Davilose

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Methylcellulose

Methylcellulose is reported as an ingredient of Davilose in the following countries:

• Portugal

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Globaxol

Globaxol may be available in the countries listed below.

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Sulfamethoxazole

Sulfamethoxazole is reported as an ingredient of Globaxol in the following countries:

• Philippines

Trimethoprim

Trimethoprim is reported as an ingredient of Globaxol in the following countries:

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Fentalis

Fentalis may be available in the countries listed below.

UK matches:

• Fentalis Reservoir Transdermal Patches (SPC)

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Fentanyl

Fentanyl is reported as an ingredient of Fentalis in the following countries:

• United Kingdom

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Glossary

SPC	Summary of Product Characteristics (UK)

Click for further information on drug naming conventions and International Nonproprietary Names.

Topimax Lyfjaver

Topimax Lyfjaver may be available in the countries listed below.

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Topiramate

Topiramate is reported as an ingredient of Topimax Lyfjaver in the following countries:

• Iceland

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Topramoxin

Topramoxin may be available in the countries listed below.

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Amoxicillin

Amoxicillin trihydrate (a derivative of Amoxicillin) is reported as an ingredient of Topramoxin in the following countries:

• Turkey

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Dexametasona Larjan

Dexametasona Larjan may be available in the countries listed below.

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Dexamethasone

Dexamethasone 21-(disodium phosphate) (a derivative of Dexamethasone) is reported as an ingredient of Dexametasona Larjan in the following countries:

• Argentina

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Celofen

Celofen may be available in the countries listed below.

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Aceclofenac

Aceclofenac is reported as an ingredient of Celofen in the following countries:

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Acyclovir

Aciclovir is reported as an ingredient of Aciclovir-800-von-Ct in the following countries:

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Bromocriptine Mesylate

Class: Ergot-derivative Dopamine Receptor Agonists
ATC Class: G02CB01
VA Class: AU900
CAS Number: 22260-51-1
Brands: Parlodel

Introduction

Ergot-derivative dopamine receptor agonist and prolactin inhibitor.^{a b}

Uses for Bromocriptine Mesylate

Hyperprolactinemic Disorders

Treatment of male and female dysfunctions associated with hyperprolactinemia, including amenorrhea and/or galactorrhea, hypogonadism, and infertility.^{a b}

Used in patients with prolactin-secreting adenomas (e.g., prolactinoma), including macroadenomas, to decrease tumor size; may be used prior to surgery in patients undergoing excision of the tumor (adenectomy).^{a b}

Treatment of female infertility associated with hyperprolactinemia; used to induce ovulation in appropriately selected anovulatory women.^b

Treatment of hypogonadism and galactorrhea that persist following radiation therapy or surgery in hyperprolactinemic males with prolactin-secreting adenomas and adequate testosterone concentrations.^{a b} Some clinicians consider bromocriptine the treatment of choice for reduction of large tumors (macroadenomas).^b

Parkinsonian Syndrome

Symptomatic management of idiopathic or postencephalitic parkinsonian syndrome.^{a b}

Used as an adjunct to levodopa for the symptomatic management of parkinsonian syndrome in patients with advanced disease.^{111 112 a}

Has been used as monotherapy for initial symptomatic management of parkinsonian syndrome†.¹¹¹ Most clinicians would use levodopa for initial therapy in individuals >70 years of age (less likely than younger individuals to develop levodopa-related motor complications and because of concerns about cognitive dysfunction), in patients with cognitive impairment, and in those with severe disease.¹¹¹ A dopamine receptor agonist may be preferred for initial therapy in patients ≤70 years of age.¹¹¹

Acromegaly

Treatment of acromegaly, alone or as adjunctive therapy with pituitary irradiation or surgery.^{a b}

Male Infertility

Has been used to increase sperm counts and restore fertility† in oligospermic men without hyperprolactinemia who are unresponsive to traditional drug therapy.^b

Neuroleptic Malignant Syndrome

Has been used to relieve extrapyramidal reactions, hyperthermia, and hypertension of neuroleptic malignant syndrome† (NMS) associated with neuroleptic drug therapy (e.g., haloperidol, fluphenazine).^b

Hepatic Encephalopathy

Has been used in the management of chronic hepatic encephalopathy†.^b

Postpartum Breast Engorgement

Used in the past for prevention of postpartum breast engorgement†;^{106 b} FDA has withdrawn approval of bromocriptine for this indication because the risk of serious, potentially fatal adverse effects^{100 102 104 107 108} outweigh the limited benefits associated with this use.^{101 103} (See Cardiovascular Effects under Cautions.)

Bromocriptine Mesylate Dosage and Administration

General

• 
  

  Individualize and adjust dosage carefully; evaluate frequently during dosage adjustment to determine lowest therapeutic dosage.^{a b}

  
  


• 
  

  Temporary dosage reduction or discontinuance may be necessary in patients developing intolerable adverse effects.^b

  
  


• 
  

  When bromocriptine is discontinued (i.e., during pregnancy) in patients being treated for hyperprolactinemic disorders, monitor patients for tumor progression or development.^b (See Warnings: Pregnancy under Cautions.)

  
  

Hyperprolactinemic Disorders

• 
  

  During initial therapy for female infertility, use a mechanical contraceptive in conjunction with bromocriptine therapy until normal ovulatory menstrual cycles have been restored; contraception can then be discontinued.^{a b}

  
  


• 
  

  If menstruation does not occur within 3 days of the expected date, discontinue bromocriptine and perform a pregnancy test.^{a b}

  
  

Parkinsonian Syndrome

• 
  

  Assess patient’s therapeutic response at 2-week intervals to ensure lowest effective dosage is not exceeded.^{a b}

  
  

Acromegaly

• 
  

  Determine serum growth hormone concentrations monthly, and adjust bromocriptine dosage based on the reduction in these concentrations and the patient’s clinical response.^{a b}

  
  


• 
  

  If an adequate response is not apparent after a brief trial with the drug and/or dosage adjustment and clinical evaluation, consider discontinuance of bromocriptine.^{a b}

  
  


• 
  

  Withdraw therapy (4- to 8-week period is usually adequate) annually in patients undergoing radiation therapy of the pituitary to determine if continued therapy with the drug and/or radiation is necessary.^{a b} If signs and/or symptoms of acromegaly recur or growth hormone concentrations increase during this period, consider additional bromocriptine therapy.^{a b}

