Topamax

Generic Name: Topiramate
Class: Anticonvulsants, Miscellaneous
VA Class: CN400
Chemical Name: 2,3:4,5-bis-O-(1-Methylethylidene)-β-d-fructopyranose sulfamate
Molecular Formula: C₁₂H₂₁NO₈S
CAS Number: 97240-79-4

Special Alerts:

[Posted 03/04/2011] ISSUE: FDA notified healthcare professionals and patients of an increased risk of development of cleft lip and/or cleft palate (oral clefts) in infants born to women treated with topiramate (Topamax) during pregnancy. Because of new human data that show an increased risk for oral clefts, topiramate is being placed in Pregnancy Category D. Pregnancy Category D means there is positive evidence of human fetal risk based on human data but the potential benefits from use of the drug in pregnant women may be acceptable in certain situations despite its risks. The patient medication guide and prescribing information for Topamax and generic topiramate will be updated with the new information.

BACKGROUND: Topiramate is an anticonvulsant medication approved for use alone or with other medications to treat patients with epilepsy who have certain types of seizures. Topiramate is also approved for use to prevent migraine headaches. The new data was from the North American Antiepileptic Drug (NAAED) Pregnancy Registry.

RECOMMENDATION: Before starting topiramate, pregnant women and women of childbearing potential should discuss other treatment options with their health care professional. Women taking topiramate should tell their health care professional immediately if they are planning to or become pregnant. Patients taking topiramate should not stop taking it unless told to do so by their health care professional. Women who become pregnant while taking topiramate should talk to their health care professional about registering with the North American Antiepileptic Drug Pregnancy Registry, a group that collects information about outcomes in infants born to women treated with antiepileptic drugs during pregnancy. For more information visit the FDA website at: and .

[UPDATE 05/05/2009] FDA notified healthcare professionals that it approved updated labeling for antiepileptic drugs used to treat epilepsy, psychiatric disorders, and other conditions (e.g., migraine and neuropathic pain syndromes). FDA also required development of a medication guide, to be issued to patients each time the product is dispensed. Since issuing safety alerts on December 16, 2008 and January 31, 2008, FDA has been working with the manufacturers of drugs in this class to better understand the suicidality risk. Eleven antiepileptic drugs were included in a pooled analysis of placebo-controlled clinical studies in which these drugs were used to treat epilepsy as well as psychiatric disorders and other conditions. The increased risk of suicidal thoughts or behavior was generally consistent among the eleven drugs, with varying mechanisms of action and across a range of indications. This observation suggests that the risk applies to all antiepileptic drugs used for any indication.

The drugs included in the analyses include (some of these drugs are also available in generic form):

• 
  

  Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)

  
  


• 
  

  Felbamate (marketed as Felbatol)

  
  


• 
  

  Gabapentin (marketed as Neurontin)

  
  


• 
  

  Lamotrigine (marketed as Lamictal)

  
  


• 
  

  Levetiracetam (marketed as Keppra)

  
  


• 
  

  Oxcarbazepine (marketed as Trileptal)

  
  


• 
  

  Pregabalin (marketed as Lyrica)

  
  


• 
  

  Tiagabine (marketed as Gabitril)

  
  


• 
  

  Topiramate (marketed as Topamax)

  
  


• 
  

  Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)

  
  


• 
  

  Zonisamide (marketed as Zonegran)

  
  

For more information visit the FDA website at: and .

[UPDATE 12/16/2008] The FDA has completed its analysis of reports of suicidality (suicidal behavior or ideation [thoughts]) from placebo-controlled clinical trials of drugs used to treat epilepsy, psychiatric disorders, and other conditions. Based on the outcome of this review, FDA is requiring that all manufacturers of drugs in this class include a Warning in their labeling and develop a Medication Guide to be provided to patients prescribed these drugs to inform them of the risks of suicidal thoughts or actions.

For more information visit the FDA website at: and .

[Posted 01/31/2008] FDA informed healthcare professionals that the Agency has analyzed reports of suicidality (suicidal behavior or ideation) from placebo-controlled clinical studies of eleven drugs used to treat epilepsy as well as psychiatric disorders, and other conditions. In the FDA’s analysis, patients receiving antiepileptic drugs had approximately twice the risk of suicidal behavior or ideation (0.43%) compared to patients receiving placebo (0.22%). The increased risk of suicidal behavior and suicidal ideation was observed as early as one week after starting the antiepileptic drug and continued through 24 weeks. The results were generally consistent among the eleven drugs. The relative risk for suicidality was higher in patients with epilepsy compared to patients who were given one of the drugs in the class for psychiatric or other conditions.

Healthcare professionals should closely monitor all patients currently taking or starting any antiepileptic drug for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.

The drugs included in the analyses include (some of these drugs are also available in generic form):

• 
  

  Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)

  
  


• 
  

  Felbamate (marketed as Felbatol)

  
  


• 
  

  Gabapentin (marketed as Neurontin)

  
  


• 
  

  Lamotrigine (marketed as Lamictal)

  
  


• 
  

  Levetiracetam (marketed as Keppra)

  
  


• 
  

  Oxcarbazepine (marketed as Trileptal)

  
  


• 
  

  Pregabalin (marketed as Lyrica)

  
  


• 
  

  Tiagabine (marketed as Gabitril)

  
  


• 
  

  Topiramate (marketed as Topamax)

  
  


• 
  

  Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)

  
  


• 
  

  Zonisamide (marketed as Zonegran)

  
  

Although the 11 drugs listed above were the ones included in the analysis, FDA expects that the increased risk of suicidality is shared by all antiepileptic drugs and anticipates that the class labeling changes will be applied broadly. For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for topiramate to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Anticonvulsant and antimigraine agent; sulfamate-substituted derivative ofd-fructose;^{1 2 3 4 5 17 18} differs structurally from other currently available anticonvulsant agents.^{1 2 3 4 5 17 18}

Uses for Topamax

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Seizure Disorders

Management (in combination with other anticonvulsants) of partial seizures in adults and children 2–16 years of age.^{1 2 4 5 6 7 8 9 10 22 25 29 30 31 32 33 34 37 38}

Management (in combination with other anticonvulsants) of primary generalized tonic-clonic seizures in adults and children 2–16 years of age.^{1 30 31 39}

Management (in combination with other anticonvulsants) of seizures associated with Lennox-Gastaut syndrome in adults and children ≥2 years of age.¹

Migraine Prophylaxis

Prophylaxis of migraine headache in adults.¹

Efficacy in the acute management (i.e., abortive therapy) of migraine headache not established.¹

Topamax Dosage and Administration

General

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Monitoring of plasma topiramate concentrations is not necessary when topiramate is added to an existing anticonvulsant regimen; however, addition of topiramate to phenytoin therapy may require adjustment of phenytoin dosage.^{1 2 4}

  
  


• 
  

  Addition or withdrawal of phenytoin and/or carbamazepine during adjunctive therapy may require adjustment of topiramate dosage.^{1 2 4 11} (See Specific Drugs under Interactions.)

  
  


• 
  

  Adjust dosage carefully and individualize according to patient response and tolerance.^{1 2 4}

  
  


• 
  

  Too rapid titration (e.g., over 3–6 weeks) to achieve target dosage and/or excessive target dosage may contribute to a higher incidence of adverse effects.^{1 2 4}

  
  

Administration

Oral Administration

Administer orally without regard to meals.^{1 2 4}

Capsule/sprinkle formulation is bioequivalent to immediate-release tablet and may be substituted as a therapeutic equivalent.¹

Capsules

Swallow capsules whole.¹

Alternatively, open capsule and sprinkle entire contents on soft food (e.g., applesauce, custard, ice cream, oatmeal, yogurt, pudding); swallow immediately without chewing.¹

Drinking fluids immediately may help to ensure that all of the mixture is swallowed.¹

Do not store the sprinkle/food mixture for use at a later time.¹

Tablets

Tablets preferably should be swallowed intact and not broken or chewed because of the bitter taste.^{1 2 4 24}

If patient has difficulty in swallowing tablets, the tablets may be crushed and mixed with oatmeal or applesauce; use immediately since stability cannot be ensured.²⁴

If tablets are broken, use immediately since stability beyond a brief period cannot be ensured.²⁴ Discard any unused portion.²⁴

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Pediatric Patients

Seizure Disorders

Partial Seizures, Primary Generalized Tonic-Clonic Seizures, or Seizures Associated with Lennox-Gastaut Syndrome

Oral

Initially, 25 mg (or less based on a range of 1–3 mg/kg daily) given nightly for the first week in children 2–16 years of age.¹ Increase dosage at 1- or 2-week intervals in increments of 1–3 mg/kg daily, administered in 2 divided doses, to achieve optimal clinical response.¹

Maintenance, 5–9 mg/kg daily in 2 divided doses.¹

Alternatively, some clinicians recommend an initial dosage of 0.5–1 mg/kg daily, with slow titration (in increments of 1–3 mg/kg every other week or in increments of 0.5–1 mg/kg per week) to obtain optimal efficacy with minimal adverse effects.^{33 36}

