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Wednesday, 16 May 2012

Phentermine

Class: Anorexigenic Agents and Respiratory and Cerebral Stimulants, Miscellaneous
VA Class: GA751
CAS Number: 122-09-8
Brands: Adipex-P, Ionamin, Phentride, Teramine

Introduction

Amphetamine congener; anorexigenic agent.^a ^b ^c

Uses for Phentermine

Exogenous Obesity

Adjunct to exercise, behavioral modification, and caloric restriction in the short-term management (a few weeks) of exogenous obesity.^a ^b ^c

May use in patients with no underlying risk factor but a pretreatment body mass index (BMI) of ≥30 kg/m² and in those with an underlying risk factor (e.g., hypertension, diabetes mellitus, hyperlipidemia) and a pretreatment BMI of ≥27 kg/m².¹⁵⁴ ^b ^c

Use only for short-term monotherapy; not for use in combination with any other drug for weight loss, including SSRI antidepressants (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) or MAO inhibitors.¹⁵⁴ ^b ^c (See Warnings under Cautions.)

Phentermine Dosage and Administration

General

Teach patient to curtail overeating and consume a suitable diet to help induce and maintain weight loss.^a

Administration

Oral Administration

Administer phentermine resin complex capsule before breakfast or 10–14 hours before retiring; swallow capsule whole.^b

Administer phentermine hydrochloride 37.5-mg capsule or tablet (Adipex-P) before or 1–2 hours after breakfast; avoid late evening administration because of possible insomnia.^c

Dosage

Available as phentermine resin complex; dosage expressed in terms of phentermine.^a ^b Also available as phentermine hydrochloride; dosage expressed in terms of phentermine hydrochloride.^a ^c

Adjust dosage according to individual response and tolerance; use the smallest dosage required to produce the desired response.^c

Adults

Exogenous Obesity

Oral

Phentermine (as resin complex): Usual dosage is 15 or 30 mg once daily.^a ^b

Phentermine hydrochloride: Usual dosage is 8 mg 3 times daily (given 30 minutes before meals)^a or 15–37.5 mg once daily (in the morning).^a ^c Alternatively, 18.75 mg twice daily.^c

Special Populations

Geriatric Patients

Select dosage with caution, starting at lower end of dosage range.^b

Cautions for Phentermine

Contraindications

Symptomatic cardiovascular disease, hyperthyroidism, moderate to severe hypertension, glaucoma, or advanced arteriosclerosis.^a ^b ^c

Agitated state or history of drug abuse.^a ^b ^c

Within 14 days of MAO inhibitor therapy.^a ^b ^c

Known hypersensitivity or idiosyncrasy to sympathomimetic amines.^a ^b ^c

Warnings/Precautions

Warnings

Concomitant Drug Therapy for Weight Loss

Avoid concomitant use with other drugs for weight loss, including anorexigenic agents (e.g., phendimetrazine), SSRI antidepressants (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline), and MAO inhibitors,¹⁵⁴ ¹⁶⁵ ¹⁶⁸ ¹⁶⁹ ^b ^c since severe adverse reactions may occur.¹⁵⁸ (See Specific Drugs under Interactions.)

Primary Pulmonary Hypertension

Risk of primary pulmonary hypertension (frequently fatal) when used in combination with at least one other anorexigenic agent, including dexfenfluramine or fenfluramine (both no longer commercially available in the US) or phendimetrazine ¹⁶⁵ ¹⁶⁷ or in those with a history of receiving at least one other anorexigenic agent.¹³³ ¹⁵³ ¹⁵⁴ ¹⁵⁵ ¹⁵⁶ ¹⁶⁵ ¹⁶⁶ ¹⁶⁷ ¹⁶⁸

Risk with use of phentermine alone cannot be ruled out;¹⁵⁴ ¹⁶⁸ ¹⁶⁹ primary pulmonary hypertension reported rarely in patients receiving phentermine alone.^b ^c

Discontinue if new, unexplained symptoms of dyspnea, angina, syncope, or edema of the lower extremities occur,¹⁵⁴ ¹⁶⁴ ¹⁶⁸ ¹⁶⁹ and evaluate for possible pulmonary hypertension.¹⁶⁴

Valvular Heart Disease

Risk of serious regurgitant valvular (principally mitral, aortic, and/or tricuspid; usually multivalvular) heart disease when used in combination with phendimetrazine¹⁶⁵ ¹⁶⁷ or with dexfenfluramine or fenfluramine (both no longer commercially available in the US).¹¹⁴ ¹¹⁵ ¹¹⁶ ¹¹⁸ ¹²² ¹²⁵ ¹²⁷ ¹²⁸ ¹²⁹ ¹³⁰ ¹³¹ ¹³² ¹³³ ¹³⁴ ¹⁵⁸ ¹⁶⁶ ¹⁶⁷ ¹⁶⁸ ¹⁶⁹

Risk with use of phentermine alone cannot be ruled out;^c valvular heart disease reported rarely in patients receiving phentermine alone.¹⁶⁸ ^c

Medical history and cardiovascular examination are recommended for patients who received dexfenfluramine or fenfluramine alone or in combination with other anorexigenic drugs (e.g., phentermine). Perform echocardiogram in those with signs/symptoms suggestive of valvular heart disease and base subsequent testing and/or treatment on the specific valve lesions. Strongly consider performing echocardiographic evaluation in all patients exposed to these anorexigenic agents who are about to undergo invasive procedures for which anti-infective prophylaxis for bacterial endocarditis is indicated. In case of emergency procedures when cardiac evaluation cannot be performed, administer preventive anti-infective therapy.

Tolerance to Anorexigenic Effect

Tolerance to anorexigenic effect usually develops within a few weeks.^b ^c When it does, discontinue therapy; do not attempt to increase effect by exceeding recommended dosage.^b ^c

CNS Effects

Performance of activities requiring mental alertness or physical coordination may be impaired.^b ^c

Abuse Potential

Potential for abuse; habituation or addiction reported with similar drugs (e.g., amphetamines).^a ^b ^c

Manifestations of chronic intoxication may include psychosis resembling schizophrenia, severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes.^b ^c

Abrupt discontinuance following prolonged high dosage may result in extreme fatigue, depression, and sleep EEG changes.^b ^c

General Precautions

Prescribe and dispense in the smallest feasible quantity to minimize possibility of overdosage.^b ^c

Hypertension

Use with caution in patients with mild hypertension; monitor BP closely.^a ^b ^c Contraindicated in those with moderate or severe hypertension.^a ^b ^c

Diabetes Mellitus

Use with caution in patients with diabetes mellitus; insulin requirements may decrease in association with phentermine use and the concomitant dietary regimen and weight loss.^a ^b ^c

Specific Populations

Pregnancy

Category C.^c ^d

Whether potential benefits outweigh risks is questionable; use during pregnancy (especially during the first trimester) probably should be considered a contraindication.^a ^d

Lactation

Not known whether phentermine is distributed into milk.^d Discontinue nursing or the drug.^c ^d

Pediatric Use

Safety and efficacy not established; use not recommended in children <16 years of age.^a ^b ^c

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution, starting at lower end of dosage range, due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.^b Monitoring of renal function may be useful.^b

Renal Impairment

Use with caution; clearance may be decreased and risk of toxicity increased.^b

Common Adverse Effects

Palpitation, tachycardia, increased BP, overstimulation, restlessness, insomnia, tremor, dizziness, headache, euphoria, dysphoria, dryness of the mouth, unpleasant taste, diarrhea, constipation, vomiting, other GI disturbances, urticaria, impotence, changes in libido.^a ^b ^c

Interactions for Phentermine

Specific Drugs

Drug	Interaction	Comments
α-Adrenergic blocking agents (e.g., guanethidine [no longer commercially available in the US])	Decreased hypotensive effect^a ^b ^c
Alcohol	Risk of adverse interaction^b
Anorexigenic agents (e.g., phendimetrazine; dexfenfluramine or fenfluramine [both no longer commercially available in the US])	Potential valvuar heart disease and primary pulmonary hypertension¹³³ ¹⁵³ ¹⁵⁴ ¹⁵⁵ ¹⁵⁶ ¹⁶⁵ ¹⁶⁶ ¹⁶⁷ ¹⁶⁸	Do not use in combination with other anorexigenic agents¹⁶⁵ ¹⁶⁷
Antidepressants, SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline)	Potentially severe adverse reactions¹⁵⁸	Concomitant use not recommended¹⁵³ ¹⁵⁴ ¹⁵⁶ ¹⁵⁸ ¹⁶⁵ ¹⁶⁸ ¹⁶⁹ ^b ^c
MAO inhibitors	Potential for hypertensive crisis^b ^c	Phentermine use within 14 days of MAO inhibitor use is contraindicated^a ^b ^c

Phentermine Pharmacokinetics

Absorption

Bioavailability

Absorption from resin complex formulation is slower and peak blood concentration is decreased but prolonged compared with the same dose of phentermine hydrochloride; no substantial difference in prolongation of blood levels with resin complex.^b

Elimination

Elimination Route

Excreted substantially in urine.^b

Stability

Storage

Oral

Phentermine Hydrochloride Capsules and Tablets

15–30°C.^a ^c

Phentermine Resin Complex Capsules

25°C (may be exposed to 15–13°C).^a ^b

ActionsActions

Produces anorexigenic effect and loss of weight.^a ^b ^c

Like other amphetamine derivatives, has no primary effect on appetite; anorexigenic action probably is secondary to CNS stimulation.^a

Inhibits uptake of norepinephrine and dopamine.^a

Combined therapy with serotoninergic fenfluramine (no longer commercially available in the US) may have provided complementary anorexigenic effects and had been used to manage obesity;¹⁰⁰ ¹⁰³ ¹¹¹ however, fenfluramine hydrochloride (Pondimin) and dexfenfluramine hydrochloride (Redux) were withdrawn from the US market in 1997 because of adverse effects associated with the drugs.¹¹⁴ ¹¹⁵ ¹¹⁶ ¹³⁵ (See Warnings under Cautions.)

