Formin may be available in the countries listed below.
Metformin hydrochloride (a derivative of Metformin) is reported as an ingredient of Formin in the following countries:
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Metformin hydrochloride (a derivative of Metformin) is reported as an ingredient of Metformin Tablets in the following countries:
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Amlodipine Qualimed may be available in the countries listed below.
Amlodipine besilate (a derivative of Amlodipine) is reported as an ingredient of Amlodipine Qualimed in the following countries:
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Nor-Tenz may be available in the countries listed below.
Brimonidine tartrate (a derivative of Brimonidine) is reported as an ingredient of Nor-Tenz in the following countries:
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Cortifoam is a brand name of hydrocortisone, approved by the FDA in the following formulation(s):
No. There is currently no therapeutically equivalent version of Cortifoam available.
Note: Fraudulent online pharmacies may attempt to sell an illegal generic version of Cortifoam. These medications may be counterfeit and potentially unsafe. If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. Ask your health care provider for advice if you are unsure about the online purchase of any medication.
See also: About generic drugs.
There are no current U.S. patents associated with Cortifoam.
Sumatriptan-Hormosan may be available in the countries listed below.
Sumatriptan succinate (a derivative of Sumatriptan) is reported as an ingredient of Sumatriptan-Hormosan in the following countries:
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Ezetimibe-MSD may be available in the countries listed below.
Ezetimibe is reported as an ingredient of Ezetimibe-MSD in the following countries:
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Dimetridazolo may be available in the countries listed below.
Dimetridazolo (DCIT) is also known as Dimetridazole (Prop.INN)
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Glossary
| DCIT | Denominazione Comune Italiana |
| Prop.INN | Proposed International Nonproprietary Name (World Health Organization) |
Class: Serums
ATC Class: J06BB05
VA Class: IM500
Brands: HyperRAB S/D, Imogam Rabies-HT
Specific immune globulin (hyperimmune globulin).202 205 Rabies immune globulin (RIG) contains antibody to rabies antigen and is used to provide antirabies antibodies for temporary passive immunity to rabies virus.201 206 207 216 RIG commercially available in the US is prepared from plasma of donors hyperimmunized with rabies vaccine201 205 206 207 and is sometimes referred to as HRIG.216 Other types of RIG (e.g., equine rabies immune globulin; ERIG) may be available in other countries.205 207 210 215
Postexposure prophylaxis of rabies in previously unvaccinated children, adolescents, and adults following exposure to rabies disease or virus.201 205 206 207 216
Used in a postexposure prophylaxis regimen that includes active immunization with rabies vaccine and passive immunization with RIG.205 207 210 216 RIG provides immediate, temporary rabies virus-neutralizing antibodies until the patient has an immunologic response to active immunization with rabies vaccine and produces virus-neutralizing antibodies.205 207 216
RIG is not included in rabies postexposure prophylaxis regimens used in individuals who previously received preexposure or postexposure regimens that included rabies vaccine.205 207 216 Passive immunization is not necessary in such individuals and may interfere with the desired anamnestic response to booster doses of rabies vaccine used for postexposure prophylaxis in such individuals.207 216
Rabies is a viral infection transmitted by saliva of infected mammals, most commonly wild, terrestrial carnivores (e.g., skunks, raccoons, foxes, coyotes) or bats.205 207 In the US, the greatest risk for naturally-acquired rabies is from contact with and bites from insectivorous bats.207 209 212 Following exposure and infection, rabies virus usually moves along a neural pathway and enters the CNS.215 216 After entrance into the CNS, the virus is unlikely to be affected by antirabies antibodies and encephalomyelitis usually develops and almost always is fatal.207 215 In the US, approximately 16,000–39,000 individuals receive rabies postexposure prophylaxis each year.206 207 216 Although there were 27 rabies cases reported in the US during 2000–2008,205 these individuals evidently did not receive rabies postexposure prophylaxis.205 Rabies prevention and control strategies in the US and elimination of canine rabies virus variants and enzootic transmission among dogs have lowered the number of rabies cases in the US to an average of 1–2 per year.212 216 However, worldwide, rabies is much more common and at least 55,000 rabies-related deaths occur each year.212 216
Whenever a possible human exposure to rabies occurs, the risk of infection must be accurately assessed to determine the need for postexposure prophylaxis.207 216 Base decisions regarding the need for postexposure prophylaxis on vaccination status of the exposed individual (see Table 1), type of exposure (bite, nonbite), information about the animal involved (type, vaccination status, condition at time of attack) (see Table 2), and rabies epidemiology in the specific geographic region.205 207 216 Consult local or state public health officials for assistance when evaluating rabies exposures and the need for postexposure prophylaxis.205 207
Any person with a history of a complete preexposure or postexposure vaccination regimen with HDCV, PCECV, or rabies vaccine adsorbed (RVA; not commercially available in the US), or previous vaccination with any other type of rabies vaccine and a documented history of antibody response to the prior vaccination
Individuals with immunosuppression should receive a 5-dose regimen of rabies vaccine; give 1 mL (HDCV or PCECV) IM once on days 0, 3, 7, 14, and 28.
Deltoid area is the only acceptable site for IM administration of rabies vaccine in adults, adolescents, and older children. For younger children, deltoid or anterolateral thigh should be used. Never administer in gluteal area.
Day 0 is the day the first dose of rabies vaccine is administered.
Adapted from Use of a Reduced (4-dose) Vaccine Schedule for Postexposure Prophylaxis to Prevent Human Rabies. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010; 59 (RR-2):1-9.
Vaccination Status | Treatment | Regimen |
|---|---|---|
Not previously vaccinated | Wound cleansing | Immediately cleanse all wounds thoroughly with soap and water; if available, irrigate wounds with virucidal agent (e.g., povidone-iodine solution) |
RIG | Administer 20 international units/kg of RIG; if anatomically feasible, infiltrate full RIG dose around and into wound(s) and give any remaining portion of the dose IM at an anatomical site distant from site of rabies vaccine administration | |
Rabies vaccine | Administer 4-dose regimen of rabies vaccine; give 1 mL (human diploid-cell vaccine [HDCV] or purified chick embryo cell culture vaccine [PCECV]) IM once on days 0, 3, 7, and 14 | |
Previously vaccinated | Wound cleansing | Immediately cleanse all wounds thoroughly with soap and water; if available, irrigate wounds with virucidal agent (e.g., povidone-iodine solution) |
RIG | RIG should not be administered | |
Rabies vaccine | Administer 2-dose regimen of rabies vaccine; give 1 mL (HDCV or PCECV) IM once on days 0 and 3 |
Regardless of immunization status, USPHS Advisory Committee on Immunization Practices (ACIP) and AAP recommend that postexposure prophylaxis of rabies begin immediately with thorough cleansing of all bite wounds and scratches using soap and water and, if available, irrigation with a virucidal agent such as povidone-iodine solution.205 207 216 Local wound treatment is an essential initial step in rabies postexposure prophylaxis in all individuals.205 207 216 (See General under Dosage and Administration.)
In previously unvaccinated children, adolescents, and adults following potential rabies exposure, a combined regimen of active immunization with a 4- or 5-dose regimen of rabies vaccine and passive immunization with a single dose of RIG is recommended as soon as possible.205 207 216 (See Table 1.)
