PROPOXYPHENE HYDROCHLORIDE- propoxyphene hydrochloride capsule
Bryant Ranch Prepack
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WARNINGS
Propoxyphene hydrochloride is an odorless, white crystalline powder with a bitter taste. It is freely soluble in water. Chemically, it is (2S,3R)-(+)-4-(dimethylamino)-3-methyl-1,2- diphenyl-2-butanol propionate (ester) hydrochloride, which can be represented by the following structural formula:
C22H29NO2•HCl M.W. 375.94
Each capsule, for oral administration, contains 65 mg propoxyphene hydrochloride. Propoxyphene hydrochloride capsules, USP contain the inactive ingredients corn starch, gelatin, lactose monohydrate, magnesium stearate, titanium dioxide, FD&C yellow #6, and D&C red #33.
Propoxyphene is a centrally acting opiate analgesic. In vitro studies demonstrated propoxyphene and the metabolite norpropoxyphene inhibit sodium channels (local anesthetic effect) with norpropoxyphene being approximately 2 fold more potent than propoxyphene and propoxyphene approximately 10 fold more potent than lidocaine. Propoxyphene and norpropoxyphene inhibit the voltage-gated potassium current carried by cardiac rapidly activating delayed rectifier (hERG) channels with approximately equal potency. It is unclear if the effects on ion channels occur within therapeutic dose range.
Peak plasma concentrations of propoxyphene are reached in 2 to 2.5 h. After a 65 mg oral dose of propoxyphene hydrochloride, peak plasma levels of 0.05 to 0.1 mcg/mL for propoxyphene and 0.1 to 0.2 mcg/mL for norpropoxyphene (major metabolite) are achieved. Repeated doses of propoxyphene at 6 h intervals lead to increasing plasma concentrations, with a plateau after the ninth dose at 48 h. Propoxyphene has a half-life of 6 to 12 h, whereas that of norpropoxyphene is 30 to 36 h.
Propoxyphene is about 80% bound to proteins and has a large volume of distribution, 16 L/kg.
Propoxyphene undergoes extensive first-pass metabolism by intestinal and hepatic enzymes. The major route of metabolism is cytochrome CYP3A4 mediated N-demethylation to norpropoxyphene, which is excreted by the kidneys. Ring hydroxylation and glucuronide formation are minor metabolic pathways.
Propoxyphene hydrochloride capsules are contraindicated in patients with known hypersensitivity to propoxyphene.
Propoxyphene hydrochloride capsules are contraindicated in patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment) and patients with acute or severe asthma or hypercarbia.
Propoxyphene hydrochloride capsules are contraindicated in any patient who has or is suspected of having paralytic ileus.
Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist. Physical dependence and tolerance are not unusual during chronic opioid therapy.
The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. In general, opioids should not be abruptly discontinued (see DOSAGE AND ADMINISTRATION, Cessation of Therapy).
If propoxyphene is abruptly discontinued in a physically dependent patient, an abstinence syndrome may occur (see DRUG ABUSE AND DEPENDENCE). If signs and symptoms of withdrawal occur, patients should be treated by reinstitution of opioid therapy followed by gradual tapered dose reduction of propoxyphene combined with symptomatic support (see DOSAGE AND ADMINISTRATION, Cessation of Therapy).
Propoxyphene may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids like propoxyphene may cause increases in the serum amylase level.
Insufficient information exists to make appropriate dosing recommendations regarding the use of either propoxyphene in patients with hepatic or renal impairment as a function of degree of impairment. Higher plasma concentrations and/or delayed elimination may occur in case of impaired hepatic function and/or impaired renal function (see CLINICAL PHARMACOLOGY).
If the drug is used in these patients, it should be used with caution because of the hepatic metabolism and renal excretion of propoxyphene metabolites.
(Also see Medication Guide.)
Propoxyphene is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4), therefore potential interactions may occur when propoxyphene is administered concurrently with agents that affect CYP3A4 activity.
The metabolism of propoxyphene may be altered by strong CYP3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazadone, amiodarone, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and verapamil) leading to enhanced propoxyphene plasma levels. Coadministration with agents that induce CYP3A4 activity may reduce the efficacy of propoxyphene. Strong CYP3A4 inducers such as rifampin may lead to enhanced metabolite (norpropoxyphene) levels.
Propoxyphene is also thought to possess CYP3A4 and CYP2D6 enzyme inhibiting properties and coadministration with drugs that rely on either of these enzymes for metabolism may result in increased pharmacologic or adverse effects of that drug. Severe neurologic signs, including coma, have occurred with concurrent use of carbamazepine (metabolized by CYP3A4).
Increased risk of bleeding has been observed with warfarin-like agents when given along with propoxyphene; however, the mechanistic basis of this interaction is unknown.
Patients receiving narcotic analgesics, general anesthetics, phenothiazines, other tranquilizers, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with propoxyphene may exhibit an additive CNS depression. Interactive effects resulting in respiratory depression, hypotension, profound sedation, or coma may result if these drugs are taken in combination with the usual dosage of propoxyphene. When such combined therapy is contemplated, the dose of one or both agents should be reduced.
Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol and buprenorphine) should be administered with caution to patients who have received or are receiving a course of therapy with a pure opioid agonist analgesic such as propoxyphene. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of propoxyphene and/or may precipitate withdrawal symptoms in these patients.
MAOIs have been reported to intensify the effects of at least one opioid drug causing anxiety, confusion and significant depression of respiration or coma. The use of propoxyphene is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
The mutagenic and carcinogenic potential of propoxyphene has not been evaluated.
In animal studies there was no effect of propoxyphene on mating behavior, fertility, duration of gestation, or parturition when rats were fed propoxyphene as a component of their daily diet at estimated daily propoxyphene intake up to 8 fold greater than the maximum human equivalent dose (HED) based on body surface area comparison. At this highest dose, fetal weight and survival on postnatal day 4 was reduced.
There are no adequate and well-controlled studies of propoxyphene in pregnant women. While there are limited data in the published literature, adequate animal reproduction studies have not been conducted with propoxyphene. Therefore, it is not known whether propoxyphene can affect reproduction or cause fetal harm when administered to a pregnant woman. Propoxyphene should be given to a pregnant woman only if clearly needed.
Propoxyphene and its major metabolite, norpropoxyphene, cross the human placenta. Neonates whose mothers have taken opiates chronically may exhibit respiratory depression or withdrawal symptoms.
In published animal reproduction studies, no teratogenic effects occurred in offspring born to pregnant rats or rabbits that received propoxyphene during organogenesis. Pregnant animals received propoxyphene doses approximately 10 fold (rats) and 4 fold (rabbits) the maximum recommended human dose (based on mg/m2 body surface area comparison).
Propoxyphene, norpropoxyphene (major metabolite), are excreted in human milk. Published studies of nursing mothers using propoxyphene detected no adverse effects in nursing infants. Based on a study of six mother-infant pairs, an exclusively breastfed infant receives approximately 2% of the maternal weight-adjusted dose. Norpropoxyphene is renally excreted, and renal clearance is lower in neonates than in adults. Therefore, it is possible that prolonged maternal propoxyphene use could result in norpropoxyphene accumulation in a breastfed infant. Watch breastfeeding infants for signs of sedation including poor feeding, somnolence, or respiratory depression. Caution should be exercised when propoxyphene is administered to a nursing woman.
Clinical studies of propoxyphene did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, postmarketing reports suggest that patients over the age of 65 may be more susceptible to CNS-related side effects. Therefore, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Decreased total daily dosage should be considered (see DOSAGE AND ADMINISTRATION).
In hospitalized patients, the most frequently reported were dizziness, sedation, nausea, and vomiting. Other adverse reactions include constipation, abdominal pain, skin rashes, lightheadedness, headache, weakness, euphoria, dysphoria, hallucinations, and minor visual disturbances.
The most frequently reported postmarketing adverse events have included completed suicide, accidental and intentional overdose, drug dependence, cardiac arrest, coma, drug ineffective, drug toxicity, nausea, respiratory arrest, cardio-respiratory arrest, death, vomiting, dizziness, convulsion, confusional state, and diarrhea.
Additional adverse experiences reported through postmarketing surveillance include:
Cardiac disorders: arrhythmia, bradycardia, cardiac/respiratory arrest, congestive arrest, congestive heart failure (CHF), tachycardia, myocardial infarction (MI)
Eye disorder: eye swelling, vision blurred
General disorder and administration site conditions: drug interaction, drug tolerance, drug withdrawal syndrome
Gastrointestinal disorder: gastrointestinal bleed, acute pancreatitis
Hepatobiliary disorder: hepatic steatosis, hepatomegaly, hepatocellular injury
Immune system disorder: hypersensitivity
Injury poisoning and procedural complications: drug toxicity, hip fracture, multiple drug overdose, narcotic overdose
Investigations: blood pressure decreased, heart rate elevated/abnormal
Metabolism and nutrition disorder: metabolic acidosis
Nervous system disorder: ataxia, coma, dizziness, somnolence, syncope
Psychiatric: abnormal behavior, confusional state, hallucinations, mental status change
Respiratory, thoracic, and mediastinal disorders: respiratory depression, dyspnoea
Skin and subcutaneous tissue disorder: rash, itch
Liver dysfunction has been reported in association with propoxyphene. Propoxyphene therapy has been associated with abnormal liver function tests and, more rarely, with instances of reversible jaundice (including cholestatic jaundice).
Subacute painful myopathy has been reported following chronic propoxyphene overdosage.
Propoxyphene hydrochloride capsules, USP are intended for the management of mild to moderate pain. The dose should be individually adjusted according to severity of pain, patient response and patient size.
Propoxyphene hydrochloride capsules, USP are given orally. The usual dosage is one 65 mg propoxyphene hydrochloride capsule, USP every 4 hours as needed for pain. The maximum dose of propoxyphene hydrochloride capsules, USP is 6 tablets per day. Do not exceed the maximum daily dose.
