Actiq

Name: Actiq

What are some things I need to know or do while I take Actiq?

  • Tell all of your health care providers that you take Actiq. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Do not stop taking Actiq all of a sudden without calling your doctor. You may have a greater risk of signs of withdrawal. If you need to stop this medicine, you will want to slowly stop it as ordered by your doctor.
  • Do not take more than what your doctor told you to take. Taking more than you are told may raise your chance of very bad side effects.
  • Do not take Actiq with other strong pain drugs or if you are using a pain patch without talking to your doctor first.
  • Avoid grapefruit and grapefruit juice.
  • This medicine may raise the chance of seizures in some people, including people who have had seizures in the past. Talk to your doctor to see if you have a greater chance of seizures while taking this medicine.
  • If you are 65 or older, use Actiq with care. You could have more side effects.
  • This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.

How is this medicine (Actiq) best taken?

Use Actiq as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Place lozenge in your mouth between the cheek and lower gum.
  • Suck oral lozenge. Do not chew, break, or crush it. Do not swallow it whole.

What do I do if I miss a dose?

  • If you use this medicine on a regular basis, use a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not use 2 doses at the same time or extra doses.
  • Many times Actiq is taken on an as needed basis. Do not take more often than told by the doctor.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Very bad dizziness or passing out.
  • Feeling confused.
  • Very upset stomach or throwing up.
  • Very hard stools (constipation).
  • Very bad belly pain.
  • Feeling very tired or weak.
  • Trouble breathing, slow breathing, or shallow breathing.
  • Noisy breathing.
  • Shortness of breath.
  • Chest pain.
  • Fast or slow heartbeat.
  • Feeling very sleepy.
  • Seizures.
  • Very bad irritation where this medicine is used.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen if you take Actiq (fentanyl lozenge) with drugs for depression, migraines, or certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
  • Taking an opioid drug like this medicine may lead to a rare but very bad adrenal gland problem. Call your doctor right away if you have very bad dizziness or passing out, very bad upset stomach or throwing up, or if you feel less hungry, very tired, or very weak.
  • Long-term use of an opioid drug like Actiq may lead to lower sex hormone levels. This may lead to signs like change in sex ability in men, no menstrual period in women, lowered interest in sex, or fertility problems. Call your doctor if you have any of these signs.

Actiq Dosage and Administration

Important Dosage and Administration Instructions

• Healthcare professionals who prescribe Actiq on an outpatient basis must enroll in the TIRF REMS Access program and comply with the requirements of the REMS to ensure safe use of Actiq [see Warnings and Precautions (5.7)]. • Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)]. • It is important to minimize the number of strengths available to patients at any time to prevent confusion and possible overdose. • Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. • Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with Actiq and adjust the dosage accordingly [see Warnings and Precautions (5.1)]. • Instruct patients and caregivers to take steps to store Actiq securely and to properly dispose of unused Actiq as soon as no longer needed [see Warnings and Precautions (5.1, 5.2), Patient Counseling Information (17)]. • Other TIRF formulations and Actiq are not equivalent. DO NOT substitute an Actiq prescription for any other TIRF formulation under any circumstances. Do not convert patients on a mcg per mcg basis from any other fentanyl product to Actiq [see Warnings and Precautions (5.5)].

Initial Dosage

Individually titrate Actiq to a dose that provides adequate analgesia and minimizes side effects. The initial dose of Actiq to treat episodes of breakthrough cancer pain is always 200 mcg. The Actiq unit should be consumed over 15 minutes. Patients should be prescribed an initial titration supply of six 200 mcg Actiq units, thus limiting the number of units in the home during titration. Patients should use up all units before increasing to a higher dose to prevent confusion and possible overdose.

Repeat Dosing

a. In cases where the breakthrough pain episode is not relieved after 15 minutes after completion of the Actiq unit (30 minutes after the start of the unit), patients may take ONLY ONE additional dose using the same strength for that episode. Thus patients should take a maximum of two doses of Actiq for any episode of breakthrough pain. b. Patients MUST wait at least 4 hours before treating another episode of breakthrough pain with Actiq.

