HepaGam B

hepatitis b immune globulin (human)

Dosage Form: injection, solution
FULL PRESCRIBING INFORMATION

Indications and Usage for HepaGam B

Prevention of Hepatitis B recurrence following Liver Transplantation

HepaGam B®, Hepatitis B Immune Globulin Intravenous (Human), is indicated for the prevention of hepatitis B recurrence following liver transplantation, in HbsAg-positive liver transplant patients.

HepaGam B should be administered intravenously for this indication.

Postexposure Prophylaxis

HepaGam B is indicated for the treatment of acute exposure to blood containing HbsAg, perinatal exposure of infants born to HbsAg-positive mothers, sexual exposure to HbsAgpositive

persons and household exposure to persons with acute HBV infection in the following settings:

Following either parenteral exposure (needlestick, bite, sharps), direct mucous membrane contact (accidental splash), or oral ingestion (pipetting accident), involving HbsAg-positive materials such as blood, plasma or serum1,2.

Perinatal Exposure of Infants Born to HbsAg-positive Mothers

Infants born to mothers positive for HbsAg with or without HbeAg1.

Sexual Exposure to HbsAg-positive Persons

Sexual partners of HbsAg-positive persons1,2.

Household Exposure to Persons with Acute HBV Infection

Infants less than 12 months old whose mother or primary caregiver is positive for HbsAg. Other household contacts with an identifiable blood exposure to the index patient.

HepaGam B is indicated for intramuscular use only for these post-exposure prophylaxis indications.

HepaGam B Dosage and Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration; if these are seen, vials should not be used. During preparation, do not shake vials; avoid foaming.

Any vial of HepaGam B that has been entered should be used promptly. Do not reuse or save for future use. This product contains no preservative; therefore, partially used vials should be discarded immediately.

Prevention of Hepatitis B recurrence following liver transplantation

For the prevention of hepatitis B recurrence following liver transplantation in HBsAg positive liver transplant patients, HepaGam B is administered intravenously according to a set dosing regimen designed to attain serum levels of antibodies to hepatitis B surface antigen (anti-HBs) greater than 500 IU/L3.

Based upon the HepaGam B clinical trial, patients should receive 20,000 IU/dose [see Clinical Trials in Liver Transplant Patients (14.1)]. The volume of each 20,000 IU dose should be calculated from the measured potency of the particular lot of HepaGam B as stamped on the vial label.

The first dose should be administered concurrently with the grafting of the transplanted liver (the anhepatic phase) with subsequent dosing as recommended in Table 1.

Table 1 - HepaGam B Dosing Regimen

Anhepatic Phase	Week 1 Post-Operative	Weeks 2-12 Post-Operative	Month 4 onwards
First dose	Daily from Day 1-7	Every two weeks from Day 14	Monthly

* Each dose should contain 20,000 IU calculated from the measured potency as stamped on the vial label [see Dosage Forms and Strengths (3)].

HepaGam B dose adjustments may be required in patients who fail to reach anti-HBs levels of 500 IU/L within the first week post-liver transplantation4. Patients who have surgical bleeding or abdominal fluid drainage (> 500 mL) or patients who undergo plasmapheresis are particularly susceptible to extensive loss of circulated anti-HBs. In these cases, the dosing regimen should be increased to a half-dose (10,000 IU calculated from the measured potency as stamped on the vial label) intravenously every 6 hours until the target anti-HBs is reached.

Hepatitis B Immune Globulin (HBIG) products are most effective in patients with no or low levels of HBV replication at the time of transplantation5.

Regular monitoring of serum HBsAg and levels of anti-HBs antibody should be performed pre-infusion to track treatment response and allow for treatment adjustment.

HepaGam B should be prepared for intravenous administration under aseptic conditions. HepaGam B should be administered through a separate intravenous line using an intravenous administration set via infusion pump.

The rate of administration should be set at 2 mL per minute.

The rate of infusion should be decreased to 1 mL per minute or slower if the patient develops discomfort, infusion-related adverse events or there is concern about the speed of infusion.

Postexposure Prophlyaxis

For postexposure prophylaxis indications, HepaGam B must be administered intramuscularly only as directed below.

It is important to use a separate vial, sterile syringe, and needle for each individual patient, to prevent transmission of infectious agents from one person to another.

HepaGam B may be administered at the same time (but at a different site), or up to one month preceding hepatitis B vaccination without impairing the active immune response to Hepatitis B Vaccine1,2.

Acute Exposure to Blood Containing HBsAg

Table 2 summarizes prophylaxis for percutaneous (needlestick, bite, sharps), ocular, or mucous membrane exposure to blood according to the source of exposure and vaccination status of the exposed person. For greatest effectiveness, passive prophylaxis with HepaGam B should be given as soon as possible after exposure, as its value after seven days following exposure is unclear1,2. An injection of 0.06 mL/kg of body weight should be administered intramuscularly as soon as possible after exposure, and within 24 hours if possible. Consult the Hepatitis B Vaccine package insert for dosage information regarding the vaccine.

For persons who refuse Hepatitis B Vaccine or are known non-responders to vaccine, a second dose of HepaGam B should be given one month after the first dose2.

Table 2 - Recommendations for Hepatitis B Prophylaxis Following Percutaneous or Permucosal Exposure¹,²

* Hepatitis B Immune Globulin Intravenous (Human) dose of 0.06 mL/kg IM † See manufacturers’ recommendation for appropriate dose. ‡ Less than 10 mIU/mL anti-HBs by radioimmunoassay, negative by enzyme immunoassay. § Two doses of Hepatitis B Immune Globulin Intravenous (Human) is preferred if no response after at least four doses of vaccine.
Source	Exposed Person
	Unvaccinated	Vaccinated
HBsAg-positive	1. Hepatitis B Immune Globulin Intravenous (Human) (HBIGIV) x 1 immediately* 2. Initiate HB vaccine series†	1. Test exposed person for anti-HBs 2. If inadequate antibody‡, Hepatitis B Immune Globulin Intravenous (Human) x 1 immediately plus either HB vaccine booster dose, or a second dose of HBIGIV*, 1 month later§
Known Source – High Risk for HBsAg-positive	1. Initiate HB vaccine series 2. Test source of HBsAg. If positive, Hepatitis B immune Globulin Intravenous (Human) (HBIGIV) x 1	1. Test source for HBsAg only if exposed is vaccine nonresponder; if source is HBsAg-positive, give Hepatitis B Immune Globulin Intravenous (Human) x 1 immediately plus either HB vaccine booster dose, or a second dose of HBIGIV*, 1 month later§
Known Source – Low Risk for HBsAg-positive	Initiate HB vaccine series	Nothing required
Unknown Source	Initiate HB vaccine series	Nothing required

Prophylaxis of Infants Born to Mothers who are Positive for HBsAg with or without HBeAg

Table 3 contains the recommended schedule of Hepatitis B prophylaxis for infants born to mothers that are either known to be positive for HBsAg or have not been screened. Infants born to mothers known to be HBsAg-positive should receive 0.5 mL HepaGam B after physiologic stabilization of the infant and preferably within 12 hours of birth. The Hepatitis B Vaccine series should be initiated simultaneously, if not contraindicated, with the first dose of the vaccine given concurrently with the HepaGam B, but at a different site. Subsequent doses of the vaccine should be administered in accordance with the recommendations of the manufacturer. Women admitted for delivery, who were not screened for HBsAg during the prenatal period, should be tested. While test results are pending, the newborn infant should receive Hepatitis B Vaccine within 12 hours of birth (see manufacturers’ recommendations for dose). If the mother is later found to be HBsAg-positive, the infant should receive 0.5 mL HepaGam B as soon as possible and within seven days of birth; however, the efficacy of HepaGam B administered after 48 hours of age is not known6. Testing for HBsAg and anti-HBs is recommended at 12-15 months of age. If HBsAg is not detectable and anti-HBs is present, the child has been protected1.