In previously vaccinated children, adolescents, and adults following potential rabies exposure, a 2-dose booster regimen of rabies vaccine (without RIG) is recommended as soon as possible.205 207 216 (See Table 1.)
During the 10-day observation period, begin postexposure prophylaxis in the exposed individual at the first sign of rabies in the dog, cat, or ferret that has bitten them. If the animal exhibits clinical signs of rabies, euthanize it immediately and perform appropriate testing.
Initiate postexposure prophylaxis as soon as possible following exposure to such wildlife, unless animal is available for testing and public health authorities are facilitating expeditious laboratory testing or it is already known that brain material from the animal has tested negative. Other factors that might influence urgency of decision-making regarding initiation of postexposure prophylaxis before diagnostic results are known include the animal species, general appearance and behavior of the animal, whether encounter was provoked by a human, and the severity and location of bites. Discontinue postexposure prophylaxis if appropriate laboratory tests (i.e., direct fluorescent antibody test) are negative.
Euthanize the animal and test as soon as possible. Holding for observation is not recommended.
Adapted from the Recommendations of the Advisory Committee on Immunization Practices (ACIP) on Human Rabies Prevention. MMWR Recomm Rep. 2008; 57 (RR-3):1-28.
Animal Type | Evaluation and Disposition of Animal | Postexposure Prophylaxis Recommendations |
|---|---|---|
Dogs, cats, ferrets | Healthy and available; confine for 10 days of observation | Do not begin prophylaxis unless animal develops clinical signs of rabies |
Rabid or suspected rabid | Immediately begin postexposure prophylaxis | |
Unknown (e.g., escaped) | Consult public health officials | |
Skunks, raccoons, foxes, and most other carnivores; bats | Regard as rabid unless animal proven negative by laboratory tests | Consider immediate postexposure prophylaxis |
Livestock, small rodents, lagomorphs (rabbits, hares), large rodents (woodchucks, beavers), other mammals | Consider individually | Consult public health officials. Bites from squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other small rodents, rabbits, and hares almost never require rabies postexposure prophylaxis |
Bite exposures include any skin penetration by teeth; all bite exposures from an animal known or suspected to be rabid, regardless of bite location, pose a potential risk of rabies transmission and require postexposure prophylaxis.205 207 Risk of transmission varies in part based on the species of biting animal, anatomic site of bite, and severity of wound.207 Rabies transmission can occur from bites of some animals (e.g., bats) that inflict rather minor injury and wounds that are difficult to detect.207
Any potential exposure to a bat requires thorough evaluation.207 If possible, the bat should be submitted for rabies diagnosis.207 Postexposure prophylaxis is not necessary if the individual can be reasonably certain a bite, scratch, or mucous membrane exposure did not occur or if the bat is available for testing and is negative for rabies virus.207 Situations that might qualify as exposures include finding a bat in the same room as a person who might be unaware that a bite or direct contact has occurred (e.g., a deeply sleeping individual awakened to find a bat in the room; an adult observes a bat in the room with a previously unattended child, mentally disabled person, or intoxicated person).207 Other household members who do not have direct contact with the bat or were awake and aware when in the room with the bat should not be considered as having exposure to rabies.207
Nonbite exposures include contamination of preexisting open wounds, abrasions, mucous membranes, or scratches with saliva or other potentially infectious material (e.g., neural tissue) from an animal known or suspected to be rabid.205 207 Although nonbite exposures only rarely cause rabies, such exposures require assessment to determine if sufficient reasons exist to consider postexposure prophylaxis.205 207 Nonbite exposures of highest risk occur in surgical recipients of corneas, solid organs, and vascular tissue transplanted from patients who died of rabies and individuals exposed to large amounts of aerosolized rabies virus.207
Other forms of contact in the absence of a bite or nonbite exposure (e.g., petting a rabid animal; contact with blood, urine, or feces of a rabid animal; contact of saliva with intact skin) are not considered exposure, and postexposure prophylaxis is not necessary.207
In health-care personnel, routine delivery of health care to a patient with rabies is not an indication for postexposure rabies prophylaxis.207 However, postexposure prophylaxis is indicated in health-care personnel if they have been bitten by the patient or if they have mucous membranes or nonintact skin (e.g., open wounds) that were contaminated with the patient's saliva or other potentially infectious material (e.g., neural tissue).207
Because the rabies incubation period in humans can range from days to years (usually 1–3 months),205 207 210 216 initiate rabies postexposure prophylaxis (regardless of the length of delay) if a documented or likely exposure has occurred and clinical signs of rabies have not appeared in the exposed individual.207
Postexposure prophylaxis failures have not been reported in the US when recommended immunization and wound management procedures were followed using commercially available rabies vaccines and RIG.206 207 216 Rare reports of failures in other countries usually involved some deviation from recommended procedures (e.g., postexposure prophylaxis not given or substantially delayed, wounds not adequately cleansed, rabies vaccine given IM into the gluteal rather than deltoid region, failure to passively immunize with RIG by infiltrating the wound site, use of less than the recommended dose of RIG, use of less than the recommended number of doses of rabies vaccine).206 207 216
Travelers to rabies-endemic countries should be warned about the risk of acquiring rabies and educated in bite prevention strategies (e.g., avoiding contact with bats, avoiding stray dogs, monkeys, or cats).210 Because appropriate preparations of RIG or rabies vaccine may be not available for postexposure prophylaxis in the destination country, CDC recommends that travelers to such countries have a preplanned strategy in place that may involve identifying a different country where appropriate postexposure prophylaxis can be obtained if necessary.210 CDC states that rabies vaccines grown in animal brains (neural tissue vaccines) still may be used in some developing countries; if offered such a brain-derived vaccines (identified by a regimen that requires 5-mL injections once daily for 14–21 days), travelers should refuse the vaccine and travel to a country where an acceptable rabies vaccine preparation and RIG are available.210 If travelers in other countries receive postexposure prophylaxis with regimens and/or preparations not recommended by ACIP (or not used in the US), additional therapy may be necessary following return to the US.207 210 In such cases, consult state and local health authorities for advice regarding the need for additional postexposure prophylaxis.207 Consider serologic testing in these travelers to verify efficacy of the regimen used and to ensure an adequate immune response.207 (See Pre- and Postvaccination Serologic Testing under Cautions.)
Rabies postexposure prophylaxis in previously unvaccinated individuals involves thorough cleansing of all bite and nonbite wounds followed by passive immunization with a single dose of RIG and active immunization with a series of 4 or 5 doses of rabies vaccine.201 205 206 207 216 210 216
RIG is not indicated for postexposure prophylaxis in individuals who previously received rabies vaccine for preexposure vaccination or postexposure prophylaxis.201 205 206 207 216 (See Specific Drugs under Interactions.)
Because rabies virus may remain localized at the site of inoculation for a variable time before entering neural tissue, immediately wash all bites and scratches with soap and water; if available, irrigate with a virucidal agent (e.g., povidone-iodine solution).201 205 207 210 216 Institute tetanus prophylaxis and measures to control secondary infection as indicated.205 207 Consider cosmetic factors and the potential for bacterial infection before deciding to suture large wounds.205 207 AAP states that, if possible, the wound should not be sutured.205
Administer by local infiltration with or without IM administration.201 205 206 207 216
Do not administer IV.201 206 (See Administration Precautions under Cautions.)