Dose Titration

From an initial dose, closely follow patients and change the dosage strength until the patient reaches a dose that provides adequate analgesia using a single Actiq dosage unit per breakthrough cancer pain episode. If signs of excessive opioid effects appear before the unit is consumed, the dosage unit should be removed from the patient’s mouth immediately, disposed of properly, and subsequent doses should be decreased. Patients should record their use of Actiq over several episodes of breakthrough cancer pain and review their experience with their physicians to determine if a dosage adjustment is warranted.

In cases where the breakthrough pain episode is not relieved 15 minutes after completion of the Actiq unit (30 minutes after the start of the unit), patients may take ONLY ONE additional dose of the same strength for that episode. Thus, patients should take a maximum of two doses of Actiq for any breakthrough pain episode.

Patients must wait at least 4 hours before treating another episode of breakthrough pain with Actiq. To reduce the risk of overdosing during titration, patients should have only one strength of Actiq available at any one time.

Maintenance Dosing

a. Once titrated to an effective dose, patients should generally use ONLY ONE Actiq unit of the appropriate strength per breakthrough pain episode. b. On those occasions when the breakthrough pain episode is not relieved 15 minutes after completion of the Actiq unit, patient may take ONLY ONE additional dose using the same strength for that episode. c. Patients MUST wait at least 4 hours before treating another episode of breakthrough pain with Actiq. Once a successful dose has been found (i.e., an average episode is treated with a single unit), patients should limit consumption to four or fewer units per day. d. Dosage adjustment of Actiq may be required in some patients in order to continue to provide adequate relief of breakthrough pain. e. Generally, the Actiq dose should be increased only when a single administration of the current dose fails to adequately treat the breakthrough pain episode for several consecutive episodes. f. If the patient experiences greater than four breakthrough pain episodes per day, the dose of the maintenance (around-the-clock) opioid used for persistent pain should be re-evaluated.

Administration of Actiq

Open the blister package with scissors immediately prior to product use. The patient should place the Actiq unit in his or her mouth between the cheek and lower gum, occasionally moving the drug matrix from one side to the other using the handle. The Actiq unit should be sucked, not chewed. A unit dose of Actiq, if chewed and swallowed, might result in lower peak concentrations and lower bioavailability than when consumed as directed [see Clinical Pharmacology (12.3)].

The Actiq unit should be consumed over a 15-minute period. Longer or shorter consumption times may produce less efficacy than reported in Actiq clinical trials. If signs of excessive opioid effects appear before the unit is consumed, remove the drug matrix from the patient’s mouth immediately and decrease future doses.

Discontinuation of Actiq

When opioid therapy is no longer required, consider discontinuing Actiq along with a gradual downward of other opioids to minimize possible withdrawal effects.

2.7 Disposal of Actiq

After consumption of the unit is complete and the matrix is totally dissolved, throw away the handle in a trash container that is out of the reach of children.

• If any of the drug matrix remains on the handle, place the handle under hot running tap water until all of the drug matrix is dissolved, and then dispose of the handle in a place that is out of the reach of children. • Dispose of handles in the child-resistant container (as described in steps 1 and 2) at least once a day.

If the temporary storage bottle provided as part of the Actiq Child Safety Kit is available, partially consumed units may be stored in the specially provided child-resistant container out of the reach of children until proper disposal is possible.

Unopened units remaining from a prescription must be properly disposed as soon as they are no longer needed.

To dispose of the unused Actiq units:

• Remove the Actiq unit from its blister package using scissors, and hold Actiq by its handle over the toilet bowl. • Using wire-cutting pliers cut off the drug matrix end so that it falls into the toilet. • Dispose of the handle in a place that is out of the reach of children. • Repeat steps 1, 2, and 3 for each Actiq unit. Flush the toilet twice after 5 units have been cut and deposited into the toilet.

Do not flush the entire Actiq units, Actiq handles, blister packages, or cartons down the toilet. Dispose of the handle where children cannot reach it.