Table 3 - Recommended Schedule of Hepatitis B Immunoprophylaxis to Prevent Perinatal Transmission of Hepatitis B Virus Infection¹

* See manufacturers’ recommendations for appropriate dose. † 0.5 mL administered IM at a site different from that used for the vaccine. ‡ See ACIP recommendation¹
Age of Infant
Administer	Infant born to mother known to be HBsAg-positive	Infant born to mother not screened for HBsAg
First Vaccination* Hepatitis B Immune Globulin Intravenous (Human)†	Birth (within 12 hours) Birth (within 12 hours)	Birth (within 12 hours) If mother is found to be HBsAg-positive, administer dose to infant as soon as possible, not later than 1 week after birth
Second Vaccination*	1 month	1-2 months
Third Vaccination*	6 months‡	6 months‡

Sexual Exposure to HBsAg-positive Persons

All susceptible persons whose sexual partners have acute hepatitis B infection should receive a single dose of HepaGam B (0.06 mL/kg) and should begin the Hepatitis B Vaccine series, if not contraindicated, within 14 days of the last sexual contact or if sexual contact with the infected person will continue. Administering the vaccine with HepaGam B may improve the efficacy of post exposure treatment. The vaccine has the added advantage of conferring long-lasting protection1,2.

Household Exposure to Persons with Acute HBV Infection

Prophylaxis of an infant less than 12 months of age with 0.5 mL HepaGam B and Hepatitis B Vaccine is indicated if the mother or primary caregiver has acute HBV infection. Prophylaxis of other household contacts of persons with acute HBV infection is not indicated unless they had an identifiable blood exposure to the index patient, such as by sharing toothbrushes or razors. Such exposures should be treated like sexual exposures. If the index patient becomes an HBV carrier, all household contacts should receive Hepatitis B Vaccine1,2.

Dosage Forms and Strengths

HepaGam B, Hepatitis B Immune Globulin Intravenous (Human), is a sterile solution of purified gamma globulin (5% or 50 mg/mL) containing anti-HBs. Each vial contains greater than 312 IU/mL of anti-HBs and is supplied in a carton containing a 1.0 mL single use vial or a carton containing a 5.0 mL single use vial. The measured potency of each lot is stamped on the vial label.

To ensure that the label claim of >312 IU/mL is maintained over the product shelf life, a higher potency of 550 IU/mL is targeted at the time of manufacture. As with other specific immune globulin products, this higher target potency is a manufacturing requirement to account for variability in the potency assay and changes in potency over time. The potency assay has a relative standard deviation (RSD) of approximately 10%. Based on statistical assessment of manufactured lots with a target potency of 550 IU/mL, the actual potency test result may vary from approximately 400 to 700 IU/mL (3x RSD). The measured potency is provided on the container label. Due to the inherent variability of the potency assay, dosing for the prevention of hepatitis B recurrence following liver transplantation should be calculated from the measured potency of the particular lot of HepaGam B as stamped on the vial label [see Dosage and Administration (2.1)].

Contraindications

Individuals known to have anaphylactic or severe systematic reactions associated with the parenteral administration of human globulin preparations should not receive HepaGam B, Hepatitis B Immune Globulin Intravenous (Human), or any other human immune globulin. HepaGam B contains less than 40 micrograms/mL of IgA. Individuals who are deficient in IgA may have the potential to develop IgA antibodies and have an anaphylactoid reaction. The physician must weigh the potential benefit of treatment with HepaGam B against the potential for hypersensitivity reactions.

For postexposure prophylaxis indications, HepaGam B must be administered intramuscularly only. In patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections, HepaGam B should be given only if the expected benefits outweigh the potential risks.

Warnings and Precautions

General

HepaGam B is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses and theoretically, the Creutzfeldt-Jakob disease agent. The risk that such products can transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. The HepaGam B manufacturing process includes a solvent/detergent treatment step (using tri-n-butyl phosphate and Triton X-100) that is effective in inactivating known enveloped viruses such as HBV, HCV, and HIV. HepaGam B is filtered using a Planova 20N Virus Filter that is effective in reducing the levels of some enveloped and non-enveloped viruses. These two processes are designed to increase product safety. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. ALL infections thought by a physician to have been transmitted by this product should be reported by the physician or other healthcare provider to Cangene Corporation at 1-800-768-2304. The physician should discuss the risks and benefits of this product with the patient.

Anaphylactic Precautions

Although allergic reactions have not been reported following HepaGam B administration [see Adverse Reactions (6.2)], the product should be administered only in a setting where appropriate equipment and personnel trained in the management of acute anaphylaxis are available. If hypotension or anaphylaxis occurs, the administration of HepaGam B should be discontinued immediately and supportive care given as needed.

Interference with Blood Glucose Testing

The maltose contained in HepaGam B can interfere with some types of blood glucose monitoring systems, i.e., those based on the glucose dehydrogenase pyrroloquinequinone (GDH-PQQ) method. This can result in falsely elevated glucose readings and, consequently, in the inappropriate administration of insulin, resulting in life-threatening hypoglycemia. Cases of true hypoglycemia may go untreated if the hypoglycemic state is masked by falsely elevated results.

Monitoring: Serum anti-HBs Antibody Levels

Liver transplant patients should be monitored regularly for serum anti-HBs antibody levels using a quantitative assay [see Dosage and Administration (2.1)].

Infusion Reactions

Certain adverse drug reactions may be related to the rate of infusion. The recommended infusion rate given under Dosage and Administration (2.1) must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period and immediately following an infusion.

Coagulation Disorders

For postexposure prophylaxis indications, HepaGam B must be administered intramuscularly only. In patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections, HepaGam B should be given only if the expected benefits outweigh the potential risks.

Adverse Reactions

Overall Adverse Reaction Profile

The most common expected adverse drug reactions for intravenous immune globulins like HepaGam B are chills, fever, headaches, vomiting, allergic reactions, nausea, arthralgia and moderate low back pain7,8. In a clinical trial in liver transplant patients, 2 adverse drug reactions of tremor and hypotension were reported in 2 of 14 patients who received intravenous infusions of HepaGam B8. In studies with healthy volunteers, only 1 adverse drug reaction of nausea was reported in the 70 adult subjects who received an intramuscular administration of HepaGam B8.

Although no anaphylactic reactions have been reported following HepaGam B administration, anaphylactic reactions have been reported following the administration of other immune globulin products on rare occasions [see Warnings and Precautions (5.2)].

Adverse Reactions in Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Hepatitis B-Related Liver Transplantation

In an ongoing clinical trial, only 2 adverse drug reactions occurred following the 313 (<1%) HepaGam B infusions in 14 liver transplant patients. A listing of all adverse events (including those assessed as unrelated to study drug) occurring in >10% of patients are summarized in Table 4 below. These adverse events were reported in an interim analysis from a one-year Phase 3 clinical trial examining HepaGam B for the prevention of hepatitis B recurrence following liver transplantation. This study utilized the recommended dosing regimen outlined in Table 1 [see Dosage and Administration (2.1)]. The 2 attributed adverse drug reactions of tremor and hypotension were reported in 2 patients. All reactions were associated with a single HepaGam B infusion during the first week post-transplant. All reactions resolved on the same day and did not recur with subsequent HepaGam B infusions.

