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Darvon-N
Overview
What is Darvon-N?
Darvon-N contains propoxyphene napsylate, USP which is an
odorless, white crystalline powder with a bitter taste. It is very slightly
soluble in water and soluble in methanol, ethanol, chloroform, and acetone.
Chemically, it is (α,1)-α-[2-(Dimethylamino)-1-methylethyl]-α-phenylphenethyl
propionate compound with 2-naphthalenesulfonic acid (1:1) monohydrate, which can
be represented by the accompanying structural formula. Its molecular weight is
565.72
Propoxyphene napsylate differs from propoxyphene hydrochloride in that it
allows more stable liquid dosage forms and tablet formulations. Because of
differences in molecular weight, a dose of 100 mg (176.8 μmol) of propoxyphene
napsylate is required to supply an amount of propoxyphene equivalent to that
present in 65 mg (172.9 μmol) of propoxyphene hydrochloride.
Each tablet of Darvon-N contains 100 mg (176.8 μmol) propoxyphene napsylate.
The tablet also contains cellulose, cornstarch, iron oxides, lactose, magnesium
stearate, silicon dioxide, stearic acid, and titanium dioxide.
What does Darvon-N look like?
What are the available doses of Darvon-N?
Sorry No records found.
What should I talk to my health care provider before I take Darvon-N?
Sorry No records found
How should I use Darvon-N?
Darvon-N is indicated for the relief of mild to moderate pain.
Darvon-N is 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.
Darvon-N is given orally. The usual dosage is one 100 mg propoxyphene
napsylate tablet every 4 hours as needed for pain. The maximum dose of Darvon-N
is 6 tablets per day.
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 Darvon-N on a regular basis for a period of
time, when therapy with Darvon-N is no longer needed for the treatment of their
pain, it may be useful to gradually discontinue the Darvon-N 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.
What interacts with Darvon-N?
Sorry No Records found
What are the warnings of Darvon-N?
Sorry No Records found
What are the precautions of Darvon-N?
Sorry No Records found
What are the side effects of Darvon-N?
Sorry No records found
What should I look out for while using Darvon-N?
Darvon-N is contraindicated in patients with known
hypersensitivity to propoxyphene.
Darvon-N is 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.
Darvon-N is contraindicated in any patient who has or is suspected of having
paralytic ileus.
BOXED WARNING
WARNINGS
There have been numerous cases of accidental and intentional overdose with propoxyphene products either alone or in combination with other CNS depressants, including alcohol. Fatalities within the first hour of overdosage are not uncommon. Many of the propoxyphene-related deaths have occurred in patients with previous histories of emotional disturbance or suicidal ideation/attempts and /or concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS-depressant drugs. Do not prescribe propoxyphene for patients who are suicidal or have a history of suicidal ideation.
The metabolism of propoxyphene may be altered by strong CYP3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazadone, amiodarone, amprenavir, aprepitant, diltiazem, erthromycin, fulconazole, fosamprenavir, grapefruit juice, and verapamil) leading to enhanced propoxyphene plasma levels. 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 (see Clinical Pharmacology - Drug Interactions, Warnings, Precautions and Dosage and Administration for further information.)
What might happen if I take too much Darvon-N?
Overdose of Darvon-N may present with the signs and symptoms of
propoxyphene overdose. Fatalities within the first hour of overdosage are not
uncommon.
In all cases of suspected overdosage, call your regional Poison Control
Center to obtain the most up-to-date information about the treatment of
overdose. This recommendation is made because, in general, information regarding
the treatment of overdosage may change more rapidly than do package inserts.
Initial consideration should be given to the management of the CNS effects of
propoxyphene overdosage. Resuscitative measures should be initiated promptly.
The manifestations of acute overdosage with propoxyphene are
those of narcotic overdosage. The patient is usually somnolent but may be
stuporous or comatose and convulsing. Respiratory depression is characteristic.
The ventilatory rate and/or tidal volume is decreased, which results in cyanosis
and hypoxia. Pupils, initially pinpoint, may become dilated as hypoxia
increases. Cheyne-Stokes respiration and apnea may occur. Blood pressure and
heart rate are usually normal initially, but blood pressure falls and cardiac
performance deteriorates, which ultimately results in pulmonary edema and
circulatory collapse, unless the respiratory depression is corrected and
adequate ventilation is restored promptly. Cardiac arrhythmias and conduction
delay may be present. A combined respiratory-metabolic acidosis occurs owing to
retained CO (hypercapnia) and to lactic acid formed
during anaerobic glycolysis. Acidosis may be severe if large amounts of
salicylates have also been ingested. Death may occur.
