Pulmotil 90

Dosage Form: FOR ANIMAL USE ONLY
Pulmotil® 90

tilmicosin

For Use in Swine Feeds Only *

ELANCO* AF0472

Net Weight:

10 kg (22.0 lb)

Type A Medicated Article

Do not feed undiluted.

CAUTION: Federal law limits this drug to use under the professional supervision of a licensed veterinarian. Animal feed bearing or containing this veterinary feed directive drug shall be fed to animals only by or upon a lawful veterinary feed directive issued by a licensed veterinarian in the course of the veterinarian's professional practice.

Active Drug Ingredient: tilmicosin (as tilmicosin phosphate) 90.7 g per lb (200 g per kg)

Inert ingredients: ground corncobs.

Description: Pulmotil is a formulation of the antibiotic tilmicosin. Tilmicosin is produced semi-synthetically and is in the macrolide class of antibiotics. Each kilogram of Type A Medicated Article contains 200 grams (0.44 lbs) of tilmicosin adsorbed onto ground corncobs.

Indications: For the control of swine respiratory disease associated with Actinobacillus pleuropneumoniae and Pasteurella multocida.

Feeding Directions: Tilmicosin is to be fed continuously at 181 grams to 363 grams per ton (200 ppm to 400 ppm) of Type C medicated feed as the sole ration for a 21-day period, beginning approximately 7 days before an anticipated disease outbreak.

IMPORTANT: Must be thoroughly mixed in feeds before use.

Mixing Directions: Thoroughly mix Pulmotil Type A medicated article with feed to provide a Type B medicated feed containing up to 36,300 grams tilmicosin per ton or to provide a complete Type C medicated feed containing 181 to 363 g tilmicosin per ton. Do not use in any feeds containing bentonite. Bentonite in feeds may affect the efficacy of tilmicosin.

Starting concentration of Pulmotil Type A Medicated Article	Amount of Type A Medicated Article to add per ton	Resulting concentration in Type B Medicated Feed
grams per pound	pounds	grams per ton	grams per pound
90.7	400	36,300	18.1
	300	27,200	13.6
	200	18,100	9.05

Starting concentration of Pulmotil Type A Medicated Article	Amount of Type A Medicated Article to add per ton	Resulting concentration in Type C Medicated Feed
grams per pound	pounds	grams per ton
90.7	4	363
	3	272
	2	181

WARNINGS: Do not allow horses or other equines access to feeds containing tilmicosin. The safety of tilmicosin has not been established in male swine intended for breeding purposes.

Feed containing tilmicosin shall not be fed to pigs for more than 21 days during each phase of production without ceasing administration for re-evaluation of antimicrobial use by a licensed veterinarian before re-initiating a further course of therapy with an appropriate antimicrobial. Veterinary Feed Directive (VFD) expiration date must not exceed 90 days from the time of issuance. VFDs for tilmicosin phosphate shall not be refilled.

RESIDUE WARNING: Feeds containing tilmicosin must be withdrawn 7 days prior to slaughter.

NOT FOR HUMAN USE

Human Safety Warning: Avoid inhalation, oral exposure, and direct contact with skin or eyes. Operators mixing and handling Pulmotil 90 should use protective clothing, impervious gloves, goggles, and a NIOSH-approved dust mask. Wash thoroughly with soap and water after handling. If accidental eye contact occurs, immediately rinse thoroughly with water. If irritation persists, seek medical attention. Not for human consumption. Keep out of reach of children. The Material Safety Data Sheet contains more detailed occupational safety information. To report adverse effects in users, to obtain more information, or to obtain a material safety data sheet, call 1-800-428-4441.

Pharmacology: Oral dosing of tilmicosin phosphate at 181 to 363 g/ton of feed results in serum tilmicosin levels, which do not correlate with efficacy. Lung concentrations of tilmicosin are significantly higher than serum. Following seven consecutive days of administering tilmicosin-medicated feeds to swine, the concentration of tilmicosin in respiratory tissues, phagocytic cells, and nasal secretions was significantly higher than that of plasma or serum. Lung levels are achieved within 2 days after beginning feeding and plateau by 4 days. Using in-vitro incubation techniques, the ratio of intracellular to extracellular concentrations of tilmicosin for neutrophils, monocyte-macrophages, and alveolar macrophages were 69, 19, and 17, respectively, after four hours of incubation. Although lower levels of accumulation were observed in-vivo, swine alveolar macrophages have been shown in-vitro and in-vivo to concentrate large amounts of tilmicosin; these cells may be important for in-vivo distribution of the drug and may serve as an important reservoir for tilmicosin in lung tissue.

Toxicology: The cardiovascular system is the target of toxicity in laboratory and domestic animals given tilmicosin by oral or parenteral routes. Primary cardiac effects are increased heart rate (tachycardia) and decreased contractility (negative inotropy). Given orally, the median lethal dose is 800 mg/kg in fasted rats and 2250 mg/kg in non-fasted rats. No compound-related lesions were found at necropsy. Results of genetic toxicology studies were all negative. Results of teratology and reproduction studies in rats were all negative. The no effect level in dogs after daily oral doses for up to one year is 4 mg/kg of body weight. Tilmicosin was included in the diet of 18 adult horses for a period of 14 days at dose levels of 400, 1200, and 2000 ppm. Some horses at both the low and high dose levels demonstrated gastrointestinal disturbance with more severe colic evident at the higher levels. One horse died after consuming the 2000 ppm diet.

Adverse Drug Reactions: No adverse toxicological effects were observed in swine given rations containing 2000 ppm tilmicosin for 42 days and 4000 ppm for 21 days.

To report adverse effects, access medical information, or obtain additional product information, call 1-800-428-4441.

Storage Information: Avoid moisture and excessive heat (40°C).

Not to be used after the date printed on the bag.

Restricted Drug (California) - Use Only as Directed

NADA # 141-064, Approved by FDA

Manufactured For:

Elanco Animal Health, A Division of Eli Lilly and Company, Indianapolis, IN 46285, USA

*Elanco®, Pulmotil® and the diagonal color bar are registered trademarks of Eli Lilly and Company.

(Lot number and expiry date are printed on the bag.)

Do not feed undiluted.