Adults

Seizure Disorders

Partial Seizures

Oral

Initially, 25–50 mg daily.^{1 2 4 24} Increase dosage at weekly intervals in increments of 25–50 mg to achieve optimal clinical response.^{1 2 4 24}

Recommended maintenance dosage is 200–400 mg daily, administered in 2 equally divided doses (morning and evening).^{1 2 4 24}

Titration in increments of 25 mg/week is associated with a lower incidence of cognitive and psychiatric adverse effects and lower discontinuance rates^{24 41} but may delay the time to reach an effective dosage.^{1 24 41}

Dosages >400 mg daily generally have not produced substantial additional improvement, but may improve seizure control in some patients, if tolerated.^{1 2 4 7 24 25}

Primary Generalized Tonic-Clonic Seizures

Oral

Initially, 25–50 mg daily.^{1 2 4 24} Increase dosage at weekly intervals in increments of 25–50 mg to achieve optimal clinical response.^{1 2 4 24}

Recommended maintenance dosage is 400 mg daily, administered in 2 equally divided doses (morning and evening).^{1 2 4 24}

Titration in increments of 25 mg/week is associated with a lower incidence of cognitive and psychiatric adverse effects and lower discontinuance rates^{24 41} but may delay the time to reach an effective dosage.^{1 24 41}

Seizures Associated with Lennox-Gastaut Syndrome

Oral

Manufacturer makes no specific dosage recommendations; in 1 controlled trial, topiramate was initiated at dosage of 1 mg/kg and titrated over 2 weeks to target dosage of approximately 6 mg/kg daily.^{1 24}

Migraine Prophylaxis

Oral

Recommended total daily dosage is 100 mg, administered in 2 divided doses.¹ Titrate therapy using the following schedule in Table 1.

Table 1. Topiramate Dosage Titration Schedule for Migraine Prophylaxis in Adults

Week	Morning Dose	Evening Dose
1	None	25 mg
2	25 mg	25 mg
3	25 mg	50 mg
4	50 mg	50 mg

Titrate dosage based on clinical outcome.¹ Use longer intervals between dose adjustments if required.¹

Prescribing Limits

Adults

Seizure Disorders

Oral

Dosages >1.6 g daily in patients with seizure disorders have not been studied.^{1 2 4}

Special Populations

Hepatic Impairment

Clearance may be decreased; however, manufacturer makes no specific recommendations regarding dosage adjustment.¹

Renal Impairment

If Cl_cr is <70 mL/minute per 1.73 m², decrease daily adult dosage by 50%.^{1 2 4} Patients with renal impairment will require a longer time to reach steady state at each dosage level.^{1 2 4}

Patients undergoing hemodialysis may require a supplemental dose following dialysis session; base amount on duration of dialysis, clearance rate of dialysis system, and the patient’s effective renal clearance of topiramate.^{1 2 4}

Geriatric Patients

If Cl_cr <70 mL/minute per 1.73 m², dosage adjustment may be necessary.¹ (See Renal Impairment under Dosage and Administration.)

Cautions for Topamax

Contraindications

• 
  

  Known hypersensitivity to topiramate or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Metabolic Acidosis

Hyperchloremic, non-anion gap, metabolic acidosis reported.^{1 43} (See Pediatric Use under Cautions.) Possible hyperventilation, nonspecific symptoms (e.g., fatigue, anorexia), cardiac arrhythmias, or stupor.^{1 43} Generally occurs early in therapy but can occur at any time.^{1 43}

Potential for serious sequelae (e.g., nephrolithiasis, nephrocalcinosis, osteomalacia and/or osteoporosis with increased risk for fractures) resulting from chronic, untreated metabolic acidosis.^{1 43}

Measure serum bicarbonate concentrations at baseline and periodically during therapy.^{1 43}

If metabolic acidosis develops and persists, consider reducing dosage or discontinuing therapy (by gradually tapering dose).^{1 43} If therapy is continued in patient with persistent acidosis, consider alkali treatment.^{1 43}

Cognitive/Neuropsychiatric Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Confusion, psychomotor slowing, difficulty with concentration/attention, difficulty with memory, speech or language problems (e.g., word-finding difficulties), psychiatric/behavioral disturbances (e.g., depression, mood problems), somnolence, and fatigue associated with use in adults.¹

Psychomotor slowing, difficulty with concentration/attention, speech disorders/related speech problems, and language problems associated with use in children 2–16 years of age; incidence of these effects is lower in children than in adults.¹

Withdrawal Seizures

Discontinue drug gradually to minimize the potential for increased seizure frequency.¹

Ocular Effects

Acute myopia with secondary angle-closure glaucoma reported.¹ Symptoms (e.g., acute onset of decreased visual acuity and/or ocular pain) typically occur within 1 month of initiating therapy.¹

If adverse ocular signs or symptoms are detected, discontinue topiramate immediately and institute appropriate measures.¹

Oligohidrosis and Hyperthermia

Possible oligohidrosis and hyperthermia, particularly in pediatric patients; rarely may require hospitalization.^{1 42}

Monitor patients, particularly pediatric patients, closely for decreased sweating and increased body temperature, particularly in warm or hot weather.¹ Ensure proper hydration before and during exercise or exposure to warm temperatures.⁴²

Consider risk of hyperthermia when used concomitantly with other drugs that predispose to heat-related disorders.¹ (See Drugs Predisposing to Heat-related Disorders under Interactions.)

Sudden, Unexplained Deaths in Epilepsy

Higher incidence of sudden and unexplained deaths than would be expected in a healthy (nonepileptic) population; however, incidence is within range of estimates for patients with epilepsy or refractory epilepsy.¹

General Precautions

Hyperammonemia

Hyperammonemia, with or without encephalopathy, reported following concomitant use with valproic acid.¹

Manifestations of hyperammonemic encephalopathy include acute alterations in level of consciousness and/or cognitive function with lethargy or vomiting.¹ In most cases, manifestations abated following discontinuance of either topiramate or valproic acid.¹

If unexplained lethargy, vomiting, or changes in mental status occur, consider possibility of hyperammonemic encephalopathy and measure ammonia concentration.¹

Kidney Stones

Increased incidence (1.5%) of kidney stone formation in clinical trials in adults; incidence higher in men than women.¹ Kidney stones also reported in children 2–16 years of age.¹

Avoid use in patients receiving other carbonic anhydrase inhibitors and in those on ketogenic diet.¹

Maintain adequate fluid intake to decrease stone formation.¹

Paresthesia

Common adverse effect; often associated with other carbonic anhydrase inhibitors.¹

Possible Prescribing and Dispensing Errors

Ensure accuracy of prescription; similarity in spelling between Topamax (topiramate) and Toprol-XL (a trade name for metoprolol succinate, a β-adrenergic blocking agent) may result in errors.^{47 48 49 50} These medication errors have been associated with serious adverse events sometimes requiring hospitalization as a result of either lack of the intended medication (e.g., seizure or hypertension recurrence) or exposure to the wrong drug (e.g., bradycardia in a patient erroneously receiving metoprolol).^{47 48 49 50}

Specific Populations

Pregnancy

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Category C.¹

Lactation

Distributed into milk in rats; limited data suggest that drug may be distributed extensively into milk in humans.¹ Use only if potential benefits outweigh the risks.¹

Pediatric Use

Safety and efficacy for management of seizure disorders not established in children <2 years of age.^{1 2} Safety and efficacy for migraine prophylaxis not established in pediatric patients.¹

Hyperchloremic, non-anion gap, metabolic acidosis reported.^{1 43} (See Metabolic Acidosis under Cautions.)

Decreases in serum bicarbonate concentrations reported in 67 or 10% of pediatric patients receiving topiramate (approximately 6 mg/kg daily) or placebo, respectively.^{1 43}

Cases of moderately severe metabolic acidosis reported in infants as young as 5 months of age, especially at dosages >5 mg/kg daily.¹ Potential for serious sequelae (e.g., osteomalacia [rickets], reduced growth rates, decrease in maximal height achieved) resulting from chronic, untreated metabolic acidosis.^{1 43}

Measure serum bicarbonate concentrations at baseline and periodically during therapy.^{1 43}

Incidence of adverse nervous system effects appears to be lower in children than adults.¹

Oligohydrosis and hyperthermia typically reported in children.^{1 42} (See Oligohidrosis and Hyperthermia under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.¹

Clearance may be decreased in patients with reduced renal function.^{1 2} (See Special Populations under Pharmacokinetics.) Monitor renal function.¹

Dosage adjustment may be necessary in geriatric patients with impaired renal function.¹ (See Special Populations under Dosage and Administration.)