  
  

Administration

Oral Administration

Administer orally with food.^{a b}

Dosage

Available as bromocriptine mesylate; dosage expressed in terms of bromocriptine.^a

Pediatric Patients

Hyperprolactinemic Disorders

Prolactin-secreting Adenomas

Oral

Children ≥11 years of age: Initially, 1.25–2.5 mg daily.^a May increase as tolerated until therapeutic response achieved.^a Usual dosage range is 2.5–10 mg daily.^a

Adults

Hyperprolactinemic Disorders

Amenorrhea, Galactorrhea, Female Infertility

Oral

Initially, 1.25–2.5 mg daily.^{a b} May increase dosage by 2.5 mg every 2–7 days, as tolerated, until therapeutic response achieved.^a Usual dosage range is 2.5–15 mg daily;^a up to 30 mg daily has been required in some patients with amenorrhea and/or galactorrhea.^b

Hypogonadism and Galactorrhea in Males

Oral

Initially, 1.25–2.5 mg daily.^{a b} May increase dosage by 2.5 mg every 2–7 days, as tolerated, until therapeutic response achieved.^a Usual dosage range is 2.5–15 mg daily;^a up to 40 mg daily has been required in some patients.^b

Prolactin-secreting Adenomas

Oral

Initially, 1.25–2.5 mg daily.^b May increase dosage by 2.5 mg every 2–7 days, as tolerated, until therapeutic response achieved.^a Usual dosage range is 2.5–15 mg daily.^a

Parkinsonian Syndrome

Oral

Initially, 1.25 mg twice daily with meals.^{a b} If needed, may increase dosage by 2.5 mg daily every 14–28 days; do not exceed 100 mg daily.^{a b}

If levodopa dosage reduced because of adverse effects, may increase daily dosage of bromocriptine gradually in 2.5-mg increments.^{a b}

Acromegaly

Oral

Initially, 1.25–2.5 mg at bedtime for 3 days.^{a b} May increase dosage by 1.25–2.5 mg daily at 3- to 7-day intervals, as tolerated, until desired therapeutic benefit achieved.^{a b}

Reevaluate patients monthly, adjust dosage based on reduction of growth hormone or clinical response.^{a b} Usual dosage range is 20–30 mg daily; do not exceed 100 mg daily.^{a b} Dosages of 20–60 mg have been administered daily in divided doses.^b

Neuroleptic Malignant Syndrome†

Oral

2.5–5 mg 2–6 times daily.^b

Hepatic Encephalopathy†

Oral

Initially, 1.25 mg daily; increase dosage by 1.25 mg daily every third day up to a total maintenance dosage of 15 mg daily.^b

Prescribing Limits

Safety of dosages >100 mg daily not established.^{a b}

Adults

Parkinsonian Syndrome

Oral

Maximum 100 mg daily.^{a b} Safety of therapy for >2 years not established.^{a b}

Special Populations

Hepatic Impairment

Decreased clearance; dosage adjustment may be necessary.^a (See Elimination under Pharmacokinetics)

Cautions for Bromocriptine Mesylate

Contraindications

• 
  

  Uncontrolled hypertension.^{a b} (See Cardiovascular Effects under Cautions.)

  
  


• 
  

  Known sensitivity to ergot alkaloids.^{a b}

  
  


• 
  

  Known hypersensitivity to bromocriptine or any ingredient in the formulation.^a

  
  

Warnings/Precautions

Warnings

Pregnancy

Mechanical contraceptive measures recommended for women not seeking pregnancy or those with large adenomas.^{a b} Perform pregnancy test every 4 weeks in amenorrheic women and, once menses are reinstated, whenever a menstrual period is missed.^{a b}

Possible sudden enlargement of underlying prolactin-secreting pituitary tumors in women with hyperprolactinemic disorders who become pregnant and discontinue bromocriptine therapy; may result from normal increases in pituitary size during pregnancy.^{a b} May cause optic nerve compression, visual impairment, or blindness, which usually disappear after delivery; regular visual field checks recommended.^{a b} Diabetes insipidus and pituitary apoplexy also may occur.^{a b} Prior to initiating therapy for amenorrhea/galactorrhea and infertility, carefully evaluate the pituitary including gadolinium-enhanced MRI to rule out pituitary tumors.^{a b c}

Discontinue therapy immediately if pregnancy occurs during therapy for hyperprolactinemic disorders and carefully observe women throughout pregnancy for signs and symptoms of tumor progression.^{a b} If reinstitution of therapy is required to control a rapidly expanding macroadenoma and a hypertensive disorder associated with pregnancy occurs, consider risks and benefits of continuing bromocriptine therapy.^a (See Cardiovascular Effects under Cautions.)

If pregnancy occurs in a woman receiving therapy for acromegaly or parkinsonian syndrome, discontinue therapy unless bromocriptine therapy is medically necessary.^a If therapy is continued and a hypertensive disorder of pregnancy occurs, discontinue therapy unless bromocriptine withdrawal is medically contraindicated.^{a b}

Only continue bromocriptine during the postpartum period in women with a cardiovascular disease history if withdrawal is considered medically contraindicated; carefully observe the patient.^a

Somnolence

Episodes of falling asleep while engaged in activities of daily living, sometimes without warning or awareness, have been reported, particularly in patients with parkinsonian syndrome.^a Consider dosage reduction or treatment discontinuance if these effects occur.^a

Cardiovascular Effects

Symptomatic hypotension reported, especially during initial treatment; use caution, especially during the first days of treatment.^{a b}

Hypertension (sometimes developing with initiation of therapy but often during the second week), seizures, and potentially fatal strokes reported, mostly in postpartum women.^a Acute MI reported rarely.^a

Seizures and strokes usually preceded by a constant and severe headache hours to days prior to event and may be preceded by visual disturbances (blurred vision, transient cortical blindness).^{a b}

Discontinue therapy immediately and evaluate patient promptly if hypertension; severe, progressive, or unremitting headache (with or without visual disturbances); or evidence of CNS toxicity occurs.^{a b}

Periodic monitoring of BP recommended, especially during the first few weeks of therapy.^a

Use with caution in patients with a history of cardiovascular disease or MI with residual atrial, nodal, or ventricular arrhythmia.^{a b}