BG7601DEAML (V06-06-2007)

Principal Display Panel

Principal Display Panel – 22 lb Bag Label

ELANCO* AF0472

Pulmotil® 90

tilmicosin

For Use in Swine Feeds Only *

Net Weight:

10 kg (22.0 lb)

Pulmotil 90  tilmicosin phosphate  granule

Product Information Product Type VFD TYPE A MEDICATED ARTICLE ANIMAL DRUG NDC Product Code (Source) 0986-0472 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TILMICOSIN PHOSPHATE (TILMICOSIN) TILMICOSIN PHOSPHATE 200 g  in 1 kg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0986-0472-09 10 kg In 1 BAG None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA141064	05/26/2010

Labeler - Elanco Animal Health Co (807447169)

Establishment
Name	Address	ID/FEI	Operations
Eli Lilly and Company Limited, Speke Operations		230761368	API MANUFACTURE, MANUFACTURE

Revised: 05/2010Elanco Animal Health Co

Pyrethrins with Piperonyl Butoxide

Class: Scabicides and Pediculicides
ATC Class: P03BA
VA Class: AP300
CAS Number: 8003-34-7
Brands: A200, Licide, Pronto, RID

Introduction

Pediculicide; fixed-combination preparation containing pyrethrins (a pediculicide) and piperonyl butoxide (has little or no insecticidal activity but potentiates that of pyrethrins).^a

Uses for Pyrethrins with Piperonyl Butoxide

Pediculosis

Topical treatment of pediculosis capitis (head lice infestation).^{103 104 107 112 117 120 121 122 123}

An alternative rather than a preferred treatment for pediculosis capitis.^{107 108} Permethrin 1% generally considered the treatment of choice, and malathion 0.5% is recommended when permethrin resistance is suspected.^{103 107 108 113 114 116 117 125}

Base selection of a pediculicide on efficacy (including both pediculicidal and ovicidal activity), safety, cost, availability, ease of application, age of patient, presence of other scalp infections, patient preference, severity of the infestation, potential for transmission, number of recurrences, and the pattern of resistance in the geographic region.¹¹³

Topical treatment of pediculosis pubis (pubic lice infestation).^{101 104 112 115 120 121 122 123} Considered a pediculicide of choice by CDC and others for treatment of pediculosis pubis, including in HIV-infected patients.^{101 104 112 115}

Topical treatment of pediculosis corporis (body lice infestation).^{103 120 121 122 123 124 125} In some cases, body louse infestations may be treated by improved hygiene and by decontaminating clothes and bedding by washing at temperatures that kill lice.^{103 125} If the infestation is severe, a pediculicide should also be used (e.g., topical permethrin, topical pyrethrins with piperonyl butoxide, topical malathion, oral ivermectin).^{124 125}

One of several options recommended for treatment of pediculosis corporis in the adjunctive treatment of epidemic (louse-borne) typhus.¹⁰³ The causative agent of epidemic typhus (Rickettsia prowazekii) is transmitted person-to-person by Pediculus humanus corporis and thorough delousing (especially among exposed contacts of individuals with typhus) is recommended in epidemic situations.¹⁰³

Scabies

Not effective for treatment of scabies (mite infestation).^a

Pyrethrins with Piperonyl Butoxide Dosage and Administration

General

Measures to Avoid Reinfestation and Transmission

• 
  

  To avoid reinfestation or transmission of pediculosis or scabies, most experts recommend that clothing and bed linen that may have been contaminated by the infested individual during the 2 days prior to treatment should be decontaminated (machine-washed in hot water and dried in a hot dryer, dry-cleaned, or treated with an appropriate pesticide) or removed from body contact for ≥72 hours.^{103 104 106 113}

  
  


• 
  

  Although it may not be necessary, items that cannot be laundered or dry-cleaned should be removed from contact and sealed in a plastic bag for 10–14 days.^{103 106 116}

  
  


• 
  

  Combs and brushes used by the infected patient may be disinfected by soaking in hot water (temperature >54°C) for 5–10 minutes;^{103 106} alternatively, they can be soaked in alcohol or a pediculicide for 1 hour.^{106 112}

  
  


• 
  

  Furniture and floors of rooms inhabited by patients infested with lice should be thoroughly vacuumed.^{103 106 116} Fumigation of living areas is not necessary and is not recommended.^{103 106 114 116}

  
  


• 
  

  In the treatment of pediculosis capitis (head lice infestation), a fine-toothed comb often is recommended to remove any remaining nits (eggs) or nit shells.^{103 106 112 113 116 117 118} Some experts do not consider nit removal necessary since only live lice can be transmitted, but recommend it for aesthetic reasons and to decrease diagnostic confusion and unnecessary retreatment.^{103 116 117 118} Others strongly recommend removal of nits (especially those within 1 cm of the scalp) since no pediculicide is 100% ovicidal and potentially viable nits may remain on the hair after pediculicide treatment.^{103 116 117 118} Although many schools will not allow children with nits to attend, AAP and other experts consider these no-nit policies excessive.^{103 114 116}

  
  

Administration

Topical Administration

Apply topically, usually as a shampoo containing 0.33% pyrethrins and 4% piperonyl butoxide.^{120 121 122 123}

For external use only.^{120 121 122 123} Do not administer orally and do not apply to mucous membranes (e.g., inside the nose, mouth, or vagina).^{120 121 122 123}

Do not apply to eyebrows or eyelashes and avoid contact with eyes.^{120 121 122 123} Eyes should be closed tightly and covered with a soft towel or washcloth while the shampoo is applied to scalp hair or washed off.^{120 121 122 123}

Shake containers of pyrethrins with piperonyl butoxide before using.^{120 123}

Dosage

Pediatric Patients

Pediculosis

Pediculosis Capitis (Head Lice Infestation) or Pediculosis Corporis (Body Lice Infestation)

Topical

Apply to dry scalp hair or other affected areas in an amount sufficient to thoroughly wet the area.^{120 121 122 123} If treating head lice, first apply behind ears and to back of neck.^{120 121} After 10 minutes, add warm water to form a good lather, wash, and thoroughly rinse with water until all lather is gone.^{120 121 122 123} Dry the hair with a clean towel and comb with a fine tooth comb to remove any remaining nits.^{120 121 122 123}

One treatment may be successful, but treatment should be repeated after 7–10 days to kill any newly hatched lice.^{103 107 113 116 117 121 122 123} Do no use more than twice in 24 hours.¹²³

Adults

Pediculosis

Pediculosis Capitis (Head Lice Infestation) or Pediculosis Corporis (Body Lice Infestation)

Topical

Apply to dry scalp hair or other affected areas in an amount sufficient to thoroughly wet the area.^{120 121 122 123} If treating head lice, first apply behind ears and to back of neck.^{120 121} After 10 minutes, add warm water to form a good lather, wash, and thoroughly rinse with water until all lather is gone.^{120 121 122 123} Dry the hair with a clean towel and comb with a fine tooth comb to remove any remaining nits.^{120 121 122 123}

One treatment may be successful, but treatment should be repeated after 7–10 days to kill any newly hatched lice.^{103 107 113 116 117 121 122 123} Do not use more than twice in 24 hours.¹²³

Pediculosis Pubis (Pubic Lice Infestation)

Topical

Apply to the pubic area.¹⁰⁴ After 10 minutes, rinse off with water.¹⁰⁴

CDC recommends reevaluating the patient 1 week after treatment if symptoms persist;¹⁰⁴ retreatment may be necessary if lice or eggs are found.¹⁰⁴ Some clinicians recommend routine retreatment 7–10 days after initial treatment.¹⁰³ If retreatment is necessary, CDC recommends use of an alternative regimen.¹⁰⁴

Cautions for Pyrethrins with Piperonyl Butoxide

Contraindications

• 
  

  Known hypersensitivity or intolerance to any ingredient in the formulation.