Infiltrate the recommended dose of RIG into the wound(s) and surrounding area if anatomically feasible.201 205 206 207 216
When the volume required to infiltrate the wound(s) exceeds the recommended dose of RIG, some clinicians recommend diluting the calculated dose in saline to yield a two- to threefold increase in solution volume to ensure that all wound areas receive adequate infiltration.205
After infiltrating wound(s) area, administer any remaining portion of the recommended RIG dose by IM injection at a site distant from where rabies vaccine is being administered.201 205 206 207 216 For adults and older children, the deltoid is the only acceptable IM injection site; for younger children, the deltoid or anterolateral thigh should be used.201 216 For children with a small muscle mass, it may be necessary to administer RIG at multiple IM sites.205
Do not administer RIG into gluteal area (buttock muscle) because of potential for injection-associated injury to the sciatic nerve.201 202 216
Avoid injection into or near blood vessels or nerves.202 206 ACIP and AAP state that aspiration (i.e., pulling back on the syringe plunger after needle insertion and before injection) is not required because large blood vessels are not present at recommended IM injection sites.202 205
To ensure delivery into muscle, IM injections should be made at a 90° angle to the skin using a needle length appropriate for the individual's age and body mass, the thickness of adipose tissue and muscle at the injection site, and the injection technique.202
Do not administer RIG in the same syringe or simultaneously at the same injection site as rabies vaccine.201 205 206 207 216 (See Specific Drugs under Interactions.)
Do not mix with other immune globulins, vaccines, or solutions.202 205
Single dose of 20 international units/kg.201 205 206 207 216 Infiltrate into and around area of wound(s); administer any remaining portion of the dose by IM injection.201 205 206 207 216 (See Administration under Dosage and Administration.)
Commercially available 2-mL vials (HyperRAB S/D, Imogam Rabies-HT) contain 300 international units of RIG (sufficient dose for a 15-kg child).201 206
Give RIG dose as soon as possible after exposure (day 0), preferably at the time of the first dose of rabies vaccine.201 205 206 207 216
If rabies vaccine is not immediately available, administer RIG and start active immunization with the vaccine as soon as possible.205 If RIG is not immediately available, it may be administered at any time through day 7 following the first vaccine dose;205 207 216 RIG is not necessary after day 7 since sufficient vaccine-induced antirabies antibody will be present in most vaccine recipients.207 Some experts suggest that if administration of both RIG and vaccine is delayed, both should be used regardless of the interval between exposure and prophylaxis.201 205 206
Do not exceed the recommended RIG dose (i.e., single dose of 20 international units/kg); do not give repeated doses of RIG.201 205 206 207 (See Specific Drugs under Interactions.)
Single dose of 20 international units/kg.201 205 206 207 216 Infiltrate into and around area of wound(s); administer any remaining portion of the dose by IM injection.201 205 206 207 216 (See Administration under Dosage and Administration.)
Commercially available 10-mL vials (HyperRAB S/D, Imogam Rabies-HT) contain 1500 international units of RIG (sufficient dose for a 75-kg adult).201 206
Give RIG dose as soon as possible after exposure (day 0), preferably at the time of the first dose of rabies vaccine.201 205 206 207 216
If rabies vaccine is not immediately available, administer RIG and start active immunization with the vaccine as soon as possible.205 If RIG is not immediately available, it may be administered at any time through day 7 following the first vaccine dose;205 207 216 RIG is not necessary after day 7 since sufficient vaccine-induced antirabies antibody will be present in most vaccine recipients.207 If administration of both RIG and vaccine is delayed, both should be used regardless of the interval between exposure and prophylaxis.201 205 206
Do not exceed the recommended RIG dose (i.e., single dose of 20 international units/kg); do not give repeated doses of RIG.201 205 206 207 (See Specific Drugs under Interactions.)
Maximum total dose of 20 international units/kg.201 205 206 207
Maximum total dose of 20 international units/kg.201 205 206 207
No specific dosage recommendations.
No specific dosage recommendations.
No specific dosage recommendations.
Repeated doses of RIG after active immunization with rabies vaccine is initiated.206 (See Specific Drugs under Interactions.)
Because RIG (HyperRAB S/D, Imogam Rabies-HT) is prepared from pooled human plasma, it is a potential vehicle for transmission of human viruses, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).201 206 208
Improved donor screening, viral-inactivation procedures (e.g., solvent/detergent treatment), and/or filtration procedures have reduced, but not completely eliminated, risk of pathogen transmission with plasma-derived preparations.201 206
The manufacturing processes for RIG include certain chemical (solvent/detergent) treatment procedures and/or heat-treatment procedures to reduce viral infectious potential.201 206
Solvent/detergent inactivation processes apparently can inactivate lipid-enveloped (e.g., hepatitis B virus [HBV], hepatitis C virus [HCV], HIV type 1 and type 2 [HIV-1 and HIV-2]), but are less effective against viruses that do not have a lipid envelope (e.g., hepatitis A virus [HAV], parvovirus B-19).201 206 Certain filtering procedures are effective in reducing levels of some enveloped and non-enveloped viruses.201 206
Because no purification method has been shown to be totally effective in removing the risk of viral infectivity from plasma-derived preparations and because new blood-borne viruses or other disease agents may emerge that may not be inactivated by the manufacturing process or the chemical (solvent/detergent) treatment procedures currently used, administer RIG only when a benefit is expected.201 206
Any infection believed to have been transmitted by RIG should be reported to the appropriate manufacturer.201 206
Anaphylaxis has been reported rarely following administration of human immune globulins.201 206
Use with caution in individuals with history of systemic allergic reactions to immune globulins.201 206
Epinephrine and other appropriate therapy should be readily available in case anaphylaxis occurs.201 206
HyperRAB S/D may contain IgA.201
Use caution in individuals with IgA deficiency since such individuals may have serum antibodies to IgA and anaphylaxis could result following administration of preparations containing IgA.201 206 Weigh potential benefits against potential for hypersensitivity reactions.201
Do not administer RIG in the same syringe or at the same injection site as rabies vaccine.201 206 207 216 (See Specific Drugs under Interactions.)
Do not administer IV.201 206 Inadvertent IV injection may result in serious systemic reactions; epinephrine should be available if an acute anaphylactic reaction occurs.201 206
May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.203 216
Recommendations regarding use of RIG in individuals with altered immunocompetence are the same as those for individuals who are not immunocompromised.203 216
If rabies postexposure prophylaxis is indicated in an immunocompromised individual, serologic testing is considered essential after completion of the postexposure prophylaxis regimen to confirm than an adequate antibody response is obtained.203 205 207 216 If an adequate antibody response is not detected after the final vaccine dose of the postexposure prophylaxis series, the patient should be managed in consultation with their clinician and appropriate public health officials.216 (See Pre- and Postvaccination Serologic Testing under Cautions.)
