Furosemide

Class: Loop Diuretics
VA Class: CV702
CAS Number: 54-31-9
Brands: Lasix

• 
  

  Furosemide is a potent diuretic that given in excessive amounts may induce a profound diuresis with water and electrolyte depletion.^{133 e} Careful medical supervision is required; dosage selection and titration should be adjusted to the individual patient’s needs.^{133 e} (See Dosage and Administration.)

  
  

Introduction

A sulfonamide, loop-type diuretic and antihypertensive agent.^{133 e}

Uses for Furosemide

Edema

Management of edema associated with CHF, hepatic cirrhosis, and renal disease (e.g., nephrotic syndrome).^{133 e}

Considered a diuretic of choice for most patients with CHF.¹³¹

IV management of acute pulmonary edema (in combination with oxygen and a cardiac glycoside).¹⁵⁰

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).^{100 101 109 124 127 133 144}

One of several preferred initial therapies in hypertensive patients with CHF or renal disease.^{100 101 109 124 127 144}

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.^{100 101 124 127 142 143 144}

Furosemide Dosage and Administration

General

Edema

• 
  

  Careful etiologic diagnosis should precede the use of any diuretic.^e

  
  


• 
  

  Hospitalization of the patient during initiation of therapy is advisable, especially for patients with hepatic cirrhosis and ascites or chronic renal failure.^{133 e}

  
  


• 
  

  Most experts state that all patients with symptomatic CHF who have evidence for, or a prior history of, fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction (≤3 g of sodium daily), an ACE inhibitor, and usually a β-blocker, with or without a cardiac glycoside.¹³¹

  
  


• 
  

  In prolonged diuretic therapy, intermittent use of the drug (e.g., on 2–4 consecutive days each week) may be advisable.^e

  
  

Hypertension

• 
  

  Monitor BP carefully, especially during initial therapy.¹³³

  
  


• 
  

  If added to regimen of a patient receiving another antihypertensive agent, reduce dosage of preexisting therapy by at least 50% initially to avoid severe hypotension; additional dosage adjustment may be required.¹³³

  
  

Administration

Administer orally, IV, or IM.^{133 150}

Oral Administration

Administer orally once (preferably in the morning)^e or twice daily .¹³³

For ease of administration and maximum dosage flexibility in children, consider use of oral solution preparation.¹⁵¹

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

IV administration may be used in emergency clinical circumstances when a rapid onset of diuresis is desired, or in patients unable to take oral medication or those with impaired GI absorption; replace with oral therapy as soon as possible.^{133 150 e}

Consider the potential risks, when using large parenteral doses; monitor patient closely.^{105 107}

Dilution

For IV infusion, dilute in 5% dextrose, 0.9% sodium chloride, or lactated Ringer’s injection and adjust pH to >5.5.^{150 e}

Whenever possible, use vials instead of ampuls to prepare large doses to prevent large quantities of glass particles from entering the solutions.^e If ampuls must be used, consider filtering through a sterile membrane filter before use to remove any particles that may be present.^e

Rate of Administration

For direct IV injection, administer slowly over a period of 1–2 minutes.^{150 e}

If high-dose parenteral furosemide therapy is necessary, the manufacturer recommends that the drug be administered as a controlled infusion at a rate not exceeding 4 mg/minute in adults.^{150 e}

Dosage

Individualize dosage according to patient’s requirements and response; titrate dosage to gain maximum therapeutic effect while using the lowest possible effective dosage.^e (See Boxed Warning.)

Pediatric Patients

Edema

Oral

2 mg/kg administered as a single dose.^{103 104 105 107 108 133} If necessary, increase in increments of 1 or 2 mg/kg every 6–8 hours^{103 104 105 107 108} to a maximum of 6 mg/kg.^{103 133} Generally not necessary to exceed individual doses of 4 mg/kg or a dosing frequency of once or twice daily.¹⁰⁴ Use minimum effective dosage for maintenance therapy.¹³³

IV or IM

1 mg/kg administered as a single IM or IV injection.^{103 104 105 106 107 108 150} If necessary for resistant forms of edema, the initial dose may be increased by 1 mg/kg^{103 104 105 108} no more often than every 2 hours until the desired effect has been obtained or up to a maximum dosage of 6 mg/kg.¹⁰³ Adequate response usually is obtained with individual parenteral doses of 1 mg/kg.^{104 105 107 108}

Acute Pulmonary Edema

IV or IM

1 mg/kg administered as a single IM or IV injection.^{103 104 105 106 107 108 150} If necessary for resistant forms of edema, the initial dose may be increased by 1 mg/kg^{103 104 105 108} no more often than every 2 hours until the desired effect has been obtained or up to a maximum dosage of 6 mg/kg.¹⁰³ Adequate response generally obtained with 1 mg/kg.^{104 105 107 108}

Hypertension†

Oral

Initially, 0.5–2 mg/kg given once or twice daily.¹⁴⁹ Increase as necessary up to a maximum of 6 mg/kg daily.¹⁴⁹

Adults

Edema

Oral

20–80 mg given as a single dose, preferably in the morning.^{133 e} If needed, repeat same dose 6–8 hours later or increase dose by 20- to 40-mg increments and give no sooner than 6–8 hours after last dose until desired diuretic response (including weight loss) is obtained.^{133 e} May titrate carefully up to 600 mg daily in severe cases.¹³³

The effective dose may be given once or twice daily thereafter, or, in some cases, by intermittent administration on 2–4 consecutive days each week.^{133 e} Dosage may be reduced for maintenance therapy.^e

IV or IM

20–40 mg given as a single IM or IV injection.^{150 e} If needed, repeat same dose 2 hours later or increase dose by 20-mg increments and give no sooner than every 2 hours until the desired diuretic response is obtained.¹⁵⁰ Effective dosages may then be given once or twice daily.¹⁵⁰

Acute Pulmonary Edema

IV

40 mg given as a single IV injection.¹⁵⁰ If needed, an 80-mg dose may be given 1 hour after the initial dose.¹⁵⁰

Hypertension

Oral

40 mg twice daily.¹³³ If desired BP not attained, consider adding other antihypertensive agents.¹³³

Usual dosage recommended by JNC 7: 10–40 mg twice daily.^{127 144}

Prescribing Limits

Pediatric Patients

Edema

Oral

Maximum of 6 mg/kg.^{103 133}

IV or IM

Maximum of 6 mg/kg in infants and children; do not exceed 1 mg/kg daily in premature infants.¹⁵⁰

Hypertension†

Oral

Maximum 6 mg/kg daily.¹⁴⁹

Adults

Edema

Oral

Maximum of 600 mg daily.¹³³

Special Populations

Renal Impairment

Higher doses may be required for patients with acute or chronic renal failure.^e

Hypertension

Higher doses may be required for patients with acute or chronic renal failure.^e

Oral

Use of ≥3 antihypertensive agents usually is required to achieve a target BP <130/80 mm Hg.¹⁴⁴

Cautions for Furosemide

Contraindications

• 
  

  Anuria.¹³³

  
  


• 
  

  Known hypersensitivity to furosemide or any ingredient in the formulation.¹³³

  
  

Warnings/Precautions

Warnings

Hepatic Effects

Sudden alterations of electrolyte balance in patients with cirrhosis may precipitate hepatic coma; use with caution in patients with hepatic cirrhosis and ascites.¹³³

Do not initiate therapy in patients with hepatic coma or electrolyte depletion until the basic condition is improved.¹³³ Therapy in such patients is best initiated in the hospital with careful monitoring of clinical status and electrolyte balance.¹³³

Renal Effects

If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, discontinue the drug.^{133 150}

Sensitivity Reactions

Anaphylaxis

Anaphylaxis (e.g., urticaria, angioedema, hypotension) within 5 minutes after IV administration reported.¹⁰²

Systemic Lupus Erythematosus

Possible exacerbation or activation of systemic lupus erythematosus.^{133 150}

Sulfonamide Sensitivity

Patients sensitive to sulfonamides may show allergic reactions to furosemide.^e

Photosensitivity

Photosensitivity may occur.¹³³

Major Toxicities

Ototoxicity

Risk of tinnitus, reversible or permanent hearing impairment increased following IV or IM administration, especially at high dosages,^{133 e} after too-rapid administration,¹³³ in patients with severely impaired renal function, and/or in patients receiving other ototoxic drugs (e.g., aminoglycosides).^{133 e} (See Specific Drugs under Interactions.)