Hepatic Impairment

Clearance may be decreased; use with caution.¹

Renal Impairment

Clearance decreased; dosage adjustment recommended for adults.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Adults receiving dosages of 50–200 mg daily (for migraine prophylaxis): paresthesia, fatigue, infection, taste perversion, nausea, anorexia, diarrhea, dizziness, weight loss, somnolence, difficulty with memory, difficulty with concentration/attention, sinusitis.¹

Adults receiving dosages of 200–400 mg daily (for management of seizure disorders): somnolence, dizziness, ataxia, speech disorders and related speech problems, psychomotor slowing, abnormal vision, difficulty with memory, paresthesia, diplopia.¹

Adults receiving dosages of 200–1000 mg daily (for management of seizure disorders): fatigue, nervousness, difficulty with concentration or attention, confusion, depression, anorexia, language problems, anxiety, mood problems, weight loss.¹

Children 2–16 years of age receiving dosages of 5–9 mg/kg daily (for management of seizure disorders): fatigue, somnolence, anorexia, nervousness, difficulty with concentration/attention, difficulty with memory, aggressive reaction, weight loss.¹

Interactions for Topamax

Does not inhibit CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, or 3A4/5.¹

Drugs Predisposing to Heat-related Disorders

Potential pharmacologic interaction (increased risk of hyperthermia) with drugs that predispose to heat-related disorders (e.g., carbonic anhydrase inhibitors, drugs with anticholinergic activity); use with caution.¹

Specific Drugs

Drug	Interaction	Comments
Amitriptyline	Increased plasma amitriptyline concentrations1	Adjust amitriptyline dosage based on patient’s clinical response, not on plasma amitriptyline concentrations1
Carbamazepine	Decreased plasma concentrations of topiramate1
Carbonic anhydrase inhibitors (e.g., acetazolamide, dichlorphenamide)	Possible increased risk of kidney stone formation; possible increased risk of hyperthermia1	Avoid concomitant use1
CNS depressants (including alcohol)	Enhanced CNS depression1	Use with extreme caution1
Digoxin	Possible decrease in serum digoxin concentrations1	Clinical significance unknown1
Dihydroergotamine	Pharmacokinetic interaction unlikely1
Haloperidol	No effect on pharmacokinetics of haloperidol1
Lamotrigine	Increased plasma topiramate concentrations1
Lithium	Decreased plasma lithium concentrations1
Metformin	Possible increase in plasma metformin concentrations;1 possible decrease in topiramate clearance1	Clinical significance unknown; monitor blood glucose control carefully when topiramate is added or discontinued in patients receiving metformin1
Oral contraceptives	Decrease in ethinyl estradiol concentrations reported in patients also receiving valproic acid, resulting in potential decrease in oral contraceptive efficacy and possible breakthrough bleeding 1
Phenytoin	Possible increase in serum phenytoin concentrations (generally in those receiving twice-daily phenytoin regimen); decreased plasma topiramate concentrations1
Propranolol	Pharmacokinetic interaction unlikely1
Risperidone	Decreased plasma risperidone concentrations1	Closely monitor clinical response1
Sumatriptan	No effect on pharmacokinetics of sumatriptan1
Valproic acid	Possible decrease in plasma concentrations of valproic acid and topiramate; possible hyperammonemia with or without encephalopathy (see Hyperammonemia under Cautions)1

Topamax Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration, with peak plasma concentrations achieved in about 2 hours.¹

Capsule/sprinkle formulation is bioequivalent to immediate-release tablet.¹

Food

Food does not affect bioavailability.^{1 46}

Distribution

Extent

Appears to cross the placenta.⁴⁵

Distributes into breast milk.⁴⁵

Plasma Protein Binding

Approximately 15–41%.¹ Fraction bound decreases with increasing plasma topiramate concentrations.¹

Elimination

Metabolism

Not extensively metabolized.¹ Six minor metabolites identified; none constitutes more than 5% of administered dose.¹

Elimination Route

Eliminated principally in urine as unchanged drug (approximately 70%).¹

Half-life

21 hours.^{1 46}

Special Populations

In pediatric patients, clearance is 50% higher, resulting in a shorter elimination half-life and lower plasma concentrations, relative to adults.¹

In geriatric patients with reduced renal function (Cl_cr reduced by 20% compared with younger adults), clearance was decreased.^{1 1}

In patients with hepatic impairment, clearance may be decreased; mechanism not fully understood.¹

In patients with moderate or severe renal impairment, clearance is reduced by 42 or 54%, respectively.¹ In patients undergoing hemodialysis, clearance is 4–6 times more rapid than in healthy individuals.^{1 2 4}

Stability

Storage

Oral

Capsules

Tight containers at ≤25° C.¹ Protect from moisture.¹

Tablets

Tight containers at 15–30° C.¹ Protect from moisture.¹

Actions

• 
  

  Mechanism of action is unknown; however, properties that may contribute to anticonvulsant and antimigraine activities, including blocking sodium channels, enhancing the inhibitory action of GABA by acting at some subtypes of GABA-A receptor, antagonizing AMPA/kainate subtype of glutamate receptor, and inhibiting carbonic anhydrase enzymes have been demonstrated in electrophysiologic and biochemical studies.^{1 2 4 15 16 17 18 19}

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Importance of taking topiramate exactly as prescribed.¹ Importance of not abruptly discontinuing therapy.¹

  
  


• 
  

  Importance of seeking immediate medical attention if blurred vision or periorbial pain develops.¹

  
  


• 
  

  Importance of maintaining adequate fluid intake, particularly in patients with predisposing factors, to minimize the risk of kidney stone formation.¹

  
  


• 
  

  Importance of considering an increase in food intake if patient is losing weight while taking topiramate.¹

  
  


• 
  

  Importance of reviewing the manufacturer’s patient information for instructions regarding administration of the capsule/sprinkle formulation.¹

  
  


• 
  

  Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.¹

  
  


• 
  

  Importance of monitoring for evidence of decreased sweating and increased body temperature, particularly in children during hot weather.^{1 42} Importance of proper hydration before and during exercise and exposure to warm temperatures.⁴²

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

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

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

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

Topiramate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	15 mg	Topamax Sprinkle (with povidone)	Ortho-McNeil
		25 mg	Topamax Sprinkle (with povidone)	Ortho-McNeil
	Tablets, film-coated	25 mg	Topamax	Ortho-McNeil
		50 mg	Topamax	Ortho-McNeil
		100 mg	Topamax	Ortho-McNeil
		200 mg	Topamax	Ortho-McNeil

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Topamax 100MG Tablets (JANSSEN): 60/$536.97 or 180/$1,589.92

Topamax 200MG Tablets (JANSSEN): 60/$626.00 or 180/$1,790.90

Topamax 25MG Tablets (JANSSEN): 60/$201.99 or 180/$574.97

Topamax 50MG Tablets (JANSSEN): 60/$382.01 or 180/$1,105.93

Topiramate 100MG Tablets (GLENMARK PHARMACEUTICALS): 60/$49.99 or 180/$129.98

Topiramate 15MG Sprinkle Capsules (TEVA PHARMACEUTICALS USA): 60/$70.99 or 180/$199.96

Topiramate 200MG Tablets (GLENMARK PHARMACEUTICALS): 60/$49.99 or 180/$129.98

Topiramate 25MG Sprinkle Capsules (TEVA PHARMACEUTICALS USA): 60/$85.99 or 180/$235.96

Topiramate 25MG Tablets (GLENMARK PHARMACEUTICALS): 60/$29.99 or 180/$79.97

Topiramate 50MG Tablets (GLENMARK PHARMACEUTICALS): 60/$39.99 or 180/$99.97

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 October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Ortho-McNeil. Topamax (topiramate) tablets and capsules prescribing information. Raritan, NJ: 2004 Aug.

2. Ortho-McNeil. Topamax (topiramate) clinical review. Raritan, NJ: undated.

3. Pugh CB, Garnett WR, Current issues in the treatment of epilepsy. Clin Pharm. 1991; 10:335-58.

4. Ortho-McNeil. Topamax (topiramate) tablets product information reference source. Raritan, NJ; 1997 Jan.

5. Rogawski MA, Porter RJ. Antiepileptic drugs: Pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacol Rev. 1990; 42:223-86. [IDIS 273932] [PubMed 2217531]

6. Faught E, Wilder BJ, Ramsay RE et al et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 200-, 400-, and 600-mg daily dosages. Neurology. 1996; 46:1684-90. [IDIS 368533] [PubMed 8649570]

7. Privitera M, Fincham R, Penry J et al et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1,000-mg daily dosages. Neurology. 1996; 46:1678-83. [IDIS 368532] [PubMed 8649569]

8. Sharief M, Viteri C, Ben-Menachem E et al. Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy. Epilepsy Res. 1996; 25:217-24. [PubMed 8956919]

9. Tassinari CA, Michelucci R, Chauvel P et al. Double-blind, placebo-controlled trial of topiramate (600 mg daily) for the treatment of refractory partial epilepsy. Epilepsia. 1996; 37:763-8. [IDIS 372665] [PubMed 8764816]

10. Ben-Menachem E, Henriksen O, Dam M et al. Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures. Epilepsia. 1996; 37:539-43. [IDIS 368333] [PubMed 8641230]

11. Bourgeois BFD. Drug interaction profile of topiramate. Epilepsia. 1996; 37(Suppl 2):S14-17.

12. McNamara JO. Drugs effective in the treatment of the epilepsies. In: Hardman JG, Limbird LE, Molinoff PB et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: Macmillan Publishing Company; 1996:461-86.

