Glustar

Glustar may be available in the countries listed below.

Ingredient matches for Glustar

Atorvastatin

Atorvastatin is reported as an ingredient of Glustar in the following countries:

• Colombia


• Venezuela

International Drug Name Search

tobramycin ophthalmic

Generic Name: tobramycin ophthalmic (TOE bra MYE sin off THAL mik)

Brand names: Aktob, Tobralcon, Tobrasol, Tobrex, Tomycine

What is tobramycin ophthalmic?

Tobramycin ophthalmic is an antibiotic.

Tobramycin ophthalmic is used to treat bacterial infections of the eyes.

Tobramycin ophthalmic may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about tobramycin ophthalmic?

Do not touch the dropper or tube opening to any surface, including your eyes or hands. The dropper or tube opening is sterile. If it becomes contaminated, it could cause an infection in the eye.

Apply light pressure to the inside corner of your eye (near your nose) after each drop to prevent the fluid from draining down the tear ducts.

What should I discuss with my healthcare provider before using tobramycin ophthalmic?

Do not use tobramycin ophthalmic if you have a viral or fungal infection in the eye. It is used to treat infections caused by bacteria only. Tobramycin ophthalmic is in the FDA pregnancy category B. This means that it is unlikely to be harmful to an unborn baby. Do not use tobramycin ophthalmic without first talking to your doctor if you are pregnant. It is not known whether tobramycin ophthalmic passes into breast milk. Do not use tobramycin ophthalmic without first talking to your doctor if you are breast-feeding a baby.

How should I use tobramycin ophthalmic?

Use tobramycin ophthalmic eyedrops or ointment exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Wash your hands before using your eyedrops or ointment.

To apply the eyedrops:

• 
  

  Shake the drops gently to be sure the medicine is well mixed. Tilt your head back slightly and pull down on your lower eyelid. Position the dropper above your eye. Look up and away from the dropper. Squeeze out a drop and close your eye. Apply gentle pressure to the inside corner of your eye (near your nose) for about 1 minute to prevent the liquid from draining down your tear duct. If you are using more than one drop in the same eye, repeat the process with about 5 minutes between drops. If you are using drops in both eyes, repeat the process in the other eye.

  
  

To apply the ointment:

• 
  

  Hold the tube in your hand for a few minutes to warm it up so that the ointment comes out easily. Tilt your head back slightly and pull down gently on your lower eyelid. Apply a thin film of the ointment into your lower eyelid. Close your eye and roll your eyeball around in all directions for 1 to 2 minutes. If you are applying another eye medication, allow at least 10 minutes before applying the other medication.

  
  

Do not touch the dropper or tube opening to any surface, including your eyes or hands. The dropper or tube opening is sterile. If it becomes contaminated, it could cause an infection in the eye. Do not use any eyedrop that is discolored or has particles in it. Store tobramycin ophthalmic at room temperature away from moisture and heat. Keep the bottle or tube properly capped.

What happens if I miss a dose?

Apply the missed dose as soon as you remember. However, if it is almost time for the next regularly scheduled dose, skip the missed dose and apply the next one as directed. Do not use a double dose of this medication.

What happens if I overdose?

An overdose of this medication is unlikely to occur. If you do suspect an overdose or if the medication has been ingested, call an emergency room or poison control center for advice.

What should I avoid while using tobramycin ophthalmic?

Do not touch the dropper or tube opening to any surface, including your eyes or hands. The dropper or tube opening is sterile. If it becomes contaminated, it could cause an infection in the eye. Use caution when driving, operating machinery, or performing other hazardous activities. Tobramycin ophthalmic may cause blurred vision. If you experience blurred vision, avoid these activities.

If you wear contact lenses, ask your doctor if you should wear them during treatment with tobramycin ophthalmic. After applying the medication, wait at least 15 minutes before inserting contact lenses, unless otherwise directed by your doctor.

Do not use other eye drops or medications during treatment with tobramycin ophthalmic unless otherwise directed by your doctor.

Tobramycin ophthalmic side effects

Serious side effects are not expected with this medication.

Commonly, some eye burning, stinging, irritation, itching, redness, blurred vision, eyelid itching, eyelid swelling, or sensitivity to light may occur.

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 other drugs will affect tobramycin ophthalmic?

Do not use other eye drops or medications during treatment with tobramycin ophthalmic unless otherwise directed by your doctor.

Drugs other than those listed here may also interact with tobramycin ophthalmic. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products.

More tobramycin ophthalmic resources

• Tobramycin ophthalmic Use in Pregnancy & Breastfeeding
• Tobramycin ophthalmic Support Group
• 3 Reviews for Tobramycin - Add your own review/rating

• AKTob Advanced Consumer (Micromedex) - Includes Dosage Information


• Tobrex Prescribing Information (FDA)


• Tobrex Drops MedFacts Consumer Leaflet (Wolters Kluwer)

Compare tobramycin ophthalmic with other medications

• Conjunctivitis, Bacterial

Where can I get more information?

• Your pharmacist has additional information about tobramycin ophthalmic written for health professionals that you may read.

Naproxene-Eurogenerics

Naproxene-Eurogenerics may be available in the countries listed below.

Ingredient matches for Naproxene-Eurogenerics

Naproxen

Naproxen is reported as an ingredient of Naproxene-Eurogenerics in the following countries:

• Luxembourg

International Drug Name Search

RabAvert

rabies vaccine

Dosage Form: injection, powder, lyophilized, for suspension
RabAvert®

Rabies Vaccine

Rabies Vaccine for Human Use

Description

RabAvert, Rabies Vaccine, produced by Novartis Vaccines and Diagnostics GmbH & Co. KG is a sterile freeze-dried vaccine obtained by growing the fixed-virus strain Flury LEP in primary cultures of chicken fibroblasts. The strain Flury LEP was obtained from American Type Culture Collection as the 59th egg passage. The growth medium for propagation of the virus is a synthetic cell culture medium with the addition of human albumin, polygeline (processed bovine gelatin) and antibiotics. The virus is inactivated with β-propiolactone, and further processed by zonal centrifugation in a sucrose density-gradient. The vaccine is lyophilized after addition of a stabilizer solution which consists of buffered polygeline and potassium glutamate. One dose of reconstituted vaccine contains less than 12 mg polygeline (processed bovine gelatin), less than 0.3 mg human serum albumin, 1 mg potassium glutamate and 0.3 mg sodium EDTA. Small quantities of bovine serum are used in the cell culture process. Bovine components originate only from the United States, Australia and New Zealand. Minimal amounts of chicken protein may be present in the final product; ovalbumin content is less than 3 ng/dose (1 mL), based on ELISA. Antibiotics (neomycin, chlortetracycline, amphotericin B) added during cell and virus propagation are largely removed during subsequent steps in the manufacturing process. In the final vaccine, neomycin is present at < 1 μg, chlortetracycline at < 20 ng, and amphotericin B at < 2 ng per dose. RabAvert is intended for intramuscular (IM) injection. The vaccine contains no preservative and should be used immediately after reconstitution with the supplied Sterile Diluent for RabAvert (Water For Injection). The potency of the final product is determined by the NIH mouse potency test using the US reference standard. The potency of one dose (1.0 mL) RabAvert is at least 2.5 IU of rabies antigen. RabAvert is a white, freeze-dried vaccine for reconstitution with the diluent prior to use; the reconstituted vaccine is a clear to slightly opaque, colorless suspension.