In the event that a caregiver requires additional assistance in disposing of excess unusable units that remain in the home after a patient has expired, instruct them to call the toll-free number for Teva Pharmaceuticals (1-888-483-8279) or seek assistance from their local DEA office.

Use in specific populations

Pregnancy

Risk Summary

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.8)]. Available data with Actiq in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, fentanyl administration to pregnant rats during organogenesis was embryocidal at doses within the range of the human recommended dosing. When administered during gestation through lactation fentanyl administration to pregnant rats resulted in reduced pup survival at doses within the range of the human recommended dosing. No evidence of malformations were noted in animal studies completed to date [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset of neonatal withdrawal symptoms usually occurs in the first days after birth. The duration and severity of neonatal opioid withdrawal syndrome may vary. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.8)].

Labor or Delivery

Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Actiq is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including Actiq, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Data

Human Data

In women treated acutely with intravenous or epidural fentanyl during labor, symptoms of neonatal respiratory or neurological depression were no more frequent than would be expected in infants of untreated mothers.

Transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl.

Animal Data

Fentanyl (25, 50, or 100 mcg/kg) citrate was administered subcutaneously to pregnant rats during the period of organogenesis (Gestation Day, GD 6 to 17). Maternal toxicity and a decrease in fetal weights were observed at 100 mcg/kg but no teratogenicity was seen in the study (the no observed effect level of 50 mcg/kg is equivalent to 0.7 times the exposure of a single human dose of 1600 mcg per pain episode, based on an AUC comparison). Fentanyl (50, 100, or 250 mcg/kg) was also administered subcutaneously to pregnant rabbits during the period of organogenesis (GD 6-18). Maternal toxicity was noted at doses >100 mcg/kg. No teratogenicity was seen in the study (250 mcg/kg dose is equivalent to 3.5 times the exposure of a single human dose of 1600 mcg per pain episode, based on an AUC comparison).

Fentanyl has been shown to embryocidal in pregnant rats at doses of 30 mcg/kg intravenously (0.2 times the 1600 mcg dose of Actiq on a mg/m2 basis) from GD 6 to 18 and 160 mcg/kg subcutaneously (1 times the 1600 mcg dose of Actiq based on a mg/m2 basis). No evidence of teratogenicity was reported.

No evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered fentanyl continuously via subcutaneously implanted osmotic minipumps at doses of 10, 100, or 500 mcg/kg/day starting 2-weeks prior to breeding and throughout pregnancy. The high dose was approximately 3 times the human dose of 1600 mcg Actiq per pain episode on a mg/m2 basis and produced mean steady-state plasma levels that are 3.4 times higher than the mean Cmax observed following administration of 1600 mcg dose of Actiq in humans.

In a postnatal development study, pregnant rats were treated from GD 6 through Lactation Day (LD) 20 with subcutaneous doses of fentanyl (25, 50, 100, and 400 mcg/kg). Maternal toxicity was noted at doses >100 mcg/kg. A reduction in pup growth and delayed attainment of developmental indices were observed at >100 mcg/kg. No difference in the number of live pups/litter was seen at birth, however, pup survival at LD 4 was reduced to 48% at 400 mcg/kg and by LD 21 pup survival was reduced to 30% and 26% at 100 and 400 mcg/kg, respectively. During lactation, fentanyl-related clinical signs (decreased activity, skin cold to touch, and moribund appearance) were noted in the F1 pups, most prominently in the 400 mcg/kg group. Pups from this group also had significantly reduced body weights throughout the lactation period. The dose of fentanyl administered to rats at which no developmental toxicity in the F1 generation was seen was 50 mcg/kg which is 0.6 times the exposure of a single human dose of 1600 mcg per pain episode, based on an AUC comparison.

Lactation

Risk Summary

Fentanyl is present in breast milk. One published lactation study reports a relative infant dose of fentanyl of 0.024%. However, there is insufficient information to determine the effects of fentanyl on the breastfed infant and the effects of fentanyl on milk production. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Actiq.