Table 4 - Adverse Events (AEs) Occurring in >10% of Liver Transplant Patients

Adverse Event by system organ class	Number of AEs (in number of patients) N=14
Blood and lymphatic systems disorder - Splenomegaly	8 (6)
Eye disorders - Presbyopia	2 (2)
Gastrointestinal disorders - Aphthous stomatitis - Diarrhoea - Dyspepsia - Gingival Hyperplasia	3 (3) 10 (8) 5 (5) 3 (3)
General disorders - Fatigue - Oedema peripheral - Pyrexia	6 (6) 3 (2) 3 (3)
Hepatobiliary disorders - Hepatobiliary disease	3 (3)
Immune system disorders - Liver transplant rejection	7 (5)
Infections and infestations - Diarrhoea Infectious - Pneumonia - Sepsis	2 (2) 2 (2) 3 (2)
Metabolism and nutrition disorders - Hyperglycaemia	4 (4)
Musculoskeletal - Back pain	2 (2)
Nervous system disorders - Amnesia - Essential Tremor - Headache	2 (2) 6 (2) 15 (9)
Psychiatric disorders - Agitation	2 (2)
Renal and urinary disorders - Nocturia	2 (2)
Respiratory, thoracic and mediastinal - Pleural effusion	3 (3)
Skin and subcutaneous tissue disorders - Pruritus - Rash	3 (3) 2 (2)
Vascular disorders - Hypertension - Hypotension	8 (7) 2 (2)

Healthy Volunteer Studies

Seventy healthy male and female volunteers received a single dose of HepaGam B intramuscularly in clinical trials8. Seventeen (17) subjects reported 30 adverse events following administration of HepaGam B. The most frequently reported adverse events included 4 subjects (6%) who experienced headache, 7 subjects (10%) who had cold symptoms or flu and 2 subjects (3%) who experienced lightheadedness/fainted. The majority of events were reported as mild and were not related to study drug. One adverse event, an episode of nausea, was considered to be drug related. There were no serious adverse events reported. A similar number of subjects in the comparator groups reported adverse events.

Postmarketing Experience

As of April 2007, there have been no postmarketing adverse events reported for HepaGam B administered IM

Drug Interactions

Live Attenuated Virus Vaccines

Immune globulin administration may impair the efficacy of live attenuated virus vaccines such as measles, rubella, mumps and varicella1,2,7. Vaccination with live virus vaccines should be deferred until approximately three months after administration of HepaGam B, Hepatitis B Immune Globulin Intravenous (Human). Persons who received HepaGam B less than 14 days after live virus vaccination should be revaccinated 3 months after the administration of the immune globulin, unless serologic test results indicate that antibodies were produced1,2.

There are no available data on drug interactions of HepaGam B with other medications.

Drug-Laboratory Interactions: Serological Testing

Antibodies present in HepaGam B may interfere with some serological tests. After administration of immune globulins like HepaGam B, a transitory increase of passively transferred antibodies in the patient’s blood may result in misleading positive results in serological testing (e.g. Coombs' test).

Drug-Laboratory Interactions: Blood Glucose Testing

HepaGam B contains maltose which can interfere with certain types of blood glucose monitoring systems. [See Warnings and Precautions (5.3).] Only testing systems that are glucose-specific should be used in patients receiving HepaGam B. This interference can result in falsely elevated glucose readings that can lead to untreated hypoglycemia or to inappropriate insulin administration, resulting in life-threatening hypoglycemia.

The product information of the blood glucose testing system, including that of the test strips, should be carefully reviewed to determine if the system is appropriate for use with maltose-containing parenteral products. If any uncertainty exists, contact the manufacturer of the testing system to determine if the system is appropriate for use with maltose-containing parenteral products.

USE IN SPECIFIC POPULATIONS

Pregnancy Category C

Animal reproduction studies have not been conducted with HepaGam B. It is also not known whether HepaGam B can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. HepaGam B should be given to a pregnant woman only if clearly indicated.

Nursing Mothers

It is not known whether HepaGam B is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when HepaGam B is administered to a nursing mother.

Overdosage

Consequences of an overdose are not known. Although no data are available, clinical experience reported with other intravenously administered human immune globulin preparations suggests that doses above 1 g immune globulin/kg body weight are tolerated. For intramuscular administration of HepaGam B, the only manifestations of overdose would be pain and tenderness at the injection site.

HepaGam B Description

HepaGam B, Hepatitis B Immune Globulin Intravenous (Human), is a solvent/detergent-treated sterile solution of purified gamma globulin containing anti-HBs. It is prepared from plasma donated by healthy, screened donors with high titers of anti-HBs that is purified by an anion-exchange column chromatography manufacturing method9,10. HepaGam B is formulated as a 5% (50 mg/mL) protein solution with 10% maltose and 0.03% polysorbate 80 at pH 5.6. It is available in 1 mL and 5 mL single dose vials. The product appears as a clear to opalescent liquid. It contains no preservatives and is intended for single use. HepaGam B may be administered intravenously or intramuscularly dependent upon indication [see Indications and Usage (1.)]. The source plasma used in the manufacture of this product was tested by FDA licensed Nucleic Acid testing (NAT) for HIV-1 and HCV and found to be negative. An investigational NAT for HBV was performed on all Source Plasma used, and found to be negative; however, the significance of a negative result has not been established. Plasma also has been tested by inprocess NAT for hepatitis A virus (HAV) and parvovirus B19 (B19) via minipool testing and the limit for B19 in the manufacturing pool is set not to exceed 104 IU of B19 DNA per mL.

The manufacturing process contains two steps implemented specifically for virus clearance. The solvent and detergent step (using tri-n-butyl phosphate and Triton X-100) is effective in the inactivation of enveloped viruses, such as hepatitis B, hepatitis C and HIV11. Virus filtration, using a Planova 20N virus filter, is effective for the removal of viruses based on their size, including some non-enveloped viruses12. These two viral clearance steps are designed to increase product safety by reducing the risk of transmission of enveloped and non-enveloped viruses. In addition to these two specific steps, the process step of anion-exchange chromatography was identified as contributing to the overall viral clearance capacity for small non-enveloped viruses.

The inactivation and reduction of known enveloped and non–enveloped model viruses were validated in laboratory studies as summarized in Table 5. The viruses employed for spiking studies were selected to represent those viruses that are potential contaminants in the product, and to represent a wide range of physiochemical properties in order to challenge the manufacturing process’s ability for viral clearance in general.

Table 5 - Virus Reduction Values Obtained Through Validation Studies⁸

* The PRV was retained by the 0.1 μm pre-filter during the virus validation. Since manufacturing employs a 0.1 μm pre-filter before the 20N filter, the claim of ≥ 5.6 reduction is considered applicable.
Enveloped	Enveloped			Non-Enveloped
Genome	RNA		DNA	RNA		DNA
Virus	HIV-1	BVDV	PRV	HAV	EMC	MMV	PPV
Family	retro	flavi	herpes	picorna		parvo
Size (nm)	80-100	50-70	120-200	25-30	30	20-25	18-24
Anion Exchange Chromatography(partitioning)	Not evaluated			2.3	n.e.	3.4	n.e.
20N Filtration(size exclusion)	≥ 4.7	≥ 3.5	≥ 5.6 *	n.e.	4.8	n.e.	4.1
Solvent/Detergent (inactivation)	≥ 4.7	≥ 7.3	≥ 5.5	Not evaluated
Total Reduction (log10)	≥ 9.4	≥ 10.8	≥ 11.1	2.3	4.8	3.4	4.1

Abbreviations:

HIV-1: human immunodeficiency virus-1; relevant virus for human immunodeficiency virus-1 and model for HIV-2

BVDV: bovine viral diarrhea virus; model virus for hepatitis C virus (HCV) and West Nile virus (WNV)

PRV: pseudorabies virus; model for large enveloped DNA viruses, including herpes

HAV: human hepatitis A virus; relevant virus for HAV and model for small non-enveloped viruses in general

EMC: encephalomyocarditis virus; model for HAV and for small non-enveloped viruses in general

MMV: murine minute virus; model for human parvovirus B19 and for small non-enveloped viruses in general

PPV: porcine parvovirus; model for human parvovirus B19 and for small non-enveloped viruses in general

n.e.: not evaluated

a The PRV was retained by the 0.1 μm pre-filter during the virus validation. Since manufacturing employs a 0.1 μm pre-filter before the 20N filter, the claim of ≥ 5.6 reduction is considered applicable.