Clinical Pharmacology

Rabies in the United States

Over the last 100 years, the epidemiology of rabies in animals in the United States has changed dramatically. More than 90% of all animal rabies cases reported annually to the Centers for Disease Control and Prevention (CDC) now occur in wildlife, whereas before 1960 the majority were in domestic animals. The principal rabies hosts today are wild terrestrial carnivores and bats. Annual human deaths have fallen from more than a hundred at the turn of the century to one to two per year despite major epizootics of animal rabies in several geographic areas. Within the United States, only Hawaii has remained rabies free. Although rabies among humans is rare in the United States, every year tens of thousands of people receive rabies vaccine for postexposure prophylaxis.

Rabies is a viral infection transmitted via the saliva of infected mammals. The virus enters the central nervous system of the host, causing an encephalomyelitis that is almost invariably fatal. The incubation period varies between 5 days and several years, but is usually between 20 and 60 days. Clinical rabies presents either in a furious or in a paralytic form. Clinical illness most often starts with prodromal complaints of malaise, anorexia, fatigue, headache, and fever followed by pain or paresthesia at the site of exposure. Anxiety, agitation, irritability may be prominent during this period, followed by hyperactivity, disorientation, seizures, aero- and hydrophobia, hypersalivation, and eventually paralysis, coma and death.

Modern day prophylaxis has proven nearly 100% successful; most human fatalities now occur in people who fail to seek medical treatment, usually because they do not recognize a risk in the animal contact leading to the infection. Inappropriate postexposure prophylaxis may also result in clinical rabies. Survival after clinical rabies is extremely rare, and is associated with severe brain damage and permanent disability.

RabAvert (in combination with passive immunization with Human Rabies Immune Globulin [HRIG] and local wound treatment) in postexposure treatment against rabies has been shown to protect patients of all age groups from rabies, when the vaccine was administered according to the CDC's Advisory Committee on Immunization Practices (ACIP) or World Health Organization (WHO) guidelines and as soon as possible after rabid animal contact. Anti-rabies antibody titers after immunization have been shown to reach levels well above the minimum antibody titer accepted as seroconversion (protective titer) within 14 days after initiating the postexposure treatment series. The minimum antibody titer accepted as seroconversion is a 1:5 titer (complete inhibition in the rapid fluorescent focus inhibition test [RFFIT] at 1:5 dilution) as specified by the CDC (1), or ≥ 0.5 IU per milliliter (mL) as specified by the WHO (2,3).

Clinical Studies

Preexposure Vaccination

The immunogenicity of RabAvert has been demonstrated in clinical trials conducted in different countries such as the USA (4,5), UK (6), Croatia (7), and Thailand (8-10). When administered according to the recommended immunization schedule (days 0, 7, 21 or 0, 7, 28), 100% of subjects attained a protective titer. In two studies carried out in the USA in 101 subjects, antibody titers > 0.5 IU/mL were obtained by day 28 in all subjects. In studies carried out in Thailand in 22 subjects, and in Croatia in 25 subjects, antibody titers of > 0.5 IU/mL were obtained by day 14 (injections on days 0, 7, 21) in all subjects.

The ability of RabAvert to boost previously immunized subjects was evaluated in three clinical trials. In the Thailand study, preexposure booster doses were administered to 10 individuals. Antibody titers of > 0.5 IU/mL were present at baseline on day 0 in all subjects (9). Titers after a booster dose were enhanced from geometric mean titers (GMT) of 1.91 IU/mL to 23.66 IU/mL on day 30. In an additional booster study, individuals known to have been immunized with Human Diploid Cell Vaccine (HDCV) were boosted with RabAvert. In this study, a booster response was observed on day 14 for all (22/22) individuals (11). In a trial carried out in the USA (4), a RabAvert IM booster dose resulted in a significant increase in titers in all (35/35) subjects, regardless of whether they had received RabAvert or HDCV as the primary vaccine.

Persistence of antibody after immunization with RabAvert has been evaluated. In a trial performed in the UK, neutralizing antibody titers > 0.5 IU/mL were present 2 years after immunization in all sera (6/6) tested.

Preexposure Vaccination in Children

Preexposure administration of RabAvert in 11 Thai children from the age of 2 years and older resulted in antibody levels higher than 0.5 IU/mL on day 14 in all children (12).

Postexposure Treatment

RabAvert, when used in the recommended postexposure WHO program of 5 to 6 IM injections of 1 mL (days 0, 3, 7, 14, 30, and one optionally on day 90) provided protective titers of neutralizing antibody (> 0.5 IU/mL) in 158/160 patients (8, 9, 13-16) within 14 days and in 215/216 patients by day 28 - 38.

Of these, 203 were followed for at least 10 months. No case of rabies was observed (8, 9, 13-20). Some patients received Human Rabies Immune Globulin (HRIG), 20 - 30 IU per kg body weight, or Equine Rabies Immune Globulin (ERIG), 40 IU per kg body weight, at the time of the first dose. In most studies (8, 9, 13, 17), the addition of either HRIG or ERIG caused a slight decrease in GMTs which was neither clinically relevant nor statistically significant. In one study (16), patients receiving HRIG had significantly lower (p < 0.05) GMTs on day 14; however, again this was not clinically relevant. After day 14 there was no statistical significance.

The results of several studies of normal volunteers receiving the postexposure WHO regimen, i.e., "simulated" postexposure, show that with sampling by day 28 - 30, 205/208 vaccinees had protective titers > 0.5 IU/mL.

No postexposure vaccine failures have occurred in the United States since cell culture vaccines have been routinely used (1). Failures have occurred abroad, almost always after deviation from the recommended postexposure treatment protocol (21-24). In two cases with bites to the face, treatment failed although no deviation from the recommended postexposure treatment protocol appeared to have occurred (25).

Postexposure Treatment in Children

In a 10-year serosurveillance study, RabAvert has been administered to 91 children aged 1 to 5 years and 436 children and adolescents aged 6 to 20 years (19). The vaccine was effective in both age groups. None of these patients developed rabies.

One newborn has received RabAvert on an immunization schedule of days 0, 3, 7, 14 and 30; the antibody concentration on day 37 was 2.34 IU/mL. There were no clinically significant adverse events (26).

Indications and Usage

RabAvert is indicated for preexposure vaccination, in both primary series and booster dose, and for postexposure prophylaxis against rabies in all age groups.

Usually, an immunization series is initiated and completed with one vaccine product. No clinical studies have been conducted that document a change in efficacy or the frequency of adverse reactions when the series is completed with a second vaccine product. However, for booster immunization, RabAvert was shown to elicit protective antibody level responses in persons tested who received a primary series with HDCV (4,11).

A. Preexposure Vaccination - See Table 1

(see also Dosage and Administration section below)

Preexposure vaccination consists of three doses of RabAvert 1.0 mL, intramuscularly (deltoid region), one each on days 0, 7, and 21 or 28 (1) (see also Table 1 for criteria for preexposure vaccination).

Preexposure vaccination does not eliminate the need for additional therapy after a known rabies exposure (see also Dosage and Administration section, subsection C).

Preexposure vaccination should be offered to persons in high-risk groups, such as veterinarians, animal handlers, wildlife officers in areas where animal rabies is enzootic, certain laboratory workers, and persons spending time in foreign countries where rabies is endemic. Persons whose activities bring them into contact with potentially rabid dogs, cats, foxes, skunks, bats, or other species at risk of having rabies should also be considered for preexposure vaccination. International travelers might be candidates for preexposure vaccination if they are likely to come in contact with animals in areas where dog rabies is enzootic and immediate access to appropriate medical care, including biologics, might be limited (27, 28)

Preexposure vaccination is given for several reasons. First, it may provide protection to persons with inapparent exposure to rabies. Second, it may protect persons whose postexposure therapy might be expected to be delayed. Finally, although it does not eliminate the need for prompt therapy after a rabies exposure, it simplifies therapy by eliminating the need for globulin and decreasing the number of doses of vaccine needed. This is of particular importance for persons at high risk of being exposed in countries where the available rabies immunizing products may carry a higher risk of adverse reactions.