  
  

Warnings/Precautions

Sensitivity Reactions

Asthmatic Episodes

May cause breathing difficulty or an asthmatic episode in susceptible individuals.^{120 121 122}

Use with caution in individuals allergic to ragweed.^{120 121 122 123}

Discontinue use and contact a clinician if breathing difficulties occur.^{120 121}

Contact Dermatitis

Pyrethrins may be contact allergens; sensitization characterized by dermatitis may be due to impurities from the pyrethrum flowers.^a

Commercially available preparations of pyrethrins are refined, and only mild skin sensitization has been reported.^a

General Precautions

Administration Precautions

Avoid contact with the eyes since ocular irritation may occur.^{120 121 122 123} Do not use for treatment of pediculosis of the eyebrows or eyelashes.^{120 121 122 123}

If accidental contact with the eyes occurs, the affected eye(s) should be flushed thoroughly with water.^{120 121 122 123} If eye irritation occurs, discontinue use and contact a clinician.^{120 121 122}

Avoid contact with mucous membranes (e.g., inside the nose, mouth, or vagina) since irritation may occur.^{120 121 122 123}

Dermatologic Reactions

Local irritation or erythema may occur.^{120 121 a}

If skin irritation or infection occurs, discontinue use and contact a clinician.^{120 121 122 123}

Do not use on acutely inflamed skin or raw, weeping surfaces.^a

Specific Populations

Pregnancy

CDC considers pyrethrins with piperonyl butoxide a pediculicide of choice when treatment is considered necessary in a pregnant woman.¹⁰⁴

Pregnant women should consult a clinician before self-medicating with pyrethrins with piperonyl butoxide ^{120 121 122}

Lactation

Not known whether distributed into milk. CDC considers pyrethrins with piperonyl butoxide a pediculicide of choice when treatment is considered necessary in a lactating woman.¹⁰⁴

Lactating women should consult a clinician before self-medicating with pyrethrins with piperonyl butoxide.^{120 121 122}

Pediatric Use

Should not be used in children <2 years of age unless directed by a clinician.^{120 121}

Keep out of reach of children.^{120 121 122}

Common Adverse Effects

Local irritation (erythema, pruritus, urticaria, edema, eczema).^{120 121 a 123}

Pyrethrins with Piperonyl Butoxide Pharmacokinetics

Absorption

Bioavailability

Pyrethrins is absorbed through intact skin when applied topically.^a Piperonyl butoxide is poorly absorbed through intact skin when applied topically.^a

Distribution

Extent

Information regarding systemic distribution of pyrethrins and piperonyl butoxide following topical application not available.^a

Elimination

Elimination Route

Information regarding elimination of pyrethrins and piperonyl butoxide following topical application not available.^a

Stability

Storage

Topical

Shampoo

Well-closed containers at <40°C, preferably between 15–30°C.^a

Actions and SpectrumActions

• 
  

  Pyrethrins (also known as pyrethrum extract) contains the purified derivatives of pyrethrum flowers (Chrysanthemum cinerariaefolium) and is a complex of substances that includes the alcohols and esters of pyrethrolone and cinerolone, the alcohol of chrysanthemic acid, and the ester of pyrethric acid.^a Piperonyl butoxide is a synthetic piperic acid derivative.^a

  
  


• 
  

  Following absorption through the chitinous exoskeleton of arthropods, pyrethrins stimulates the nervous system and blocks nerve impulse transmissions, resulting in paralysis and death.^a

  
  


• 
  

  Piperonyl butoxide has little or no insecticidal activity, but potentiates that of pyrethrins by inhibiting the hydrolytic enzymes responsible for metabolism of pyrethrins in arthropods.^a

  
  


• 
  

  Pyrethrins is active against Pediculus humanus var. capitis (head louse), P. humanus var. corporis (body louse), and Phthirus pubis (pubic or crab louse), and may have some activity against their nits (eggs).^a Pyrethrins also is toxic to houseflies, fleas, chiggers, and mosquitoes.^a

  
  


• 
  

  Therapeutic failure and resistance to pyrethrins has been reported in P. humanus.^{107 116} The prevalence of resistance in the US is unclear.^{103 116}

  
  


• 
  

  Treatment failures do not necessarily mean resistance is present since failures can also be related to misdiagnosis, noncompliance with the treatment regimen, and reinfestation.^{108 116}

  
  

Advice to Patients

• 
  

  Importance of using only as directed.^{120 121 122 123}

  
  


• 
  

  Advise patients regarding personal protective measures to avoid reinfestation or transmission of lice.^{103 104 106 113}

  
  


• 
  

  Importance of not using on eyebrows or eyelashes and avoiding contact with the eyes since ocular irritation may occur.^{120 121 122 123} If accidental contact with the eyes occurs, the affected eye(s) should be flushed thoroughly with water.^{120 121 122 123}

  
  


• 
  

  Importance of avoiding contact with mucous membranes (e.g., inside the nose, mouth, vagina).^{120 121 122 123}

  
  


• 
  

  Advise patients to discontinue treatment and consult their clinician if skin or scalp irritation or infection is present or develops, if eyebrows or eyelashes are infested with lice, or if eye irritation occurs.^{120 121 122 123}

  
  


• 
  

  Advise patients using pyrethrins with piperonyl butoxide that breathing problems or asthmatic episodes may occur in susceptible individuals.^{120 121} If breathing difficulties occur, discontinue treatment and consult a clinician.^{120 121}

  
  


• 
  

  Importance of immediately consulting clinician and/or poison control center if pyrethrins with piperonyl butoxide is accidentally ingested.^{120 121}

  
  


• 
  

  Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{120 121 122}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{120 121 122}

  
  


• 
  

  Importance of informing patients of other important precautionary information.^{120 121 122} (See Cautions.)

  
  

Preparations

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

Pyrethrins with Piperonyl Butoxide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Topical	Shampoo	Pyrethrins 0.33% with Piperonyl Butoxide 4%	A200 Lice Killing Shampoo (with benzyl alcohol and isopropyl alcohol)	Hogil
			A200 Lice Treatment Kit (with benzyl alcohol and isopropyl alcohol; with comb and lice control spray)	Del
			Licide (with benzyl alcohol 2.4% and petroleum distillate 1.2%)	Reese
			Pronto Plus Lice Killing Mousse Shampoo Plus Vitamin E (with benzyl alcohol and isopropyl alcohol)	Del
			Pronto Plus Lice Killing Shampoo (with benzyl alcohol and isopropyl alcohol)	Del
			RID Maximum Strength Lice Killing Shampoo (with isopropyl alcohol)	Bayer

Disclaimer

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

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

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

References

Only references cited for selected revisions after 1984 are available electronically.

101. Brown S, Becher J, Brady W. Treatment of ectoparasitic infections: review of the English-language literature, 1982-1992. Clin Infect Dis. 1995; 20:S104-9. [IDIS 345865] [PubMed 7540875]

103. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

104. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2006. MMWR Recomm Rep. 2006; 55(RR-11):1-94.

105. Wilson DC, Leyva WH, King LE. Arthropod bites and stings. In: Fitzpatrick TB, Eisen AZ, Wolff K et al, eds. Dermatology in general medicine. 4th ed. New York: McGraw Hill Inc. 1993:2810-26.

106. Centers for Disease Control and Prevention. Treating head lice. From the CDC website () Accessed 2003 Aug 5.

107. Anon. Drugs for parasitic infections. Med Lett Drugs Ther. Aug 2004. From the Medical Letter web site ()

108. Anon. Drugs for head lice. Med Lett Drugs Ther. 1997; 39:6-7. [PubMed 9008683]

109. Reviewers’ comments (personal observations) on permethrin 84:04.12.

110. Lindane Shampoo, USP, 1% prescribing information. From the FDA web site (). Accessed 2003 Apr 4.

111. Mathieu ME, Wilson BB. Scabies. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practices of infectious diseases. 5th ed. New York: Churchill Livingstone; 2000:2974-6.