13. Membrane potentials and action potentials. In: Guyton AC. Textbook of medical physiology. 8th ed. Philadelphia: WB Saunders; 1991:51-66.

14. Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. 1994; 330:613-22. [IDIS 326265] [PubMed 7905600]

15. Dichter MA, Brodie MJ. New antiepileptic drugs. N Engl J Med. 1996; 334:1583-90. [IDIS 366423] [PubMed 8628341]

16. White HS, Brown SD, Wolf HH et al. The anticonvulsant topiramate potentiates GABA-evoked chloride current in mouse cortical neurons. Epilepsia. 1994; 35(Suppl 8):S67.

17. Shank RP, Gardocki JF, Vaught JL et al. Topiramate: preclinical evaluation of structurally novel anticonvulsant. Epilepsia. 1994; 35:450-60. [PubMed 8156972]

18. Edmonds HL Jr, Jiang YD, Zhang PY et al. Anticonvulsant activity of topiramate and phenytoin in a rat model of ischemia-induced epilepsy. Life Sci. 1996; 59:PL127-31. [PubMed 8761322]

19. White HS. Clinical significance of animal seizure models and mechanism of action studies of potential antiepileptic drugs. Epilepsia. 1997; 38(Suppl 1):S9-17. [PubMed 9092952]

20. Nakamura J, Tamura S, Kanda T et al. Inhibition by topiramate of seizures in spontaneously epileptic rats and DBA/2 mice. Eur J Pharmacol. 1994; 254:83-9. [PubMed 8206119]

21. Kanda T, Kurokawa M, Tamura S et al. Topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of spontaneously epileptic rats (SER). Life Sci. 1996; 59:1607-16. [PubMed 8913326]

22. Reife RA, Pledger GW. Topiramate as adjunctive therapy in refractory partial epilepsy: pooled analysis of data from five double-blind, placebo-controlled trials. Epilepsia. 1997; 38(Suppl 1):S31-3. [IDIS 384611] [PubMed 9092956]

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Tazorac

tazarotene

Dosage Form: gel
Tazorac®

(tazarotene) Gel 0.05%

(tazarotene) Gel 0.1%

FOR DERMATOLOGIC USE ONLY

NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE.

DESCRIPTION

Tazorac® Gel is a translucent, aqueous gel and contains the compound tazarotene, a member of the acetylenic class of retinoids. It is for topical dermatologic use only. The active ingredient is represented by the following structural formula:

Formula: C21H21NO2S

Molecular Weight: 351.46

Chemical Name: Ethyl 6-[(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate

Contains:

Active: Tazarotene 0.05% or 0.1% (w/w)

Preservative: Benzyl alcohol 1% (w/w)

Inactives: Ascorbic acid, butylated hydroxyanisole, butylated hydroxytoluene, carbomer homopolymer type B, edetate disodium, hexylene glycol, poloxamer 407, polyethylene glycol 400, polysorbate 40, purified water, and tromethamine.

CLINICAL PHARMACOLOGY

Tazarotene is a retinoid prodrug which is converted to its active form, the cognate carboxylic acid of tazarotene (AGN 190299), by rapid deesterification in animals and man. AGN 190299 (“tazarotenic acid”) binds to all three members of the retinoic acid receptor (RAR) family: RARα, RARβ, and RARγ but shows relative selectivity for RARβ, and RARγ and may modify gene expression. The clinical significance of these findings is unknown.

Psoriasis: The mechanism of tazarotene action in psoriasis is not defined. Topical tazarotene blocks induction of mouse epidermal ornithine decarboxylase (ODC) activity, which is associated with cell proliferation and hyperplasia. In cell culture and in vitro models of skin, tazarotene suppresses expression of MRP8, a marker of inflammation present in the epidermis of psoriasis patients at high levels. In human keratinocyte cultures, it inhibits cornified envelope formation, whose build-up is an element of the psoriatic scale. Tazarotene also induces the expression of a gene which may be a growth suppressor in human keratinocytes and which may inhibit epidermal hyperproliferation in treated plaques. However, the clinical significance of these findings is unknown.

Acne: The mechanism of tazarotene action in acne vulgaris is not defined. However, the basis of tazarotene's therapeutic effect in acne may be due to its anti-hyperproliferative, normalizing-of-differentiation and anti-inflammatory effects. Tazarotene inhibited corneocyte accumulation in rhino mouse skin and cross-linked envelope formation in cultured human keratinocytes. The clinical significance of these findings is unknown.

Pharmacokinetics: Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. Little parent compound could be detected in the plasma. Tazarotenic acid was highly bound to plasma proteins (greater than 99%). Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways. The half-life of tazarotenic acid was approximately 18 hours, following topical application of tazarotene to normal, acne or psoriatic skin.

The human in vivo studies described below were conducted with tazarotene gel applied topically at approximately 2 mg/cm2 and left on the skin for 10 to 12 hours. Both the peak plasma concentration (Cmax) and area under the plasma concentration time curve (AUC) refer to the active metabolite only.

Two single, topical dose studies were conducted using 14C-tazarotene gel. Systemic absorption, as determined from radioactivity in the excreta, was less than 1% of the applied dose (without occlusion) in six psoriatic patients and approximately 5% of the applied dose (under occlusion) in six healthy subjects. One non-radiolabeled single-dose study comparing the 0.05% gel to the 0.1% gel in healthy subjects indicated that the Cmax and AUC were 40% higher for the 0.1% gel.

After 7 days of topical dosing with measured doses of tazarotene 0.1% gel on 20% of the total body surface without occlusion in 24 healthy subjects, the Cmax for tazarotenic acid was 0.72 ± 0.58 ng/mL (mean ± SD) occurring 9 hours after the last dose, and the AUC0-24hr for tazarotenic acid was 10.1 ± 7.2 ng·hr/mL. Systemic absorption was 0.91 ± 0.67% of the applied dose.

In a 14-day study in five psoriatic patients, measured doses of tazarotene 0.1% gel were applied daily by nursing staff to involved skin without occlusion (8 to 18% of total body surface area; mean ± SD: 13 ± 5%). The Cmax for tazarotenic acid was 12.0 ± 7.6 ng/mL occurring 6 hours after the final dose, and the AUC0-24hr for tazarotenic acid was 105 ± 55 ng·hr/mL. Systemic absorption was 14.8 ± 7.6% of the applied dose. Extrapolation of these results to represent dosing on 20% of total body surface yielded estimates for tazarotenic acid with Cmax of 18.9 ± 10.6 ng/mL and AUC0-24hr of 172 ± 88 ng·hr/mL.

An in vitro percutaneous absorption study, using radiolabeled drug and freshly excised human skin or human cadaver skin, indicated that approximately 4 to 5% of the applied dose was in the stratum corneum (tazarotene: tazarotenic acid = 5:1) and 2 to 4% was in the viable epidermis-dermis layer (tazarotene: tazarotenic acid = 2:1) 24 hours after topical application of the gel.

Clinical Studies

Psoriasis: In two large vehicle-controlled clinical studies, tazarotene 0.05% and 0.1% gels applied once daily for 12 weeks were significantly more effective than vehicle in reducing the severity of the clinical signs of stable plaque psoriasis covering up to 20% of body surface area. In one of the studies, patients were followed up for an additional 12 weeks following cessation of therapy with Tazorac® Gel. Mean baseline scores and changes from baseline (reductions) after treatment in these two studies are shown in the following table:

Plaque Elevation, Scaling, and Erythema in Two Controlled Clinical Trials for Psoriasis

Plaque elevation, scaling, and erythema scored on a 0-4 scale with 0=none, 1=mild, 2=moderate, 3=severe and 4=very severe. B*=Mean Baseline Severity: C-12*=Mean Change from Baseline at end of 12 weeks of therapy: C-24*=Mean Change from Baseline at week 24 (12 weeks after the end of therapy).
		Tazorac® 0.05% Gel				Tazorac® 0.1% Gel				Vehicle Gel
		Trunk/Arm/Leg Lesions		Knee/Elbow Lesions		Trunk/Arm/Leg Lesions		Knee/Elbow Lesions		Trunk/Arm/Leg Lesions		Knee/Elbow Lesions
		N=108	N=111	N=108	N=111	N=108	N=112	N=108	N=112	N=108	N=113	N=108	N=113
Plaque Elevation	B* C-12* C-24*	2.5 -1.4 -1.2	2.6 -1.3	2.6 -1.3 -1.1	2.6 -1.1	2.5 -1.4 -1.1	2.6 -1.4	2.6 -1.5 -1.0	2.6 -1.3	2.4 -0.8 -0.9	2.6 -0.7	2.6 -0.7 -0.7	2.6 -0.6
Scaling	B* C-12* C-24*	2.4 -1.1 -0.9	2.5 -1.1	2.5 -1.1 -0.8	2.6 -0.9	2.4 -1.3 -1.0	2.6 -1.3	2.5 -1.2 -0.8	2.7 -1.2	2.4 -0.7 -0.8	2.6 -0.7	2.5 -0.6 -0.7	2.7 -0.6
Erythema	B* C-12* C-24*	2.4 -1.0 -1.1	2.7 -0.8	2.2 -0.9 -0.7	2.5 -0.8	2.4 -1.0 -0.9	2.8 -1.1	2.3 -1.0 -0.8	2.5 -0.8	2.3 -0.6 -0.7	2.7 -0.5	2.2 -0.5 -0.6	2.5 -0.5

