Remifentanil is the active ingredient in Ultiva, an intravenous (IV) opioid for pain.

• The drug is a highly potent narcotic that the Drug Enforcement Administration has listed as a Schedule II drug under the Controlled Substances Act.
• Remifentanil (sold under the brand name Ultiva) is a synthetic opioid administered as a pain reliever during and after surgical procedures with general anesthesia.
• It is not available from local pharmacies.
• Remifentanil is as potent as fentanyl, which itself can be up to 100 times more powerful than morphine.
• It is intended for adults during surgery or immediately after that for those who are in intensive care units.

Remifentanil should always be administered under the supervision of an anesthesia practitioner and the person should be on supplemental oxygen while taking the drug.

Like all Schedule II opioids, remifentanil has a high potential for addiction. However, the drug has unique pharmacological properties that make it less likely to be misused. Although the onset of remifentanil is quick, around one minute, the drug's effects completely wear off within 5 to 10 minutes. For this reason, remifentanil is less appealing than other opioids for recreational use and is rarely targeted by illicit drug dealers for distribution.

Remifentanil (marketed by Abbott as Ultiva) is a potent ultra short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. ULTIVA is a u-opioid agonist with rapid onset and peak effect, and short duration of action. The u-opioid activity of ULTIVA is antagonized by opioid antagonists such as naloxone. ULTIVA is indicated for IV administration:

1. As an analgesic agent for use during the induction and maintenance of general anesthesia for inpatient and outpatient procedures.
2. For continuation as an analgesic into the immediate postoperative period in adult patients under the direct supervision of an anesthesia practitioner in a postoperative anesthesia care unit or intensive care setting.
3. As an analgesic component of monitored anesthesia care in adult patients.

Remifentanil:
https://drugs.ncats.io/drug/P10582JYYK

1996 Article:
Remifentanil is an opioid acting on mu-type receptors, pure and simple. It has exactly the same effects of any available fentanyl-type opioid with the same maximum efficacy. It has approximately the same potency as fentanyl, but precise potency comparisons are complicated because of the unique pharmacokinetic characteristics of remifentanil and are of minor importance in its use in clinical practice. In practical terms, dosage guidelines are provided to initiate administration of this drug safely and effectively given its unique pharmacokinetic features. In fact, these features mandate an approach to the administration of remifentanil different from that commonly employed for the currently available opioids.

Two major pharmacokinetic characteristics of remifentanil are most important to the clinical anesthesiologist:

1. A very rapid achievement of the peak effect of an intravenous dose (matched only by alfentanil among currently available opioids)
2. A consistently rapid elimination of the drug with virtually complete cessation of its effects within five to ten minutes after discontinuing its administration.

Each of these pharmacokinetic features has potential advantages and disadvantages in clinical practice. Among the opioids, remifentanil behaves like it has an "on and off switch" and the practitioner needs to be aware of five ways in which the patient can manifest undesirable effects and for which anesthesiologists and anesthetists must be prepared.

The extremely rapid achievement of the peak effect for any dose makes it easy to recognize the dose-effect relationship and facilitates titration of dose vs. effect, allowing rapid control of responses to noxious or painful stimuli. An "excessive dose" for a given patient can lead to the rapid onset of intense side effects, most notably hypotension and bradycardia, apnea and muscular rigidity.

Ultiva (remifentanil hydrochloride)

