Adverse Drug Reaction Overview Intravenous Use The most frequent adverse reactions in 320 patients administered sufentanil intravenously were: hypotension (7%); hypertension (3%); chest wall rigidity (3%); bradycardia (3%).
Other adverse reactions that may occur (reported incidence of less than 1%) are: cardiovascular: tachycardia, arrhythmia; gastrointestinal: nausea, vomiting; respiratory: apnea, postoperative respiratory depression, bronchospasm; dermatological: itching; central nervous system: chills; miscellaneous: intraoperative muscle movement.
Allergic reactions and asystole have been reported; but since several drugs were coadministered during anesthesia, it is uncertain whether there is a causal relationship to the drug. Epidural Use The frequency of adverse experiences associated with the use of epidural sufentanil was evaluated in 1478 postoperative patients and 14,467 parturients.
The most frequently reported adverse experiences were somnolence or sedation, pruritus, nausea, vomiting and urinary retention. 5% of postoperative patients, respectively. These episodes developed early after drug administration and were resolved within 1 hour.
Concomitant use of epinephrine may reduce the incidence and severity of respiratory depression. No respiratory depressive episodes were observed in patients receiving epidural sufentanil during labour and delivery. Other observed adverse experiences include: cardiovascular: hypotension (2%); central nervous system: motor block (18%, labour patients only), dizziness (2%), euphoria (2%); urinary system disorders: urinary incontinence (1%); miscellaneous: fever (1%), shivering (2%), pain at injection site (1%), miosis (1%).
Adverse experiences that occurred in less than 1% of patients are: bradycardia, hypopnea, rash, headache, and confusion. Sufentanil Citrate Injection USP Page 16 of 42 Opioid Adverse Events Adverse effects of Sufentanil Citrate Injection USP (sufentanil) injection are similar to those of other opioid analgesics, and represent an extension of pharmacological effects of the drug class.
The major hazards of opioids include respiratory and central nervous system depression and to a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest.
Sedation:
Sedation is a common side effect of opioid analgesics, especially in opioid naïve individuals. Sedation may also occur partly because patients often recuperate from prolonged fatigue after the relief of persistent pain. Most patients develop tolerance to the sedative effects of opioids within three to five days and, if the sedation is not severe, will not require any treatment except reassurance.
If excessive sedation persists beyond a few days, the dose of the opioid should be reduced and alternate causes investigated. Some of these are: concurrent CNS depressant medication, hepatic or renal dysfunction, brain metastases, hypercalcemia and respiratory failure.
If it is necessary to reduce the dose, it can be carefully increased again after three or four days if it is obvious that the pain is not being well controlled. Dizziness and unsteadiness may be caused by postural hypotension, particularly in elderly or debilitated patients, and may be alleviated if the patient lies down.
Nausea and Vomiting:
Nausea is a common side effect on initiation of therapy with opioid analgesics and is thought to occur by activation of the chemoreceptor trigger zone, stimulation of the vestibular apparatus and through delayed gastric emptying. The prevalence of nausea declines following continued treatment with opioid analgesics.
When instituting therapy with an opioid for chronic pain, the routine prescription of an antiemetic should be considered. In the cancer patient, investigation of nausea should include such causes as constipation, bowel obstruction, uremia, hypercalcemia, hepatomegaly, tumor invasion of celiac plexus and concurrent use of drugs with emetogenic properties.
Persistent nausea which does not respond to dosage reduction may be caused by opioid-induced gastric stasis and may be accompanied by other symptoms including anorexia, early satiety, vomiting and abdominal fullness. These symptoms respond to chronic treatment with gastrointestinal prokinetic agents.
Constipation:
Practically all patients become constipated while taking opioids on a persistent basis. In some patients, particularly the elderly or bedridden, fecal impaction may result. It is essential to caution the patients in this regard and to institute an appropriate regimen of bowel management at the start of prolonged opioid therapy.
Stimulant laxatives, stool softeners, and other appropriate measures should be used as required. As fecal impaction may present as overflow diarrhea, the presence of constipation should be excluded in patients on opioid therapy prior to initiating treatment for diarrhea.
Post-Market Adverse Drug Reactions Post-marketing reports describe patients with symptoms suggestive of, or diagnostic of, serotonin syndrome following the concomitant use of fentanyl with a serotonergic drug, such as Selective Serotonin Reuptake Inhibitor or a Serotonin Norepinephrine Reuptake Inhibitor (see DRUG INTERACTIONS).
Sufentanil Citrate Injection USP Page 17 of 42 Post-marketing adverse reports include: laryngospasm, dizziness, myoclonic movements, respiratory depression and cough. DRUG INTERACTIONS Overview As sufentanil is used for intravenous anesthesia and epidural analgesia during childbirth, drug interactions with medications used in general anaesthesia and obstetrics are likely.
Drug-Drug Interactions Cytochrome P450 3A4 (CYP 3A4) Enzyme Inhibitors:
Sufentanil is metabolised mainly via the human cytochrome CYP 3A4 enzyme. However, no in vivo inhibition by erythromycin (a known cytochrome CYP 3A4 enzyme inhibitor) has been observed. Although clinical […]