The product potency is expressed in international units (IU) by comparison to the World Health Organization (WHO) standard Hepatitis B Immune Globulin. Each vial contains greater than 312 IU/mL. The measured potency of each lot is stamped on the vial label [see Dosage Forms and Strengths (3.)].

HepaGam B - Clinical Pharmacology

Mechanism of Action

HBIGIV products provide passive immunization for individuals exposed to the hepatitis B virus, by binding to the surface antigen and reducing the rate of hepatitis B infection13-16.

Hepatitis B virus reinfection following liver transplantation is the consequence of exposure of the new liver graft to hepatitis B virus. Reinfection may occur immediately at the time of liver reperfusion due to circulating virus or later from virus retained in extrahepatic sites.

The mechanism whereby hepatitis B Immune globulin (HBIG) protects the transplanted liver against HBV reinfection is not well understood. HBIG may protect naive hepatocytes against infection through blockage of a putative HBV receptor17. Alternatively, HBIG may neutralize circulating virions through immune precipitation and immune complex formation or may trigger an antibody-dependent cell-mediated cytotoxicity response resulting in target cell lysis17, 18. In addition, HBIG has been reported to bind to hepatocytes and interact with HBsAg within cells19. Regardless of the mechanism, there is evidence of a dose-dependent response to HBIG treatment5,8.

Postexposure Prophylaxis

Clinical studies conducted prior to 1983 with hepatitis B immune globulins similar to HepaGam B demonstrated the advantage of simultaneous administration of hepatitis B vaccine and Hepatitis B Immune Globulin (Human), by the i.m. route. The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) advises that the combination prophylaxis be provided following certain instances of hepatitis B exposure.1,2 Recommendations on post-exposure prophylaxis are based on available efficacy data, primarily from studies in neonates1,2. Cases of hepatitis B are rarely seen following exposure to HBV in persons with pre-existing anti-HBs antibodies.

Infants born to HBsAg-positive mothers are at risk of being infected with HBV and becoming chronic carriers1.  The risk is especially great if the mother is also HBeAg-positive1. For an infant with perinatal exposure to an HBsAg-positive and HBeAg-positive mother, a regimen combining one dose of Hepatitis B Immune Globulin (Human) at birth with the hepatitis B vaccine series started soon after birth has been shown to be 85-98% effective in preventing development of the HBV carrier state1,2. Regimens involving either multiple doses of Hepatitis B Immune Globulin (Human) alone or the vaccine series alone have a 70-75% efficacy, while a single dose of Hepatitis B Immune Globulin (Human) alone has 50% efficacy1,2.

Since infants have close  contact with primary caregivers and have a higher risk of becoming HBV carriers after acute HBV infection, prophylaxis of an infant less than 12 months of age with Hepatitis B Immune Globulin (Human) and Hepatitis B Vaccine is indicated if the mother or primary caregiver has acute HBV infection1.

Sexual partners of HBsAg-positive persons are at increased risk of acquiring HBV infection. A single dose of Hepatitis B immune Globulin (Human) is 75% effective if administered within two weeks of the last sexual exposure to a person with acute hepatitis B1,2.

HBV infection is a well-recognized risk to health-care personnel (HCP). The risk of HBV infection is primarily related to the degree of contact with blood in the work place and also to the hepatitis B e antigen (HBeAg) status of the source person. In studies of HCP who sustained injuries from needles contaminated with blood containing HBV, the risk of developing clinical hepatitis if the blood was hepatitis B surface antigen (HBsAg) and HBeAg-positive was 22%-31%; the risk of developing serologic evidence of HBV infection was 37%-62%. In comparison, the risk of developing clinical hepatitis from needles contaminated with HBsAg-positive, HBeAg-negative blood is 1%-6%, and the risk of developing serological evidence of HBV infection is 23%-37%20. The current recommendations of the Advisory Committee on Immunization Practices1,2, recommends postexposure prophylaxis with hepatitis B immune globulin and/or hepatitis B vaccine series for any susceptible, unvaccinated person who sustains an occupational blood or body fluid exposure.

The pharmacokinetic profile of HepaGam B has been evaluated in two clinical trials [see Clinical Studies (14.2)]. The comparative bioavailability of HepaGam B and another commercially available hepatitis B immunoglobulin product indicates that HepaGam B has similar efficacy.

Nonclinical Toxicology

Nonclinical pharmacology studies have not been performed with Hepatitis B Immune Globulin Intravenous (Human) as there is broad experience in humans with intravenous and intramuscular administration of immune globulin products. Since the product is of human origin, immunogenicity is expected when administered to animals.

Toxicology studies have not been performed with Hepatitis B Immune Globulin Intravenous (Human) because the product has been formulated with ingredients that are know to be non-toxic at the levels at which they are present in the final product.

Clinical Studies

Clinical Trials in Liver Transplant Patients

A clinical trial examining the effectiveness of HepaGam B in the prevention of hepatitis B recurrence following liver transplantation is currently ongoing. The study is a multi-center, open-labeled, superiority study involving HBsAg-positive/HBeAg-negative liver transplant patients. The study included two arms, an active treatment group of patients enrolled to receive the described dosing regimen of HepaGam B starting during transplant and continuing over the course of a year, and a retrospective untreated control group of historical patients with data gathered by chart review.

An interim report of this study evaluated the data from 30 liver transplant patients, 16 HepaGam B patients who have completed the study and 14 retrospective untreated control patients. The patients in both groups were HBsAg-positive/HBeAg-negative liver transplant patients who met similar entry criteria, had similar medical history and had similar status at transplant based on MELD and/or ChildPugh-Turcotte scores.

In the active treatment group, HepaGam B doses of 35 mL started during transplant according to the regimen identified in Table 1 [see Dosing and Administration (2.1)]. As a result of the targeted potency of 550 IU/mL at the time of manufacture [see Dosage Forms and Strengths (3.)], the 35 mL doses of HepaGam B used in this study actually contained between 17,000 and 23,000 IU anti-HBs. These 35 mL doses consistently yielded anti-HBs trough levels > 500 IU/L (99% of all anti-HBs levels were > 500 IU/L; see Figure 1).

Figure 1: Frequency Histogram of Trough anti-HBs Levels more than 30 days after Transplant

Values below the target trough were only observed in the 2 patients with HBV recurrence who had anti-HBs levels <150 IU/L at the time of seroconversion.

For the efficacy endpoint of the proportion of patients with HBV recurrence (HBsAg positive and/or HBeAg positive after 4 weeks post-OLT), a significant treatment effect was observed. As summarized in Table 6, HBV recurrence was seen in 2/15 or 13% of HepaGam B patients compared to 12/14 or 86% of retrospective untreated control patients (see Table 6). One of the 16 HepaGam B patients died 2 weeks post-transplant was excluded from all efficacy analyses, but was included for safety analyses. The death was not HBV or study drug related.