If high-dose IV therapy is indicated, administer by slow IV infusion (e.g., at a rate not exceeding 4 mg/minute in adults).^{133 150}

General Precautions

Fluid, Electrolyte, and Cardiovascular Effects

Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism, particularly in elderly patients.¹³³ (See Boxed Warning.)

Risk of orthostatic hypotension, especially with brisk diuresis.^{133 150 151} May be aggravated by concomitant use with alcohol, barbiturates, or narcotics.^{133 151 e}

Risk of hypokalemia, especially with brisk diuresis, inadequate oral electrolyte intake, when cirrhosis is present, or during concomitant use of corticosteroids or ACTH.^{133 150} Concomitant therapy with digitalis may exaggerate metabolic effects of hypokalemia, especially myocardial effects.^{133 150}

Observe carefully for manifestations of fluid and electrolyte depletion (e.g., dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, nausea, vomiting).¹³³

Endocrine Effects

Possible increased blood glucose and alterations in glucose tolerance tests (with abnormalities of the fasting and 2-hour postprandial sugar); precipitation of diabetes mellitus rarely reported.^{133 150} Monitor urine and blood glucose concentrations periodically in patients with diabetes and those suspected of latent diabetes.^e

Possible hyperuricemia and precipitation of gout;^{133 150} use with caution in patients with a history of gout or elevated serum uric acid concentrations.^e

Patient Monitoring

Monitor regularly for the possible occurrence of blood dyscrasias, liver or kidney damage, or other idiosyncratic reactions.^{133 150}

Serum electrolytes (particularly potassium), CO₂, creatinine and BUN should be determined frequently during the first few months of therapy and periodically thereafter.^{133 150}

Elective Surgery

Discontinue therapy 1 week (oral furosemide) or 2 days (parenteral furosemide) before elective surgery.^e

Specific Populations

Pregnancy

Category C.¹³³

Lactation

Distributed into milk.¹³³ Use with caution.¹³³

Pediatric Use

Risk of persistent patent ductus arteriosus (PDA) may be increased in premature neonates with respiratory distress syndrome (RDS) who receive furosemide during the first weeks of life.^{103 e}

Do not exceed dosage of 1 mg/kg per 24 hours in premature neonates with <31 weeks’ postconception age (gestational age at birth plus postnatal age); risk of potentially toxic furosemide plasma concentrations with higher dosages.¹⁵⁰

Renal calcification reported in severely premature infants treated with IV furosemide for edema due to PDA and hyaline membrane disease; concomitant chlorothiazide therapy may decrease hypercalciuria and dissolve some calculi.¹⁵⁰

Hearing loss reported in neonates; possibly secondary to renal immaturity.^{103 125 126 150}

Oral solutions contain sorbitol; high dosages may cause diarrhea in children.^e

Hepatic Impairment

Use with caution.^{133 e}

Renal Impairment

Use with caution.^{133 e}

Common Adverse Effects

Orthostatic hypotension, dizziness, electrolyte imbalance (hyponatremia, hypokalemia, hypochloremia) tinnitus, photosensitivity.^{133 e}

Interactions for Furosemide

Specific Drugs

Drug	Interaction	Comments
Alcohol	May aggravate orthostatic hypotension133 151 e
Anticonvulsant agents (e.g., phenytoin sodium, phenobarbital)	Possible reduced diuretic effecte
Antidiabetic agents (e.g., insulin, oral agents)	Possible antagonism of hypoglycemic effect as result of hypokalemia133	Observe for possible decreased diabetic control; correct potassium deficit and/or adjust dosage of antidiabetic agente
Antihypertensive agents	Additive antihypertensive effect; orthostatic hypotension may occur133	Reduce dosage of both drugse Concomitant therapy generally used to therapeutic advantagee
Barbiturates	May aggravate orthostatic hypotension133 151 e
Cardiac glycoside (e.g., digoxin)	Possible electrolyte disturbances (e.g., hypokalemia, hypomagnesemia), increased risk of digitalis toxicity, and/or fatal cardiac arrhythmias e	Monitor electrolytes; correct hypokalemia e
Chloral hydrate	Possible reaction characterized by diaphoresis, flushes, hypertension, and uneasiness in patients with acute MI and CHFe	Consider alternate hypnotic drug (e.g., a benzodiazepine) in patients who require IV furosemidee
Diuretics, loop (e.g., bumetanide, ethacrynic acid, torsemide)	Share similar diuretic mechanisms e	No therapeutic rationale for concomitant usee
Diuretics, potassium- sparing (e.g., amiloride, spironolactone, triamterene)	Possible reduction in potassium loss 133	May be used to therapeutic advantage133
Diuretics, thiazides	Additive diuretic effecte	Use reduced dosage of furosemide when added to existing diuretic regimene
Drugs that cause potassium loss (e.g., corticosteroids, corticotropin, amphotericin B)	Additive hypokalemic effects133 e	Monitor electrolytes; correct hypokalemia 133 e
Indomethacin	Possible decreased diuretic and natriuretic effect133	Monitor closely to determine if desired diuretic and/or hypotensive effect is obtained133
Lithium	Reduced renal clearance of lithium and increased risk of lithium toxicity 133	Avoid concomitant use;133 e if concomitant therapy is necessary, monitor for lithium toxicitye
Narcotics	May aggravate orthostatic hypotension133 151 e
Neuromuscular blocking agents, nondepolarizing (e.g., atracurium besylate, tubocurarine chloride)	Potential for prolonged neuromuscular blockadee
Norepinephrine	Decreased arterial responsive to norepinephrine133	Norepinephrine may still be used effectively133
Ototoxic drugs (e.g., aminoglycoside antibiotics)	Possible additive ototoxic effect, especially in patients with impaired renal function133	Avoid concomitant use except in life-threatening situations133
Salicylates (e.g., aspirin, NSAIAs)	Possible transient reductions in Clcr in patient with chronic renal insufficiencye Possible weight gain and increased Scr, serum potassium concentrations, and BUN (NSAIAs)133	Monitor for toxicity133
Succinylcholine	May potentiate action of succinylcholine133
Sucralfate	Possible reduced natriuretic and antihypertensive effects133	Do not administer simultaneously; separate administration by ≥2 hours133 Observe closely for desired diuretic and/or antihypertensive effect133
Uricosuric drugs (probenecid, sulfinpyrazone)	Possible antagonism of uricosuric effectse	Monitor serum uric acid concentrationse

Furosemide Pharmacokinetics

Absorption

Bioavailability

Mean oral bioavailability of furosemide from commercially available tablets and oral solution is 64% and 60%, respectively.¹³³

Commercially available tablets and oral solution are bioequivalent.¹³³

Onset

Following oral administration, onset of diuresis occurs within 30 minutes to 1 hour; maximal effect after 1–2 hours.^{133 e}

Following IV administration, diuresis occurs within 5 minutes and peaks within 20–60 minutes.^{150 e}

Onset of diuresis after IM administration occurs somewhat later than after IV administration.¹⁵⁰

Maximum hypotensive effect may not be apparent until after several days of therapy.^e

Duration

Diuretic effect persists 6–8 hours following oral administration and approximately 2 hours following IV administration.^{133 150 e}

Food

Food does not appear to affect diuretic effect.^e

Special Populations

In patients with severely impaired renal function, the diuretic response may be prolonged.^e

Distribution

Extent

Crosses the placenta and is distributed into milk.^e

Plasma Protein Binding

Approximately 95% bound to plasma proteins (mainly albumin) in both normal and azotemic patients.^{133 e}

Elimination

Metabolism

Metabolized in the liver to the defurfurylated derivative, 4-chloro-5-sulfamoylanthranilic acid.^e

Elimination Route

Rapidly excreted in urine by glomerular filtration and by secretion from the proximal tubule.^e

Approximately 50% of an oral dose and 80% of an IV or IM dose are excreted in urine within 24 hours; 69–97% of these amounts is excreted in the first 4 hours.^{150 e} The remainder of the drug is eliminated by nonrenal mechanisms including degradation in the liver and excretion of unchanged drug in the feces.^e

Half-life

Biphasic;^e terminal half-life is approximately 2 hours.¹³³

Special Populations

Hepatic or renal impairment prolongs the elimination half-life of the drug.^e

In patients with marked renal impairment without liver disease, nonrenal clearance is increased to the extent that up to 98% of the drug is cleared within 24 hours.^e