Clinical Considerations

Monitor infants exposed to Actiq through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

Females and Males of Reproductive Potential

Infertility

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6.2), Clinical Pharmacology (12.2), Nonclinical Toxicology (13.1)].

Pediatric Use

Safety and effectiveness in pediatric patients below 16 years of age have not been established.

In a clinical study, 15 opioid-tolerant pediatric patients with breakthrough pain, ranging in age from 5 to 15 years, were treated with Actiq. The study was too small to allow conclusions on safety and efficacy in this patient population. Twelve of the fifteen opioid-tolerant children and adolescents aged 5 to 15 years in this study received Actiq at doses ranging from 200 mcg to 600 mcg. The mean (CV%; range) dose-normalized (to 200 mcg) Cmax and AUC0-8 values were 0.87 ng/mL (51%; 0.42-1.30) and 4.54 ng.h/mL (42%; 2.37-6.0), respectively, for children ages 5 to <11 years old (N = 3) and 0.68 ng/mL (72%; 0.15-1.44) and 8.38 (192%; 0.84-50.78), respectively, for children ages ≥11 to <16 y (N = 9).

Geriatric Use

Of the 257 patients in clinical studies of Actiq in breakthrough cancer pain, 61 (24%) were 65 years of age and older, while 15 (6%) were 75 years of age and older. Those patients over the age of 65 years were titrated to a mean dose that was about 200 mcg less than the mean dose titrated to by younger patients. No difference was noted in the safety profile of the group over 65 years of age as compared to younger patients in Actiq clinical trials.

Elderly patients have been shown to be more sensitive to the effects of fentanyl when administered intravenously, compared with the younger population. Therefore, exercise caution when individually titrating Actiq in elderly patients to provide adequate efficacy while minimizing risk.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of Actiq slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.9)].

Fentanyl is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Patients with Renal or Hepatic Impairment

Insufficient information exists to make recommendations regarding the use of Actiq in patients with impaired renal or hepatic function. Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system and mostly eliminated in urine. If the drug is used in these patients, it should be used with caution because of the hepatic metabolism and renal excretion of fentanyl.

Sex

Both male and female opioid-tolerant cancer patients were studied for the treatment of breakthrough cancer pain. No clinically relevant sex differences were noted either in dosage requirement or in observed adverse reactions.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Life-Threatening Respiratory Depression

Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting Actiq or when the dosage is increased, and that it can occur even at recommended dosages [see Warnings and Precautions (5.1)]. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.

Accidental Ingestion

• Physicians and dispensing pharmacists must specifically question patients or caregivers about the presence of children in the home (on a full time or visiting basis) and counsel them regarding the dangers to children from inadvertent exposure [see Warnings and Precautions (5.2)]. • Inform patients that accidental ingestion, especially in children, may result in respiratory depression or death [see Warnings and Precautions (5.2)]. • Instruct patients to take steps to store Actiq securely and to dispose of unused Actiq [see Warnings and Precautions (5.2, 5.7), Patient Counseling Information, Disposal of Used Actiq Units]. • Instruct patients and caregivers to keep both used and unused Actiq out of the reach of children [see Warnings and Precautions (5.2)]. • Inform patients and their caregivers that, in the event that a unit is not completely consumed, it must be properly disposed as soon as possible [see Warnings and Precautions (5.2), Patient Counseling Information, Disposal of Used Actiq Units].   Actiq Child Safety Kit   Provide patients and their caregivers who have children in the home or visiting with an Actiq Child Safety Kit, which contains educational materials and safe interim storage containers to help patients store Actiq and other medicines out of the reach of children. To obtain a supply of Child Safety Kits, health care professionals can call 1-888-534-3119.

Interactions with Benzodiazepines and Other CNS Depressants (including Alcohol)

Inform patients and caregivers that potentially fatal additive effects may occur if Actiq is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions (5.4), Drug Interactions (7)].

Addiction, Abuse, and Misuse

Inform patients that the use of Actiq, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.6)]. Instruct patients not to share Actiq with others and to take steps to protect Actiq from theft or misuse.