112. Meinking TL, Entzel P, Villar ME et al. Comparative efficacy of treatments for pediculosis capitis infections. Arch Dermatol. 2001; 137:287-92. [IDIS 461253] [PubMed 11255326]

113. Jones KN, English JC. Review of common therapeutic options in the United States for the treatment of pediculosis capitis. Clin Infect Dis. 2003; 36:1355-61. [IDIS 511964] [PubMed 12766828]

114. Roberts RJ. Head lice. N Engl J Med. 2002; 346:1645-50. [IDIS 481320] [PubMed 12023998]

115. Wendel K, Rompalo A. Scabies and Pediculosis pubis: an update of treatment regimens and general review. Clin Infect Dis. 2002; 35(Suppl 2):S146-51.

116. American Academy of Pediatrics. Head lice. Pediatrics. 2002; 110:638-43. [IDIS 486240] [PubMed 12205271]

117. Burkhart CG, Burkhart CN, Burkhart KM. An assessment of topical and oral prescription and over-the-counter treatments for head lice. J Am Acad Dermatol. 1998; 38:979-82. [IDIS 405854] [PubMed 9632008]

118. Burkhart CN, Burkhart CG, Pchalek I et al. The adherent cylindrical nit structure and its chemical denaturation in vitro: an assessment with therapeutic implications for head lice. Arch Pediatr Adolescent Med. 1998; 152:711- 2.

119. Reviewers’ comments (personal observations) on Permethrin 84:04.12.

120. Del Pharmaceuticals. Pronto maximum strength lice killing shampoo (pyrethrins with piperonyl butoxide) product information. Farmington, NY; 2002.

121. Bayer Healthcare. Rid (pyrethrins with piperonyl butoxide) product information. Morristown, NJ.

122. Hogli Pharmaceutical Corp. A200 lice killing shampoo (pyrethrins with piperonyl butoxide) product information.

123. Del Pharmaceuticals. Pronto plus lice killing mousse shampoo kit (pyrethrins with piperonyl butoxide) product information. Farmington, NY; 2007.

124. Centers for Disease Control and Prevention. Body lice infestation. From the CDC website () Accessed 2007 Jun 14.

125. Flinders DC, De Schweinitz P. Pediculosis and scabies. Am Fam Physician. 2004; 69:341-50. [IDIS 510826] [PubMed 14765774]

a. AHFS Drug Information 2006. McEvoy GK, ed. Pyrethrins with piperonyl butoxide. American Society of Health-System Pharmacists; 2006:3509-10.

More Pyrethrins with Piperonyl Butoxide resources

• Pyrethrins with Piperonyl Butoxide Dosage
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Triaminic Long Acting Cough

Generic Name: dextromethorphan (dex troe meth OR fan)

Brand Names: Babee Cof, Benylin DM Pediatric, Buckley's Mixture Cough Suppressant, Buckleys Mixture, Creo-Terpin, Creomulsion, Delsym, Delsym 12 Hour Cough Relief, Delsym 12 Hour Cough Relief for Children & Adults, DexAlone, Elixsure Cough, Hold DM, Pediacare, Robitussin CoughGels, Robitussin Honey Cough, Robitussin Maximum Strength, Robitussin Pediatric Cough Suppressant, Scot-Tussin Diabetic, Scot-Tussin DM Cough Chasers, Silphen DM, St. Joseph Cough Suppressant, Sucrets DM Cough, Theraflu Thin Strips Cough, Triaminic Long Acting Cough, Triaminic Softchew, Vicks 44 Cough Relief

What is Triaminic Long Acting Cough (dextromethorphan)?

Dextromethorphan is a cough suppressant. It affects the signals in the brain that trigger cough reflex.

Dextromethorphan is used to treat a cough.

Dextromethorphan will not treat a cough that is caused by smoking, asthma, or emphysema.

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

What is the most important information I should know about Triaminic Long Acting Cough (dextromethorphan)?

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not use dextromethorphan if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take dextromethorphan before the MAO inhibitor has cleared from your body. Do not use any other over-the-counter cough, cold, or allergy medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of one or more types of medicine. Read the label of any other medicine you are using to see if it contains dextromethorphan. Dextromethorphan will not treat a cough that is caused by smoking, asthma, or emphysema.

What should I discuss with my healthcare provider before taking Triaminic Long Acting Cough (dextromethorphan)?

Do not use dextromethorphan if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take dextromethorphan before the MAO inhibitor has cleared from your body.

Ask a doctor or pharmacist about using this medicine if you have emphysema or chronic bronchitis.

This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. This medication may pass into breast milk and could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Artificially-sweetened liquid forms of cough medicine may contain phenylalanine. This would be important to know if you have phenylketonuria (PKU). Check the ingredients and warnings on the medication label if you are concerned about phenylalanine.

How should I take Triaminic Long Acting Cough (dextromethorphan)?

Use this medication exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger amounts, or use it for longer than recommended. Cough medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving cough or cold medicine to a child. Death can occur from the misuse of cough or cold medicine in very young children.

Measure the liquid form of this medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Allow the dextromethorphan lozenge or disintegrating strip to dissolve in your mouth.

Drink extra fluids to help loosen the congestion and lubricate your throat while you are taking this medication. Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash.

If you need to have any type of surgery, tell the surgeon ahead of time if you have taken a cough medicine within the past few days.

Store dextromethorphan at room temperature, away from heat, light, and moisture.

What happens if I miss a dose?

Since cough medicine is usually taken only as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include feeling restless or nervous.

What should I avoid while taking Triaminic Long Acting Cough (dextromethorphan)?

Avoid drinking alcohol. It can increase some of the side effects of dextromethorphan. This medication can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid taking diet pills, caffeine pills, or other stimulants (such as ADHD medications) without your doctor's advice. Taking a stimulant together with cough medicine can increase your risk of unpleasant side effects.

Do not use any other over-the-counter cough, cold, or allergy medication without first asking your doctor or pharmacist. Dextromethorphan is contained in many combination medicines available over the counter. If you take certain products together you may accidentally take too much of this medicine. Read the label of any other medicine you are using to see if it contains dextromethorphan.

Triaminic Long Acting Cough (dextromethorphan) side effects

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

• 
  

  severe dizziness, anxiety, restless feeling, or nervousness;

  
  


• 
  

  confusion, hallucinations; or

  
  


• 
  

  slow, shallow breathing.

  
  

Less serious side effects are more likely, such as stomach upset.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Triaminic Long Acting Cough (dextromethorphan)?