Not removed by hemodialysis.¹³³

Stability

Storage

Oral

Solution or Tablets

Tight, light resistant containers at 15–30°C.^{133 151}

Parenteral

Injection

15–30°C; protect from light.¹⁵⁰ Discard unused portion.¹⁵⁰

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Do not mix with strongly acidic solutions (i.e., pH < 5.5), such as those containing ascorbic acid, amrinone, ciprofloxacin, labetalol, tetracycline, milrinone, epinephrine, or norepinephrine, because furosemide may be precipitated.^{150 e}

Solution Compatibility^a

Compatible
Alcohol 5% and dextrose 5%
Amino acids 4.25%, dextrose 25%
Dextrose 5% in Ringer’s injection, lactated
Dextrose 5% in sodium chloride 0.9%
Dextrose 5, 10, or 20% in water
Invert sugar 10% in Electrolyte #1
Mannitol 20%
Ringer’s injection, lactated
Sodium chloride 0.9%
Sodium lactate (1/6) M
Incompatible
Fructose 10% in water
Invert sugar 10% in Electrolyte #2

Drug Compatibility

Admixture Compatibilitya

Compatible
Amikacin sulfate
Aminophylline
Ampicillin sodium
Atropine sulfate
Bumetanide
Calcium gluconate
Cefuroxime sodium
Cimetidine HCl
Dexamethasone sodium phosphate
Diamorphine HCl
Digoxin
Epinephrine HCl
Heparin sodium
Hydrocortisone sodium succinate
Isosorbide dinitrate
Kanamycin sulfate
Lidocaine HCl
Midazolam HCl
Meropenem
Morphine sulfate
Nitroglycerin
Penicillin G
Potassium chloride
Ranitidine HCl
Scopolamine butylbromide
Sodium bicarbonate
Sulphadimidine
Theophylline
Tobramycin sulfate
Incompatible
Buprenorphine HCl
Chlorpromazine HCl
Diazepam
Dobutamine HCl
Erythromycin lactobionate
Isoproterenol HCl
Meperidine HCl
Metoclopramide HCl
Papaveretum
Prochlorperazine edisylate
Promethazine HCl
Variable
Amiodarone HCl
Gentamicin sulfate
Hydrocortisone sodium succinate
Verapamil HCl

Y-Site Compatibilitya

Compatible
Allopurinol sodium
Amifostine
Amikacin sulfate
Amphotericin B cholesteryl sulfate complex
Aztreonam
Bivalirudin
Bleomycin sulfate
Cefepime HCl
Ceftazidime
Cisplatin
Cladribine
Cyclophosphamide
Cytarabine
Dexmedetomidine HCl
Docetaxel
Doxorubicin HCl liposome injection
Epinephrine HCl
Etoposide phosphate
Fentanyl citrate
Fludarabine phosphate
Fluorouracil
Foscarnet sodium
Granisetron HCl
Heparin sodium
Hetastarch in lactated electrolyte injection (Hextend)
Hydrocortisone sodium succinate
Hydromorphone HCl
Indomethacin sodium trihydrate
Kanamycin sulfate
Leucovorin calcium
Linezolid
Lorazepam
Melphalan HCl
Meropenem
Methotrexate sodium
Mitomycin
Nitroglycerin
Norepinephrine bitartrate
Paclitaxel
Piperacillin sodium–tazobactam sodium
Potassium chloride
Propofol
Ranitidine HCl
Remifentanil HCl
Sargramostim
Sodium nitroprusside
Tacrolimus
Tirofiban HCl
Teniposide
Thiotepa
Tirofiban
Tobramycin sulfate
Vitamin B complex with C
Incompatible
Amsacrine
Azithromycin
Chlorpromazine HCl
Ciprofloxacin
Clarithromycin
Diltiazem HCl
Droperidol
Esmolol HCl
Fenoldopam mesylate
Filgrastim
Fluconazole
Gatifloxacin
Gemcitabine HCl
Gentamicin sulfate
Hydralazine HCl
Idarubicin HCl
Levofloxacin
Metoclopramide HCl
Midazolam HCl
Milrinone lactate
Nicardipine HCl
Ondansetron HCl
Quinidine gluconate
Thiopental sodium
Vecuronium bromide
Vinblastine sulfate
Vincristine sulfate
Vinorelbine tartrate
Variable
Amiodarone HCl
Dobutamine HCl
Dopamine HCl
Doxorubicin HCl
Famotidine
Labetalol HCl
Meperidine HCl
Morphine sulfate

ActionsActions

• 
  

  Inhibits primarily the absorption of sodium and chloride not only in the proximal and distal tubules but also in the ascending limb of the loop of Henle.^{133 e} Does not inhibit carbonic anhydrase and is not an aldosterone antagonist.^e

  
  


• 
  

  Mechanism of hypotensive effect not definitively determined but presumed to result from decreased plasma volume.^e

  
  


• 
  

  Induces greater diuresis and electrolyte loss than with thiazides or most other diuretics except ethacrynic acid.^e

  
  


• 
  

  Possesses some renal vasodilator effect; renal vascular resistance decreases and renal blood flow increases following administration.^e

  
  

Advice to Patients

• 
  

  Risks associated with excessive fluid loss or electrolyte imbalance.¹³³

  
  


• 
  

  Potential for postural hypotension; importance of rising slowly from a seated position.¹³³

  
  


• 
  

  Importance of discussing dietary measures and supplementation to prevent or correct hypokalemia.¹³³

  
  


• 
  

  Importance of informing patients with diabetes mellitus that blood glucose and urine glucose concentrations may increase.^{133 e}

  
  


• 
  

  Importance of informing patients of possible photosensitivity.^{133 e}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., appetite suppressants, cold remedies) as well as any concomitant illnesses.^{133 e}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{133 e}

  
  


• 
  

  Importance of informing patients of other important precautionary information.^{133 e} (See Cautions.)

  
  

Preparations

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

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

Furosemide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	40 mg/5 mL*	Furosemide Solution (with alcohol 0.2% and sorbitol)	Roxane
		10 mg/mL*	Furosemide Solution	Morton Grove, Roxane
	Tablets	20 mg*	Furosemide Tablets	IVAX, Mylan, Qualitest, Roxane, Sandoz, UDL
			Lasix	Sanofi-Aventis
		40 mg*	Furosemide Tablets	IVAX, Mylan, Qualitest, Roxane, Sandoz, UDL
			Lasix (scored)	Sanofi-Aventis
		80 mg*	Furosemide Tablets	Mylan, Qualitest, Roxane, Sandoz, UDL
			Lasix	Sanofi-Aventis
Parenteral	Injection	10 mg/mL*	Furosemide Injection	American Pharmaceutical Partners, American Regent, Hospira, IMS

Comparative Pricing

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

Furosemide 10MG/ML Solution (MORTON GROVE PHARMACEUTICALS): 120/$15.99 or 360/$35.97

Furosemide 10MG/ML Solution (ROXANE): 60/$17.99 or 120/$25.98

Furosemide 20MG Tablets (SANDOZ): 100/$13.99 or 200/$18.97

Furosemide 40MG Tablets (SANDOZ): 100/$13.99 or 200/$19.96

Furosemide 80MG Tablets (SANDOZ): 30/$12.99 or 60/$15.98

Lasix 20MG Tablets (SANOFI-AVENTIS U.S.): 30/$24.25 or 90/$45.92

Lasix 40MG Tablets (SANOFI-AVENTIS U.S.): 30/$25.99 or 90/$54.91

Lasix 80MG Tablets (SANOFI-AVENTIS U.S.): 30/$35.99 or 90/$85.97

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 April 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

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

100. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1984; 144:1045-57. [IDIS 184763] [PubMed 6143542]

101. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1980 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1980; 140:1280-5. [IDIS 375724] [PubMed 6775608]

102. Hansbrough JR, Wedner HJ, Chaplin DD et al. Anaphylaxis to intravenous furosemide. J Allergy Clin Immunol. 1987; 80:538-41. [IDIS 235418] [PubMed 3668117]

103. Hoechst-Roussel. Lasix (furosemide) injection, oral solution, and tablets prescribing information (dated 1994 Oct). In: Physicians’ desk reference. 50th ed. Montvale NJ: Medical Economics Company Inc; 1996:1240-2.

