Chemmart Sotalol may be available in the countries listed below.
Sotalol hydrochloride (a derivative of Sotalol) is reported as an ingredient of Chemmart Sotalol in the following countries:
International Drug Name Search
Rx ONLY
WARNING
Apnea is experienced by about 10 to 12% of neonates with congenital heart defects treated with Alprostadil Injection, USP. Apnea is most often seen in neonates weighing less than 2 kg at birth and usually appears during the first hour of drug infusion. Therefore, respiratory status should be monitored throughout treatment, and Alprostadil Injection, USP should be used where ventilatory assistance is immediately available.
Alprostadil Injection, USP for intravascular infusion contains 500 micrograms Alprostadil, more commonly known as prostaglandin E1, in 1 mL dehydrated alcohol.
The chemical name for Alprostadil is (1R,2R,3R)-3-Hydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxocyclopentane heptanoic acid, and the molecular weight is 354.49.
Alprostadil is a white to off-white crystalline powder with a melting point between 110° and 116° C. Its solubility at 35° C is 8000 micrograms per 100 mL double distilled water. The structural formula is represented below:
Molecular Formula - C20H34O5
Alprostadil (prostaglandin E1) is one of a family of naturally occurring acidic lipids with various pharmacologic effects. Vasodilation, inhibition of platelet aggregation, and stimulation of intestinal and uterine smooth muscle are among the most notable of these effects. Intravenous doses of 1 to 10 micrograms of Alprostadil per kilogram of body weight lower the blood pressure in mammals by decreasing peripheral resistance. Reflex increases in cardiac output and rate accompany the reduction in blood pressure.
Smooth muscle of the ductus arteriosus is especially sensitive to Alprostadil, and strips of lamb ductus markedly relax in the presence of the drug. In addition, administration of Alprostadil reopened the closing ductus of new-born rats, rabbits, and lambs. These observations led to the investigation of Alprostadil in infants who had congenital defects which restricted the pulmonary or systemic blood flow and who depended on a patent ductus arteriosus for adequate blood oxygenation and lower body perfusion.
In infants with restricted pulmonary blood flow, about 50% responded to Alprostadil infusion with at least a 10 torr increase in blood pO2 (mean increase about 14 torr and mean increase in oxygen saturation about 23%). In general, patients who responded best had low pretreatment blood pO2 and were 4 days old or less.
In infants with restricted systemic blood flow, Alprostadil often increased pH in those having acidosis, increased systemic blood pressure, and decreased the ratio of pulmonary artery pressure to aortic pressure.
Alprostadil must be infused continuously because it is very rapidly metabolized. As much as 80% of the circulating Alprostadil may be metabolized in one pass through the lungs, primarily by β- and ω- oxidation. The metabolites are excreted primarily by the kidney, and excretion is essentially complete within 24 hours after administration. No unchanged Alprostadil has been found in the urine, and there is no evidence of tissue retention of Alprostadil or its metabolites.
Alprostadil injection is indicated for palliative, not definitive, therapy to temporarily maintain the patency of the ductus arteriosus until corrective or palliative surgery can be performed in neonates who have congenital heart defects and who depend upon the patent ductus for survival. Such congenital heart defects include pulmonary atresia, pulmonary stenosis, tricuspid atresia, tetralogy of Fallot, interruption of the aortic arch, coarctation of the aorta, or transposition of the great vessels with or without other defects.
In infants with restricted pulmonary blood flow, the increase in blood oxygenation is inversely proportional to pretreatment pO2 values; that is, patients with low pO2 values respond best, and patients with pO2 values of 40 torr or more usually have little response.
Alprostadil injection should be administered only by trained personnel in facilities that provide pediatric intensive care.
None.
See WARNING box.
NOTE: Alprostadil injection must be diluted before it is administered. See dilution instructions in DOSAGE AND ADMINISTRATION section.