Fibrotic Effects

Pleural and pericardial effusions, constrictive pericarditis, and pleural and pulmonary fibrosis reported, especially in patients receiving high-dose, long-term therapy; usually resolves slowly with discontinuance of therapy.^{a b} Consider discontinuance of therapy if these disorders occur.^a

Observe patients receiving long-term (e.g., 6–36 months), high-dose (e.g., 20–100 mg daily) therapy for pulmonary changes (e.g., infiltrates, effusion, and thickening of the pleura).^{a b} Thoroughly evaluate unexplained pleuropulmonary disorders and consider discontinuance of therapy.^a

Retroperitoneal fibrosis reported rarely in patients receiving long-term (e.g., 2–10 years), high-dose (30–140 mg daily) therapy.^{a b} Monitor for manifestations (e.g., back pain, lower extremity edema, impaired kidney function); discontinue therapy if fibrotic changes are diagnosed or suspected.^a

General Precautions

Nervous System Effects

Confusion and mental disturbances may occur in patients with parkinsonian syndrome receiving high-dose therapy; usually resolve within 2–3 weeks after discontinuance.^a Use caution in patients who manifest mild dementia.^a

Visual or auditory hallucinations reported in patients with parkinsonian syndrome; hallucinations usually resolve following dosage reduction, but discontinuance of drug may occasionally be necessary.^{a b} Rarely, hallucinations may persist for several weeks following discontinuance of the drug.^{a b} Use with caution in patients with a history of psychosis.^a

CSF rhinorrhea reported rarely in patients with prolactin-secreting adenomas who previously underwent transsphenoidal surgery and/or radiation therapy and who were receiving the drug for tumor recurrence; may also occur in patients with previously untreated prolactinoma that extends into the sphenoid sinus.^{a b}

Lactose Intolerance

Use not recommended in patients with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption.^a

Ocular Effects

Secondary visual field loss due to chiasmal herniation may occur in patients with macroprolactinoma effectively treated for hyperprolactinemia.^{a b} Monitor patients and consider decreasing dosage if this occurs.^a

Relative efficacy of bromocriptine therapy versus surgery in preserving the visual fields in patients with hyperprolactinemic disorders not known.^{a b} Patients with rapidly progressing visual field loss should be evaluated by a neurosurgeon.^{a b}

Digital Vasospasm

Cold-sensitive digital vasospasm reported in patients being treated for acromegaly; usually resolves following a reduction in dosage and may be prevented by keeping fingers warm.^a

Growth Hormone-secreting Tumors

Possible expansion of growth hormone-secreting tumors in patients with acromegaly.^{a b} Careful monitoring recommended; if evidence of tumor expansion occurs, discontinue therapy and consider alternative therapies.^{a b}

Adequate Patient Monitoring

Evaluate hepatic, hematopoietic, cardiovascular, and renal function periodically in patients receiving prolonged therapy with bromocriptine (e.g., treatment of parkinsonian syndrome).^a

GI Bleeding

Severe GI bleeding from peptic ulcers, sometimes fatal, reported in patients with acromegaly.^{a b} Closely monitor patients with a history of peptic ulcer or GI bleeding.^{a b} Thoroughly evaluate signs and symptoms of peptic ulcer; institute appropriate therapy if necessary.^{a b}

Specific Populations

Pregnancy

Category B.^a (See Warnings: Pregnancy under Cautions.)

Lactation

Use not recommended in nursing women because bromocriptine interferes with lactation.^{a b}

Pediatric Use

Safety and efficacy established for children ≥16 years of age for treatment of prolactin-secreting adenomas.^a However, bromocriptine has been evaluated in well-controlled clinical trials in children ≥11 years of age.^a

Safety and efficacy not established for other uses.^a

Geriatric Use

Insufficient experience in clinical trials with patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; consider age-related decreases in hepatic, renal, or cardiac function in this population.^{a b}

Hepatic Impairment

Use with caution; safety and efficacy not established.^{a b} Reduced dosage may be required.^{a b}

Renal Impairment

Use with caution; safety and efficacy not established.^{a b}

Common Adverse Effects

Patients with hyperprolactinemia: Nausea, headache, fatigue, dizziness, lightheadedness, vomiting, abdominal cramps, constipation, diarrhea, drowsiness, nasal congestion.^a

Patients with acromegaly: Nausea, constipation, postural/orthostatic hypotension, anorexia, dry mouth/nasal stuffiness, indigestion/dyspepsia, digital vasospasm, drowsiness.^a

Patients with parkinsonian syndrome: Nausea, involuntary movements, hallucinations, confusion, “on-off” episodes, dizziness, drowsiness, faintness/fainting, vomiting, asthenia, abdominal discomfort, visual disturbance, ataxia, insomnia, depression, hypotension, shortness of breath, constipation, vertigo.^a

Interactions for Bromocriptine Mesylate

Metabolized principally by CYP3A; potent inhibitor of CYP3A4.^a

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma bromocriptine concentrations).^a

Drugs Metabolized by Hepatic Microsomal Enzymes

Potent substrates of CYP3A4: Potential pharmacokinetic interaction (increased plasma substrate concentrations).^a However, not expected to alter metabolism of CYP3A4 substrates, due to low free concentrations of bromocriptine.^a

Drugs That Increase Prolactin Concentrations

Potential inhibition of bromocriptine's effectiveness in reducing serum prolactin concentrations.^a

Specific Drugs

Drug	Interaction	Comments
Alcohol	May potentiate adverse effects of bromocriptinea Possible decreased alcohol toleranceb	Limit alcohol intakea b
Antidepressants, tricyclics (amitriptyline, imipramine)	Potential reduced efficacy of bromocriptine b	Consider increasing bromocriptine dosageb
Antifungals, azoles	Possible interference with bromocriptine metabolisma	Use concomitantly with cautiona
Antihypertensives	Potential additive hypotensive effectsa b	Careful adjustment of antihypertensive dosage may be necessarya b Use with cautiona b
Antipsychotic agents (haloperidol, phenothiazines)	Possible reduced efficacy of bromocriptinea b	Increased bromocriptine dosage may be required if used concomitantlyb
Butyrophenones (e.g., droperidol)	Potential reduced bromocriptine concentrationsa b	Consider increasing bromocriptine dosageb
Dopamine antagonists (e.g., metoclopromide, pimozide)	Possible reduced efficacy of bromocriptinea
Ergot alkaloids	Potential for severe adverse effects (e.g., hypertension, myocardial infarction)a b (see Cardiovascular Effects under Cautions)	Concomitant use not recommendeda b
HIV protease inhibitors	Possible interference with bromocriptine metabolisma	Use concomitantly with cautiona
Levodopa	Potential additive therapeutic and neurologic effectsb	May be used to therapeutic advantage; consider decreasing levodopa dosageb
Macrolide antibiotics (e.g., erythromycin)	Increased plasma bromocriptine concentrationsa
Methyldopa	Possible reduced efficacy of bromocriptineb	Increased bromocriptine dosage may be required if used concomitantlyb
Octreotide	Increased concentrations of bromocriptinea
Reserpine	Possible reduced efficacy of bromocriptinea b	Increased bromocriptine dosage may be required if used concomitantlyb