In some instances, booster doses of vaccine should be administered to maintain a serum titer corresponding to at least complete neutralization at a 1:5 serum dilution by the RFFIT (see Table 1); each booster immunization consists of a single dose. See Clinical Pharmacology. Serum antibody determinations to decide upon the need for a booster dose is suggested by the ACIP and is considered cost-effective.

Table 1: Rabies Preexposure prophylaxis guide – United States, 1999

Adapted from the Recommendations of the Advisory Committee on Immunization Practices: Human Rabies Prevention – United States, 1999. (1)
* Judgment of relative risk and extra monitoring of vaccination status of laboratory workers is the responsibility of the laboratory supervisor (29).
** Minimum acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by RFFIT. A booster dose should be administered if the titer falls below this level.
Risk Category and Nature of Risk	Typical Populations	Preexposure Recommendations
Continuous. Virus present continuously, often in high concentrations. Specific exposures likely to go unrecognized. Bite, nonbite or aerosol exposure.	Rabies research lab workers,* rabies biologics production workers.	Primary course. Serologic testing every 6 months; booster vaccination if antibody titer is below acceptable level.*
Frequent. Exposure usually episodic, with source recognized, but exposure might be unrecognized. Bite, nonbite or aerosol exposure.	Rabies diagnostic lab workers,* spelunkers, veterinarians and staff, and animal-control and wildlife workers in rabies enzootic areas.	Primary course. Serologic testing every 2 years; booster vaccination if antibody titer is below acceptable level.**
Infrequent (greater than population-at-large). Exposure nearly always episodic with source recognized. Bite or nonbite exposure.	Veterinarians and animal- control and wildlife workers in areas with low rabies rates. Veterinary students. Travelers visiting areas where rabies in enzootic and immediate access to appropriate medical care including biologics is limited.	Primary course. No serologic testing or booster vaccination.**
Rare (population-at-large). Exposures always episodic. with source recognized. Bite or nonbite exposure.	US population-at-large, including persons in rabies-epizootic areas.	No vaccination necessary.

B. Postexposure Treatment - See Table 2

(see also Dosage and Administration section below)

The following recommendations are only a guide. In applying them, take into account the animal species involved, the circumstances of the bite or other exposure, the immunization status of the animal, and presence of rabies in the region (as outlined below). Local or state public health officials should be consulted if questions arise about the need for rabies prophylaxis (1).

TABLE 2: RABIES POSTEXPOSURE PROPHYLAXIS GUIDE – UNITED STATES, 1999

Adapted from the Recommendations of the Advisory Committee on Immunization Practices: Human Rabies Prevention – United States, 1999. (1)
* During the 10-day observation period, begin postexposure prophylaxis at the first sign of rabies in a dog, cat or ferret that has bitten someone. If the animal exhibits clinical signs of rabies, it should be euthanized immediately and tested.
** The animal should be euthanized and tested as soon as possible. Holding for observation is not recommended. Discontinue vaccine if immunofluorescence test results of the animal are negative.
Animal type	Evaluation and disposition of animal	Postexposure prophylaxis recommendations
Dogs, cats and ferrets	Healthy and available for 10 days observation Rabid or suspected rabid Unknown (e.g., escaped)	Should not begin prophylaxis unless animal develops clinical signs of rabies* Immediately vaccinate Consult public health officials
Skunks, raccoons, bats, foxes, and most other carnivores	Regarded as rabid unless animal proven negative by laboratory tests**	Consider immediate vaccination
Livestock, small rodents, lagomorphs (rabbits and hares), large rodents (woodchucks and beavers), and other mammals	Consider individually	Consult public health officials. Bites of squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other small rodents, rabbits, and hares almost never require antirabies postexposure prophylaxis

In the United States, the following factors should be considered before antirabies treatment is initiated.

Species of Biting Animal

Wild terrestrial animals (especially skunks, raccoons, foxes and coyotes) and bats are the animals most commonly infected with rabies and are the most important potential source of infection for both humans and domestic animals. Unless a wild animal is tested and shown not to be rabid, postexposure prophylaxis should be initiated upon bite or nonbite exposure to the animals (see definition in "Type of Exposure" below). If treatment has been initiated and subsequent testing in a qualified laboratory shows the exposing animal is not rabid, postexposure prophylaxis can be discontinued (1).

The likelihood of rabies in a domestic animal varies from region to region; hence the need for postexposure prophylaxis also varies (1).

Small rodents (such as squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) and lagomorphs (including rabbits and hares) are almost never found to be infected with rabies and have not been known to transmit rabies to humans in the United States. Bites from large rodents such as woodchucks (including groundhogs) and beavers, should be considered as possible rabies exposures, especially in regions where rabies is enzootic in raccoons (30). In all cases involving rodents, the state or local health department should be consulted before a decision is made to initiate antirabies postexposure prophylaxis (1).

Circumstances of Biting Incident

An UNPROVOKED attack is more likely than a provoked attack to indicate the animal is rabid. Bites inflicted on a person attempting to feed or handle an apparently healthy animal should generally be regarded as PROVOKED. A currently vaccinated dog, cat or ferret is unlikely to become infected with rabies (1).

Type of Exposure

Rabies is transmitted by introducing the virus into open cuts or wounds in skin or via mucous membranes. The likelihood of rabies infection varies with the nature and extent of exposure. Two categories of exposure should be considered:

Bite: Any penetration of the skin by teeth. Bites to highly innervated areas such as the face and hands carry the highest risk, but the site of the bite should not influence the decision to begin treatment. Recent epidemiologic data suggest that even the very limited injury inflicted by a bat bite (compared to lesions caused by terrestrial carnivores) should prompt consideration of postexposure prophylaxis unless the bat is available for testing and is negative for evidence of rabies (1).

Nonbite: The contamination of open wounds, abrasions, mucous membranes, or theoretically, scratches, with saliva or other potentially infectious material (such as neural tissue) from a rabid animal constitutes a nonbite exposure. In all instances of potential human exposures involving bats, and the bat is not available for testing, postexposure prophylaxis might be appropriate even if a bite, scratch or mucous membrane exposure is not apparent when there is reasonable probability that such exposure might have occurred. Postexposure prophylaxis can be considered for persons who were in the same room as the bat and who might be unaware that a bite or direct contact had occurred (e.g., a sleeping person awakens to find a bat in the room or an adult witnesses a bat in the room with a previously unattended child, mentally disabled person, or intoxicated person) and rabies cannot be ruled out by testing the bat. Other contact by itself, such as petting a rabid animal and contact with blood, urine, or feces (e.g., guano) of a rabid animal, does not constitute an exposure and is not an indication for prophylaxis. Because the rabies virus is inactivated by desiccation and ultraviolet irradiation, in general, if the material containing the virus is dry, the virus can be considered noninfectious. Two cases of rabies have been attributed to probable aerosol exposures in laboratories, and two cases of rabies in Texas could possibly have been due to airborne exposures in caves containing millions of bats (1).

The only documented cases for rabies from human-to-human transmission occurred in eight patients, including two in the USA, who received corneas transplanted from persons who died of rabies undiagnosed at the time of death (1). Stringent guidelines for acceptance of donor corneas have been implemented to reduce this risk.