104. Engle MA, Lewy JE, Lewy PR et al. The use of furosemide in the treatment of edema in infants and children. Pediatrics. 1978; 62:811-8. [IDIS 118470] [PubMed 724325]

105. Baliga R, Lewy JE. Pathogenesis and treatment of edema. Pediatr Clin North Am. 1987; 34:639-48. [PubMed 3588044]

106. Repetto HA, Lewy JE, Braudo JL et al. The renal functional response to furosemide in children with acute glomerulonephritis. J Pediatr. 1972; 80:660-6. [PubMed 5015080]

107. Lewy JE. Diuretics in infancy. Controversies Nephrol. 1981; 27:33-44.

108. Lewy JE, Moel DI. Pathogenesis and management of edema in the newborn. Clin Perinatol. 1975; 2:117-23. [PubMed 1102212]

109. 1988 Joint National Committee. The 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988; 148:1023-38. [IDIS 242588] [PubMed 3365073]

110. Lardinois CK, Neuman SL. The effects of antihypertensive agents on serum lipids and lipoproteins. Arch Intern Med. 1988; 148:1280-8. [IDIS 242671] [PubMed 2897834]

111. Holland OB, Pool PE. Metabolic changes with antihypertensive therapy of the salt-sensitive patient. Am J Cardiol. 1988; 61:53-9H.

112. Weinberger MH. Diuretics and their side effects: dilemma in the treatment of hypertension. Hypertension. 1988; 11(Suppl II):II-16-20.

113. Ames R. Effects of diuretic drugs on the lipid profile. Drugs. 1988; 36(Suppl 2):33-40. [IDIS 248276] [PubMed 3063504]

114. Lasser NL, Grandits G, Caggiula AW et al. Effects of antihypertensive therapy on plasma lipids and lipoproteins in the Multiple Risk Factor Intervention Trial. Am J Med. 1984; 76(Suppl 2A):52-66. [IDIS 182290] [PubMed 6367451]

115. Bloomgarden ZT, Ginsberg-Fellner F, Rayfield EJ et al. Elevated hemoglobin A_1c and low-density lipoprotein cholesterol levels in thiazide-treated diabetic patients. Am J Med. 1984; 77:823-7. [IDIS 192589] [PubMed 6496535]

116. Gluck Z, Baumgartner G, Weidmann P et al. Increased ratio between serum beta- and alpha-lipoproteins during diuretic therapy: an adverse effect? Clin Sci Mol Med Suppl. 1978; 4:325-8s.

117. Ames RP, Hill P. Antihypertensive therapy and the risk of coronary heart disease. J Cardiovasc Pharmacol. 1982; 4(Suppl 2):S206-12. [PubMed 6177958]

118. Ames RP, Hill P. Improvement of glucose tolerance and lowering of glycohemoglobin and serum lipid concentrations after discontinuance of antihypertensive drug treatment. Circulation. 1982; 65:899-904. [IDIS 150695] [PubMed 7042109]

119. Perola P, Lehto H, Lammintausta R et al. Metabolic effects of furosemide and the combination of furosemide and triamterene. Curr Ther Res. 1985; 37:545-53.

120. Weinberger MH. Antihypertensive therapy and lipids: evidence, mechanisms, and implications. Arch Intern Med. 1985; 145:1102-5. [IDIS 200606] [PubMed 2860883]

121. Gerlag PGG, van Meijel JJM. High-dose furosemide in the treatment of refractory congestive heart failure. Arch Intern Med. 1988; 148:286-91. [IDIS 238227] [PubMed 3341836]

122. Weidmann P, Gerber A. Effects of treatment with diuretics on serum proteins. J Cardiovasc Pharmacol. 1984; 6(Suppl 1):S260-8. [PubMed 6204152]

Mavik

Generic Name: trandolapril (Oral route)

tran-DOE-la-pril

Oral route(Tablet)

ACE inhibitors can cause injury or death to the developing fetus when used during the second and third trimesters. Stop therapy as soon as possible when pregnancy is detected .

Commonly used brand name(s)

In the U.S.

• Mavik

Available Dosage Forms:

• Capsule


• Tablet

Therapeutic Class: Antihypertensive

Pharmacologic Class: ACE Inhibitor

Uses For Mavik

Trandolapril is used alone or together with other medicines to treat high blood pressure (hypertension). High blood pressure adds to the work load of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys resulting in a stroke, heart failure, or kidney failure. Hypertension may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled .

Trandolapril works by blocking an enzyme in the body that is necessary to produce a substance that causes blood vessels to tighten. As a result, the blood vessels relax. This lowers blood pressure and increases the supply of blood and oxygen to the heart .

Trandolapril is also used in some patients after a heart attack. After a heart attack, some of the heart muscle is damaged and weakened. The heart muscle may continue to weaken as time goes by. This makes it more difficult for the heart to pump blood. Trandolapril may be started within the first few days after a heart attack to increase survival rate. Trandolapril helps slow down further weakening of the heart .

This medicine is available only with your doctor's prescription .

Before Using Mavik

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

Allergies

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

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of trandolapril in the pediatric population. Safety and efficacy have not been established .

Geriatric

Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of trandolapril in the elderly. However, elderly patients are more likely to have age-related kidney or heart problems, which may require caution in patients receiving trandolapril .

Pregnancy

	Pregnancy Category	Explanation
1st Trimester	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.
2nd Trimester	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.
3rd Trimester	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

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. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alteplase, Recombinant


• Amiloride


• Azathioprine


• Azilsartan Medoxomil


• Candesartan Cilexetil


• Canrenoate


• Eplerenone


• Eprosartan


• Losartan


• Olmesartan Medoxomil


• Potassium


• Spironolactone


• Telmisartan


• Triamterene


• Valsartan

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac


• Acemetacin


• Alclofenac


• Aliskiren


• Apazone


• Azosemide


• Bemetizide


• Bendroflumethiazide


• Benoxaprofen


• Benzthiazide


• Bromfenac


• Bufexamac


• Bumetanide


• Bupivacaine


• Buthiazide


• Capsaicin


• Carprofen


• Chlorothiazide


• Chlorthalidone


• Clometacin


• Clonixin


• Clopamide


• Cyclopenthiazide


• Cyclothiazide


• Dexketoprofen


• Diclofenac


• Diflunisal


• Dipyrone


• Droxicam


• Ethacrynic Acid


• Etodolac


• Etofenamate


• Felbinac


• Fenbufen


• Fenoprofen


• Fentiazac


• Floctafenine


• Flufenamic Acid


• Flurbiprofen


• Furosemide


• Gold Sodium Thiomalate


• Hydrochlorothiazide


• Hydroflumethiazide


• Ibuprofen


• Indapamide


• Indomethacin


• Indoprofen


• Isoxicam


• Ketoprofen


• Ketorolac


• Lithium


• Lornoxicam


• Meclofenamate


• Mefenamic Acid


• Meloxicam


• Methyclothiazide


• Metolazone


• Nabumetone


• Naproxen


• Niflumic Acid


• Nimesulide


• Oxaprozin


• Oxyphenbutazone


• Phenylbutazone


• Pirazolac


• Piretanide


• Piroxicam


• Pirprofen


• Polythiazide


• Propyphenazone


• Proquazone


• Quinethazone


• Sulindac


• Suprofen


• Tenidap


• Tenoxicam


• Tiaprofenic Acid


• Tolmetin


• Torsemide


• Trichlormethiazide


• Xipamide


• Zomepirac

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Angioedema, history of—Trandolapril may increase the risk of this condition occurring again .

• Dehydration or


• Diarrhea or


• Heart failure or


• Hyponatremia (low sodium in the blood) or


• Kidney disease—These conditions may cause the blood pressure to fall too low with trandolapril .

• Liver disease—The effects of trandolapril may be increased because of slower removal from the body.

Proper Use of Mavik

In addition to the use of trandolapril, treatment for your high blood pressure may include weight control and changes in the types of foods you eat, especially foods high in sodium. Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet.

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well.

Remember that this medicine will not cure your high blood pressure but it does help control it. Therefore, you must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease.

Dosing

The dose of this medicine 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 this medicine. 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 oral dosage form (tablets):
  
  • For high blood pressure:
    
    • Adults—At first, 1 to 2 milligrams (mg) once a day. Then, your doctor may increase your dose to 2 to 4 mg per day taken as a single dose or divided into two doses.
    
    
    • Children—Use and dose must be determined by your doctor .
    