Before taking dextromethorphan, tell your doctor if you are using any of the following drugs:

• 
  

  celecoxib (Celebrex);

  
  


• 
  

  cinacalcet (Sensipar);

  
  


• 
  

  darifenacin (Enablex);

  
  


• 
  

  imatinib (Gleevec);

  
  


• 
  

  quinidine (Quinaglute, Quinidex);

  
  


• 
  

  ranolazine (Ranexa)

  
  


• 
  

  ritonavir (Norvir);

  
  


• 
  

  sibutramine (Meridia);

  
  


• 
  

  terbinafine (Lamisil);

  
  


• 
  

  medicines to treat high blood pressure; or

  
  


• 
  

  antidepressant medications such as amitriptyline (Elavil, Etrafon), bupropion (Wellbutrin, Zyban), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), imipramine (Janimine, Tofranil), paroxetine (Paxil), sertraline (Zoloft), and others.

  
  

This list is not complete and there may be other drugs that can interact with dextromethorphan. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Triaminic Long Acting Cough resources

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• Triaminic Long Acting Cough Drug Interactions
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• Cough

Where can I get more information?

• Your pharmacist can provide more information about dextromethorphan.

See also: Triaminic Long Acting Cough side effects (in more detail)

Phenylephrine Complex

Dosage Form: oral liquid
Phenylephrine Complex Liquid

Antihistamine/Nasal Decongestant/Antitussive

Sugar Free • Alcohol Free • Dye Free

Phenylephrine Complex Description

Phenylephrine Complex Liquid is a strawberry-flavored, clear liquid available for oral administration. Each teaspoonful (5 mL) contains:

Phenylephrine HCl	7.5 mg
Brompheniramine Maleate	4 mg
Dextromethorphan HBr	15 mg

INACTIVE INGREDIENTS: Sodium Benzoate, Citric Acid, Saccharin Sodium, Sorbitol Solution, Glycerin, Strawberry Flavor, Purified Water.

Phenylephrine HCl is a nasal decongestant with the chemical name Benzenemethanol, 3-hydroxy-α-[(methylamino)methyl]-, hydrochloride (R)-. Its structure is as follows:

C9H13NO2•HCl                            M.W. 203.67

Brompheniramine Maleate is an antihistamine with the chemical name: 2-Pyridinepropanamine, γ-(4-bromophenyl)-N,N-dimethyl-, (±)-, (Z)-2-butenedioate (1:1). Its structure is as follows:

C16H19BrN2•C4H4O4                  M.W. 435.31

Dextromethorphan Hydrobromide is an antitussive with the chemical name 3-Methoxy-17- methyl-9α, 13α, 14α –morphinan hydrobromide monohydrate. Its structure is as follows:

C18H25NO•HBr•H2O                  M.W. 370.32

Phenylephrine Complex - Clinical Pharmacology

Phenylephrine HCl

Phenylephrine HCl is a sympathomimetic amine which acts predominantly by a direct action on alpha (α) adrenergic receptors. In therapeutic doses, the drug has no significant stimulant effect on the beta (β) adrenergic receptors of the heart. Clinically, phenylephrine shrinks swollen mucous membranes, reduces tissue hyperemia, edema, and nasal congestion; and increases nasal airway patency. In therapeutic doses the drug causes little, if any, central nervous system (CNS) stimulation.

Brompheniramine Maleate

Brompheniramine Maleate is an alkylamine-type antihistamine and is among the most potent H1 blockers, and are generally effective in relatively low doses. Although brompheniramine is not so prone as other types of antihistamines to cause drowsiness, a significant proportion of patients do experience this effect. CNS stimulation is more common with alkylamines.

Dextromethorphan

Dextromethorphan acts centrally to elevate the threshold for coughing. It has no analgesic or addictive properties. The onset of antitussive action occurs in 15 to 30 minutes after administration and is of long duration.

Indications and Usage for Phenylephrine Complex

Phenylephrine Complex Liquid is indicated for temporarily relieving symptoms of upper respiratory tract disorders such as nasal congestion, vasomotor rhinitis and hay fever; as well as for the temporary relief of coughs associated with respiratory tract infections and related conditions such as pharyngitis, bronchitis, and asthma, when these conditions are complicated by tenacious mucus and/or mucus plugs and congestion. Phenylephrine Complex Liquid is effective in a productive as well as a nonproductive cough, but is of particular value in a dry, nonproductive cough which tends to injure the mucous membrane of the air passages.

Contraindications

Phenylephrine Complex Liquid is contraindicated in infants and newborns, and in patients with a known hypersensitivity to any of the components. It is also contraindicated in patients with severe hypertension, severe coronary artery disease, hyperthyroidism, and in patients on MAO inhibitor therapy (or for 14 days after stopping MAOI therapy). Patient idiosyncrasy to adrenergic agents may be manifested by insomnia, dizziness, weakness, tremor, or arrhythmias. Patients known to be hypersensitive to other sympathomimetic amines may exhibit cross sensitivity with phenylephrine.

Warnings

Do not exceed recommended dosage. If nervousness, dizziness, or sleeplessness occurs, discontinue use and consult a doctor. If symptoms do not improve within 7 days or are accompanied by a fever, consult a doctor. Do not take this product for persistent or chronic cough such as occurs with smoking, asthma, or emphysema, or if cough is accompanied by excessive phlegm (mucus) unless directed by a doctor. A persistent cough may be a sign of a serious condition. If cough persists for more than 1 week, tends to recur, or is accompanied by fever, rash, or persistent headache, consult a doctor.

May cause excitability especially in children. Sedatives and tranquilizers may increase the drowsiness effect. Do not give this product to children who are taking sedatives or tranquilizers, without first consulting the child's doctor.

Do not take this product, unless directed by a doctor, if you have a breathing problem such as emphysema or chronic bronchitis, or if you have glaucoma or difficulty in urination due to enlargement of the prostate gland. May cause drowsiness; alcohol, sedatives, and tranquilizers may increase the drowsiness effect. Avoid alcoholic beverages while taking this product. Do not take this product if you are taking sedatives or tranquilizers, without first consulting your doctor. Use caution when driving a motor vehicle or operating machinery.

If pregnant, or planning to become pregnant or are currently breast-feeding please contact your physician, or health-care provider before using or continuing use.

Sympathomimetic amines should be used judiciously and sparingly in patients with hypertension, ischemic heart disease, diabetes mellitus, increased intraocular pressure, hyperthyroidism, or prostatic hypertrophy. Sympathomimetics may produce central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension. Do not exceed recommended dosage. Discontinue use if adverse reactions occur. Hypertensive crises can occur with concurrent use of phenylephrine and MAO inhibitors (and for 14 days after stopping MAO inhibitor therapy), indomethacin, or with beta-blockers and methyldopa. If a hypertensive crisis occurs, these drugs should be discontinued immediately and therapy to lower blood pressure should be instituted. Fever should be managed by means of external cooling.

Precautions

Information for Patients

Use caution when driving a motor vehicle or operating machinery.

Stimulants, such as phenylephrine, are banned and tested for by the U.S. Olympic Committee (USOC) and the National Collegiate Athletic Association (NCAA).

General

Use with caution in patients with diabetes, hypertension, or cardiovascular disease. Before prescribing medication to suppress or modify cough, it is important to ascertain the underlying cause of the cough, that modification of cough does not increase the risk of clinical or physiological complications, and that appropriate therapy for the primary disease is instituted. Antihistamines have an atropine-like action and therefore should be used with caution in patients with a history of bronchial asthma, increased intraocular pressure, hypothyroidism, cardiovascular disease and hypertension.

