Atrovent

Generic Name: Ipratropium Bromide
Class: Antimuscarinics/Antispasmodics
Molecular Formula: C₂₀H₃₀BrNO₃•H₂O
CAS Number: 66985-17- 9

Introduction

Bronchodilator; a nonselective, competitive antagonist at muscarinic receptors.^{2 224 225 232}

Uses for Atrovent

Bronchospasm in COPD

Long-term treatment of reversible bronchospasm associated with COPD,^{1 2 4 58 76 114 115 118 120 121 122 123 124 127 128 130 228 230 244 245 253 254 255 256 257 258 259 260 261 262 263 267 278 281 285 292 293 294} including chronic bronchitis^{1 2 4 36 55 61 76 90 116 117 119 120 121 124 125 129 131 281} and emphysema.^{1 2 4 90 91 119 120 125 281 343 344 345 347}

Fixed combination with albuterol sulfate is used for the symptomatic management of bronchospasm associated with COPD in patients who continue to have evidence of bronchospasm despite the regular use of an orally inhaled bronchodilator and who require a second bronchodilator.^{320 347}

Bronchospasm in Asthma

Has been used for symptomatic treatment of acute or chronic bronchial asthma†;^{36 55 56 76 91 92 115 124 125 129 153 161 162 164 180 181 211 225 228 268 302 303 331 336 337} β₂-adrenergic agonist bronchodilators generally preferred initially for relief of bronchospasm in asthmatic patients.^{161 164 225 257 268 302 303 331 337}

May be useful as alternative therapy in adults experiencing adverse effects (e.g., tachycardia, arrhythmia, tremor) with a β-adrenergic agonist†.^{331 336 337}

Some clinicians consider ipratropium as adjunctive therapy in patients with moderate or severe exacerbations (peak expiratory flow rate ≤80% of predicted) of asthma† who fail to respond adequately to β-adrenergic agonists and corticosteroids.^{331 337}

May be useful for prevention or reversal of bronchospasm induced by β-adrenergic blocking agents† (e.g., propranolol) in asthmatic patients; β-adrenergic bronchodilators generally ineffective for this indication in such patients.^{31 191 194 225 268}

Atrovent Dosage and Administration

Administration

Administer by oral inhalation using an oral aerosol inhaler^{1 10 320} or via nebulization.^{4 281 329}

Oral Inhalation via Metered-dose Aerosol

Ipratropium Bromide

Aerosol delivers ≥200 metered sprays per canister.¹

Patient should be instructed to clear excessive sputum from chest before inhalation.¹⁰

Shake well immediately prior to use.^{1 10 320} Actuate aerosol inhaler 3 times prior to the initial use or if it has not been used for >24 hours.¹

Do not use mouthpiece for other aerosol drugs.¹

Exhale slowly and completely and place the mouthpiece of the inhaler well into the mouth with the lips closed around it.^{10 348} To avoid contact of the drug with the eyes and subsequent adverse effects, close eyes during inhalation of aerosol.^{1 10 348} Inhale slowly and deeply through the mouth while actuating the inhaler.^{1 10} Hold the breath for 10 seconds, withdraw the mouthpiece, and exhale slowly.^{1 10}

Allow ≥15 seconds to elapse between subsequent inhalations from the aerosol inhaler.^{10 348}

Wash the mouthpiece in hot running water as needed.^{10 348} If soap is used, rinse mouthpiece thoroughly with plain water.^{10 348}

Ipratropium Bromide and Albuterol Sulfate

Aerosol delivers ≥200 metered sprays per canister.³⁴⁶

Shake well immediately prior to use.³⁴⁶ Actuate 3 times prior to the initial use or if it has not been used for >24 hours.³⁴⁶ Do not use actuator provided for other aerosol drugs.³⁴⁶ To avoid contact of the drug with the eyes and subsequent adverse effects, close eyes during inhalation of aerosol.³⁴⁶

Exhale deeply and place mouthpiece of the inhaler into the mouth.³⁴⁶ Inhale slowly and deeply through the mouth while actuating the inhaler.³⁴⁶ Hold the breath for 10 seconds, withdraw the mouthpiece, and exhale slowly.³⁴⁶ Allow approximately 2 minutes to elapse and repeat the procedure.³⁴⁶ Rinse the mouthpiece in hot water as needed.³⁴⁶ If soap is used, rinse the mouthpiece thoroughly with plain water.³⁴⁶ When dry, replace the cap on the mouthpiece when the inhaler is not in use.³⁴⁶

Oral Inhalation via Nebulization

Ipratropium Bromide

Empty entire contents of the single-use vial of solution into the nebulizer reservoir and attach reservoir to the mouthpiece or face mask and to the compressor according to the manufacturer’s instructions.^{4 328 350}

Use care when a face mask is used to avoid leakage since transient blurred vision and other adverse effects may result if the drug enters the eyes.^{2 225 250 275 328 350} (See Ocular Effects under Cautions.) Use of a mouthpiece may avoid inadvertent entry of drug into the eye.⁴

Place the mouthpiece of the nebulizer in the mouth or put on the nebulizer face mask.^{4 15 328} Breathe as calmly, deeply, and evenly as possible until the nebulizer stops producing mist.^{4 328}

Duration of treatment usually is about 5–15 minutes.^{4 328}

Ipratropium Bromide and Albuterol Sulfate

Empty entire contents of the single-use vial of solution into the nebulizer reservoir and attach reservoir to the mouthpiece or face mask and to the compressor according to the manufacturer’s instructions.³²⁸

Place the mouthpiece of the nebulizer in the mouth or put on the nebulizer face mask.³²⁸ Breathe as calmly, deeply, and evenly as possible until the nebulizer stops producing mist.³²⁸

Duration of treatment usually is about 5–15 minutes.³²⁸

Clean the nebulizer after use according to the manufacturer’s instructions.³²⁸

Dosage

Available as ipratropium bromide.