Bromocriptine Mesylate Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability 28%, with peak plasma concentration usually attained within 1–3 hours.^a

Onset

Following oral administration, onset of prolactin-lowering effect begins within 1–2 hours of ingestion, with maximal benefit within 5–10 hours.^a Parkinsonian effects may begin 30–90 minutes after ingestion, with maximal benefit within approximately 2 hours.^b

Duration

Maximum prolactin-lowering effects generally persist for 8–12 hours.^a

Distribution

Extent

Does not distribute appreciably into erythrocytes.^{a b}

Plasma Protein Binding

90–96% (mainly albumin).^a

Elimination

Metabolism

Undergoes extensive first-pass biotransformation in the liver, primarily via CYP3A and hydroxylation, to form inactive metabolites.^{a b}

Elimination Route

Bromocriptine and its metabolites eliminated principally (85%) in feces via biliary excretion and to a lesser extent (6%) in urine.^{a b}

Half-life

Biphasic; terminal half-life is approximately 15 hours.^a

Special Populations

Hepatic impairment decreases elimination, resulting in increased plasma bromocriptine concentrations.^a

Stability

Storage

Oral

Capsules and Tablets

Tight, light-resistant containers at <25°C.^a

ActionsActions

• 
  

  A dopamine receptor agonist that activates postsynaptic dopamine receptors that modulate the secretion of prolactin from the anterior pituitary. ^a

  
  


• 
  

  Substantially reduces serum prolactin concentrations by inhibiting release of prolactin from the anterior pituitary gland; directly affects the pituitary and/or stimulates postsynaptic dopamine receptors in the hypothalamus to release prolactin-inhibitory factor via a complicated catecholamine pathway.^b

  
  


• 
  

  Causes transient increases in somatropin (growth hormone) secretion in individuals with normal growth hormone concentrations; paradoxically causes sustained suppression of growth hormone secretion in patients with acromegaly.^{a b}

  
  


• 
  

  Relieves symptoms of parkinsonism by directly stimulating dopamine receptors in the corpus striatum;^{a b} dysregulation of brain serotonin activity may also occur.^b

  
  

Advice to Patients

• 
  

  Risk of dizziness, drowsiness, or faintness; use caution when driving or operating machinery.^{a b}

  
  


• 
  

  Risk of somnolence; possibility of falling asleep during activities of daily living.^{a b} If this occurs, patients should not drive or participate in potentially dangerous activities until episodes resolve.^{a b}

  
  


• 
  

  Importance of immediately informing clinician if persistent watery nasal discharge occurs in patients being treated for macroadenoma or in patients who have had recent transsphenoidal surgery.^a

  
  


• 
  

  Advise patients being treated for macroadenoma that discontinuance of bromocriptine may result in rapid regrowth of tumor and recurrence of original symptoms.^a

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses, such as hypertension or hypotension.^a

  
  


• 
  

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

  
  


• 
  

  Importance of using a method of contraception and monitoring regular pregnancy tests in patients treated for amenorrhea, as pregnancy may occur prior to the return of menses.^a

  
  


• 
  

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

  
  

Preparations

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

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

Bromocriptine Mesylate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	5 mg (of bromocriptine)*	Bromocriptine Mesylate Tablets	Sandoz
			Parlodel	Novartis
	Tablets	2.5 mg (of bromocriptine)*	Bromocriptine Mesylate Tablets	Lek, Sandoz
			Parlodel SnapTabs (with povidone; scored)	Novartis

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.

Bromocriptine Mesylate 2.5MG Tablets (MYLAN): 30/$64.99 or 90/$174.97

Bromocriptine Mesylate 5MG Capsules (MYLAN): 30/$135.99 or 90/$385.97

Parlodel 2.5MG Tablets (NOVARTIS): 30/$165.99 or 90/$497.98

Parlodel 5MG Capsules (NOVARTIS): 30/$259.99 or 90/$709.96

Disclaimer

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

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

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 2007. 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

100. Anon. Sandoz withdrawing Parlodel postpartum lactation suppression indication. Prescription Pharm Biotechnol. 1994; 56(Aug 22):T&G1-2.

101. Anon. Bromocriptine indication withdrawn. FDA Med Bulletin. 1994; 24:2.

102. Anon. Sandoz will halt promotion of bromocriptine for suppression of lactation. Am J Hosp Pharm. 1994; 51:2626.

103. Hartwig SC, Smeenk DA, Michaels MR. Drug-use evaluation program for postpartum bromocriptine therapy. Am J Hosp Pharm. 1990; 47:2514-5. [PubMed 2278264]

104. Larrazet F, Spaulding C, Lobreau HJ et al. Possible bromocriptine-induced myocardial infarction. Ann Intern Med. 1993; 118:199-200. [IDIS 308704] [PubMed 8417637]

105. Sandoz, East Hanover, NJ: Personal communication.

106. Sandoz. Parlodel (bromocriptine mesylate) Snap-Tabs tablets and capsules prescribing information dated Sep 1993. In: Physicians’ desk reference. 49th ed. Montvale, NJ: Medical Economics Company, Inc. 1994:2178-80.

107. Rothman KJ, Funch DP, Dreyer NA. Bromocriptine and puerperal seizures. Epidemiology. 1990; 1:232-8. [PubMed 2081258]

108. Eickman FM. Recurrent myocardial infarction in a postpartum patient receiving bromocriptine. Clin Cardiol. 1992; 15:781-3. [PubMed 1395192]

109. Gittelman D. Bromocriptine associated with postpartum hypertension, seizures, and pituitary hemorrhage. Gen Hosp Psychiatry. 1991; 13:278-80. [PubMed 1874430]

110. Food and Drug Administration. Sandoz Pharmaceutical Corp.; Bromocriptine mesylate (Parlodel); withdrawal of approval of the indication for the prevention of physiological lactation. [Docket No. 94N-0304.] Fed Regist. 1995; 60:3404-5.

111. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology. 2001; 56:S1-S88.

112. Anon. Initial treatment of Parkinson’s disease: wait just a minute. Med Lett Drugs Ther. 2001; 43:59-60. [PubMed 11445778]

a. Novartis. Parlodel (bromocriptine mesylate) SnapTabs tablets and capsules prescribing information. Suffern, NY; 2006 May.

b. AHFS drug information 2006. McEvoy GK, ed. Bromocriptine mesylate. Bethesda, MD: American Society of Health-System Pharmacists; 2006:3610-4.

c. Schleachte, JA. Prolactinoma. NEJM. 2007; 349;21:2035-41.

More Bromocriptine Mesylate resources

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

• Bromocriptine Prescribing Information (FDA)


• bromocriptine Advanced Consumer (Micromedex) - Includes Dosage Information


• Bromocriptine MedFacts Consumer Leaflet (Wolters Kluwer)


• Cycloset Prescribing Information (FDA)


• Cycloset MedFacts Consumer Leaflet (Wolters Kluwer)


• Cycloset Consumer Overview


• Parlodel Prescribing Information (FDA)

Compare Bromocriptine Mesylate with other medications

• Acromegaly
• Diabetes, Type 2
• Hyperprolactinemia
• Parkinson's Disease
• Tardive Dyskinesia

Mycoder

Mycoder may be available in the countries listed below.

Ingredient matches for Mycoder

Fluconazole

Fluconazole is reported as an ingredient of Mycoder in the following countries:

• Bangladesh

International Drug Name Search

Isotard

Isotard may be available in the countries listed below.

UK matches:

• Isotard 25, 40, 50 and 60 mg XL Tablets
• Isotard XL (SPC)

Ingredient matches for Isotard

Isosorbide Dinitrate

Isosorbide Dinitrate is reported as an ingredient of Isotard in the following countries:

• Israel

Isosorbide Mononitrate

Isosorbide Mononitrate is reported as an ingredient of Isotard in the following countries:

• United Kingdom

International Drug Name Search

Glossary

SPC	Summary of Product Characteristics (UK)

Click for further information on drug naming conventions and International Nonproprietary Names.

Brilinta

Pronunciation: tye-KA-grel-or
Generic Name: Ticagrelor
Brand Name: Brilinta

Brilinta can cause serious and sometimes fatal bleeding problems. Do not use Brilinta if you have an active bleeding problem or a history of bleeding in the brain.

Tell your doctor if you have recently had surgery or if you are scheduled to have surgery. You may need to stop taking Brilinta before you have surgery. Discuss any questions or concerns with your doctor.

Brilinta should be taken along with aspirin. Do not exceed the dose of aspirin recommended by your doctor while you are taking Brilinta. Taking doses of aspirin that are higher than the dose recommended while you are taking Brilinta may decrease Brilinta's effectiveness.

Brilinta is used for:

Reducing the risk of stroke, heart attack, or death in certain patients who have had a heart attack or who have angina (chest pain). It should be used along with aspirin as directed by your doctor. It also may be used for other conditions as determined by your doctor.

Brilinta is a platelet aggregation inhibitor. It works by slowing or stopping platelets from sticking to blood vessel walls or injured tissues.

Do NOT use Brilinta if:

• you are allergic to any ingredient in Brilinta


• you have an active bleeding problem (eg, bleeding stomach ulcer, bleeding in the brain) or a history of bleeding in the brain


• you have severe liver problems


• you are taking certain azole antifungals (eg, itraconazole, ketoconazole, voriconazole), carbamazepine, dexamethasone, certain macrolide antibiotics (eg, clarithromycin), nefazodone, phenobarbital, phenytoin, certain protease inhibitors (eg, atazanavir, ritonavir), rifampin, or telithromycin

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

Before using Brilinta:

Some medical conditions may interact with Brilinta. 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 liver or kidney problems, lung or breathing problems (eg, asthma, chronic obstructive pulmonary disease [COPD]), recent stomach or bowel bleeding, or a history of ulcers or bowel polyps


• if you have had a recent injury or surgery, including dental surgery; if you will be having surgery or a dental procedure; or if you are on dialysis


• if you have certain irregular heartbeat problems (eg, sick sinus syndrome, second- or third-degree heart block), or you have fainting caused by slow heartbeat and you do not have a permanent pacemaker


• if you have a history of bleeding or clotting problems, stroke, gouty arthritis, or high blood uric acid levels


• if you have received medicine to dissolve a blood clot (eg, alteplase) within 24 hours of taking Brilinta


• if you take another medicine to prevent or treat blood clots

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

• Anticoagulants (eg, heparin, warfarin), direct thrombin inhibitors (eg, dabigatran, desirudin), nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, celecoxib, ibuprofen), rivaroxaban, or salicylates (eg, aspirin) because the risk of bleeding may be increased


• Azole antifungals (eg, fluconazole, ketoconazole, voriconazole), macrolide antibiotics (eg, clarithromycin, erythromycin), nefazodone, protease inhibitors (eg, amprenavir, atazanavir, ritonavir), or telithromycin because they may increase the risk of Brilinta's side effects


• Carbamazepine, dexamethasone, efavirenz, hydantoins (eg, phenytoin), phenobarbital, primidone, rifamycins (eg, rifampin), or St. John's wort because they may decrease Brilinta's effectiveness


• Digoxin, lovastatin, or simvastatin because the risk of their side effects may be increased by Brilinta

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

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

• Brilinta comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Brilinta refilled.


• Take Brilinta by mouth with or without food.


• Take Brilinta on a regular schedule to get the most benefit from it.


• If you miss a dose of Brilinta, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

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

Important safety information:

• Brilinta may cause dizziness. This effect may be worse if you take it with alcohol or certain medicines. Use Brilinta with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not stop taking Brilinta without checking with your doctor. This may increase the risk of certain heart problems. If you need to stop taking Brilinta, follow your doctor's directions carefully.