Bite and nonbite exposure from humans with rabies theoretically could transmit rabies, but no laboratory-diagnosed cases occurring under such situations have been documented. Each potential exposure to human rabies should be carefully evaluated to minimize unnecessary rabies prophylaxis (1).

Postexposure Treatment Schedule

(see also Dosage and Administration section below)

The essential components of rabies postexposure prophylaxis are prompt local treatment of wounds and administration of both Human Rabies Immune Globulin (HRIG) and vaccine.

A complete course of postexposure treatment for previously unvaccinated adults and children consists of a total of 5 doses of vaccine, each 1.0 mL: one IM injection (deltoid) on each of days 0, 3, 7, 14 and 28. For previously immunized adults and children, a total of 2 doses of vaccine, each 1.0 mL: one IM injection (deltoid) on each of days 0 and 3. No HRIG should be administered to previously vaccinated persons as it may blunt their rapid memory response to rabies antigen.

1. Local Treatment of Wounds

Immediate and thorough washing of all bite wounds and scratches with soap and water is an important measure for preventing rabies. In animal studies, thorough local wound cleansing alone has been shown to reduce markedly the likelihood of rabies. Whenever possible, bite injuries should not be sutured to avoid further and/or deeper contamination. Tetanus prophylaxis and measures to control bacterial infection should be given as indicated (1).

2. Postexposure Prophylaxis of Rabies

The regimen for postexposure prophylaxis depends on whether or not the patient has been previously immunized against rabies (see below). For persons who have not previously been immunized against rabies, the schedule consists of an initial injection IM of HRIG exactly 20 IU per kilogram body weight in total. If anatomically feasible, the FULL DOSE of HRIG should be thoroughly infiltrated in the area around and into the wounds. Any remaining volume of HRIG should be injected IM at a site distant from rabies vaccine administration. HRIG should never be administered in the same syringe or in the same anatomical site as the rabies vaccine. HRIG is administered only once (for specific instructions for HRIG use, see the product package insert). The HRIG injection is followed by a series of 5 individual injections of RabAvert (1.0 mL each) given IM on days 0, 3, 7, 14 and 28. Postexposure rabies prophylaxis should begin the same day exposure occurred or as soon after exposure as possible. The combined use of HRIG and RabAvert is recommended by the CDC for both bite and non-bite exposures, regardless of the interval between exposure and initiation of treatment.

In the event that HRIG is not readily available for the initiation of treatment, it can be given through the seventh day after administration of the first dose of vaccine. HRIG is not indicated beyond the seventh day because an antibody response to RabAvert is presumed to have begun by that time (1).

The sooner treatment is begun after exposure, the better. However, there have been instances in which the decision to begin treatment was made as late as 6 months or longer after exposure due to delay in recognition that an exposure had occurred. Postexposure antirabies treatment should always include administration of both passive antibody (HRIG) and immunization, with the exception of persons who have previously received complete immunization regimens (preexposure or postexposure) with a cell culture vaccine, or persons who have been immunized with other types of vaccines and have had documented rabies antibody titers. Persons who have previously received rabies immunization should receive 2 IM doses of RabAvert: 1 on day 0 and another on day 3. They should not be given HRIG as this may blunt their rapid memory response to rabies antigen.

3. Postexposure Prophylaxis Outside the United States

If postexposure treatment is begun outside the United States with regimens or biologics that are not used in the United States, it may be prudent to provide additional treatment when the patient reaches the USA. State or local health departments should be contacted for specific advice in such cases (1).

Contraindications

In view of the almost invariably fatal outcome of rabies, there is no contraindication to postexposure prophylaxis, including pregnancy (1).

Hypersensitivity

History of anaphylaxis to the vaccine or any of the vaccine components constitutes a contraindication to preexposure vaccination with this vaccine.

In the case of postexposure prophylaxis, if an alternative product is not available, the patient should be vaccinated with caution with the necessary medical equipment and emergency supplies available and observed carefully after vaccination. A patient's risk of acquiring rabies must be carefully considered before deciding to discontinue vaccination. Advice and assistance on the management of serious adverse reactions for persons receiving rabies vaccines may be sought from the state health department or CDC.

Warnings

Anaphylaxis, encephalitis including death, meningitis, neuroparalytic events such as encephalitis, transient paralysis, Guillain-Barre Syndrome, myelitis, and retrobulbar neuritis; and multiple sclerosis have been reported to be temporally associated with the use of RabAvert. See Precautions and Adverse Events sections. A patient's risk of developing rabies must be carefully considered, however, before deciding to discontinue immunization.

RabAvert MUST NOT BE USED SUBCUTANEOUSLY OR INTRADERMALLY.

RabAvert must be injected intramuscularly. For adults, the deltoid area is the preferred site of immunization; for small children and infants, administration into the anterolateral zone of the thigh is preferred. The use of the gluteal region should be avoided, since administration in this area may result in lower neutralizing antibody titers (1).

DO NOT INJECT INTRAVASCULARLY.

Unintentional intravascular injection may result in systemic reactions, including shock. Immediate measures include catecholamines, volume replacement, high doses of corticosteroids, and oxygen.

Development of active immunity after vaccination may be impaired in immune-compromised individuals. Please refer to Drug Interactions, under Precautions.

This product contains albumin, a derivative of human blood. It is present in RabAvert at concentrations of less than 0.3 mg/dose. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeld-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

Precautions

General

Care is to be taken by the health care provider for the safe and effective use of the product. The health care provider should also question the patient, parent or guardian about 1) the current health status of the vaccinee; and 2) reactions to a previous dose of RabAvert, or a similar product. Preexposure vaccination should be postponed in the case of sick and convalescent persons, and those considered to be in the incubation stage of an infectious disease. A separate, sterile syringe and needle or a sterile disposable unit should be used for each patient to prevent transmission of hepatitis and other infectious agents from person to person. Needles should not be recapped and should be properly disposed of. As with any rabies vaccine, vaccination with RabAvert may not protect 100% of susceptible individuals.

Hypersensitivity

At present there is no evidence that persons are at increased risk if they have egg hypersensitivities that are not anaphylactic or anaphylactoid in nature. Although there is no safety data regarding the use of RabAvert in patients with egg allergies, experience with other vaccines derived from primary cultures of chick embryo fibroblasts demonstrates that documented egg hypersensitivity does not necessarily predict an increased likelihood of adverse reactions. There is no evidence to indicate that persons with allergies to chickens or feathers are at increased risk of reaction to vaccines produced in primary cultures of chick embryo fibroblasts.

Since reconstituted RabAvert contains processed bovine gelatin and trace amounts of chicken protein, neomycin, chlortetracycline and amphotericin B, the possibility of allergic reactions in individuals hypersensitive to these substances should be considered when administering the vaccine.

Epinephrine injection (1:1000) must be immediately available should anaphylactic or other allergic reactions occur.

When a person with a history of hypersensitivity must be given RabAvert, antihistamines may be given; epinephrine (1:1000), volume replacement, corticosteroids and oxygen should be readily available to counteract anaphylactic reactions.

Drug Interactions

Radiation therapy, antimalarials, corticosteroids, other immunosuppressive agents and immunosuppressive illnesses can interfere with the development of active immunity after vaccination, and may diminish the protective efficacy of the vaccine. Preexposure vaccination should be administered to such persons with the awareness that the immune response may be inadequate. Immunosuppressive agents should not be administered during postexposure therapy unless essential for the treatment of other conditions. When rabies postexposure prophylaxis is administered to persons receiving corticosteroids or other immunosuppressive therapy, or who are immunosuppressed, it is important that a serum sample on day 14 (the day of the fourth vaccination) be tested for rabies antibody to ensure that an acceptable antibody response has been induced (1).

