Loceryl Cream

Loceryl Cream

amorolfine

CREAM

Loceryl 0.25% Cream

amorolfine

Read all of this leaflet carefully before you start using this medicine.

• Keep this leaflet. You may need to read it again.


• If you have any further questions, ask your doctor or pharmacist.


• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.


• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

• 1. What Loceryl is and what it is used for


• 2. Before you use Loceryl


• 3. How to use Loceryl


• 4. Possible side effects


• 5. How to store Loceryl


• 6. Further information

What Loceryl is and what it is used for

• Loceryl is used to treat certain fungal infections of the skin (e.g. athlete’s foot).


• Loceryl contains the active substance amorolfine (as the hydrochloride), which belongs to a group of medicines known as antifungals.

Before you use Loceryl

Do not use Loceryl

• If you are allergic (hypersensitive) to amorolfine or any of the other ingredients of Loceryl (see section 6 for other ingredients).


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

Take special care with Loceryl

• Avoid the cream coming into contact with the eyes, ears or mucous membranes (e.g. mouth and nostrils).

Using other medicines

There are no known interactions with other medicines.

Nail varnish or artificial nails should not be used while using Loceryl.

Please tell your doctor or pharmacist if you are using or have recently used any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

You should not use Loceryl and tell your doctor if you are pregnant, planning to become pregnant or are breast-feeding.

Your doctor will then decide whether you should use Loceryl.

Ask your doctor or pharmacist for advice before taking any medicine.

Important information about some of the ingredients of Loceryl

This medicinal product contains stearyl alcohol which may cause local skin reaction (e.g. contact dermatitis).

How to use Loceryl

• Always use Loceryl exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.


• The cream should be rubbed gently into the infected skin area each evening after washing. It is important to continue using the cream until the infection clears up and for about 3 to 5 days after that. This generally means that you will need to use the cream for at least 2 to 3 weeks, but for some foot infections up to 6 weeks treatment may be needed.

If you get Loceryl in your eyes or ears

If you get Loceryl in your eyes or ears wash out with water immediately and contact your doctor, pharmacist or nearest hospital straight away.

If you accidently swallow Loceryl

If you, or anyone else, accidentally swallows the cream contact your doctor, pharmacist or nearest hospital straight away.

If you forget to use Loceryl

If you miss a treatment one evening, do not worry. Apply the cream the next evening and continue as directed by your doctor.

If you stop using Loceryl

Do not stop using Loceryl before your doctor tells you to or your infection could come back.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Loceryl Cream Side Effects

Like all medicines, Loceryl can cause side effects, although not everybody gets them.

In addition to the beneficial effects of Loceryl, it is possible that unwanted effects will occur during treatment, even when it is used as directed.

Rare side effects (occurring in less than 1 in 1000 people)

Loceryl may cause skin irritation (redness, itching or a burning feeling).

Very rare side effects (occurring in less than 1 in 10,000 people)

An allergic skin reaction (contact dermatitis) may occur

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How to store Loceryl

• Keep out of the reach and sight of children.


• Do not use Loceryl after the expiry date which is stated on the tube and carton. The expiry date refers to the last day of that month.


• Keep the pack away from heat (store below 30°C).

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further information

What Loceryl contains

Loceryl contains 0.25% w/w of the active substance amorolfine (as the hydrochloride) The other ingredients are 2-phenoxy ethanol, polyoxyl 40 stearate, stearyl alcohol, liquid paraffin, white soft paraffin, carbomer, sodium hydroxide, disodium edetate and purified water.

What Loceryl looks like and contents of the pack

Loceryl is available in a tube with a screw cap. Each tube contains 20 g of cream.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Galderma (UK) Limited

Meridien House

69-71 Clarendon Road

Watford

Herts

WD17 1DS

UK

(PL 10590/0041)

Manufacturer:

Laboratoires Galderma

ZI- Montdésir

74540 Alby-sur-Chéran

France

Further information

You can get more information on Loceryl Cream from your doctor or pharmacist.

This leaflet was last approved in 12/2007.

P22366-4

Sumycin

Generic Name: Tetracycline
Class: Tetracyclines
VA Class: AM250
CAS Number: 60-54-8

Introduction

Antibacterial; antibiotic derived from Streptomyces aureofaciens^{b c d} or produced semisynthetically from oxytetracycline.^b

Uses for Sumycin

Respiratory Tract Infections

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae.^{c d 104}

Treatment of respiratory tract infections caused by Haemophilus influenzae, Streptococcus pneumoniae, or Klebsiella.^{c d 104} Should only be used for treatment of infections caused by these bacteria when in vitro susceptibility tests indicate the organism is susceptible.^{c d a}

Acne

Adjunctive treatment of moderate to severe inflammatory acne.^{a c d} Not indicated for treatment of noninflammatory acne.^a

Actinomycosis

Treatment of actinomycosis caused by Actinomyces israelii;^{104 114 c d} oral tetracyclines (usually doxycycline or tetracycline) used as follow-up after initial parenteral penicillin G.¹¹⁴

Amebiasis

Adjunct to amebicides for treatment of acute intestinal amebiasis.^{c d} Tetracyclines not included in current recommendations for treatment of amebiasis caused by Entamoeba.^{112 114}

Anthrax

Alternative to doxycycline for postexposure prophylaxis to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized Bacillus anthracis spores (inhalational anthrax).¹²² Initial drug of choice for such prophylaxis is ciprofloxacin or doxycycline;^{114 122 123 127} doxycycline is the preferred tetracycline because of ease of administration and proven efficacy in monkey studies.¹²²

Alternative to doxycycline for treatment of inhalational anthrax when a parenteral regimen is not available (e.g., supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting).^{c d 122 123} A multiple-drug parenteral regimen (ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective) is preferred for treatment of inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.^{122 123 i}

Balantidiasis

Treatment of balantidiasis† caused by Balantidium coli; drug of choice.^{112 114}

Bartonella Infections

Treatment of bartonellosis caused by Bartonella bacilliformis.^{c d}

Brucellosis

Treatment of brucellosis;^{104 114 c d} tetracyclines (usually doxycycline or tetracycline) considered drugs of choice.^{104 114} Used in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin),¹¹⁴ especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis).¹¹⁴

Burkholderia Infections

Treatment of glanders† caused by Burkholderia mallei.^{104 m} Experience is limited regarding treatment of human cases; optimum regimens not identified.^{123 m} Some clinicians suggest streptomycin used in conjunction with tetracycline or chloramphenicol or imipenem monotherapy.¹⁰⁴ Other clinicians suggest that, pending results of in vitro susceptibility tests, regimens used for treatment of melioidosis can be used for initial empiric treatment of glanders.¹²³ Doxycycline is the preferred tetracycline for treatment of melioidosis caused by susceptible B. pseudomallei.^{123 m}

Campylobacter Infections

Treatment of infections caused by Campylobacter.^{c d} Tetracyclines (usually doxycycline) are alternatives,¹¹⁴ not drugs of choice for C. jejuni.^{104 114}

Chancroid

Treatment of chancroid caused by Haemophilus ducreyi.^{c d} Not included in CDC recommendations for treatment of chancroid;¹⁰¹ CDC and others recommend azithromycin, ceftriaxone, ciprofloxacin, or erythromycin.^{101 102}

Chlamydial Infections

Treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis.^{c d 102} Doxycycline is the preferred tetracycline for treatment of these infections, including presumptive treatment of chlamydial infections in patients with gonorrhea.¹⁰¹

Treatment of trachoma and inclusion conjunctivitis caused by C. trachomatis.^{c d 104} Consider that anti-infectives may not eliminate C. trachomatis in all cases of chronic trachoma.^{c d}

Treatment of lymphogranuloma venereum (genital, inguinal, or anorectal infections) caused by C. trachomatis.^{c d 102 104} Doxycycline is the preferred tetracycline for these infections.^{101 114}

Treatment of psittacosis (ornithosis) caused by C. psittaci.^{100 104 114 c d} Doxycycline and tetracycline are drugs of choice.^{100 114} For initial treatment of severely ill patients, use IV doxycycline.¹⁰⁰

Clostridium Infections

Alternative for treatment of infections caused by Clostridium.^{c d} Tetracyclines are alternatives to metronidazole or penicillin G for adjunctive treatment of C. tetani infections.¹⁰⁴

Dientamoeba fragilis Infections

Treatment of Dientamoeba fragilis infections.¹¹² Drugs of choice are iodoquinol, paromomycin, tetracycline, or metronidazole.¹¹²

Enterobacteriaceae Infections

Treatment of infections caused by susceptible Escherichia coli, Enterobacter aerogenes, Klebsiella, or Shigella.^{c d} Only use for treatment of infections caused by these common gram-negative bacteria when other appropriate anti-infectives are contraindicated or ineffective^a and when in vitro susceptibility tests indicate the organism is susceptible.^{a c d}

Fusobacterium Infections

Alternative to penicillin G for the treatment of infections caused by Fusobacterium fusiforme (Vincent's infection).^{c d}

Gonorrhea and Associated Infections

Alternative for treatment of uncomplicated gonorrhea caused by susceptible Neisseria gonorrhoeae.^{c d} Tetracyclines are considered inadequate therapy and are not recommended by CDC for treatment of gonorrhea.^{101 a}

Empiric treatment of epididymitis most likely caused by N. gonorrhoeae or C. trachomatis; used in conjunction with IM ceftriaxone.¹⁰²

Granuloma Inguinale (Donovanosis)

Treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis.^{c d} Doxycycline is the tetracycline recommended as drug of choice by CDC.¹⁰¹