Drug Interactions

Beta-adrenergic blockers and MAO inhibitors (or for 14 days after stopping MAOI therapy) may potentiate the pressor effect of phenylephrine. Concurrent use of digitalis glycosides may increase the possibility of cardiac arrhythmias. Sympathomimetics may reduce the hypotensive effects of guanethidine, mecamylamine, methyldopa, reserpine and veratrum alkaloids. Concurrent use of tricyclic antidepressants may antagonize the effects of phenylephrine. Use of other vasopressor drugs during halothane anesthesia may cause serious cardiac arrhythmias. Do not use if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson's disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No adequate and well-controlled studies have been conducted to determine whether the components of this product have a potential for carcinogenesis, mutagenesis or impairment of fertility.

Pregnancy

Category C

It is not known whether this product can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. This product should be given to a pregnant woman only if the potential benefit justifies potential risk to the fetus.

Nursing Mothers

Small amounts of phenylephrine are excreted in breast milk. Use of this product by nursing mothers is not recommended because of the higher than usual risk for infants from sympathomimetic amines.

Geriatric Use

The elderly (60 years and older) are more likely to experience adverse reactions to sympathomimetics.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 6 years have not been established.

Adverse Reactions

The most frequent adverse reactions with this combination product are: sedation; dryness of mouth, nose and throat; thickening of bronchial secretions; dizziness.

Other adverse reactions may include:

Dermatologic: Urticaria, drug rash, photosensitivity, pruritus.

Cardiovascular: Hypotension, hypertension, cardiac arrhythmias, palpitations.

CNS: Disturbed coordination, tremor, irritability, drowsiness, insomnia, visual disturbances, weakness, nervousness, convulsions, headache, euphoria, and dysphoria.

Urinary System: Urinary frequency, difficult urination.

Gastrointestinal System: Epigastric discomfort, anorexia, nausea, vomiting, diarrhea, constipation.

Respiratory System: Tightness of chest and wheezing, shortness of breath.

Hematologic System: Hemolytic anemia, thrombocytopenia, agranulocytosis.

Drug Abuse and Dependence

Central nervous system stimulants have been abused. At high doses, subjects commonly experience an elevation of mood, a sense of increased energy and alertness, and decreased appetite. Some individuals become anxious, irritable, and loquacious. In addition to the marked euphoria, the user experiences a sense of markedly enhanced physical strength and mental capacity. With continued use, tolerance develops, the user increases the dose, and toxic signs and symptoms appear. Depression may follow rapid withdrawal.

There is no information to indicate that abuse or dependency occurs with guaifenesin or with the combination of guaifenesin, dextromethorphan and phenylephrine.

Overdosage

This product is comprised of three pharmacologically different components. Therefore, it is difficult to predict the exact manifestation of symptoms in a given individual. A description of symptoms which are likely to appear after ingestion of an excess of the individual components follows:

Signs and Symptoms

Dextromethorphan in toxic doses will cause drowsiness, ataxia, nystagmus, opisthotonos and convulsive seizures. Overdosage with sympathomimetic amines can cause cardiac arrhythmias, cerebral hemorrhage and pulmonary edema. It can also cause palpitation, tremor, dizziness, vomiting, fear, labored breathing, headache, dryness of mouth, pallor, weakness, panic, anxiety, confusion, hallucinations, and delirium.

Treatment

Treatment of acute overdosage would probably be based upon treating the patient for the symptoms of overdosage of phenylephrine as follows: The treatment of overdosage should provide symptomatic and supportive care. If the amount ingested is considered dangerous or excessive, induce vomiting with ipecac syrup unless the patient is convulsing, comatose, or has lost the gag reflex, in which case perform gastric lavage using a large bore tube. If indicated, follow with activated charcoal and a saline cathartic.

Phenylephrine Complex Dosage and Administration

Adults and Children 12 years of age or older: 1 teaspoonful every 6 hours.

Do not exceed 6 teaspoonfuls in a 24-hour period.

Children 6 to 12 years of age: ½ teaspoonful every 6 hours.

Do not exceed 3 teaspoonfuls in a 24-hour period.

This product is not indicated for use in children under 6 years of age. (see PRECAUTIONS, Pediatric Use.)

How is Phenylephrine Complex Supplied

Phenylephrine Complex Liquid is a clear, strawberry-flavored, sugar-free, alcohol-free, dye-free liquid supplied in 16 fl. oz. bottles, NDC 51991-660-16.

Dispense in a tight, light-resistant container, with a child-resistant closure as defined in the USP/NF.

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). See USP Controlled Room Temperature. Protect from freezing.

Warning

Keep this and all medications out of the reach of children. In case of accidental overdose, seek professional assistance or contact a poison control center immediately.

All prescription substitutions using this product shall be pursuant to state statutes as applicable. This is not an Orange Book product.

Rx Only

Manufactured by: Tri-Med Laboratories, Inc., Somerset, NJ 08873

Distributed by: Breckenridge Pharmaceutical, Inc., Boca Raton, FL 33487

Iss. 8/09

PRINCIPAL DISPLAY PANEL - 473 mL Bottle

Breckenridge

Pharmaceutical, Inc.

NDC 51991-660-16

Phenylephrine

Complex Liquid

Antihistamine/Decongestant/

Antitussive

• Sugar Free


• Alcohol Free


• Dye Free

Description: Each 5 mL (one teaspoonful) for oral

administration contains:

Phenylephrine HCl........................................7.5 mg

Brompheniramine Maleate ..............................4 mg

Dextromethorphan HBr..................................15 mg

INACTIVE INGREDIENTS: Sodium Benzoate,

Citric Acid, Saccharin Sodium, Sorbitol Solution,

Glycerin, Strawberry Flavor, Purified Water.

Rx Only

Net Contents:

16 fl. oz. (One Pint) 473 mL

Phenylephrine Complex  phenylephrine hydrochloride, dextromethorphan hydrobromide and brompheniramine maleate  liquid

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 51991-660 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Phenylephrine Hydrochloride (Phenylephrine) Phenylephrine Hydrochloride 7.5 mg  in 5 mL Dextromethorphan Hydrobromide (Dextromethorphan) Dextromethorphan Hydrobromide 15 mg  in 5 mL BROMPHENIRAMINE MALEATE (BROMPHENIRAMINE) BROMPHENIRAMINE MALEATE 4 mg  in 5 mL

Inactive Ingredients Ingredient Name Strength sodium benzoate   citric acid monohydrate   saccharin sodium   sorbitol   glycerin   water

Product Characteristics Color      Score      Shape Size Flavor STRAWBERRY Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 51991-660-16 473 mL In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
UNAPPROVED DRUG OTHER		11/20/2009	10/31/2011

Labeler - Breckenridge Pharmaceutical, Inc. (150554335)

Establishment
Name	Address	ID/FEI	Operations
Trimed		182050567	MANUFACTURE

Revised: 10/2010Breckenridge Pharmaceutical, Inc.

More Phenylephrine Complex resources

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

Compare Phenylephrine Complex with other medications

• Cough and Nasal Congestion

Precedex

dexmedetomidine hydrochloride

Dosage Form: injection, solution
FULL PRESCRIBING INFORMATION

Indications and Usage for Precedex

Intensive Care Unit Sedation

Precedex® is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. Precedex should be administered by continuous infusion not to exceed 24 hours.