Global improvement over baseline at the end of 12 weeks of treatment in these two studies is shown in the following table:

	Tazorac® 0.05% Gel		Tazorac® 0.1% Gel		Vehicle Gel
	N=81	N=93	N=79	N=69	N=84	N=91
100% improvement	2 (2%)	1 (1%)	0	0	1 (1%)	0
≥75% improvement	23 (28%)	17 (18%)	30 (38%)	17 (25%)	10 (12%)	9 (10%)
≥50% improvement	42 (52%)	39 (42%)	51 (65%)	36 (52%)	28 (33%)	21 (23%)
1-49% improvement	21 (26%)	32 (34%)	18 (23%)	23 (33%)	27 (32%)	32 (35%)
No change or worse	18 (22%)	22 (24%)	10 (13%)	10 (14%)	29 (35%)	38 (42%)

The 0.1% gel was more effective than the 0.05% gel, but the 0.05% gel was associated with less local irritation than the 0.1% gel (see ADVERSE REACTIONS section).

Acne: In two large vehicle-controlled studies, tazarotene 0.1% gel applied once daily was significantly more effective than vehicle in the treatment of facial acne vulgaris of mild to moderate severity. Percent reductions in lesion counts after treatment for 12 weeks in these two studies are shown in the following table:

Reduction in Lesion Counts after Twelve Weeks of Treatment in Two Controlled Clinical Trials for Acne

	Tazorac® 0.1% Gel		Vehicle Gel
	N=150	N=149	N=148	N=149
Noninflammatory lesions	55%	43%	35%	27%
Inflammatory lesions	42%	47%	30%	28%
Total lesions	52%	45%	33%	27%

Global improvement over baseline at the end of 12 weeks of treatment in these two studies is shown in the following table:

	Tazorac® 0.1% Gel		Vehicle Gel
	N=105	N=117	N=117	N=110
100% improvement	1 (1%)	0	0	0
≥75% improvement	40 (38%)	21 (18%)	23 (20%)	11 (10%)
≥50% improvement	71 (68%)	56 (48%)	47 (40%)	32 (29%)
1-49% improvement	23 (22%)	49 (42%)	48 (41%)	46 (42%)
No change or worse	11 (10%)	12 (10%)	22 (19%)	32 (29%)

INDICATIONS AND USAGE

Tazorac® (tazarotene) Gel 0.05% and 0.1% are indicated for the topical treatment of patients with stable plaque psoriasis of up to 20% body surface area involvement.

Tazorac® (tazarotene) Gel 0.1% is also indicated for the topical treatment of patients with facial acne vulgaris of mild to moderate severity.

The efficacy of Tazorac® Gel in the treatment of acne previously treated with other retinoids or resistant to oral antibiotics has not been established.

CONTRAINDICATIONS

Retinoids may cause fetal harm when administered to a pregnant woman.

In rats, tazarotene 0.05% gel, administered topically during gestation days 6 through 17 at 0.25 mg/kg/day (1.5 mg/m2/day) resulted in reduced fetal body weights and reduced skeletal ossification. Rabbits dosed topically with 0.25 mg/kg/day (2.75 mg/m2 total body surface area/day) tazarotene gel during gestation days 6 through 18 were noted with single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. Systemic daily-exposure (AUCde) to tazarotenic acid at topical doses of 0.25 mg/kg/day tazarotene in a gel formulation in rats and rabbits represented 0.62 and 6.7 times, respectively, the AUC0-24h observed in psoriatic patients treated with 2 mg/cm2 of tazarotene gel 0.1% (extrapolated for topical application over a 20% body surface area), and 0.78 and 8.4 times, respectively, the maximum AUC0-24h in acne patients treated with 2 mg/cm2 of tazarotene gel 0.1% over a 15% (targeted) body surface area.

As with other retinoids, when tazarotene was given orally to experimental animals, developmental delays were seen in rats, and teratogenic effects and post-implantation loss were observed in rats and rabbits at AUCde values that were 0.55 and 13.2 times, respectively, the AUC0-24h observed in psoriatic patients treated with 2 mg/cm2 of tazarotene gel 0.1% (extrapolated for topical application over a 20% body surface area), and 0.68 and 16.4 times, respectively, the maximum AUC0-24h in acne patients treated with 2 mg/cm2 of tazarotene gel 0.1% over a 15% (targeted) body surface area.

In a study of the effect of oral tazarotene on fertility and early embryonic development in rats, decreased number of implantation sites, decreased litter size, decreased numbers of live fetuses, and decreased fetal body weights, all classic developmental effects of retinoids, were observed when female rats were administered 2 mg/kg/day from 15 days before mating through gestation day 7. A low incidence of retinoid-related malformations at that dose was reported to be related to treatment. This dose produced an AUCde that was 1.7 times the AUC0-24h observed in psoriatic patients treated with 2 mg/cm2 tazarotene gel 0.1% (extrapolated for topical application over a 20% body surface area) and 2.1 times the maximum AUC0-24h in acne patients treated with 2 mg/cm2 of tazarotene gel 0.1% over a 15% (targeted) body surface area.

SYSTEMIC EXPOSURE TO TAZAROTENIC ACID IS DEPENDENT UPON THE EXTENT OF THE BODY SURFACE AREA TREATED. IN PATIENTS TREATED TOPICALLY OVER SUFFICIENT BODY SURFACE AREA, EXPOSURE COULD BE IN THE SAME ORDER OF MAGNITUDE AS IN THESE ORALLY TREATED ANIMALS. ALTHOUGH THERE MAY BE LESS SYSTEMIC EXPOSURE IN THE TREATMENT OF ACNE OF THE FACE ALONE DUE TO LESS SURFACE AREA FOR APPLICATION, TAZAROTENE IS A TERATOGENIC SUBSTANCE, AND IT IS NOT KNOWN WHAT LEVEL OF EXPOSURE IS REQUIRED FOR TERATOGENICITY IN HUMANS (SEE CLINICAL PHARMACOLOGY: PHARMACOKINETICS).

There were thirteen reported pregnancies in patients who participated in clinical trials for topical tazarotene. Nine of the patients were found to have been treated with topical tazarotene, and the other four had been treated with vehicle. One of the patients who was treated with tazarotene cream elected to terminate the pregnancy for non-medical reasons unrelated to treatment. The other eight pregnant women who were inadvertently exposed to topical tazarotene during clinical trials subsequently delivered apparently healthy babies. As the exact timing and extent of exposure in relation to the gestation times are not certain, the significance of these findings is unknown.

Tazorac® Gel is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, treatment should be discontinued and the patient apprised of the potential hazard to the fetus. Women of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when Tazorac® Gel is used. The possibility that a woman of child-bearing potential is pregnant at the time of institution of therapy should be considered. A negative result for pregnancy test having a sensitivity down to at least 50 mIU/mL for human chorionic gonadotropin (hCG) should be obtained within 2 weeks prior to Tazorac® Gel therapy, which should begin during a normal menstrual period (see also PRECAUTIONS: Pregnancy: Teratogenic Effects).

Tazorac® Gel is contraindicated in individuals who have shown hypersensitivity to any of its components.

WARNINGS

Pregnancy Category X. See CONTRAINDICATIONS section. Women of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when Tazorac® Gel is used. The possibility that a woman of child-bearing potential is pregnant at the time of institution of therapy should be considered. A negative result for pregnancy test having a sensitivity down to at least 50 mIU/mL for hCG should be obtained within 2 weeks prior to Tazorac® Gel therapy, which should begin during a normal menstrual period.

PRECAUTIONS

General: Tazorac® Gel should be applied only to the affected areas. For external use only. Avoid contact with eyes, eyelids, and mouth. If contact with eyes occurs, rinse thoroughly with water. The safety of use of Tazorac® Gel over more than 20% of body surface area has not been established in psoriasis or acne.

Retinoids should not be used on eczematous skin, as they may cause severe irritation.

Because of heightened burning susceptibility, exposure to sunlight (including sunlamps) should be avoided unless deemed medically necessary, and in such cases, exposure should be minimized during the use of Tazorac® Gel. Patients must be warned to use sunscreens (minimum SPF of 15) and protective clothing when using Tazorac® Gel. Patients with sunburn should be advised not to use Tazorac® Gel until fully recovered. Patients who may have considerable sun exposure due to their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using Tazorac® Gel and ensure that the precautions outlined in the Information for Patients subsection are observed.

Tazorac® Gel should be administered with caution if the patient is also taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the increased possibility of augmented photosensitivity.

