"The U.S. Food and Drug Administration today approved Hysingla ER (hydrocodone bitartrate), an extended-release (ER) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternat"...
(Generic versions may still be available.)
During clinical trials, the most frequently reported adverse reactions 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:
Eye disorder: eye swelling, vision blurred
General disorder and administration site conditions: drug ineffective, drug interaction, drug tolerance, influenza type illness, drug withdrawal syndrome
Gastrointestinal disorder: gastrointestinal bleed, acute pancreatitis
Immune system disorder: hypersensitivity
Injury poisoning and procedural complications: drug toxicity, hip fracture, multiple drug overdose, narcotic overdose
Metabolism and nutrition disorder: metabolic acidosis
Psychiatric: abnormal behavior, confusional state, hallucinations, mental status change
Skin and subcutaneous tissue disorder: rash, itch
Liver dysfunction has been reported in association with both active components of Darvocet-N (propoxyphene napsylate and acetaminophen) 50 and Darvocet-N (propoxyphene napsylate and acetaminophen) 100. Propoxyphene therapy has been associated with abnormal liver function tests and, more rarely, with instances of reversible jaundice (including cholestatic jaundice). Hepatic necrosis may result from acute overdose of acetaminophen (see OVERDOSAGE). In chronic ethanol abusers, this has been reported rarely with short-term use of acetaminophen dosages of 2.5 to 10 g/day. Fatalities have occurred.
There have also been postmarketing reports of renal papillary necrosis associated with chronic acetaminophen use, particularly when the dosage is greater than recommended and when combined with aspirin. Subacute painful myopathy has been reported following chronic propoxyphene overdosage.
Drug Abuse And Dependence
Darvocet-N (propoxyphene napsylate and acetaminophen) is a Schedule IV narcotic under the U.S. Controlled Substances Act. Darvocet-N (propoxyphene napsylate and acetaminophen) can produce drug dependence of the morphine type, and therefore, has the potential for being abused. Psychic dependence, physical dependence and tolerance may develop upon repeated administration. Darvocet-N (propoxyphene napsylate and acetaminophen) should be prescribed and administered with the same degree of caution appropriate to the use of other narcotic-containing medications.
Since Darvocet-N (propoxyphene napsylate and acetaminophen) is a mu-opioid agonist, it may be subject to misuse, abuse, and addiction. Addiction to opioids prescribed for pain management has not been estimated. However, requests for opioids from opioid-addicted patients occur. As such, physicians should take appropriate care in prescribing Darvocet-N (propoxyphene napsylate and acetaminophen) .
Opioid analgesics may cause psychological and physical dependence. Physical dependence results in withdrawal symptoms in patients who abruptly discontinue the drug after long term administration. Also, symptoms of withdrawal may be precipitated through the administration of drugs with mu-opioid antagonist activity, e.g., naloxone or mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine, dezocine) (see OVERDOSAGE). Physical dependence usually does not occur to a clinically significant degree, until after several weeks of continued opioid usage. Tolerance, in which increasingly larger doses are required to produce the same degree of analgesia, is initially manifested by a shortened duration of an analgesic effect and subsequently, by decreases in the intensity of analgesia.
In chronic pain patients, and in opioid-tolerant cancer patients, the administration of Darvocet-N (propoxyphene napsylate and acetaminophen) should be guided by the degree of tolerance manifested and the doses needed to adequately relieve pain.
The severity of the Darvocet-N (propoxyphene napsylate and acetaminophen) abstinence syndrome may depend on the degree of physical dependence. Withdrawal is characterized by rhinitis, myalgia, abdominal cramping, and occasional diarrhea. Most observable symptoms disappear in 5 to 14 days without treatment; however, there may be a phase of secondary or chronic abstinence which may last for 2 to 6 months characterized by insomnia, irritability, and muscular aches. The patient may be detoxified by gradual reduction of the dose. Gastrointestinal disturbances or dehydration should be treated with supportive care.
Read the Darvocet-N (propoxyphene napsylate and acetaminophen) Side Effects Center for a complete guide to possible side effects
Drug Interactions with Propoxyphene
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 Darvocet-N (propoxyphene napsylate and acetaminophen) 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 Darvocet-N (propoxyphene napsylate and acetaminophen) . When such combined therapy is contemplated, the dose of one or both agents should be reduced.
Mixed Agonist/Antagonist Opioid Analgesics
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 Darvocet-N (propoxyphene napsylate and acetaminophen) . In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of Darvocet-N (propoxyphene napsylate and acetaminophen) and/or may precipitate withdrawal symptoms in these patients.
Monoamine Oxidase Inhibitors (MAOIs)
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 Darvocet-N (propoxyphene napsylate and acetaminophen) is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
Drug Interactions with Acetaminophen
Alcohol: Hepatotoxicity has occurred in chronic alcoholics following various dose levels (moderate to excessive) of acetaminophen.
Anticholinergics: The onset of acetaminophen effect may be delayed or decreased slightly, but the ultimate pharmacological effect is not significantly affected by anticholinergics.
Oral Contraceptives: Increase in glucuronidation resulting in increased plasma clearance and a decreased half-life of acetaminophen.
Beta Blockers (Propranolol): Propranolol appears to inhibit the enzyme systems responsible for the glucuronidation and oxidation of acetaminophen. Therefore, the pharmacologic effects of acetaminophen may be increased.
Probenecid: Probenecid may increase the therapeutic effectiveness of acetaminophen slightly.
Zidovudine: The pharmacologic effects of zidovudine may be decreased because of enhanced nonhepatic or renal clearance of zidovudine.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/20/2010
Additional Darvocet-N Information
Darvocet-N - User Reviews
Darvocet-N User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Chronic Pain/Back Pain
Find tips and advances in treatment.