Table 6 - Interim Results of Study HB-005 for the Prevention of Hepatitis B Recurrence Following Liver Transplantation

	HepaGam B	Retrospective Untreated Control	P-value (Fisher's Exact Test)
HBV Recurrence Proportion, % (95% confidence interval)	13.3 (1.7 -40.5)	85.7 (57.2 -98.2)	< 0.001

The conclusion that HepaGam B m

HibTITER

Pronunciation: hem-OFF-fil-us
Generic Name: Haemophilus B Oligosaccharide Conjugate Vaccine
Brand Name: HibTITER

HibTITER is used for:

Preventing infection caused by Haemophilus influenza type B bacteria.

HibTITER is a vaccine. It works by stimulating the body to produce antibodies against the organism that causes the infection.

Do NOT use HibTITER if:

• you are allergic to any ingredient in HibTITER, including diphtheria toxoid

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

Before using HibTITER:

Some medical conditions may interact with HibTITER. 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 blood clotting problems (eg, thrombocytopenia)


• if you have a fever, an infection, a weakened immune system, or HIV, or you are taking medicines that suppress the immune system (eg, corticosteroids)

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

• Immunosuppressive agents (eg, corticosteroids such as hydrocortisone) because the effectiveness of HibTITER may be decreased


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

This may not be a complete list of all interactions that may occur. Ask your health care provider if HibTITER 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 HibTITER:

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

• HibTITER is usually administered as an injection at your doctor's office, hospital, or clinic. If you are using HibTITER at home, carefully follow the injection procedures taught to you by your health care provider.


• If you miss a dose of HibTITER, contact your doctor.

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

Important safety information:

• If your child has a fever or infection, your doctor may delay giving the vaccine.


• HibTITER may cause fever, irritability, and redness, tenderness, or a lump at the injection site. These symptoms should go away within 1 to 2 days.


• HibTITER is not recommended for use in CHILDREN younger than 6 weeks of age. Safety and effectiveness in this age group have not been confirmed.


• PREGNANCY and BREAST-FEEDING: HibTITER is not recommended for use in pregnant women. If you think you may be pregnant, discuss with your doctor the benefits and risks of using HibTITER during pregnancy.

Possible side effects of HibTITER:

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; fever; irritability; loss of appetite; prolonged crying; redness, tenderness, or a lump at the injection site; sleepiness; 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).

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: HibTITER 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.

Proper storage of HibTITER:

HibTITER is usually handled and stored by a health care provider. If you are using HibTITER at home, store HibTITER as directed by your pharmacist or health care provider. Keep HibTITER out of the reach of children and away from pets.

General information:

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


• HibTITER 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 HibTITER. 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 HibTITER resources

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

• HibTITER Concise Consumer Information (Cerner Multum)


• Hibtiter Advanced Consumer (Micromedex) - Includes Dosage Information

Compare HibTITER with other medications

• Haemophilus influenzae Prophylaxis

Zantryl

Generic Name: phentermine (FEN ter meen)

Brand Names: Adipex-P, Oby-Cap, T-Diet, Zantryl

What is Zantryl (phentermine)?

Phentermine is a stimulant that is similar to an amphetamine. Phentermine is an appetite suppressant that affects the central nervous system.

Phentermine is used together with diet and exercise to treat obesity (overweight) in people with risk factors such as high blood pressure, high cholesterol, or diabetes.

Phentermine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Zantryl (phentermine)?

Do not use phentermine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects. Taking phentermine together with other diet medications such as fenfluramine (Phen-Fen) or dexfenfluramine (Redux) can cause a rare fatal lung disorder called pulmonary hypertension. Do not take phentermine with any other diet medications without your doctor's advice. Phentermine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of phentermine.

Phentermine is only part of a complete program of treatment that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely.

Phentermine may be habit-forming and should be used only by the person it was prescribed for. Never share phentermine with another person, especially someone with a history of drug abuse or addiction. Keep track of the amount of medicine used from each new bottle. Phentermine is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription. Do not stop using phentermine suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using phentermine.

What should I discuss with my healthcare provider before taking Zantryl (phentermine)?

Do not use phentermine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Taking phentermine together with other diet medications such as fenfluramine (Phen-Fen) or dexfenfluramine (Redux) can cause a rare fatal lung disorder called pulmonary hypertension. Do not take phentermine with any other diet medications without your doctor's advice.

You should not take phentermine if you are allergic to it, or if you have:

• 
  

  coronary artery disease (hardening of the arteries);

  
  


• 
  

  heart disease;

  
  


• 
  

  severe or uncontrolled high blood pressure;

  
  


• 
  

  overactive thyroid;

  
  


• 
  

  glaucoma;

  
  


• 
  

  if you have a history of drug or alcohol abuse; or

  
  


• 
  

  if you are allergic to other diet pills, amphetamines, stimulants, or cold medications.

  
  

To make sure you can safely take phentermine, tell your doctor if you have any of these other conditions:

• 
  

  high blood pressure;

  
  


• 
  

  diabetes; or

  
  


• 
  

  a thyroid disorder.

  
  

FDA pregnancy category C. It is not known whether phentermine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Phentermine can pass into breast milk and may harm a nursing baby. You should not breast-feed while taking phentermine. Do not give this medication to a child younger than 16 years old. Phentermine may be habit-forming and should be used only by the person it was prescribed for. Never share phentermine with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

How should I take Zantryl (phentermine)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

It is best to take phentermine on an empty stomach before breakfast or within 2 hours after breakfast.

To prevent sleep problems, take this medication early in the day, no later than 6:00 pm.

Talk with your doctor if you have increased hunger or if you otherwise think the medication is not working properly. Taking more of this medication will not make it more effective and can cause serious, life-threatening side effects.

Phentermine should be taken only for a short time, such as a few weeks.

Do not stop taking phentermine suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using phentermine. Store at room temperature away from moisture and heat. Keep track of the amount of medicine used from each new bottle. Phentermine is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of phentermine can be fatal.

Overdose symptoms may include confusion, hallucinations, panic, feeling hostile or aggressive, nausea, vomiting, diarrhea, stomach cramps, irregular heartbeat, rapid breathing, overactive reflexes, confusion, hallucinations, seizure (convulsions), feeling light-headed, or fainting.

What should I avoid while taking Zantryl (phentermine)?

Drinking alcohol can increase certain side effects of phentermine. Phentermine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Zantryl (phentermine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

• 
  

  feeling short of breath, even with mild exertion;

  
  


• 
  

  chest pain, feeling like you might pass out;

  
  


• 
  

  swelling in your ankles or feet;

  
  


• 
  

  pounding heartbeats or fluttering in your chest;

  
  


• 
  

  confusion or irritability, unusual thoughts or behavior;

  
  


• 
  

  feelings of extreme happiness or sadness; or

  
  


• 
  

  dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure).

  
  

Less serious side effects may include:

• 
  

  feeling restless or hyperactive;

  
  


• 
  

  headache, dizziness, tremors;

  
  


• 
  

  sleep problems (insomnia);

  
  


• 
  

  dry mouth or an unpleasant taste in your mouth;

  
  


• 
  

  diarrhea or constipation, upset stomach; or

  
  


• 
  

  increased or decreased interest in sex, impotence.

  
  

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 Zantryl (phentermine)?

Tell your doctor about all other medicines you use, especially:

• 
  

  blood pressure medications;

  
  


• 
  

  insulin or oral diabetes medication; or

  
  


• 
  

  an antidepressant such as citalopram (Celexa), fluoxetine (Prozac, Sarafem, Symbyax), paroxetine (Paxil), sertraline (Zoloft), and others.