Transmucosal Immediate-Release Fentanyl (TIRF) REMS

  Advise patients of the following information pertaining to the TIRF REMS • Inform outpatients that they must be enrolled in the TIRF REMS Access program before they can receive Actiq. • Allow patients the opportunity to ask questions and discuss any concerns regarding Actiq or the TIRF REMS Access program. • As required by the TIRF REMS Access program, review the contents of the Actiq Medication Guide with every patient before initiating treatment with Actiq. • Advise the patient that Actiq is available only from pharmacies that are enrolled in the TIRF REMS Access program, and provide them with the telephone number and website for information on how to obtain the drug. • Advise the patient that only enrolled healthcare providers may prescribe Actiq. • Inform the patient that they must sign the Patient-Prescriber Agreement to acknowledge that they understand the risks of Actiq. • Advise patients that they may be requested to participate in a survey to evaluate the effectiveness of the TIRF REMS Access program [see Warnings and Precautions (5.7)].

Serotonin Syndrome

Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications [see Warnings and Precautions (5.10), Drug Interactions (7)].

MAOI Interaction

Inform patients to avoid taking Actiq while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking Actiq [see Warnings and Precautions (5.10, 5.18); Drug Interactions (7)].

Adrenal Insufficiency

Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [see Warnings and Precautions (5.11)].

Important Administration Instructions [see Dosage and Administration (2)]

• Instruct patients not to take Actiq for acute pain, postoperative pain, pain from injuries, headache, migraine or any other short-term pain, even if they have taken other opioid analgesics for these conditions. • Instruct patients on the meaning of opioid tolerance and that Actiq is only to be used as a supplemental pain medication for patients with pain requiring around-the-clock opioids, who have developed tolerance to the opioid medication, and who need additional opioid treatment of breakthrough pain episodes. • Instruct patients that, if they are not taking an opioid medication on a scheduled basis (around-the-clock), they should not take Actiq. • Instruct patients that, if the breakthrough pain episode is not relieved 15 minutes after finishing the Actiq unit, they may take only one additional unit of Actiq using the same strength for that episode. Thus, patients should take no more than two units of Actiq for any breakthrough pain episode. • Instruct patients that they MUST wait at least 4 hours before treating another episode of breakthrough pain with Actiq. • Instruct patients NOT to share Actiq and that sharing Actiq with anyone else could result in the other individual’s death due to overdose. • Make patients aware that Actiq contains fentanyl which is a strong pain medication similar to hydromorphone, methadone, morphine, oxycodone, and oxymorphone. • Caution patients to talk to their doctor if breakthrough pain is not alleviated or worsens after taking Actiq. • Instruct patients to use Actiq exactly as prescribed by their doctor and not to take Actiq more often than prescribed.

Hypotension

Inform patients that Actiq may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [see Warnings and Precautions (5.12)].

Anaphylaxis

Inform patients that anaphylaxis have been reported with ingredients contained in Actiq. Advise patients how to recognize such a reaction and when to seek medical attention [see Contraindications (4), Adverse Reactions (6).]

Pregnancy

  Neonatal Opioid Withdrawal Syndrome   Inform patients that prolonged use of Actiq during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see Warnings and Precautions (5.8), Use in Specific Populations (8.1)].   Embryo-Fetal Toxicity   Inform female patients of reproductive potential that Actiq can cause fetal harm and to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)].

Lactation

Advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Instruct nursing mothers to seek immediate medical care if they notice these signs [see Use in Specific Populations (8.2)].

Infertility

Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible [see Use in Specific Populations (8.3)].

Driving or Operating Heavy Machinery

Inform patients that Actiq may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication [see Warnings and Precautions (5.16)].

Constipation

Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Adverse Reactions (6), Clinical Pharmacology (12.2)].

Dental Decay

Because each Actiq unit contains approximately 2 grams of sugar (hydrated dextrates), frequent consumption may increase the risk of dental decay. The occurrence of dry mouth associated with the use of opioid medications (such as fentanyl) may add to this risk.