HRIG must not be administered at more than the recommended dose, since active immunization to the vaccine may be impaired.

No data are available regarding the concurrent administration of RabAvert with other vaccines.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies with RabAvert have not been conducted to assess the potential for carcinogenesis, mutagenesis, or impairment of fertility.

Use in Pregnancy

Pregnancy Category C. Animal reproductive studies have not been conducted with RabAvert. It is also not known whether RabAvert can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. RabAvert should be given to a pregnant woman only if clearly needed. The ACIP has issued recommendations for use of rabies vaccine in pregnant women (1).

Use in Nursing Mothers

It is not known whether RabAvert is excreted in animal or human milk, but many drugs are excreted in human milk. Although there are no data, because of the potential consequences of inadequately treated rabies exposure, nursing is not considered a contraindication to postexposure prophylaxis. If the risk of exposure to rabies is substantial, preexposure vaccination might also be indicated during nursing.

Pediatric Use

Children and infants receive the same dose of 1 mL, given IM, as do adults.

Only limited data on the safety and efficacy of RabAvert in the pediatric age group are available. However, in three studies some preexposure and postexposure experience has been gained (12, 19, 26; see also Clinical Studies in Clinical Pharmacology section).

Geriatric Use

Clinical studies of RabAvert did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Adverse Reactions

In very rare cases, neurological and neuroparalytical events have been reported in temporal association with administration of RabAvert (see also Warnings section). These include cases of hypersensitivity (see Contraindications, Warnings, and Precautions sections).

The most commonly occurring adverse reactions are injection site reactions, such as injection site erythema, induration and pain; flu-like symptoms, such as asthenia, fatigue, fever, headache, myalgia and malaise; arthralgia, dizziness, lymphadenopathy, nausea, and rash.

A patient's risk of acquiring rabies must be carefully considered before deciding to discontinue vaccination. Advice and assistance on the management of serious adverse reactions for persons receiving rabies vaccines may be sought from the state health department or CDC (see also Contraindications section).

Local reactions such as induration, swelling and reddening have been reported more often than systemic reactions. In a comparative trial in normal volunteers, Dreesen et al. (4) described their experience with RabAvert compared to a HDCV rabies vaccine. Nineteen subjects received RabAvert and 20 received HDCV. The most commonly reported adverse reaction was pain at the injection site, reported in 45% of the HDCV group, and 34% of the RabAvert group. Localized lymphadenopathy was reported in about 15% of each group. The most common systemic reactions were malaise (15 % RabAvert group vs. 25 % HDCV group), headache (10 % RabAvert group vs. 20 % HDCV group), and dizziness (15 % RabAvert group vs. 10 % HDCV group). In a recent study in the USA (5), 83 subjects received RabAvert and 82 received HDCV. Again, the most common adverse reaction was pain at the injection site in 80% in the HDCV group and 84% in the RabAvert group. The most common systemic reactions were headache (52% RabAvert group vs. 45% HDCV group), myalgia (53% RabAvert group vs. 38% HDCV group) and malaise (20% RabAvert group vs. 17% HDCV group). None of the adverse events were serious, almost all adverse events were of mild or moderate intensity. Statistically significant differences between vaccination groups were not found. Both vaccines were generally well tolerated.

Uncommonly observed adverse events include temperatures above 38°C (100°F), swollen lymph nodes, pain in limbs and gastrointestinal complaints. In rare cases, patients have experienced severe headache, fatigue, circulatory reactions, sweating, chills, monoarthritis and allergic reactions; transient paresthesias and one case of suspected urticaria pigmentosa have also been reported.

Observed During Clinical Practice (See Warnings and Precautions)

The following adverse reactions have been identified during post approval use of RabAvert. Because these reactions are reported voluntarily from a population of uncertain size, estimates of frequency cannot be made. These events have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to RabAvert, or a combination of these factors:

 

Allergic: Anaphylaxis, Type III hypersensitivity-like reactions, bronchospasm, urticaria, pruritis, edema

 

CNS: Neuroparalysis, encephalitis, meningitis, transient paralysis, Guillain-Barre Syndrome, myelitis, retrobulbar neuritis, multiple sclerosis, vertigo, visual disturbance

 

Cardiac: Palpitations, hot flush

 

Local: Extensive limb swelling

The use of corticosteroids to treat life-threatening neuroparalytic reactions may inhibit the development of immunity to rabies (see Precautions, Drug Interactions).

Once initiated, rabies prophylaxis should not be interrupted or discontinued because of local or mild systemic adverse reactions to rabies vaccine. Usually such reactions can be successfully managed with anti-inflammatory and antipyretic agents.

Reporting of Adverse Events

Adverse events should be reported by the health care provider or patient to the US Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS). Report forms and information about reporting requirements or completion of the form can be obtained from VAERS by calling the toll-free number 1-800-822-7967 (1). In the USA, such events can be reported to the Professional Services department, Novartis Vaccines and Diagnostics, Inc.: phone: 1-800-244-7668.

Dosage and Administration

The individual dose for adults, children, and infants is 1 mL, given intramuscularly.

In adults, administer vaccine by IM injection into the deltoid muscle. In small children and infants, administer vaccine into the anterolateral zone of the thigh. The gluteal area should be avoided for vaccine injections, since administration in this area may result in lower neutralizing antibody titers. Care should be taken to avoid injection into or near blood vessels and nerves. After aspiration, if blood or any suspicious discoloration appears in the syringe, do not inject but discard contents and repeat procedure using a new dose of vaccine, at a different site.

A. Preexposure Dosage

1. Primary Immunization

In the United States, the Advisory Committee on Immunization Practices (ACIP) recommends three injections of 1.0 mL each: one injection on day 0 and one on day 7, and one either on day 21 or 28 (for criteria for preexposure vaccination, see Table 1).

2. Booster Immunization

The individual booster dose is 1 mL, given intramuscularly.

Booster immunization is given to persons who have received previous rabies immunization and remain at increased risk of rabies exposure by reasons of occupation or avocation.

Persons who work with live rabies virus in research laboratories or vaccine production facilities (continuous-risk category: see Table 1) should have a serum sample tested for rabies antibodies every 6 months. The minimum acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by the rapid fluorescent focus inhibition test (RFFIT). A booster dose should be administered if the titer falls below this level.

The frequent-risk category includes other laboratory workers such as those doing rabies diagnostic testing, spelunkers, veterinarians and staff, animal-control and wildlife officers in areas where rabies is epizootic. Persons in the frequent-risk category should have a serum sample tested for rabies antibodies every 2 years and, if the titer is less than complete neutralization at a 1:5 serum dilution by RFFIT, should have a booster dose of vaccine. Alternatively, a booster can be administered in the absence of a titer determination.

The infrequent-risk category, including veterinarians, animal-control and wildlife officers working in areas of low rabies enzooticity (infrequent-exposure group) and international travelers to rabies enzootic areas do not require routine preexposure booster doses of RabAvert after completion of a full primary preexposure vaccination scheme (Table 1).

B. Postexposure Dosage

Immunization should begin as soon as possible after exposure. A complete course of immunization consists of a total of 5 injections of 1 mL each: one injection on each of days 0, 3, 7, 14 and 28 in conjunction with the administration of HRIG on day 0. For children, see Pediatric Use section under Precautions.

Begin with the administration of HRIG. Give 20 IU/kg body weight.