The administration of Alprostadil injection to neonates may result in gastric outlet obstruction secondary to antral hyperplasia. This effect appears to be related to duration of therapy and cumulative dose of the drug. Neonates receiving Alprostadil injection at recommended doses for more than 120 hours should be closely monitored for evidence of antral hyperplasia and gastric outlet obstruction.
Alprostadil injection should be infused for the shortest time and at the lowest dose that will produce the desired effects. The risks of long-term infusion of Alprostadil injection should be weighed against the possible benefits that critically ill infants may derive from its administration.
Cortical proliferation of the long bones, first observed in dogs, has also been observed in infants during long-term infusions of Alprostadil. The cortical proliferation in infants regressed after withdrawal of the drug.
In infants treated with Alprostadil injection at the usual doses for 10 hours to 12 days and who died of causes unrelated to ductus structural weakness, tissue sections of the ductus and pulmonary arteries have shown intimal lacerations, a decrease in medial muscularity and disruption of the medial and internal elastic lamina. Localized and aneurysmal dilatations and vessel wall edema also were seen compared to a series of pathological specimens from infants not treated with Alprostadil injection. The incidence of such structural alterations has not been defined.
Because Alprostadil inhibits platelet aggregation, use Alprostadil injection cautiously in neonates with bleeding tendencies.
Alprostadil injection should not be used in neonates with respiratory distress syndrome. A differential diagnosis should be made between respiratory distress syndrome (hyaline membrane disease) and cyanotic heart disease (restricted pulmonary blood flow). If full diagnostic facilities are not immediately available, cyanosis (pO2 less than 40 torr) and restricted pulmonary blood flow apparent on an X-ray are appropriate indicators of congenital heart defects.
In all neonates, arterial pressure should be monitored intermittently by umbilical artery catheter, auscultation, or with a Doppler transducer. Should arterial pressure fall significantly, decrease the rate of infusion immediately.
In infants with restricted pulmonary blood flow, measure efficacy of Alprostadil injection by monitoring improvement in blood oxygenation. In infants with restricted systemic blood flow, measure efficacy by monitoring improvement of systemic blood pressure and blood pH.
No drug interactions have been reported between Alprostadil injection and the therapy standard in neonates with restricted pulmonary or systemic blood flow. Standard therapy includes antibiotics, such as penicillin and gentamicin; vasopressors, such as dopamine and isoproterenol; cardiac glycosides; and diuretics, such as furosemide.
Long-term carcinogenicity studies and fertility studies have not been done. The Ames and Alkaline Elution assays reveal no potential for mutagenesis.
Apnea has been reported in about 12% of the neonates treated. (See WARNING box.) Other common adverse reactions reported have been fever in about 14% of the patients treated and seizures in about 4%. The following reactions have been reported in less than 1% of the patients: cerebral bleeding, hyperextension of the neck, hyperirritability, hypothermia, jitteriness, lethargy, and stiffness.
The most common adverse reactions reported have been flushing in about 10% of patients (more common after intraarterial dosing), bradycardia in about 7%, hypotension in about 4%, tachycardia in about 3%, cardiac arrest in about 1%, and edema in about 1%. The following reactions have been reported in less than 1% of the patients: congestive heart failure, hyperemia, second degree heart block, shock, spasm of the right ventricle infundibulum, supraventricular tachycardia, and ventricular fibrillation.
The following reactions have been reported in less than 1% of the patients: bradypnea, bronchial wheezing, hypercapnia, respiratory depression, respiratory distress, and tachypnea.
See WARNINGS.
The most common adverse reaction reported has been diarrhea in about 2% of the patients. The following reactions have been reported in less than 1% of the patients: gastric regurgitation, and hyperbilirubinemia.
The most common hematologic event reported has been disseminated intravascular coagulation in about 1% of the patients. The following events have been reported in less than 1% of the patients: anemia, bleeding, and thrombocytopenia.
Anuria and hematuria have been reported in less than 1% of the patients.
Cortical proliferation of the long bones has been reported.
See PRECAUTIONS.