Advice to Patients

Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.^a ^b ^c

Importance of immediately informing clinicians if any deterioration in exercise tolerance occurs.¹⁵⁴ ¹⁶⁸ ¹⁶⁹ ^b ^c

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and alcohol consumption.^b ^c

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

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

Preparations

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

Subject to control under the Federal Controlled Substances Act of 1970 as schedule IV (C-IV) drugs.^a ^b ^c

Phentermine (as a Resin Complex)
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	15 mg (of phentermine)	Ionamin ( C-IV)	Celltech
		30 mg (of phentermine)	Ionamin ( C-IV)	Celltech

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

Phentermine Hydrochloride
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	15 mg*
		18.75 mg*
		30 mg*
		37.5 mg*	Adipex-P ( C-IV)	Gate
	Tablets	8 mg*
		37.5 mg*	Adipex-P ( C-IVscored)	Gate

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 05/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Adipex-P 37.5MG Tablets (GATE): 10/$32.99 or 20/$54.98

Phentermine HCl 15MG Capsules (KVK TECH): 10/$24.99 or 20/$35.98

Phentermine HCl 30MG Capsules (SANDOZ): 10/$19.99 or 20/$29.98

Phentermine HCl 37.5MG Capsules (KVK TECH): 10/$17.99 or 20/$23.98

Phentermine HCl 37.5MG Tablets (KVK TECH): 10/$14.99 or 20/$21.98

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 01, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

100. Anon. Fluoxetine (Prozac) and other drugs for treatment of obesity. Med Lett Drugs Ther. 1994; 36:107-8. [PubMed 7968782]

101. Goldstein DJ, Potvin JH. Long-term weight loss: the effect of pharmacologic agents. Am J Clin Nutr. 1994; 60:647-57. [IDIS 338812] [PubMed 7942569]

102. Hirsch J. Comments on “long-term weight loss: the effect of pharmacologic agents,” by DJ Goldstein and JH Potvin. Am J Clin Nutr. 1994; 60:658- 9.

103. Weintraub M, Sundaresan PR, Madan M et al. Long-term weight control study I (weeks 0 to 34): the enhancement of behavior modification, caloric restriction, and exercise by fenfluramine plus phentermine versus placebo. Clin Pharmacol Ther. 1992; 51:586-94. [IDIS 297380] [PubMed 1587072]

104. Weintraub M, Sundaresan PR, Schuster B et al. Long-term weight control study II (weeks 34 to 104): an open-label study of continuous fenfluramine plus phentermine versus targeted intermittent medication as adjuncts to behavior modification, caloric restriction, and exercise. Clin Pharmacol Ther. 1992; 51:595-601. [IDIS 297381] [PubMed 1587073]

105. Weintraub M, Sundaresan PR, Schuster B et al. Long-term weight control study III (weeks 104 to 156): an open-label study of dose adjustment of fenfluramine and phentermine. Clin Pharmacol Ther. 1992; 51:602- 7. [IDIS 297382] [PubMed 1587074]

106. Weintraub M, Sundaresan PR, Schuster B et al. Long-term weight control study IV (weeks 156 to 190): the second double-blind phase. Clin Pharmacol Ther. 1992; 51:608- 14. [IDIS 297383] [PubMed 1587075]

107. Weintraub M, Sundaresan PR, Schuster B et al. Long-term weight control study V (weeks 190 to 210): follow-up of participants after cessation of medication. Clin Pharmacol Ther. 1992; 51:615-8. [PubMed 1587076]

108. Weintraub M, Sundaresan PR, Cox C. Long-term weight control study VI: individual participant response patterns. Clin Pharmacol Ther. 1992; 51:619-33. [PubMed 1587077]

109. Weintraub M, Sundaresan PR, Schuster B. Long-term weight control study VII (weeks 0 to 210): serum lipid changes. Clin Pharmacol Ther. 1992; 51:634-41. [PubMed 1587078]

110. Weintraub M. Long-term weight control study: conclusions. Clin Pharmacol Ther. 1992; 51:642-6. [PubMed 1587079]

111. Silverstone T. Appetite suppressants: a review. Drugs. 1992; 43:820-36. [PubMed 1379155]

112. Atkinson RL, Hubbard VS. Report on the NIH Workshop on Pharmacologic Treatment of Obesity. Am J Clin Nutr. 1994; 60:153-6. [IDIS 335513] [PubMed 7913290]

113. Wyeth-Ayerst Laboratories, Philadelphia, PA: Personal communication.

114. Deitch MW. Dear health care provider letter: Pondimin and Redux to be voluntarily withdrawn. Philadelphia, PA: Wyeth-Ayerst; 1997 Sep 15.

115. Wyeth-Ayerst. Pondimin and Redux to be voluntarily withdrawn. Philadelphia, PA: 1997 Sep 15. Press release.

116. Bachorik L. FDA announces withdrawal of fenfluramine and dexfenfluramine. HHS News. P97-32. Food and Drug Administration; 1997 Sep 15.

117. Curfman GD. Diet pills redux. N Engl J Med. 1997; 337:629-30. [IDIS 391140] [PubMed 9271487]

118. Lumpkin MM. FDA public health advisory: reports of valvular heart disease in patients receiving concomitant fenfluramine and phentermine. Rockville, MD: Food and Drug Administration; 1997 Jul 8.

119. Deitch MW. Dear health care provider letter regarding labeling changes for Pondimin and Redux. Philadelphia, PA: Wyeth-Ayerst; 1997 Jul 24.

120. Food and Drug Administration Center for Drug Evaluation and Research. “FEN-PHEN” update. Rockville, MD; 1997 Aug 28.

121. Food and Drug Administration. Update to FDA questions & answers on pen-phen [sic], fenfluramine or dexfenfluramine. Rockville, MD; 1997 Sep 19.

122. Connolly HM, Crary JL, McGoon MD et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997; 337:581-8. [IDIS 391136] [PubMed 9271479]

123. Mark EJ, Patalas ED, Chang HT et al. Fatal pulmonary hypertension associated with short-term use of fenfluramine and phentermine. N Engl J Med. 1997; 337:602-5. [IDIS 391138] [PubMed 9271482]

124. Wyeth-Ayerst Laboratories. Fen/phen—obesity revision: Wyeth-Ayerst to add labeling information to antiobesity therapies. Philadelphia, PA; 1997 Jul 28.

125. Anon. FDA steps up campaign to discourage off-label “fen/phen” use with public health advisory; agency coordinates message with NEJM, Mayo clinic. FDC Rep. 1997; (Jul 14):4-5.

126. Anon. Health advisory on fenfluramine/phentermine for obesity. HHS News. P97-20. Rockville, MD: Food and Drug Administration; 1997 Jul 8.

127. Anon. Knoll Meridia studies continue after Redux, Pondimin withdrawal: lawsuits call for Wyeth to fund medical monitoring of patients exposed to drugs. FDC Rep. 1997; (Sep 22):5.

128. US Food and Drug Administration. Questions and answers about Phen/fen and valvular heart disease. Rockville, MD; 1997 July 8.

129. Plutowski S (Mayo Foundation for Medical Education and Research). Valvular heart disease associated with commonly prescribed diet pills. Rochester, MN; 1997 Jul 8. Press release from website (www.MAYO.edu).

130. Mayo Foundation for Medical Education and Research. Information for physicians regarding pharmacologic therapy for obesity. Rochester, MN; 1997 Jul 7. Press release from website (www.MAYO.edu).