Precedex has been continuously infused in mechanically ventilated patients prior to extubation, during extubation, and post-extubation. It is not necessary to discontinue Precedex prior to extubation.

Procedural Sedation

Precedex is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures.

Precedex Dosage and Administration

Dosing Guidelines

• 
  

  Precedex dosing should be individualized and titrated to desired clinical response.

  
  


• 
  

  Precedex is not indicated for infusions lasting longer than 24 hours.

  
  


• 
  

  Precedex should be administered using a controlled infusion device.

  
  

Dosage Information

Table 1: Dosage Information

INDICATION	DOSAGE AND ADMINISTRATION
Initiation of Intensive Care Unit Sedation	For adult patients: a loading infusion of one mcg/kg over 10 minutes.  For patients being converted from alternate sedative therapy: a loading dose may not be required [see Dosage and Administration: Maintenance of Intensive Care Unit Sedation (2.2)].  For patients over 65 years of age: a dose reduction should be considered [see Use in Specific Populations (8.5)].  For patients with impaired hepatic-function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Maintenance of Intensive Care Unit Sedation	For adult patients: a maintenance infusion of 0.2 to 0.7 mcg/kg/hr. The rate of the maintenance infusion should be adjusted to achieve the desired level of sedation.  For patients over 65 years of age: a dose reduction should be considered [see Use in Specific Populations (8.5)].  For patients with impaired hepatic function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Initiation of Procedural Sedation	For adult patients: a loading infusion of one mcg/kg over 10 minutes. For less invasive procedures such as ophthalmic surgery, a loading infusion of 0.5 mcg/kg given over 10 minutes may be suitable.  For awake fiberoptic intubation patients: a loading infusion of one mcg/kg over 10 minutes.  For patients over 65 years of age: a loading infusion of 0.5 mcg/kg over 10 minutes [see Use in Specific Populations (8.5)].  For patients with impaired hepatic function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Maintenance of Procedural Sedation	For adult patients: the maintenance infusion is generally initiated at 0.6 mcg/kg/hr and titrated to achieve desired clinical effect with doses ranging from 0.2 to 1 mcg/kg/hr. The rate of the maintenance infusion should be adjusted to achieve the targeted level of sedation.  For awake fiberoptic intubation patients: a maintenance infusion of 0.7 mcg/kg/hr is recommended until the endotracheal tube is secured.  For patients over 65 years of age: a dose reduction should be considered [see Use in Specific Populations (8.5)].  For patients with impaired hepatic function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Dosage Adjustment

Due to possible pharmacodynamic interactions, a reduction in dosage of Precedex or other concomitant anesthetics, sedatives, hypnotics or opioids may be required when co-administered [see Drug Interactions (7.1)].

Dosage reductions may need to be considered for patients with hepatic impairment, and geriatric patients [see Warnings and Precautions (5.6), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Preparation of Solution

Precedex must be diluted in 0.9% sodium chloride solution to achieve required concentration (4 mcg/mL) prior to administration. Preparation of solutions is the same, whether for the loading dose or maintenance infusion.

Strict aseptic technique must always be maintained during handling of Precedex.

To prepare the infusion, withdraw 2 mL of Precedex and add to 48 mL of 0.9% sodium chloride injection to a total of 50 mL. Shake gently to mix well.

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

Administration with Other Fluids

 Precedex infusion should not be co-administered through the same intravenous catheter with blood or plasma because physical compatibility has not been established.

 Precedex has been shown to be incompatible when administered with the following drugs: amphotericin B, diazepam.

 Precedex has been shown to be compatible when administered with the following intravenous fluids:

•  0.9% sodium chloride in water


•  5% dextrose in water


•  20% mannitol


•  Lactated Ringer's solution


•  100 mg/mL magnesium sulfate solution


•  0.3% potassium chloride solution

Compatibility with Natural Rubber

Compatibility studies have demonstrated the potential for absorption of Precedex to some types of natural rubber. Although Precedex is dosed to effect, it is advisable to use administration components made with synthetic or coated natural rubber gaskets.

Dosage Forms and Strengths

200 mcg/2 mL (100 mcg/mL) in a glass vial

Contraindications

None

Warnings and Precautions

Drug Administration

 Precedex should be administered only by persons skilled in the management of patients in the intensive care or operating room setting. Due to the known pharmacological effects of Precedex, patients should be continuously monitored while receiving Precedex.

Hypotension, Bradycardia, and Sinus Arrest

 Clinically significant episodes of bradycardia and sinus arrest have been reported with Precedex administration in young, healthy volunteers with high vagal tone or with different routes of administration including rapid intravenous or bolus administration.

 Reports of hypotension and bradycardia have been associated with Precedex infusion. If medical intervention is required, treatment may include decreasing or stopping the infusion of Precedex, increasing the rate of intravenous fluid administration, elevation of the lower extremities, and use of pressor agents. Because Precedex has the potential to augment bradycardia induced by vagal stimuli, clinicians should be prepared to intervene. The intravenous administration of anticholinergic agents (e.g., glycopyrrolate, atropine) should be considered to modify vagal tone. In clinical trials, glycopyrrolate or atropine were effective in the treatment of most episodes of Precedex-induced bradycardia. However, in some patients with significant cardiovascular dysfunction, more advanced resuscitative measures were required.

 Caution should be exercised when administering Precedex to patients with advanced heart block and/or severe ventricular dysfunction. Because Precedex decreases sympathetic nervous system activity, hypotension and/or bradycardia may be expected to be more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension and in elderly patients.

 In clinical trials where other vasodilators or negative chronotropic agents were co-administered with Precedex an additive pharmacodynamic effect was not observed. Nonetheless, caution should be used when such agents are administered concomitantly with Precedex.

Transient Hypertension

 Transient hypertension has been observed primarily during the loading dose in association with the initial peripheral vasoconstrictive effects of Precedex. Treatment of the transient hypertension has generally not been necessary, although reduction of the loading infusion rate may be desirable.

Arousability

 Some patients receiving Precedex have been observed to be arousable and alert when stimulated. This alone should not be considered as evidence of lack of efficacy in the absence of other clinical signs and symptoms.

Withdrawal

Intensive Care Unit Sedation 

 With administration up to 7 days, regardless of dose, 12 (5%) Precedex subjects experienced at least 1 event related to withdrawal within the first 24 hours after discontinuing study drug and 7 (3%) Precedex subjects experienced at least 1 event 24 to 48 hours after end of study drug. The most common events were nausea, vomiting, and agitation.

 Tachycardia and hypertension requiring intervention in the 48 hours following study drug discontinuation occurred at frequencies of <5%. If tachycardia and/or hypertension occurs after discontinuation of Precedex supportive therapy is indicated.

Procedural Sedation 

 Withdrawal symptoms were not seen after discontinuation of short term infusions of Precedex (<6 hours).

Tolerance and Tachyphylaxis

 Use of dexmedetomidine beyond 24 hours has been associated with tolerance and tachyphylaxis and a dose-related increase in adverse reactions [see Adverse Reactions (6.1)].