Helicobacter pylori Infection and Duodenal Ulcer Disease

Treatment of Helicobacter pylori infection and duodenal ulcer (active or a history of duodenal ulcer);^{104 e} eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.^{104 e}

Used in a multiple-drug regimen that includes tetracycline, metronidazole, and bismuth subsalicylate and a histamine H₂-receptor antagonist.^e If initial 14-day regimen does not eradicate H. pylori, a retreatment regimen that does not include metronidazole should be used.^e

Leptospirosis

Tetracyclines are alternatives to penicillin G for treatment of leptosporosis†.¹⁰⁴ Doxycycline is the preferred tetracycline for treatment or prevention of these infections.^l

Listeria Infections

Alternative for treatment of listeriosis caused by Listeria monocytogenes.^{c d} Not usually considered a drug of choice or alternative for these infections.^{104 114}

Malaria

Treatment of uncomplicated malaria† caused by chloroquine-resistant Plasmodium falciparum or chloroquine-resistant P. vivax and when the plasmodial species has not been identified.^{112 129}

CDC and others state treatments of choice for uncomplicated chloroquine-resistant P. falciparum malaria are a regimen of oral quinine in conjunction with oral doxycycline, tetracycline, or clindamycin or a regimen of atovaquone and proguanil.^{112 129} A regimen of quinine and doxycycline (or tetracycline) generally preferred over quinine and clindamycin,¹²⁹ except for young children or pregnant women who should not receive tetracyclines.¹²⁹ Quinine in conjunction with tetracycline (or doxycycline) also a regimen of choice for chloroquine-resistant P. vivax malaria.^{112 129}

Treatment of severe malaria caused by P. falciparum†;^{112 129} used in conjunction with IV quinidine gluconate initially and then oral quinine when an oral regimen is tolerated.^{112 129}

Active only against asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages) and cannot prevent delayed primary attacks or relapse of P. vivax malaria or provide a radical cure; primaquine usually also is indicated to eradicate hypnozoites and prevent relapse in patients treated for P. vivax malaria.^{112 129}

Assistance with diagnosis or treatment of malaria available from the CDC Malaria Epidemiology Branch by contacting the CDC Malaria Hotline at 770-488-7788 from 8:00 a.m. to 4:30 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours, on weekends, and holidays.¹²⁹

Nocardiosis

Tetracyclines are alternatives to co-trimoxazole for treatment of nocardiosis† caused by Nocardia.^{104 114}

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU) caused by Ureaplasma urealyticum, C. trachomatis, or Mycoplasma.^{c d 104} Doxycycline usually is the tetracycline of choice for NGU.^{101 102}

Consider that some cases of recurrent urethritis following tetracycline treatment may be caused by tetracycline-resistant U. urealyticum.¹⁰¹

Pasteurella multocida Infections

Treatment of infections caused by Pasteurella multocida†.^{104 114} Tetracyclines (usually doxycycline) are alternatives to penicillin G.^{104 114}

Plague

Treatment of plague caused by Yersinia pestis,^{c d 104 114 124} including naturally occurring or endemic bubonic, septicemic, or pneumonic plague and plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism.¹²⁴ Regimen of choice is streptomycin or gentamicin;^{104 114 123 124} alternatives are doxycycline, tetracycline, ciprofloxacin, or chloramphenicol.^{123 124} For plague meningitis, some experts recommend that chloramphenicol be included in the treatment regimen.¹²³

Postexposure prophylaxis following a high-risk exposure to Y. pestis† (e.g., household, hospital, or other close contact with an individual who has pneumonic plague; laboratory exposure to viable Y. pestis; confirmed exposure in the context of biologic warfare or bioterrorism).^{123 124} Doxycycline may be drug of choice;^{114 123 124} alternatives are tetracycline, ciprofloxacin, or chloramphenicol.¹²³ Prophylaxis not required for asymptomatic contacts of individuals with bubonic plague, but observe such contacts for 1 week and initiate treatment if symptoms occur.¹²³

Rat-bite Fever

Treatment of rat-bite fever† caused by Streptobacillus moniliformis or Spirillum minus.^{104 114} Tetracyclines (usually doxycycline) are alternatives to penicillin G.^{104 114}

Relapsing Fever

Treatment of relapsing fever caused by Borrelia recurrentis.^{104 c d} Tetracyclines are drugs of choice.¹⁰⁴

Rickettsial Infections

Treatment of rickettsial infections including Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae.^{114 123 c d} Doxycycline is the drug of choice for most rickettsial infections.^{114 a j}

Syphilis

Alternative to penicillin G for treatment of primary, secondary, latent, or tertiary syphilis (not neurosyphilis) in nonpregnant adults and adolescents hypersensitive to penicillins.^{101 114 c d} Use tetracyclines only if compliance and follow-up can be ensured since efficacy not well documented.¹⁰¹

Tularemia

Treatment of tularemia caused by Francisella tularensis, including naturally occurring or endemic tularemia and tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism.^{104 114 123 c d f} Drugs of choice are streptomycin or gentamicin; alternatives are tetracyclines (usually doxycycline), ciprofloxacin, or chloramphenicol.^{104 114 f} Risk of relapse and primary treatment failure may be higher with the alternatives.^f

Postexposure prophylaxis of tularemia† following a high-risk laboratory exposure to F. tularensis (e.g., spill, centrifuge accident, needlestick injury) or in individuals exposed to the organism in the context of biologic warfare or bioterrorism.^{123 f} Drugs of choice are doxycycline, tetracycline, or ciprofloxacin.^{123 f} Postexposure prophylaxis usually not recommended after exposure to natural or endemic tularemia (e.g., tick bite, rabbit or other animal exposure) and is unnecessary in close contacts of tularemia patients since human-to-human transmission does not occur.^f

Vibrio Infections

Treatment of cholera caused by Vibrio cholerae.^{104 114 c d h} Doxycycline and tetracycline are drugs of choice; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.^{104 114 c d h}

Treatment of severe V. parahaemolyticus† infection when anti-infective therapy is indicated in addition to supportive care.^h

Treatment of infections caused by V. vulnificus†.¹⁰⁴ Optimum anti-infective therapy has not been identified; a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime) is recommended.^{104 g h} Because the case fatality rate associated with V. vulnificus is high, initiate anti-infective therapy promptly if indicated.^g

Yaws

Alternative to penicillin G for treatment of yaws caused by Treponema pertenue.^{104 c d}

Yersinia Infections

Treatment of plague or postexposure prophylaxis of plague†.^{c d 104 114 123 124} (See Plague in Uses.)

Treatment of GI infections caused by Yersinia enterocolitica† or Y. pseudotuberculosis†.¹¹⁴ These GI infections usually are self-limited, but IDSA, AAP, and others recommend anti-infectives for severe infections or when septicemia or other invasive disease occurs.¹¹⁴ Some clinicians suggest the role of oral anti-infectives in management of enterocolitis, pseudoappendicitis syndrome, or mesenteric adenitis caused by Yersinia needs further evaluation.¹¹⁴

Sumycin Dosage and Administration

Administration

Oral Administration

Administer orally.^{c d}

Administer capsules and tablets with adequate amounts of fluid to reduce the risk of esophageal irritation and ulceration.^{c d}

Dosage

Available as tetracycline^d and tetracycline hydrochloride;^c dosage expressed in terms of tetracycline hydrochloride.^{c d}

Pediatric Patients

General Pediatric Dosage

Oral

Children >8 years of age: 25–50 mg/kg daily in 4 divided doses.^c

Balantidiasis†

Oral

Children ≥8 years of age: 40 mg/kg daily (up to 2 g) in 4 divided doses given for 10 days.^{112 114}

Brucellosis

Oral

Children ≥8 years of age: 30–40 mg/kg daily (up to 2 g) in 4 divided doses.¹¹⁴ Duration of treatment usually is 4–6 weeks; more prolonged treatment may be necessary for severe infections or when there are complications.¹¹⁴

If infection is severe or if endocarditis, meningitis, or osteomyelitis are present, administer IM streptomycin or gentamicin during the first 7–14 days of tetracycline therapy.^{114 c d} Rifampin can be administered concomitantly (with or without an aminoglycoside) to decrease the risk of relapse.¹¹⁴

Dientamoeba fragilis Infection†

Oral

Children ≥8 years of age: 40 mg/kg daily (up to 2 g) in 4 divided doses given for 10 days.¹¹²

Malaria†

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

Children ≥8 years of age: 6.25 mg/kg 4 times daily given for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).^{112 129}

Treatment of Uncomplicated P. vivax Malaria†

Oral

Children ≥8 years of age: 6.25 mg/kg 4 times daily given for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).¹²⁹

In addition, a 14-day regimen of oral primaquine (0.6 mg/kg once daily) also may be indicated to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.¹²⁹

Treatment of Severe P. falciparum Malaria†

Oral

Children ≥8 years of age: 6.25 mg/kg 4 times daily given for 7 days; used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.¹²⁹ If an IV tetracycline is necessary initially, use IV doxycycline until oral therapy can be tolerated.¹²⁹

Plague

Treatment of Pneumonic Plague

Oral

Children >8 years of age: 25–50 mg/kg daily in 4 divided doses^b given for ≥10–14 days.^{123 124}

Prompt initiation of treatment (within 18–24 hours of symptom onset) is essential.^{123 124} A parenteral regimen (e.g., IM streptomycin, IM or IV gentamicin, IV doxycycline) is preferred for initial treatment; an oral regimen may be substituted when the patient's condition improves or if a parenteral regimen is unavailable.^{123 124}

Postexposure Prophylaxis following High-risk Exposure†

Oral

Children >8 years of age: 25–50 mg/kg daily in 2 or 4 equally divided doses.^b

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days^{123 124} or the duration of exposure risk plus 7 days.¹²³