    
  
  
  • For treatment after a heart attack:
    
    • Adults—At first, 1 milligram (mg) once a day. Then, your doctor may increase your dose to 4 mg per day taken as a single dose.
    
    
    • Children—Use and dose must be determined by your doctor .
    
    
  
  

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.

Storage

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

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Mavik

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and to check for unwanted effects. Blood tests may be needed to check for unwanted effects .

Using this medicine while you are pregnant can harm your unborn baby. If you think you have become pregnant while using this medicine, tell your doctor right away .

Stop using this medicine and call your doctor right away if you have swelling of the face, arms, legs, eyes, lips, or tongue, or problems with swallowing or breathing. These are symptoms of a condition called angioedema .

Stop using this medicine and call your doctor right away if you have severe stomach pain. This could be a symptom of a condition called intestinal angioedema .

You may experience lightheadedness during the first few days with this medicine. If this becomes severe and you faint, stop using this medicine and talk to your doctor right away .

Tell your doctor immediately if you have any signs of infection such as chills, sore throat, or fever. These may be symptoms of an immune system condition called neutropenia .

This medicine may increase the amount of potassium in your blood. Do not use salt substitutes containing potassium without first checking with your doctor .

Check with your doctor right away if you have symptoms of jaundice (yellow skin or eyes) because these may be signs of a serious liver condition .

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery or medical tests .

Mavik 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:

More common

• Abdominal pain


• blurred vision


• confusion


• difficult breathing


• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly


• fainting


• irregular heartbeat


• nausea or vomiting


• nervousness


• numbness or tingling in hands, feet, or lips


• shortness of breath


• sweating


• unusual tiredness or weakness


• weakness or heaviness of legs

Less common

• Abdominal cramps


• chest pain or discomfort


• cool, sweaty skin


• difficulty in speaking


• double vision


• inability to move arms, legs, or facial muscles


• inability to speak


• mood or mental changes


• muscle cramps in hands, arms, feet, legs, or face


• numbness and tingling around the mouth, fingertips, or feet


• pain, tension, and weakness upon walking that subsides during periods of rest


• seizures


• slow heartbeat


• tremor

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:

More common

• Acid or sour stomach


• belching


• cough


• heartburn


• indigestion


• stomach discomfort, upset, or pain

Less common

• Burning feeling in chest or stomach


• difficulty in moving


• joint pain


• muscle aches, pain, or stiffness


• swollen joints


• tenderness in stomach area

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

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

See also: Mavik side effects (in more detail)

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

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

More Mavik resources

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

• Mavik Prescribing Information (FDA)


• Mavik MedFacts Consumer Leaflet (Wolters Kluwer)


• Mavik Concise Consumer Information (Cerner Multum)


• Mavik Monograph (AHFS DI)


• Trandolapril Prescribing Information (FDA)


• Trandolapril Professional Patient Advice (Wolters Kluwer)

Compare Mavik with other medications

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Imitrex Injection

Generic Name: sumatriptan succinate

Dosage Form: injection
IMITREX®

(sumatriptan succinate)

Injection

For Subcutaneous Use Only.

Imitrex Injection Description

IMITREX (sumatriptan succinate) Injection is a selective 5-hydroxytryptamine1 receptor subtype agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-indole-5-methanesulfonamide succinate (1:1), and it has the following structure:

The empirical formula is C14H21N3O2S•C4H6O4, representing a molecular weight of 413.5.

Sumatriptan succinate is a white to off-white powder that is readily soluble in water and in saline.

Imitrex Injection is a clear, colorless to pale yellow, sterile, nonpyrogenic solution for subcutaneous injection. Each 0.5 mL of Imitrex Injection 8 mg/mL solution contains 4 mg of sumatriptan (base) as the succinate salt and 3.8 mg of sodium chloride, USP in Water for Injection, USP. Each 0.5 mL of Imitrex Injection 12 mg/mL solution contains 6 mg of sumatriptan (base) as the succinate salt and 3.5 mg of sodium chloride, USP in Water for Injection, USP. The pH range of both solutions is approximately 4.2 to 5.3. The osmolality of both injections is 291 mOsmol.

Imitrex Injection - Clinical Pharmacology

Mechanism of Action

Sumatriptan is a selective agonist for a vascular 5-hydroxytryptamine1 receptor subtype (probably a member of the 5-HT1D family) with no significant affinity (as measured using standard radioligand binding assays) or pharmacological activity at 5-HT2, 5-HT3 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic; dopamine1; dopamine2; muscarinic; or benzodiazepine receptors.

The vascular 5-HT1 receptor subtype to which sumatriptan binds selectively, and through which it presumably exerts its antimigrainous effect, is present on cranial arteries in both dog and primate, on the human basilar artery, and in the vasculature of the isolated dura mater of humans. In these tissues, sumatriptan activates this receptor to cause vasoconstriction, an action in humans correlating with the relief of migraine and cluster headache. In the anesthetized dog, sumatriptan selectively reduces the carotid arterial blood flow with little or no effect on arterial blood pressure or total peripheral resistance. In the cat, sumatriptan selectively constricts the carotid arteriovenous anastomoses while having little effect on blood flow or resistance in cerebral or extracerebral tissues.

Corneal Opacities

Dogs receiving oral sumatriptan developed corneal opacities and defects in the corneal epithelium. Corneal opacities were seen at the lowest dosage tested, 2 mg/kg/day, and were present after 1 month of treatment. Defects in the corneal epithelium were noted in a 60-week study. Earlier examinations for these toxicities were not conducted and no-effect doses were not established; however, the relative exposure at the lowest dose tested was approximately 5 times the human exposure after a 100-mg oral dose or 3 times the human exposure after a 6-mg subcutaneous dose.

Melanin Binding

In rats with a single subcutaneous dose (0.5 mg/kg) of radiolabeled sumatriptan, the elimination half-life of radioactivity from the eye was 15 days, suggesting that sumatriptan and its metabolites bind to the melanin of the eye. The clinical significance of this binding is unknown.

Pharmacokinetics

Pharmacokinetic parameters following a 6-mg subcutaneous injection into the deltoid area of the arm in 9 males (mean age: 33 years, mean weight: 77 kg) were systemic clearance: 1,194 ± 149 mL/min (mean ± S.D.), distribution half-life: 15 ± 2 minutes, terminal half-life: 115 ± 19 minutes, and volume of distribution central compartment: 50 ± 8 liters. Of this dose, 22% ± 4% was excreted in the urine as unchanged sumatriptan and 38% ± 7% as the indole acetic acid metabolite.

After a single 6-mg subcutaneous manual injection into the deltoid area of the arm in 18 healthy males (age: 24 ± 6 years, weight: 70 kg), the maximum serum concentration (Cmax) was (mean ± standard deviation) 74 ± 15 ng/mL and the time to peak concentration (Tmax) was 12 minutes after injection (range: 5 to 20 minutes). In this study, the same dose injected subcutaneously in the thigh gave a Cmax of 61 ± 15 ng/mL by manual injection versus 52 ± 15 ng/mL by autoinjector techniques. The Tmax or amount absorbed was not significantly altered by either the site or technique of injection.

The bioavailability of sumatriptan via subcutaneous site injection to 18 healthy male subjects was 97% ± 16% of that obtained following intravenous injection. Protein binding, determined by equilibrium dialysis over the concentration range of 10 to 1,000 ng/mL, is low, approximately 14% to 21%. The effect of sumatriptan on the protein binding of other drugs has not been evaluated.

Special Populations

Renal Impairment: The effect of renal impairment on the pharmacokinetics of sumatriptan has not been examined, but little clinical effect would be expected as sumatriptan is largely metabolized to an inactive substance.

Hepatic Impairment: The effect of hepatic disease on the pharmacokinetics of subcutaneously and orally administered sumatriptan has been evaluated. There were no statistically significant differences in the pharmacokinetics of subcutaneously administered sumatriptan in hepatically impaired patients compared with healthy controls. However, the liver plays an important role in the presystemic clearance of orally administered sumatriptan. Accordingly, the bioavailability of sumatriptan following oral administration may be markedly increased in patients with liver disease. In 1 small study of hepatically impaired patients (N = 8) matched for sex, age, and weight with healthy subjects, the hepatically impaired patients had an approximately 70% increase in AUC and Cmax and a Tmax 40 minutes earlier compared with the healthy subjects.