Attention should be directed first to establishing a patent
airway and to restoring ventilation. Mechanically assisted ventilation, with or
without oxygen, may be required, and positive pressure respiration may be
desirable if pulmonary edema is present. The opioid antagonist naloxone will
markedly reduce the degree of respiratory depression, and should be administered
promptly, preferably intravenously. The duration of action of the antagonist may
be brief. If no response is observed after 10 mg of naloxone have been
administered, the diagnosis of propoxyphene toxicity should be questioned.
In addition to the use of an opioid antagonist, the patient may require
careful titration with an anticonvulsant to control convulsions. Activated
charcoal can adsorb a significant amount of ingested propoxyphene. Dialysis is
of little value in poisoning due to propoxyphene. Efforts should be made to
determine whether other agents, such as alcohol, barbiturates, tranquilizers, or
other CNS depressants, were also ingested, since these increase CNS depression
as well as cause specific toxic effects or death.
How should I store and handle Darvon-N?
Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP] .Darvon-N Tablets are available in: The 100 mg tablets are buff colored, elliptical shaped, film coated, and imprinted with the script “DARVON-N 100” on one side of the tablet, using edible black ink. They are available as follows: Store at 25°C (77°F); excursions are permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Inform patients of the availability of a Medication Guide for Darvon/Darvon-N that accompanies each prescription dispensed. Instruct patients to read the Darvon/Darvon-N Medication Guide prior to using Darvon. Darvon, Darvon-N, Darvocet, and Darvocet-N are registered trademarks of Xanodyne Pharmaceuticals, Inc. © 2009 Xanodyne Pharmaceuticals, Inc. Marketed by: XanodyneNewport, KY41071 PI-512-AREV. 09-2009Darvon-N Tablets are available in: The 100 mg tablets are buff colored, elliptical shaped, film coated, and imprinted with the script “DARVON-N 100” on one side of the tablet, using edible black ink. They are available as follows: Store at 25°C (77°F); excursions are permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Inform patients of the availability of a Medication Guide for Darvon/Darvon-N that accompanies each prescription dispensed. Instruct patients to read the Darvon/Darvon-N Medication Guide prior to using Darvon. Darvon, Darvon-N, Darvocet, and Darvocet-N are registered trademarks of Xanodyne Pharmaceuticals, Inc. © 2009 Xanodyne Pharmaceuticals, Inc. Marketed by: XanodyneNewport, KY41071 PI-512-AREV. 09-2009Darvon-N Tablets are available in: The 100 mg tablets are buff colored, elliptical shaped, film coated, and imprinted with the script “DARVON-N 100” on one side of the tablet, using edible black ink. They are available as follows: Store at 25°C (77°F); excursions are permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Inform patients of the availability of a Medication Guide for Darvon/Darvon-N that accompanies each prescription dispensed. Instruct patients to read the Darvon/Darvon-N Medication Guide prior to using Darvon. Darvon, Darvon-N, Darvocet, and Darvocet-N are registered trademarks of Xanodyne Pharmaceuticals, Inc. © 2009 Xanodyne Pharmaceuticals, Inc. Marketed by: XanodyneNewport, KY41071 PI-512-AREV. 09-2009Darvon-N Tablets are available in: The 100 mg tablets are buff colored, elliptical shaped, film coated, and imprinted with the script “DARVON-N 100” on one side of the tablet, using edible black ink. They are available as follows: Store at 25°C (77°F); excursions are permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Inform patients of the availability of a Medication Guide for Darvon/Darvon-N that accompanies each prescription dispensed. Instruct patients to read the Darvon/Darvon-N Medication Guide prior to using Darvon. Darvon, Darvon-N, Darvocet, and Darvocet-N are registered trademarks of Xanodyne Pharmaceuticals, Inc. © 2009 Xanodyne Pharmaceuticals, Inc. Marketed by: XanodyneNewport, KY41071 PI-512-AREV. 09-2009Darvon-N Tablets are available in: The 100 mg tablets are buff colored, elliptical shaped, film coated, and imprinted with the script “DARVON-N 100” on one side of the tablet, using edible black ink. They are available as follows: Store at 25°C (77°F); excursions are permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Inform patients of the availability of a Medication Guide for Darvon/Darvon-N that accompanies each prescription dispensed. Instruct patients to read the Darvon/Darvon-N Medication Guide prior to using Darvon. Darvon, Darvon-N, Darvocet, and Darvocet-N are registered trademarks of Xanodyne Pharmaceuticals, Inc. © 2009 Xanodyne Pharmaceuticals, Inc. Marketed by: XanodyneNewport, KY41071 PI-512-AREV. 09-2009Darvon-N Tablets are available in: The 100 mg tablets are buff colored, elliptical shaped, film coated, and imprinted with the script “DARVON-N 100” on one side of the tablet, using edible black ink. They are available as follows: Store at 25°C (77°F); excursions are permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Inform