131. Mayo Foundation for Medical Education and Research. Heart valve disease and fen-phen: NEJM waives embargo for Mayo Clinic announcement. Rochester, MN; 1997 Jul 8. Press release from website (www.MAYO.edu).

132. Anon. FDA fenfluramine/Redux epidemiological analysis of HMO records supports findings of valvulopathy in asymptomatic patients reported from five surveys. FDC Rep. 1997; (Sep 15):3-5.

133. Connolly HM, Crary JL, McGoon MD et al, for the Mayo Foundation for Medical Education and Research. Valvular heart disease associated with fenfluramine-phentermine. Rochester, MN; 1997 Jul 8.

134. Mayo Foundation for Medical Education and Research. Information and recommendations for people taking fenfluramine and phentermine. Rochester, MN; 1997 Jul 8.

135. Wyeth-Ayerst. An important message to patients who have used Pondimin (fenfluramine hydrochloride) tablets C-IV or Redux (dexfenfluramine hydrochloride) capsules C-IV. Personal communication. Sept 15, 1997.

136. Graham DJ, Green L. Further cases of valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997; 337:635. [IDIS 391141] [PubMed 9280830]

137. Cannistra LB, Davis SM, Bauman AG. Valvular heart disease associated with dexfenfluramine. N Engl J Med. 1997; 337:636. [IDIS 391142] [PubMed 9280831]

138. McCann UD, Selden LS, Rubin LJ et al. Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine. JAMA. 1997; 278:666-72. [IDIS 391172] [PubMed 9272900]

139. McCann U, Hatzidimitriou G, Ridenour A et al. Dexfenfluramine and serotonin neurotoxicity: further preclinical evidence that clinical caution is indicated. J Pharmacol Exp Ther. 1994; 269:792-8. [PubMed 7514223]

140. Voelker R. Obesity drug renews toxicity debate. JAMA. 1994; 272:1087-8. [PubMed 7933303]

141. Cacoub P, Dorent R, Nataf P et al. Pulmonary hypertension and dexfenfluramine. Eur J Clin Pharmacol. 1995; 48:81-3. [IDIS 347133] [PubMed 7621854]

142. Davis R, Faulds D. Dexfenfluramine: an updated review of its therapeutic use in the management of obesity. Drugs. 1996; 52:696-724. [PubMed 9118819]

143. Cerda JJ. The pharmacologic management of obesity. J Fl Med Assoc. 1997; 84:89-92.

144. AH Robins. Pondimin (fenfluramine hydrochloride) tablets prescribing information. Richmond, VA; 1996 Nov 25.

145. Food and Drug Administration. Compounding of fenfluramine and dexfenfluramine products. Rockville, MD; 1997 Oct 2.

146. American College of Cardiology. Statement of the American College of Cardiology on recommendations for patients who have used anorectic drugs. 1997 Oct 18.

147. American College of Cardiology. ACC comments on public health recommendations for former diet drug patients. 1997 Nov 18.

148. Centers for Disease Control and Prevention. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: U.S. Department of Health and Human Services interim public health recommendations, November 1997. MMWR Morb Mortal Wkly Rep. 1997; 46:1061-6. [IDIS 395477] [PubMed 9385873]

149. Dajani AS, Taubert KA, Wilson W et al. Prevention of bacterial endocarditis: recommendations by the American Heart Association. JAMA. 1997; 277:1794-801. [IDIS 385878] [PubMed 9178793]

150. Ho H, Lockitch G, Eaves L et al. Blood serotonin concentrations and fenfluramine therapy in autistic children. J Pediatr. 1986; 108:465-9. [IDIS 213273] [PubMed 2936877]

151. Geller E, Ritvo ER, Freeman BJ et al. Preliminary observations on the effect of fenfluramine on blood serotonin and symptoms in three autistic boys. N Engl J Med. 1982; 307:165-9. [IDIS 152819] [PubMed 7088052]

152. Reviewers’ comments (personal observations).

153. Medeva. Statement on obesity treatment medication and importance of physician-patient dialogue. Rochester, NY; 1997 Nov 25. Press release.

154. Medeva. Ionamin (C-IV) (phentermine resin capsules) prescribing information. Rochester, NY; 1997 Oct.

155. Coyne CT. Dear health care professional letter regarding labeling changes of Ionamin (phentermine resin capsules). Rochester, NY: Medeva; 1997 Aug 8.

156. Coyne CT. Dear doctor or health care professional letter regarding appropriate use of Ionamin (phentermine resin capsules). Rochester, NY: Medeva; 1997 Sep 18.

157. SoRelle R. Fen-phen and risk of valvular disease. Circulation. 1997; 96:1705-6. [PubMed 9323046]

158. Bostwick JM, Brown TM. A toxic reaction from combining fluoxetine and phentermine. J Clin Psychopharmacol. 1996; 16:189-90. [IDIS 365793] [PubMed 8690835]

159. Nightingale SL. From the Food and Drug Administration: interim recommendations issued for patients exposed to fenfluramine and dexfenfluramine. JAMA. 1997; 278:1728. [PubMed 9388135]

160. Bachorik L (US Food and Drug Administration). Interim recommendations issued for patients exposed to fenfluramine and dexfenfluramine. HHS News. Press release No. P97-36. 1997 Nov 13.

161. Department of Health and Human Services. Questions and answers concerning the Department of Health and Human Services (DHHS) interim recommendations issued for patients who have taken either fenfluramine or dexfenfluramine. 1997 Nov 13.

162. Anon. Recommendations issued for patients who took fenfluramine, dexfenfluramine. Am J Health-Syst Pharm. 1998; 55:18.

163. American Heart Association National Center. Statement of the American Heart Association on recommendations for patients who have used fenfluramine/phentermine. 1997 Oct.

164. Thomas SH, Butt AY, Corris PA et al. Appetite suppressants and primary pulmonary hypertension in the United Kingdom. Br Heart J. 1995; 74:660-3. [IDIS 359639] [PubMed 8541174]

165. Wyeth-Ayerst. Dear health care professional letter regarding valvular irregularities and primary pulmonary hypertension associated with the use of Plegine. Philadelphia, PA: Wyeth-Ayerst; 1998 Jun 15.

166. Dillon KA, Putnam KG, Avorn JL. Death from irreversible pulmonary hypertension associated with short-term use of fenfluramine and phentermine. JAMA. 1997; 278:1320. [IDIS 393112] [PubMed 9343461]

167. Wyeth-Ayerst. Plegine (phendimetrazine tartrate) tablets prescribing information. In: Physicians’ desk reference. 52nd ed. Montvale, NJ: Medical Economics Company Inc; 1998(Suppl A):A304.

168. SmithKline Beecham. Fastin (phentermine hydrochloride) capsules prescribing information. In: Physicians’ desk reference. 52nd ed. Montvale, NJ: Medical Economics Company Inc; 1998(Suppl A):A292-3.

169. Medeva Pharmaceuticals. Ionamin (phentermine resin) prescribing information. In: Physicians’ desk reference. 52nd ed. Montvale, NJ: Medical Economics Company Inc; 1998(Suppl A):A203-4.

a. AHFS Drug Information 2005. McEvoy GK, ed. Phentermine. Bethesda, MD: American Society of Health-System Pharmacists; 2005: 2384-5.

b. Celltech. Ionamin (phentermine resin) capsules prescribing information. Rochester, NY; 2003 Mar.

c. Gate Pharmaceuticals. Adipex-P (phentermine hydrochloride) capsules and tablets prescribing infomation. Sellersville, PA; 2000 Nov.

d. Phentermine. In: Briggs GG, Freeman RK, Yaffe SJ, eds. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 6th ed. Phildephia: Lippincott, Williams & Wilkins; 2002:1109-10.

More Phentermine resources

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

Phentermine Prescribing Information (FDA)

Phentermine MedFacts Consumer Leaflet (Wolters Kluwer)

phentermine Concise Consumer Information (Cerner Multum)

phentermine Advanced Consumer (Micromedex) - Includes Dosage Information

Adipex-P Prescribing Information (FDA)

Ionamin Prescribing Information (FDA)

Ionamin Concise Consumer Information (Cerner Multum)

Ionamin MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Phentermine with other medications

Obesity
Weight Loss

Monday, 14 May 2012

Pyrroxate

Pronunciation: ah-seet-ah-MIN-oh-fen/klor-fen-EER-a-meen/fen-ill-EF-rin
Generic Name: Acetaminophen/Chlorpheniramine/Phenylephrine
Brand Name: Examples include Pyrroxate and Dryphen

Pyrroxate is used for:

Relieving symptoms of colds, hay fever, and allergies such as headache, sinus pain, nasal and sinus congestion, sneezing, watery eyes, runny nose, fever, and itching of the nose or throat. It may also be used for other conditions as determined by your doctor.

