Alfentanil

Indications General anesthesia in spontaneously breathing patients. As an adjunct during induction of anesthesia. As an analgesic adjunct for maintenance of anesthesia. As an analgesic component during monitored anesthesia care (MAC). Preparation & Administration For IV preparation, add 20–230 mL of diluent to achieve a final concentration of 40 mg/mL. Keep naloxone and resuscitation equipment readily available. May be administered by incremental IV injection as an analgesic adjunct with barbiturate/nitrous oxide/oxygen anesthesia. For general surgical procedures, it may be used for induction and maintenance analgesia according to the duration and requirements of anesthesia. Continuous IV infusion may be used when prolonged analgesia is required. Dose should be calculated based on ideal body weight. Intravenous Adult Dose Anesthesia <30 minutes: Induction: 8–20 mcg/kg IV Maintenance: 3–5 mcg/kg IV increments every 5–20 minutes, or 0.5–1 mcg/kg/min IV Total dose: 8–40 mcg/kg IV Anesthesia 30–60 minutes: Induction: 20–50 mcg/kg IV Maintenance: 5–15 mcg/kg IV increments every 5–20 minutes Total dose: Up to 75 mcg/kg IV Anesthesia >45 minutes: Induction: 130–245 mcg/kg IV Maintenance: 0.5–1.5 mcg/kg/min IV or with another general anesthetic Total dose: Depends on the duration of surgery. Continuous infusion for anesthesia >45 minutes: Induction: 50–75 mcg/kg IV Maintenance: 0.5–3 mcg/kg/min IV Total dose: Depends on the duration of surgery. Pediatric Use Children <12 years: Use for anesthesia is not recommended. Children >12 years: Adult dosing may be used: Anesthesia <30 minutes: Induction 8–20 mcg/kg IV; maintenance 3–5 mcg/kg IV every 5–20 minutes or 0.5–1 mcg/kg/min IV; total dose 8–40 mcg/kg IV. Anesthesia 30–60 minutes: Induction 20–50 mcg/kg IV; maintenance 5–15 mcg/kg IV every 5–20 minutes; total dose up to 75 mcg/kg IV. Anesthesia >45 minutes: Induction 130–245 mcg/kg IV; maintenance 0.5–1.5 mcg/kg/min IV or with another general anesthetic. Continuous infusion: Induction 50–75 mcg/kg IV; maintenance 0.5–3 mcg/kg/min IV. Contraindications & Precautions Obstructive airway disease. Respiratory depression. Hypersensitivity to alfentanil or its components. Increased intracranial pressure. Avoid administration during labor or before cord clamping during Cesarean section. Contraindicated with concomitant MAOI therapy or within 14 days of MAOI treatment. Mechanism of Action Alfentanil is a short-acting opioid analgesic related to fentanyl. It binds to stereospecific opioid receptors in the central nervous system, altering the perception of pain, increasing the pain threshold, and inhibiting ascending pain pathways. Important Warnings Opioid therapy exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which may lead to overdose and death. Assess each patient's risk before prescribing and regularly monitor for the development of these behaviors or conditions. Use caution in patients with hypovolemia, cardiovascular disease, bradyarrhythmias, history of drug abuse or acute alcohol intoxication, head injury, intracranial lesions, increased intracranial pressure, pulmonary disease, reduced respiratory reserve, COPD or other obstructive pulmonary disease, kyphoscoliosis, compromised intracerebral compliance, or hypothyroidism. Use caution in patients with hepatic or renal impairment and in elderly or debilitated patients. Monitor pediatric patients carefully. The medicine may impair cognitive function. Patients should not drive or operate machinery if affected. Monitoring Continuously monitor vital signs. Monitor oxygen saturation, blood pressure, and heart rate. Closely monitor patients after surgery for delayed respiratory or other adverse effects. Side Effects Common / Very Common Nausea (28%) Vomiting (18%) Hypertension (18%) Chest wall rigidity (17%) Arrhythmia (14%) Bradycardia (14%) Tachycardia (12%) Less Common Hypotension (10%) Apnea (3–9%) Dizziness (3–9%) Skeletal muscle movements (3–9%) Blurred vision (1–3%) Postoperative respiratory depression (1–3%) Postoperative sedation (1–3%) Rare Sweating Warmth of the face, neck, and upper chest Pruritus Urticaria Respiratory depression Circulatory depression Respiratory arrest Shock Cardiac arrest Visual disturbances Mental clouding or depression Restlessness Agitation Dyspnea Seizures Pregnancy Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Available data in pregnant women are insufficient to determine the drug-associated risk of major birth defects or miscarriage. During labor or delivery, opioids cross the placenta and may cause respiratory depression and psychophysiological effects in the newborn. An opioid antagonist such as naloxone should be readily available to reverse opioid-induced respiratory depression in the newborn. Use during labor and immediately before delivery is not recommended when short-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics may temporarily reduce the strength, duration, and frequency of uterine contractions, potentially prolonging labor. Newborns exposed to opioids during labor should be monitored for excessive sedation and respiratory depression. Breastfeeding The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for therapy. Monitor breastfed infants exposed to the medicine through breast milk for excessive sedation and respiratory depression. Withdrawal symptoms may occur in breastfed infants when maternal opioid therapy is discontinued or breastfeeding is stopped. Use with caution during breastfeeding. Drug Interactions CYP3A4 inhibitors such as ketoconazole, itraconazole, fluconazole, voriconazole, ritonavir, erythromycin, diltiazem, and cimetidine may increase the risk of prolonged or delayed respiratory depression. Barbiturates, benzodiazepines, neuroleptics, halogenated anesthetic gases, and other CNS depressants such as alcohol may enhance respiratory depression. May increase propofol blood concentrations by approximately 17%. Drugs that depress cardiac function or increase vagal tone, such as beta-blockers and anesthetic agents, may increase the risk of bradycardia or hypotension. Non-vagolytic muscle relaxants may increase the risk of bradycardia and cardiac arrest. MAO inhibitors (MAOIs): Concomitant use may rarely cause serious and unpredictable reactions and should be avoided.