Because bleeding may occur following IM administration in individuals with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or in those receiving anticoagulant therapy, use caution in such individuals.201 202 206
ACIP states that IM injections can be used in individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient's bleeding risk determines that the injection can be administered with reasonable safety.202 In these cases, use a fine needle (23 gauge) to administer the dose and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.202 205 If patient is receiving antihemophilia therapy, administer the IM dose shortly after a scheduled dose of such therapy.202
Advise the individual and/or their family about the risk of hematoma from IM injections.202
RIG provides only short-term protection against rabies.207 Half-life of RIG following an IM dose is approximately 21 days.207
Rabies postexposure prophylaxis includes combined passive immunization with RIG and active immunization with rabies vaccine to provide effective and more prolonged immunity against rabies.201 205 206 207 216 Additional (booster) doses of RIG not recommended.201 205 206 207
Serologic testing is not indicated prior to postexposure prophylaxis in previously vaccinated individuals who are exposed to rabies.207 Such testing is inappropriate because it would delay postexposure prophylaxis and, although antirabies neutralizing antibodies are an important component of immunity, other immune effectors also play a role in disease prevention.207
Serologic confirmation of rabies immunity following postexposure prophylaxis is not necessary in most individuals because of the high rate of response among immunocompetent adults, adolescents, and children when the recommended rabies postexposure regimen is used (i.e., proper wound care followed by a single dose of RIG and a 4- or 5-dose regimen of a cell culture-derived rabies vaccine).205 207 210 216
When postexposure prophylaxis against rabies is indicated in an immunocompromised individual, serologic testing is considered essential after completion of the postexposure prophylaxis regimen to confirm that an adequate antibody response was obtained.203 205 207 216 This includes individuals receiving immunosuppressive agents (e.g., those receiving corticosteroids for the treatment of life-threatening neuroparalytic reactions to rabies vaccine).207 (See Individuals with Altered Immunocompetence under Cautions.)
Consider serologic testing to confirm that an adequate antibody response was obtained in travelers who received rabies postexposure prophylaxis with regimens and/or preparations not currently recommended by ACIP.207 (See Postexposure Prophylaxis of Rabies under Uses.)
If serologic testing for serum antirabies antibody is performed 1–2 weeks after postexposure prophylaxis is completed, ACIP defines an adequate antibody response as complete virus neutralization at a 1:5 serum dilution when determined by rapid fluorescent-focus inhibition test (RFFIT).207 216 WHO states that an enterobius antibody titer of ≥0.5 international units/mL can be considered protective.215
Category C.201 206
Pregnancy is not considered a contraindication for postexposure prophylaxis with RIG because of the potential risks of inadequately treated rabies exposure.206 207
ACIP states there are no known risks for the fetus associated with use of immune globulin preparations for passive immunization of pregnant women.202
Not known whether RIG is distributed into milk or if transmission of RIG to a nursing infant would present any unusual risk.a
HyperRAB S/D: Safety and efficacy not established in children.201
ACIP and AAP recommend that postexposure prophylaxis (including use of RIG) in children follow the same guidelines as those in adults.205 207
Information not available regarding differences in efficacy and safety between geriatric and younger individuals.
Injection site reactions (e.g., tenderness, pain, muscle soreness, stiffness),201 206 207 low-grade fever,201 headache.206 207
Immune globulins, including RIG, are not expected to have a clinically important effect on the immune response to inactivated vaccines or toxoids; inactivated vaccines, recombinant vaccines, polysaccharide vaccines, and toxoids may be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after administration of RIG.202 205
Antibodies present in immune globulins, including RIG, may interfere with the immune response to certain live virus vaccines (e.g., measles, mumps, and rubella virus vaccine live (MMR), rotavirus vaccine live oral, varicella virus vaccine live); these vaccines should not be administered simultaneously with or for specified intervals before or after administration of RIG.201 202 204 205 206 (See Specific Drugs under Interactions.) There is no evidence that immune globulin preparations interfere with the immune response to yellow fever virus vaccine live, typhoid vaccine live oral, influenza virus vaccine live intranasal, or poliovirus vaccine live oral (OPV; no longer commercially available in the US).202 205
Drug | Interaction | Comments |
|---|---|---|
Immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticosteroids, radiation) | Potential for decreased antibody response to postexposure prophylaxis using combined active immunization with rabies vaccine and passive immunization with RIG; increased risk of rabies infection despite use of postexposure prophylaxis203 205 207 210 216 | Avoid immunosuppressive therapy in patients receiving rabies postexposure prophylaxis unless such therapy is considered essential for treatment of other serious conditions203 207 216 If rabies postexposure prophylaxis is used in an individual receiving immunosuppressive agents, perform serologic testing for rabies antibody after completion of the postexposure regimen to confirm adequate immune response203 207 (See Pre- and Postvaccination Serologic Testing under Cautions.) |
Measles, mumps, and rubella vaccine (MMR) | RIG may interfere with the immune response to measles and rubella antigens contained in MMR; the effect of RIG on the immune response to mumps antigens contained in the vaccine is unknown201 202 205 206 | Manufacturers of HyperRAB S/D and Imogam Rabies-HT state that MMR should not be administered within 3 months after RIG201 206 ACIP and AAP state that MMR and RIG should not be administered simultaneously and that MMR should not be administered within 4 months after RIG202 205 ACIP and AAP also state that if RIG must be administered within 14 days after a dose of MMR, revaccination is necessary at least 4 months after RIG, unless serologic testing indicates an adequate antibody response to all 3 vaccine antigens202 205 |
Rabies vaccine | RIG, may partially suppress the active immune response to rabies vaccine;201 206 207 there is evidence that a single RIG dose of 20 international units/kg given at the same time as the first dose of rabies vaccine provides maximum circulating antirabies antibody with minimal interference with the active immune response to the vaccine201 206 Neutralization of rabies vaccine may occur if RIG and rabies vaccine are mixed in the same syringe or administered into the same injection site201 202 205 206 207 Repeating the dose of RIG may interfere with the active immune response to rabies vaccine 206 | If rabies postexposure prophylaxis requires active immunization with rabies vaccine and passive immunization with RIG, a single dose of RIG should be administered simultaneously with the first vaccine dose;201 206 207 216 infiltrate the full RIG dose into and around the wound(s) if anatomically feasible and administer any remaining portion of the RIG dose IM (using a different syringe and injection site than rabies vaccine)201 202 205 206 207 216 To minimize potential suppression of the active immune response to the vaccine, do not exceed the recommended dosage of RIG (20 international units/kg) and do not give repeated RIG doses201 206 207 RIG may be administered simultaneously with or through day 7 after the first dose of rabies vaccine without impairing the active immune response to the vaccine201 205 206 207 216 RIG is not indicated for postexposure prophylaxis in individuals who previously received recommended preexposure or postexposure regimens of human diploid-cell rabies vaccine (Imovax), purified chick embryo cell culture (RabAvert), Imovax Rabies I.D. (no longer commercially available in the US]), or rabies vaccine adsorbed (RVA) (no longer commercially available in the US) or in those who previously received other rabies vaccines and have documented adequate antirabies antibody titers205 206 207 216 |
Rotavirus vaccine | RIG may interfere with the immune response to rotavirus vaccine202 |
In the US, Eloxatin (oxaliplatin systemic) is a member of the drug class alkylating agents and is used to treat Colorectal Cancer.
US matches:
UK matches:
Oxaliplatin is reported as an ingredient of Eloxatin in the following countries:
International Drug Name Search
Glossary
| SPC | Summary of Product Characteristics (UK) |
Clomifene Citrate may be available in the countries listed below.
Clomifene Citrate (BANM) is also known as Clomifene (Rec.INN)
International Drug Name Search
Glossary
| BANM | British Approved Name (Modified) |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Mytaderm may be available in the countries listed below.