Pyrroxate is an antihistamine, decongestant, and pain reliever combination. It works by blocking histamine, a substance in the body that causes sneezing, runny nose, and watery eyes. It also relieves nasal congestion and pain associated with sinus pressure, and dries the nose and chest.

Do NOT use Pyrroxate if:

you are allergic to any ingredient in Pyrroxate

you are taking sodium oxybate (GHB) or a monoamine oxidase (MAO) inhibitor (eg, phenelzine)

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

Before using Pyrroxate:

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

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

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

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

if you have breathing problems (eg, emphysema, asthma), heart disease, diabetes, difficulty urinating, an enlarged prostate, glaucoma, high blood pressure, an overactive thyroid, liver or kidney problems, adrenal gland problems (eg, pheochromocytoma), sleep apnea, trouble sleeping, stomach problems, urinary blockage, or viral hepatitis

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

Catechol-O-methyltransferase (COMT) inhibitors (eg, entacapone), droxidopa, isoniazid, sodium oxybate (GHB), or tricyclic antidepressants (eg, amitriptyline) because the risk of side effects may be increased

Blood thinners (eg, warfarin), bromocriptine, furazolidone, MAO inhibitors (eg, phenelzine), or selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine) because the actions and side effects may be increased

Certain high blood pressure medicines such as beta-blockers (eg, atenolol) and guanethidine because these medicines may be less effective

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

How to use Pyrroxate:

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

Pyrroxate may be taken with food if it upsets your stomach.

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

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

Important safety information:

Pyrroxate may cause drowsiness or dizziness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Pyrroxate. Using Pyrroxate alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.

Pyrroxate will add to the effects of alcohol and other depressants. Ask your pharmacist if you have questions about which medicines are depressants.

Do not exceed the recommended dose of Pyrroxate. Doing so will not improve your condition faster and may increase your risk for side effects.

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

Pyrroxate contains acetaminophen. Before you begin taking any new prescription or nonprescription medicine, read the ingredients to see if it also contains acetaminophen. If it does or if you are uncertain, contact your doctor or pharmacist.

Do not take diet or appetite control medicines while you are taking Pyrroxate without checking with your doctor.

If you consume 3 or more alcohol-containing drinks every day, ask your doctor whether you should take Pyrroxate or other pain relievers/fever reducers. Acetaminophen may cause liver damage. Alcohol use combined with Pyrroxate may increase your risk for liver damage.

If you have trouble sleeping, ask your doctor or pharmacist about the best time of the day to take Pyrroxate.

Caution is advised when using Pyrroxate in the ELDERLY because they may be more sensitive to its effects.

Use Pyrroxate with extreme caution in CHILDREN younger than 12 years of age. Safety and effectiveness in this age group have not been confirmed.

PREGNANCY and BREAST-FEEDING: It is unknown if Pyrroxate can cause harm to the fetus. If you become pregnant while taking Pyrroxate, discuss with your doctor the benefits and risks of using Pyrroxate during pregnancy. Some of the ingredients in Pyrroxate are excreted in breast milk. If you are or will be breast-feeding while you are using Pyrroxate, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Pyrroxate:

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

Dizziness; drowsiness; dry mouth, nose, or throat; headache; nausea; nervousness; trouble sleeping.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; dark urine or pale stools; difficulty urinating; hallucinations; high blood pressure; rapid pulse; severe nervousness; stomach pain; tremors; unusual fatigue; yellowing of the skin or eyes.

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

See also: Pyrroxate side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include fast or irregular heartbeat; fever; hallucinations; nausea; seizures; sweating; tremors; trouble breathing; unusual drowsiness or dizziness; vomiting.

Proper storage of Pyrroxate:

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

General information:

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

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

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

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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Pyrroxate resources

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

Pyrroxate Concise Consumer Information (Cerner Multum)

Compare Pyrroxate with other medications

Cold Symptoms
Sinus Symptoms

Friday, 11 May 2012

Ultram

Pronunciation: TRAM-a-dol
Generic Name: Tramadol
Brand Name: Ultram

Ultram is used for:

Treating moderate to moderately severe pain.

Ultram is an analgesic. It works in certain areas of the brain and nervous system to decrease pain.

Do NOT use Ultram if:

you are allergic to any ingredient in Ultram

you have had a severe allergic reaction (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue) to codeine or another opioid (eg, morphine)

you have severe or persistent diarrhea caused by antibiotic use

you have suicidal thoughts or actions, or have a history of alcohol or other substance abuse

you are intoxicated with alcohol, opioids or narcotics (eg, codeine, morphine), or sedatives or sleeping medicines (eg, temazepam, zolpidem)

you are taking carbamazepine, nefazodone, sodium oxybate (GHB), a thioxanthene (eg, thiothixene), or another product that contains tramadol

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

Before using Ultram:

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

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

if you are taking any prescription (especially depression medicines) or nonprescription medicine, herbal preparation, or dietary supplement

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

if you have liver, kidney, or thyroid problems; a blockage in the bladder; diabetes; heart problems (eg, cor pulmonale); high blood pressure; pancreas problems; prostate problems; or metabolism problems

if you have or recently have had any head injury, brain injury or tumor, increased pressure in the brain, or infection of the brain or nervous system

if you have a history of a recent stomach or bowel surgery, or any other stomach or bowel problems (eg, pain, inflammation, ulcers)

if you have a history of lung or breathing problems (eg, asthma, chronic obstructive pulmonary disease [COPD]) or seizures (eg, epilepsy)

if you drink alcohol; are going through withdrawal from alcohol or other substances; or have a history of alcohol or other substance abuse, mood or mental problems (eg, depression), or suicidal thoughts or actions

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

Alpha-2 receptor blockers (eg, yohimbine), azole antifungals (eg, ketoconazole), linezolid, lithium, macrolide antibiotics (eg, erythromycin), monoamine oxidase inhibitors (MAOIs) (eg, phenelzine, selegiline), nefazodone, quinidine, selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine, paroxetine), serotonin-norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine), St. John's wort, tricyclic antidepressants (eg, amitriptyline), or "triptans" (eg, sumatriptan) because the risk of seizures or serotonin syndrome may be increased

Anorexiants (eg, phentermine), butyrophenones (eg, haloperidol), cyclobenzaprine, furazolidone, loxapine, certain medicines for mental or mood disorders (eg, olanzapine), molindone, opioid pain medicines (eg, codeine, hydrocodone), phenothiazines (eg, promethazine), sleeping medicines (eg, zolpidem), sodium oxybate (GHB), thioxanthenes (eg, thiothixene), or tiagabine because the risk of side effects, including excessive drowsiness, trouble breathing, liver problems, or seizures, may be increased

Carbamazepine because it may decrease Ultram's effectiveness; the risk of seizures may also be increased

Other products containing tramadol because they may increase the risk of Ultram's side effects

Rifampin because it may decrease Ultram's effectiveness

Anticoagulants (eg, warfarin) or digoxin because the risk of their side effects may be increased by Ultram

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

How to use Ultram:

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

Take Ultram by mouth with or without food.

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

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

Important safety information:

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

Do not drink alcohol while you are using Ultram.

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

Ultram may cause dizziness; alcohol, hot weather, exercise, or fever may increase this effect. To prevent it, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of this effect.

Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.

Ultram may increase your risk of seizures. Your risk may be greater if you also have certain medical conditions, use certain medicines, or if you use a lot of alcohol. Talk to your doctor to see if you may have a greater risk of seizures while taking Ultram.

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

Serotonin syndrome is a possibly fatal syndrome that can be caused by Ultram. Your risk may be greater if you take Ultram with certain other medicines (eg, "triptans," MAOIs, antidepressants). Symptoms may include agitation; confusion; hallucinations; coma; fever; fast or irregular heartbeat; tremor; excessive sweating; and nausea, vomiting, or diarrhea. Contact your doctor at once if you have any of these symptoms.

Use Ultram with caution in the ELDERLY; they may be more sensitive to its effects, especially constipation, weakness or tiredness, severe light-headedness, and indigestion.

Ultram should not be used in CHILDREN younger than 16 years; safety and effectiveness in these children have not been confirmed.

PREGNANCY and BREAST-FEEDING: Ultram has been shown to cause harm to the fetus. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Ultram while you are pregnant. Ultram is found in breast milk. Do not breast-feed while taking Ultram.

When used for long periods of time or at high doses, Ultram may not work as well and may require higher doses to obtain the same effect as when originally taken. This is known as TOLERANCE. Talk with your doctor if Ultram stops working well. Do not take more than prescribed.

Some people who use Ultram for a long time without a break may develop a physical need to continue taking it. This is known as physical DEPENDENCE.