patients of the availability of a Medication Guide for Darvon/Darvon-N that accompanies each prescription dispensed. Instruct patients to read the Darvon/Darvon-N Medication Guide prior to using Darvon. Darvon, Darvon-N, Darvocet, and Darvocet-N are registered trademarks of Xanodyne Pharmaceuticals, Inc. © 2009 Xanodyne Pharmaceuticals, Inc. Marketed by: XanodyneNewport, KY41071 PI-512-AREV. 09-2009Darvon-N Tablets are available in: The 100 mg tablets are buff colored, elliptical shaped, film coated, and imprinted with the script “DARVON-N 100” on one side of the tablet, using edible black ink. They are available as follows: Store at 25°C (77°F); excursions are permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Inform patients of the availability of a Medication Guide for Darvon/Darvon-N that accompanies each prescription dispensed. Instruct patients to read the Darvon/Darvon-N Medication Guide prior to using Darvon. Darvon, Darvon-N, Darvocet, and Darvocet-N are registered trademarks of Xanodyne Pharmaceuticals, Inc. © 2009 Xanodyne Pharmaceuticals, Inc. Marketed by: XanodyneNewport, KY41071 PI-512-AREV. 09-2009Darvon-N Tablets are available in: The 100 mg tablets are buff colored, elliptical shaped, film coated, and imprinted with the script “DARVON-N 100” on one side of the tablet, using edible black ink. They are available as follows: Store at 25°C (77°F); excursions are permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Inform patients of the availability of a Medication Guide for Darvon/Darvon-N that accompanies each prescription dispensed. Instruct patients to read the Darvon/Darvon-N Medication Guide prior to using Darvon. Darvon, Darvon-N, Darvocet, and Darvocet-N are registered trademarks of Xanodyne Pharmaceuticals, Inc. © 2009 Xanodyne Pharmaceuticals, Inc. Marketed by: XanodyneNewport, KY41071 PI-512-AREV. 09-2009Darvon-N Tablets are available in: The 100 mg tablets are buff colored, elliptical shaped, film coated, and imprinted with the script “DARVON-N 100” on one side of the tablet, using edible black ink. They are available as follows: Store at 25°C (77°F); excursions are permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Inform patients of the availability of a Medication Guide for Darvon/Darvon-N that accompanies each prescription dispensed. Instruct patients to read the Darvon/Darvon-N Medication Guide prior to using Darvon. Darvon, Darvon-N, Darvocet, and Darvocet-N are registered trademarks of Xanodyne Pharmaceuticals, Inc. © 2009 Xanodyne Pharmaceuticals, Inc. Marketed by: XanodyneNewport, KY41071 PI-512-AREV. 09-2009Darvon-N Tablets are available in: The 100 mg tablets are buff colored, elliptical shaped, film coated, and imprinted with the script “DARVON-N 100” on one side of the tablet, using edible black ink. They are available as follows: Store at 25°C (77°F); excursions are permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Inform patients of the availability of a Medication Guide for Darvon/Darvon-N that accompanies each prescription dispensed. Instruct patients to read the Darvon/Darvon-N Medication Guide prior to using Darvon. Darvon, Darvon-N, Darvocet, and Darvocet-N are registered trademarks of Xanodyne Pharmaceuticals, Inc. © 2009 Xanodyne Pharmaceuticals, Inc. Marketed by: XanodyneNewport, KY41071 PI-512-AREV. 09-2009Darvon-N Tablets are available in: The 100 mg tablets are buff colored, elliptical shaped, film coated, and imprinted with the script “DARVON-N 100” on one side of the tablet, using edible black ink. They are available as follows: Store at 25°C (77°F); excursions are permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Inform patients of the availability of a Medication Guide for Darvon/Darvon-N that accompanies each prescription dispensed. Instruct patients to read the Darvon/Darvon-N Medication Guide prior to using Darvon. Darvon, Darvon-N, Darvocet, and Darvocet-N are registered trademarks of Xanodyne Pharmaceuticals, Inc. © 2009 Xanodyne Pharmaceuticals, Inc. Marketed by: XanodyneNewport, KY41071 PI-512-AREV. 09-2009
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
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 μg/mL for propoxyphene and 0.1 to 0.2 μg/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.
In 48 h, approximately 20 to 25% of the administered dose of
propoxyphene is excreted via the urine, most of which is free or conjugated
norpropoxyphene. The renal clearance rate of propoxyphene is 2.6 L/min.
After oral administration of propoxyphene in elderly patients
(70-78 years), much longer half-lives of propoxyphene and norpropoxyphene have
been reported (propropoxyphene 13 to 35 h, norpropoxyphene 22 to 41 h). In
addition, the AUC was an average of 3-fold higher and the Cmax was an average of
2.5-fold higher in the elderly when compared to a younger (20-28 years)
population. Longer dosage intervals may be considered in the elderly because the
metabolism of propoxyphene may be reduced in this patient population. After
multiple oral doses of propoxyphene in elderly patients (70-78 years), the Cmax
of the metabolite (norpropoxyphene) was increased 5-fold.