Sepsis has been reported in about 2% of the patients. Peritonitis has been reported in less than 1% of the patients. Hypokalemia has been reported in about 1%, and hypoglycemia and hyperkalemia have been reported in less than 1% of the patients.
Apnea, bradycardia, pyrexia, hypotension, and flushing may be signs of drug overdosage. If apnea or bradycardia occurs, discontinue the infusion, and provide appropriate medical treatment. Caution should be used in restarting the infusion. If pyrexia or hypotension occurs, reduce the infusion rate until these symptoms subside. Flushing is usually a result of incorrect intraarterial catheter placement, and the catheter should be repositioned.
The preferred route of administration for Alprostadil injection is continuous intravenous infusion into a large vein. Alternatively, Alprostadil injection may be administered through an umbilical artery catheter placed at the ductal opening. Increases in blood pO2 (torr) have been the same in neonates who received the drug by either route of administration.
Begin infusion with 0.05 to 0.1 micrograms Alprostadil per kilogram of body weight per minute. A starting dose of 0.1 micrograms per kilogram of body weight per minute is the recommended starting dose based on clinical studies; however, adequate clinical response has been reported using a starting dose of 0.05 micrograms per kilogram of body weight per minute. After a therapeutic response is achieved (increased pO2 in infants with restricted pulmonary blood flow or increased systemic blood pressure and blood pH in infants with restricted systemic blood flow), reduce the infusion rate to provide the lowest possible dosage that maintains the response. This may be accomplished by reducing the dosage from 0.1 to 0.05 to 0.025 to 0.01 micrograms per kilogram of body weight per minute. If response to 0.05 micrograms per kilogram of body weight per minute is inadequate, dosage can be increased up to 0.4 micrograms per kilogram of body weight per minute although, in general, higher infusion rates do not produce greater effects.
To prepare infusion solutions, dilute 1 mL of Alprostadil Injection with Sodium Chloride Injection or Dextrose Injection. Undiluted Alprostadil Injection may interact with the plastic sidewalls of volumetric infusion chambers causing a change in the appearance of the chamber and creating a hazy solution. Should this occur, the solution and the volumetric infusion chamber should be replaced.
When using a volumetric infusion chamber, the appropriate amount of intravenous infusion solution should be added to the chamber first. The undiluted Alprostadil Injection solution should then be added to the intravenous infusion solution, avoiding direct contact of the undiluted solution with the walls of the volumetric infusion chamber.
Dilute to volumes appropriate for the pump delivery system available. Prepare fresh infusion solutions every 24 hours. Discard any solution more than 24 hours old.
| Add 1 vial (500 mcg) Alprostadil to: | Approximate Concentration of resulting solution (mcg/mL) | Infusion rate (mL/min/kg of body weight) |
| 250 mL | 2 | 0.05 |
| 100 mL | 5 | 0.02 |
| 50 mL | 10 | 0.01 |
| 25 mL | 20 | 0.005 |
Example: To provide 0.1 micrograms/kilogram of body weight per minute to an infant weighing 2.8 kilograms using a solution of 1 mL Alprostadil Injection, USP (500 mcg/mL), in 100 mL of saline or dextrose: INFUSION RATE = 0.02 mL/min per kg x 2.8 kg = 0.056 mL/min or 3.36 mL/hr.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Alprostadil Injection, USP is available as follows:
NDC 55390-503-10 – 1 mL vials, individually-boxed.
Each mL contains 500 micrograms Alprostadil in dehydrated alcohol.
Store in a refrigerator at 2° to 8° C (36° to 46° F).
Manufactured by: Distributed by:
Ben Venue Laboratories, Inc. Bedford Laboratories
Bedford, OH 44146 Bedford, OH 44146
August 2000 VALP00
Novation, the supply company of VHA and UHC, and NOVAPLUS are trademarks of Novation, LLC.