If you suddenly stop taking Ultram, you may experience WITHDRAWAL symptoms, including anxiety; diarrhea; fever, runny nose, or sneezing; goose bumps and abnormal skin sensations; nausea; vomiting; pain; rigid muscles; rapid heartbeat; seeing, hearing or feeling things that are not there; shivering or tremors; sweating; and trouble sleeping.

Possible side effects of Ultram:

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

Constipation; diarrhea; dizziness; drowsiness; dry mouth; headache; increased sweating; indigestion; mild itching; nausea; trouble sleeping; vomiting; weakness.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); agitation; chest pain; confusion; difficult or painful urination; disorientation; excessive sweating; fainting; fast or irregular heartbeat; fever; hallucinations; loss of coordination; mood or mental changes (eg, depression); red, blistered, swollen, or peeling skin; seizures; severe dizziness or light-headedness; severe nausea, vomiting, or diarrhea; severe or persistent headache; slow or shallow breathing; suicidal thoughts or behaviors; tremor; vision problems.

See also: Ultram side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center ( http://www.aapcc.org), or emergency room immediately. Symptoms may include bluish skin; cold, clammy skin; difficult, shallow, or slow breathing; drowsiness leading to unresponsiveness or coma; excessive sweating; limp muscles; pinpoint pupils; seizures; slow or irregular heartbeat.

Proper storage of Ultram:

Store Ultram at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Ultram out of the reach of children and away from pets.

General information:

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

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

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

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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Ultram resources

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

Ultram Monograph (AHFS DI)

Ultram Advanced Consumer (Micromedex) - Includes Dosage Information

Ultram Consumer Overview

Ultram Prescribing Information (FDA)

ConZip Prescribing Information (FDA)

Rybix ODT Prescribing Information (FDA)

Ryzolt Consumer Overview

Ryzolt Prescribing Information (FDA)

Ultram ER Prescribing Information (FDA)

Compare Ultram with other medications

Back Pain
Pain

Atropisol

Generic Name: atropine, homatropine, and scopolamine (Ophthalmic route)

Commonly used brand name(s)

In the U.S.

AK-Dilate

AK-Pentolate

Altafrin

Atropine Care

Cyclogyl

Cyclomydril

Eye Cool

Homatropaire

Isopto Atropine

Isopto Homatropine

Isopto Hyoscine

Mydfrin

Mydral

Mydriacyl

Neofrin

Neo-Synephrine

Paremyd

In Canada

Ak-Dilate

Ak-Pentolate

Atropine

Atropine-Ak

Atropine Eye Ointment

Atropine Ointment

Atropisol

Minims Phenylephrine Hydrochloride

Available Dosage Forms:

Ointment

Solution

Uses For Atropisol

Ophthalmic atropine, homatropine, and scopolamine are used to dilate (enlarge) the pupil of the eye. They are used before eye examinations, before and after eye surgery, and to treat certain eye conditions, such as uveitis or posterior synechiae.

These medicines are available only with your doctor's prescription.

Before Using Atropisol

Allergies

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

Pediatric

Infants and young children and children with blond hair or blue eyes may be especially sensitive to the effects of atropine, homatropine, or scopolamine. This may increase the chance of side effects during treatment . Children should use a lower strength of this medicine.

Geriatric

Elderly people are especially sensitive to the effects of atropine, homatropine, or scopolamine. This may increase the chance of side effects during treatment.

Pregnancy

Studies on effects in pregnancy have not been done in either humans or animals. However, these medicines may be absorbed into the body.

Breast Feeding

These medicines may be absorbed into the body. Atropine passes into the breast milk in very small amounts and may cause side effects, such as fast pulse, fever, or dry skin, in babies of nursing mothers using ophthalmic atropine. It is not known whether homatropine or scopolamine passes into breast milk. Although most medicines pass into breast milk in small amounts, many of them may be used safely while breast-feeding. Mothers who are using one of these medicines and who wish to breast-feed should discuss this with their doctor.

Interactions with Medicines

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

Interactions with Food/Tobacco/Alcohol

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

Proper Use of atropine, homatropine, and scopolamine

This section provides information on the proper use of a number of products that contain atropine, homatropine, and scopolamine. It may not be specific to Atropisol. Please read with care.

To use the ophthalmic solution (eye drops) form of this medicine:

First, wash your hands. Tilt the head back and, pressing your finger gently on the skin just beneath the lower eyelid, pull the lower eyelid away from the eye to make a space. Drop the medicine into this space. Let go of the eyelid and gently close the eyes. Do not blink. Keep the eyes closed and apply pressure to the inner corner of the eye with your finger for 2 or 3 minutes to allow the medicine to be absorbed by the eye.

Immediately after using the eye drops, wash your hands to remove any medicine that may be on them. If you are using the eye drops for an infant or child, be sure to wash his or her hands immediately afterwards also, and do not let any of the medicine get in his or her mouth. In addition, wipe off any medicine that may have accidentally gotten on the infant or child, including his or her face or eyelids.

To keep the medicine as germ-free as possible, do not touch the applicator tip to any surface (including the eye). Also, keep the container tightly closed.

To use the ointment form of this medicine:

First, wash your hands. Tilt the head back and, pressing your finger gently on the skin just beneath the lower eyelid, pull the lower eyelid away from the eye to make a space. Squeeze a thin strip of ointment into this space. A 1/3- to ½;-cm (approximately ⅛-inch in infants and young children and ¼-inch in older children and adults) strip of ointment is usually enough, unless you have been told by your doctor to use a different amount. Let go of the eyelid and gently close the eyes. Keep the eyes closed for 1 or 2 minutes to allow the medicine to be absorbed by the eye.

Immediately after using the eye ointment, wash your hands to remove any medicine that may be on them. If you are using the eye ointment for an infant or child, be sure to wash his or her hands immediately afterwards also, and do not let any of the medicine get in his or her mouth. In addition, wipe off any medicine that may have accidentally gotten on the infant or child, including his or her face or eyelids.

To keep the medicine as germ-free as possible, do not touch the applicator tip to any surface (including the eye). After using the eye ointment, wipe the tip of the ointment tube with a clean tissue and keep the tube tightly closed.

Use this medicine only as directed. Do not use more of it and do not use it more often than your doctor ordered. To do so may increase the chance of too much medicine being absorbed into the body and the chance of side effects. This is especially important when this medicine is used in infants and children, since overdose is very dangerous in infants and children.

Dosing

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

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

For atropine

For ophthalmic ointment dosage form:
- For uveitis:
  - Adults—Use a thin strip of the ointment in the eye one or two times a day.
  - Children—Use a thin strip of the ointment in the eye one to three times a day.
- For eye examinations:
  - Adults—Use and dose must be determined by your doctor.
  - Children—Use a thin strip of the ointment in the eye three times a day for one to three days before the examination.

For ophthalmic solution (eye drops) dosage form:
- For uveitis:
  - Adults—Use one drop in the eye one or two times a day.
  - Children—Use one drop in the eye one to three times a day.
- For eye examinations:
  - Adults—Use and dose must be determined by your doctor.
  - Children—Use one drop in the eye two times a day for one to three days before the examination.

For homatropine

For ophthalmic solution (eye drops) dosage form:
- For uveitis:
  - Adults and children—Use 1 or 2 drops in the eye two or three times a day.
- For eye examinations:
  - Adults—Use 1 or 2 drops in the eye. May be repeated every five to ten minutes for two or three doses.
  - Children—Use 1 or 2 drops in the eye every ten minutes for two or three doses.

For scopolamine

For ophthalmic solution (eye drops) dosage form:
- For uveitis:
  - Adults and children—Use one drop in the eye up to four times a day.
- For eye examinations:
  - Adults—Use one drop in the eye one hour before the examination.
  - Children—Use one drop in the eye two times a day for two days before the examination.
- For posterior synechiae:
  - Adults—Use one drop in the eye every ten minutes for three doses.
  - Children—Use and dose must be determined by your doctor.
- For use before and after surgery:
  - Adults and children—Use one drop in the eye one to four times a day.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose of this medicine and your dosing schedule is:

One dose a day—Apply the missed dose as soon as possible. However, if you do not remember the missed dose until the next day, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

More than one dose a day—Apply the missed dose as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

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

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Atropisol

After you apply this medicine to your eyes:

Your pupils will become unusually large and you will have blurring of vision, especially for close objects. Make sure your vision is clear before you drive, use machines, or do anything else that could be dangerous if you are not able to see well.

Your eyes will become more sensitive to light than they are normally. Wear sunglasses to protect your eyes from sunlight and other bright lights.

These effects may continue for several days after you stop using this medicine. However, check with your doctor if they continue longer than:

14 days if you are using atropine.

3 days if you are using homatropine.

7 days if you are using scopolamine.

