Overdose of Limifen in details
Overdosage would be manifested by extension of the pharmacological actions of Limifen as with other potent opioid analgesics. No experience of overdosage with Limifen was reported during clinical trials. The intravenous LD50 of Limifen is 43 to 51 mg/kg in rats, 72 to 74 mg/kg in mice, 72 to 82 mg/kg in guinea pigs and 60 to 88 mg/kg in dogs.
Intravenous administration of an opioid antagonist such as naloxone should be employed as a specific antidote to manage respiratory depression.
The duration of respiratory depression following overdosage with Limifen may be longer than the duration of action of the opioid antagonist. Administration of an opioid antagonist should not preclude immediate establishment of a patent airway, administration of oxygen, and assisted or controlled ventilation as indicated for hypoventilation or apnea. If respiratory depression is associated with muscular rigidity, a neuromuscular blocking agent may be required to facilitate assisted or controlled ventilation.
Intravenous fluids and vasoactive agents may be required to manage hemodynamic instability.
Limifen warnings
Limifen SHOULD BE ADMINISTERED ONLY BY PERSONS SPECIFICALLY TRAINED IN THE USE OF INTRAVENOUS AND GENERAL ANESTHETIC AGENTS AND IN THE MANAGEMENT OF RESPIRATORY EFFECTS OF POTENT OPIOIDS.
AN OPIOID ANTAGONIST, RESUSCITATIVE AND INTUBATION EQUIPMENT AND OXYGEN SHOULD BE READILY AVAILABLE.
BECAUSE OF THE POSSIBILITY OF DELAYED RESPIRATORY DEPRESSION, MONITORING OF THE PATIENT MUST CONTINUE WELL AFTER SURGERY.
Limifen administered in initial dosages up to 20 mcg/kg may cause skeletal muscle rigidity, particularly of the truncal muscles. The incidence and severity of muscle rigidity is usually dose-related. Administration of Limifen at anesthetic induction dosages (above 130 mcg/kg) will consistently produce muscular rigidity with an immediate onset. The onset of muscular rigidity occurs earlier than with other opioids. Limifen may produce muscular rigidity that involves all skeletal muscles, including those of the neck and extremities. The incidence may be reduced by: 1) routine methods of administration of neuromuscular blocking agents for balanced opioid anesthesia; 2) administration of up to 1/4 of the full paralyzing dose of a neuromuscular blocking agent just prior to administration of Limifen at dosages up to 130 mcg/kg; following loss of consciousness, a full paralyzing dose of a neuromuscular blocking agent should be administered; or 3) simultaneous administration of Limifen and a full paralyzing dose of a neuromuscular blocking agent when Limifen is used in rapidly administered anesthetic dosages (above 130 mcg/kg).
The neuromuscular blocking agent used should be appropriate for the patient's cardiovascular status. Adequate facilities should be available for postoperative monitoring and ventilation of patients administered Limifen. It is essential that these facilities be fully equipped to handle all degrees of respiratory depression.
PATIENTS RECEIVING MONITORED ANESTHESIA CARE (MAC) SHOULD BE CONTINUOUSLY MONITORED BY PERSONS NOT INVOLVED IN THE CONDUCT OF THE SURGICAL OR DIAGNOSTIC PROCEDURE; OXYGEN SUPPLEMENTATION SHOULD BE IMMEDIATELY AVAILABLE AND PROVIDED WHERE CLINICALLY INDICATED; OXYGEN SATURATION SHOULD BE CONTINUOUSLY MONITORED; THE PATIENT SHOULD BE OBSERVED FOR EARLY SIGNS OF HYPOTENSION, APNEA, UPPER AIRWAY OBSTRUCTION AND/OR OXYGEN DESATURATION.
Severe and unpredictable potentiation of monoamine oxidase (MAO) inhibitors has been reported for other opioid analgesics, and rarely with Limifen. Therefore when Limifen is administered to patients who have received MAO inhibitors within 14 days, appropriate monitoring and ready availability of vasodilators and betablockers for the treatment of hypertension is recommended.
What should I discuss with my healthcare provider before taking Limifen?
- If you have an allergy to Limifen or any other part of this medicine.
- If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
- If you have any of these health problems: Lung or breathing problems like asthma, trouble breathing, or sleep apnea; high levels of carbon dioxide in the blood; or stomach or bowel block or narrowing.
- If you are taking any of these drugs: Buprenorphine, butorphanol, nalbuphine, or pentazocine.
- If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking Limifen within 14 days of those drugs can cause very bad high blood pressure.
- If you are taking any of these drugs: Linezolid or methylene blue.
This is not a list of all drugs or health problems that interact with this medicine.
Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Limifen with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
Limifen precautions
DELAYED RESPIRATORY DEPRESSION, RESPIRATORY ARREST, BRADYCARDIA, ASYSTOLE, ARRHYTHMIAS AND HYPOTENSION HAVE ALSO BEEN REPORTED. THEREFORE, VITAL SIGNS MUST BE MONITORED CONTINUOUSLY.
General: The initial dose of Limifen should be appropriately reduced in elderly and debilitated patients. The effect of the initial dose should be considered in determining supplemental doses. In obese patients (more than 20% above ideal total body weight), the dosage of Limifen should be determined on the basis of lean body weight.
In one clinical trial, the dose of Limifen required to produce anesthesia, as determined by appearance of delta waves in EEG, was 40% lower in geriatric patients than that needed in healthy young patients.