Betamethasone 17α-valerate (a derivative of Betamethasone) is reported as an ingredient of Mytaderm in the following countries:
Neomycin sulfate (a derivative of Neomycin) is reported as an ingredient of Mytaderm in the following countries:
International Drug Name Search
Lebopride may be available in the countries listed below.
Sulpiride is reported as an ingredient of Lebopride in the following countries:
International Drug Name Search
Class: Opiate Agonists
VA Class: CN101
Chemical Name: 3-[4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidine]propanoic acid methyl ester, hydrochloride salt
Molecular Formula: C20H28N2O5 HCl
CAS Number: CAS-132539-07-2; CAS-132875-61-7
Brands: Ultiva
Selective μ-receptor opiate agonist; fentanyl analog.1 2 3 4 10 11 12
As the analgesic component in the induction and maintenance of general anesthesia for inpatient and outpatient procedures.1 2 3 9 10 12 Although remifentanil has been used as the primary agent for induction of anesthesia, its use as the sole agent in general anesthesia is not recommended because loss of consciousness cannot be ensured and a high incidence of apnea, muscle rigidity, or tachycardia is possible.1 2 3
May be continued in the immediate postoperative period in adults for whom later transition to longer-acting analgesics is desired; must be used under direct supervision of an anesthesia clinician in a postoperative anesthesia care unit or intensive care unit (ICU).1 25 36 37 38 39 40 41 Long-term (i.e., >16 hours) use of remifentanil in ICU patients has not been established to date.1
May be particularly useful in surgical procedures requiring a rapid onset of analgesia and rapid recovery.2 3 8
As the analgesic component of monitored anesthesia care (e.g., in conjunction with local or regional anesthesia for surgical procedures, including ophthalmic surgery,1 32 33 breast biopsy,31 34 35 and other superficial surgical procedures1 31 ) in adults.1 9
Selection of preanesthetic medication(s) must be based on the individual needs of the patient; in clinical studies, remifentanil recipients frequently received a benzodiazepine.1
Selection of concomitant anesthetic agent(s) must be based on the individual needs of the patient.1
Synergistic activity with other anesthetics; dosage adjustment for concomitantly administered anesthetic(s) may be needed.1 3 (See Specific Drugs under Interactions.)
Clear remifentanil from the IV tubing upon discontinuance of the drug to prevent subsequent inadvertent administration of residual drug.1 (See Discontinuance of Therapy under Cautions.)
Residual analgesic activity absent within 5–10 minutes of drug discontinuance.1 Consider administering alternative analgesics prior to remifentanil discontinuance in surgical patients who may experience postoperative pain.1 3 9 10 Choose analgesic based on surgical procedure and level of follow-up care.1
For solution and drug compatibility information, see Compatibility under Stability.
Use a controlled-infusion device to ensure precise control of flow rate during continuous IV infusion of the drug.1
Inject remifentanil into IV tubing at or close to the venous cannula.1
Administration of remifentanil into the same IV tubing with blood products is not recommended, since premature metabolism of the drug by nonspecific esterases may occur.1
Clear remifentanil from the IV tubing upon discontinuance of the drug to prevent subsequent inadvertent administration of residual drug.1 (See Discontinuance of Therapy under Cautions.)
Reconstitute vials containing 1, 2, or 5 mg of remifentanil by adding 1 mL of diluent (sterile water for injection or other compatible IV fluid [see Compatibility under Stability]) per mg of drug.1 Shake well to dissolve.1 Resultant solution contains approximately 1 mg of remifentanil per mL.1
Reconstituted solutions must be diluted prior to administration.1
Dilute reconstituted solution to desired concentration (20, 25, 50, or 250 mcg/mL; see Table 1) in a compatible IV solution.1 (See Storage and also see Compatibility, under Stability.)
| Final Volume (mL) After Reconstitution and Dilution | ||
|---|---|---|---|
Final Concentration (mcg/mL) | 1-mg Vial | 2-mg Vial | 5-mg Vial |
20 | 50 | 100 | 250 |
25 | 40 | 80 | 200 |
50 | 20 | 40 | 100 |
250 | ... | ... | 20 |
A final concentration of 25 mcg/mL is recommended when the drug is used for monitored analgesia care.1 A final concentration of 20 or 25 mcg/mL is recommended for pediatric patients ≥1 year of age.1 Use of 250-mcg/mL solutions of the drug for infusion of dosages of 0.0125–0.025 mcg/kg per minute is not recommended.1
Individualize rate of administration based on patient response.1 3 For recommended dosage ranges and continuous infusion rates, see Dosage under Dosage and Administration.
Administer rapid IV (bolus) doses of remifentanil only during the maintenance phase of general anesthesia.1
In nonintubated patients, administer single doses of remifentanil over 30–60 seconds.1
Induction of anesthesia: Administer remifentanil as a continuous IV infusion.1 If intubation is to occur within 8 minutes after initiation of the infusion, an initial dose of the drug may be given over 30–60 seconds.1
Maintenance of anesthesia: Administer remifentanil as a continuous IV infusion.1 May administer rapid IV (bolus) doses every 2–5 minutes in response to light anesthesia or transient episodes of intense surgical stress.1
Analgesia in the immediate postoperative period: Administer as a continuous IV infusion.1 Infusion rates >0.2 mcg/kg per minute are associated with respiratory depression.1 Supplemental rapid IV (bolus) doses of remifentanil are not recommended because of risk for respiratory depression and muscle rigidity.1
Monitored anesthesia care: Administer prior to local or regional (nerve block) anesthesia as a single IV dose given over 30–60 seconds; alternatively, administer as a continuous IV infusion.1 Supplemental rapid IV (bolus) doses of remifentanil are not recommended because of risk for respiratory depression and muscle rigidity.1
Not recommended.1
| Infusion Rate (mL/kg per hour) | |||
|---|---|---|---|---|
Dosage (mcg/kg per minute) | 20 mcg/mL | 25 mcg/mL | 50 mcg/mL | 250 mcg/mL |
0.0125 | 0.038 | 0.03 | 0.015 | — |
0.025 | 0.075 | 0.06 | 0.03 | — |
0.05 | 0.15 | 0.12 | 0.06 | 0.012 |
0.075 | 0.23 | 0.18 | 0.09 | 0.018 |
0.1 | 0.3 | 0.24 | 0.12 | 0.024 |
0.15 | 0.45 | 0.36 | 0.18 | 0.036 |
0.2 | 0.6 | 0.48 | 0.24 | 0.048 |
0.25 | 0.75 | 0.6 | 0.3 | 0.06 |
0.5 | 1.5 | 1.2 | 0.6 | 0.12 |
0.75 | 2.25 | 1.8 | 0.9 | 0.18 |
1 | 3 | 2.4 | 1.2 | 0.24 |
1.25 | 3.75 | 3 | 1.5 | 0.3 |
1.5 | 4.5 | 3.6 | 1.8 | 0.36 |
1.75 | 5.25 | 4.2 | 2.1 | 0.42 |
2 | 6 | 4.8 | 2.4 | 0.48 |
Risk of muscle rigidity is related to the dose and rate of IV administration.1 11 Chest wall rigidity reported after single doses of >1 mcg/kg administered over 30–60 seconds, with infusion rates >0.1 mcg/kg per minute, or following single doses of <1 mcg/kg administered in conjunction with a continuous infusion of the drug.1 Supplemental doses of 0.5–1 mcg/kg and incremental increases in infusion rate of >0.05 mcg/kg per minute associated with transient and reversible muscle rigidity.1 Prior or simultaneous administration of propofol or thiopental or a neuromuscular blocking agent may attenuate the development of rigidity.1 For excessive rigidity, consider decreasing the infusion rate or discontinuing the infusion of remifentanil or administering a neuromuscular blocking agent or naloxone.1 (See Musculoskeletal Effects under Cautions.)