Atropisol Side Effects

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

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

Symptoms of too much medicine being absorbed into the body

Clumsiness or unsteadiness

confusion or unusual behavior

dryness of skin

fast or irregular heartbeat

fever

flushing or redness of face

seeing, hearing, or feeling things that are not there

skin rash

slurred speech

swollen stomach in infants

thirst or unusual dryness of mouth

unusual drowsiness, tiredness, or weakness

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

Blurred vision

brief burning or stinging of the eyes

eye irritation not present before use of this medicine

increased sensitivity of eyes to light

swelling of the eyelids

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

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

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

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

Thursday, 10 May 2012

Value Health Cold Relief Powders Lemon

Value Health Cold Relief Powders Lemon

(Ascorbic Acid, Paracetamol)

5 sachets

Read all of this carton for full instructions.

Uses: This medicine contains paracetamol to relieve pain and reduce fever, and vitamin C. It can be used to relieve the symptoms of colds and flu (fever, aches and pains) and increase the body’s level of vitamin C to replace the vitamin that is lost when you have a cold or flu.

Before you take this medicine

Contains Paracetamol

Do not take with any other paracetamol-containing products.

Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage.

Do not take:

If you are allergic to any of the ingredients

If you have severe liver or kidney problems

If you have an intolerance to some sugars, unless your doctor tells you to (this medicine contains sucrose)

Talk to your pharmacist or doctor:

If you have other liver or kidney problems (including a disease caused by drinking alcohol)

If you take other medicines – metoclopramide or domperidone (for feeling sick or being sick), colestyramine (for reducing blood fat levels), warfarin or other blood thinners

If you are on a controlled salt (sodium) diet (this medicine contains 148 mg sodium)

If you are pregnant

You can take this medicine if you are breastfeeding.

Each sachet contains 2.7 g sucrose. This should be taken into account if you have diabetes.

How to take this medicine

Check the sachet is not broken before use. If it is, do not take the powder.

Empty the contents of one sachet into a beaker or tumbler. Fill with freshly boiled water and stir until dissolved. Allow to cool and drink the solution.

Adults and children of 12 years and over

Take one sachet, dissolved in water

At bedtime and every 4 hours during the day, if you need to.

Don't take more than 4 sachets in 24 hours.

Do not give to children under 12 years.

Do not exceed the stated dose.

Do not take this medicine for more than 3 days unless your doctor tells you to.

If symptoms persist consult your doctor.

Possible side effects

Most people will not have problems, but some may get some:

If you get any of these serious side effects, stop taking the powder.
See a doctor at once:

Difficulty in breathing, swelling of the lips, face, tongue or throat (severe allergic reaction)

These other effects are less serious.
If they bother you talk to a pharmacist:

Skin rash

Unusual bruising or infections such as sore throat – this may be a sign of very rare changes in the blood

If any side effect becomes severe, or you notice any side effect not listed here, please tell your pharmacist or doctor.

Keep all medicines out of the sight and reach of children.

Use by the date on the end flap of the carton.

Active ingredients

Each sachet contains Ascorbic Acid 50 mg, Paracetamol 650 mg.

Also contains: sucrose, citric acid, sodium citrate, magnesium carbonate, sodium saccharin, maize starch, colour (betacarotene), flavour (lemon).

PL00014/5213

Text prepared 10/07

Manufactured for the Marketing Authorisation holder

Value Health Nottingham

NG2 3AA

Hamol Limited Nottingham

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BTC21557 vD 11/07/08

Wednesday, 9 May 2012

Levofloxacin Tablets

FULL PRESCRIBING INFORMATION

Warning

Fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants [see Warnings and Precautions (5.1)].

Fluoroquinolones, including levofloxacin, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid levofloxacin in patients with a known history of myasthenia gravis [see Warnings and Precautions (5.2)].

Indications and Usage for Levofloxacin Tablets

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Levofloxacin Tablets and other antibacterial drugs, Levofloxacin Tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Levofloxacin Tablets are indicated for the treatment of adults (≥18 years of age) with mild, moderate, and severe infections caused by susceptible strains of the designated microorganisms in the conditions listed in this section. Levofloxacin injection is indicated when intravenous administration offers a route of administration advantageous to the patient (e.g., patient cannot tolerate an oral dosage form).

Culture and susceptibility testing

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to levofloxacin [see Clinical Pharmacology (12.4)]. Therapy with Levofloxacin Tablets may be initiated before results of these tests are known; once results become available, appropriate therapy should be selected.

As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with Levofloxacin Tablets. Culture and susceptibility testing performed periodically during therapy will provide information about the continued susceptibility of the pathogens to the antimicrobial agent and also the possible emergence of bacterial resistance.

Nosocomial Pneumonia

Levofloxacin Tablets are indicated for the treatment of nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, or Streptococcus pneumoniae. Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal β-lactam is recommended [see Clinical Studies (14.1)].

Community-Acquired Pneumonia: 7 to 14 day Treatment Regimen

Levofloxacin Tablets are indicated for the treatment of community-acquired pneumonia due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.2)].

MDRSP isolates are strains resistant to two or more of the following antibacterials: penicillin (MIC ≥2 mcg/mL), 2nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

Community-Acquired Pneumonia: 5-day Treatment Regimen

Levofloxacin Tablets are indicated for the treatment of community-acquired pneumonia due to Streptococcus pneumoniae (excluding multi-drug-resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.3)].

Acute Bacterial Sinusitis: 5-day and 10 to 14 day Treatment Regimens

Levofloxacin Tablets are indicated for the treatment of acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis [see Clinical Studies (14.4)].

Acute Bacterial Exacerbation of Chronic Bronchitis

Levofloxacin Tablets are indicated for the treatment of acute bacterial exacerbation of chronic bronchitis due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis.

Complicated Skin and Skin Structure Infections

Levofloxacin Tablets are indicated for the treatment of complicated skin and skin structure infections due to methicillin-susceptible Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, or Proteus mirabilis [see Clinical Studies (14.5)].

Uncomplicated Skin and Skin Structure Infections

Levofloxacin Tablets are indicated for the treatment of uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections, due to methicillin-susceptible Staphylococcus aureus, or Streptococcus pyogenes.

Chronic Bacterial Prostatitis

Levofloxacin Tablets are indicated for the treatment of chronic bacterial prostatitis due to Escherichia coli, Enterococcus faecalis, or methicillin-susceptible Staphylococcus epidermidis [see Clinical Studies (14.6)].

Complicated Urinary Tract Infections: 5-day Treatment Regimen

Levofloxacin Tablets are indicated for the treatment of complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis [see Clinical Studies (14.7)].

Complicated Urinary Tract Infections: 10-day Treatment Regimen

Levofloxacin Tablets are indicated for the treatment of complicated urinary tract infections (mild to moderate) due to Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa [see Clinical Studies (14.8)].

Acute Pyelonephritis: 5 or 10-day Treatment Regimen

Levofloxacin Tablets are indicated for the treatment of acute pyelonephritis caused by Escherichia coli, including cases with concurrent bacteremia [see Clinical Studies (14.7, 14.8)].

Uncomplicated Urinary Tract Infections

Levofloxacin Tablets are indicated for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus.

Inhalational Anthrax (Post-Exposure)

Levofloxacin Tablets are indicated for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis. The effectiveness of Levofloxacin Tablets is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. Levofloxacin Tablets have not been tested in humans for the post-exposure prevention of inhalation anthrax. The safety of Levofloxacin Tablets in adults for durations of therapy beyond 28 days or in pediatric patients for durations of therapy beyond 14 days has not been studied. Prolonged Levofloxacin Tablets therapy should only be used when the benefit outweighs the risk [see Dosage and Administration (2.1, 2.2) and Clinical Studies (14.9)].

Levofloxacin Tablets Dosage and Administration

Dosage in Adult Patients with Normal Renal Function

The usual dose of Levofloxacin Tablets is 250 mg, 500 mg, or 750 mg administered orally every 24 hours, as indicated by infection and described in Table 1.

These recommendations apply to patients with creatinine clearance ≥ 50 mL/min. For patients with creatinine clearance <50 mL/min, adjustments to the dosing regimen are required [see Dosage and Administration (2.3)].