Propoxyphene has not been studied in pediatric patients.
No formal pharmacokinetic study of propoxyphene has been
conducted in patients with mild, moderate or severe hepatic impairment.
After oral administration of propoxyphene in patients with cirrhosis, plasma
concentrations of propoxyphene were considerably higher and norpropoxyphene
concentrations were much lower than in control patients. This is presumably
because of a decreased first-pass metabolism of orally administered propoxyphene
in these patients. The AUC ratio of norpropoxyphene: propoxyphene was
significantly lower in patients with cirrhosis (0.5 to 0.9) than in controls
(2.5 to 4).
No formal pharmacokinetic study of propoxyphene has been
conducted in patients with mild, moderate or severe renal impairment.
After oral administration of propoxyphene in anephric patients, the AUC and
Cmax values were an average of 76% and 88% greater, respectively. Dialysis
removes only insignificant amounts (8%) of administered dose of propoxyphene.
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. On the other hand,
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. Coadministration with a drug that is a substrate of CYP3A4 or
CYP2D6, may result in higher plasma concentrations and increased pharmacologic
or adverse effects of that drug.
Non-Clinical Toxicology
Darvon-N is contraindicated in patients with known hypersensitivity to propoxyphene.Darvon-N is 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.
Darvon-N is contraindicated in any patient who has or is suspected of having paralytic ileus.
BOXED WARNING
WARNINGS
There have been numerous cases of accidental and intentional overdose with propoxyphene products either alone or in combination with other CNS depressants, including alcohol. Fatalities within the first hour of overdosage are not uncommon. Many of the propoxyphene-related deaths have occurred in patients with previous histories of emotional disturbance or suicidal ideation/attempts and /or concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS-depressant drugs. Do not prescribe propoxyphene for patients who are suicidal or have a history of suicidal ideation.
The metabolism of propoxyphene may be altered by strong CYP3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazadone, amiodarone, amprenavir, aprepitant, diltiazem, erthromycin, fulconazole, fosamprenavir, grapefruit juice, and verapamil) leading to enhanced propoxyphene plasma levels. 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 (see Clinical Pharmacology - Drug Interactions, Warnings, Precautions and Dosage and Administration for further information.)
Combined use of haloperidol and lithium. An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and FBS) followed by irreversible brain damage has occurred in a few patients treated with lithium plus haloperidol. A causal relationship between these events and the concomitant administration of lithium and haloperidol has not been established; however, patients receiving such combined therapy should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear.
The possibility of similar adverse interactions with other antipsychotic medication exists.
Lithium may prolong the effects of neuromuscular blocking agents. Therefore, neuromuscular blocking agents should be given with caution to patients receiving lithium.
Caution should be used when lithium and diuretics or angiotensin converting enzyme (ACE) inhibitors are used concomitantly because sodium loss may reduce the renal clearance of lithium and increase serum lithium levels with risk of lithium toxicity. When such combinations are used, the lithium dosage may need to be decreased, and more frequent monitoring of lithium plasma levels is recommended.
Non-Steroidal Anti-Inflammatory Drugs (NSAIDS): Lithium levels should be closely monitored when patients initiate or discontinue NSAID use. In some cases, lithium toxicity has resulted from interactions between an NSAID and lithium. Indomethacin and piroxicam have been reported to increase significantly steady-state plasma lithium concentrations. There is also evidence that other nonsteriodal anti-inflammatory agents, including the selective cyclooxygenase-2 (COX-2) inhibitors, have the same effect. In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg BID with celecoxib 200 mg BID as compared to subjects receiving lithium alone.
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 Darvon-N is abruptly discontinued in a physically dependent patient, an abstinence syndrome may occur (see Drug Abuse and Dependance). If signs and symptoms of withdrawal occur, patients should be treated by reinstitution of opioid therapy followed by gradual tapered dose reduction of Darvon-N combined with symptomatic support (see Dosage and Administration: Cessation of Therapy).
Darvon-N 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 Darvon-N 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.
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 Darvon-N. 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 Darvon-N. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of Darvon-N 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 Darvon-N 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/m 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 Darvon-N is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Darvon-N 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:
Eye disorder:
General disorder and administration site conditions:
Gastrointestinal disorder:
Hepatobiliary disorder:
Immune system disorder:
Injury poisoning and procedural complications:
Investigations:
Metabolism and nutrition disorder:
Nervous system disorder:
Psychiatric:
Respiratory, thoracic, and mediastinal disorders:
Skin and subcutaneous tissue disorder:
Liver dysfunction has been reported in association with Darvon-N. 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.
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
While we update our database periodically, we cannot guarantee it is always updated to the latest version.
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Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72Tips
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Interactions
Interactions
A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).