—At first, 100 micrograms (mcg) for each pain episode. If instructed by your doctor, this dose may be repeated after waiting 30 minutes between doses. Your doctor may adjust your dose as needed. However, the maximum number of pain episodes that can be treated each day is 4.
    • Children—Use and dose must be determined by your doctor.
  • For transmucosal dosage form (lozenges):
    • Adults and children 16 years of age and older—At first, 200 micrograms (mcg) for each pain episode. If instructed by your doctor, this dose may be repeated after waiting 15 minutes between doses. Your doctor may adjust your dose as needed. However, the maximum number of units that can be used each day is 4.
    • Children younger than 16 years of age—Use and dose must be determined by your doctor.
  • For sublingual dosage form (spray):
    • Adults—At first, 100 micrograms (mcg) or 1 spray for each pain episode. If instructed by your doctor, this dose may be repeated once after waiting 30 minutes. Additional pain episodes may be treated after a minimum of 4 hours.
    • Children—Use and dose must be determined by your doctor.
  • For sublingual dosage form (tablets):
    • Adults—At first, 100 micrograms (mcg) for each pain episode. If instructed by your doctor, this dose may be repeated after waiting 30 minutes between doses. Your doctor may adjust your dose as needed. However, the maximum number of pain episodes that can be treated each day is 4.
    • Children—Use and dose must be determined by your doctor.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Abstral® tablets: If you have questions about the best way to dispose of the tablets you do not use, ask your pharmacist or call 1-888-227-8725.

Actiq® lozenges: If you have questions about the best way to dispose of the lozenges you do not use, ask your pharmacist or call 1-800-896-5855.

Fentora® tablets: If you have questions about the best way to dispose of the tablets you do not use, ask your pharmacist or call 1-800-896-5855.

Onsolis® film: If you have questions about the best way to dispose of the films you do not use, ask your pharmacist or call 1-800-526-3840.

Subsys® spray: Place the used spray unit into a disposal bag. Seal the disposal bag and throw it into a trash container that is out of the reach of children. For the unopened spray units, use the disposal bottle to empty the liquid from each unit. Place the disposal bottle in a bag and seal it. Throw the bag into a trash container that is out of the reach of children. If you have questions, call 1-877-978-2797.

Actiq is contraindicated in:

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Fentanyl was evaluated for carcinogenic potential in a 104-week rat study and in a 6-month Tg.AC transgenic mouse study. In rats, doses up to 50 mcg/kg in males and 100 mcg/kg in females were administered subcutaneously and no treatment-related neoplasms were observed (doses are equivalent to 1.13 and 2.7 times the exposure of a single human dose of 1600 mcg per pain episode, respectively, based on an AUC comparison). In a 26-week transgenic mice model (Tg.AC), at topical doses up to 50 mcg/dose/day, no increase in the occurrence of treatment-related neoplasms was observed.

Mutagenesis

Fentanyl citrate was not mutagenic in the in vitro Ames reverse mutation assay in S. typhimurium or E. coli, or the mouse lymphoma mutagenesis assay, and was not clastogenic in the in vivo mouse micronucleus assay.

Impairment of Fertility

In a fertility study, female rats were administered fentanyl subcutaneously for 14 days prior to mating with untreated males at doses up to 300 mcg/kg and no effects on female fertility were observed. The systemic exposure at the dose of 300 mcg/kg was approximately 4.0-times the exposure of a single human dose of 1600 mcg per pain episode, based on an AUC comparison. Males were administered fentanyl subcutaneously for 28 days prior to mating with untreated females at doses up to 300 mcg/kg. At 300 mcg/kg, adverse effects on sperm parameters, which affected fertility, were observed. These effects included decreased percent mobile sperm, decreased sperm concentrations as well as an increase in the percent abnormal sperm. The dose in males at which no effects on fertility were observed was 100 mcg/kg, which is approximately 2.7 times the exposure of a single human dose of 1600 mcg per pain episode, based on an AUC comparison.

Fentanyl has been shown to impair fertility in rats at doses of 30 mcg/kg IV and 160 mcg/kg subcutaneously. Conversion to the human equivalent doses indicates that this is within the range of the human recommended dosing for Actiq.

Actiq is supplied in six dosage strengths. Each unit is individually wrapped in a child-resistant, protective blister package. These blister packages are packed 30 per shelf carton for use when patients have been titrated to the appropriate dose.

Each dosage unit has a white to off-white color. Each individual solid drug matrix is marked with “Actiq” and the strength of the unit (“200”, “400”, “600”, “800”, “1200”, or “1600”). The dosage strength is also marked on the handle tag, the blister package and the carton. See blister package and carton for product information.

Note: Colors are a secondary aid in product identification. Please be sure to confirm the printed dosage before dispensing.

Store at 20-25ºC (68-77ºF) with excursions permitted between 15° and 30°C (59° to 86°F) until ready to use. (See USP Controlled Room Temperature.) Protect Actiq from freezing and moisture. Do not use if the blister package has been opened.

Actiq® (oral transmucosal fentanyl citrate) 200 mcg CII, 30 Unit Carton Text

Only for patients already taking around-the-clock opioids (narcotics) such as fentanyl or morphine.

CII

Actiq®

(oral transmucosal fentanyl citrate)

equivalent to 200 mcg fentanyl base

PATIENTS MUST BE TOLERANT TO AROUND-THE-CLOCK OPIOID THERAPY

DO NOT SUBSTITUTE Actiq FOR OTHER FENTANYL PRODUCTS

WARNING: Keep out of the reach of children.

for important warnings and directions.

Safety Kit with important additional information about safe use.

storage, and disposal of this medication.

Included as part of the "PRECAUTIONS" Section

Actiq is part of the drug class:

• Opioid anesthetics

If you take too much Actiq, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If Actiq is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.