Adjunct in maintenance of general anaesthesia, Induction of anaesthesia, Analgesia in patients with spontaneous respiration

Alfentanil is a short-acting opioid analgesic related to fentanyl. It binds w/ stereospecific receptors w/in the CNS, thereby altering pain perception, increasing pain threshold, and inhibiting ascending pain pathways.

Adult Dose: Intravenous Adult: Incremental Injection: Anesthesia 45 Minutes Induction: 130-245 mcg/kg IV Maintenance: 0.5-1.5 mcg/kg/min IV or other general anesthetic Total dose: depends on duration of operation Continuous Infusion: For Anesthesia >45 Minutes Induction: 50-75 mcg/kg IV Maintenance: 0.5-3 mcg/kg/min IV Total dose: depends on duration of operation Child Dose: Dose should be calculated based on ideal body weight Intravenous Child: 12 years Incremental Injection: Anesthesia 45 Minutes Induction: 130-245 mcg/kg IV Maintenance: 0.5-1.5 mcg/kg/min IV or other general anesthetic Total dose: depends on duration of operation Continuous Infusion: For Anesthesia >45 Minutes Induction: 50-75 mcg/kg IV Maintenance: 0.5-3 mcg/kg/min IV Total dose: depends on duration of operation

IV Preparation Add 20 mL to 230 mL of diluent for a final concentration of 40 mg/mL IV Administration Keep Naloxone and resuscitation equip available By incremental injection as analgesic adjunct to anesthesia with barbiturate/nitrous oxide/oxygen for short surgical procedures (expected duration <1 hr) By continuous infusion as a maintenance analgesic with nitrous oxide/oxygen for general surgical procedures By IV injection in aesthetic doses for anesthesia induction for general surgical procedures with a minimum expected duration of 45 min By IV inj as the analgesic component for monitored anesthesia care (MAC)

>10% Arrhythmia (14%) Bradycardia (14%) Chest wall rigidity (17%) Hypertension (18%) Nausea (28%) Vomiting (18%) Tachycardia (12%) 1-10% Apnea (3-9%) Blurred vision (1-3%) Dizziness (3-9%) Hypotension (10%) Post-op respiratory depression (1-3%) Skeletal muscle movements (3-9%) Postoperative sedation (1-3%) <1% Sweating, flushing Warmness of the face/neck/upper thorax Pruritus Urticaria Respiratory (undefined) Respiratory/circulatory depression Respiratory arrest Shock Cardiac arrest Nervous System (undefined) Dizziness Visual disturbances Mental clouding/depression Sedation Coma Euphoria Dysphoria Weakness Faintness Agitation Restlessness Nervousness Seizures

Therapy exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death; assess each patient’s risk prior to prescribing therapy, and monitor all patients regularly for the development of these behaviors and conditions. Patient w/ hypovolaemia, CV disease (e.g. acute MI), bradyarrhythmias, history of drug abuse or acute alcoholism, head injury, intracranial lesions, increased intracranial pressure, pulmonary disease, decreased resp reserve, compromised respiration, COPD or other obstructive pulmonary disease, kyphoscoliosis or other skeletal disorder, and compromised intracerebral compliance, hypothyroidism. Hepatic and renal impairment. Elderly and debilitated patients. Childn. Pregnancy and lactation. Patient Counselling This drug may cause impaired cognitive function, if affected, do not drive or operate machinery. Monitoring Parameters Continuously monitor vital signs, oxygen saturation, BP, and heart rate. Monitor the patient well after surgery for delayed effects.

Obstructive airway disease, resp depression. Hypersensitivity, Increased intracranial pressure. Admin in labour or before clamping of cord during caesarean section. Concomitant use during or w/in 14 days of MAOI therapy.

Increased risk of prolonged/delayed resp depression w/ CYP3A4 isoenzyme inhibitors (e.g. ketoconazole, itraconazole, fluconazole, voriconazole, ritonavir, erythromycin, diltiazem, cimetidine). Enhanced resp depressant effect w/ barbiturates, benzodiazepines, neuroleptics, halogenic gases, and non-selective CNS depressants (e.g. alcohol). May increase blood concentration of propofol by 17%. May predispose to bradycardia or hypotension w/ drugs that depress the heart or increase vagal tone (e.g. β-blockers, anaesth agents). May cause bradycardia and cardiac arrest w/ non-vagolytic muscle relaxants. Potentially Fatal: Rarely, may cause severe and unpredictable potentiation of MAOIs.

Pregnancy Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage Labor or delivery Opioids cross placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in neonate; drug is not recommended for use in women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions that temporarily reduce strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression Lactation The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy; capsules and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition Monitor infants exposed to drug through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast- feeding is stopped Withdrawal signs can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped or when breastfeeding is stopped; naloxone may precipitate opioid withdrawal in a breast-fed infant whose mother received opioid analgesics Lactation: use with caution