Some individuals may experience excessive pruritus, burning, skin redness or peeling. If these effects occur, the medication should either be discontinued until the integrity of the skin is restored, or the dosing should be reduced to an interval the patient can tolerate. However, efficacy at reduced frequency of application has not been established. Alternatively, patients with psoriasis who are being treated with the 0.1% concentration can be switched to the lower concentration.

Weather extremes, such as wind or cold, may be more irritating to patients using Tazorac® Gel.

Information for Patients: See attached Patient Package Insert.

Drug Interactions: Concomitant dermatologic medications and cosmetics that have a strong drying effect should be avoided. It is also advisable to "rest" a patient's skin until the effects of such preparations subside before use of Tazorac® Gel is begun.

In a study of 27 healthy female subjects between the ages of 20–55 years receiving a combination oral contraceptive tablet containing 1 mg norethindrone and 35 mcg ethynyl estradiol, concomitant use of tazarotene did not affect the pharmacokinetics of norethindrone and ethynyl estradiol over a complete cycle.

The impact of tazarotene on the pharmacokinetics of progestin only oral contraceptives (i.e., minipills) has not been evaluated.

Carcinogenesis, Mutagenesis, Impairment of Fertility: A long-term study of tazarotene following oral administration of 0.025, 0.050, and 0.125 mg/kg/day to rats showed no indications of increased carcinogenic risks. Based on pharmacokinetic data from a shorter-term study in rats, the highest dose of 0.125 mg/kg/day was anticipated to give systemic exposure (AUCde) in the rat equivalent to 0.32 times the AUC0-24h observed in psoriatic patients treated with 2 mg/cm2 of tazarotene gel 0.1% (extrapolated for topical application over a 20% body surface area), and 0.38 times the maximum AUC0-24h in acne patients treated with 2 mg/cm2 of tazarotene gel 0.1% over a 15% (targeted) body surface area.

In evaluation of photo co-carcinogenicity, median time to onset of tumors was decreased and the number of tumors increased in hairless mice following chronic topical dosing with intercurrent exposure to ultraviolet radiation at tazarotene concentrations of 0.001%, 0.005%, and 0.01% in a gel formulation for up to 40 weeks.

A long-term topical application study of up to 0.1% tazarotene in a gel formulation in mice terminated at 88 weeks showed that dose levels of 0.05, 0.125, 0.25, and 1 mg/kg/day (reduced to 0.5 mg/kg/day for males after 41 weeks due to severe dermal irritation) revealed no apparent carcinogenic effects when compared to vehicle control animals; untreated control animals were not completely evaluated. Systemic exposure (AUC0-12h) at the highest dose was 2 times the AUC0-24h observed in psoriatic patients treated with 2 mg/cm2 of tazarotene gel 0.1% (extrapolated for topical application over a 20% body surface area), and 2.5 times the maximum AUC0-24h in acne patients treated with 2 mg/cm2 of tazarotene gel 0.1% over a 15% (targeted) body surface area.

Tazarotene was found to be non-mutagenic in the Ames assay using Salmonella and E. coli and did not produce structural chromosomal aberrations in a human lymphocyte assay. Tazarotene was also non-mutagenic in the CHO/HGPRT mammalian cell forward gene mutation assay and was non-clastogenic in the in vivo mouse micronucleus test.

No impairment of fertility occurred in rats when male animals were treated for 70 days prior to mating and female animals were treated for 14 days prior to mating and continuing through gestation and lactation with topical doses of tazarotene gel of up to 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure (AUCde) in the rat would be equivalent to 0.31 times the AUC0-24h observed in psoriatic patients treated with 2 mg/cm2 of tazarotene gel 0.1% (extrapolated for topical application over a 20% body surface area), and 0.38 times the maximum AUC0-24h in acne patients treated with 2 mg/cm2 of tazarotene gel 0.1% over a 15% (targeted) body surface area.

No impairment of mating performance or fertility was observed in male rats treated for 70 days prior to mating with oral doses of up to 1 mg/kg/day tazarotene, which produced an AUCde that was 0.95 times the AUC0-24h observed in psoriatic patients treated with 2 mg/cm2 of tazarotene gel 0.1% (extrapolated for topical application over a 20% body surface area), and 1.2 times the maximum AUC0-24h in acne patients treated with 2 mg/cm2 of tazarotene gel 0.1% over a 15% (targeted) body surface area.

No effect on parameters of mating performance or fertility was observed in female rats treated for 15 days prior to mating and continuing through day 7 of gestation with oral doses of tazarotene up to 2 mg/kg/day. However, there was a significant decrease in the number of estrous stages and an increase in developmental effects at 2 mg/kg/day (see CONTRAINDICATIONS). This dose produced an AUC0-24h which was 1.7 times that observed in psoriatic patients treated with 2 mg/cm2 of tazarotene gel 0.1% (extrapolated for topical application over a 20% body surface area), and 2.1 times the maximum AUC0-24h in acne patients treated with 2 mg/cm2 of tazarotene gel 0.1% over a 15% (targeted) body surface area.

Reproductive capabilities of F1 animals, including F2 survival and development, were not affected by topical administration of tazarotene gel to female F0 parental rats from gestation day 16 through lactation day 20 at the maximum tolerated dose of 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure (AUCde) in the rat would be equivalent to 0.31 times the AUC0-24h observed in psoriatic patients treated with 2 mg/cm2 of tazarotene gel 0.1% (extrapolated for topical application over a 20% body surface area), and 0.38 times the maximum AUC0-24h in acne patients treated with 2 mg/cm2 of tazarotene gel 0.1% over a 15% (targeted) body surface area.

Pregnancy

Teratogenic Effects: Pregnancy Category X: See CONTRAINDICATIONS section. Women of child-bearing potential should use adequate birth-control measures when Tazorac® Gel is used. The possibility that a woman of child-bearing potential is pregnant at the time of institution of therapy should be considered. A negative result for pregnancy test having a sensitivity down to at least 50 mIU/mL for hCG should be obtained within 2 weeks prior to Tazorac® Gel therapy, which should begin during a normal menstrual period. There are no adequate, well-controlled studies in pregnant women. Although there may be less systemic exposure in the treatment of acne of the face alone due to less surface area for application, tazarotene is a teratogenic substance, and it is not known what level of exposure is required for teratogenicity in humans (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

Nursing Mothers

After single topical doses of 14C-tazarotene to the skin of lactating rats, radioactivity was detected in milk, suggesting that there would be transfer of drug-related material to the offspring via milk. It is not known whether this drug is excreted in human milk. Caution should be exercised when tazarotene is administered to a nursing woman.

Pediatric Use

The safety and efficacy of tazarotene have not been established in pediatric patients under the age of 12 years.

Geriatric Use

Of the total number of subjects in clinical studies of tazarotene gels, 0.05% and 0.1% for plaque psoriasis, 163 were over the age of 65. Subjects over 65 years of age experienced more adverse events and lower treatment success rates after 12 weeks of use of Tazorac® Gel compared with those 65 years of age and younger. Currently there is no other reliable clinical experience on the differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals can not be ruled out. Tazarotene gel for the treatment of acne has not been clinically evaluated in persons over the age of 65.

Adverse Reactions

In human dermal safety studies, tazarotene 0.05% and 0.1% gels did not induce allergic contact sensitization, phototoxicity or photoallergy.

Psoriasis: The most frequent adverse events reported with Tazorac® Gel 0.05% and 0.1% were limited to the skin. Those occurring in 10 to 30% of patients, in descending order, included pruritus, burning/stinging, erythema, worsening of psoriasis, irritation, and skin pain. Events occurring in 1 to 10% of patients included rash, desquamation, irritant contact dermatitis, skin inflammation, fissuring, bleeding, and dry skin. Increases in “psoriasis worsening” and “sun-induced erythema” were noted in some patients over the 4th to 12th months as compared to the first three months of a 1 year study. In general, the incidence of adverse events with Tazorac® Gel 0.05% was 2 to 5% lower than that seen with Tazorac® Gel 0.1%.

Acne: The most frequent adverse events reported with Tazorac® Gel 0.1% in the treatment of acne occurring in 10 to 30% of patients, in descending order, included desquamation, burning/stinging, dry skin, erythema and pruritus. Events occurring in 1 to 10% of patients included irritation, skin pain, fissuring, localized edema and skin discoloration.

Postmarketing Experience

The following adverse reactions have been identified during postmarketing use of Tazorac® Gel 0.05% and 0.1% in clinical practice. Because they are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Tazorac® Gel. The reactions include: blister, rash, skin discoloration (including skin hyperpigmentation or skin hypopigmentation), and pain.

OVERDOSAGE

Excessive topical use of Tazorac® Gel may lead to marked redness, peeling, or discomfort (see PRECAUTIONS: General).

Tazorac® Gels 0.05% and 0.1% are not for oral use. Oral ingestion of the drug may lead to the same adverse effects as those associated with excessive oral intake of Vitamin A (hypervitaminosis A) or other retinoids. If oral ingestion occurs, the patient should be monitored, and appropriate supportive measures should be administered as necessary.