• Do not exceed the dose of aspirin recommended by your doctor while you are taking Brilinta. Before you start any new medicine, check the label to see if it has aspirin in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• Brilinta reduces the action of the 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 Brilinta before you receive any medical or dental care, emergency care, or surgery. You may need to stop Brilinta before you have certain types of surgery.


• Use Brilinta with caution in the ELDERLY; they may be more sensitive to its effects, especially bleeding problems.


• Brilinta should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Avoid becoming pregnant while you are taking Brilinta. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Brilinta while you are pregnant. It is not known if Brilinta is found in breast milk. Do not breast-feed while taking Brilinta.

Possible side effects of Brilinta:

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:

Back pain; cough; diarrhea; dizziness; headache; nausea; minor bleeding; tiredness.

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); bleeding in the eye; bloody or black, tarry stools; chest pain; coughing up blood; dark or bloody urine; fainting; fast, slow, or irregular heartbeat; light-headedness; purple skin patches; severe or persistent headache or dizziness; shortness of breath; symptoms of stroke (eg, sudden numbness or weakness of an arm, leg, or the face; one-sided weakness; sudden confusion, trouble speaking, or trouble understanding others; loss of balance, coordination, or trouble walking; sudden severe headache or dizziness with no known cause); unusual bruising; unusual, prolonged, or severe bleeding (eg, excessive bleeding from cuts, increased menstrual bleeding, nosebleeds, unexplained vaginal bleeding, unusual bleeding from the gums when brushing); vomiting blood or vomit that looks like coffee grounds.

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: Brilinta 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 irregular heartbeat; severe diarrhea, nausea, or vomiting; unusual bruising or bleeding.

Proper storage of Brilinta:

Store Brilinta at room temperature, between 59 and 86 degrees F (15 and 30 degrees C) in its original container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Brilinta out of the reach of children and away from pets.

General information:

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


• Brilinta 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 Brilinta. 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 Brilinta resources

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

• Brilinta Consumer Overview


• Brilinta Advanced Consumer (Micromedex) - Includes Dosage Information


• Ticagrelor Professional Patient Advice (Wolters Kluwer)

Compare Brilinta with other medications

• Acute Coronary Syndrome

Clomipramin-CT

Clomipramin-CT may be available in the countries listed below.

Ingredient matches for Clomipramin-CT

Clomipramine

Clomipramine hydrochloride (a derivative of Clomipramine) is reported as an ingredient of Clomipramin-CT in the following countries:

• Germany

International Drug Name Search

Ufonitren

Ufonitren may be available in the countries listed below.

Ingredient matches for Ufonitren

Omeprazole

Omeprazole is reported as an ingredient of Ufonitren in the following countries:

• Ethiopia


• Greece


• Latvia

International Drug Name Search

Quedox

Quedox may be available in the countries listed below.

Ingredient matches for Quedox

Clarithromycin

Clarithromycin is reported as an ingredient of Quedox in the following countries:

• Mexico

International Drug Name Search

Procardia XL

See also: Generic Procardia

Procardia XL is a brand name of nifedipine, approved by the FDA in the following formulation(s):

PROCARDIA XL (nifedipine - tablet, extended release; oral)

• 
  Manufacturer: PFIZER
  
  Approval date: September 6, 1989
  
  Strength(s): 30MG ^[AB2], 60MG ^[AB2], 90MG ^[RLD][AB2]

Has a generic version of Procardia XL been approved?

Yes. The following products are equivalent to Procardia XL:

nifedipine tablet, extended release; oral

• 
  Manufacturer: MATRIX LABS LTD
  
  Approval date: September 13, 2010
  
  Strength(s): 30MG ^[AB2], 60MG ^[AB2], 90MG ^[AB2]


• 
  Manufacturer: MYLAN
  
  Approval date: June 21, 2010
  
  Strength(s): 30MG ^[AB2], 60MG ^[AB2], 90MG ^[AB2]


• 
  Manufacturer: OSMOTICA PHARM
  
  Approval date: November 21, 2005
  
  Strength(s): 30MG ^[AB2], 60MG ^[AB2]


• 
  Manufacturer: OSMOTICA PHARM
  
  Approval date: October 3, 2007
  
  Strength(s): 90MG ^[AB2]


• 
  Manufacturer: VALEANT INTL
  
  Approval date: September 27, 2000
  
  Strength(s): 60MG ^[AB2]


• 
  Manufacturer: VALEANT INTL
  
  Approval date: February 6, 2001
  
  Strength(s): 30MG ^[AB2]

Note: Fraudulent online pharmacies may attempt to sell an illegal generic version of Procardia XL. These medications may be counterfeit and potentially unsafe. If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. Ask your health care provider for advice if you are unsure about the online purchase of any medication.

See also: About generic drugs.

Related Patents

There are no current U.S. patents associated with Procardia XL.

See also...

• Procardia XL Sustained-Release Tablets Consumer Information (Wolters Kluwer)
• Procardia XL Consumer Information (Cerner Multum)
• Procardia XL Advanced Consumer Information (Micromedex)
• Nifedipine Consumer Information (Drugs.com)
• Nifedipine Consumer Information (Wolters Kluwer)
• Nifedipine Sustained-Release Tablets Consumer Information (Wolters Kluwer)
• Nifedipine Consumer Information (Cerner Multum)
• Nifedipine Advanced Consumer Information (Micromedex)
• Nifedipine AHFS DI Monographs (ASHP)

Farmicetina

Farmicetina may be available in the countries listed below.

Ingredient matches for Farmicetina

Chloramphenicol

Chloramphenicol is reported as an ingredient of Farmicetina in the following countries:

• Argentina

International Drug Name Search

Calcitonine

Calcitonine may be available in the countries listed below.

Ingredient matches for Calcitonine

Calcitonin

Calcitonine (DCF) is known as Calcitonin in the US.

International Drug Name Search

Glossary

DCF	Dénomination Commune Française

Click for further information on drug naming conventions and International Nonproprietary Names.

Spektramox

Spektramox may be available in the countries listed below.

Ingredient matches for Spektramox

Amoxicillin

Amoxicillin trihydrate (a derivative of Amoxicillin) is reported as an ingredient of Spektramox in the following countries:

• Denmark


• Sweden

Clavulanate

Clavulanic Acid potassium (a derivative of Clavulanic Acid) is reported as an ingredient of Spektramox in the following countries:

• Denmark


• Sweden

International Drug Name Search

Etibi

Etibi may be available in the countries listed below.