Vial Label 500 mcg (0.5 mg)/mL
Unit Carton 500 mcg (0.5 mg)/mL
| Alprostadil Alprostadil injection | ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| ANDA | ANDA074815 | 03/04/2005 | |
| Labeler - Bedford Laboratories (884528407) |
In some countries, this medicine may only be approved for veterinary use.
In the US, Etodolac (etodolac systemic) is a member of the drug class nonsteroidal anti-inflammatory agents and is used to treat Juvenile Rheumatoid Arthritis, Osteoarthritis, Pain and Rheumatoid Arthritis.
US matches:
Rec.INN
M01AB08
0041340-25-4
C17-H21-N-O3
287
Analgesic, antipyretic and anti-inflammatory agent
Non-steroidal anti-inflammatory drug, NSAID
Pyrano[3,4-b]indole-1-acetic acid, 1,8-diethyl-1,3,4,9-tetrahydro-
International Drug Name Search
Glossary
| BAN | British Approved Name |
| DCF | Dénomination Commune Française |
| DCIT | Denominazione Comune Italiana |
| IS | Inofficial Synonym |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
Treating acid indigestion, heartburn, and sour stomach. It may also be used for other conditions as determined by your doctor.
Aluminum/Magnesium Chewable Tablets are an antacid. It works by neutralizing acid in the stomach.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Aluminum/Magnesium Chewable Tablets. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Aluminum/Magnesium Chewable Tablets. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Aluminum/Magnesium Chewable Tablets may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Aluminum/Magnesium Chewable Tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Aluminum/Magnesium Chewable Tablets.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Constipation; diarrhea.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); loss of appetite; muscle weakness; nausea; slow reflexes; vomiting.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center (http://www.aapcc.org ), or emergency room immediately.
Store Aluminum/Magnesium Chewable Tablets between 59 and 86 degrees F (15 and 30 degrees C). Store in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Aluminum/Magnesium Chewable Tablets out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Aluminum/Magnesium Chewable Tablets. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
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. [see Contraindications (4)]
Death has been reported in children who have accidentally ingested Actiq. Actiq must be kept out of reach of children. [see Patient Counseling Information (17.3) and How Supplied/Storage and Handling (16.1)]
The concomitant use of Actiq with CYP3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression [see Drug Interactions (7)].
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. [see Dosage and Administration (2.1)]
- 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. [see Warnings and Precautions (5.10)] Further information is available at www.TIRFREMSAccess.com or by calling 1-866-822-1483.
Actiq (oral transmucosal fentanyl citrate) is indicated for the management of breakthrough 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. Patients considered opioid tolerant are those who are taking around-the-clock medicine consisting of at least 60 mg of oral morphine daily, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oral oxycodone daily, at least 8 mg of oral hydromorphone daily, at least 25 mg oral oxymorphone daily, or an equianalgesic dose of another opioid daily for a week or longer. Patients must remain on around-the-clock opioids when taking Actiq.
This product must not be used in opioid non-tolerant patients because life-threatening respiratory depression and death could occur at any dose in patients not on a chronic regimen of opioids. For this reason, Actiq is contraindicated in the management of acute or postoperative pain.
Actiq is intended to be used only in the care of opioid-tolerant cancer patients and only by oncologists and pain specialists who are knowledgeable of and skilled in the use of Schedule II opioids to treat cancer pain.
Limitations of Use:
As a part of the TIRF REMS Access program, Actiq may be dispensed only to outpatients enrolled in the program [see Warnings and Precautions (5.10)]. For inpatient administration of Actiq (e.g., hospitals, hospices, and long-term care facilities that prescribe for inpatient use), patient and prescriber enrollment is not required.
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 (5.10)].
As with all opioids, the safety of patients using such products is dependent on health care professionals prescribing them in strict conformity with their approved labeling with respect to patient selection, dosing, and proper conditions for use.
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.
From this initial dose, closely follow patients and change the dosage level 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.
Actiq Titration Process
See Boxed Warning
*Available dosage strengths include: 200, 400, 600, 800, 1200, and 1600 mcg.