Dosage of oral inhalation aerosol expressed in terms of the monohydrate.^{1 320}

Dosage of inhalation solution for nebulization expressed in terms of anhydrous drug.^{4 329 330}

Using in vitro testing at an average flow rate of 3.6 L per minute for an average of ≤15 minutes, the Pari-LC Plus nebulizer delivered at the mouthpiece approximately 46 or 42% of the original dosage of albuterol or ipratropium bromide, respectively.³²⁷

Pediatric Patients

COPD

Inhalation

Patients ≥12 years of age: 36 mcg (2 inhalations) 4 times daily via a metered-dose aerosol, given alone or in fixed combination with albuterol (90 mcg via the mouthpiece).^{1 2 320} Additional inhalations should not exceed 216 mcg (12 inhalations) of ipratropium bromide in 24 hours.^{1 320}

Patients ≥12 years of age: 500 mcg (contents of 1 unit-dose vial) 3 or 4 times daily (i.e., every 6–8 hours) via a nebulizer.^{4 329}

Adults

COPD

Inhalation

Initially, 36 mcg (2 inhalations) 4 times daily via a metered-dose aerosol, given alone or in fixed combination with albuterol (90 mcg from the mouthpiece).^{1 2 320} Additional inhalations should not exceed 216 mcg (12 inhalations) in 24 hours.^{1 320}

Initially, 500 mcg 3 or 4 times daily (i.e., every 6–8 hours) via a nebulizer.^{4 329} With ipratropium bromide in fixed combination with albuterol sulfate (DuoNeb), 500 mcg 4 times daily.³²⁷ Additional inhalations should not exceed 6 inhalations daily.³²⁷

Prescribing Limits

Pediatric Patients

COPD

Inhalation

Maximum 216 mcg (12 inhalations via a metered-dose inhaler) in 24 hours.^{1 320}

Maximum 12 inhalations via metered-dose inhaler in 24 hours with the fixed combination of ipratropium bromide and albuterol sulfate.³²⁰

500 mcg 3–4 times daily via a nebulizer in patients ≥12 years of age.^{4 329}

Adults

COPD

Inhalation

Maximum 216 mcg (12 inhalations via a metered-dose inhaler) in 24 hours;^{1 320} frequency of administration should not exceed 4 times daily.^{1 267 323}

Maximum 12 inhalations via metered-dose inhaler in 24 hours with the fixed combination of ipratropium bromide and albuterol sulfate.³²⁰

500 mcg 3–4 times daily via a nebulizer.^{4 329}

Special Populations

Geriatric Patients

Dosage adjustments based solely on age are not necessary.^{1 4}

Cautions for Atrovent

Contraindications

• 
  

  Known hypersensitivity to the drug or any other component of the formulation, or to atropine or its derivatives.^{1 4 329}

  
  


• 
  

  Known hypersensitivity to soya lecithin or related food products, including soybeans and peanuts.^{1 277 320}

  
  

Warnings/Precautions

Warnings

Acute Bronchospasm

Delayed onset of action; not indicated for initial treatment.^{1 4} Generally should not be used alone for the management of acute bronchospasm, when a rapid response is required.^{1 4 164 225}

Sensitivity Reactions

Immediate hypersensitivity reactions, including rash, angioedema of the tongue, lips, and face, urticaria, bronchospasm, oropharyngeal edema, and anaphylactic reaction.^{1 4 196 213 277 285 320 329}

Possible paradoxical bronchospasm.^{1 4 190 191 196 270 271 272 273 320}

General Precautions

Worsening COPD

Contact a clinician immediately if a previously effective dosage regimen fails to provide the usual relief (e.g., need to increase the dose or frequency of administration of the drug).¹ Do not increase the dose or frequency of inhalation without consultation with a clinician.¹

Ocular Effects

Possible temporary blurred vision,^{1 2 4 10 328 349} mydriasis,^{1 225 250 275} ocular pain,^{4 328 329 349} conjunctival or corneal congestion associated with visual halos or colored images,¹ or precipitation or worsening of angle-closure glaucoma^{4 173 329 337 349} following inadvertent contact of ipratropium with the eyes.^{4 190 191 328 349}

Minimize ocular exposure by using a mouthpiece rather than a face mask during administration via a nebulizer.^{4 190 191 329} During oral inhalation of aerosol, close eyes.^{1 2} Inhalation aerosol should not be administered using the open-mouth technique in these patients with angle-closure glaucoma.^{173 190 191} Use with caution in patients with angle-closure glaucoma.^{1 4}

Genitourinary Effects

Possible urinary retention/difficulty,^{1 4 251 252 320 329} urinary tract infection,^{4 320 329} or dysuria.^{4 320}

Use with caution in patients with bladder neck obstruction or prostatic hypertrophy.^{1 4 190 191 225 329}

Cardiovascular Effects

Possible adverse cardiovascular effects (e.g., tachycardia, palpitations, aggravated hypotension or hypertension).^{1 4 329}

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category B.¹

Lactation

Use with caution.^{1 2 4 329}

Pediatric Use

Safety and efficacy of oral inhalation not established in children <12 years of age.^{1 4 320 329}

Hepatic Impairment

Use with caution.^{4 329}

Renal Impairment

Use with caution.^{4 329}

Common Adverse Effects

Bronchitis, upper respiratory tract infection,³²⁰ cough,^{1 2 4 87 120 285} and dryness of the mouth,^{1 2 14 16 60 90 120 127} throat,^{1 75 90} or tongue⁸⁷ with ipratropium aerosol. Adverse effects resulting in discontinuance of nebulized ipratropium most frequently include bronchitis, dyspnea, and bronchospasm.^{4 329}

Interactions for Atrovent

Limited systemic absorption following oral inhalation; interactions with systemically administered drugs unlikely.^{2 190 191}

Specific Drugs

Drug	Interaction	Comments
Antimuscarinic agents	Potential pharmacodynamic interaction (additive effects)1 320	Caution advised with concomitant administration1
Methylxanthine derivatives	No adverse drug interactions reported115 120 121 132 157 158 149 187 220 261 305 329
β-Adrenergic agonists	Potential pharmacodynamic interaction (additive effects)4 6 133 147 152 155 225 228 246 248 260 262 278 279 285 287 288 289	If concomitant therapy is required, consider cautious use of cardioselective β-adrenergic blocking agents115 132 139 146 153 154 181 216
Corticosteroids	No adverse drug interactions reported91 115 119 120 121 124 132 153 154 160 329
Cromolyn sodium	No adverse drug interactions reported132 159

Atrovent Pharmacokinetics

Absorption

Bioavailability

Only minimally absorbed into systemic circulation following oral inhalation.^{1 2 4 6 14 106 228 229 230}

Onset

Bronchodilation evident within 15 minutes following oral aerosol inhalation^{1 2 111 120 230} and within 15–30 minutes following oral inhalation via nebulization.^{4 86 281}

Duration

Bronchodilation generally persists for 3–4 hours following oral aerosol inhalation^{1 2 111 120 230} and for 4–5 hours following nebulization.^{4 86 281}

Distribution

Extent

Does not readily penetrate the CNS.^{2 4 12} It is not known whether the drug crosses the placenta or is distributed into milk.^{1 4 6}

Plasma Protein Binding

0–9%.^{1 4}

Elimination

Metabolism

Metabolized partially to at least 8 metabolites.^{4 8 106}

Elimination Route

Excreted principally in feces as unchanged drug.^{2 3 6 7 107 109} Following oral inhalation of radiolabeled ipratropium bromide, about 69 and 3.2% of the dose was excreted in feces and urine, respectively, within 6–7 days.^{6 106 109} Undergoes some biliary elimination.^{6 7}