Syphilis

Primary or Secondary Syphilis

Oral

Children >8 years of age: 500 mg 4 times daily given for 14 days.^{101 102 114}

Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis)

Oral

Children >8 years of age: 500 mg 4 times daily given for 14 days for early latent syphilis (duration <1 year) or 500 mg 4 times daily given for 28 days for late latent syphilis (duration≥1 year), latent syphilis of unknown duration, or tertiary syphilis.^{101 102 114}

Vibrio Infections

Cholera

Oral

Children >8 years of age: 50 mg/kg daily in 4 divided doses given for 3 days.¹¹⁴

Adults

General Adult Dosage

Oral

1–2 g daily in 2–4 divided doses.^{c d}

500 mg twice daily or 250 mg 4 times daily may be adequate for mild to moderate infections; severe infections may required 500 mg 4 times daily.^{c d}

Respiratory Tract Infections

Mycoplasma pneumoniae Infections

Oral

1–2 g daily in 2–4 equally divided doses.^b Duration of treatment usually is 1–4 weeks.^b

Acne

Oral

1 g daily given in divided doses; when improvement occurs in 1–2 weeks, decrease slowly to a maintenance dosage of 125–500 mg daily.^{b c d} Continue maintenance dosage until clinical improvement allows discontinuation of the drug.^b

Actinomycosis

Oral

1–2 g daily for 6–12 months as follow-up to penicillin G.^b

Anthrax

Postexposure Prophylaxis following Exposure in the Context of Biologic Warfare or Bioterrorism

Oral

500 mg every 6 hours given for ≥60 days.¹²²

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear,^{123 k} but prolonged postexposure prophylaxis usually required.^{122 123} A duration of 60 days may be adequate for a low-dose exposure, but a duration >4 months may be necessary to reduce the risk following a high-dose exposure.^k CDC recommends that postexposure prophylaxis following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures) be continued for 60 days.^{122 123} The US Working Group on Civilian Biodefense and the US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommends that postexposure prophylaxis be continued for at least 60 days in individuals who are not fully immunized against anthrax and when anthrax vaccine is unavailable or cannot be used for postexposure vaccination.¹²³

Treatment of Inhalational Anthrax

Oral

500 mg every 6 hours.¹²²

Initial parenteral regimen preferred; use oral regimen for initial treatment only when a parenteral regimen is not available (e.g., supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting).^{122 i} Continue for total duration of ≥60 days if inhalational anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.^{102 123 i}

Balantidiasis†

Oral

500 mg 4 times daily given for 10 days.¹¹²

Brucellosis

Oral

500 mg 4 times daily given for 3 weeks.^{c d}

If infection is severe or if endocarditis, meningitis, or osteomyelitis are present, administer IM streptomycin or gentamicin during the first 7–14 days of tetracycline therapy.^{114 c d} Rifampin can be administered concomitantly to decrease the risk of relapse (with or without an aminoglycoside).¹¹⁴

Burkholderia Infections†

Melioidosis†

Oral

2–3 g daily given for 1–3 months.^b In severe cases, some clinicians recommend concomitant chloramphenicol during the first month.^b In patients with extrapulmonary suppurative lesions, continue tetracycline therapy for 6–12 months.^b

Campylobacter Infections

Campylobacter fetus Infections

Oral

1–2 g daily given for 10 days.^b

Chancroid

Oral

1–2 g daily given for 2–4 weeks.^b

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections

Oral

500 mg 4 times daily given for ≥7 days.^{102 c d}

Psittacosis (Ornithosis)

Oral

500 mg 4 times daily given for ≥10–14 days after defervescence.¹⁰⁰

Dientamoeba fragilis Infection†

Oral

500 mg 4 times daily for 10 days.¹¹²

Gonorrhea and Associated Infections

Uncomplicated Gonorrhea

Oral

500 mg 4 times daily given for 7 days.^{c d} No longer recommended for gonorrhea by CDC or other experts.^{101 102}

Empiric Treatment of Epididymitis†

Oral

500 mg 4 times daily given for 10 days; as follow-up to a single dose of IM ceftriaxone.¹⁰²

Granuloma Inguinale (Donovanosis)

Oral

1–2 g daily given for 2–4 weeks.^b

Helicobacter pylori Infection and Duodenal Ulcer Disease

Oral

500 mg in conjunction with metronidazole (250 mg) and bismuth subsalicylate (525 mg) 4 times daily (at meals and at bedtime) for 14 days; these drugs should be given concomitantly with usual dosage of an H₂-receptor antagonist.¹¹⁰

Leptospirosis†

Oral

1–2 g daily given for 5–7 days.^b

Malaria†

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

250 mg 4 times daily given for 7 days; used in conjunction with quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).^{112 129}

Treatment of Uncomplicated P. vivax Malaria†

Oral

250 mg 4 times daily given for 7 days; used in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).¹²⁹

In addition, a 14-day regimen of oral primaquine (30 mg once daily) also may be indicated to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.¹²⁹

Treatment of Severe P. falciparum Malaria†

Oral

250 mg 4 times daily for 7 days; used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.¹²⁹ If an IV tetracycline is necessary initially, use IV doxycycline until oral therapy can be tolerated.¹²⁹

Plague

Treatment

Oral

2–4 g daily in 4 divided doses^b given for ≥10–14 days.^{b 123}

Prompt initiation of treatment (within 18–24 hours of symptom onset) is essential.^{123 124} A parenteral regimen (e.g., IM streptomycin, IM or IV gentamicin, IV doxycycline) is preferred for initial treatment; an oral regimen may be substituted when the patient's condition improves or if a parenteral regimen is unavailable.^{123 124}

Postexposure Prophylaxis following High-risk Exposure†

Oral

1–2 g daily in 2 or 4 divided doses.¹²³

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days^{123 124} or the duration of exposure risk plus 7 days.¹²³

Relapsing Fever

Oral

1–2 g daily until afebrile for 7 days.^b A single 500-mg dose may be effective in some patients.^b

Rickettsial Infections

Oral

1–2 g daily in 2–4 divided doses.^b Duration of treatment usually is ≥3–7 days or until patients has been afebrile for approximately 2–3 days.^b

Q Fever

Oral

500 mg every 6 hours given for ≥14 days for treatment of acute Q fever.¹²³

For prophylaxis against Q fever†, 500 mg every 6 hours given for ≥5–7 days may prevent clinical disease if initiated 8–12 days after exposure; such prophylaxis is not effective and may only prolong the onset of disease if given immediately (1–7 days) after exposure.¹²³

Syphilis

Primary or Secondary Syphilis

Oral

500 mg 4 times daily given for 14 days recommended by CDC and others.^{101 102} Manufacturer recommends a total dosage of 30–40 g in equally divided doses given over 10–15 days.^{c d}

Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis)

Oral

500 mg 4 times daily given for 14 days for early latent syphilis (duration <1 year) or 500 mg 4 times daily given for 28 days for late latent syphilis (duration≥1 year), latent syphilis of unknown duration, or tertiary syphilis.^{101 102}

Tularemia

Treatment

Oral

500 mg 4 times daily¹²³ given for ≥14–21 days.^{123 f} Relapse may occur as long as 6 months after treatment with tetracycline; however, retreatment with the same dosage usually is curative.^b

Postexposure Prophylaxis following High-risk Exposure†

Oral

500 mg 4 times daily.¹²³

Initiate postexposure prophylaxis within 24 hours of exposure and continue for ≥14 days.^{123 f}

Vibrio Infections

Cholera

Oral

1–2 g daily given for 2–3 days.^b 500 mg 4 times daily for 3 days also has been recommended.¹⁰³

Yaws

Oral

1–2 g daily given for 10–14 days.^b

Prescribing Limits

Pediatric Patients

Malaria

Treatment of Severe P. falciparum Malaria†

Oral

Children ≥8 years of age: Maximum 1g daily.¹²⁹

Special Populations

Renal Impairment

Adjust dosage by decreasing doses or increasing dosing interval.^{c d}

Cautions for Sumycin

Contraindications

• 
  

  Known hypersensitivity to any tetracycline.^{c d}

  
  


• 
  

  Helidac Therapy (kit containing tetracycline, metronidazole, bismuth subsalicylate) contraindicated in pregnant or nursing women, pediatric patients, patients with hepatic or renal impairment, patients with known allergy to aspirin or salicylates, and those with known hypersensitivity to any component of the kit.^e

  
  

Warnings/Precautions

Warnings

Dental and Bone Effects

Use during tooth development (e.g., pregnancy, children <8 years of age) may cause permanent yellow-gray to brown discoloration of teeth and enamel hypoplasia.^{c d} Effects are most common following long-term use, but may occur following repeated short-term use.^{c d}

Tetracyclines form a stable calcium complex in any bone-forming tissue.^{c d} Reversible decrease in fibula growth rate has occurred in young animals receiving oral tetracycline.^{c d}

Use not recommended in children <8 years of age unless other appropriate drugs are ineffective or are contraindicated or unless the benefits in certain indications (e.g., anthrax) outweigh the risks.^{114 c d} (See Pediatric Use under Cautions.)

Fetal/Neonatal Morbidity

Animal studies indicate possible fetal toxicity (e.g., retardation of skeletal development) and embryotoxicity.^{c d} If used during pregnancy or if patient becomes pregnant while receiving tetracycline, patient should be apprised of the potential hazard to the fetus.^{c d} (See Pregnancy under Cautions.)

Renal Effects

Tetracyclines have antianabolic effects and may increase BUN.^{c d}

In patients with impaired renal function, high serum tetracycline concentrations may result in azotemia, hyperphosphatemia, and acidosis.^{c d} Excessive drug accumulation and possible liver toxicity may occur if usual dosage is used patients with renal impairment.^{c d} (See Renal Impairment under Dosage and Administration.)