Hepatic Impairment

 Since Precedex clearance decreases with severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see Dosage and Administration (2.2)].

Adverse Reactions

Clinical Studies Experience

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

 Use of Precedex has been associated with the following serious adverse reactions:

• 
  

   Hypotension, bradycardia and sinus arrest [see Warnings and Precautions (5.2)]

  
  


• 
  

   Transient hypertension [see Warnings and Precautions (5.3)]

  
  

 Most common treatment-emergent adverse reactions, occurring in greater than 2% of patients in both Intensive Care Unit and procedural sedation studies include hypotension, bradycardia and dry mouth.

Intensive Care Unit Sedation

 Adverse reaction information is derived from the continuous infusion trials of Precedex for sedation in the Intensive Care Unit setting in which 1007 patients received Precedex. The mean total dose was 7.4 mcg/kg (range: 0.8 to 84.1), mean dose per hour was 0.5 mcg/kg/hr (range: 0.1 to 6.0) and the mean duration of infusion of 15.9 hours (range: 0.2 to 157.2). The population was between 17 to 88 years of age, 43% ≥65 years of age, 77% male and 93% Caucasian. Treatment-emergent adverse reactions occurring at an incidence of >2% are provided in Table 2. The most frequent adverse reactions were hypotension, bradycardia and dry mouth [see Warnings and Precautions (5.2)].

Table 2: Adverse Reactions With an Incidence >2%—Intensive Care Unit Sedation Population <24 hours*

Adverse Event		All Precedex (N = 1007) (%)	Randomized Precedex (N = 798) (%)	Placebo (N = 400) (%)	Propofol (N = 188) (%)
Hypotension		25%	24%	12%	13%
Hypertension		12%	13%	19%	4%
Nausea		9%	9%	9%	11%
Bradycardia		5%	5%	3%	0
Atrial fibrillation		4%	5%	3%	7%
Pyrexia		4%	4%	4%	4%
Dry mouth		4%	3%	1%	1%
Vomiting		3%	3%	5%	3%
Hypovolemia		3%	3%	2%	5%
Atelectasis		3%	3%	3%	6%
Pleural effusion		2%	2%	1%	6%
Agitation		2%	2%	3%	1%
Tachycardia		2%	2%	4%	1%
Anemia		2%	2%	2%	2%
Hyperthermia		2%	2%	3%	0
Chills		2%	2%	3%	2%
Hyperglycemia		2%	2%	2%	3%
Hypoxia		2%	2%	2%	3%
Post-procedural hemorrhage		2%	2%	3%	4%
Pulmonary edema		1%	1%	1%	3%
Hypocalcemia		1%	1%	0	2%
Acidosis		1%	1%	1%	2%
Urine output decreased		1%	1%	0	2%
Sinus tachycardia		1%	1%	1%	2%
Ventricular tachycardia		<1%	1%	1%	5%
Wheezing		<1%	1%	0	2%
Edema peripheral		<1%	0	1%	2%
* 26 subjects in the all Precedex group and 10 subjects in the randomized Precedex group had exposure for greater than 24 hours.

 

 Adverse reaction information was also derived from the placebo-controlled, continuous infusion trials of Precedex for sedation in the surgical intensive care unit setting in which 387 patients received Precedex for less than 24 hours. The most frequently observed treatment-emergent adverse events included hypotension, hypertension, nausea, bradycardia, fever, vomiting, hypoxia, tachycardia and anemia (see Table 3).

 

Table 3: Treatment-Emergent Adverse Events Occurring in >1% Of All Dexmedetomidine-Treated Patients in the Randomized Placebo-controlled Continuous Infusion <24 Hours ICU Sedation Studies

Adverse Event	Randomized Dexmedetomidine (N = 387)	Placebo (N = 379)
Hypotension	28%	13%
Hypertension	16%	18%
Nausea	11%	9%
Bradycardia	7%	3%
Fever	5%	4%
Vomiting	4%	6%
Atrial Fibrillation	4%	3%
Hypoxia	4%	4%
Tachycardia	3%	5%
Hemorrhage	3%	4%
Anemia	3%	2%
Dry Mouth	3%	1%
Rigors	2%	3%
Agitation	2%	3%
Hyperpyrexia	2%	3%
Pain	2%	2%
Hyperglycemia	2%	2%
Acidosis	2%	2%
Pleural Effusion	2%	1%
Oliguria	2%	<1%
Thirst	2%	<1%

 

 In a controlled clinical trial, Precedex was compared to midazolam for ICU sedation exceeding 24 hours duration. Key treatment emergent adverse events occurring in dexmedetomidine or midazolam treated patients in the randomized active comparator continuous infusion long-term intensive care unit sedation study are provided in Table 4. The number (%) of subjects who had a dose-related increase in treatment-emergent adverse events by maintenance adjusted dose rate range in the Precedex group is provided in Table 5.

 

Table 4: Key Treatment-Emergent Adverse Events Occurring in Dexmedetomidine- or Midazolam-Treated Patients in the Randomized Active Comparator Continuous Infusion Long-Term Intensive Care Unit Sedation Study*

Adverse Event	Dexmedetomidine (n=244)	Midazolam (n=122)
Hypotension1	56%	56%
Hypotension requiring intervention	28%	27%
Bradycardia2	42%	19%
Bradycardia requiring intervention	5%	1%
Systolic Hypertension3	28%	42%
Tachycardia4	25%	44%
Tachycardia requiring intervention	10%	10%
Diastolic Hypertension3	12%	15%
Hypertension3	11%	15%
Hypertension requiring intervention†	19%	30%
Hypokalemia	9%	13%
Pyrexia	7%	2%
Agitation	7%	6%
Hyperglycemia	7%	2%
Constipation	6%	6%
Hypoglycemia	5%	6%
Respiratory Failure	5%	3%
Renal Failure Acute	2%	1%
Acute Respiratory Distress Syndrome	2%	1%
Generalized edema	2%	6%
Hypomagnesemia	1%	7%
† Includes any type of hypertension. 1 Hypotension was defined in absolute terms as Systolic blood pressure of <80 mmHg or Diastolic blood pressure of <50 mmHg or in relative terms as ≤30% lower than pre-study drug infusion value. 2 Bradycardia was defined in absolute terms as <40 bpm or in relative terms as ≤30% lower than pre-study drug infusion value. 3 Hypertension was defined in absolute terms as Systolic blood pressure >180 mmHg or Diastolic blood pressure of >100 mmHg or in relative terms as ≥30% higher than pre-study drug infusion value. 4 Tachycardia was defined in absolute terms as >120 bpm or in relative terms as ≥30% greater than pre-study drug infusion value.

 The following adverse events occurred between 2 and 5% for Precedex and Midazolam, respectively: renal failure acute (2.5%, 0.8%), acute respiratory distress syndrome (2.5%, 0.8%), and respiratory failure (4.5%, 3.3%).

 

Table 5. Number (%) of subjects who had a dose-related increase in Treatment Emergent Adverse Events by maintenance adjusted dose rate range in the Precedex group

Precedex mcg/kg/hr
Adverse Event	≤ 0.7* N = 95	> 0.7 to ≤ 1.1* N = 78	> 1.1* N = 71
Constipation	6%	5%	14%
Agitation	5%