Age: The pharmacokinetics of sumatriptan in the elderly (mean age: 72 years, 2 males and 4 females) and in patients with migraine (mean age: 38 years, 25 males and 155 females) were similar to that in healthy male subjects (mean age: 30 years) (see PRECAUTIONS: Geriatric Use).

Race: The systemic clearance and Cmax of sumatriptan were similar in black (n = 34) and Caucasian (n = 38) healthy male subjects.

Drug Interactions

Monoamine Oxidase Inhibitors: In vitro studies with human microsomes suggest that sumatriptan is metabolized by monoamine oxidase (MAO), predominantly the A isoenzyme. In a study of 14 healthy females, pretreatment with MAO-A inhibitor decreased the clearance of sumatriptan. Under the conditions of this experiment, the result was a 2-fold increase in the area under the sumatriptan plasma concentration x time curve (AUC), corresponding to a 40% increase in elimination half-life. No significant effect was seen with an MAO-B inhibitor.

Pharmacodynamics

Typical Physiologic Responses:

Blood Pressure: See WARNINGS: Increase in Blood Pressure.

Peripheral (Small) Arteries: In healthy volunteers (N = 18), a study evaluating the effects of sumatriptan on peripheral (small vessel) arterial reactivity failed to detect a clinically significant increase in peripheral resistance.

Heart Rate: Transient increases in blood pressure observed in some patients in clinical studies carried out during sumatriptan’s development as a treatment for migraine were not accompanied by any clinically significant changes in heart rate.

Respiratory Rate: Experience gained during the clinical development of sumatriptan as a treatment for migraine failed to detect an effect of the drug on respiratory rate.

Clinical Trials

Migraine

In US controlled clinical trials enrolling more than 1,000 patients during migraine attacks who were experiencing moderate or severe pain and 1 or more of the symptoms enumerated in Table 2, onset of relief began as early as 10 minutes following a 6-mg Imitrex Injection. Smaller doses of sumatriptan may also prove effective, although the proportion of patients obtaining adequate relief is decreased and the latency to that relief is greater.

In 1 well-controlled study where placebo (n = 62) was compared with 6 different doses of Imitrex Injection (n = 30 each group) in a single-attack, parallel-group design, the dose response relationship was found to be as shown in Table 1.

Table 1. Dose Response Relationship for Efficacy

IMITREX Dose (mg)	% Patients With Reliefa at 10 Minutes	% Patients With Reliefa at 30 Minutes	% Patients With Reliefa at 1 Hour	% Patients With Reliefa at 2 Hours	Adverse Events Incidence (%)
Placebo	5	15	24	21	55
1	10	40	43	40	63
2	7	23	57	43	63
3	17	47	57	60	77
4	13	37	50	57	80
6	10	63	73	70	83
8	23	57	80	83	93

aRelief is defined as the reduction of moderate or severe pain to no or mild pain after dosing without use of rescue medication.

In 2 US well-controlled clinical trials in 1,104 migraine patients with moderate or severe migraine pain, the onset of relief was rapid (less than 10 minutes) with Imitrex Injection 6 mg. Headache relief, as evidenced by a reduction in pain from severe or moderately severe to mild or no headache, was achieved in 70% of the patients within 1 hour of a single 6-mg subcutaneous dose of Imitrex Injection. Headache relief was achieved in approximately 82% of patients within 2 hours, and 65% of all patients were pain free within 2 hours.

Table 2 shows the 1- and 2-hour efficacy results for Imitrex Injection 6 mg.

Table 2. Efficacy Data From US Phase III Trials

1-Hour Data	Study 1		Study 2
	Placebo (n = 190)	IMITREX 6 mg (n = 384)	Placebo (n = 180)	IMITREX 6 mg (n = 350)
Patients with pain relief (grade 0/1)	18%	70%a	26%	70%a
Patients with no pain	5%	48%a	13%	49%
Patients without nausea	48%	73%a	50%	73%a
Patients without photophobia	23%	56%a	25%	58%*
Patients with little or no clinical disabilityb	34%	76%a	34%	76%a
2-Hour Data	Study 1		Study 2
	Placeboc	IMITREX 6 mgd	Placeboc	IMITREX 6 mgd
Patients with pain relief (grade 0/1)	31%	81%a	39%	82%a
Patients with no pain	11%	63%a	19%	65%a
Patients without nausea	56%	82%a	63%	81%a
Patients without photophobia	31%	72%a	35%	71%a
Patients with little or no clinical disabilityb	42%	85%a	49%	84%a

ap<0.05 versus placebo.

bA successful outcome in terms of clinical disability was defined prospectively as ability to work mildly impaired or ability to work and function normally.

cIncludes patients that may have received an additional placebo injection 1 hour after the initial injection.

dIncludes patients that may have received an additional 6 mg of Imitrex Injection 1 hour after the initial injection.

Imitrex Injection also relieved photophobia, phonophobia (sound sensitivity), nausea, and vomiting associated with migraine attacks. Similar efficacy was seen when patients self-administered Imitrex Injection using an autoinjector.

The efficacy of Imitrex Injection is unaffected by whether or not migraine is associated with aura, duration of attack, gender or age of the patient, or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers).

Cluster Headache

The efficacy of Imitrex Injection in the acute treatment of cluster headache was demonstrated in 2 randomized, double-blind, placebo-controlled, 2-period crossover trials. Patients age 21 to 65 were enrolled and were instructed to treat a moderate to very severe headache within 10 minutes of onset. Headache relief was defined as a reduction in headache severity to mild or no pain. In both trials, the proportion of individuals gaining relief at 10 or 15 minutes was significantly greater among patients receiving 6 mg of Imitrex Injection compared with those who received placebo (see Table 3). One study evaluated a 12-mg dose; there was no statistically significant difference in outcome between patients randomized to the 6- and 12-mg doses.

Table 3. Efficacy Data From the Pivotal Cluster Headache Studies

	Study 1		Study 2
	Placebo (n = 39)	IMITREX 6 mg (n = 39)	Placebo (n = 88)	IMITREX 6 mg (n = 92)
Patients with pain relief (no/mild)
5 minutes postinjection	8%	21%	7%	23%a
10 minutes postinjection	10%	49%a	25%	49%
15 minutes postinjection	26%	74%a	35%	75%a

ap<0.05.

(n = Number of headaches treated.)

The Kaplan-Meier (product limit) Survivorship Plot (Figure 1) provides an estimate of the cumulative probability of a patient with a cluster headache obtaining relief after being treated with either sumatriptan or placebo.

Figure 1. Time to Relief From Time of Injectiona

aPatients taking rescue medication were censored at 15 minutes.

The plot was constructed with data from patients who either experienced relief or did not require (request) rescue medication within a period of 2 hours following treatment. As a consequence, the data in the plot are derived from only a subset of the 258 headaches treated (rescue medication was required in 52 of the 127 placebo-treated headaches and 18 of the 131 sumatriptan-treated headaches).

Other data suggest that treatment with sumatriptan is not associated with an increase in early recurrence of headache and has little effect on the incidence of latter-occurring headaches (i.e., those occurring after 2, but before 18 or 24 hours).

Indications and Usage for Imitrex Injection

Imitrex Injection is indicated for 1) the acute treatment of migraine attacks with or without aura and 2) the acute treatment of cluster headache episodes.

Imitrex Injection is not for use in the management of hemiplegic or basilar migraine (see CONTRAINDICATIONS).

Contraindications

Imitrex Injection should not be given intravenously because of its potential to cause coronary vasospasm.

Imitrex Injection should not be given to patients with history, symptoms, or signs of ischemic cardiac, cerebrovascular, or peripheral vascular syndromes. In addition, patients with other significant underlying cardiovascular diseases should not receive Imitrex Injection. Ischemic cardiac syndromes include, but are not limited to, angina pectoris of any type (e.g., stable angina of effort, vasospastic forms of angina such as the Prinzmetal variant), all forms of myocardial infarction, and silent myocardial ischemia. Cerebrovascular syndromes include, but are not limited to, strokes of any type as well as transient ischemic attacks. Peripheral vascular disease includes, but is not limited to, ischemic bowel disease (see WARNINGS: Other Vasospasm-Related Events and WARNINGS: Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events).

Because Imitrex Injection may increase blood pressure, it should not be given to patients with uncontrolled hypertension.