Do not use tetracycline preparations past their expiration dates.^{c d} Outdated tetracycline preparations are highly nephrotoxic and have, on occasion, produced a Fanconi-like syndrome.^{c d}

Laboratory Monitoring

Periodically assess organ system function, including renal, hepatic and hematopoietic, during long-term therapy.^{c d}

Helidac Therapy

When the kit containing tetracycline, metronidazole, and bismuth subsalicylate (Helidac Therapy) is used for the treatment of H. pylori infection and duodenal ulcer disease, the cautions, precautions, and contraindications associated with metronidazole and bismuth subsalicylate must be considered in addition to those associated with tetracycline.^e

Sensitivity Reactions

Photosensitivity Reactions

Photosensitivity, manifested by an exaggerated sunburn reaction, reported with tetracyclines.^{c d}

Photosensitivity reactions may develop within a few minutes to several hours after sun exposure and usually persist 1–2 days after discontinuance of the drug.^a Most reactions result from accumulation of tetracyclines in skin and are phototoxic in nature; photoallergic reactions may also occur.^a

Discontinue drug at first evidence of skin erythema.^{c d}

Hypersensitivity Reactions

Oral suspension contains sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.^d

Cross-sensitization occurs among the various tetracyclines.^{c d}

General Precautions

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.^{c d} Discontinue drug and institute appropriate therapy if superinfection occurs.^{c d}

Nervous System Effects

Possibility of bulging fontanels in infants and benign intracranial hypertension (pseudotumor cerebri) in adults.^{c d} Effects usually resolve when drug discontinued, but possibility for permanent sequelae exists.^{c d}

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of tetracycline and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.^{c d}

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^{c d} In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.^{c d}

Because many strains of Acinetobacter, Bacteroides, Enterobacter, E. coli, Klebsiella, Shigella, S. pyogenes (group A β-hemolytic streptococci), S. pneumoniae, enterococci, and α-hemolytic streptococci are resistant to tetracycline, in vitro susceptibility tests should be performed if the drug is used for treatment of infections caused by these bacteria.^{c d}

Incision and drainage or other surgical procedures should be performed in conjunction with tetracycline therapy when indicated.^{c d}

Specific Populations

Pregnancy

Category D.^{c d} (See Fetal/Neonatal Morbidity under Cautions.)

Should not be used in pregnant women unless, in the judgement of the clinician, it is essential for the welfare of the patient and benefits outweigh the risks.^{c d}

CDC and others state tetracyclines can be used when necessary for treatment of inhalational anthrax in pregnant women.^{122 i} Since adverse effects on developing teeth and bones are dose-related, CDC suggests the drug might be used for a short period (7–14 days) before 6 months of gestation;ⁱ some clinicians recommend periodic liver function testing if used in pregnant women.¹²²

Malaria infection in pregnant women is associated with high risks of maternal and perinatal morbidity and mortality (e.g., miscarriage, premature delivery, low birth weight, congenital infection and/or perinatal death)¹

Cytarabine Injection Solution 20mg / ml

1. Name Of The Medicinal Product

Cytarabine 20 mg/ml Injection

2. Qualitative And Quantitative Composition

Each 1 ml contains 20 mg of cytarabine.

Presentations	100 mg/5 ml	500 mg/25 ml	1 g/50 ml
Amount cytarabine present	100 mg	500 mg	1 g

For excipients see 6.1.

3. Pharmaceutical Form

Solution for injection.

Clear, colourless solution.

4. Clinical Particulars

4.1 Therapeutic Indications

Cytarabine may be used alone or in combination with other antineoplastic agents. It is indicated alone or in combination for induction of remission and/or maintainance in patients with acute myeloid leukaemia, acute non-lymphoblastic leukaemias, acute lymphoblastic leukaemias, acute lymphocytic leukaemia, erythroleukaemia, blast crises of chronic myeloid leukaemia, diffuse histiocytic lymphomas (non-hodgkin's lymphomas of high malignancy), meningeal leukaemia and meningeal neoplasms. Clinicians should refer to the current literature on combination therapy before initiating treatment.

4.2 Posology And Method Of Administration

Cytarabine 20 mg/ml Injection is a ready to use solution and is suitable for intravenous, subcutaneous and intrathecal use.

Cytarabine 20 mg/ml Injection can be diluted with Sterilised Water for Injections BP, Glucose Intravenous Infusion BP or Sodium Chloride Intravenous Infusion BP. Prepared infusions, in the recommended diluents should be used immediately. Alternatively, the diluted infusion fluids may be stored at 2-8°C, protected from light, but portions remaining unused after 24 hours must be discarded.

Remission Induction: Adults

Continuous Dosing: The usual dose in leukaemia, is 2 mg/kg by rapid intravenous injection daily for ten days. If after ten days neither therapeutic response not toxicity has been observed, the dose may be increased to 4 mg/kg until a therapeutic response or toxicity is evident. Daily blood counts should be taken. Almost all patients can be carried to toxicity with these doses.

Alternatively, 0.5 to 1 mg/kg may be infused daily in 1-24 hours for ten days, and then at a rate of 2 mg/kg/day until toxicity is observed. Continue to toxicity or until remission occurs. Results from one hour infusions have been satisfactory in the majority of patients.

Intermittent dosing: Cytarabine may be given as intermittent intravenous doses of 3-5 mg/kg daily, for five consecutive days This course of treatment can be repeated after an interval of 2 to 9 days, and repeated until the therapeutic response or toxicity is exhibited.

Evidence of bone marrow inprovement has been reported to occur 7-64 days days after the beginning of therapy.

In general, if a patient shows neither remission or toxicity after a trial period, then cautiously administered higher doses can be administered. Generally patients tolerate higher doses given by rapid intravenous injection rather than slow infusion.

As a single agent for induction of remissions in patients with acute leukaemia, cytarabine has been given in doses of 200 mg/m² by continuous intravenous infusion for five days at approximately 2 week intervals.

Maintainance therapy: To maintain remission, doses of 1-1.5 mg/kg may be given intravenously or subcutaneously, once or twice weekly.

Leukaemic Meningitis: Therapy for established meningitis employs a wide variety of dose regimens but a recommended total daily dose not exceeding 100 mg, alternating with methotrexate (given either systemically or intrathecally) is recommended. Cytarabine has been given intrathecally at doses of 10-30 mg/m² three times a week until cerebro-spinal fluid findings return to normal.

Myelosuppression, anaemia and thrombocytopenia occur almost to all patients given daily infusions or injections. Myelosuppression is biphasic and nadirs at 7-9 and 15-24 days. Evidence of bone marrow improvement may be expected 7-64 (mean 28) days after the beginning of treatment.

Children: Children appear to tolerate higher doses of cytarabine than adults, and where the range of doses is given, children should receive the higher dose.

Elderly: No data is available to suggest that a change in dose is necessary in the elderly. However, the elderly patient is more susceptable to toxic reactions and therefore particular attention should be paid to drug induced leucopenia, thrombocytopenia and anaemia.

4.3 Contraindications

Cytarabine is contraindicated in patients with known hypersensitivity to the drug. Therapy with cytarabine should not be considered in patients with pre-existing drug-induced bone marrow suppression, unless in the opinion of the physician the potential benefits outweigh the hazards. Cytarabine should not be used in the management of non-malignant disease, except for immunosuppression.

4.4 Special Warnings And Precautions For Use

Cytarabine is a potent bone marrow suppressant. Patients receiving the drug should be kept under close medical supervision. Leucocyte and platelet counts should be performed frequently and daily during induction. One case of anaphylaxis that resulted in cardiopulmonary arrest and necessitated resuscitiation has been reported. This occurred immediately after intravenous cytarabine was administered.

Severe and at times fatal central nervous system (CNS), gastrointestinal (GI) and pulmonary toxicity (different from that seen with conventional therapy regimens of dosage schedules). These reactions include reversible corneal toxicity; cerebral and cerebellar dysfunction, usually reversible; severe gastrointestinal ulceration including pneumatosis cysteroides intestinalis, leading to peritonitis; sepsis and liver abscess; and pulmonary oedema.

Central Nervous System: Rarely, neurological effects such as quadriplegia and paralysis have been reported with cytosine arabinoside and have been predominantly associated with intrathecal administration. Isolated cases have also been reported with high intravenous doses during combination chemotherapeutic regimens.

Cytarabine has been shown to be mutagenic and carcinogenic in animals.

Cytarabine should only be used under the constant supervision by physicians experienced in therapy with cytotoxic agents. Hyperuricaemia secondary to lysis of neoplastic cells may occur in patients receiving cytarabine; serum uric acid concentrations should be monitored.

Periodic determinations of renal and hepatic functions and bone marrow should also be performed and the drug should be used with caution in patients with impaired hepatic function.

However, dosage reduction does not appear to be necessary in patients with impaired renal function. The human liver apparently detoxifies a substantial fraction of the administered dose. The drug should be used with caution and at a reduced dose when liver function is poor. Frequent platelet and leucocyte counts are manditory. Therapy should be suspended or modified when drug-induced bone marrow depression results in a platelet count of less than 50,000 or a polymorphonuclear count of under 1000 per mm³. Counts may continue to fall after the therapy has been discontinued and may reach lowest values after five to seven days. Therapy may be restarted when the bone marrow appears to be recovering on successive bone marrow studies. Therapy should not wait until the normal blood values are obtained to be re-initiated.

When intravenous doses are given quickly, patients may become nauseated and may vomit for several hours afterwards. The problem tends to be less severe when infused.