Maximum Dosage:
Prescribers Digital Reference
Ultiva - Drug Summary: https://www.pdr.net/drug-summary/Ultiva-remifentanil-hydrochloride-1076
IV opioid dosage should be individualized based on clinical response and cardiorespiratory parameters.
Adults:	For anesthesia, 1 mcg/kg/dose IV; continuous infusion rates greater than 2 mcg/kg/minute IV should be administered only after careful consideration.
Geriatric:	For anesthesia, 1 mcg/kg/dose IV; continuous infusion rates greater than 2 mcg/kg/minute IV should be administered only after careful consideration. Starting doses should be decreased by 50%.
Adolescents:	For general anesthesia maintenance, 1 mcg/kg/dose IV; continuous infusion rates greater than 1.3 mg/kg/minute IV should be administered only after careful consideration. Safety and efficacy have not been established for other indications; however, doses up to 1.25 mcg/kg/dose IV have been used off-label for intubation.
Children:	For general anesthesia maintenance, 1 mcg/kg/dose IV; continuous infusion rates greater than 1.3 mg/kg/minute IV should be administered only after careful consideration. Safety and efficacy have not been established for other indications; however, doses up to 4 mcg/kg/dose IV have been used off-label for intubation.
Infants:	For general anesthesia maintenance, 1 mcg/kg/dose IV; continuous infusion rates greater than 1 mg/kg/minute IV should be administered only after careful consideration. Safety and efficacy have not been established for other indications; however, doses up to 4 mcg/kg/dose IV have been used off-label for intubation.
Neonates:	Neonates: For general anesthesia maintenance, 1 mcg/kg/dose IV; continuous infusion rates greater than 1 mg/kg/minute IV should be administered only after careful consideration. Safety and efficacy have not been established for other indications; however, doses up to 3 mcg/kg/dose IV have been used off-label for intubation. Premature Neonates 28 weeks gestation and older: Safety and efficacy have not been established; however, doses up to 2 mcg/kg/dose IV have been used off-label for intubation.

Important Information:

Remifentanil can slow or stop your breathing, and may be habit-forming. MISUSE OF remifentanil CAN CAUSE ADDICTION, OVERDOSE, OR DEATH.

Remifentanil can cause side effects that may impair your thinking or reactions. You should not plan on driving or doing anything that requires you to be awake and alert right after you are treated with remifentanil. Dizziness or severe drowsiness can cause falls or other accidents.

Interactions:

Drug Interactions (327) Alcohol/Food Interactions (1) Disease Interactions (11)

What other drugs will affect Remifentanil?
Tell your doctor if you have used an MAO inhibitor in the past 14 days. MAO inhibitors include isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, and tranylcypromine. Other drugs may affect remifentanil, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

A total of 327 drugs are known to interact with Remifentanil.

• 124 major drug interactions
• 202 moderate drug interactions
• 1 minor drug interaction

Remifentanil Interactions:
https://www.drugs.com/mtm/remifentanil.html

Remifentanil Monograph for Professionals:
https://www.drugs.com/monograph/remifentanil.html

Ultiva (remifentanil)

Side Effects:
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
RxList
Ultiva (remifentanil): https://www.rxlist.com/ultiva-drug/patient-images-side-effects.htm
Like other opioid medicines, remifentanil can slow your breathing. Death may occur if breathing becomes too weak.
Your caregivers will watch for any side effects you have, such as: noisy breathing, sighing, shallow breathing, breathing that stops during sleep fast or slow heart rate stiff muscles severe weakness, feeling light-headed or fainting
Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.
Serious side effects may be more likely in older adults and those who are overweight, malnourished, or debilitated.
Common side effects may include: slow breathing slow heart rate muscle stiffness feeling light-headed
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is the most important information I should know about remifentanil?
Remifentanil can slow or stop your breathing, and may be habit-forming. MISUSE OF THIS MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH.

Remifentanil (Ultiva):
https://www.uofmhealth.org/health-library/d04034a1

Ultiva (remifentanil) (Rx)

Black Box Warnings:
Ultiva (remifentanil) (Rx): https://reference.medscape.com/drug/ultiva-remifentanil-343316
Addiction, abuse, and misuse 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

Pediatric:
Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of remifentanil injection when given with an anesthetic before or during an operation in children. Appropriate studies on the relationship of age to the effects of remifentanil injection for the relief of pain after surgery have not been performed in the pediatric population.

Safety and efficacy have not been established.

Geriatric:
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of remifentanil injection in the elderly. However, elderly patients may be more sensitive to the effects of remifentanil injection than younger adults, which may require caution and an adjustment in the dose for patients receiving remifentanil.