In patients with compromised liver function and in geriatric patients, the plasma clearance of Limifen may be reduced and postoperative recovery may be prolonged.
Induction doses of Limifen should be administered slowly (over three minutes). Administration may produce loss of vascular tone and hypotension. Consideration should be given to fluid replacement prior to induction.
Diazepam administered immediately prior to or in conjunction with high doses of Limifen may produce vasodilation, hypotension and result in delayed recovery.
Bradycardia produced by Limifen may be treated with atropine. Severe bradycardia and asystole have been successfully treated with atropine and conventional resuscitative methods.
The hemodynamic effects of a particular muscle relaxant and the degree of skeletal muscle relaxation required should be considered in the selection of a neuromuscular blocking agent.
Following an anesthetic induction dose of Limifen, requirements for volatile inhalation anesthetics or Limifen infusion are reduced by 30 to 50% for the first hour of maintenance.
Limifen infusions should be discontinued at least 10 to 15 minutes prior to the end of surgery during general anesthesia. During administration of Limifen for Monitored Anesthesia Care (MAC), infusions may be continued to the end of the procedure.
Respiratory depression caused by opioid analgesics can be reversed by opioid antagonists such as naloxone. Because the duration of respiratory depression produced by Limifen may last longer than the duration of the opioid antagonist action, appropriate surveillance should be maintained. As with all potent opioids, profound analgesia is accompanied by respiratory depression and diminished sensitivity to CO2 stimulation which may persist into or recur in the postoperative period. Intraoperative hyperventilation may further alter postoperative response to CO2. Appropriate postoperative monitoring should be employed, particularly after infusions and large doses of Limifen, to ensure that adequate spontaneous breathing is established and maintained in the absence of stimulation prior to discharging the patient from the recovery area.
Head Injuries: Limifen should be used with caution in patients with head injury or increased intracranial pressure, due to the increased risk of respiratory depression. As with all opioids, Limifen may obscure the clinical course of patients with head injuries and should be used only if clinically indicated.
Impaired Respiration: Limifen should be used with caution in patients with pulmonary disease, decreased respiratory reserve or potentially compromised respiration. In such patients, opioids may additionally decrease respiratory drive and increase airway resistance. During anesthesia, this can be managed by assisted or controlled respiration.
Impaired Hepatic or Renal Function: In patients with liver or kidney dysfunction, Limifen should be administered with caution due to the importance of these organs in the metabolism and excretion of Limifen.
Drug Interactions: Both the magnitude and duration of central nervous system and cardiovascular effects may be enhanced when Limifen is administered in combination with other CNS depressants such as barbiturates, tranquilizers, opioids, or inhalation general anesthetics. Postoperative respiratory depression may be enhanced or prolonged by these agents. In such cases of combined treatment, the dose of one or both agents should be reduced. Limited clinical experience indicates that requirements for volatile inhalation anesthetics are reduced by 30 to 50% for the first sixty (60) minutes following Limifen induction. The concomitant use of erythromycin with Limifen can significantly inhibit Limifen clearance and may increase the risk of prolonged or delayed respiratory depression.
Cimetidine reduces the clearance of Limifen. Therefore smaller Limifen doses will be required with prolonged administration and the duration of action of Limifen may be extended.
Perioperative administration of drugs affecting hepatic blood flow or enzyme function may reduce plasma clearance and prolong recovery.
Carcinogenesis, Mutagenesis and Impairment of Fertility: No long-term animal studies of Limifen have been performed to evaluate carcinogenic potential. No structural chromosome mutations were produced in the in vivo micronucleus test in female rats at single intravenous doses of Limifen as high as 20 mg/kg body weight (approximately 40 times the upper human dose), equivalent to a dose of 103 mg/m2 body surface area. No dominant lethal mutations were produced in the in vivo dominant lethal test in male and female mice at the maximum intravenous dose of 20 mg/kg (60 mg/m2). No mutagenic activity was revealed in the in vitro Ames Salmonella typhimurium test, with and without metabolic activation.
Pregnancy Category C: Limifen has been shown to have an embryocidal effect in rats and rabbits when given in doses 2.5 times the upper human dose for a period of 10 days to over 30 days. These effects could have been due to maternal toxicity (decreased food consumption with increased mortality) following prolonged administration of the drug.
No evidence of teratogenic effects has been observed after administration of Limifen in rats or rabbits.
There are no adequate and well-controlled studies in pregnant women. Limifen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Labor and Delivery: There are insufficient data to support the use of Limifen in labor and delivery. Placental transfer of the drug has been reported; therefore, use in labor and delivery is not recommended.
Nursing Mothers: In one study of nine women undergoing postpartum tubal ligation, significant levels of Limifen were detected in colostrum four hours after administration of 60 mcg/kg of Limifen, with no detectable levels present after 28 hours. Caution should be exercised when Limifen is administered to a nursing woman.
Pediatric Use: Adequate data to support the use of Limifen in children under 12 years of age are not presently available.
References
- DrugBank. "ALFENTANIL". http://www.drugbank.ca/drugs/DB00802 (accessed September 17, 2018).
- MeSH. "Anesthetics, Intravenous". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
Reviews
Consumer reviews
There are no reviews yet. Be the first to write one! |
Information checked by Dr. Sachin Kumar, MD Pharmacology