Table 1: Dosage in Adult Patients with Normal Renal Function (creatinine clearance ≥ 50 mL/min)
Type of Infection1	Dosed Every 24 hours	Duration (days)2
1 Due to the designated pathogens [see Indications and Usage (1)]. 2 Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. 3 Due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Indications and Usage (1.2)]. 4 Due to Streptococcus pneumoniae (excluding multi-drug-resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Indications and Usage (1.3)]. 5 This regimen is indicated for cUTI due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and AP due to E. coli, including cases with concurrent bacteremia. 6 This regimen is indicated for cUTI due to Enterococcus faecalis, Enterococcus cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; and for AP due to E. coli. 7 Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)]. 8 The safety of Levofloxacin Tablets in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged Levofloxacin Tablets therapy should only be used when the benefit outweighs the risk.
Nosocomial Pneumonia	750 mg	7-14
Community Acquired Pneumonia3	500 mg	7-14
Community Acquired Pneumonia4	750 mg	5
Acute Bacterial Sinusitis	750 mg	5
Acute Bacterial Sinusitis	500 mg	10-14
Acute Bacterial Exacerbation of Chronic Bronchitis	500 mg	7
Complicated Skin and Skin Structure Infections (SSSI)	750 mg	7-14
Uncomplicated SSSI	500 mg	7-10
Chronic Bacterial Prostatitis	500 mg	28
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)5	750 mg	5
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)6	250 mg	10
Uncomplicated Urinary Tract Infection	250 mg	3
Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kg and ≥ 6 months of age7,8 Pediatric patients < 50 kg and ≥ 6 months of age7,8	500 mg see Table 2 below (2.2)	608 608

Dosage in Pediatric Patients

The dosage in pediatric patients ≥ 6 months of age is described below in Table 2.

Table 2: Dosage in Pediatric Patients ≥ 6 months of age
1 Due to Bacillus anthracis [see Indications and Usage (1.13)] 2 Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. 3 Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)] 4 The safety of Levofloxacin Tablets in pediatric patients for durations of therapy beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged Levofloxacin Tablets therapy should only be used when the benefit outweighs the risk.
Type of Infection1	Dose	Freq. Once every	Duration2
Inhalational Anthrax (post-exposure)3, 4
Pediatric patients > 50 kg and ≥ 6 months of age	500 mg	24 hr	60 days4
Pediatric patients < 50 kg and ≥ 6 months of age	8 mg/kg (not to exceed 250 mg per dose)	12 hr	60 days4

Dosage Adjustment in Adults with Renal Impairment

Administer Levofloxacin Tablets with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.

No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.

In patients with impaired renal function (creatinine clearance <50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance [see Use in Specific Populations (8.6)].

Table 3 shows how to adjust dose based on creatinine clearance.

Table 3: Dosage Adjustment in Adult Patients with Renal Impairment (creatinine clearance <50 mL/min)
Dosage in Normal Renal Function Every 24 hours	Creatinine Clearance 20 to 49 mL/min	Creatinine Clearance 10 to 19 mL/min	Hemodialysis or Chronic Ambulatory Peritoneal Dialysis (CAPD)
750 mg	750 mg every 48 hours	750 mg initial dose, then 500 mg every 48 hours	750 mg initial dose, then 500 mg every 48 hours
500 mg	500 mg initial dose, then 250 mg every 24 hours	500 mg initial dose, then 250 mg every 48 hours	500 mg initial dose, then 250 mg every 48 hours
250 mg	No dosage adjustment required	250 mg every 48 hours. If treating uncomplicated UTI, then no dosage adjustment is required	No information on dosing adjustment is available

Drug Interaction With Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins

Levofloxacin Tablets should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine chewable/buffered tablets or the pediatric powder for oral solution [see Drug Interactions (7.1) and Patient Counseling Information (17.2)].

Administration Instructions

Food and Levofloxacin Tablets

Levofloxacin Tablets can be administered without regard to food.

Hydration for Patients Receiving Levofloxacin Tablets

Adequate hydration of patients receiving oral Levofloxacin Tablets should be maintained to prevent the formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones [see Adverse Reactions (6.1) and Patient Counseling Information (17.2)].

Dosage Forms and Strengths

Levofloxacin Tablets, 250 mg are terra pink colored capsule shaped, biconvex film-coated tablets, debossed with ‘13’ on one side and ‘T’ on the other side.

Levofloxacin Tablets, 500 mg are peach colored capsule shaped, biconvex film-coated tablets, debossed with ‘12’ on one side and ‘T’ on the other side.

Levofloxacin Tablets, 750 mg are white capsule shaped, biconvex film-coated tablets, debossed with ‘11’ on one side and ‘T’ on the other side.

Contraindications

Levofloxacin Tablets are contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials [see Warnings and Precautions (5.3)].

Warnings and Precautions

Tendinopathy and Tendon Rupture

Fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in older patients usually over 60 years of age, in those taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Factors, in addition to age and corticosteroid use, that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have been reported in patients taking fluoroquinolones who do not have the above risk factors. Tendon rupture can occur during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. Levofloxacin should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug [see Adverse Reactions (6.3); Patient Counseling Information (17.3)].

Exacerbation of Myasthenia Gravis

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid levofloxacin in patients with a known history of myasthenia gravis [see Adverse Reactions (6.3); Patient Counseling Information (17.3)].

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with fluoroquinolones, including levofloxacin. These reactions often occur following the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat, or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), dyspnea, urticaria, itching, and other serious skin reactions. Levofloxacin should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity. Serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated [see Adverse Reactions (6); Patient Counseling Information (17.3)].

Other Serious and Sometimes Fatal Reactions

Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with fluoroquinolones, including levofloxacin. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:

fever, rash, or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson Syndrome);

vasculitis; arthralgia; myalgia; serum sickness;

allergic pneumonitis;

interstitial nephritis; acute renal insufficiency or failure;

hepatitis; jaundice; acute hepatic necrosis or failure;

anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities.

The drug should be discontinued immediately at the first appearance of skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted [see Adverse Reactions (6); Patient Counseling Information (17.3)].

Hepatotoxicity

Postmarketing reports of severe hepatotoxicity (including acute hepatitis and fatal events) have been received for patients treated with levofloxacin. No evidence of serious drug-associated hepatotoxicity was detected in clinical trials of over 7,000 patients. Severe hepatotoxicity generally occurred within 14 days of initiation of therapy and most cases occurred within 6 days. Most cases of severe hepatotoxicity were not associated with hypersensitivity [see Warnings and Precautions (5.4)]. The majority of fatal hepatotoxicity reports occurred in patients 65 years of age or older and most were not associated with hypersensitivity. Levofloxacin should be discontinued immediately if the patient develops signs and symptoms of hepatitis [see Adverse Reactions (6); Patient Counseling Information (17.3)].

Central Nervous System Effects

Convulsions, and toxic psychoses, increased intracranial pressure (including pseudotumor cerebri) have been reported in patients receiving fluoroquinolones, including levofloxacin. Fluoroquinolones may also central nervous system stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, nightmares, insomnia, and, rarely, suicidal thoughts or acts. These reactions may occur following the first dose. If these reactions occur in patients receiving levofloxacin, the drug should be discontinued and appropriate measures instituted. As with other fluoroquinolones, levofloxacin should be used with caution in patients with a known or suspected central nervous system (CNS) disorder that may predispose them to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose them to seizures or lower the seizure threshold (e.g., certain drug therapy, renal dysfunction.) [see Adverse Reactions (6); Drug Interactions (7.4, 7.5); Patient Counseling Information (17.3)].

Clostridium difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including levofloxacin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated [see Adverse Reactions (6.2), Patient Counseling Information (17.3)].

Peripheral Neuropathy

Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones, including levofloxacin. Levofloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation in order to prevent the development of an irreversible condition [see Adverse Reactions (6), Patient Counseling Information (17.3)].

Prolongation of the QT Interval

Some fluoroquinolones, including levofloxacin, have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. Rare cases of torsade de pointes have been spontaneously reported during postmarketing surveillance in patients receiving fluoroquinolones, including levofloxacin. Levofloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval [see Adverse Reactions (6.3), Use in Specific Populations (8.5), and Patient Counseling Information (17.3)].

Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals

Levofloxacin is indicated in pediatric patients (≥6 months of age) only for the prevention of inhalational anthrax (post-exposure) [see Indications and Usage (1.13)]. An increased incidence of musculoskeletal disorders (arthralgia, arthritis, tendinopathy, and gait abnormality) compared to controls has been observed in pediatric patients receiving levofloxacin [see Use in Specific Populations (8.4)].

In immature rats and dogs, the oral administration of levofloxacin resulted in increased osteochondrosis. Histopathological examination of the weight-bearing joints of immature dogs dosed with levofloxacin revealed persistent lesions of the cartilage. Other fluoroquinolones also produce similar erosions in the weight-bearing joints and other signs of arthropathy in immature animals of various species [see Animal Toxicology and/or Pharmacology (13.2)].

Blood Glucose Disturbances

As with other fluoroquinolones, disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported with levofloxacin, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glyburide) or with insulin. In these patients, careful monitoring of blood glucose is recommended. If a hypoglycemic reaction occurs in a patient being treated with levofloxacin, levofloxacin should be discontinued and appropriate therapy should be initiated immediately [see Adverse Reactions (6.2); Drug Interactions (7.3); Patient Counseling Information (17.4)].