Other Interactions:

• Ethanol

Other Medical Problems:
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, or history of
• Brain tumor
• Breathing or lung problems (eg, apnea, COPD, cor pulmonale, respiratory depression)
• Drug dependence, especially with narcotics, or history of
• Head injury, history of - May increase risk for more serious side effects

• Gallbladder problems
• Heart disease
• Hypotension (low blood pressure)
• Pancreatitis (inflammation of the pancreas)
• Seizures, history of
• Slow heartbeat - Use with caution. May make these conditions worse

Remifentanil (Intravenous Route) (Ultiva):
https://www.mayoclinic.org/drugs-supplements/remifentanil-intravenous-route/description/drg-20073019

Half time is reliably less than 10 minutes:
Remifentanil (Ultiva) is a potent (~200-300 times more than morphine), short acting, titratable narcotic infusion I use for moderate/deep sedation and maintaining general anesthetics. Unlike many drugs which rely on hepatic and/or renal metabolism, remifentanil's metabolism is through nonspecific plasma esterases. This explains why the drug does not "build up" compared to other infusions. Consequently, remifentanil's context-sensitive half time remains independent of the duration of the infusion. In other words, it doesn't matter if you run the infusion for an hour or twelve hours, the drug's half time is reliably less than 10 minutes.

As a powerful narcotic, it also confers a degree of synergy with hypnotics like propofol allowing me to use a lower dose of the latter to promote hemodynamic stability and faster/cleaner emergences. Remifentanil also has a fair amount of data suggesting acute opioid tolerance and paradoxical hyperalgesia (increased sensitization to noxious stimuli) from its usage. Whenever I use it in the perioperative setting, I'm mindful that its analgesic effects will quickly subside and affect post-operative pain management for the aforementioned reasons. In anticipation, I incorporate multimodal techniques whenever possible by administering longer acting narcotics, local infiltration, regional techniques, ketamine, NSAIDs, gabapentinoids, etc.

Indication: Analgesia:
Opioid analgesics are often used during general anaesthesia. Remifentanil is an opioid agonist with a structure related to fentanyl.

• An infusion of remifentanil rapidly produces analgesia. It can be used as an adjunct during induction and during the maintenance of anaesthesia when endotracheal intubation and controlled ventilation are planned.
• Remifentanil is rapidly metabolised by circulating and tissue esterases. It has a half-life of 3-10 minutes and a rapid offset of action. The effect of the drug usually wears off within 5-10 minutes. As remifentanil is not approved for postoperative analgesia, another analgesic should be given before the infusion is stopped.
• Like other opioids, remifentanil can cause respiratory depression, hypotension and bradycardia. These can be managed by reducing the rate of infusion, but the drug should not be used for spontaneous ventilation anaesthesia.
• A rapid onset of action can be associated with muscle rigidity. If a bolus dose is used during induction, it should be given slowly over a minute. To avoid giving a bolus during infusions, a dedicated intravenous line or fast-flowing intravenous line is recommended.
• The pharmacokinetics of remifentanil offer some advantages over other opioid agonists. However, anaesthetists will need to be alert to the potential adverse effects, particularly if the drug is used during induction. Its use as a sole agent in general anaesthesia is contraindicated.

Who should not take Remifentanil Solution, Reconstituted (Recon Soln)?
The following conditions are contraindicated with this drug. Check with your physician if you have any of the following:

Conditions:

• Decreased function of the adrenal gland
• Drug abuse
• Slow heartbeat
• Low blood pressure
• Decreased lung function
• Acute inflammation of the pancreas
• Seizures
• Inherited dysfunction of autonomic nerve function
• History of opioid overdose

Allergies:

• Opioids-Meperidine and Related

Who should not take Remifentanil Solution, Reconstituted (Recon Soln)?
https://www.webmd.com/drugs/2/drug-14214/remifentanil-intravenous/details/list-contraindications

How does remifentanil work in labour?
An NHS hospital in Southampton described the process on their website (in 2011) as follows:

• A drip is inserted into a vein in your arm or hand and attached to a patient-controlled analgesia (PCA) pump.
• You press the button on the pump and a small dose of remifentanil is given directly into your vein providing pain relief on demand, reducing the severity of labour pain.
• This starts working within 5 minutes of the drip being connected. You need to press the button every time you have a contraction because each dose of remifentanil wears off within a few minutes.
• Remifentanil actually takes about 10 minutes to clear from the body - unless of course you keep pumping it in.

Instead of an epidural?
Calls for rethink on childbirth pain relief as research shows remifentanil works better than pethidine.

Pethidine is given as an injection, but a new study funded by the National Institute for Health Research shows that remifentanil, which women control by pressing a button when they feel pain, appears to be more effective. Women using remifentanil were half as likely to end up asking for an epidural, which blocks all pain and sensation and often leads to a forceps delivery.