Half-life

1.6 hours (t_½β with IV administration).^{4 190 229}

Stability

Storage

Oral Inhalation

15–30 °C (metered-dose inhalers or inhalation solution of ipratropium bromide).^{1 3 4 281 320}

2–25°C (oral inhalation solution of ipratropium bromide in fixed combination with albuterol sulfate); protect from light.^{327 328}

ActionsActions

• 
  

  A nonselective competitive antagonist at muscarinic receptors present in airways and other organs.^{2 224 225 232}

  
  


• 
  

  Relaxes smooth muscles of bronchi and bronchioles.^{1 2 4 6}

  
  


• 
  

  Blocks acetylcholine-induced stimulation of guanyl cyclase and reduces formation of cyclic guanosine monophosphate (cGMP), a mediator of bronchoconstriction.^{1 2 4 6}

  
  


• 
  

  Exhibits greater antimuscarinic activity on bronchial smooth muscle than on secretory (e.g., salivary, gastric) glands.^{6 7 12 16 18 34 225}

  
  


• 
  

  Tolerance to bronchodilating effect does not develop with prolonged use.^{4 14 90 91 92 115 116 117 118 119 120 121 168 225 278}

  
  

Advice to Patients

• 
  

  Importance of providing patients with a copy of the manufacturer’s patient information.^{1 4}

  
  


• 
  

  Importance of using proper administration technique.^{1 4}

  
  


• 
  

  Importance of advising patients that oral inhalation is not intended for occasional use.^{1 4} Use consistently throughout the course of therapy for maximum effectiveness.^{1 4}

  
  


• 
  

  Importance of contacting a clinician if symptoms of COPD are not relieved by usually effective doses or if they worsen.¹ Do not increase the dosage or frequency of administration without consultation with a clinician.¹

  
  


• 
  

  Importance of advising patients to close their eyes during oral inhalation of aerosol^{1 2} to avoid inadvertent contact of the drug with the eyes and subsequent adverse effects.^{1 10}

  
  


• 
  

  Importance of contacting a clinician immediately if ocular symptoms develop.¹

  
  


• 
  

  Importance of advising patients that blurring of vision, precipitation or aggravation of narrow angle glaucoma, mydriasis, visual halos, colored images in association with conjunctival or corneal congestion, or eye pain or discomfort may result from contact of the inhalation solution with the eyes.¹

  
  


• 
  

  Importance of informing clinicians if ocular adverse effects develop.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.³²⁰

  
  


• 
  

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

  
  

Preparations

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

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ipratropium Bromide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral Inhalation	Aerosol	18 mcg/metered spray	Atrovent (with chlorofluorohydrocarbon propellants and soya lecithin)	Boehringer Ingelheim
	Solution, for nebulization	0.02%*	Atrovent (preservative-free)	Boehringer Ingelheim
			Ipratropium Bromide Inhalation Solution (preservative-free)	Alpharma, Dey, Holopack, Nephron, Novex, Roxane, RxElite, Teva, Warrick

Ipratropium Bromide Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral Inhalation Only	Aerosol	18 mcg with Albuterol Sulfate 90 mcg (of albuterol) per metered spray	Combivent (with chlorofluorohydrocarbon propellants and soya lecithin)	Boehringer Ingelheim
	Solution, for nebulization	0.5 mg with Albuterol Sulfate 2.5 mg (of albuterol) per 3 mL	DuoNeb	Dey

Comparative Pricing

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

Combivent 103-18MCG/ACT Aerosol (BOEHRINGER INGELHEIM): 14/$189.99 or 44/$535.94

DuoNeb 0.5-2.5 (3)MG/3ML Solution (DEY LABS): 180/$134.89 or 540/$386.3

DuoNeb 0.5-2.5 (3)MG/3ML Solution (DEY LABS): 90/$73.58 or 270/$207.64

Ipratropium Bromide 0.02% Solution (WATSON LABS): 62/$13.99 or 125/$18.98

Ipratropium-Albuterol 0.5-2.5 (3)MG/3ML Solution (MYLAN): 90/$39.99 or 270/$99.96

Disclaimer

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

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

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Boehringer Ingelheim. Atrovent (ipratropium bromide) inhalation aerosol prescribing information. Ridgefield, CT; 2002 Mar 27.

2. Boehringer Ingelheim. Atrovent product monograph. Ridgefield, CT; 1987 Feb.

3. Boehringer Ingelheim. Atrovent product information form for American Hospital Formulary Service. Ridgefield, CT; 1987 Feb.

4. Boehringer Ingelheim. Atrovent (ipratropium bromide) 0.02% inhalation solution prescribing information. Ridgefield, CT; 1998 Oct.

5. Budavari S, O’Neil MJ, Smith A et al, eds. The Merck index. 11th ed. Rahway, NJ: Merck & Co., Inc; 1989:4956-7.

6. Pakes GE, Brogden RN, Heel RC et al. Ipratropium bromide: a review of its pharmacological properties and therapeutic efficacy in asthma and chronic bronchitis. Drugs. 1980; 20:237-66. [IDIS 124386] [PubMed 6448137]

7. Bauer R, Banholzer R, Grieben C et al. Ipratropium bromide. In: Goldberg ME, ed. Pharmacological and biochemical properties of drug substances. 1979; 2:489-515.

8. Deckers W. The chemistry of new derivatives of tropane alkaloids and the pharmacokinetics of a new quaternary compound. Postgrad Med J. 1975; 51(Suppl 7):76-81. [PubMed 134360]

9. Winthrop-Breon. How to correctly use your Tornalate (bitolterol meyslate) metered dose inhaler. New York; 1985 Jan.

10. Boehringer Ingelheim. Questions and answers about Atrovent (ipratropium bromide) inhalation aerosol 18 mcg per puff. Ridgefield, CT; 1987 Mar.

11. Brown JH. Atropine, scopolamine, and related antimuscarinic drugs. In: Gilman AG, Rall TW, Nies AS et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:159-60.

12. Englehardt A. Pharmacology and toxicology of Atrovent. Scand J Respir Dis. 1979; 103(Suppl):110-5.

13. Bauer R, Kuhn FJ, Stockhaus K et al. Allgemeine Pharmakologie und seckretionshemmende Wirkung von (8r)-3α-Hydroxy-8-isopropyl- 1αH,5αH-tropaniumbromid-()tropat (Ipratropiumbromid). (German; with English abstract.) Arzneim-Forsch. 1976; 26:974-80.

14. Gross NJ, Skorodin MS. Anticholinergic, antimuscarinic bronchodilators. Am Rev Respir Dis. 1984; 129:856-70. [IDIS 185268] [PubMed 6372560]

15. Genentech, Inc. Patient information booklet: your guide to Pulmozyme (dornase alfa) therapy for cystic fibrosis (CF). South San Francisco, CA; 1994.