  
  

This list is not complete and other drugs may interact with phentermine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Zantryl resources

• Zantryl Side Effects (in more detail)
• Zantryl Use in Pregnancy & Breastfeeding
• Zantryl Drug Interactions
• Zantryl Support Group
• 1 Review for Zantryl - Add your own review/rating

• Phentermine Prescribing Information (FDA)


• Phentermine Monograph (AHFS DI)


• Adipex-P MedFacts Consumer Leaflet (Wolters Kluwer)


• Adipex-P Prescribing Information (FDA)


• Fastin Advanced Consumer (Micromedex) - Includes Dosage Information


• Ionamin MedFacts Consumer Leaflet (Wolters Kluwer)


• Ionamin Prescribing Information (FDA)

Compare Zantryl with other medications

• Obesity
• Weight Loss

Where can I get more information?

• Your pharmacist can provide more information about phentermine.

See also: Zantryl side effects (in more detail)

halcinonide Topical application

hal-SIN-oh-nide

Commonly used brand name(s)

In the U.S.

• Halog

In Canada

• Halog Cream


• Halog Ointment


• Halog Solution

Available Dosage Forms:

• Solution


• Cream


• Ointment

Therapeutic Class: Corticosteroid, Strong

Pharmacologic Class: Adrenal Glucocorticoid

Uses For halcinonide

Halcinonide topical is used to help relieve redness, itching, swelling, or other discomfort caused by skin conditions. halcinonide is a corticosteroid (cortisone-like medicine or steroid).

halcinonide is available only with your doctor's prescription.

Before Using halcinonide

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For halcinonide, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to halcinonide or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of halcinonide topical in the pediatric population. However, because of halcinonide's toxicity, it should be used with caution. Children may absorb large amounts through the skin, which can cause serious side effects. If your child is using halcinonide, follow your doctor's instructions very carefully.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of halcinonide topical in the elderly.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of halcinonide. Make sure you tell your doctor if you have any other medical problems, especially:

• Cushing's syndrome (adrenal gland disorder) or


• Diabetes or


• Hyperglycemia (high blood sugar) or


• Intracranial hypertension (increased pressure in the head)—Use with caution. May make these conditions worse.

• Infection of the skin at or near the place of application or


• Large sores, broken skin, or severe skin injury at the place of application—The chance of side effects may be increased.

Proper Use of halcinonide

It is very important that you use halcinonide only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects or skin irritation.

halcinonide is for use on the skin only. Do not get it in your eyes, nose, mouth, or vagina. Do not use it on skin areas that have cuts, scrapes, or burns. If it does get on these areas, rinse it off right away with water.

halcinonide should only be used for skin conditions that your doctor is treating. Check with your doctor before using it for other conditions, especially if you think that a skin infection may be present. halcinonide should not be used to treat certain kinds of skin infections or conditions, such as severe burns.

To use:

• Wash your hands with soap and water before and after using halcinonide.


• Apply a thin layer of halcinonide to the affected area of the skin. Rub it in gently.


• Do not bandage or otherwise wrap the skin being treated unless directed to do so by your doctor.


• If the medicine is applied to the diaper area of an infant, do not use tight-fitting diapers or plastic pants unless directed to do so by your doctor.


• If your doctor ordered an occlusive dressing or airtight covering to be applied over the medicine, make sure you know how to apply it. Occlusive dressings increase the amount of medicine absorbed through your skin, so use them only as directed. If you have any questions about this, check with your doctor.

Dosing

The dose of halcinonide will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of halcinonide. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For topical dosage forms (cream and ointment):
  
  • For redness, itching, and swelling of the skin:
    
    • Adults—Apply to the affected area of the skin two to three times per day.
    
    
    • Children—Apply to the affected area of the skin two to three times per day.
    
    
  
  

Missed Dose

If you miss a dose of halcinonide, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using halcinonide

It is very important that your doctor check the progress of you or your child at regular visits for any unwanted effects that may be caused by halcinonide.

If your or your child's symptoms do not improve within a few days, or if they become worse, check with your doctor.

Using too much of halcinonide or using it for a long time may increase your risk of having adrenal gland problems. The risk is greater for children and patients who use large amounts for a long time. Talk to your doctor right away if you or your child have more than one of these symptoms while you are using halcinonide: blurred vision; dizziness or fainting; a fast, irregular, or pounding heartbeat; increased thirst or urination; irritability; or unusual tiredness or weakness.

Stop using halcinonide and check with your doctor right away if you or your child have a skin rash, burning, stinging, swelling, or irritation on the skin.

Do not use cosmetics or other skin care products on the treated areas.

halcinonide Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Incidence not known

• Blistering, burning, crusting, dryness, or flaking of the skin


• irritation


• itching, scaling, severe redness, soreness, or swelling of the skin


• redness and scaling around the mouth


• thinning of the skin with easy bruising, especially when used on the face or where the skin folds together (e.g. between the fingers)

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known

• Acne or pimples


• burning and itching of the skin with pinhead-sized red blisters


• burning, itching, and pain in hairy areas, or pus at the root of the hair


• increased hair growth on the forehead, back, arms, and legs


• lightening of normal skin color


• lightening of treated areas of dark skin


• reddish purple lines on the arms, face, legs, trunk, or groin


• softening of the skin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: halcinonide Topical application side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More halcinonide Topical application resources

• Halcinonide Topical application Side Effects (in more detail)
• Halcinonide Topical application Use in Pregnancy & Breastfeeding
• Halcinonide Topical application Drug Interactions
• Halcinonide Topical application Support Group
• 0 Reviews for Halcinonide Topical application - Add your own review/rating

Compare halcinonide Topical application with other medications

• Atopic Dermatitis
• Dermatitis
• Eczema
• Psoriasis

Actemra

Generic Name: tocilizumab (TOE si LIZ oo mab)

Brand Names: Actemra

What is tocilizumab?

Tocilizumab reduces the effects of a substance in the body that can cause inflammation.

Tocilizumab is used to treat moderate to severe rheumatoid arthritis in adults. It is sometimes given together with other arthritis medications.

Tocilizumab is also used to treat systemic juvenile idiopathic arthrits (or "Still disease") in children who are at least 2 years old. It is sometimes given together with methotrexate (Rheumatrex, Trexall).

Tocilizumab is usually given after other medications have been tried without successful treatment of symptoms.

Tocilizumab may also be used for purposes not listed in this medication guide.

What is the most important information I should know about tocilizumab?

Serious and sometimes fatal infections may occur during treatment with tocilizumab. Contact your doctor right away if you have signs of infection such as: fever, chills, body aches, flu symptoms, cough, sweating, feeling short of breath, diarrhea, weight loss, sores on your skin, painful urination, or feeling very tired.

Before you start treatment with tocilizumab, your doctor may perform tests to make sure you do not have tuberculosis or other infections.

Tell your doctor if you have an active or recent infection, liver disease or hepatitis B, diabetes, diverticulitis, stomach ulcer or bleeding, high cholesterol, multiple sclerosis, HIV/AIDS, a weak immune system, or a history of cancer.

Tocilizumab can lower the blood cells that help your body fight infections. Avoid being near people who are sick or have infections.

Do not receive a "live" vaccine while you are being treated with tocilizumab.

Treatment with tocilizumab may increase your risk of developing certain types of cancer. Talk to your doctor about your specific risk.

What should I discuss with my healthcare provider before I receive tocilizumab?

Tell your doctor if you have ever had tuberculosis, if anyone in your household has tuberculosis, or if you have recently traveled to an area where tuberculosis is common.