Ingredient matches for Etibi

Ethambutol

Ethambutol dihydrochloride (a derivative of Ethambutol) is reported as an ingredient of Etibi in the following countries:

• Austria


• Canada

International Drug Name Search

OQ-Miot

OQ-Miot may be available in the countries listed below.

Ingredient matches for OQ-Miot

Acetylcholine

Acetylcholine Chloride is reported as an ingredient of OQ-Miot in the following countries:

• Colombia

International Drug Name Search

Mefoxil

Mefoxil may be available in the countries listed below.

Ingredient matches for Mefoxil

Cefoxitin

Cefoxitin sodium salt (a derivative of Cefoxitin) is reported as an ingredient of Mefoxil in the following countries:

• Greece

International Drug Name Search

Tinidazol

Tinidazol may be available in the countries listed below.

Ingredient matches for Tinidazol

Tinidazole

Tinidazole is reported as an ingredient of Tinidazol in the following countries:

• Chile


• Colombia


• Ecuador


• Georgia


• Lithuania


• Peru


• Venezuela

International Drug Name Search

Trihexyphenidyl

In the US, Trihexyphenidyl (trihexyphenidyl systemic) is a member of the drug class anticholinergic antiparkinson agents and is used to treat Cerebral Spasticity, Extrapyramidal Reaction and Parkinson's Disease.

US matches:

• Trihexyphenidyl


• Trihexyphenidyl Elixir


• Trihexyphenidyl Hydrochloride


• Trihexyphenidyl Oral Solution

Scheme

Rec.INN

ATC (Anatomical Therapeutic Chemical Classification)

N04AA01

CAS registry number (Chemical Abstracts Service)

0000144-11-6

Chemical Formula

C20-H31-N-O

Molecular Weight

301

Therapeutic Category

Treatment of Parkinson's disease: Central anticholinergic

Chemical Name

1-Piperidinepropanol, α-cyclohexyl-α-phenyl-

Foreign Names

• Trihexyphenidylum (Latin)
• Trihexyphenidyl (German)
• Trihexyphénidyle (French)
• Trihexifenidilo (Spanish)

Generic Names

• Benzhexol (OS: BAN)
• Triesifenidile (OS: DCIT)
• Trihexyphenidyl (OS: BAN)
• Trihexyphénidyle (OS: DCF)
• Win 511 (IS)
• Trihexyphenidyl Hydrochloride (OS: BANM, JAN)
• Benzhexol Hydrochloride (IS)
• Parkidyl (IS)
• Trihexyphenidyl Hydrochloride (PH: BP 2010, JP XIV, Ph. Int. 4, USP 32, Ph. Eur. 6)
• Trihexyphénidyle (chlorhydrate de) (PH: Ph. Eur. 6)
• Trihexyphenidylhydrochlorid (PH: Ph. Eur. 6)
• Trihexyphenidyli hydrochloridum (PH: Ph. Int. 4, Ph. Eur. 6)

Brand Names

• Apo-Trihex
  Apotex, Singapore; Apotex, Vietnam



• Artandyl
  Synco, Hong Kong



• Artane
  Aventis, Tunisia; Lederle, Israel; Teofarma, Portugal



• Parkizol
  Hikma, Tunisia; IBN, Tunisia



• Sizomax-T3 (Trihexyphenidyl and Risperidone)
  RPG, India



• SPMC Benzhexol
  SPMC, Sri Lanka



• Tonaril
  Chile, Chile



• Apo-Trihex
  Apotex, Canada



• Artane
  Cyanamid, Ethiopia; Hemofarm, Serbia; Lederle, Chile; Sanofi-Aventis, France; Sigma, Australia; Teofarma, Belgium; Teofarma, Germany; Teofarma, Spain; Teofarma, Italy; Teofarma, Luxembourg; Teofarma, Netherlands; Wyeth, Argentina; Wyeth, Brazil; Wyeth, Peru; Wyeth, Taiwan; Wyeth KK, Japan



• B.H.L.
  CCPC, Taiwan



• Beahexol
  Beacons, Singapore



• Benzhexol
  Remedica, Malta



• Broflex
  Alliance, United Kingdom



• Cyclodol
  BHFZ, Georgia; Grindeks, Estonia; Grindeks, Lithuania; Grindeks, Latvia; Grindex, Georgia



• Ea Ten
  Heng Hsin, Taiwan



• Hexymer
  Mersifarma, Indonesia



• Hipokinon
  Psicofarma, Mexico



• Pacitane
  Wyeth, India



• Pakisonal
  Takata Seiyaku, Japan



• Pargitan
  Nevada Pharma, Sweden



• Parkinane LP
  Eisai, France



• Parkines
  Towa Yakuhin, Japan



• Parkisan
  Actavis, Georgia



• Parkopan
  Hexal, Germany; Hexal, Poland; Sandoz, Estonia; Sandoz, Lithuania; Sandoz, Latvia



• Partane
  Taro, Israel



• Pyramistin
  Astellas, Japan



• Rodenal
  Rekah, Israel



• Romparkin
  Terapia, Romania



• Sedrena
  Daiichi Sankyo, Japan



• Stobrun
  Taiyo Pharmaceutical, Japan



• Tenvatil
  Drugtech-Recalcine, Chile



• Tremin
  Schering-Plough, Japan



• Trihexifenidilo Cevallos
  Cevallos, Argentina



• Trihexifenidilo Clorhidrato
  Bestpharma, Chile



• Trihexifenidilo
  Labinco, Colombia



• Trihexin
  Kyorin Rimedio, Japan



• Trihexyphenidyl Hydrochloride
  Mikart, United States; Pharmaceutical Associates, United States; Pharmaceutical Ventures, United States; URL, United States; Vintage, United States; Watson, United States



• Trihexyphenidyl
  Alliance, United Kingdom; Remedica, Cyprus



• Triphedinon
  Kyowa Yakuhin, Japan

International Drug Name Search

Glossary

BAN	British Approved Name
BANM	British Approved Name (Modified)
DCF	Dénomination Commune Française
DCIT	Denominazione Comune Italiana
IS	Inofficial Synonym
JAN	Japanese Accepted Name
OS	Official Synonym
PH	Pharmacopoeia Name
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)

Click for further information on drug naming conventions and International Nonproprietary Names.