16. Bleichert A. Zur Frage der Nebenwirkungen anticholinerger Drogen in Abhängigkeit von der Applikationsart: inhalation versus intravenöse Injektion von Ipratropiumbromid. (German; with English abstract.) Arzneim-Forsch. 1976; 26:1010-3.

17. Otto P. Untersuchungen über die Hemmung der Magensaftsekretion beim Menschen durch den Atropinabkömmling N-Isopropyl-nortropintropasäureester-brommethylat. (German; with English abstract.) Arzneim-Forsch. 1973; 23:1334-6.

18. Bauer R, Püschmann S, Wick H et al. Wirkung von (8r)-3α-Hydroxy-8-isopropyl-1αH,5αH-tropaniumbromid-()- tropat (Ipratropiumbromid) auf Spasmen des Tracheobronchialbaumes und die Bronchialsekretion, die Speichelsekretion, EKG und Herzfrequenz. (German; with English abstract.) Arzneim-Forsch. 1976; 26:981-5.

19. Morris HG. Review of ipratropium bromide in induced bronchospasm in patients with asthma. Am J Med. 1986; 81(Suppl 5A):36-44. [IDIS 228924] [PubMed 2947459]

20. Cockcroft DW, Ruffin RE, Hargreave FE. Effect of Sch1000 in allergen-induced asthma. Clin Allergy. 1978; 8:361-72. [PubMed 152170]

21. Bandouvakis J, Cartier A, Roberts R et al. The effect of ipratropium and fenoterol on methacholine- and histamine-induced bronchoconstriction. Br J Dis Chest. 1981; 75:295-305. [PubMed 6457620]

22. Woenne R, Kattan M, Orange RP et al. Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorpheniramine maleate. J Allergy Clin Immunol. 1978; 62:119-24. [IDIS 115343] [PubMed 149804]

23. Giulekas D, Tsakalos N, Georgopoulos D et al. Effect of ipratropium bromide on repeated methacholine challenges. Ann Allergy. 1985; 55:835-9. [IDIS 209734] [PubMed 2934009]

24. Larsson K. Ipratropium bromide: bronchodilator action and effect on methacholine-induced bronchoconstriction. J Asthma. 1987; 24:29-35. [PubMed 2975285]

25. de Vries K. The protective effect of inhaled Sch 1000 MDI on bronchoconstriction induced by serotonin, histamine, acetylcholine and propranolol. Postgrad Med J. 1975; 51(Suppl 7):106.

26. Nolte D. The action of Sch 1000 MDI on experimental bronchoconstriction induced by various types of nonspecific and pharmacodynamic irritants in young asthmatics. Postgrad Med J. 1975; 51(Suppl 7):103.

27. Beumer HM. The antagonistic effect of several doses of inhaled Sch 1000 administered by metered dose inhaler (MDI) on a Bird respirator on acetylcholine-induced bronchospasm. Postgrad Med J. 1975; 51(Suppl 7):101-2.

28. Harnett J, Spector SL. Blocking effect of SCH 1000, isoproterenol, and the combination on methacholine and histamine inhalations. J Allergy Clin Immunol. 1976; 57:261.

29. Kersten W. The role of Sch 1000 MDI in preventing a rise in total airways resistance (R_t) induced by inhaled allergen in patients with atopic asthma. Postgrad Med J. 1975; 51(Suppl 7):103.

30. Killian D, Mellon A, Hargreave FE. Protective effect of drugs on histamine-induced asthma. J Allergy Clin Immunol. 1976; 57:263.

31. Germouty J. The possible antagonism between Sch 1000 MDI and beta-blocking agents. Postgrad Med. 1975; 51(Suppl 7):103.

32. Chan-Yeung M. The effect of Sch 1000 and disodium cromoglycate on exercise-induced asthma. Chest. 1977; 71:320-3. [PubMed 138577]

33. Tullett WM, Patel KR, Berkin KE et al. Effect of lignocaine, sodium cromoglycate, and ipratropium bromide in exercise-induced asthma. Thorax. 1982; 37:737-40. [PubMed 6218645]

34. Hartley JPR, Davies BH. Cholinergic blockade in the prevention of exercise-induced asthma. Thorax. 1980; 35:680-5. [PubMed 6449753]

35. Borut TC, Tashkin DP, Fischer TJ et al. Comparison of aerosolized atropine sulfate and Sch 1000 on exercise-induced bronchospasm in children. J Allergy Clin Immunol. 1977; 60:127-33. [IDIS 92840] [PubMed 141471]

36. Poppius H, Salorinne Y, Viljanen AA. Inhalation of a new anticholinergic drug, Sch 1000, in asthma and chronic bronchitis: effect on airway resistance, thoracic gas volume, blood gases and exercise-induced asthma. Bull Physiopathol Resp. 1972; 8:643-52.

37. Poppius H, Salorinne Y, Viljanen AA. The role of Sch 1000 MDI in preventing exercise-induced asthma. Postgrad Med J. 1975; 51(Suppl 7):105.

38. Weinberg EG. Experience with Sch 1000 MDI in the treatment of exercise-induced asthma in children. Postgrad Med J. 1975; 51(Suppl 7):128.

39. Thomson NC, Patel KR, Kerr JW. Sodium cromoglycate and ipratropium bromide in exercise-induced asthma. Thorax. 1978; 33:694-9. [PubMed 154747]

40. Sanguinetti CM, De Luca S, Gasparini S et al. Evaluation of Duovent in the prevention of exercise-induced asthma. Respiration. 1986; 50(Suppl 2):181-5. [PubMed 2951802]

41. Dry J, Pradalier A, Leynadier F et al. Recherche d’une prévention de la bronchoconstriction induite par une épreuve d’efforts chez l’asthmatique par un atropinique de synthèse: le Sch 1000. (French; with English abstract.) Thérapie. 1977; 32:181-8.

42. Anderson S, Seale JP, Ferris L et al. An evaluation of pharmacotherapy for exercise-induced asthma. J Allergy Immunol. 1979; 64:612-24.

43. Poppius H, Sovijärvi ARA, Tammilehto L. Controlled study on the preventing effect of inhaled ipratropium powder on asthma induced by breathing cold air during exercise. Respiration. 1984; 46(Suppl):45-6. [PubMed 6436932]

44. Wolkove N, Kreisman H, Frank H et al. The effect of ipratropium on exercise-induced bronchoconstriction. Ann Allergy. 1981; 47:311-5. [IDIS 164243] [PubMed 6459045]

45. Scano G, Stendardi L, Gigliotti G et al. Comparative effects of SCH 1000 and fenoterol after histamine-induced bronchoconstricition in asymptomatic asthmatics. Intl J Clin Pharmacol Ther Toxicol. 1984; 22:81-5.