To make sure you can safely use tocilizumab, tell your doctor if you have any of these other conditions:

• 
  

  an active or recent infection (such as herpes, pneumonia, or yeast infection);

  
  


• 
  

  signs of infection such as fever, chills, cough, body aches, diarrhea, weight loss, painful urination, or coughing up blood;

  
  


• 
  

  open sores or skin wounds;

  
  


• liver disease;


• 
  

  diverticulitis, stomach ulcer, or a history of stomach or intestinal bleeding;

  
  


• 
  

  diabetes;

  
  


• 
  

  a weak immune system;

  
  


• 
  

  high cholesterol;

  
  


• 
  

  hepatitis B (or if you are a carrier of the virus);

  
  


• 
  

  a nerve-muscle disease such as multiple sclerosis;

  
  


• 
  

  HIV or AIDS;

  
  


• 
  

  a history of cancer; or

  
  


• 
  

  if you are scheduled to receive any vaccines.

  
  

FDA pregnancy category C. It is not known whether tocilizumab will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication..

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of tocilizumab on the baby.

It is not known whether tocilizumab passes into breast milk. You should not breast-feed while you are using tocilizumab.

Treatment with tocilizumab may increase your risk of developing certain types of cancer. Talk to your doctor about your specific risk.

How is tocilizumab given?

Before you start treatment with tocilizumab, your doctor may perform tests to make sure you do not have tuberculosis or other infections.

Tocilizumab is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting. Tocilizumab must be given slowly, and the IV infusion can take 1 hour to complete.

This medication is usually given every 4 weeks.

Tocilizumab can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood need to be tested often. Visit your doctor regularly.

Contact your doctor right away if you have signs of infection such as: fever, chills, body aches, flu symptoms, cough, sweating, feeling short of breath, diarrhea, weight loss, sores on your skin, painful urination, or feeling very tired.

Some infections are more likely to occur in certain areas of the world. Tell your doctor where you live and where you have recently traveled or plan to travel to during treatment. If you need to have surgery, tell the surgeon ahead of time that you are using tocilizumab.

You may be treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your tocilizumab injection.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while receiving tocilizumab?

Do not receive a "live" vaccine while using tocilizumab, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), oral polio, chickenpox (varicella), BCG (Bacillus Calmette and Guérin), and nasal flu vaccine.

Avoid being near people who are sick or have infections.

Tocilizumab side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Serious and sometimes fatal infections may occur during treatment with tocilizumab. Call your doctor right away if you have signs of infection such as:

• 
  

  fever, flu symptoms, mouth and throat ulcers, weight loss, feeling very tired;

  
  


• 
  

  sores in your mouth and throat or on your skin;

  
  


• 
  

  easy bruising, unusual bleeding (nose, mouth, vagina, or rectum);

  
  


• 
  

  purple or red pinpoint spots under your skin;

  
  


• 
  

  cough with yellow or green mucus, stabbing chest pain, feeling short of breath;

  
  


• 
  

  pain or burning when you urinate.

  
  

Call your doctor at once if you have any of these other serious side effects:

• 
  

  severe stomach pain with constipation;

  
  


• 
  

  bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

  
  


• 
  

  painful blistering skin rash with burning, itching, or tingly feeling; or

  
  


• 
  

  upper stomach pain, vomiting, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

  
  

Less serious side effects may include:

• 
  

  runny or stuffy nose, sinus pain, sore throat;

  
  


• 
  

  headache, dizziness;

  
  


• 
  

  itching; or

  
  


• 
  

  mild stomach cramps.

  
  

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 tocilizumab?

Tell your doctor about all other medications you use, especially:

• 
  

  birth control pills;

  
  


• 
  

  a blood thinner such as warfarin (Coumadin);

  
  


• 
  

  cyclosporine (Gengraf, Neoral, Sandimmune);

  
  


• 
  

  digoxin (digitalis, Lanoxin, Lanoxicaps);

  
  


• 
  

  omeprazole (Prilosec);

  
  


• 
  

  sirolimus (Rapamune) or tacrolimus (Prograf);

  
  


• 
  

  theophylline (Elixophyllin, Theo-24, Uniphyl);

  
  


• 
  

  abatacept (Orencia), adalimumab (Humira), anakinra (Kineret) certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), or rituximab (Rituxan);

  
  


• 
  

  atorvastatin (Lipitor), lovastatin (Mevacor) and other cholesterol-lowering medications;

  
  


• 
  

  seizure medication such as carbamazepine (Carbatrol, Tegretol), divalproex (Depakote), phenytoin (Dilantin), or valproic acid (Depakene);

  
  


• 
  

  a heart rhythm medication such as disopyramide (Norpace), procainamide (Pronestyl), or quinidine (Quin-G);

  
  


• 
  

  other drugs that weaken your immune system (such as cancer medicine or steroids); or

  
  


• 
  

  any other pain or arthritis medications (both prescription and over-the-counter) including methotrexate (Rheumatrex), aspirin, or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), etodolac (Lodine), indomethacin (Indocin), meloxicam (Mobic), nabumetone (Relafen), piroxicam (Feldene), and others.

  
  

This list is not complete and many other drugs may interact with tocilizumab. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

More Actemra resources

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

• Actemra Prescribing Information (FDA)


• Actemra Monograph (AHFS DI)


• Actemra Advanced Consumer (Micromedex) - Includes Dosage Information


• Actemra Consumer Overview


• Actemra MedFacts Consumer Leaflet (Wolters Kluwer)


• Tocilizumab Professional Patient Advice (Wolters Kluwer)

Compare Actemra with other medications

• Juvenile Idiopathic Arthritis
• Rheumatoid Arthritis

Where can I get more information?

• Your doctor or pharmacist can provide more information about tocilizumab.

See also: Actemra side effects (in more detail)

Hurricaine

Generic Name: benzocaine topical (BENZ oh kane TOP ik al)

Brand Names: Americaine, Americaine Hemorrhoidal, Anacaine, Anbesol Gel, Anbesol Liquid, Babee Teething Lotion, Benzo-O-Stetic, Boil Ease Pain Relieving, Cepacol Extra Strength, Cepacol Fizzlers, Dent-O-Kain, Dermoplast, Detane, Hurricaine, Lanacane, Maintain, Medicone Maximum Strength, Num-Zit, Numzident, Orabase, Orabase Gel-B, Orajel, Orajel Denture, Oral Pain Relief, OraMagic Plus, Outgro Pain Relief, Retre-Gel, Rid-A-Pain, Skeeter Stik, Solarcaine Aerosol, Sting-Kill, Topex, Trocaine, Vagisil Feminine Cream, zilactin-B

What is Hurricaine (benzocaine topical)?

Benzocaine is a local anesthetic (numbing medication). It works by blocking nerve signals in your body.

Benzocaine topical is used to reduce pain or discomfort caused by minor skin irritations, sore throat, sunburn, teething pain, vaginal or rectal irritation, ingrown toenails, hemorrhoids, and many other sources of minor pain on a surface of the body. Benzocaine is also used to numb the skin or surfaces inside the mouth, nose, throat, vagina, or rectum to lessen the pain of inserting a medical instrument such as a tube or speculum.

There are many brands and forms of benzocaine topical available and not all brands are listed on this leaflet.

Benzocaine topical may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Hurricaine (benzocaine topical)?

There are many brands and forms of benzocaine topical available and not all brands are listed on this leaflet.

Benzocaine topical used in the mouth or throat may cause a life-threatening condition in which the amount of oxygen in your blood stream becomes dangerously low. This condition is called methemoglobinemia (met-HEEM-oh glo-bin-EE-mee-a) and it may occur after only one use of benzocaine or after several uses.

Signs and symptoms of methemoglobinemia may occur within minutes or up to 2 hours after using benzocaine topical in the mouth or throat. GET EMERGENCY MEDICAL HELP IF YOU HAVE ANY OF THESE SYMPTOMS: headache, tired feeling, confusion, fast heart rate, and feeling light-headed or short of breath, with a pale, blue, or gray appearance of your skin, lips, or fingernails.