Once titrated to an effective dose, patients should generally use ONLY ONE Actiq unit of the appropriate strength per breakthrough pain episode.
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.
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.
Dosage adjustment of Actiq may be required in some patients in order to continue to provide adequate relief of breakthrough pain.
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.
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.
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.
For patients requiring discontinuation of opioids, a gradual downward titration is recommended because it is not known at what dose level the opioid may be discontinued without producing the signs and symptoms of abrupt withdrawal.
Each dosage unit has white to off-white color and is a solid drug matrix on a handle. Each strength is marked on the individual solid drug matrix and the handle tag. Actiq is available in 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1200 mcg and 1600 mcg strengths [see How Supplied/Storage and Handling (16.3)].
Actiq is contraindicated in opioid non-tolerant patients. Actiq is contraindicated in the management of acute or postoperative pain including headache/migraine and dental pain. Life-threatening respiratory depression and death could occur at any dose in opioid non-tolerant patients.
Patients considered opioid tolerant are those who are taking around-the-clock medicine consisting of at least 60 mg of oral morphine daily, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oral oxycodone daily, at least 8 mg of oral hydromorphone daily, at least 25 mg oral oxymorphone daily, or an equianalgesic dose of another opioid daily for a week or longer.
Actiq is contraindicated in patients with known intolerance or hypersensitivity to any of its components or the drug fentanyl. Anaphylaxis and hypersensitivity have been reported in association with the use of Actiq.
See Boxed Warning - WARNING:RISK OF RESPIRATORY DEPRESSION, MEDICATION ERRORS, ABUSE POTENTIAL
Respiratory depression is the chief hazard of opioid agonists, including fentanyl, the active ingredient in Actiq. Respiratory depression is more likely to occur in patients with underlying respiratory disorders and elderly or debilitated patients, usually following large initial doses in opioid non-tolerant patients, or when opioids are given in conjunction with other drugs that depress respiration.
Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with the “sighing” pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. This makes overdoses involving drugs with sedative properties and opioids especially dangerous.
When prescribing, DO NOT convert a patient to Actiq from any other fentanyl product on a mcg per mcg basis as Actiq and other fentanyl products are not equivalent on a microgram per microgram basis.
Actiq is NOT a generic version of Fentora®. When dispensing, DO NOT substitute an Actiq prescription for a Fentora prescription under any circumstances. Fentora and Actiq are not equivalent. Substantial differences exist in the pharmacokinetic profile of Actiq compared to other fentanyl products including Fentora that result in clinically important differences in the rate and extent of absorption of fentanyl. As a result of these differences, the substitution of Actiq for any other fentanyl product may result in a fatal overdose.
There are no safe conversion directions available for patients on any other fentanyl products. (Note: This includes oral, transdermal, or parenteral formulations of fentanyl.) Therefore, for opioid tolerant patients, the initial dose of Actiq should always be 200 mcg. Each patient should be individually titrated to provide adequate analgesia while minimizing side effects [see Dosage and Administration (2.2)].
Patients and their caregivers must be instructed that Actiq contains a medicine in an amount which can be fatal to a child. Death has been reported in children who have accidentally ingested Actiq. Patients and their caregivers must be instructed to keep both used and unused dosage units out of the reach of children. While all units should be disposed of immediately after use, partially consumed units represent a special risk to children. In the event that a unit is not completely consumed it must be properly disposed as soon as possible [see How Supplied/Storage and Handling (16.1, 16.2), Patient Counseling Information (17.3), and Medication Guide].
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.
Actiq could be fatal to individuals for whom it is not prescribed and for those who are not opioid-tolerant.
The concomitant use of Actiq with other CNS depressants, including other opioids, sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, skeletal muscle relaxants, sedating antihistamines, and alcoholic beverages may produce increased depressant effects (e.g., respiratory depression, hypotension, and profound sedation). Concomitant use with potent inhibitors of cytochrome P450 3A4 isoform (e.g., erythromycin, ketoconazole, and certain protease inhibitors) may increase fentanyl levels, resulting in increased depressant effects [see Drug Interactions (7)].