46. Dorward AJ, Patel KR. A comparison of ketotifen with clemastine, ipratropium bromide and sodium cromoglycate in exercise-induced asthma. Clin Allergy. 1982; 12:355-61. [PubMed 6214337]

47

Fluor-Op

fluorometholone

Dosage Form: Ophthalmic Suspension, USP 0.1%

Fluor-Op®

(FLUOROMETHOLONE OPHTHALMIC SUSPENSION, USP) 0.1%

DESCRIPTION

Fluor-Op (fluorometholone ophthalmic suspension, USP) 0.1%, is a topical anti-inflammatory agent for ophthalmic use.

Chemical Name: 9-fluoro-11ß,17-dihydroxy-6α-methylpregna-1,4-diene-3,20-dione.

Contains:

Fluorometholone 0.1%

with: polyvinyl alcohol 1.4%; benzalkonium chloride 0.004%, edetate disodium; sodium chloride; sodium phosphate monobasic, monohydrate; sodium phosphate dibasic, anhydrous; polysorbate 80; sodium hydroxide to adjust the pH, and purified water.

CLINICAL PHARMACOLOGY

Corticosteroids inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.

There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

Corticosteroids are capable of producing a rise in intraocular pressure. In clinical studies on patients' eyes treated with both dexamethasone and fluorometholone 0.1% suspensions, fluorometholone demonstrated a lower propensity to increase intraocular pressure than did dexamethasone.

INDICATIONS AND USAGE

Fluor-Op is indicated for the treatment of corticosteroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe.

CONTRAINDICATIONS

Fluor-Op suspension is contraindicated in most viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. Fluor-Op suspension is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of this preparation and to other corticosteroids.

WARNINGS

Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Prolonged use may suppress the host immune response and thus increase the hazard of secondary ocular infections.

Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning. Use of topical corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation.

Acute purulent untreated infections of the eye may be masked or activity enhanced by the presence of corticosteroid medication.

If this product is used for 10 days or longer, intraocular pressure should be routinely monitored even though it may be difficult in children and uncooperative patients. Steroids should be used with caution in the presence of glaucoma. Intraocular pressure should be checked frequently.

The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation.

Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution; frequent slit lamp microscopy is recommended.

Corticosteroids are not effective in mustard gas keratitis and Sjögren’s keratoconjunctivitis.

PRECAUTIONS

General

The initial prescription and renewal of the medication order beyond 20 milliliters of Fluor-Op suspension should be made by a physician only after examination of the patient with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. If signs and symptoms fail to improve after two days, the patient should be re-evaluated.

As fungal infections of the cornea are particularly prone to develop coincidentally with long-term local corticosteroid applications, fungal invasion should be suspected in any persistent corneal ulceration where a corticosteroid has been used or is in use. Fungal cultures should be taken when appropriate.

If this product is used for 10 days or longer, intraocular pressure should be monitored (see WARNINGS).

Information to the Patient

If inflammation or pain persists longer than 48 hours or becomes aggravated, the patient should be advised to discontinue use of the medication and consult a physician.

This product is sterile when packaged. To prevent contamination, care should be taken to avoid touching the bottle tip to eyelids or to any other surface. The use of this bottle by more than one person may spread infection. Keep bottle tightly closed when not in use. Keep out of reach of children.

Carcinogenesis, mutagenesis, impairment of fertility

No studies have been conducted in animals or in humans to evaluate the possibility of these effects with fluorometholone.

Pregnancy

Teratogenic effects. Pregnancy Category C

Fluorometholone has been shown to be embryocidal and teratogenic in rabbits when administered at low multiples of the human ocular dose. Fluorometholone was applied ocularly to rabbits daily on days 6-18 of gestation, and dose related fetal loss and fetal abnormalities including cleft palate, deformed rib cage, anomalous limbs and neural abnormalities such as encephalocele, craniorachischisis, and spina bifida were observed. There are no adequate and well-controlled studies of fluorometholone in pregnant women, and it is not known whether fluorometholone can cause fetal harm when administered to a pregnant women. Fluorometholone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Because of the potential for serious adverse reactions in nursing infants from fluorometholone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in children below the age of two years have not been established.

ADVERSE REACTIONS

Adverse reactions include, in decreasing order of frequency, elevation of intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage, posterior subcapsular cataract formation, and delayed wound healing.

Although systemic effects are extremely uncommon, there have been rare occurrences of systemic hypercorticoidism after use of topical steroids.

Corticosteroid-containing preparations have also been reported to cause acute uveitis and perforation of the globe. Keratitis, conjunctivitis, corneal ulcers, mydriasis, conjunctival hyperemia, loss of accommodation and ptosis have occasionally been reported following use of corticosteroids.

The development of secondary ocular infection (bacterial, fungal and viral) has occurred. Fungal and viral infections of the cornea are particularly prone to develop coincidentally with long-term applications of steroids. The possibility of fungal invasion should be considered in any persistent corneal ulceration where steroid treatment has been used (see WARNINGS).

DOSAGE AND ADMINISTRATION

Instill one drop into the conjunctival sac two to four times daily. During the initial 24 to 48 hours, the dosage may be increased to one application every four hours. Care should be taken not to discontinue therapy prematurely.

If signs and symptoms fail to improve after two days, the patient should be re-evaluated (see PRECAUTIONS).

The dosing of Fluor-Op suspension may be reduced, but care should be taken not to discontinue therapy prematurely. In chronic conditions, withdrawal of treatment should be carried out by gradually decreasing the frequency of applications.

HOW SUPPLIED

Fluor-Op (fluorometholone ophthalmic suspension, USP) 0.1% is supplied in plastic dropper bottles in the following sizes:

5 mL…………………………………………………………………………..NDC 58768-358-05

10 mL…………………………………………………………………………NDC 58768-358-10

15 mL…………………………………………………………………………NDC 58768-358-15

Store at controlled room temperature 15°-30°C (59°-86°F). Protect from freezing. Shake well before using. Keep bottle tightly closed when not in use.