When given intrathecally, as with any other intrathecal drug, care must be taken with radiotherapy given either during or after treatment; it is well recognised that this can exacerbate the toxicity of radiotherapy.

The safety of the drug has not been established in infants.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

i) Cardiac Glycosides

GI absorption of oral digoxin tablets may be substantially reduced in patients receiving combination chemotherapy regimens (including regimens containing cytarabine), possibly as a result of temporary damage to intestinal mucosa caused by the cytotoxic agents. Limited data suggest that the extent of GI absorption of digitoxin is not substantially affected by concomitant administration of combination chemotherapy regimens known to decrease absorption of digoxin.

ii) Anti-Infective Agents

One in vitro study indicates that cytarabine may antagonise the activity of gentamicin against Klebsiella pneumoniae. Limited data may suggest that cytarabine may antagonise the anti-infective activity of flucytosine, possibly by competitive inhibition of the anti-infective uptake by fungi.

4.6 Pregnancy And Lactation

Use in Pregnancy

Cytarabine is teratogenic in some animal species. It should not be used in pregnant women (especially during the first trimester) or in those who may become pregnant, unless the possible benefits outweigh the potential risks. Women who are, or become, pregnant during treatment with cytarabine should be informed of the risks.

Use in Lactation

It is not known if cytarabine or its metabolite is distributed into breast milk, and it should not be used.

4.7 Effects On Ability To Drive And Use Machines

No documented effect on ability to drive or operate machinery.

4.8 Undesirable Effects

Haematological Effects:

The major adverse effect of cytarabine is the haematological toxicity. Myelosuppression is manifested by megaloblastosis, reticulocytopenia, thrombocytopenia and anaemia.

These appear to be more evident after high doses and continuous infusions; the severity depends on the dose of the drug and schedule of administration.

GI Effects:

Nausea and vomiting occur and are generally more frequent following rapid intravenous administration than with continuous intravenous infusion of the drug.

Diarrhoea, anorexia, oral and anal inflammation or ulceration and less frequently abdominal pain, sore throat, oesphagitis, oesophageal ulceration and gastrointestinal haemorrhage may also occur.

Other reported adverse effects of cytarabine include fever, rash, alopecia, skin ulceration, conjunctivitis, chest pain, urinary retention, dizziness, neuritis or neural toxicity and pain, cellulitis or thrombophlebitis at the site of injection. Cytarabine has also been associated with renal dysfunction, hepatic dysfunction and jaundice in some patients. It has also been associated with sepsis, irritation or sepsis at the injection site, neuritis or neurotoxicity rash, freckling, skin and mucosal bleeding, chest pain, joint pain and reduction in reticulocytes.

A cytarabine reaction is characterised by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis and malaise. It usually occurs 6-12 hours after administration. Corticosteroids have been shown to be beneficial in treating or preventing this syndrome. If the symptoms of the syndrome are serious enough to warrant treatment, corticosteroids should be contemplated as well as continuation of cytarabine therapy.

4.9 Overdose

Cessation of therapy followed by management of ensuing bone marrow depression including whole blood or platelet transfusion and antibiotics as required.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Cytarabine (ARA-C) is metabolised in vivo to ARA-CTP phosphorylated compound. This competitively inhibits DNA polymerase and may also inhibit certain acid kinase enzymes. Primarily the drug acts as a false nucleoside and competes for enzymes involved in the conversion of cytidine nucleotide to deoxycytidine nucleotide and also incorporation into the DNA.

Cytarabine has no effect on non proliferating cells nor on proliferating cells unless in the S phase. It is a cell cycle specific antineoplastic drug.

5.2 Pharmacokinetic Properties

Oral administration is ineffective due to rapid deamination in the gut. Cytidine deaminase is concentrated in the liver and intravenous doses show biphasic elimination with half lifes of approximately 10 minutes and 1-3 hours.

After 24 hours 80% of a dose has been eliminated either as the inactive metabolite or as the unchanged cytarabine, mostly in urine but some in bile.

CSF levels of 50% of plasma levels are achieved with intravenous infusion. Intrathecal dosing results in slower elimination (T1/2 2-11 hours).

Cytarabine is rapidly and widely distributed into tissues, crosses the blood brain barrier and also the placenta.

5.3 Preclinical Safety Data

There is no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium Chloride

Water for Injections

6.2 Incompatibilities

Solutions of cytarabine have been reported to be incompatible with various drugs, i.e. carbenicillin sodium, cephalothin sodium, fluorouracil, gentamicin sulphate, heparin sodium, hydrocortisone sodium succinate, insulin-regular, methylprednisolone sodium succinate, nafacillin sodium, oxacillin sodium, penicillin G sodium. However, the incompatibility depends on several factors (e.g. concentrations of the drug, specific diluents used, resulting pH, temperature). Specialised references should be consulted for specific compatibility information.

6.3 Shelf Life

Before use: 12 months.

In use: Chemical and physical in-use stability has been demonstrated for 7 days at room temperature.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless dilution has taken place in controlled and validated aseptic conditions.

6.4 Special Precautions For Storage

Do not store above 25°C. Keep container in the outer carton .

6.5 Nature And Contents Of Container

Clear Type I glass vials, rubber stopper.

Clear Type I Onco-Tain® Vials, rubber stopper.

Pack sizes 5's, 25's and 50's.

Not all presentations and pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Hospira UK Ltd

Queensway

Royal Leamington Spa

Warwickshire CV31 3RW

United Kingdom.

8. Marketing Authorisation Number(S)

PL 04515/0040

9. Date Of First Authorisation/Renewal Of The Authorisation

7^th July 1992/10^th October 2006

10. Date Of Revision Of The Text

08^th February 2010

Chlorpromazine Concentrate

Pronunciation: klor-PROE-ma-zeen
Generic Name: Chlorpromazine
Brand Name: Generic only. No brands available.

Chlorpromazine Concentrate is an antipsychotic. It may increase the risk of death when used to treat mental problems caused by dementia in elderly patients. Most of the deaths were linked to heart problems or infection. Chlorpromazine Concentrate is not approved to treat mental problems caused by dementia. Discuss any questions or concerns with your doctor.

Chlorpromazine Concentrate is used for:

Treating certain mental or mood disorders (eg, schizophrenia), the manic phase of manic-depressive disorder, anxiety and restlessness before surgery, the blood disease porphyria, severe behavioral and conduct disorders in children, nausea and vomiting, and severe hiccups. It is also used with other medicines to treat symptoms associated with tetanus. It may also be used for other conditions as determined by your doctor.

Chlorpromazine Concentrate is a phenothiazine. Exactly how it works is not known.

Do NOT use Chlorpromazine Concentrate if:

• you are allergic to any ingredient in Chlorpromazine Concentrate or to other phenothiazines (eg, thioridazine)


• you have severe drowsiness


• you have recently taken large amounts of alcohol or medicines that may cause drowsiness, such as barbiturates (eg, phenobarbital) or narcotic pain medicines (eg, codeine)


• you are taking certain antiarrhythmic medicines (eg, amiodarone, dofetilide, dronedarone, quinidine, sotalol), cisapride, pergolide, pimozide, quetiapine, or ziprasidone

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

Before using Chlorpromazine Concentrate:

Some medical conditions may interact with Chlorpromazine Concentrate. 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 heart problems, low blood pressure, blood problems, bone marrow problems, low white blood cell count, diabetes, liver problems (eg, cirrhosis), kidney problems, neuroleptic malignant syndrome (NMS), an enlarged prostate gland, seizures or epilepsy, or an adrenal gland tumor (pheochromocytoma)


• if you have asthma, lung infection, or other lung problems (eg, emphysema); increased pressure in the eyes; glaucoma; or if you are at risk for glaucoma


• if you have Alzheimer disease, dementia, Parkinson disease, or Reye syndrome


• if you have had high blood prolactin levels or a history of certain types of cancer (eg, breast, pancreas, pituitary, brain), or if you are at risk of breast cancer


• if you are regularly exposed to extreme heat or organophosphate insecticides


• if you have a history of alcohol abuse or if you consume more than 3 alcoholic drinks per day

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

• Lithium because the risk of a severe and sometimes permanent nervous system problem (encephalopathic syndrome) characterized by weakness, lethargy, fever, tremor, confusion, or uncontrolled muscle movements may be increased


• Certain antiarrhythmic medicines (eg, amiodarone, dofetilide, dronedarone, quinidine , sotalol), cisapride, pergolide, pimozide, quetiapine, or ziprasidone because the risk of side effects, such as racing heartbeat, dizziness, fainting, and life-threatening irregular heartbeat leading to unconsciousness, may be increased by Chlorpromazine Concentrate


• Many prescription and nonprescription medicines (eg, used for allergies, blood clotting problems, cancer, infections, inflammation, aches and pains, heart problems, high blood pressure, high cholesterol, mental or mood problems, nausea or vomiting, Parkinson disease, seizures, stomach problems), multivitamin products, and herbal or dietary supplements (eg, herbal teas, coenzyme Q10, garlic, ginseng, gingko, St. John's wort) may interact with Chlorpromazine Concentrate, increasing the risk of side effects

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

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

• Take Chlorpromazine Concentrate by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.


• Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.


• Mix your dose in water or juice just before taking it. You may mix Chlorpromazine Concentrate with tomato or fruit juice, milk, simple syrup, orange syrup, carbonated beverages, coffee, tea, or water. Semisolid foods (eg, soups, puddings) may also be used.


• If you miss a dose of Chlorpromazine Concentrate, 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 Chlorpromazine Concentrate.

Important safety information:

• Chlorpromazine Concentrate may cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Chlorpromazine Concentrate with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not drink alcohol while you are using Chlorpromazine Concentrate.