Imitrex Injection and any ergotamine-containing or ergot-type medication (like dihydroergotamine or methysergide) should not be used within 24 hours of each other, nor should Imitrex Injection and another 5-HT1 agonist.

Imitrex Injection should not be administered to patients with hemiplegic or basilar migraine.

Imitrex Injection is contraindicated in patients with hypersensitivity to sumatriptan or any of its components.

Imitrex Injection is contraindicated in patients with severe hepatic impairment.

Warnings

Imitrex Injection should only be used where a clear diagnosis of migraine or cluster headache has been established. The prescriber should be aware that cluster headache patients often possess one or more predictive risk factors for coronary artery disease (CAD).

Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events

Sumatriptan should not be given to patients with documented ischemic or vasospastic CAD (see CONTRAINDICATIONS). It is strongly recommended that sumatriptan not be given to patients in whom unrecognized CAD is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, male over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient’s medical history or electrocardiographic investigations reveal findings indicative of or consistent with coronary artery vasospasm or myocardial ischemia, sumatriptan should not be administered (see CONTRAINDICATIONS).

For patients with risk factors predictive of CAD who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of sumatriptan injection take place in the setting of a physician’s office or similar medically staffed and equipped facility. Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should be given to obtaining an electrocardiogram (ECG) during the interval immediately following the first dose in these patients with risk factors.

It is recommended that patients who are intermittent long-term users of sumatriptan and who have or acquire risk factors predictive of CAD, as described above, undergo periodic interval cardiovascular evaluation as they continue to use sumatriptan. In considering this recommendation for periodic cardiovascular evaluation, it is noted that patients with cluster headache are predominantly male and over 40 years of age, which are risk factors for CAD.

The systematic approach described above is intended to reduce the likelihood that patients with unrecognized cardiovascular disease will be inadvertently exposed to sumatriptan.

Drug-Associated Cardiac Events and Fatalities

Serious adverse cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and death have been reported within a few hours following the administration of Imitrex Injection or IMITREX® (sumatriptan succinate) Tablets. Considering the extent of use of sumatriptan in patients with migraine, the incidence of these events is extremely low.

The fact that sumatriptan can cause coronary vasospasm, that some of these events have occurred in patients with no prior cardiac disease history and with documented absence of CAD, and the close proximity of the events to sumatriptan use support the conclusion that some of these cases were caused by the drug. In many cases, however, where there has been known underlying CAD, the relationship is uncertain.

Premarketing Experience With Sumatriptan: Among the more than 1,900 patients with migraine who participated in premarketing controlled clinical trials of subcutaneous sumatriptan, there were 8 patients who sustained clinical events during or shortly after receiving sumatriptan that may have reflected coronary artery vasospasm. Six of these 8 patients had ECG changes consistent with transient ischemia, but without accompanying clinical symptoms or signs. Of these 8 patients, 4 had either findings suggestive of CAD or risk factors predictive of CAD prior to study enrollment.

Of 6,348 patients with migraine who participated in premarketing controlled and uncontrolled clinical trials of oral sumatriptan, 2 experienced clinical adverse events shortly after receiving oral sumatriptan that may have reflected coronary vasospasm. Neither of these adverse events was associated with a serious clinical outcome.

Among approximately 4,000 patients with migraine who participated in premarketing controlled and uncontrolled clinical trials of sumatriptan nasal spray, 1 patient experienced an asymptomatic subendocardial infarction possibly subsequent to a coronary vasospastic event.

Postmarketing Experience With Sumatriptan: Serious cardiovascular events, some resulting in death, have been reported in association with the use of Imitrex Injection or IMITREX Tablets. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to determine definitively the proportion of the reported cases that were actually caused by sumatriptan or to reliably assess causation in individual cases. On clinical grounds, the longer the latency between the administration of IMITREX and the onset of the clinical event, the less likely the association is to be causative. Accordingly, interest has focused on events beginning within 1 hour of the administration of IMITREX.

Cardiac events that have been observed to have onset within 1 hour of sumatriptan administration include: coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia and ventricular fibrillation, cardiac arrest, and death.

Some of these events occurred in patients who had no findings of CAD and appear to represent consequences of coronary artery vasospasm. However, among domestic reports of serious cardiac events within 1 hour of sumatriptan administration, the majority had risk factors predictive of CAD and the presence of significant underlying CAD was established in most cases (see CONTRAINDICATIONS).

Drug-Associated Cerebrovascular Events and Fatalities

Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with oral or subcutaneous sumatriptan, and some have resulted in fatalities. The relationship of sumatriptan to these events is uncertain. In a number of cases, it appears possible that the cerebrovascular events were primary, sumatriptan having been administered in the incorrect belief the symptoms experienced were a consequence of migraine when they were not. As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions. It should also be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., cerebrovascular accident, transient ischemic attack).

Other Vasospasm-Related Events

Sumatriptan may cause vasospastic reactions other than coronary artery vasospasm. Both peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea have been reported. Very rare reports of transient and permanent blindness and significant partial vision loss have been reported with the use of sumatriptan. Visual disorders may also be part of a migraine attack.

Serotonin Syndrome

The development of a potentially life-threatening serotonin syndrome may occur with triptans, including treatment with IMITREX, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram) or SNRI (e.g., venlafaxine, duloxetine) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Increase in Blood Pressure

Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions in patients with and without a history of hypertension. Sumatriptan is contraindicated in patients with uncontrolled hypertension (see CONTRAINDICATIONS). Sumatriptan should be administered with caution to patients with controlled hypertension as transient increases in blood pressure and peripheral vascular resistance have been observed in a small proportion of patients.

Concomitant Drug Use

In patients taking MAO-A inhibitors, sumatriptan plasma levels attained after treatment with recommended doses are nearly double those obtained under other conditions. Accordingly, the coadministration of sumatriptan and an MAO-A inhibitor is not generally recommended. If such therapy is clinically warranted, however, suitable dose adjustment and appropriate observation of the patient is advised (see CLINICAL PHARMACOLOGY: Drug Interactions: Monoamine Oxidase Inhibitors).

Use in Women of Childbearing Potential

See PRECAUTIONS: Pregnancy.

Hypersensitivity

Hypersensitivity (anaphylaxis/anaphylactoid) reactions have occurred on rare occasions in patients receiving sumatriptan. Such reactions can be life threatening or fatal. In general, hypersensitivity reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens (see CONTRAINDICATIONS).

Precautions

General

Chest, jaw, or neck tightness is relatively common after administration of Imitrex Injection. Chest discomfort and jaw or neck tightness have been reported following use of IMITREX Tablets and have also been reported infrequently following the administration of IMITREX® (sumatriptan) Nasal Spray. Only rarely have these symptoms been associated with ischemic ECG changes. However, because sumatriptan may cause coronary artery vasospasm, patients who experience signs or symptoms suggestive of angina following sumatriptan should be evaluated for the presence of CAD or a predisposition to Prinzmetal variant angina before receiving additional doses of sumatriptan and should be monitored electrocardiographically if dosing is resumed and similar symptoms recur. Similarly, patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud syndrome, following sumatriptan should be evaluated for atherosclerosis or predisposition to vasospasm (see WARNINGS: Risk of Myocardial Ischemia and/or Infarction and Other Adverse Cardiac Events and WARNINGS: Other Vasospasm-Related Events).

IMITREX should also be administered with caution to patients with diseases that may alter the absorption, metabolism, or excretion of drugs, such as impaired hepatic or renal function.

There have been rare reports of seizure following administration of sumatriptan. Sumatriptan should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.

Care should be taken to exclude other potentially serious neurologic conditions before treating headache in patients not previously diagnosed with migraine or cluster headache or who experience a headache that is atypical for them. There have been rare reports where patients received sumatriptan for severe headaches that were subsequently shown to have been secondary to an evolving neurologic lesion (see WARNINGS: Drug-Associated Cerebrovascular Events and Fatalities). For a given attack, if a patient does not respond to the first dose of sumatriptan, the diagnosis of migraine or cluster headache should be reconsidered before administration of a second dose.

Overuse of acute migraine treatments has been associated with the exacerbation of headache (medication overuse headache) in susceptible patients. Withdrawal of the treatment may be necessary.