Rx only

Mfd. by OMJ Pharmaceuticals, Inc.,

San Germán, P.R., 00683 for:

Novartis Ophthalmics

Duluth, GA 30097

6069-B

Fluor-Op  fluorometholone  suspension

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 58768-358 Route of Administration OPHTHALMIC DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Fluorometholone (Fluorometholone) Active 0.1 MILLILITER  In 100 MILLILITER benzalkonium chloride Inactive 0.004 MILLILITER  In 100 MILLILITER edetate disodium Inactive   polysorbate 80 Inactive   polyvinyl alcohol Inactive 1.4 MILLILITER  In 100 MILLILITER water Inactive   sodium chloride Inactive   sodium hydroxide Inactive   sodium phosphate dibasic, anhydrous Inactive   sodium phosphate monobasic, monohydrate Inactive

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 58768-358-05 5 mL (MILLILITER) In 1 BOTTLE, DROPPER None 2 58768-358-10 10 mL (MILLILITER) In 1 BOTTLE, DROPPER None 3 58768-358-15 15 mL (MILLILITER) In 1 BOTTLE, DROPPER None

Revised: 05/2006Novartis Ophthalmics

More Fluor-Op resources

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

• Fluor-Op MedFacts Consumer Leaflet (Wolters Kluwer)


• Flarex Concise Consumer Information (Cerner Multum)


• Flarex Suspension MedFacts Consumer Leaflet (Wolters Kluwer)

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• Eye Dryness/Redness
• Eye Redness/Itching
• Eyelash Hypotrichosis

Thrombin

Class: Hemostatics
CAS Number: 9002-04-4
Brands: Thrombin-JMI

• 
  

  Use of topical thrombin (bovine) can stimulate antibody formation against bovine thrombin and/or bovine factor V, potentially resulting in severe hemorrhagic or thrombotic complications; rarely fatal.^{100 103 104 105 106 107 109 110 111 112} (See Antibody Formation under Cautions.)

  
  


• 
  

  Consult expert in coagulation disorders if patient exhibits abnormal coagulation test results, bleeding, or thrombosis.¹⁰⁰ Do not readminister drug to patients with evidence of anti-bovine thrombin antibodies.^{100 103 104 105 106 107 109 111}

  
  

Introduction

Hemostatic agent.^{100 b}

Uses for Thrombin

Hemorrhage

Aids hemostasis at accessible sites of oozing blood and minor bleeding from capillaries and small venules.¹⁰⁰ In various types of surgery, may be used in conjunction with an absorbable gelatin sponge.¹⁰⁰

Does not control arterial bleeding when used alone.^b

Thrombin Dosage and Administration

General

• 
  

  The concentration of thrombin solutions used depends on the severity of bleeding.^{100 109 b}

  
  

Administration

Topical Administration

Apply topically as a powder or solution; do not inject.^{100 102}

Prepare and administer solution according to manufacturer’s recommendations.¹⁰⁰ Use solution promptly upon removal from container.¹⁰⁰

Spray reconstituted solution directly onto bleeding surfaces (using a sterile syringe and spray tip, spray pump and actuator, or nasal delivery device) or apply with an absorbable gelatin sponge;¹⁰⁰ do not leave solution in syringe as an intermediate step when preparing the spray delivery device.¹⁰²

Alternatively, flood surfaces with thrombin solution using a sterile syringe and small gauge needle.¹⁰⁰ To avoid inadvertent intravascular administration, label syringes containing reconstituted thrombin (bovine) with a warning against IV injection and keep separate from parenteral preparations.¹⁰²

May apply as a dry powder; preferred method of application to oozing surfaces in some cases.^{100 102}

May use in conjunction with a bovine gelatin-based hemostatic matrix (e.g., FloSeal NT).¹⁰⁰

Before application, sponge (do not wipe) recipient surface free of blood; otherwise, blood may clot on surface layers while bleeding continues underneath clot.¹⁰⁰ After application, avoid sponging treated areas so clot is not disturbed.¹⁰⁰

When used with an absorbable gelatin sponge, immerse sponge strips of the desired size in the solution and knead vigorously with moistened, gloved fingers to remove trapped air and facilitate saturation.¹⁰⁰ Apply the saturated sponge to the bleeding area and hold in place with a cotton pledget or small gauze sponge until hemostasis occurs.¹⁰⁰ Consult manufacturer’s information for detailed instructions on use of absorbable gelatin sponge preparations.¹⁰⁰

Reconstitution

To prepare a solution containing 1000 units/mL of thrombin (bovine), transfer entire contents of the supplied diluent vial (5 or 20 mL) to a vial containing 5000 or 20,000 units, respectively, of lyophilized thrombin via a syringe or transfer needle.¹⁰⁰ Consult manufacturer’s instructions for appropriate use of the transfer device.¹⁰⁰

Use an appropriate volume of the 0.9% sodium chloride diluent to prepare other concentrations.¹⁰⁰

Dosage

Adults

Hemorrhage

Topical

Plastic surgery, dental extractions, skin grafting, other general uses: Solutions containing approximately 100 units/mL are frequently used.^{100 b}

Profuse bleeding (e.g., from cut surfaces of the liver or spleen): Solutions containing 1000 units/mL may be required.^{100 b}

Cautions for Thrombin

Contraindications

• 
  

  Known sensitivity to any ingredient in the formulation and/or to material of bovine origin.¹⁰⁰

  
  

Warnings/Precautions

Warnings

Effects on Hemostasis

Because of its hemostatic activity, thrombin should not be injected or otherwise allowed to enter large blood vessels; may result in extensive intravascular clotting and even death.^{100 102}

Abnormalities in hemostasis reported, ranging from asymptomatic alterations in coagulation test results (e.g., PT, PTT) to severe bleeding or thrombosis (rarely fatal); may be related to antibody formation.^{100 103 105 106 108 109 110 111 112} (See Antibody Formation under Cautions.)

Consult an expert in coagulation disorders if patient exhibits abnormal coagulation test results, bleeding, or thrombosis.¹⁰⁰ Consider underlying immunologic mechanisms with any contemplated intervention.^{100 106}

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis with profound bradycardia and hypotension reported rarely.^{101 b}

Potential allergic reactions in patients sensitive to bovine materials.¹⁰⁰

Antibody Formation

Can stimulate antibody formation against bovine thrombin and/or bovine factor V (a potential contaminant in some bovine thrombin preparations).^{100 103 104 105 106 109 110 111 112} Such antibodies may cross-react with human factor V, potentially resulting in a factor V deficiency and hemorrhagic complications; paradoxical thrombosis also has occurred.^{100 103 105 106 107 109 111 112} (See Effects on Hemostasis under Cautions.) Antibodies may develop as early as 8 days after use and may persist for months to years following initial exposure.^{103 105 106 111} Not known whether highly purified preparations (i.e., containing no detectable levels of factor Va) are associated with reduced risk of immunogenicity.^{100 109}

Patients with evidence of anti-bovine thrombin antibodies should not be reexposed to the drug; increased likelihood of antibody formation with repeated application.^{100 103 104 105 106 107 109 111}

General Precautions

Concomitant Absorbable Gelatin Sponge

Consult prescribing information for absorbable gelatin sponge preparations when used concomitantly.¹⁰⁰

Specific Populations

Pregnancy

Category C.¹⁰⁰

Pediatric Use

Safety and efficacy not established.¹⁰⁰

Stability

Storage

Topical

Powder

2–25°C.¹⁰⁰ May refrigerate reconstituted solution at 2–8°C for up to 24 hours or store at room temperature for up to 8 hours.¹⁰⁰

ActionsActions

• 
  

  Causes clotting of whole blood or plasma without the addition of other substances.^{100 b} Affects hemostasis principally by converting fibrinogen to fibrin; several other mechanisms (e.g., stimulation of platelet release reaction, aggregation of platelets) may be involved.^{100 109 b}

  
  


• 
  

  Rate of blood clotting depends on concentration of thrombin and fibrinogen.^{100 b}

  
  


• 
  

  Does not clot blood when clotting defect is the rare absence of fibrinogen.¹⁰⁰

  
  

Advice to Patients

• 
  

  Importance of informing clinician of allergy to bovine materials. (See Cautions.)¹⁰⁰

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁰⁰

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹⁰⁰

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹⁰⁰ (See Cautions.)