Photosensitivity/Phototoxicity

Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of fluoroquinolones after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if photosensitivity/phototoxicity occurs [see Adverse Reactions (6.3); Patient Counseling Information (17.3)].

Development of Drug Resistant Bacteria

Prescribing levofloxacin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria [see Patient Counseling Information (17.1)].

Adverse Reactions

Serious and Otherwise Important Adverse Reactions

The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:

Tendon Effects [see Warnings and Precautions (5.1)]

Exacerbation of Myasthenia Gravis [see Warnings and Precautions (5.2)]

Hypersensitivity Reactions [see Warnings and Precautions (5.3)]

Other Serious and Sometimes Fatal Reactions [see Warnings and Precautions (5.4)]

Hepatotoxicity [see Warnings and Precautions (5.5)]

Central Nervous System Effects [see Warnings and Precautions (5.6)]

Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.7)]

Peripheral Neuropathy [see Warnings and Precautions (5.8)]

Prolongation of the QT Interval [see Warnings and Precautions (5.9)]

Musculoskeletal Disorders in Pediatric Patients [see Warnings and Precautions (5.10)]

Blood Glucose Disturbances [see Warnings and Precautions (5.11)]

Photosensitivity/Phototoxicity [see Warnings and Precautions (5.12)]

Development of Drug Resistant Bacteria [see Warnings and Precautions (5.13)]

Crystalluria and cylindruria have been reported with quinolones, including levofloxacin. Therefore, adequate hydration of patients receiving levofloxacin should be maintained to prevent the formation of a highly concentrated urine [see Dosage and Administration (2.5)].

Clinical Trial Experience

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

The data described below reflect exposure to levofloxacin in 7537 patients in 29 pooled Phase 3 clinical trials. The population studied had a mean age of 50 years (approximately 74% of the population was < 65 years of age), 50% were male, 71% were Caucasian, 19% were Black. Patients were treated with levofloxacin for a wide variety of infectious diseases [see Indications and Usage (1)]. Patients received levofloxacin doses of 750 mg once daily, 250 mg once daily, or 500 mg once or twice daily. Treatment duration was usually 3 to 14 days, and the mean number of days on therapy was 10 days.

The overall incidence, type and distribution of adverse reactions was similar in patients receiving levofloxacin doses of 750 mg once daily, 250 mg once daily, and 500 mg once or twice daily. Discontinuation of levofloxacin due to adverse drug reactions occurred in 4.3% of patients overall, 3.8% of patients treated with the 250 mg and 500 mg doses and 5.4% of patients treated with the 750 mg dose. The most common adverse drug reactions leading to discontinuation with the 250 and 500 mg doses were gastrointestinal (1.4%), primarily nausea (0.6%); vomiting (0.4%); dizziness (0.3%); and headache (0.2%). The most common adverse drug reactions leading to discontinuation with the 750 mg dose were gastrointestinal (1.2%), primarily nausea (0.6%), vomiting (0.5%); dizziness (0.3%); and headache (0.3%).

Adverse reactions occurring in ≥1% of levofloxacin-treated patients and less common adverse reactions, occurring in 0.1 to <1% of levofloxacin-treated patients, are shown in Table 4 and Table 5, respectively. The most common adverse drug reactions (≥3%) are nausea, headache, diarrhea, insomnia, constipation, and dizziness.

Table 4: Common (≥1%) Adverse Reactions Reported in Clinical Trials with Levofloxacin
System/Organ Class	Adverse Reaction	% (N = 7537)
a N = 7274 b N = 3758 (women)
Infections and Infestations	moniliasis	1
Psychiatric Disorders	insomniaa [see Warnings and Precautions (5.6)]	4
Nervous System Disorders	headache dizziness [see Warnings and Precautions (5.6)]	6 3
Respiratory, Thoracic and Mediastinal Disorders	dyspnea [see Warnings and Precautions (5.3)]	1
Gastrointestinal Disorders	nausea diarrhea constipation abdominal pain vomiting dyspepsia	7 5 3 2 2 2
Skin and Subcutaneous Tissue Disorders	rash [see Warnings and Precautions (5.3)] pruritus	2 1
Reproductive System and Breast Disorders	vaginitis	1b
General Disorders and Administration Site Conditions	edema injection site reaction chest pain	1 1 1

Table 5: Less Common (0.1 to 1%) Adverse Reactions Reported in Clinical Trials with Levofloxacin (N = 7537)
System/Organ Class	Adverse Reaction
a N = 7274
Infections and Infestations	genital moniliasis
Blood and Lymphatic System Disorders	anemia thrombocytopenia granulocytopenia [see Warnings and Precautions (5.4)]
Immune System Disorders	allergic reaction [see Warnings and Precautions (5.3, 5.4)]
Metabolism and Nutrition Disorders	hyperglycemia hypoglycemia [see Warnings and Precautions (5.11)] hyperkalemia
Psychiatric Disorders	anxiety agitation confusion depression hallucination nightmarea [see Warnings and Precautions (5.6)] sleep disordera anorexia abnormal dreaminga
Nervous System Disorders	tremor convulsions [see Warnings and Precautions (5.6)] paresthesia [see Warnings and Precautions (5.8)] vertigo hypertonia hyperkinesias abnormal gait somnolencea syncope
Respiratory, Thoracic and Mediastinal Disorders	epistaxis
Cardiac Disorders	cardiac arrest palpitation ventricular tachycardia ventricular arrhythmia
Vascular Disorders	phlebitis
Gastrointestinal Disorders	gastritis stomatitis pancreatitis esophagitis gastroenteritis glossitis pseudomembranous/C. difficile colitis [see Warnings and Precautions (5.7)]
Hepatobiliary Disorders	abnormal hepatic function increased hepatic enzymes increased alkaline phosphatase
Skin and Subcutaneous Tissue Disorders	urticaria [see Warnings and Precautions (5.3)]
Musculoskeletal and Connective Tissue Disorders	arthralgia tendinitis [see Warnings and Precautions (5.1)] myalgia skeletal pain
Renal and Urinary Disorders	abnormal renal function acute renal failure [see Warnings and Precautions (5.4)]

In clinical trials using multiple-dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctate lenticular opacities, have been noted in patients undergoing treatment with quinolones, including levofloxacin. The relationship of the drugs to these events is not presently established.

Postmarketing Experience

Table 6 lists adverse reactions that have been identified during post-approval use of levofloxacin. Because these reactions are reported voluntarily from a population of uncertain size, reliably estimating their frequency or establishing a causal relationship to drug exposure is not always possible.

Table 6: Postmarketing Reports Of Adverse Drug Reactions
System/Organ Class	Adverse Reaction
Blood and Lymphatic System Disorders	pancytopenia aplastic anemia leucopenia hemolytic anemia [see Warnings and Precautions (5.4)] eosinophilia
Immune System Disorders	hypersensitivity reactions, sometimes fatal including: anaphylactic/anaphylactoid reactions anaphylactic shock angioneurotic edema serum sickness [see Warnings and Precautions (5.3, 5.4)]
Psychiatric Disorders	psychosis paranoia isolated reports of suicide attempt and suicidal ideation [see Warnings and Precautions (5.6)]
Nervous System Disorders	exacerbation of myasthenia gravis [see Warnings and Precautions (5.2)] anosmia ageusia parosmia dysgeusia peripheral neuropathy [see Warnings and Precautions (5.8)] isolated reports of encephalopathy abnormal electroencephalogram (EEG) dysphonia pseudotumor cerebri [see Warnings and Precautions (5.6)]
Eye Disorders	vision disturbance, including diplopia visual acuity reduced vision blurred scotoma
Ear and Labyrinth Disorders	hypoacusis tinnitus
Cardiac Disorders	isolated reports of torsade de pointes electrocardiogram QT prolonged [see Warnings and Precautions (5.9)] tachycardia
Vascular Disorders	vasodilatation
Respiratory, Thoracic and Mediastinal Disorders	isolated reports of allergic pneumonitis [see Warnings and Precautions (5.4)]
Hepatobiliary Disorders	hepatic failure (including fatal cases) hepatitis jaundice [see Warnings and Precautions (5.4, 5.5)]
Skin and Subcutaneous Tissue Disorders	bullous eruptions to include: Stevens-Johnson Syndrome toxic epidermal necrolysis erythema multiforme [see Warnings and Precautions (5.4)] photosensitivity/phototoxicity reaction [see Warnings and Precautions (5.12)] leukocytoclastic vasculitis
Musculoskeletal and Connective Tissue Disorders	tendon rupture [see Warnings and Precautions (5.1)] muscle injury, including rupture rhabdomyolysis
Renal and Urinary Disorders	interstitial nephritis [see Warnings and Precautions (5.4)]
General Disorders and Administration Site Condi