Post-marketing reports of dental decay have been received in patients taking Actiq [see Adverse Reactions (6.2)]. In some of these patients, dental decay occurred despite reported routine oral hygiene. As dental decay in cancer patients may be multi-factorial, patients using Actiq should consult their dentist to ensure appropriate oral hygiene.

Diabetic Patients

Advise diabetic patients that Actiq contains approximately 2 grams of sugar per unit.

Disposal of Used Actiq Units

Instruct patients on proper disposal of completely used and partially used Actiq units as follows:

1. After consumption of the unit is complete and the matrix is totally dissolved, throw away the handle in a trash container that is out of the reach of children. 2. If any of the drug matrix remains on the handle, place the handle under hot running tap water until all of the drug matrix is dissolved, and then dispose of the handle in a place that is out of the reach of children. 3. Dispose of handles in the child-resistant container (as described in steps 1 and 2) at least once a day.

If the patient does not entirely consume the unit and the remaining drug cannot be immediately dissolved under hot running water, the patient or caregiver must temporarily store the Actiq unit in the specially provided child-resistant container out of the reach of children until proper disposal is possible.

Disposal of Unopened Actiq Units When No Longer Needed

Patients and members of their household must be advised to dispose of any unopened units remaining from a prescription as soon as they are no longer needed.

To dispose of the unused Actiq units:

• Remove the Actiq unit from its blister package using scissors, and hold the Actiq by its handle over the toilet bowl. • Using wire-cutting pliers cut off the drug matrix end so that it falls into the toilet. • Dispose of the handle in a place that is out of the reach of children. • Repeat steps 1, 2, and 3 for each Actiq unit. Flush the toilet twice after 5 units have been cut and deposited into the toilet.

Do not flush the entire Actiq units, Actiq handles, blister packages, or cartons down the toilet. Dispose of the handle where children cannot reach it.

Detailed instructions for the proper storage, administration, disposal, and important instructions for managing an overdose of Actiq are provided in the Actiq Medication Guide. Encourage patients to read this information in its entirety and give them an opportunity to have their questions answered.

In the event that a caregiver requires additional assistance in disposing of excess unusable units that remain in the home after a patient has expired, instruct them to call the toll-free number for Teva Pharmaceuticals (1-888-483-8279) or seek assistance from their local DEA office.

ACT-012

Distributed By:

Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

Actiq is a trademark of Cephalon, Inc. or its affiliates.

©2016 Cephalon, Inc., a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved.

Uses of Actiq

Actiq is a prescription medication used to treat breakthrough cancer pain in cancer patients 16 years of age and older who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Manufacturer

  • Cephalon, Inc.

Actiq FDA Warning

WARNING: RISK OF RESPIRATORY DEPRESSION, MEDICATION ERRORS, ABUSE POTENTIAL

RESPIRATORY DEPRESSION

Fatal respiratory depression has occurred in patients treated with ACTIQ, including following use in opioid non-tolerant patients and improper dosing.The substitution of ACTIQ for any other fentanyl product may result in fatal overdose.

Due to the risk of respiratory depression, ACTIQ is contraindicated in the management of acute or postoperative pain including headache/migraine and in opioid non-tolerant patients. 

Death has been reported in children who have accidentally ingested ACTIQ. ACTIQ must be kept out of reach of children. 

The concomitant use of ACTIQ with CYP3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression.

MEDICATION ERRORS

Substantial differences exist in the pharmacokinetic profile of ACTIQ compared to other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl that could result in fatal overdose.

- When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl products to ACTIQ. 

- When dispensing, do not substitute an ACTIQ prescription for other fentanyl products.

ABUSE POTENTIAL

ACTIQ contains fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics.

ACTIQ can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing ACTIQ in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion.

Because of the risk for misuse, abuse, addiction, and overdose, ACTIQ is available only through a restricted program required by the Food and Drug Administration, called a Risk Evaluation and Mitigation Strategy (REMS). Under the Transmucosal Immediate Release Fentanyl (TIRF) REMS Access program, outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors must enroll in the program. Further information is available at www.TIRFREMSAccess.com or by calling 1-866-822-1483.

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