  
  

Preparations

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

Thrombin (Bovine)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Topical	Powder	5000 units	Thrombin-JMI (with 0.9% sodium chloride diluent)	King
			Thrombin-JMI (with 0.9% sodium chloride diluent; epistaxis kit also contains nasal delivery device and syringe)	King
		20,000 units	Thrombin-JMI (with 0.9% sodium chloride diluent)	King
			Thrombin-JMI (with 0.9% sodium chloride diluent; syringe spray kit also contains sterile syringe with transfer device and spray tip)	King
			Thrombin-JMI (with 0.9% sodium chloride diluent; pump spray kit also contains spray pump and actuator)	King

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 February 01, 2010. 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.

100. King Pharmaceuticals, Inc. Thrombin-JMI (thrombin, topical USP) bovine origin prescribing information. Bristol, TN; 2007 Nov.

101. Rothenberg DM, Moy JN. Anaphylactic reaction to topical bovine thrombin. Anesthesiology. 1993; 78:779-82. [IDIS 316352] [PubMed 8096685]

102. Cohen MR, Smetzer JL. ISMP medical error report analysis: Danger of giving topical thrombin intravascularly. Hosp Pharm. 2007; 42:284-5.

103. Winterbottom N, Kuo JM, Nguyen K et al. Antigenic responses to bovine thrombin exposure during surgery: a prospective study of 309 patients. J Applied Research. 2002; 2:1–11.

104. Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Ferraris SP et al. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007; 83:S27-86. [PubMed 17462454]

105. Ortel TL, Mercer MC, Thames EH et al. Immunologic impact and clinical outcomes after surgical exposure to bovine thrombin. Ann Surg. 2001; 233:88-96. [PubMed 11141230]

106. Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure. Transfusion. 2002; 42:18-26. [PubMed 11896308]

107. Doria C, Fischer CP, Wood CG et al. Phase 3, randomized, double-blind study of plasma-derived human thrombin versus bovine thrombin in achieving hemostasis in patients undergoing surgery. Curr Med Res Opin. 2008; 24:785-94. [PubMed 18241525]

108. Chapman WC, Singla N, Genyk Y et al. A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis. J Am Coll Surg. 2007; 205:256-65. [PubMed 17660072]

109. Cheng CM, Meyer-Massetti C, Kayser SR. A review of three stand-alone topical thrombins for surgical hemostasis. Clin Ther. 2009; 31:32-41. [PubMed 19243705]

110. Clark J, Crean S, Reynolds MW. Topical bovine thrombin and adverse events: a review of the literature. Curr Med Res Opin. 2008; 24:2071-87. [PubMed 18549663]

111. Dorion RP, Hamati HF, Landis B et al. Risk and clinical significance of developing antibodies induced by topical thrombin preparations. Arch Pathol Lab Med. 1998; 122:887-94. [PubMed 9786349]

112. Lundblad RL, Bradshaw RA, Gabriel D et al. A review of the therapeutic uses of thrombin. Thromb Haemost. 2004; 91:851-60. [PubMed 15116244]

b. AHFS Drug Information 2004. McEvoy GK, ed. Heparin. Bethesda, MD: American Society of Health-System Pharmacists; 2004: 1454-5.

More Thrombin resources

• Thrombin Use in Pregnancy & Breastfeeding
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• Recothrom Prescribing Information (FDA)


• Recothrom Consumer Overview


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• Hemostasis

Vitaphil Plus DHA 90

Generic Name: prenatal multivitamins (PRE nay tal VYE ta mins)

Brand Names: Advance Care Plus, Bright Beginnings, Cavan Folate, Cavan One, Cavan-Heme OB, Cenogen Ultra, CitraNatal Rx, Co Natal FA, Complete Natal DHA, Complete-RF, CompleteNate, Concept OB, Docosavit, Dualvit OB, Duet, Edge OB, Elite OB 400, Femecal OB, Folbecal, Folcaps Care One, Folivan-OB, Foltabs, Gesticare, Icar Prenatal, Icare Prenatal Rx, Inatal Advance, Infanate DHA, Kolnatal DHA, Lactocal-F, Marnatal-F, Maternity, Maxinate, Mission Prenatal, Multi-Nate 30, Multinatal Plus, Nata 29 Prenatal, Natachew, Natafort, Natelle, Neevo, Nestabs, Nexa Select with DHA, Novanatal, NovaStart, O-Cal Prenatal, OB Complete, OB Natal One, Ob-20, Obtrex DHA, OptiNate, Paire OB Plus DHA, PNV Select, PNV-Total, PR Natal 400, Pre-H-Cal, Precare, PreferaOB, Premesis Rx, PrenaCare, PrenaFirst, PrenaPlus, Prenatabs OBN, Prenatabs Rx, Prenatal 1 Plus 1, Prenatal Elite, Prenatal Multivitamins, Prenatal Plus, Prenatal S, Prenatal-U, Prenate Advanced Formula, Prenate DHA, Prenate Elite, Prenavite FC, PreNexa, PreQue 10, Previte Rx, PrimaCare, Pruet DHA, RE OB Plus DHA, Renate, RightStep, Rovin-NV, Se-Care, Se-Natal One, Se-Plete DHA, Se-Tan DHA, Select-OB, Seton ET, Strongstart, Stuart Prenatal with Beta Carotene, Tandem OB, Taron-BC, Tri Rx, TriAdvance, TriCare, Trimesis Rx, Trinate, Triveen-PRx RNF, UltimateCare Advance, Ultra-Natal, Vemavite PRX 2, VeNatal FA, Verotin-BY, Verotin-GR, Vinacal OR, Vinatal Forte, Vinate Advanced (New Formula), Vinate AZ, Vinate Care, Vinate Good Start, Vinate II (New Formula), Vinate III, Vinate One, Vitafol-OB, VitaNatal OB plus DHA, Vitaphil, Vitaphil Aide, Vitaphil Plus DHA, Vitaspire, Viva DHA, Vol-Nate, Vol-Plus, Vol-Tab Rx, Vynatal F.A., Zatean-CH, Zatean-PN

What are Vitaphil Plus DHA 90 (prenatal multivitamins)?

There are many brands and forms of prenatal vitamin available and not all brands are listed on this leaflet.