DOSAGE AND ADMINISTRATION

General: Application may cause excessive irritation in the skin of certain sensitive individuals. In cases where it has been necessary to temporarily discontinue therapy, or the dosing has been reduced to a lower concentration (in patients with psoriasis) or to an interval the patient can tolerate, therapy can be resumed, or the drug concentration or frequency of application can be increased as the patient becomes able to tolerate the treatment. Frequency of application should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance. Efficacy has not been established for less than once daily dosing frequencies.

For Psoriasis: It is recommended that treatment start with Tazorac® 0.05% Gel, with strength increased to 0.1% if tolerated and medically indicated. Apply Tazorac® Gel once a day, in the evening, to psoriatic lesions, using enough (2 mg/cm2) to cover only the lesion with a thin film to no more than 20% of body surface area. If a bath or shower is taken prior to application, the skin should be dry before applying the gel. If emollients are used, they should be applied at least an hour before application of Tazorac® Gel. Because unaffected skin may be more susceptible to irritation, application of tazarotene to these areas should be carefully avoided. Tazorac® Gel was investigated for up to 12 months during clinical trials for psoriasis.

For Acne: Cleanse the face gently. After the skin is dry, apply a thin film of Tazorac® Gel 0.1% (2 mg/cm2) once a day, in the evening, to the skin where acne lesions appear. Use enough to cover the entire affected area. Tazorac® Gel was investigated for up to 12 weeks during clinical trials for acne.

HOW SUPPLIED

Tazorac® (tazarotene) Gel is available in concentrations of 0.05% and 0.1%. It is available in a collapsible aluminum tube with a tamper-evident aluminum membrane over the opening and a white propylene screw cap, in 30 g and 100 g sizes.

	Tazorac® Gel 0.05%	Tazorac® Gel 0.1%
30 g	NDC 0023-8335-03	NDC 0023-0042-03
100 g	NDC 0023-8335-10	NDC 0023-0042-10

NOTE: Store at 25°C (77°F): excursions permitted to 15-30°C (59-86°F).

Rx Only

Revised: 03/2011

© 2011 Allergan, Inc.

Irvine, CA 92612, U.S.A.

® marks owned by Allergan, Inc.

U.S. Patents 5,914,334 and 6,258,830

Made in the U.S.A.

71722US13C

Pharmacist: Please cut or tear at dotted line and provide this patient package insert to your customer.

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Tazorac®

(tazarotene) Gel 0.05%

(tazarotene) Gel 0.1%

INFORMATION FOR PATIENTS

Please read this leaflet carefully before you start to use your medicine. Read the information you get every time you get more medicine. There may be new information about the drug. This leaflet does not take the place of talks with your doctor. If you have any questions, or are not sure about anything, ask your doctor or pharmacist.

USES

Tazorac® Gel 0.05% is used in the treatment of stable plaque psoriasis covering up to 20% of body surface area.

Tazorac® Gel 0.1% is used in the treatment of stable plaque psoriasis covering up to 20% of body surface area and in the treatment of mild to moderately severe facial acne.

BEFORE YOU USE THIS MEDICINE

You should be aware that:

      (a) Tazorac® Gel should not be used if you are pregnant, attempting to become pregnant or at high risk of pregnancy. Consult your physician for adequate birth control measures if you are a female of child-bearing potential. If you are able to become pregnant, take a pregnancy test within 2 weeks prior to beginning to use Tazorac® Gel to be sure you are not pregnant. If you have menstrual periods, begin taking Tazorac® Gel during a normal menstrual period. These actions help assure that you are not pregnant when you begin use.

      (b) Tazorac® Gel should be used with caution if you are also using other topical agents with a strong skin drying effect, products with high concentrations of alcohol, astringents, spices, the peel of lime, medicated soaps or shampoos, permanent wave solutions, electrolysis, hair depilatories or waxes, or other preparations or processes that might dry or irritate the skin, unless otherwise instructed by your health care practitioner.

      (c) Tazorac® Gel should not be used if you have sunburn, eczema or other chronic skin condition(s). Tazorac® Gel may cause severe irritation if applied to eczematous skin. If you have sunburn, you should wait until full recovery before using Tazorac® Gel.

      (d) Tazorac® Gel should not be used if you are inherently sensitive to sunlight.

      (e) Tazorac® Gel should not be used if you are taking other drugs that increase your sensitivity to sunlight (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides). Inform your physician if you are taking any other medications.

      (f) You should use protective clothing and sunscreens with minimum SPF of 15 during the day when being treated with Tazorac® Gel. You should avoid direct sun exposure as much as possible and avoid sunlamps totally while being treated with Tazorac® Gel, unless advised otherwise by your doctor.

      (g) If you have considerable sun exposure due to occupation, particular caution as described above should be exercised when using Tazorac® Gel.

      (h) Weather extremes, such as wind or cold, may be more irritating to your skin while you are using Tazorac® Gel.

BEFORE YOU USE THIS MEDICINE

Tell your doctor:

      (a) if you are pregnant or are considering becoming pregnant.

      (b) if you are breast-feeding. We do not know if tazarotene can pass through the milk to the baby. The potential harm to the baby is unknown.

      (c) if you are allergic to any ingredients in this medicine.

      (d) if you are already using other products that make your skin dry.

      (e) if you have a skin condition called eczema.

      (f) if you will be subject to excessive sun exposure.

      (g) if you are taking Vitamin A supplements.

HOW TO USE THIS PRODUCT

• Read the directions on your prescription label carefully. Ask your doctor or pharmacist to explain anything that you do not understand.


• If you become pregnant while using Tazorac® Gel, you should immediately discontinue its use and contact your doctor.


• If you use a cream or lotion to soften or lubricate your skin, apply Tazorac® Gel after ensuring that there is no more cream or lotion on the skin.


• With use of Tazorac® Gel, some people notice a feeling of itching, burning or stinging. If irritation is excessive, consult your healthcare provider, who may adjust your medication temporarily to a more comfortable level. Effectiveness of this medication when used less often than once daily has not been proven.


• Do not cover treated areas with dressings or bandages.


• Never use more Tazorac® Gel than instructed and never use it more often than instructed, as application of larger amounts of medication than recommended will not lead to more rapid or better results, and marked redness, peeling or discomfort may occur.


• Wash your hands after applying the medication unless you are treating your hands for psoriasis. If the gel accidentally gets on areas you do not need to treat, wash it off.


• Keep Tazorac® Gel away from your eyes, eyelids, and mouth. If it gets in contact with your eyes, wash them with large amounts of cool water, and contact a doctor if eye irritation persists.

MISSED DOSES

If you forget or miss a dose of Tazorac® Gel, do not try to "make it up." Return to your normal application schedule as soon as you can.

INSTRUCTIONS SPECIFIC TO TREATMENT OF PSORIASIS

• 
  

  If you bathe or shower before using Tazorac® Gel, be sure the skin is dry before application. Apply a thin film of the gel to your psoriasis lesions once a day before going to bed.

  
  


• 
  

  Carefully avoid application to apparently uninvolved skin. Tazorac® Gel may be more irritating to non-lesional skin.

  
  


• 
  

  If you need to treat you

Sulfacleanse 8/4

Generic Name: sodium sulfacetamide and sulfur

Dosage Form: topical lotion
SULFACLEANSE TM 8/4 TOPICAL SUSPENSION REV.1.0 Sodium sulfacetamide is a sulfonamide with antibacterial activity while sulfur acts as a keratolytic agent. Chemically sodium sulfacetamide is N-[(4-aminophenyl) sulfonyl]-acetamide, monosodium salt, monohydrate.

Each mL of SulfaCleanse™ 8/4 contains 80mg of sodium sulfacetamide and 40mg of sulfur in a formulation consisting of: aloe, butylated hydroxytoluene, cetyl alcohol, disodium oleamido MEA sulfosuccinate, edetate disodium, fragrance, glyceryl stearate, green tea, magnesium aluminum silicate, methylparaben, PEG-100 stearate, propylparaben, purified water, sodium cocoyl isethionate, sodium methyl cocoyl taurate, sodium thiosulfate, stearyl alcohol, xanthan gum.

The most widely accepted mechanism of action of sulfonamides is the Woods-Fildes theory, which is based on the fact that sulfonamides act as competitive antagonists to para- aminobenzoic acid (PABA), an essential component for bacterial growth. While absorption through intact skin has not been determined, sodium sulfacetamide is readily absorbed from the gastrointestinal tract when taken orally and excreted in the urine, largely unchanged. The biological half-life has variously been reported as 7 to 12.8 hours. The exact mode of action of sulfur in the treatment of acne is unknown, but it has been reported that it inhibits the growth of Propionibacterium acnes and the formation of free fatty acids.

SulfaCleanse™ 8/4 is indicated for the topical control of acne vulgaris, acne rosacea and seborrheic dermatitis.

SulfaCleanse™ 8/4 is contraindicated for use by patients having known hypersensitivity to sulfonamides, sulfur or any other component of this preparation. SulfaCleanse™ 8/4 is not to be used by patients with kidney disease.