• Check with your doctor before you use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Chlorpromazine Concentrate; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Chlorpromazine Concentrate may cause dizziness, light-headedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.


• Do not become overheated in hot weather or while you are being active; heatstroke may occur.


• Chlorpromazine Concentrate may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to Chlorpromazine Concentrate. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.


• Chlorpromazine Concentrate may lower the ability of your body to fight infection. Avoid contact with people who have colds or infections. Tell your doctor if you notice signs of infection like fever, sore throat, rash, or chills.


• Some patients who take Chlorpromazine Concentrate may develop muscle movements that they cannot control. This is more likely to happen in elderly patients, especially women. The chance that this will happen or that it will become permanent is greater in those who take Chlorpromazine Concentrate in higher doses or for a long time. Muscle problems may also occur after short-term treatment with low doses. Tell your doctor at once if you have muscle problems with your arms; legs; or your tongue, face, mouth, or jaw (eg, tongue sticking out, puffing of cheeks, mouth puckering, chewing movements) while taking Chlorpromazine Concentrate.


• Neuroleptic malignant syndrome (NMS) is a possibly fatal syndrome that can be caused by Chlorpromazine Concentrate. Symptoms may include fever; stiff muscles; confusion; abnormal thinking; fast or irregular heartbeat; and sweating. Contact your doctor at once if you have any of these symptoms.


• Tell your doctor or dentist that you take Chlorpromazine Concentrate before you receive any medical or dental care, emergency care, or surgery.


• Chlorpromazine Concentrate may increase the amount of a certain hormone (prolactin) in your blood. Symptoms may include enlarged breasts, missed menstrual period, decreased sexual ability, or nipple discharge. Contact your doctor right away if you experience any of these symptoms.


• Chlorpromazine Concentrate may raise or lower your blood sugar. High blood sugar may make you feel confused, drowsy, or thirsty. It can also make you flush, breathe faster, or have a fruit-like breath odor. Low blood sugar may make you anxious, sweaty, weak, dizzy, drowsy, or faint. It may also make your vision change; give you a headache, chills, or tremors; or make you more hungry. If these symptoms occur, tell your doctor right away.


• Diabetes patients - Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Chlorpromazine Concentrate may cause the results of some pregnancy tests to be wrong. Check with your doctor if you have questions or concerns about your pregnancy test results.


• Chlorpromazine Concentrate may interfere with certain lab tests, including phenylketonuria (PKU) tests. Be sure your doctor and lab personnel know you are taking Chlorpromazine Concentrate.


• Lab tests, including liver function, complete blood cell counts, and eye exams, may be performed while you use Chlorpromazine Concentrate. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Chlorpromazine Concentrate with caution in the ELDERLY; they may be more sensitive to its effects, especially dizziness, light-headedness (especially upon standing), rapid heartbeat, breathing problems, urinary retention, and constipation.


• Chlorpromazine Concentrate should not be used in CHILDREN younger than 6 months old; 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 Chlorpromazine Concentrate while you are pregnant. Using Chlorpromazine Concentrate during the third trimester may result in uncontrolled muscle movements or withdrawal symptoms in the newborn. Discuss any questions or concerns with your doctor. Chlorpromazine Concentrate is found in breast milk. Do not breast-feed while taking Chlorpromazine Concentrate.

If you suddenly stop taking Chlorpromazine Concentrate, you may experience WITHDRAWAL symptoms, including nausea, vomiting, dizziness, and tremors.

Possible side effects of Chlorpromazine Concentrate:

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:

Agitation; constipation; dizziness; drowsiness; dry mouth; enlarged pupils; jitteriness; nausea; stuffy nose.

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); changes in menstrual period; changes in sexual ability; confusion; dark urine; difficulty swallowing; drooling; fainting; fast or irregular heartbeat; fever, chills, or sore throat; involuntary movements or spasms of the arms and legs, tongue, face, mouth, or jaw; mask-like face; muscle restlessness; prolonged or painful erection; restlessness; seizures; severe constipation; severe or persistent dizziness; shuffling walk; sleeplessness; stiff or rigid muscles; stomach pain; sweating; tremor; trouble urinating; unusual bruising or bleeding; unusual eye movements or inability to move your eyes; unusual mood or mental changes, including lack of response to your surroundings; unusual tiredness or weakness; unusually pale skin; vision changes; 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: Chlorpromazine 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 agitation; fainting; involuntary movements or muscle spasms; irregular heartbeat; light-headedness; loss of consciousness; restlessness; seizures; severe drowsiness or dizziness; tremors; twitching.

Proper storage of Chlorpromazine Concentrate:

Store Chlorpromazine Concentrate at room temperature, between 59 and 86 degrees F (15 and 30 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Chlorpromazine Concentrate out of the reach of children and away from pets.

General information:

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


• Chlorpromazine Concentrate 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.


• If using Chlorpromazine Concentrate for an extended period of time, obtain refills before your supply runs out.


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

This information is a summary only. It does not contain all information about Chlorpromazine Concentrate. 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 Chlorpromazine resources

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

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• Psychosis
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HepatAmine

Dosage Form: injection
HepatAmine®

(8% Amino Acid Injection)

Protect from light until use.

HepatAmine Description

HepatAmine (8% Amino Acid Injection) is a sterile, nonpyrogenic, hypertonic solution containing crystalline amino acids. A 500 mL unit provides a total of 40 g of amino acids and 6 g of nitrogen (38 g of protein equivalent).

Each 100 mL contains:

Essential Amino Acids

Isoleucine USP..............................................0.90 g

Leucine USP.................................................1.10 g

Lysine...........................................................0.61 g

  (added as Lysine Acetate USP....................0.86 g)

Methionine USP............................................0.10 g

Phenylalanine USP.........................................0.10 g

Threonine USP..............................................0.45 g

Tryptophan USP.........................................0.066 g

Valine USP...................................................0.84 g

Nonessential Amino Acids

Alanine USP..................................................0.77 g

Arginine USP.................................................0.60 g

Histidine USP.................................................0.24 g

Proline USP...................................................0.80 g

Serine USP....................................................0.50 g

Glycine USP..................................................0.90 g

Cysteine....................................................<0.014 g

  (as Cysteine HCl•H2O USP....................<0.020 g)

Phosphoric Acid NF....................................0.115 g

Sodium Bisulfite (as an antioxidant)................<0.1 g

Water for Injection USP......................................qs

pH adjusted with Glacial Acetic Acid USP

pH: 6.5 (6.0–6.8)

Calculated Osmolarity: 785 mOsmol/liter

Concentration of Electrolytes (mEq/liter): Sodium 10; Chloride <3

Phosphate (HPO

HepatAmine - Clinical Pharmacology

HepatAmine provides a mixture of essential and nonessential amino acids with high concentrations of the branched chain amino acids isoleucine, leucine, and valine, and low concentrations of methionine and the aromatic amino acids phenylalanine and tryptophan, relative to general purpose amino acid injections. This amino acid composition has been specifically formulated to provide a well tolerated nitrogen source for nutritional support and therapy of patients with liver disease who have hepatic encephalopathy.

The precise mechanisms which produce the therapeutic effects of HepatAmine are not known. The etiopathology of hepatic encephalopathy is also unknown and is thought to be of multifactorial origin. The rationale for HepatAmine is based on observations of plasma amino acid imbalances in patients with liver disease and on theories which postulate that these abnormal patterns are causally related to the development of hepatic encephalopathy.

Clinical studies in patients with hepatic encephalopathy showed that infusion of HepatAmine reversed the abnormal plasma amino acid pattern characterized by decreased levels of branched chain amino acids and elevated levels of aromatic amino acids and methionine. The trend toward normalization of these amino acids was generally associated with an improvement in mental status and EEG patterns. This clinical response was observed in the majority of patients studied. Nitrogen balance was significantly improved and mortality reduced in these typically protein-intolerant patients who received substantial amounts of protein equivalent as HepatAmine® (8% Amino Acid Injection).

When infused with hypertonic dextrose as a calorie source, supplemented with electrolytes, vitamins, and minerals, HepatAmine provides total parenteral nutrition in patients with liver disease, with the exception of essential fatty acids.

Phosphate is a major intracellular anion which participates in providing energy for metabolism of substrates and contributes to significant metabolic and enzymatic reactions in all organs and tissues. It exerts a modifying influence on calcium levels, a buffering effect on acid-base equilibrium, and has a primary role in the renal excretion of hydrogen ions.

It is thought that the acetate from lysine acetate and acetic acid, under the conditions of parenteral nutrition, does not impact net acid-base balance when renal and respiratory functions are normal. Clinical evidence seems to support this thinking; however, confirmatory experimental evidence is not available.

The amounts of sodium and chloride present are not of clinical significance.

Indications and Usage for HepatAmine

HepatAmine is indicated for the treatment of hepatic encephalopathy in patients with cirrhosis or hepatitis. HepatAmine provides nutritional support for patients with these diseases of the liver who require parenteral nutrition and are intolerant of general purpose amino acid injections, which are contraindicated in patients with hepatic coma.

Contraindications

HepatAmine is contraindicated in patients with anuria, inborn errors of amino acid metabolism, especially those involving branched chain amino acid metabolism such as Maple Syrup Urine Disease and Isovaleric Acidemia, or hypersensitivity to one or more amino acids present in the solution.

Warnings

This product contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Safe, effective use of parenteral nutrition requires a knowledge of nutrition as well as clinical expertise in recognition and treatment of the complications which can occur. Frequent clinical evaluation and laboratory determinations are necessary for proper monitoring of parenteral nutrition. Studies should include blood sugar, serum proteins, kidney and liver function tests, electrolytes, hemogram, carbon dioxide content, serum osmolarities, blood cultures, and blood ammonia levels.