Patients receiving propoxyphene and any CYP3A4 inhibitor should be carefully monitored for an extended period of time and dosage adjustments should be made if warranted.
Consideration should be given to a reduced total daily dosage in elderly patients and in patients with hepatic or renal impairment.
For patients who used propoxyphene hydrochloride capsules, USP on a regular basis for a period of time, when therapy with propoxyphene hydrochloride capsules, USP is no longer needed for the treatment of their pain, it may be useful to gradually discontinue the propoxyphene hydrochloride capsules, USP over time to prevent the development of an opioid abstinence syndrome (narcotic withdrawal). In general, therapy can be decreased by 25% to 50% per day with careful monitoring for signs and symptoms of withdrawal (see DRUG ABUSE AND DEPENDENCE for description of the signs and symptoms of withdrawal). If the patient develops these signs or symptoms, the dose should be raised to the previous level and titrated down more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both.
PROPOXYPHENE HYDROCHLORIDE CAPSULES, USPCIV
Rx only
Read this Medication Guide before you start taking propoxyphene hydrochloride capsules, USP, and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.
What is the most important information I should know about propoxyphene hydrochloride capsules, USP?
Propoxyphene hydrochloride capsules, USP, and other medicines that contain propoxyphene can cause serious side effects, including:
Overdoses by accident or on purpose (intentional overdose). Overdoses with propoxyphene hydrochloride capsules, USP may happen when they are taken by themselves, or with alcohol or other medicines that can also decrease your breathing and make you very sleepy.
Take propoxyphene hydrochloride capsules, USP exactly as prescribed. Do not change your dose or stop taking propoxyphene hydrochloride capsules, USP without first talking to your doctor.
What are propoxyphene hydrochloride capsules, USP?
It is not known if propoxyphene hydrochloride capsules, USP are safe and effective in children younger than age 18.
Who should not take propoxyphene hydrochloride capsules, USP?
Do not take propoxyphene hydrchloride capsules, USP if you:
What should I tell my doctor before taking propoxyphene hydrochloride capsules, USP?
Before you take propoxyphene hydrochloride capsules, USP, tell your doctor:
Symptoms of withdrawal in a newborn baby may include:
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Tell your doctor about all the medicines you take, including prescription, and non-prescription medicines, vitamins, and herbal supplements. Propoxyphene hydrochloride capsules, USP interact with many medicines and may lead to serious side effects. The doses of certain medicines may need to be changed.
Especially tell your doctor if you take:
See “What is the most important information I should know about propoxyphene hydrochloride capsules, USP?”
Ask your doctor or pharmacist if you are not sure if your medicine is one listed above.
Know the medicines you take. Keep a list of them to show to your doctor and pharmacist when you get a new medicine.
How should I take propoxyphene hydrochloride capsules, USP?
See “What is the most important information I should know about propoxyphene hydrochloride capsules, USP?”
Signs and symptoms of an overdose of propoxyphene hydrochloride capsules, USP include:
What are the possible side effects of propoxyphene hydrochloride capsules, USP?
Propoxyphene hydrochloride capsules, USP can cause serious side effects, including:
See “What is the most important information I should know about propoxyphene hydrochloride capsules, USP?”
Tell your doctor if you have any of these withdrawal symptoms while you slowly stop taking propoxyphene hydrochloride capsules, USP. You may need to stop propoxyphene hydrochloride capsules, USP more slowly.
Common side effects of propoxyphene hydrochloride capsules, USP include:
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Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also report side effects to TEVA USA, PHARMACOVIGILANCE at 1-888-838-2872, X6351.
How should I store propoxyphene hydrochloride capsules, USP?
Keep propoxyphene hydrochloride capsules, USP and all medicines out of the reach of children.
General information about propoxyphene hydrochloride capsules, USP
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use propoxyphene hydrochloride capsules, USP for a purpose for which they were not prescribed. Do not give propoxyphene hydrochloride capsules, USP to others even if they have the same symptoms you have. They may harm them and is against the law.
This Medication Guide summarizes the most important information about propoxyphene hydrochloride capsules. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about propoxyphene hydrochloride capsules, USP that is written for health professionals. For more information, call 1-888-838-2872, MEDICAL AFFAIRS.
What are the ingredients in propoxyphene hydrochloride capsules, USP?
Active ingredient: propoxyphene hydrochloride
Inactive ingredients: corn starch, gelatin, lactose monohydrate, magnesium stearate, titanium dioxide, FD&C yellow #6, and D&C red #33.
TEVA PHARMACEUTICALS USA
Sellersville, PA 18960
Iss. 10/2009
PROPOXYPHENE HYDROCHLORIDE
propoxyphene hydrochloride capsule |
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Labeler - Bryant Ranch Prepack (171714327) |
Registrant - Bryant Ranch Prepack (171714327) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
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Bryant Ranch Prepack | 171714327 | REPACK(63629-1359) , RELABEL(63629-1359) |