Prenatal vitamins are a combination of many different vitamins that are normally found in foods and other natural sources.

Prenatal vitamins are used to provide the additional vitamins needed during pregnancy. Minerals may also be contained in prenatal multivitamins.

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

What is the most important information I should know about prenatal vitamins?

There are many brands and forms of prenatal vitamin available and not all brands are listed on this leaflet.

Never take more than the recommended dose of a multivitamin. Avoid taking any other multivitamin product within 2 hours before or after you take your prenatal vitamins. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

Many multivitamin products also contain minerals such as calcium, iron, magnesium, potassium, and zinc. Minerals (especially taken in large doses) can cause side effects such as tooth staining, increased urination, stomach bleeding, uneven heart rate, confusion, and muscle weakness or limp feeling. Read the label of any multivitamin product you take to make sure you are aware of what it contains.

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of vitamins A, D, E, or K can cause serious or life-threatening side effects and can also harm your unborn baby. Certain minerals contained in a prenatal multivitamin may also cause serious overdose symptoms or harm to the baby if you take too much.

Overdose symptoms may include stomach pain, vomiting, diarrhea, constipation, loss of appetite, hair loss, peeling skin, tingly feeling in or around your mouth, changes in menstrual periods, weight loss, severe headache, muscle or joint pain, severe back pain, blood in your urine, pale skin, and easy bruising or bleeding.

Do not take this medication with milk, other dairy products, calcium supplements, or antacids that contain calcium. Calcium may make it harder for your body to absorb certain ingredients of the multivitamin.

What should I discuss with my healthcare provider before taking prenatal vitamins?

Many vitamins can cause serious or life-threatening side effects if taken in large doses. Do not take more of this medication than directed on the label or prescribed by your doctor.

Before taking prenatal vitamins, tell your doctor about all of your medical conditions.

You may need to continue taking prenatal vitamins if you breast-feed your baby. Ask your doctor about taking this medication while breast-feeding.

How should I take prenatal vitamins?

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

Never take more than the recommended dose of prenatal vitamins.

Many multivitamin products also contain minerals such as calcium, iron, magnesium, potassium, and zinc. Minerals (especially taken in large doses) can cause side effects such as tooth staining, increased urination, stomach bleeding, uneven heart rate, confusion, and muscle weakness or limp feeling. Read the label of any multivitamin product you take to make sure you are aware of what it contains.

Take your prenatal vitamin with a full glass of water.

Swallow the regular tablet or capsule whole. Do not break, chew, crush, or open it.

The chewable tablet must be chewed or allowed to dissolve in your mouth before swallowing. You may also allow the chewable tablet to dissolve in drinking water, fruit juice, or infant formula (but not milk or other dairy products). Drink this mixture right away.

Use prenatal vitamins regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Store at room temperature away from moisture and heat. Keep prenatal vitamins in their original container. Storing vitamins in a glass container can ruin the medication.

What happens if I miss a dose?

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

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of vitamins A, D, E, or K can cause serious or life-threatening side effects and can also harm your unborn baby. Certain minerals contained in a prenatal multivitamin may also cause serious overdose symptoms or harm to the baby if you take too much.

Overdose symptoms may include stomach pain, vomiting, diarrhea, constipation, loss of appetite, hair loss, peeling skin, tingly feeling in or around your mouth, changes in menstrual periods, weight loss, severe headache, muscle or joint pain, severe back pain, blood in your urine, pale skin, and easy bruising or bleeding.

What should I avoid while taking prenatal vitamins?

Avoid taking any other multivitamin product within 2 hours before or after you take your prenatal vitamins. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

Avoid the regular use of salt substitutes in your diet if your multivitamin contains potassium. If you are on a low-salt diet, ask your doctor before taking a vitamin or mineral supplement.

Do not take this medication with milk, other dairy products, calcium supplements, or antacids that contain calcium. Calcium may make it harder for your body to absorb certain ingredients of the prenatal vitamin.

Prenatal vitamins 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.

When taken as directed, prenatal vitamins are not expected to cause serious side effects. Less serious side effects may include:

• 
  

  upset stomach;

  
  


• 
  

  headache; or

  
  


• 
  

  unusual or unpleasant taste in your mouth.

  
  

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 prenatal vitamins?

Vitamin and mineral supplements can interact with certain medications, or affect how medications work in your body. Before taking a prenatal vitamin, tell your doctor if you also use:

• 
  

  diuretics (water pills);

  
  


• 
  

  heart or blood pressure medications;

  
  


• 
  

  tretinoin (Vesanoid);

  
  


• 
  

  isotretinoin (Accutane, Amnesteen, Clavaris, Sotret);

  
  


• 
  

  trimethoprim and sulfamethoxazole (Cotrim, Bactrim, Gantanol, Gantrisin, Septra, TMP/SMX); or

  
  


• 
  

  an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Cataflam, Voltaren), indomethacin (Indocin), meloxicam (Mobic), and others.

  
  

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

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• Vitaphil Plus DHA 90 Use in Pregnancy & Breastfeeding
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• Paire OB Plus DHA Prescribing Information (FDA)


• PreNexa MedFacts Consumer Leaflet (Wolters Kluwer)


• PreNexa Prescribing Information (FDA)


• PreferaOB Prescribing Information (FDA)


• Prenatal Plus Prescribing Information (FDA)


• Prenatal Plus Iron Prescribing Information (FDA)


• Prenate Elite Prescribing Information (FDA)


• Prenate Elite MedFacts Consumer Leaflet (Wolters Kluwer)


• Prenate Elite tablets


• Prenate Essential Prescribing Information (FDA)


• PrimaCare Advantage MedFacts Consumer Leaflet (Wolters Kluwer)


• PrimaCare ONE capsules


• PrimaCare One MedFacts Consumer Leaflet (Wolters Kluwer)


• Renate DHA Prescribing Information (FDA)


• Se-Natal 19 Chewable Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Se-Natal 19 Prescribing Information (FDA)


• Tandem DHA Prescribing Information (FDA)


• Tandem OB Prescribing Information (FDA)


• TriAdvance Prescribing Information (FDA)


• Triveen-One MedFacts Consumer Leaflet (Wolters Kluwer)


• Triveen-PRx RNF Prescribing Information (FDA)


• UltimateCare ONE NF Prescribing Information (FDA)


• Ultra NatalCare MedFacts Consumer Leaflet (Wolters Kluwer)


• Vinate AZ Prescribing Information (FDA)


• Vitafol-One MedFacts Consumer Leaflet (Wolters Kluwer)


• Zatean-CH Prescribing Information (FDA)

Compare Vitaphil Plus DHA 90 with other medications

• Vitamin/Mineral Supplementation during Pregnancy/Lactation

Where can I get more information?

• Your pharmacist can provide more information about prenatal vitamins.