Administration of amino acids in the presence of impaired renal function or gastrointestinal bleeding may augment an already elevated blood urea nitrogen. Patients with azotemia from any cause should not be infused with amino acids without regard to total nitrogen intake.

Administration of intravenous solutions can cause fluid and/or solute overload resulting in dilution of serum electrolyte concentrations, over-hydration, congested states, or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentrations of the solutions. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentrations of the solutions.

Precautions

General

Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient warrants such evaluation. Significant deviations from normal concentrations may require the use of additional electrolyte supplements.

Strongly hypertonic nutrient solutions should be administered through an indwelling intravenous catheter with the tip located in the superior vena cava.

Special care must be taken when giving hypertonic dextrose to a diabetic or prediabetic patient. To prevent severe hyperglycemia in such patients, insulin may be required.

Peripheral intravenous administration of HepatAmine® (8% Amino Acid Injection) requires appropriate dilution and provision of adequate calories. Care should be taken to assure proper placement of the needle within the lumen of the vein. The venipuncture site should be inspected frequently for signs of infiltration. If venous thrombosis or phlebitis occurs, discontinue infusions or change infusion site and initiate appropriate treatment.

Care should be taken to avoid circulatory overload, particularly in patients with cardiac insufficiency.

In patients with myocardial infarct, infusion of amino acids should always be accompanied by dextrose since in anoxia, free fatty acids cannot be utilized by the myocardium and energy must be produced anaerobically from glycogen or glucose.

Infusion of HepatAmine may not affect the clinical course of patients with fulminant hepatitis who have a poor prognosis and are generally unresponsive to treatment. It has been shown that the abnormal plasma amino acid pattern in fulminant hepatitis differs from that in chronic liver disease.

Extraordinary electrolyte losses such as may occur during protracted nasogastric suction, vomiting, diarrhea, or gastrointestinal fistula drainage may necessitate additional electrolyte supplementation.

Administration of glucose at a rate exceeding the patient's utilization rate may lead to hyperglycemia, coma, and death.

Metabolic acidosis can be prevented or readily controlled by adding a portion of the cations in the electrolyte mixture as acetate salts and in the case of hyperchloremic acidosis, by keeping the total chloride content of the infusate to a minimum.

HepatAmine contains less than 3 mEq chloride per liter.

HepatAmine contains 10 mmole/liter of phosphate. Some patients, especially those with hypophosphatemia, may require additional phosphate. To prevent hypocalcemia, calcium supplementation should always accompany phosphate administration. To assure adequate intake, serum levels should be monitored frequently.

HepatAmine has not been adequately studied in pregnant women and pediatric patients; therefore, its safe use in such patients has not been demonstrated.

To minimize the risk of possible incompatibilities arising from mixing this solution with other additives that may be prescribed, the final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration.

Use HepatAmine only if solution is clear, the seal unbroken, and vacuum is present.

Drug product contains no more than 25 µg/L of aluminum.

Laboratory Tests

Frequent clinical evaluation and laboratory determinations are necessary for proper monitoring during administration.

Laboratory tests should include measurement of blood sugar, electrolyte, and serum protein concentrations; kidney and liver function tests; and evaluation of acid-base balance and fluid balance. Other laboratory tests may be suggested by the patient's condition.

Drug Interactions

Some additives may be incompatible. Consult with pharmacist. When introducing additives, use aseptic techniques. Mix thoroughly. Do not store.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No in vitro or in vivo carcinogenesis, mutagenesis, or fertility studies have been conducted with HepatAmine® (8% Amino Acid Injection).

Pregnancy

Teratogenic Effects - Pregnancy Category C.

Pregnancy Category C. Animal reproduction studies have not been conducted with HepatAmine (8% Amino Acid Injection). It is also not known whether HepatAmine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HepatAmine should be given to a pregnant woman only if clearly needed.

Labor and Delivery

Information is unknown.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when HepatAmine is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of amino acid injections in pediatric patients have not been established by adequate and well-controlled studies. However, the use of amino acid injections in pediatric patients as an adjunct in the offsetting of nitrogen loss or in the treatment of negative nitrogen balance is well established in the medical literature.

See WARNINGS and DOSAGE AND ADMINISTRATION.

Geriatric Use

Clinical studies of HepatAmine did not include sufficient numbers of subjects age 65 years 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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

See WARNINGS.

Special Precautions for Central Venous Nutrition

Administration by central venous catheter should be used only by those familiar with this technique and its complications.

Central venous nutrition may be associated with complications which can be prevented or minimized by careful attention to all aspects of the procedure, including solution preparation, administration, and patient monitoring. It is essential that a carefully prepared protocol, based on current medical practices, be followed, preferably by an experienced team.

Although a detailed discussion of the complications is beyond the scope of this insert, the following summary lists those based on current literature.

Technical.

The placement of a central venous catheter should be regarded as a surgical procedure. One should be fully acquainted with various techniques of catheter insertion as well as recognition and treatment of complications. For details of techniques and placement sites, consult the medical literature. X-ray is the best means of verifying catheter placement. Complications known to occur from the placement of central venous catheters are pneumothorax, hemothorax, hydrothorax, artery puncture and transection, injury to the brachial plexus, malposition of the catheter, formation of arterio-venous fistula, phlebitis, thrombosis, pericardial tamponade, and air and catheter embolus.

Septic.

The constant risk of sepsis is present during total parenteral nutrition. Since contaminated solutions and infusion catheters are potential sources of infection, it is imperative that the preparation of solutions and the placement and care of catheters be accomplished under controlled aseptic conditions.

Solutions should ideally be prepared in the hospital pharmacy in a laminar flow hood. The key factor in their preparation is careful aseptic technique to avoid inadvertent touch contamination during mixing of solutions and subsequent admixtures.

Solutions should be used promptly after mixing. Any storage should be under refrigeration for as brief a time as possible. Administration time for a single bottle and set should never exceed 24 hours.

Consult the medical literature for a discussion of the management of sepsis. In brief, typical management includes replacing the solution being administered with a fresh container and set, and culturing the contents for bacterial or fungal contamination. If sepsis persists and another source of infection is not identified, the catheter is removed, the proximal tip cultured, and a new catheter reinserted when the fever has subsided. Non-specific, prophylactic antibiotic treatment is not recommended.

Clinical experience indicates that the catheter is likely to be the prime source of infection as opposed to aseptically prepared and properly stored solutions.

Metabolic.

The following metabolic complications have been reported during the use of central venous nutrition; metabolic acidosis, hypophosphatemia, alkalosis, hyperglycemia and glycosuria, osmotic diuresis and dehydration, rebound hypoglycemia, elevated liver enzymes, hypo- and hyper-vitaminosis, electrolyte imbalances and hyperammonemia in pediatric patients. Frequent clinical evaluation and laboratory determinations are necessary, especially during the first few days of therapy to prevent or minimize these complications.

Adverse Reactions

See WARNINGS and Special Precautions for Central Venous Nutrition.

Reactions reported in clinical studies as a result of infusion of the parenteral fluid were water weight gain, edema, increase in BUN, and dilutional hyponatremia. Asterixis was reported to have worsened in one patient during infusion of HepatAmine® (8% Amino Acid Injection).

Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia.

Symptoms may result from an excess or deficit of one or more of the ions present in the solution; therefore, frequent monitoring of electrolyte levels is essential.

Phosphorus deficiency may lead to impaired tissue oxygenation and acute hemolytic anemia. Relative to calcium, excessive phosphorus intake can precipitate hypocalcemia with cramps, tetany and muscular hyperexcitability.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.

Overdosage

In the event of a fluid or solute overload during parenteral therapy, reevaluate the patient's condition, and institute appropriate corrective treatment.

HepatAmine Dosage and Administration

The objective of nutritional management of patients with liver disease is the provision of sufficient amino acid and caloric support for protein synthesis without exacerbating hepatic encephalopathy.

The total daily dose of HepatAmine depends on daily protein requirements and on the patient's metabolic and clinical response. The determination of nitrogen balance and accurate daily body weights, corrected for fluid balance, are probably the best means of assessing individual protein requirements. Dosage should also be guided by the patient's fluid intake limits and glucose and nitrogen tolerances, as well as by metabolic and clinical response.

The recommended dosage is 80–120 grams of amino acids (12–18 grams of nitrogen) as HepatAmine® (8% Amino Acid Injection) per day. Typically, 500 mL of 8% HepatAmine appropriately mixed with 500 mL of 50% dextrose supplemented with electrolytes and vitamins is administered over an 8–12 hour period. This results in a total daily fluid intake of approximately 2–3 liters. Patients with fluid restrictions may only tolerate 1–2 liters. Although nitrogen requirements may be higher in severely hypercatabolic or depleted patients, provision of additional nitrogen may not be possible due to fluid intake limits, nitrogen, or glucose intolerance.

In many patients, provision of adequate calories in the form of hypertonic dextrose may require the administration of exogenous insulin to prevent hyperglycemia and glycosuria. To prevent rebound hypoglycemia, a solution containing 5% dextrose should be administered when hypertonic dextrose solutions are abruptly discontinued.

Fat emulsion coadministration should be considered when prolonged (more than 5 days) parenteral nutrition is required in order to prevent essential fatty acid deficiency (E.F.A.D.). Serum lipids should be monitored for evidence of E.F.A.D. in patients maintained on fat free TPN.