Patients on concomitant CNS depressants must be monitored for a change in opioid effects. Consideration should be given to adjusting the dose of Actiq if warranted.
Opioid analgesics impair the mental and/or physical ability required for the performance of potentially dangerous tasks (e.g., driving a car or operating machinery). Warn patients taking Actiq of these dangers and counsel them accordingly.
Because potent opioids can cause respiratory depression, titrate Actiq with caution in patients with chronic obstructive pulmonary disease or preexisting medical conditions predisposing them to respiratory depression. In such patients, even normal therapeutic doses of Actiq may further decrease respiratory drive to the point of respiratory failure.
Administer Actiq with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO2 retention such as those with evidence of increased intracranial pressure or impaired consciousness. Opioids may obscure the clinical course of a patient with a head injury and should be used only if clinically warranted.
Intravenous fentanyl may produce bradycardia. Therefore, use Actiq with caution in patients with bradyarrhythmias.
Actiq is not recommended for use in patients who have received MAO inhibitors within 14 days, because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.
Because of the risk for misuse, abuse, addiction, and overdose [see Drug Abuse and Dependence (9)], Actiq is available only through a restricted program called the TIRF REMS Access program. Under the TIRF REMS Access program, outpatients, healthcare professionals who prescribe for outpatient use, pharmacies, and distributors must enroll in the program. For inpatient administration (e.g., hospitals, hospices, and long-term care facilities that prescribe for inpatient use) of Actiq, patient and prescriber enrollment is not required.
Required components of the TIRF REMS Access program are:
• Healthcare professionals, who prescribe Actiq for outpatient use, must review the prescriber educational materials for the TIRF REMS Access program, enroll in the program, and comply with the REMS requirements.
• To receive Actiq, outpatients must understand the risks and benefits and sign a Patient-Prescriber Agreement.
• Pharmacies that dispense Actiq must enroll in the program, and agree to comply with the REMS requirements.
• Wholesalers and distributors that distribute Actiq must enroll in the program, and distribute only to authorized pharmacies.
Further information, including a list of qualified pharmacies/distributors, is available at www.TIRFREMSAccess.com or by calling 1-866-822-1483.
The safety of Actiq has been evaluated in 257 opioid-tolerant chronic cancer pain patients. The duration of Actiq use varied during the open-label study. Some patients were followed for over 21 months. The average duration of therapy in the open-label study was 129 days.
The adverse reactions seen with Actiq are typical opioid side effects. Frequently, these adverse reactions will cease or decrease in intensity with continued use of Actiq, as the patient is titrated to the proper dose. Expect opioid side effects and manage them accordingly.
The most serious adverse reactions associated with all opioids including Actiq are respiratory depression (potentially leading to apnea or respiratory arrest), circulatory depression, hypotension, and shock. Follow all patients for symptoms of respiratory depression.
Because the clinical trials of Actiq were designed to evaluate safety and efficacy in treating breakthrough cancer pain, all patients were also taking concomitant opioids, such as sustained-release morphine or transdermal fentanyl, for their persistent cancer pain. The adverse event data presented here reflect the actual percentage of patients experiencing each adverse effect among patients who received Actiq for breakthrough cancer pain along with a concomitant opioid for persistent cancer pain. There has been no attempt to correct for concomitant use of other opioids, duration of Actiq therapy, or cancer-related symptoms. Adverse reactions are included regardless of causality or severity.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Three short-term clinical trials with similar titration schemes were conducted in 257 patients with malignancy and breakthrough cancer pain. Data are available for 254 of these patients. The goal of titration in these trials was to find the dose of Actiq that provided adequate analgesia with acceptable side effects (successful dose). Patients were titrated from a low dose to a successful dose in a manner similar to current titration dosing guidelines. Table 1 lists, by dose groups, adverse reactions with an overall frequency of 1% or greater that occurred during titration and are commonly associated with opioid administration or are of particular clinical interest. The ability to assign a dose-response relationship to these adverse reactions is limited by the titration schemes used in these studies. Adverse reactions are listed in descending order of frequency within each body system.