Doses of 0.5–1 mcg/kg administered in conjunction with a continuous infusion of the drug and incremental increases in infusion rate of >0.05 mcg/kg per minute are associated with transient and reversible respiratory depression and apnea.1 In spontaneously breathing patients, manage respiratory depression by reducing infusion rate of remifentanil by 50% or by temporarily discontinuing the infusion.1 (See Respiratory Depression under Cautions.)
Available as remifentanil hydrochloride; dosage expressed in terms of remifentanil.1
Synergistic activity with other anesthetics; dosage adjustment of concomitantly administered anesthetic(s) may be needed.1 3 (See Specific Drugs under Interactions.)
Manufacturer makes no specific recommendations regarding use or dosage of remifentanil in adolescents ≥13 years of age.1 41
In conjunction with 70% nitrous oxide: Initial remifentanil infusion rate of 0.4 mcg/kg per minute.1 Because neonatal clearance of remifentanil is variable and may average twice that observed in young adults, some neonates may require increased infusion rate to maintain adequate anesthesia; titrate dosage carefully according to individual requirements.1 Recommended infusion rate: 0.4–1 mcg/kg per minute.1
Rapid IV (bolus) doses of 1 mcg/kg could be administered every 2–5 minutes in response to signs of inadequate anesthesia in clinical trials in full-term neonates and infants up to 2 months of age with American Society of Anesthesiologists (ASA) physical status of I or II.1 16 30 Individualize dosage.1 Some neonates, including those receiving potent inhalation anesthetics or neuraxial anesthesia, those with substantial comorbidities or fluid shifts, and those who have not received atropine premedication, may require smaller bolus doses of remifentanil to avoid hypotension and/or bradycardia.1
In conjunction with nitrous oxide plus halothane (0.3–1.5 minimum alveolar concentration [MAC]), sevoflurane (0.3–1.5 MAC), or isoflurane (0.4–1.5 MAC): Remifentanil 0.25 mcg/kg per minute in patients with ASA physical status of I, II, or III.1 Adjust infusion rate upward by 50% or downward by 25–50% based on patient's response at intervals of 2–5 minutes.1 Recommended infusion rate: 0.05–1.3 mcg/kg per minute.1 May administer rapid IV (bolus) doses of 1 mcg/kg every 2–5 minutes in response to light anesthesia or transient episodes of intense surgical stress.1
An initial dose of 1 mcg/kg may be administered over 30–60 seconds.1 13
At remifentanil infusion rates >1 mcg/kg per minute, consider increases in dosage of concomitant anesthetic agent(s) to increase depth of anesthesia.1
Remifentanil 0.5–1 mcg/kg per minute given in conjunction with a volatile anesthetic or hypnotic agent in patients with ASA physical status of I, II, or III.1
If intubation is to occur within 8 minutes after initiation of the remifentanil infusion, an initial dose of 1 mcg/kg may be given over 30–60 seconds.1
In conjunction with 66% nitrous oxide: Remifentanil 0.4 mcg/kg per minute in patients with ASA physical status of I, II, or III.1 Adjust infusion rate upward by 25–100% or downward by 25–50% based on patient's response at intervals of 2–5 minutes.1 Recommended infusion rate: 0.1–2 mcg/kg per minute.1 May administer rapid IV (bolus) doses of 1 mcg/kg every 2–5 minutes in response to light anesthesia or transient episodes of intense surgical stress.1
In conjunction with isoflurane (0.4–1.5 MAC) or propofol (100–200 mcg/kg per minute): Remifentanil 0.25 mcg/kg per minute in patients with ASA physical status of I, II, or III.1 Adjust infusion rate upward by 25–100% or downward by 25–50% based on patient's response at intervals of 2–5 minutes.1 Recommended infusion rate: 0.05–2 mcg/kg per minute.1 May administer rapid IV (bolus) doses of 1 mcg/kg every 2–5 minutes in response to light anesthesia or transient episodes of intense surgical stress.1
At remifentanil infusion rates >1 mcg/kg per minute, consider increases in dosage of concomitant anesthetic agent(s) to increase depth of anesthesia.1
Initial postoperative infusion rate of 0.1 mcg/kg per minute in patients with ASA physical status of I, II, or III.1 Adjust infusion rate in increments of 0.025 mcg/kg per minute at 5-minute intervals based on level of analgesia and respiratory rate.1 Recommended infusion rate: 0.025–0.2 mcg/kg per minute.1
Supplemental rapid IV (bolus) doses of remifentanil are not recommended because of risk for respiratory depression and muscle rigidity.1
Infusion rates >0.2 mcg/kg per minute associated with respiratory depression.1
Remifentanil 1 mcg/kg per minute in patients with ASA physical status of III or IV.1 Excessive hypotension reported in clinical studies when dosage of concomitantly administered propofol exceeded 0.5 mg/kg over 1 minute followed by 10 mg every 10 seconds until loss of consciousness.1
As the analgesic component of a high-dose-opiate, balanced or IV anesthetic regimen, remifentanil 1 mcg/kg per minute in patients with ASA physical status of III or IV.1 Recommended infusion rate: 0.125–4 mcg/kg per minute.1 Supplemental rapid IV (bolus) doses of 0.5–1 mcg/kg may be administered.1 41
Remifentanil 1 mcg/kg per minute in patients with ASA physical status of III or IV.1 Recommended infusion rate: 0.05–1 mcg/kg per minute.1
Supplemental oxygen strongly recommended for patients receiving remifentanil for monitored anesthesia care.1
When used alone prior to local or regional anesthesia in patients with ASA physical status of I, II, or III, single remifentanil dose of 1 mcg/kg (over 30–60 seconds) administered 90 seconds before the local anesthetic.1 When used in this manner in conjunction with midazolam 2 mg, reduce remifentanil dose to 0.5 mcg/kg (over 30–60 seconds).1
When used alone in patients with ASA physical status of I, II, or III, remifentanil 0.1 mcg/kg per minute, beginning 5 minutes before the local anesthetic.1 Because of risk of respiratory depression, reduce infusion rate to 0.05 mcg/kg per minute following nerve block placement.1 Adjust subsequent infusion rate in increments of 0.025 mcg/kg per minute at 5-minute intervals based on level of analgesia and respiratory rate.1 Recommended infusion rate: 0.025–0.2 mcg/kg per minute.1
When used in conjunction with midazolam 2 mg, remifentanil 0.05 mcg/kg per minute, beginning 5 minutes before the local anesthetic.1 Because of risk of respiratory depression, reduce infusion rate to 0.025 mcg/kg per minute following nerve block placement.1 Adjust subsequent infusion rate in increments of 0.025 mcg/kg per minute at 5-minute intervals based on level of analgesia and respiratory rate.1 Recommended infusion rate: 0.025–0.2 mcg/kg per minute.1
Infusion rates >0.2 mcg/kg per minute associated with respiratory depression.1
Administration of rapid IV (bolus) doses of remifentanil concomitantly with a continuous infusion of the drug in spontaneously breathing patients is not recommended.1 11
Decrease initial and, possibly, subsequent doses of remifentanil by 50% in patients >65 years of age; titrate cautiously.1 2 9 12 (See Geriatric Use under Cautions.)