The provision of sufficient intracellular electrolytes, principally potassium, magnesium, and phosphate, is required for optimum utilization of amino acids. Approximately 60–180 mEq of potassium, 10–30 mEq of magnesium, and 10–40 mmole of phosphate per day appear necessary to achieve optimum metabolic response. In addition, sufficient quantities of the major extracellular electrolytes sodium, calcium, and chloride, must be given. In patients with hyperchloremic or other metabolic acidoses, sodium and potassium may be added as the acetate salts to provide bicarbonate precursor. The electrolyte content of HepatAmine must be considered when calculating daily electrolyte intake. Serum electrolytes, including magnesium and phosphorus, should be monitored frequently.

Pediatric Use

Use of HepatAmine in pediatric patients is governed by the same considerations that affect the use of any amino acid solution in pediatrics. The amount administered is dosed on the basis of grams of amino acids/kg of body weight/day. Two to three g/kg of body weight for infants with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance. Solutions administered by peripheral vein should not exceed twice normal serum osmolarity (718 mOsmol/L).

Hypertonic mixtures of amino acids and dextrose may be safely administered by continuous infusion through a central venous catheter with the tip located in the superior vena cava. Initial infusion rates should be slow, and gradually increased to the recommended 60–125 mL/hr. If administration rate should fall behind schedule, no attempt to "catch up" to planned intake should be made. In addition to meeting protein needs, the rate of administration, particularly during the first few days of therapy, is governed by the patient's glucose tolerance. Daily intake of amino acids and dextrose should be increased gradually to the maximum required dose as indicated by frequent determinations of glucose levels in blood and urine.

For patients in whom the central venous route is not indicated and who can consume adequate calories enterally, 8% HepatAmine may be administered by peripheral vein with or without parenteral carbohydrate calories. Such infusates can be prepared by dilution of 8% HepatAmine with Sterile Water for Injection or 5%–10% dextrose to prepare isotonic or slightly hypertonic solutions for peripheral infusion. It is essential that peripheral infusion be accompanied by adequate caloric supplementation. In pediatric patients, the final solution should not exceed twice normal serum osmolarity (718 mOsmol/L).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Care must be taken to avoid incompatible admixtures. Consult with pharmacist.

How is HepatAmine Supplied

HepatAmine® (8% Amino Acid Injection) is supplied sterile and nonpyrogenic in glass containers with solid stoppers packaged 6 per case.

NDC	Cat. No.	Size
HepatAmine® (8% Amino Acid Injection)
0264-9371-55	S9371-SS	500 mL

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended that the product be stored at room temperature (25°C); however, brief exposure up to 40°C does not adversely affect the product.

Protect from light until use.

Rx only

Revised: March 2009

HepatAmine is a registered trademark of B. Braun Medical Inc.

Directions for Use of B. Braun Glass Containers with Solid Stoppers

Designed for use with a vented set. Use 18 to 22 gauge needle size for spiking/admixing or withdrawing solutions from the glass bottle.

Before use, perform the following checks:

• Inspect each container. Read the label. Ensure solution is the one ordered and is within the expiration date.


• Invert container and carefully inspect the solution in good light for cloudiness, haze, or particulate matter; check the bottle for cracks or other damage. In checking for cracks, do not be confused by normal surface marks and seams on the bottom and sides of the bottle. These are not flaws. Look for bright reflections that have depth and penetrate into the wall of the bottle. Reject any such bottle.


• To remove the outer closure, lift the tear tab and pull up, over, and down until it is below the stopper (See Figure 1). Use a circular pulling motion on the tab until it breaks away.
  
  
  


• Grasp and remove the metal disk, exercising caution not to touch the exposed sterile stopper surface.

Warning: Some additives may be incompatible. Consult with pharmacist. When introducing additives, use aseptic techniques. Mix thoroughly. Do not store.

• 5.Refer to Directions for Use of the set being used. Insert the set spike into the large round outlet port of the stopper and hang container.


• 6.After admixture and during administration, reinspect the solution frequently. If any evidence of solution contamination or instability is found or if the patient exhibits any signs of fever, chills or other reactions not readily explainable, discontinue administration immediately and notify the physician.


• 7.When adding medication to the container during administration, swab the triangular medication site, inject medication and mix thoroughly by gentle agitation.


• 8.
  

  Spiking, additions, or transfers should be made immediately after exposing the sterile stopper surface. Check for vacuum at first puncture of stopper. Admixture by needle or syringe should be made through the triangular (

  
  
  
  


• 9.If the first puncture of the stopper is the administration set spike, insert the spike fully into the outlet port of the stopper and promptly invert the bottle. Verify vacuum by observing rising air bubbles. Do not use the bottle if vacuum is not present.


• 10.If admixture or set insertion is not performed immediately following removal of protective metal disk, swab stopper surface.

B. Braun Medical Inc.

Irvine, CA 92614-5895 USA

Made in USA

Y36-002-686

Principal display panel

500 mL

NDC 0264-9371-55

S9371-SS

HepatAmine® (8% Amino Acid Injection)

Protect from light until use.

Each 100 mL contains:

Essential Amino Acids - Isoleucine USP 0.90 g

Leucine USP 1.10 g; Lysine 0.61 g (added as Lysine Acetate USP 0.86 g)

Methionine USP 0.10 g; Phenylalanine USP 0.10 g

Threonine USP 0.45 g; Tryptophan USP 0.066 g

Valine USP 0.84 g

Nonessential Amino Acids - Alanine USP 0.77 g

Arginine USP 0.60 g; Histidine USP 0.24 g

Proline USP 0.80 g; Serine USP 0.50 g

Glycine USP 0.90 g; Cysteine <0.014 g (as Cystein HCI•H20 USP <0.020 g)

B. Braun Medical Inc.

Irvine, CA USA 92614-5895

Phosphoric Acid NF 0.115 g

Sodium Bisulfite (antioxidant) <0.1 g

Water for Injection USP qs

pH adjusted with Glacial Acetic Acid USP

pH: 6.5 (6.0-6.8)

Calculated Osmolarity: 785 mOsmol/liter

Electrolytes (mEq/liter): Sodium 10; Chloride <3

Phosphate (HPO

Acetate Approx. 62 (see Package Insert)

Sterile, nonpyrogenic. Single dose container.

For intravenous use only.

Use only if solution is clear and vacuum is present.

Recommended Storage:

Room temperature (25°C). Avoid excessive heat. Protect from freezing.

See Package Insert.

Rx only

U.S. Patent No. 3,950,529

HepatAmine is a registered trademark of B. Braun Medical Inc.

Y37-002-151

Made in USA

HK-35907

Principal Display Panel

500 mL

NDC 0264-9371-55

S9371-SS

HepatAmine®

(8% Amino Acid Injection)

Protect from light until use.

Each 100 mL contains:

Essential Amino Acids -

Isoleucine USP 0.90 g; Leucine USP 1.10 g

Lysine 0.61 g (added as Lysine Acetate USP 0.86 g)

Methionine USP 0.10 g; Phenylalanine USP 0.10 g

Threonine USP 0.45 g; Tryptophan USP 0.066 g

Valine USP 0.84 g

Nonessential Amino Acids -

Alanine USP 0.77 g; Arginine USP 0.60 g

Histidine USP 0.24 g; Proline USP 0.80 g

Serine USP 0.50 g; Glycine USP 0.90 g

Cysteine <0.014 g (as Cystein HCI•H20 USP <0.020 g)

Phosphoric Acid NF 0.115 g

Sodium Bisulfite (antioxidant) <0.1 g

Water for Injection USP qs

pH adjusted with Glacial Acetic Acid USP

pH: 6.5 (6.0-6.8)

Calculated Osmolarity: 785 mOsmol/liter

Electrolytes (mEq/liter): Sodium 10; Chloride <3

Phosphate (HPO

Acetate Approx. 62 (see Package Insert)

See adjacent panel for further product information.

B. Braun Medical Inc.

Irvine, CA USA 92614-5895

HK-35907

X12-001-408

HepatAmine  isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, tryptophan, valine, alani  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0264-9371 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ISOLEUCINE (ISOLEUCINE) ISOLEUCINE 0.9 g  in 100 mL LEUCINE (LEUCINE) LEUCINE 1.1 g  in 100 mL LYSINE (LYSINE) LYSINE 0.61 g  in 100 mL METHIONINE (METHIONINE) METHIONINE 0.1 g  in 100 mL PHENYLALANINE (PHENYLALANINE) PHENYLALANINE 0.1 g  in 100 mL THREONINE (THREONINE) THREONINE 0.45 g  in 100 mL TRYPTOPHAN (TRYPTOPHAN) TRYPTOPHAN 0.066 g  in 100 mL VALINE (VALINE) VALINE 0.84 g  in 100 mL ALANINE (ALANINE) ALANINE 0.77 g  in 100 mL ARGININE (ARGININE) ARGININE 0.6 g  in 100 mL HISTIDINE (HISTIDINE) HISTIDINE 0.24 g  in 100 mL PROLINE (PROLINE) PROLINE 0.8 g  in 100 mL SERINE (SERINE) SERINE 0.5 g  in 100 mL GLYCINE (GLYCINE) GLYCINE 0.9 g  in 100 mL CYSTEINE (CYSTEINE) CYSTEINE 0.014 g  in 100 mL

Inactive Ingredients Ingredient Name Strength WATER   PHOSPHORIC ACID 0.115 g  in 100 mL SODIUM BISULFITE 0.1 g  in 100 mL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0264-9371-55 6 CONTAINER In 1 CASE contains a CONTAINER 1 500 mL In 1 CONTAINER This package is contained within the CASE (0264-9371-55)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA018676	08/03/1982

Labeler - B. Braun Medical Inc. (002397347)

Establishment
Name	Address	ID/FEI	Operations
B. Braun Medical Inc.		037425308	MANUFACTURE

Revised: 10/2010B. Braun Medical Inc.

More HepatAmine resources

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• HepatAmine Dosage
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• HepatAmine Support Group
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