Binding to Melanin-Containing Tissues

Because sumatriptan binds to melanin, it could accumulate in melanin-rich tissues (such as the eye) over time. This raises the possibility that sumatriptan could cause toxicity in these tissues after extended use. However, no effects on the retina related to treatment with sumatriptan were noted in any of the toxicity studies. Although no systematic monitoring of ophthalmologic function was undertaken in clinical trials, and no specific recommendations for ophthalmologic monitoring are offered, prescribers should be aware of the possibility of long-term ophthalmologic effects (see CLINICAL PHARMACOLOGY: Melanin Binding).

Corneal Opacities

Sumatriptan causes corneal opacities and defects in the corneal epithelium in dogs; this raises the possibility that these changes may occur in humans. While patients were not systematically evaluated for these changes in clinical trials, and no specific recommendations for monitoring are being offered, prescribers should be aware of the possibility of these changes (see CLINICAL PHARMACOLOGY: Corneal Opacities).

Patients who are advised to self-administer Imitrex Injection in medically unsupervised situations should receive instruction on the proper use of the product from the physician or other suitably qualified health care professional prior to doing so for the first time.

Information for Patients

With the autoinjector, the needle penetrates approximately 1/4 of an inch (5 to 6 mm). Since the injection is intended to be given subcutaneously, intramuscular or intravascular delivery should be avoided. Patients should be directed to use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle. See PATIENT INFORMATION at the end of this labeling for the text of the separate leaflet provided for patients.

Patients should be cautioned about the risk of serotonin syndrome with the use of sumatriptan or other triptans, especially during combined use with SSRIs or SNRIs.

Laboratory Tests

No specific laboratory tests are recommended for monitoring patients prior to and/or after treatment with sumatriptan.

Drug Interactions

Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome: Cases of life-threatening serotonin syndrome have been reported during combined use of SSRIs or SNRIs and triptans (see WARNINGS).

Migraine Prophylactic Medications: There is no evidence that concomitant use of migraine prophylactic medications has any effect on the efficacy of sumatriptan. In 2 Phase III trials in the US, a retrospective analysis of 282 patients who had been using prophylactic drugs (verapamil n = 63, amitriptyline n = 57, propranolol n = 94, for 45 other drugs n = 123) were compared with those who had not used prophylaxis (N = 452). There were no differences in relief rates at 60 minutes postdose for Imitrex Injection, whether or not prophylactic medications were used.

Ergot-Containing Drugs: Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because there is a theoretical basis that these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and sumatriptan within 24 hours of each other should be avoided (see CONTRAINDICATIONS).

Monoamine Oxidase-A Inhibitors: MAO-A inhibitors reduce sumatriptan clearance, significantly increasing systemic exposure. Therefore, the use of sumatriptan in patients receiving MAO-A inhibitors is not ordinarily recommended. If the clinical situation warrants the combined use of sumatriptan and an MAOI, the dose of sumatriptan employed should be reduced (see CLINICAL PHARMACOLOGY: Drug Interactions: Monoamine Oxidase Inhibitors and WARNINGS: Concomitant Drug Use).

Drug/Laboratory Test Interactions

IMITREX is not known to interfere with commonly employed clinical laboratory tests.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In carcinogenicity studies, rats and mice were given sumatriptan by oral gavage (rats: 104 weeks) or drinking water (mice: 78 weeks). Average exposures achieved in mice receiving the highest dose were approximately 110 times the exposure attained in humans after the maximum recommended single dose of 6 mg. The highest dose to rats was approximately 260 times the maximum single dose of 6 mg on a mg/m2 basis. There was no evidence of an increase in tumors in either species related to sumatriptan administration.

Sumatriptan was not mutagenic in the presence or absence of metabolic activation when tested in 2 gene mutation assays (the Ames test and the in vitro mammalian Chinese hamster V79/HGPRT assay). In 2 cytogenetics assays (the in vitro human lymphocyte assay and the in vivo rat micronucleus assay) sumatriptan was not associated with clastogenic activity.

A fertility study (Segment I) by the subcutaneous route, during which male and female rats were dosed daily with sumatriptan prior to and throughout the mating period, has shown no evidence of impaired fertility at doses equivalent to approximately 100 times the maximum recommended single human dose of 6 mg on a mg/m2 basis. However, following oral administration, a treatment-related decrease in fertility, secondary to a decrease in mating, was seen for rats treated with 50 and 500 mg/kg/day. The no-effect dose for this finding was approximately 8 times the maximum recommended single human dose of 6 mg on a mg/m2 basis. It is not clear whether the problem is associated with the treatment of males or females or both.

Pregnancy

Pregnancy Category C. Sumatriptan has been shown to be embryolethal in rabbits when given daily at a dose approximately equivalent to the maximum recommended single human subcutaneous dose of 6 mg on a mg/m2 basis. There is no evidence that establishes that sumatriptan is a human teratogen; however, there are no adequate and well-controlled studies in pregnant women. Imitrex Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In assessing this information, the following additional findings should be considered.

Embryolethality: When given intravenously to pregnant rabbits daily throughout the period of organogenesis, sumatriptan caused embryolethality at doses at or close to those producing maternal toxicity. The mechanism of the embryolethality is not known. These doses were approximately equivalent to the maximum single human dose of 6 mg on a mg/m2 basis.

The intravenous administration of sumatriptan to pregnant rats throughout organogenesis at doses that are approximately 20 times a human dose of 6 mg on a mg/m2 basis, did not cause embryolethality. Additionally, in a study of pregnant rats given subcutaneous sumatriptan daily prior to and throughout pregnancy, there was no evidence of increased embryo/fetal lethality.

Teratogenicity: Term fetuses from Dutch Stride rabbits treated during organogenesis with oral sumatriptan exhibited an increased incidence of cervicothoracic vascular and skeletal abnormalities. The functional significance of these abnormalities is not known. The highest no-effect dose for these effects was 15 mg/kg/day, approximately 50 times the maximum single dose of 6 mg on a mg/m2 basis.

In a study in rats dosed daily with subcutaneous sumatriptan prior to and throughout pregnancy, there was no evidence of teratogenicity.

Pregnancy Registry: To monitor fetal outcomes of pregnant women exposed to IMITREX, GlaxoSmithKline maintains a Sumatriptan Pregnancy Registry. Physicians are encouraged to register patients by calling (800) 336-2176.

Nursing Mothers

Sumatriptan is excreted in human breast milk following subcutaneous administration. Infant exposure to sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with Imitrex Injection.

Pediatric Use

Acticin Cream

Pronunciation: per-METH-rin
Generic Name: Permethrin
Brand Name: Examples include Acticin and Elimite

Acticin Cream is used for:

Treating scabies.

Acticin Cream is a scabicide. It works by killing the scabies mite (Sarcoptes scabiei).

Do NOT use Acticin Cream if:

• you are allergic to any ingredient in Acticin Cream

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

Before using Acticin Cream:

Some medical conditions may interact with Acticin Cream. 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

Some MEDICINES MAY INTERACT with Acticin Cream. Because little, if any, of Acticin Cream is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Acticin Cream 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 Acticin Cream:

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

• Thoroughly massage into the skin from the head to the soles of the feet. It is not necessary to put the medicine on the scalp except in children and older patients.


• Remove the medicine by washing after 8 to 14 hours.


• You may experience itching after treatment. This is not a sign of treatment failure. However if living mites are seen after 14 days, retreatment is necessary.


• If you miss a dose of Acticin Cream, use it as soon as you remember. Continue to use it as directed by your doctor.

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

Important safety information:

• Acticin Cream is for external use only. Do not use it near the eyes or allow it to come into contact with the inside of the nose, mouth, or genitals. Irritation may occur if Acticin Cream comes into contact with these areas. If Acticin Cream gets in your eyes, flush with water immediately.


• Acticin Cream should not be used in CHILDREN younger than 2 months old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Acticin Cream while you are pregnant. It is not known if Acticin Cream is found in breast milk after topical use. Do not breast-feed while using Acticin Cream.

Possible side effects of Acticin Cream:

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:

Itching; mild burning or stinging; redness; swelling.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue).

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

See also: Acticin 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. Acticin Cream may be harmful if swallowed. Symptoms may include dizziness; headache; loss of appetite; loss of consciousness; seizures; vomiting; weakness.

Proper storage of Acticin Cream:

Store Acticin Cream at room temperature, between 59 and 77 degrees F (15 and 25 degrees C). Store away from heat, moisture, and light. Keep Acticin Cream out of the reach of children and away from pets.

General information:

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


• Acticin Cream 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 Acticin Cream. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Acticin resources

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

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