Consider extending anticipated time to clinical effect by 50–100% in geriatric patients.9 (See Absorption: Special Populations under Pharmacokinetics.)
Base initial dosage on an estimate of ideal (lean) body weight if body weight exceeds ideal weight by >30%.1 Base subsequent dosage reductions on an estimate of ideal body weight.2 9 12
Contains glycine; contraindicated for epidural or intrathecal administration.1 2 3 9
Known hypersensitivity to fentanyl analogs.1
Shares the toxic potentials of the opiate agonists; observe the usual precautions of opiate agonist therapy.1 2 3
Remifentanil should only be administered by persons trained in the use of anesthetic drugs and the management of respiratory effects of opiates, including respiratory and cardiac resuscitation.1 Such training must include the establishment and maintenance of a patent airway and assisted ventilation.1
Do not use for diagnostic or therapeutic procedures outside a monitored anesthesia care setting.1 Patients receiving the drug for monitored anesthesia care should be continuously monitored by persons not involved in the conduct of the surgical or diagnostic procedure.1
Monitor oxygen saturation continuously and have resuscitative and intubation equipment, oxygen, and an opiate antagonist readily available.1
Clear remifentanil from the IV tubing upon drug discontinuance; failure to remove residual remifentanil associated with respiratory depression, apnea, and muscle rigidity upon administration of fluids or drugs through the same tubing.1
Apnea and dose-dependent respiratory depression reported with remifentanil.1 2 3 9 11 Remifentanil infusion rates of 0.05–0.1 mcg/kg per minute are associated with minimal decreases in respiratory rate; doses of 0.5–1 mcg/kg administered in conjunction with a continuous IV infusion of the drug, incremental increases in infusion rate of >0.05 mcg/kg per minute, and plasma concentrations >5 ng/mL are associated with transient and reversible respiratory depression and apnea.1 Peak respiratory depression after rapid IV (bolus) doses generally occurs within 2.5–5 minutes.2 8 11
Respiratory depression may occur up to 30 minutes after discontinuance of remifentanil infusion secondary to residual effects of concomitant anesthetics.1 Monitor patients in postoperative period to ensure adequate recovery without stimulation.1 To date, no reported cases of remifentanil-induced delayed respiratory depression occurring >30 minutes after drug discontinuance.1
Recovery of respiratory drive after a 3-hour infusion was faster and less variable with remifentanil than with alfentanil (when dosed to produce equal levels of respiratory depression). 1
Manage respiratory depression in spontaneously breathing patients by reducing infusion rate of remifentanil by 50% or by temporarily discontinuing the infusion.1 Spontaneous respiration occurs at plasma remifentanil concentrations of 4–5 ng/mL in the absence of other anesthetic agents.1 In patients undergoing general anesthesia, rate of respiratory recovery is dependent upon concomitant anesthetics.1 (See Duration under Pharmacokinetics.)
Supplemental oxygen strongly recommended for patients receiving remifentanil for monitored anesthesia care.1
Dose-dependent muscle rigidity, particularly involving respiratory muscles.1 Chest wall rigidity may occur following single remifentanil doses of >1 mcg/kg given over 30–60 seconds, with infusion rates of >0.1 mcg/kg per minute, or following single doses of <1 mcg/kg administered in conjunction with a continuous infusion of the drug.1 Peripheral rigidity may occur at lower doses.1 Supplemental doses of 0.5–1 mcg/kg, incremental increases in infusion rate of >0.05 mcg/kg per minute, and plasma concentrations >5 ng/mL are associated with transient and reversible muscle rigidity.1
To manage rigidity occurring during anesthesia induction, administer a neuromuscular blocking agent prior to or simultaneously with the induction regimen.1 Administration of an induction dose of propofol or thiopental or a paralyzing dose of a muscle relaxant prior to or simultaneously with remifentanil during anesthesia induction decreased incidence of muscle rigidity from 20% to <1% in clinical studies.1
To treat rigidity in spontaneously breathing patients, decrease remifentanil infusion rate or discontinue the drug; resolution of rigidity evident within minutes after infusion discontinuance.1 For life-threatening rigidity, administer rapid-onset neuromuscular blocking agent or naloxone.1
Monitor vital signs and oxygenation continuously during remifentanil administration.1
Dose-dependent bradycardia and hypotension reported in premedicated patients who received remifentanil doses of <2 mcg/kg over 1 minute.1 Additional doses of >2 mcg/kg (up to 30 mcg/kg) did not produce further decreases in heart rate or BP.1 Duration of hemodynamic change directly proportional to plasma concentrations of the drug, with peak hemodynamic effects occurring within 3–5 minutes after a single remifentanil dose or infusion rate increase.1
Bradycardia responsive to ephedrine or antimuscarinic agents (e.g., atropine, glycopyrrolate).1 Hypotension responsive to decreases in rate of administration of remifentanil or concomitant anesthetics, administration of IV fluids, or catecholamines (e.g., ephedrine, epinephrine, norepinephrine).1 (See Elimination: Special Populations, under Pharmacokinetics.)
Intraoperative awareness reported in patients <55 years of age when remifentanil administered with propofol (≤75 mcg/kg per minute).1
Because of rapid offset of action (within 5–10 minutes) after drug discontinuance, patients undergoing surgical procedures should receive other analgesics prior to remifentanil discontinuance.1 3
Do not use remifentanil as the sole agent for induction of anesthesia since loss of consciousness cannot be ensured and a high incidence of apnea, muscle rigidity, or tachycardia is possible.1 3
Use remifentanil with caution in morbidly obese individuals since alterations in cardiovascular and respiratory physiology may be present.1
Category C.1
Safety of remifentanil during labor or delivery not established to date.1 Respiratory depression and other opiate effects may occur in neonates whose mothers are given remifentanil shortly prior to delivery.1
Not known whether remifentanil is distributed into human milk.1 However, other fentanyl analogs distribute into human milk.1 Caution if used in nursing women.1
Safety and efficacy of remifentanil for use in the maintenance phase of general anesthesia in outpatient and inpatient surgery have been established in pediatric patients from birth to 12 years of age.1
Safety and efficacy of remifentanil as an analgesic in the immediate postoperative period or as an analgesic component of monitored anesthesia care have not been established in pediatric patients.1
Geriatric patients may be twice as sensitive to the pharmacodynamic effects of remifentanil compared with young adults; monitor carefully.1 3 9 Adjust dosage accordingly.1 2 9 12 (See Geriatric Patients under Dosage and Administration.)
Geriatric patients may exhibit reduced clearance of remifentanil;1 2 9 12 however, half-life is unchanged, and plasma concentrations decline as rapidly after drug discontinuance as in young adults.1 (See Elimination: Special Populations, under Pharmacokinetics.)
Pharmacodynamics (ventilatory response to hypercarbia) of remifentanil are unaltered in patients with severe hepatic impairment awaiting liver transplantation.1
Pharmacokinetics of remifentanil and its metabolite are unaltered in the presence of hepatic impairment.1 2 3 12
Pharmacodynamics (ventilatory response to hypercarbia) of remifentanil are unaltered in patients with end-stage renal disease.1
Pharmacokinetics of remifentanil are unaltered in the presence of renal impairment, including end-stage renal disease.1 2 12 (See Elimination: Special Populations, under Pharmacokinetics.)