| *Any Dose = A patient who experienced the same adverse event at multiple doses was only counted once. | |||||
| Dose Group | Percentage of Patients Reporting Event | ||||
| 200- 600 mcg (n=230) | 800- 1400 mcg (n=138) | 1600 mcg (n=54) | >1600 mcg (n=41) | Any Dose* (n=254) | |
| Body As A Whole | |||||
| Asthenia | 6 | 4 | 0 | 7 | 9 |
| Headache | 3 | 4 | 6 | 5 | 6 |
| Accidental Injury | 1 | 1 | 4 | 0 | 2 |
| Digestive | |||||
| Nausea | 14 | 15 | 11 | 22 | 23 |
| Vomiting | 7 | 6 | 6 | 15 | 12 |
| Constipation | 1 | 4 | 2 | 0 | 4 |
| Nervous | |||||
| Dizziness | 10 | 16 | 6 | 15 | 17 |
| Somnolence | 9 | 9 | 11 | 20 | 17 |
| Confusion | 1 | 6 | 2 | 0 | 4 |
| Anxiety | 3 | 0 | 2 | 0 | 3 |
| Abnormal Gait | 0 | 1 | 4 | 0 | 2 |
| Dry Mouth | 1 | 1 | 2 | 0 | 2 |
| Nervousness | 1 | 1 | 0 | 0 | 2 |
| Vasodilatation | 2 | 0 | 2 | 0 | 2 |
| Hallucinations | 0 | 1 | 2 | 2 | 1 |
| Insomnia | 0 | 1 | 2 | 0 | 1 |
| Thinking Abnormal | 0 | 1 | 2 | 0 | 1 |
| Vertigo | 1 | 0 | 0 | 0 | 1 |
| Respiratory | |||||
| Dyspnea | 2 | 3 | 6 | 5 | 4 |
| Skin | |||||
| Pruritus | 1 | 0 | 0 | 5 | 2 |
| Rash | 1 | 1 | 0 | 2 | 2 |
| Sweating | 1 | 1 | 2 | 2 | 2 |
| Special Senses | |||||
| Abnormal Vision | 1 | 0 | 2 | 0 | 2 |
The following adverse reactions not reflected in Table 1 occurred during titration with an overall frequency of 1% or greater and are listed in descending order of frequency within each body system.
Body as a Whole: Pain, fever, abdominal pain, chills, back pain, chest pain, infection
Cardiovascular: Migraine
Digestive: Diarrhea, dyspepsia, flatulence
Metabolic and Nutritional: Peripheral edema, dehydration
Nervous: Hypesthesia
Respiratory: Pharyngitis, cough increased
The following reactions occurred during titration with an overall frequency of less than 1% and are listed in descending order of frequency within each body system.
Body as a Whole: Flu syndrome, abscess, bone pain
Cardiovascular: Deep thrombophlebitis, hypertension, hypotension
Digestive: Anorexia, eructation, esophageal stenosis, fecal impaction, gum hemorrhage, mouth ulceration, oral moniliasis
Hemic and Lymphatic: Anemia, leukopenia
Metabolic and Nutritional: Edema, hypercalcemia, weight loss
Musculoskeletal: Myalgia, pathological fracture, myasthenia
Nervous: Abnormal dreams, urinary retention, agitation, amnesia, emotional lability, euphoria, incoordination, libido decreased, neuropathy, paresthesia, speech disorder
Respiratory: Hemoptysis, pleural effusion, rhinitis, asthma, hiccup, pneumonia, respiratory insufficiency, sputum increased
Skin and Appendages: Alopecia, exfoliative dermatitis
Special Senses: Taste perversion
Urogenital: Vaginal hemorrhage, dysuria, hematuria, urinary incontinence, urinary tract infection
A long-term extension study was conducted in 156 patients with malignancy and breakthrough cancer pain who were treated for an average of 129 days. Data are available for 152 of these patients. Table 2 lists by dose groups, adverse reactions with an overall frequency of 1% or greater that occurred during the long-term extension study and are commonly associated with opioid administration or are of particular clinical interest. Adverse reactions are listed in descending order of frequency within each body system.