Remifentanil is being used in some maternity units, but there has not yet been sufficient proof that it is better than pethidine. Both drugs are out of patent so there is no basic cost differential.

Remifentanil has the big advantage of being cleared from the body very fast - within 10 minutes - so women are able to dose themselves just during contractions.

Breastfeeding:

Summary of Use During Lactation:

Because the half-life of remifentanil is extremely short, it is unlikely to cause any adverse effects in the breastfed newborn if it is given to the mother for labor analgesia or a surgical procedure.

Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics.

Once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of remifentanil to a few days.

However, because no information is available on the use of remifentanil during breastfeeding, an alternate drug may be preferred if the mother requires prolonged administration of remifentanil during the early postpartum period.

If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately.

Drug Levels:
Remifentanil is administered intravenously and has a half-life of about 3 minutes in adults. Its oral bioavailability is unknown.

Effects on Lactation and Breastmilk:

Narcotics can increase serum prolactin.

However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.

Alternate Drugs to Consider:

• Acetaminophen
• Butorphanol
• Fentanyl
• Hydromorphone
• Ibuprofen
• Morphine

Remifentanil Drug Levels and Effects:
https://www.ncbi.nlm.nih.gov/books/NBK501253/

Remifentanil: Clinical use of an evanescent opioid:
Remifentanil is a selective m opioid receptor agonist, of higher potency than alfentanil, but with pharmacological effects that essentially parallel those of alfentanil and other opioids in this class. Unlike these other opioids, however, remifentanil is rapidly hydrolyzed by nonspecific plasma and tissue esterases: this imparts brevity of action, precise and easily titrated effects (attributable to rapid onset and offset kinetics), non- cumulative opioid effects and rapid recovery after cessation of administration (attributable to rapid clearance). The onset of action of remifentanil is similar to that of alfentanil, although its offset is considerably more rapid and independent of the duration of infusion. The context-sensitive half-life remains very short (3 to 4 minutes), independent of the duration of infusion. These characteristics facilitate titration of dose to effect and also allow the use of very high doses (ED99) without fear of prolonging recovery.

The unique pharmacokinetic profile of remifentanil facilitates 'real time' management of intraoperative stress, as well as provision of optimal intraoperative analgesia without compromising recovery for a variety of surgical procedures. It is tempting to speculate that these characteristics will make remifentanil an easy drug to titrate, and also that clinicians will have less need to consider patient covariates such as extremes of age or size when choosing a dosing regimen. However, the rapid onset of drug effect may be accompanied by rapid onset of adverse events such as apnea and muscle rigidity. The rapid offset of drug effect can result in patients who are in severe pain at a time when the anesthesiologist is ill equipped to deal the problem - for example when the patient is in transit to the recovery room.

Sound-alike/look-alike issues:
Remifentanil may be confused with alfentanil

High alert medication:
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic.

• A potent, short-acting synthetic opioid analgesic
• Used as an opioid analgesic that has a rapid onset and rapid recovery time.
• Used for:
  • Sedation
  • Combined with other medications for use in general anesthesia
• Considered a soft drug, one that is rapidly metabolized to an inactive form.
• Accumulation does not occur with remifentanil and its context-sensitive half-life remains at 4 minutes after a 4-hour infusion.
• Most common side effects:
  • A sense of extreme dizziness
  • Intense itching (pruritus), often around the face
• Approximately twice as potent as fentanyl, and 100-200 times as potent as morphine.

Remifentanil has made possible the use of high-dose opioid and low-dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics.

Due to its quick metabolism and short effects, remifentanil has opened up new possibilities in anesthesia. When remifentanil is used together with a hypnotic (i.e. one that produces sleep) it can be used in relative high doses. This is because remifentanil will be rapidly eliminated from the blood plasma on termination of the remifentanil infusion, hence the effects of the drug will quickly dissipate even after very long infusions. Owing to synergism between remifentanil and hypnotic drugs (such as propofol) the dose of the hypnotic can be substantially reduced. This leads often to more hemodynamic stability during surgery and a quicker post-operative recovery time.

While opiates function similarly, with respect to analgesia, the pharmacokinetics of remifentanil allows for quicker post-operative recovery.