Respiratory depression,1 9 10 11 bradycardia,1 2 9 10 11 12 hypotension,1 2 9 10 11 12 skeletal muscle rigidity,1 2 9 10 11 12 nausea,1 2 9 11 12 vomiting,1 2 9 11 12 pruritus,1 9 headache,1 shivering,1 2 11 12 dizziness.1
Drug | Interaction | Comments |
|---|---|---|
Anesthetics (e.g., isoflurane, propofol, thiopental) | Synergistic effect when administered concomitantly with remifentanil1 2 3 12 Clearance of remifentanil unaltered by thiopental, isoflurane, or propofol1 Propofol or thiopental may attenuate development of remifentanil-associated muscle rigidity1 | May need to reduce dosage of anesthetic by up to 75%1 3 |
Antimuscarinics (atropine, glycopyrrolate) | May blunt the potential for remifentanil-associated bradycardia1 3 | |
Cholinesterase inhibitors | Remifentanil hydrolysis was not inhibited by neostigmine or physostigmine in vitro1 9 | |
Esmolol | Remifentanil hydrolysis was not inhibited by esmolol in vitro1 Esmolol metabolism was not altered by remifentanil9 | |
Midazolam | Synergistic effect when administered concomitantly with remifentanil1 2 3 9 Remifentanil hydrolysis was not inhibited by midazolam in vitro1 | May need to reduce midazolam dosage by up to 75%1 |
Neuromuscular blocking agents | May attenuate development of remifentanil-associated muscle rigidity1 Remifentanil hydrolysis was not inhibited by atracurium or mivacurium in vitro1 Succinylcholine metabolism was not altered by remifentanil 9 | |
Temazepam | Clearance of remifentanil unaltered by temazepam1 |
Rapid onset of action (within 1–1.5 minutes) and peak analgesic effect (within 1–3 minutes).1 2 4 8 9 10 12 Remifentanil has a faster onset of action than fentanyl or sufentanil.8 9
Short duration of action.1 2 3 4 Remifentanil has a shorter duration of action than alfentanil or fentanyl.10
Recovery is rapid (within 3–15 minutes), predictable, and independent of duration of infusion.1 2 8 10 12 Remifentanil does not accumulate during prolonged administration; therefore, its duration of action (unlike that of other fentanyl analogs) does not increase proportionally with duration of administration.1 8
In full-term neonates and infants <8 weeks of age receiving maintenance anesthesia with remifentanil (0.4–1 mcg/kg per minute) and nitrous oxide, median times to spontaneous purposeful movement and extubation were 6.5 (range: 1–13) and 8.5 (range: 1–14) minutes, respectively.1 16
In patients undergoing general surgery and receiving remifentanil as a component of anesthesia, extubation occurred in a median time of 5 (range: -3–17) and 10 (range: 0–32) minutes in outpatients and inpatients, respectively.1 2 Recovery was faster when used in conjunction with nitrous oxide and propofol than when used in conjunction with isoflurane.1 In those receiving maintenance anesthesia with remifentanil (0.2–0.5 mcg/kg per minute) in conjunction with isoflurane, enflurane, or propofol, with or without nitrous oxide, median or mean times to spontaneous ventilation were 2–11 or 6–8 minutes, respectively.2 21 22 23 24 25 26 27 28 29 In patients receiving maintenance anesthesia with remifentanil (0.2–0.4 mcg/kg per minute) in conjunction with isoflurane or propofol, with or without nitrous oxide, median time to respond to verbal commands was 5–15 minutes.2 21 22 25 26 27 28 29
In patients undergoing neurosurgery and receiving maintenance anesthesia with remifentanil (0.2–0.25 mcg/kg per minute) in conjunction with IV (propofol) and/or inhalation anesthetics (isoflurane, nitrous oxide), median time to respond to verbal commands and median time to extubation were 5–13 and 5–11 minutes, respectively.1 2 17 18 19
Exhibits a linear, dose-dependent pharmacokinetic profile.2 9 12 Plasma concentration of drug directly correlates with patient response and decreases 50% in 3–6 minutes after a 1-minute infusion or after prolonged continuous infusion (due to rapid distribution and elimination) and is independent of duration of drug administration.1 2 3 4 9 11 12
New steady-state concentrations evident within 5–10 minutes after change in infusion rate.1 Increasing or decreasing the infusion rate by 0.1 mcg/kg per minute generally produces a 2- to 2.5-ng/mL change in plasma remifentanil concentrations within 5–10 minutes.1 A new, higher steady-state concentration may be achieved more rapidly (within 3–5 minutes) in intubated patients if 1 mcg/kg of remifentanil is given by rapid IV (bolus) injection in conjunction with an infusion rate increase.1
In patients with end-stage renal disease, recovery times appear to be similar to those in patients with normal renal function.2
In obese patients undergoing outpatient surgery, mean recovery and extubation times after maintenance anesthesia with remifentanil (0.05–2 mcg/kg per minute) in conjunction with sevoflurane and nitrous oxide were 6 and 7 minutes, respectively.2 20
In children 2–12 years of age receiving maintenance anesthesia with remifentanil (0.2–1.95 mcg/kg per minute) in conjunction with nitrous oxide or with nitrous oxide and either halothane or sevoflurane, times to spontaneous purposeful movement and extubation were 1–24 minutes.1 13 14 In children 1–12 years of age receiving maintenance anesthesia with remifentanil (up to 0.75 mcg/kg per minute) in conjunction with nitrous oxide and isoflurane, median times to spontaneous purposeful movement and extubation were 15 (range: 2–75) and 13 (range: 4–31) minutes, respectively.1 15
Onset of action may be delayed in geriatric patients compared with younger individuals.9
Faster recovery times reported for patients <60 years of age compared with those >60 years of age receiving remifentanil in conjunction with propofol; mean time to spontaneous respiration was 0.8 versus 3.2 minutes, respectively, and mean time to extubation was 5 versus 9 minutes, respectively.2
Rapidly distributed throughout blood and highly perfused tissues; subsequently distributed into peripheral tissues; unlike other opiate agonists, remifentanil does not accumulate at high doses or with prolonged administration.1 2 3 11 12
Rapidly equilibrates across blood-brain barrier.1 2 9 12
Crosses placenta;2 9 12 average maternal remifentanil concentrations are about twice those observed in fetus.1
70–92% (primarily α1-acid glycoprotein).1 2 8 9 12
Distribution volumes generally correlate with total body weight; however, in markedly obese patients, distribution volume correlates better with ideal body weight.1 2
Distribution volume is increased in younger children and declines to young healthy adult values by 17 years of age.1
Rapidly and extensively (>95%) hydrolyzed at the propanoic acid-methyl ester linkage by nonspecific esterases in blood and tissues, resulting in formation of an inactive carboxylic acid metabolite; undergoes N-dealkylation to a lesser extent.1 2 3 4 8 9 10 12 Remifentanil is not metabolized by plasma cholinesterase and is not appreciably metabolized in the liver or lungs.1 2 3
Rapidly eliminated; ≥88% of dose eliminated in urine as carboxylic acid metabolite.1 2 3 9 11