| * Any Dose = A patient who experienced the same adverse event at multiple doses was only counted once. | |||||
| Dose Group | Percentage of Patients Reporting Event | ||||
| 200- 600 mcg (n=98) | 800- 1400 mcg (n=83) | 1600 mcg (n=53) | >1600 mcg (n=27) | Any Dose* (n=152) | |
| Body As A Whole | |||||
| Asthenia | 25 | 30 | 17 | 15 | 38 |
| Headache | 12 | 17 | 13 | 4 | 20 |
| Accidental Injury | 4 | 6 | 4 | 7 | 9 |
| Hypertonia | 2 | 2 | 2 | 0 | 3 |
| Digestive | |||||
| Nausea | 31 | 36 | 25 | 26 | 45 |
| Vomiting | 21 | 28 | 15 | 7 | 31 |
| Constipation | 14 | 11 | 13 | 4 | 20 |
| Intestinal Obstruction | 0 | 2 | 4 | 0 | 3 |
| Cardiovascular | |||||
| Hypertension | 1 | 1 | 0 | 0 | 1 |
| Nervous | |||||
| Dizziness | 12 | 10 | 9 | 0 | 16 |
| Anxiety | 9 | 8 | 8 | 7 | 15 |
| Somnolence | 8 | 13 | 8 | 7 | 15 |
| Confusion | 2 | 5 | 13 | 7 | 10 |
| Depression | 9 | 4 | 2 | 7 | 9 |
| Insomnia | 5 | 1 | 8 | 4 | 7 |
| Abnormal Gait | 5 | 1 | 0 | 0 | 4 |
| Dry Mouth | 3 | 1 | 2 | 4 | 4 |
| Nervousness | 2 | 2 | 0 | 4 | 3 |
| Stupor | 4 | 1 | 0 | 0 | 3 |
| Vasodilatation | 1 | 1 | 4 | 0 | 3 |
| Thinking Abnormal | 2 | 1 | 0 | 0 | 2 |
| Abnormal Dreams | 1 | 1 | 0 | 0 | 1 |
| Convulsion | 0 | 1 | 2 | 0 | 1 |
| Myoclonus | 0 | 0 | 4 | 0 | 1 |
| Tremor | 0 | 1 | 2 | 0 | 1 |
| Vertigo | 0 | 0 | 4 | 0 | 1 |
| Respiratory | |||||
| Dyspnea | 15 | 16 | 8 | 7 | 22 |
| Skin | |||||
| Rash | 3 | 5 | 8 | 4 | 8 |
| Sweating | 3 | 2 | 2 | 0 | 4 |
| Pruritus | 2 | 0 | 2 | 0 | 2 |
| Special Senses | |||||
| Abnormal Vision | 2 | 2 | 0 | 0 | 3 |
| Urogenital | |||||
| Urinary Retention | 1 | 2 | 0 | 0 | 2 |
The following reactions not reflected in Table 2 occurred with an overall frequency of 1% or greater in the long-term extension study and are listed in descending order of frequency within each body
In the US, Skelid (tiludronate systemic) is a member of the drug class bisphosphonates and is used to treat Paget's Disease.
US matches:
UK matches:
Tiludronic Acid disodium salt (a derivative of Tiludronic Acid) is reported as an ingredient of Skelid in the following countries:
International Drug Name Search
Glossary
| SPC | Summary of Product Characteristics (UK) |
In the US, INOmax (nitric oxide systemic) is a member of the drug class miscellaneous respiratory agents and is used to treat Respiratory Failure.
US matches:
Nitric oxide is reported as an ingredient of INOmax in the following countries:
International Drug Name Search