Do not use benzocaine topical if you have ever had methemoglobinemia in the past. Do not use this medicine on a child younger than 2 years old without medical advice. An overdose of numbing medications can cause fatal side effects if too much of the medicine is absorbed through your skin and into your blood. This is more likely to occur when using a numbing medicine without the advice of a medical doctor (such as during a cosmetic procedure like laser hair removal). Overdose symptoms may include uneven heartbeats, seizure (convulsions), coma, slowed breathing, or respiratory failure (breathing stops).

Use the smallest amount of this medication needed to numb the skin or relieve pain. Do not use large amounts of benzocaine topical, or cover treated skin areas with a bandage or plastic wrap without medical advice. Be aware that many cosmetic procedures are performed without a medical doctor present.

Your body may absorb more of this medication if you use too much, if you apply it over large skin areas, or if you apply heat, bandages, or plastic wrap to treated skin areas. Skin that is cut or irritated may also absorb more topical medication than healthy skin.

Before using benzocaine topical, tell your doctor if you have any type of inherited enzyme deficiency, heart disease, a breathing disorder such as asthma, bronchitis, or emphysema, or if you smoke.

If you are treating a sore throat, call your doctor if the pain is severe or lasts longer than 2 days, especially if you also develop a fever, headache, skin rash, swelling, nausea, vomiting, cough, or breathing problems.

What should I discuss with my health care provider before using Hurricaine (benzocaine topical)?

Do not use benzocaine topical if you have ever had methemoglobinemia in the past. An overdose of numbing medications can cause fatal side effects if too much of the medicine is absorbed through your skin and into your blood. This is more likely to occur when using a numbing medicine without the advice of a medical doctor (such as during a cosmetic procedure like laser hair removal). Overdose symptoms may include uneven heartbeats, seizure (convulsions), coma, slowed breathing, or respiratory failure (breathing stops).

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have:

• 
  

  asthma, bronchitis, emphysema, or other breathing disorder;

  
  


• 
  

  heart disease;

  
  


• 
  

  a personal or family history of methemoglobinemia, or any genetic (inherited) enzyme deficiency; or

  
  


• 
  

  if you smoke.

  
  

FDA pregnancy category C. It is not known whether benzocaine topical will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.. It is not known whether benzocaine topical passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Do not use this medicine on a child younger than 2 years old without medical advice.

How should I use Hurricaine (benzocaine topical)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

Your body may absorb more of this medication if you use too much, if you apply it over large skin areas, or if you apply heat, bandages, or plastic wrap to treated skin areas. Skin that is cut or irritated may also absorb more topical medication than healthy skin.

Use the smallest amount of medicine needed to numb the skin or relieve pain. Do not use large amounts of benzocaine topical, or cover treated skin areas with a bandage or plastic wrap without medical advice. Be aware that many cosmetic procedures are performed without a medical doctor present.

This medication comes with instructions for safe and effective application. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

To treat minor skin conditions, apply a thin layer of benzocaine topical to the affected area up to 4 times per day. If using the spray, hold the container 6 to 12 inches away from the skin. Do not spray this medication onto your face. Spray it instead on your hands and then rub it onto the face, avoiding contact with your eyes.

To treat hemorrhoids, clean the area with soap and water before applying benzocaine topical. Apply the medication up to 6 times per day. If you are using the rectal suppository, try to empty your bowel and bladder before inserting the suppository. Remove the outer wrapper from the suppository before inserting it. Avoid handling the suppository too long or it will melt in your hands.

Do not use benzocaine topical to treat large skin areas or deep puncture wounds. Avoid using the medicine on skin that is raw or blistered, such as a severe burn or abrasion.

Call your doctor if your symptoms do not improve or if they get worse within the first 7 days of using benzocaine topical. Also call your doctor if your symptoms had cleared up but then came back.

If you are treating a sore throat, call your doctor if the pain is severe or lasts longer than 2 days, especially if you also develop a fever, headache, skin rash, swelling, nausea, vomiting, cough, or breathing problems.

Store at room temperature away from moisture and heat. Do not freeze.

What happens if I miss a dose?

Since benzocaine topical is used as needed, you may not be on a dosing schedule. If you are using the medication regularly, use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of benzocaine topical applied to the skin can cause life-threatening side effects such as uneven heartbeats, seizure (convulsions), coma, slowed breathing, or respiratory failure (breathing stops).

What should I avoid while taking Hurricaine (benzocaine topical)?

Avoid eating within 1 hour after using benzocaine topical on your gums or inside your mouth.

Benzocaine topical is for use only on the surface of your body, or just inside the mouth, vagina, or rectum. Avoid getting this medication in your eyes. Avoid swallowing the gel, liquid, or ointment while applying it to your gums or the inside of your mouth. The throat spray or oral lozenge may be swallowed gradually during use.

Do not apply other medications to the same affected areas you treat with benzocaine topical, unless your doctor has told you otherwise.

Hurricaine (benzocaine topical) side effects

Benzocaine topical used in the mouth or throat may cause a life-threatening condition in which the amount of oxygen in your blood stream becomes dangerously low. This condition is called methemoglobinemia (met-HEEM-oh glo-bin-EE-mee-a) and it may occur after only one use of benzocaine or after several uses.

Signs and symptoms may occur within minutes or up to 2 hours after using benzocaine topical in the mouth or throat. GET EMERGENCY MEDICAL HELP IF YOU HAVE:

• 
  

  headache, tired feeling, confusion;

  
  


• 
  

  fast heart rate;

  
  


• 
  

  feeling light-headed or short of breath; and

  
  


• 
  

  pale, blue, or gray appearance of your skin, lips, or fingernails.

  
  

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using benzocaine topical and call your doctor at once if you have any of these other serious side effects:

• 
  

  headache, weakness, dizziness, breathing problems, fast heart rate, and gray or bluish colored skin (rare but serious side effects of benzocaine);

  
  


• 
  

  severe burning, stinging, or sensitivity where the medicine is applied;

  
  


• 
  

  swelling, warmth, or redness; or

  
  


• 
  

  oozing, blistering, or any signs of infection.

  
  

Less serious side effects may include:

• 
  

  mild stinging, burning, or itching where the medicine is applied;

  
  


• 
  

  skin tenderness or redness; or

  
  


• 
  

  dry white flakes where the medicine was applied.

  
  

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 Hurricaine (benzocaine topical)?

It is not likely that other drugs you take orally or inject will have an effect on topically applied benzocaine topical. But many drugs can interact with each other. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Hurricaine resources

• Hurricaine Side Effects (in more detail)
• Hurricaine Use in Pregnancy & Breastfeeding
• Hurricaine Support Group
• 0 Reviews for Hurricaine - Add your own review/rating

• Hurricaine Advanced Consumer (Micromedex) - Includes Dosage Information


• Americaine Ointment MedFacts Consumer Leaflet (Wolters Kluwer)


• Anacaine Advanced Consumer (Micromedex) - Includes Dosage Information


• Benz-O-Sthetic Gel MedFacts Consumer Leaflet (Wolters Kluwer)


• Lanacane Aerosol Spray MedFacts Consumer Leaflet (Wolters Kluwer)


• OraMagic Plus Suspension MedFacts Consumer Leaflet (Wolters Kluwer)


• Rid-A-Pain Topical Advanced Consumer (Micromedex) - Includes Dosage Information

Compare Hurricaine with other medications

• Oral and Dental Conditions

Where can I get more information?

• Your pharmacist can provide more information about benzocaine topical.

See also: Hurricaine side effects (in more detail)