Although rare, sensitivity to sodium sulfacetamide may occur. Therefore, caution and careful supervision should be observed when prescribing this drug for patients who may be prone to hypersensitivity to topical sulfonamides. Systemic toxic reactions such as agranulocytosis, acute hemolytic anemia, purpura hemorrhagica, drug fever, jaundice, and contact dermatitis indicate hypersensitivity to sulfonamides. Particular caution should be employed if areas of denuded or abraded skin are involved.

FOR EXTERNAL USE ONLY. Keep away from eyes. Keep out of reach of children. Keep container tightly closed.

General – If irritation develops, use of the product should be discontinued and appropriate therapy instituted. Patients should be carefully observed for possible local irritation or sensitization during long-term therapy. The object of this therapy is to achieve desquamation without irritation, but sodium sulfacetamide and sulfur can cause reddening and scaling of the epidermis. These side effects are not unusual in the treatment of acne vulgaris, but patients should be cautioned about the possibility.

Information for Patients – Avoid contact with eyes, eyelids, lips and mucous membranes. If accidental contact occurs, rinse with water. If excessive irritation develops, discontinue use and consult your physician.

Carcinogenesis, Mutagenesis and Impairment

of Fertility – Long-term studies in animals have not been performed to evaluate carcinogenic potential.

Category C – Animal reproduction studies have not been conducted with SulfaCleanse™ 8/4. It is also not known whether SulfaCleanse™ 8/4 can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. SulfaCleanse™ 8/4 should be given to a pregnant woman only if clearly needed.

It is not known whether sodium sulfacetamide is excreted in the human milk following topical use of SulfaCleanse™ 8/4. However, small amounts of orally administered sulfonamides have been reported to be eliminated in human milk. In view of this and because many drugs are excreted in human milk, caution should be exercised when SulfaCleanse™ 8/4 is administered to a nursing woman.

Safety and effectiveness in children under the age of 12 has not been established.

Although rare, sodium sulfacetamide may cause local irritation.

Apply SulfaCleanse™ 8/4 once or twice daily to affected areas, or as directed by your physician. Wet skin and liberally apply to areas to be cleansed. Massage gently into skin for 10-20 seconds, working into a full lather, rinse thoroughly and pat dry. If drying occurs, it may be controlled by rinsing off SulfaCleanse™ 8/4 sooner or using less often.

SulfaCleanse™ 8/4 is available in a 16 fl. oz. (473 mL) bottle, NDC 42546-175-16.

Store at controlled room temperature 20°-25° C (68°-77° F); excursions permitted to 15°-30°C (59°-86°F).

Protect from freezing.


KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

NDC 42546-175-16

SulfaCleanseTM 8/4 (sodium sulfacetamide 8% and sulfur 4%)

Topical Suspension in a vehicle containing Green Tea and Aloe

Rx only

16 fl oz (473 ml)

PruGen, Inc. Pharmaceuticals

Sulfacleanse 8/4  sodium sulfacetamide and sulfur  lotion

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 42546-175 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SULFACETAMIDE SODIUM (SULFACETAMIDE) SULFACETAMIDE SODIUM 80 mg  in 1 mL SULFUR (SULFUR) SULFUR 40 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength Aloe   BUTYLATED HYDROXYTOLUENE   Cetyl alcohol   Disodium oleamido MEA-sulfosuccinate   EDETATE DISODIUM   GLYCERYL MONOSTEARATE   Green tea leaf   MAGNESIUM ALUMINUM SILICATE   METHYLPARABEN   PEG-100 STEARATE   PROPYLPARABEN   WATER   SODIUM COCOYL ISETHIONATE   TAURINE   SODIUM THIOSULFATE   STEARYL ALCOHOL   XANTHAN GUM

Product Characteristics Color yellow Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 42546-175-16 1 BOTTLE In 1 BOX contains a BOTTLE, PUMP 1 473 mL In 1 BOTTLE, PUMP This package is contained within the BOX (42546-175-16)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
unapproved drug other		05/01/2011

Labeler - PruGen, Inc. (929922750)

Revised: 05/2011PruGen, Inc.

More Sulfacleanse 8/4 resources

• Sulfacleanse 8/4 Side Effects (in more detail)
• Sulfacleanse 8/4 Use in Pregnancy & Breastfeeding
• Sulfacleanse 8/4 Drug Interactions
• Sulfacleanse 8/4 Support Group
• 18 Reviews for Sulfacleanse 8/4 - Add your own review/rating

Compare Sulfacleanse 8/4 with other medications

• Acne
• Rosacea
• Seborrheic Dermatitis

Ticarcillin

Generic Name: Ticarcillin (TYE-kar-SIL-in)
Brand Name: Ticar

Ticarcillin is used for:

Treating infections caused by certain bacteria.

Ticarcillin is a penicillin antibiotic. It works by blocking the growth of the bacteria's cell wall, resulting in the death of the bacteria.

Do NOT use Ticarcillin if:

• you are allergic to any ingredient in Ticarcillin or to penicillin antibiotics (eg, amoxicillin)


• you are taking a tetracycline antibiotic (eg, doxycycline)

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

Before using Ticarcillin:

Some medical conditions may interact with Ticarcillin. 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 had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to a cephalosporin (eg, cephalexin) or other beta-lactam antibiotic (eg, imipenem)


• if you have kidney problems, bleeding or clotting problems, or abnormal blood electrolyte levels, or if you are dehydrated


• if you are on a low-salt diet

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

• Tetracyclines (eg, doxycycline) because they may decrease Ticarcillin's effectiveness


• Anticoagulants (eg, warfarin) because their effectiveness may be decreased or the risk of their side effects may be increased by Ticarcillin


• Heparin or methotrexate because the risk of their side effects may be increased by Ticarcillin


• Aminoglycosides (eg, gentamicin) or oral contraceptives (eg, birth control pills) because their effectiveness may be decreased by Ticarcillin

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

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

• Ticarcillin is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Ticarcillin at home, a health care provider will teach you how to use it. Be sure you understand how to use Ticarcillin. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.


• Do not use Ticarcillin if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.


• To clear up your infection completely, use Ticarcillin for the full course of treatment. Keep using it even if you feel better in a few days.


• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.


• If you miss a dose of Ticarcillin, use 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 use 2 doses at once.

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

Important safety information:

• Ticarcillin only works against bacteria; it does not treat viral infections (eg, the common cold).


• Be sure to use Ticarcillin for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future.


• Long-term or repeated use of Ticarcillin may cause a second infection. Tell your doctor if signs of a second infection occur. Your medicine may need to be changed to treat this.


• Mild diarrhea is common with antibiotic use. However, a more serious form of diarrhea (pseudomembranous colitis) may rarely occur. This may develop while you use the antibiotic or within several months after you stop using it. Contact your doctor right away if stomach pain or cramps, severe diarrhea, or bloody stools occur. Do not treat diarrhea without first checking with your doctor.


• Ticarcillin may reduce the number of clot-forming cells (platelets) in your blood. Avoid activities that may cause bruising or injury. Tell your doctor if you have unusual bruising or bleeding. Tell your doctor if you have dark, tarry, or bloody stools.


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


• Hormonal birth control (eg, birth control pills) may not work as well while you are using Ticarcillin. To prevent pregnancy, use an extra form of birth control (eg, condoms).


• Ticarcillin may interfere with certain lab test results. Be sure your doctor and lab personnel know you are using Ticarcillin.


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


• Use Ticarcillin with extreme caution in CHILDREN younger than 10 years old who have diarrhea or an infection of the stomach or bowel.


• PREGNANCY and BREAST-FEEDING: If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using Ticarcillin while you are pregnant. It is not known if Ticarcillin is found in breast milk. If you are or will be breast-feeding while you use Ticarcillin, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Ticarcillin:

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:

Changes in taste and smell; diarrhea; gas; giddiness; headache; nausea; pain, swelling, or redness at the injection site; stomach pain; vomiting.

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); bloody stools; chest pain; dark urine; fever, chills, or sore throat; joint or muscle pain; red, swollen, or blistered skin; seizures; severe diarrhea; severe stomach pain/cramps; swelling in the mouth; unusual bruising or bleeding; unusual tiredness or weakness; vaginal irritation or discharge; vein swelling or tenderness; yellowing of the eyes or skin.

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. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch .

See also: Ticarcillin side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include agitation; confusion; hallucinations; seizures; severe excitability; tremor; unconsciousness.

Proper storage of Ticarcillin:

Ticarcillin is usually handled and stored by a health care provider. If you are using Ticarcillin at home, store Ticarcillin as directed by your pharmacist or health care provider. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Ticarcillin out of the reach of children and away from pets.

General information:

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


• Ticarcillin 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.

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

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

• ticarcillin Concise Consumer Information (Cerner Multum)


• Ticar Advanced Consumer (Micromedex) - Includes Dosage Information


• Ticar Prescribing Information (FDA)


• Ticarcillin Disodium and Clavulanate Potassium Monograph (AHFS DI)

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• Bone infection
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• Peritonitis
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• Urinary Tract Infection