This formula is applicable to all age groups, including infants and children. The recommended dosage of HRIG should not exceed 20 IU/kg body weight because it may otherwise interfere with active antibody production. Since vaccine-induced antibody appears within 1 week, HRIG is not indicated more than 7 days after initiating postexposure prophylaxis with RabAvert. If anatomically feasible, the FULL DOSE of HRIG should be thoroughly infiltrated in the area around and into the wounds. Any remaining volume of HRIG should be injected IM at a site distant from rabies vaccine administration. HRIG should never be administered in the same syringe or in the same anatomical site as the rabies vaccine.

Because the antibody response following the recommended immunization regimen with RabAvert has been satisfactory, routine post-immunization serologic testing is not recommended. Serologic testing is indicated in unusual circumstances, as when the patient is known to be immunosuppressed. Contact the appropriate state health department or the CDC for recommendations.

C. Postexposure Prophylaxis of Previously Immunized Persons

When rabies exposure occurs in a previously vaccinated person, then that person should receive two IM (deltoid) doses (1.0 mL each) of RabAvert: one immediately and one 3 days later. HRIG should not be given in these cases. Persons considered to have been immunized previously are those who received a complete preexposure vaccination or postexposure prophylaxis with RabAvert or other tissue culture vaccines or have been documented to have had a protective antibody response to another rabies vaccine. If the immune status of a previously vaccinated person is not known, full postexposure antirabies treatment (HRIG plus 5 doses of vaccine) is recommended. In such cases, if a protective titer can be demonstrated in a serum sample collected before vaccine is given, treatment can be discontinued after at least two doses of vaccine.

Instructions for Reconstituting RabAvert

Using the longer of the 2 needles supplied, withdraw the entire contents of the Sterile Diluent for RabAvert into the syringe. Insert the needle at a 45° angle and slowly inject the entire contents of the diluent vial into the vaccine vial. Mix gently to avoid foaming. The white, freeze-dried vaccine dissolves to give a clear or slightly opaque suspension. Withdraw the total amount of dissolved vaccine into the syringe and replace the long needle with the smaller needle for IM injection. The reconstituted vaccine should be used immediately.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. If either of these conditions exists, the vaccine should not be administered. A separate, sterile syringe and needle or a sterile disposable unit should be used for each patient to prevent transmission of hepatitis and other infectious agents from person to person. Needles should not be recapped and should be properly disposed of.

The lyophilization of the vaccine is performed under reduced pressure and the subsequent closure of the vials needs to be done under vacuum. Additionally, if there is no negative pressure in the vial, injection of Sterile Diluent for RabAvert would lead to an excess positive pressure in the vial. After reconstitution of the vaccine, it is recommended to unscrew the syringe from the needle to eliminate the negative pressure. After that, the vaccine can be easily withdrawn from the vial. It is not recommended to induce excess pressure, since over-pressurization will create the problems in withdrawing the proper amount of the vaccine.

How Supplied

Package with:

 

1 vial of freeze-dried vaccine containing a single dose

 

1 vial of Sterile Diluent for RabAvert (1 mL)

 

1 disposable syringe

 

1 smaller needle for injection, 25 gauge × 1 "

 

1 longer needle for reconstitution, 21 gauge ×1.5 "

N.D.C.# 63851-501-01

CAUTION: Federal law prohibits dispensing without a prescription

Storage

RabAvert should be stored protected from light at 2°C to 8°C (36°F to 46°F). After reconstitution the vaccine is to be used immediately. The vaccine may not be used after the expiration date given on package and container.

References

1. CDC. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Human Rabies Prevention – United States, 1999. Morbidity and Mortality Weekly Report Recommendations and Report, January 8, 1999, Vol.48, RR-1, pg1.1-21.


2. Smith JS, Yager, P

Axert

Generic Name: Almotriptan Malate
Class: Selective Serotonin Agonists
VA Class: CN105
Chemical Name: Hydroxybutanedioate-1-[[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl]sulfonyl]pyrrolidine
Molecular Formula: C₁₇H₂₅N₃O₂S•C₄H₆O₅
CAS Number: 181183-52-8

Introduction

Selective serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptor agonist (“triptan”).^{1 2 3 5 12}

Uses for Axert

Vascular Headaches

Acute treatment of migraine attacks with or without aura.^{1 9}

Not recommended for management of hemiplegic or basilar migraine or for prophylaxis of migraine.¹

Safety and efficacy not established for management of cluster headaches.¹

Axert Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.^{1 5 10 16}

Dosage

Available as almotriptan malate; dosage is expressed in terms of almotriptan.¹

Adults

Vascular Headaches

Migraine

Oral

6.25 or 12.5 mg as a single dose;^{1 4 5} individualize dosage selection,¹ weighing the possible benefit (greater effectiveness)^{1 4 5} and risks (increased adverse effects)⁷ of the 12.5-mg dose.⁷ In clinical studies, doses >12.5 mg did not lead to substantially greater response.¹

If headache recurs, dose may be repeated after 2 hours.¹

Following failure to respond to first dose, reconsider diagnosis of migraine prior to administration of a second dose.¹

Prescribing Limits

Adults

Vascular Headaches

Migraine

Oral

Maximum 12.5 mg as a single dose; do not exceed 2 doses in any 24-hour period.¹

Safety of treating an average of >4 headaches per 30-day period has not been established.¹

Special Populations

Hepatic Impairment

Initial dose of 6.25 mg; maximum dosage of 12.5 mg over a 24-hour period.¹

Renal Impairment

Initial dose of 6.25 mg; maximum dosage of 12.5 mg over a 24-hour period.¹

Geriatric Patients

Cautious dosage selection recommended; generally start at low end of dosing range due to greater frequency of decreased hepatic, renal, or cardiac function and of concomitant illnesses or other drug therapy in geriatric population.¹

In geriatric patients with normal renal function for their age, dosage is the same as that recommended for younger adults.¹

Cautions for Axert

Contraindications

• 
  

  Known or suspected ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).¹

  
  


• 
  

  Coronary artery vasospasm (e.g., Prinzmetal variant angina).¹

  
  


• 
  

  Other serious underlying cardiovascular disease (e.g., uncontrolled hypertension).¹

  
  


• 
  

  Hemiplegic or basilar migraine.¹

  
  


• 
  

  Treatment within previous 24 hours with another 5-HT₁ receptor agonist or an ergot alkaloid.¹ (See Specific Drugs under Interactions.)

  
  


• 
  

  Known hypersensitivity to almotriptan or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Use only in patients in whom a clear diagnosis of migraine has been established.¹

Cardiac Effects

Possible myocardial ischemia and/or infarction, coronary vasospasm, life-threatening cardiac rhythm disturbances, and death.^{1 5}

Use not recommended in patients with known or suspected ischemic or vasospastic heart disease or in patients in whom unrecognized CAD is likely (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, or family history of CAD) unless there is satisfactory evidence from prior cardiovascular evaluation that patient does not have CAD, ischemic heart disease, or other underlying cardiovascular disease.¹

Administer initial dose to patients with risk factors for CAD who have completed satisfactory cardiovascular evaluation under medical supervision (e.g., in clinician’s office, possibly followed by ECG) unless patient previously received the drug.¹

Periodic cardiovascular evaluation recommended in patients with risk factors for CAD if receiving intermittent long-term therapy.¹

Patients with symptoms suggestive of angina after receiving almotriptan should be evaluated for the presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses; if administration is resumed and such signs or symptoms recur, ECG evaluation recommended.¹

Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage, stroke, and other cerebrovascular events, sometimes fatal.¹

Risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA) may be increased in patients with migraine.¹

Other Cardiovascular or Vasospastic Effects

Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea reported with use of 5-HT₁ receptor agonists.¹ Further evaluation recommended if signs or symptoms of decreased arterial flow (e.g., ischemic colitis, Raynaud’s phenomenon) occur following administration.¹

Substantial increases in BP, including hypertensive crises, reported rarely with 5-HT₁ receptor agonists in patients with or without history of hypertension.¹

Increases in mean pulmonary artery pressure observed following administration of a 5-HT₁ receptor agonist to patients with suspected CAD who were undergoing cardiac catheterization.¹

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported during concurrent therapy with 5-HT₁ receptor agonists (“triptans”) and SSRIs or selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs).^{11 a} Symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).^{11 a}

General Precautions

Ocular Effects

Possible accumulation of almotriptan in melanin-rich tissues (e.g., eye) over time, resulting in potential toxicity in these tissues with extended use.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk in rats; not known whether distributed into milk in humans.¹ Caution advised if almotriptan is used.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age; use not recommended.^{1 7}

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.¹ (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution; dosage adjustment recommended.¹ (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use with caution; dosage adjustment recommended.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Nausea, somnolence, headache, paresthesia, dry mouth.¹

Interactions for Axert

Metabolized principally by MAO-A, CYP3A4, and CYP2D6.^{1 b}

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (decreased almotriptan metabolism) with concomitant use of CYP3A4 inhibitors.¹

Specific Drugs

Drug	Interaction	Comments
Alcohol	Pharmacokinetic or pharmacologic interaction unlikely15
Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and SNRIs (e.g., duloxetine, venlafaxine)	Potentially life-threatening serotonin syndrome1 5 11 a Potential increase in plasma almotriptan concentrations with concurrent fluoxetine administration1 14	Observe carefully if used concomitantly, particularly during treatment initiation, dosage increases, or when another serotonergic agent is initiated1 11 a No dosage adjustment required if fluoxetine is used concomitantly1 14
Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide)	Additive vasospastic effects1	Use within 24 hours contraindicated1 5
5-HT1 receptor agonists	Additive vasospastic effects1	Use within 24 hours contraindicated1 5
Itraconazole	Potential decrease in almotriptan metabolism1
Ketoconazole	Potential decrease in almotriptan metabolism1
MAO inhibitors	Potential decrease in almotriptan metabolism1	No dosage adjustment required1
Propranolol	Pharmacokinetic interaction unlikely1 5
Ritonavir	Potential decrease in almotriptan metabolism1
Verapamil	Potential increase in plasma almotriptan concentrations1 5	No dosage adjustment required1 5

Axert Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract.^{1 b} Absolute bioavailability is approximately 70%.^{1 b c}

Peak plasma concentrations attained within 1–3 hours after oral administration.^{1 b c}

Food

Food does not affect pharmacokinetics.^{1 10}

Distribution

Extent

Appears to be widely distributed throughout the body.^c

Distributed into milk in rats; not known whether distributed into milk in humans.¹

Plasma Protein Binding

Approximately 35%.¹

Elimination

Metabolism

Metabolized to inactive metabolites principally via MAO-mediated oxidative deamination, CYP3A4, and CYP2D6, with minor contribution of flavin monooxygenase.^{1 b}

Elimination Route

Excreted in urine (75%) and feces (13%), with 40% of dose recovered in urine as unchanged drug.¹

Half-life

3–4 hours.^{1 b c}

Special Populations

Pharmacokinetics not evaluated in patients with hepatic impairment.¹ Based on mechanism of almotriptan clearance, maximum decrease in clearance of 60% would be expected.¹

In patients with moderate or severe renal impairment, clearance is reduced by approximately 40 or 65%, respectively; peak plasma concentrations increased by approximately 80% in these patients.¹

In healthy geriatric patients, clearance is decreased, resulting in increases in half-life and AUC compared with younger adults; not considered clinically important.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

ActionsActions

• 
  

  Binds with high affinity to 5-HT_1D, 5-HT_1B, and 5-HT_1F receptors.¹

  
  


• 
  

  Structurally and pharmacologically related to other selective 5-HT_1B/1D receptor agonists (e.g., eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan).^{2 3 12}

  
  


• 
  

  Precise mechanism of action not established;⁷ may ameliorate migraine through selective constriction of certain intracranial blood vessels, inhibition of neuropeptide release, and reduced transmission in trigeminal pain pathway.^{1 3 5 12}

  
  

Advice to Patients

• 
  

  Importance of immediately informing clinician if tightness, pain, pressure, or heaviness in chest, throat, neck, or jaw occurs and of not taking almotriptan again until evaluated by clinician.¹

  
  


• 
  

  Importance of taking almotriptan exactly as prescribed.¹

  
  


• 
  

  Importance of providing patient a copy of manufacturer’s patient information.¹

  
  


• 
  

  Risk of somnolence; importance of exercising caution when driving or operating machinery.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).¹

  
  


• 
  

  Importance of informing patients of risk of serotonin syndrome with concurrent use of almotriptan and an SSRI or SNRI.¹¹ Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.¹¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Almotriptan Malate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	6.25 mg (of almotriptan)	Axert	Ortho-McNeil
		12.5 mg (of almotriptan)	Axert	Ortho-McNeil

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Axert 12.5MG Tablets (ORTHO-MCNEIL PHARMACEUTICAL): 12/$308.98 or 36/$904.98

Axert 6.25MG Tablets (ORTHO-MCNEIL PHARMACEUTICAL): 6/$166.98 or 18/$475.96

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions June 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Ortho-McNeil Pharmaceutical, Inc. Axert (almotriptan malate) tablets prescribing information. Chicago, IL; 2005 Jun.

2. Deleu D, Hanssens Y. Current and emerging second-generation triptans in acute migraine therapy: a comparative review. J Clin Pharmacol. 2000; 40:687-700. [IDIS 449430] [PubMed 10883409]

3. Palacios JM, Rabasseda X, Castaner J et al. Almotriptan. Drugs Future. 1999; 24:367-74.

4. Pascual J, Falk RM, Piessens F et al. Consistent efficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: results of a large, randomized, double-blind, placebo-controlled study. Cephalalgia. 2000; 20:588-96. [PubMed 11075844]

5. Pharmacia Corporation. Axert (almotriptan) tablets comprehensive review. Chicago, IL; 2001 Jan.

6. Spierings ELH, Gomez-Mancilla B, Grosz DE et al. Oral almotriptan vs oral sumatriptan in the abortive treatment of migraine. Arch Neurol. 2001; 58:944-50. [PubMed 11405809]

7. Pharmacia & Upjohn. Chicago, IL; Personal communication.

8. Pascaul J, Falk R, Docekal et al. Tolerability and efficacy of almotriptan in the long-term treatment of migraine. Eur Neurol. 2001; 45:206-13. [PubMed 11385257]

9. Matchar DB, Young WB, Rosenberg JH et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. St. Paul, MN; 2001. From the American Academy of Neurology web site .

10. Jansat JM, Martinez-Tobed A, Garcia E et al. Effect of food intake on the bioavailability of almotriptan, an antimigraine compound, in healthy volunteers: an open, randomized, crossover, single-dose clinical trial. Int J Clin Pharmacol Ther. 2006; 44:185-90. [PubMed 16625988]

11. Food and Drug Administration. Public health advisory: combined use of 5-hydroxytryptamine receptor agonists (triptans), selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephirne reuptake inhibitors (SNRIs) may result in life-threatening serotonin syndrome. Rockville, MD; 2006 Jul 19. From the FDA website: ( and , ).

12. Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000; 60:1259-87. [PubMed 11152011]

13. Fleishaker JC, Sisson TA, Carel BJ et al. Pharmacokinetic interaction between verapamil and almotriptan in healthy volunteers. Clin Pharmacol Ther. 2000; 67:498-503. [PubMed 10824628]

14. Fleishaker JC, Ryan KK, Carel BJ et al. Evaluation of the potential pharmacokinetic interaction between almotriptan and fluoxetine in healthy volunteers. J Clin Pharmacol. 2001; 41:217-23. [PubMed 11210405]

15. Cabarrocas X, Salva M, Pavesi M et al. Ethanol does not significantly affect the bioavailability of almotriptan: an open, randomized, crossover, single-dose, phase I clinical trial in healthy volunteers. Int J Clin Pharmacol Ther. 2006; 44:443-8. [PubMed 16995333]

16. Ortho-McNeil Pharmaceutical, Inc. Axert—Answers to FAQs. From the Ortho-McNeil website.

a. Ortho-McNeil Pharmaceutical, Inc. Axert (almotriptan malate) tablets prescribing information. Raritan, NJ; 2007 Jan.

b. Gras J, Llenas J, Jansat JM et al. Almotriptan, a new anti-migraine agent: a review. CNS Drug Rev. 2002; 8:217-34. [PubMed 12353056]

c. Jansat JM, Costa J, Salva P, Fernandez FJ, Martinez-Tobed A. Absolute bioavailability, pharmacokinetics, and urinary excretion of the novel antimigraine agent almotriptan in healthy male volunteers. J Clin Pharmacol. 2002; 42:1303-10. [PubMed 12463724]

More Axert resources

• Axert Side Effects (in more detail)
• Axert Use in Pregnancy & Breastfeeding
• Drug Images
• Axert Drug Interactions
• Axert Support Group
• 9 Reviews for Axert - Add your own review/rating

• Axert Prescribing Information (FDA)


• Axert Concise Consumer Information (Cerner Multum)


• Axert Advanced Consumer (Micromedex) - Includes Dosage Information


• Axert MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Axert with other medications

• Migraine

Tefamin

Tefamin may be available in the countries listed below.

Ingredient matches for Tefamin

Aminophylline

Aminophylline is reported as an ingredient of Tefamin in the following countries:

• Italy

International Drug Name Search

Topiramat beta

Topiramat beta may be available in the countries listed below.

Ingredient matches for Topiramat beta

Topiramate

Topiramate is reported as an ingredient of Topiramat beta in the following countries:

• Germany

International Drug Name Search

Augmentin

Pronunciation: a-MOX-i-SIL-in/KLAV-ue-la-nate
Generic Name: Amoxicillin/Clavulanate
Brand Name: Augmentin

Augmentin is used for:

Treating infections caused by certain bacteria.

Augmentin is a penicillin antibiotic. It works by killing sensitive bacteria.

Do NOT use Augmentin if:

• you are allergic to any ingredient in Augmentin or another penicillin antibiotic (eg, ampicillin)


• you have a history of liver problems or yellowing of the eyes or skin caused by Augmentin


• you have infectious mononucleosis (mono)


• you are taking a tetracycline antibiotic (eg, doxycycline)


• you have recently received or will be receiving live oral typhoid vaccine

Contact your doctor or health care provider right away if any of these apply to you.

Before using Augmentin:

Some medical conditions may interact with Augmentin. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of allergies, asthma, hay fever, or hives


• if you have had a severe allergic reaction (eg, severe rash, hives, breathing difficulties, dizziness) to a cephalosporin (eg, cephalexin) or another beta-lactam antibiotic (eg, imipenem)


• if you have kidney problems or gonorrhea


• if you have a history of liver problems or yellowing of the eyes or skin

Some MEDICINES MAY INTERACT with Augmentin. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Anticoagulants (eg, warfarin) because the risk of bleeding may be increased


• Probenecid because it may increase the amount of Augmentin in your blood


• Chloramphenicol, macrolide antibiotics (eg, erythromycin), sulfonamides (eg, sulfamethoxazole), or tetracycline antibiotics (eg, doxycycline) because they may decrease Augmentin's effectiveness


• Methotrexate because the risk of its side effects may be increased by Augmentin


• Live oral typhoid vaccine or hormonal birth control (eg, birth control pills) because their effectiveness may be decreased by Augmentin

This may not be a complete list of all interactions that may occur. Ask your health care provider if Augmentin may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Augmentin:

Use Augmentin as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Augmentin by mouth at the start of a meal to decrease the chance of stomach upset.


• To clear up your infection completely, take Augmentin for the full course of treatment. Keep taking it even if you feel better in a few days.


• If you miss a dose of Augmentin, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Augmentin.

Important safety information:

• Augmentin may cause dizziness. This effect may be worse if you take it with alcohol or certain medicines. Use Augmentin with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Augmentin only works against bacteria; it does not treat viral infections (eg, the common cold).


• Be sure to use Augmentin for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future.


• Long-term or repeated use of Augmentin may cause a second infection. Tell your doctor if signs of a second infection occur. Your medicine may need to be changed to treat this.


• Mild diarrhea is common with antibiotic use. However, a more serious form of diarrhea (pseudomembranous colitis) may rarely occur. This may develop while you use the antibiotic or within several months after you stop using it. Contact your doctor right away if stomach pain or cramps, severe diarrhea, or bloody stools occur. Do not treat diarrhea without first checking with your doctor.


• Hormonal birth control (eg, birth control pills) may not work as well while you are using Augmentin. To prevent pregnancy, use an extra form of birth control (eg, condoms).


• Brown, yellow, or gray tooth discoloration has occurred rarely in some patients taking Augmentin. It occurred most often in children. The discoloration was reduced or removed by brushing or dental cleaning in most cases. Contact your doctor if you experience this effect.


• Diabetes patients - Augmentin may cause the results of some tests for urine glucose to be wrong. Ask your doctor before you change your diet or the dose of your diabetes medicine.


• Lab tests, including liver function, kidney function, and complete blood cell counts, may be performed if you use Augmentin for a long period of time. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Augmentin with caution in the ELDERLY; they may be more sensitive to its effects, especially patients with kidney problems.


• Use Augmentin with extreme caution in CHILDREN younger than 10 years old who have diarrhea or an infection of the stomach or bowel.


• Augmentin should not be used in CHILDREN who weigh less than 88 lbs (40 kg); safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Augmentin while you are pregnant. Augmentin is found in breast milk. If you are or will be breast-feeding while you use Augmentin, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Augmentin:

All medicines may cause side effects, but many people have no, or minor side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Diarrhea; nausea; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody stools; confusion; dark urine; fever, chills, or persistent sore throat; red, swollen, blistered, or peeling skin; seizures; severe diarrhea; stomach pain or cramps; unusual bruising or bleeding; vaginal discharge or irritation; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Augmentin side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include decreased urination; severe nausea, vomiting, or diarrhea; stomach pain; unusual drowsiness.

Proper storage of Augmentin:

Store Augmentin at or below 77 degrees F (25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Augmentin out of the reach of children and away from pets.

General information:

• If you have any questions about Augmentin, please talk with your doctor, pharmacist, or other health care provider.


• Augmentin is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Augmentin. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Augmentin resources

• Augmentin Side Effects (in more detail)
• Augmentin Dosage
• Augmentin Use in Pregnancy & Breastfeeding
• Drug Images
• Augmentin Drug Interactions
• Augmentin Support Group
• 55 Reviews for Augmentin - Add your own review/rating

• Augmentin Consumer Overview


• Augmentin Prescribing Information (FDA)


• Augmentin Advanced Consumer (Micromedex) - Includes Dosage Information


• Augmentin ES-600 Prescribing Information (FDA)


• Augmentin XR Prescribing Information (FDA)

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