Denorex Medicated Shampoo and Conditioner

Generic Name: coal tar topical (KOL TAR TOP ik al)

Brand Names: Balnetar, Betatar Gel, Coal Tar, Cutar, Denorex, Denorex Dry Scalp, Denorex Extra Strength, Denorex Medicated Shampoo and Conditioner, DHS Tar Shampoo, Doak Tar, Doak Tar Oil, Elta Tar, Fototar, G-TAR, Ionil T, Ionil T Plus, MG 217 Psoriasis, MG217 Medicated Tar, Neutrogena T/Derm, Neutrogena T/Gel, Neutrogena T/Gel Extra Strength, Oxipor VHC, PC Tar, Pentrax, Pentrax Gold, Polytar, Psoriasin, Psorigel, T/Gel Conditioner, Tegrin Medicated, Tegrin Medicated Soap, Therapeutic, Theraplex T, Zetar

What is coal tar?

Coal tar is a by-product of coal processing.

Coal tar topical (for the skin) is used to treat the skin symptoms of psoriasis, including dryness, redness, flaking, scaling, and itching. Coal tar is not a cure for psoriasis, and it will provide only temporary relief of skin symptoms.

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

What is the most important information I should know about coal tar?

You should not use this medication if you are allergic to coal tar.

Before using coal tar, tell your doctor if you are allergic to any drugs, or if you are receiving ultraviolet radiation treatment for your psoriasis.

Do not use coal tar to treat the skin of your groin or rectal area.

Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds). Coal tar can make your skin more sensitive to sunlight and sunburn may result. Stop using coal tar and call your doctor at once if you have severe stinging, burning, swelling, or other irritation of the treated skin. Do not use coal tar to treat large skin areas. Do not use coal tar over long periods of time without your doctor's advice.

Call your doctor if your symptoms do not improve, or if they get worse after using coal tar.

Coal tar is not a cure for psoriasis, and it will provide only temporary relief of skin symptoms.

What should I discuss with my health care provider before using coal tar?

You should not use this medication if you are allergic to coal tar.

Before using coal tar, tell your doctor if you are allergic to any drugs, or if you are receiving ultraviolet radiation treatment for your psoriasis.

This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether coal tar passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Coal tar products may contain lanolin, mineral oil, or other emulsifiers. Check the label of any coal tar product you are using. Talk with your doctor before using coal tar if you are allergic to any of the ingredients.

How should I use coal tar?

Use this medication as directed on the label, or as your doctor has prescribed. Do not use the medication in larger amounts or for longer than recommended.

Apply coal tar cream, lotion, ointment, or solution according the directions on the medication label. Some forms of coal tar may be applied 1 to 4 times per day.

To use coal tar bath oil, pour 1 to 3 capfuls into a warm bath before bathing. The oil can make the bathtub slippery. Take care to avoid a fall.

Shake the coal tar shampoo well just before each use. Use enough shampoo to create a rich lather. Massage the shampoo into your scalp and rinse thoroughly. Apply the shampoo a second time and leave it on your scalp for 5 minutes. Rinse thoroughly. Do not use coal tar to treat large skin areas. Do not use coal tar over long periods of time without your doctor's advice.

Call your doctor if your symptoms do not improve, or if they get worse after using coal tar.

Coal tar shampoo may discolor blond or colored hair. This effect is usually temporarily.

Some forms of coal tar can stain fabric or other surfaces.

Store coal tar at room temperature away from moisture and heat. Keep the medicine tightly closed with not in use.

What happens if I miss a dose?

Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

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

Symptoms of a coal tar overdose are not known.

What should I avoid while using coal tar?

Avoid getting this medication in your eyes. If this does occur, rinse with water.

Do not use coal tar to treat the skin of your groin or rectal area.

Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds). Coal tar can make your skin more sensitive to sunlight and sunburn may result.

Coal tar side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using coal tar and call your doctor at once if you have severe stinging, burning, swelling, or other irritation of the treated skin.

Less serious side effects may include mild skin irritation or skin rash.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect coal tar?

Do not use coal tar together with other psoriasis medications unless your doctor tells you to.

There may be other drugs that can interact with coal tar. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Denorex Medicated Shampoo and Conditioner resources

• Denorex Medicated Shampoo and Conditioner Use in Pregnancy & Breastfeeding
• 0 Reviews for Denorex Medicated and Conditioner - Add your own review/rating

• Betatar Gel Topical Advanced Consumer (Micromedex) - Includes Dosage Information


• Coal Tar Foam MedFacts Consumer Leaflet (Wolters Kluwer)


• Denorex Shampoo MedFacts Consumer Leaflet (Wolters Kluwer)


• Doak Tar Shampoo MedFacts Consumer Leaflet (Wolters Kluwer)


• Fototar Ointment MedFacts Consumer Leaflet (Wolters Kluwer)


• MG217 Medicated Tar Lotion MedFacts Consumer Leaflet (Wolters Kluwer)


• Psoriasin Prescribing Information (FDA)

Compare Denorex Medicated Shampoo and Conditioner with other medications

• Dermatitis
• Psoriasis
• Seborrheic Dermatitis

Where can I get more information?

• Your pharmacist can provide more information about coal tar.

Topfena

Topfena may be available in the countries listed below.

Ingredient matches for Topfena

Ketoprofen

Ketoprofen is reported as an ingredient of Topfena in the following countries:

• France

International Drug Name Search

Teatcare

Teatcare may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Teatcare

Chlorhexidine

Chlorhexidine digluconate (a derivative of Chlorhexidine) is reported as an ingredient of Teatcare in the following countries:

• New Zealand

International Drug Name Search

Lignocaine Hydrochloride Injection BP

Lignocaine Hydrochloride Injection BP may be available in the countries listed below.

Ingredient matches for Lignocaine Hydrochloride Injection BP

Lidocaine

Lidocaine hydrochloride (a derivative of Lidocaine) is reported as an ingredient of Lignocaine Hydrochloride Injection BP in the following countries:

• New Zealand

International Drug Name Search

Fluvoxin

Fluvoxin may be available in the countries listed below.

Ingredient matches for Fluvoxin

Fluvoxamine

Fluvoxamine maleate (a derivative of Fluvoxamine) is reported as an ingredient of Fluvoxin in the following countries:

• India

International Drug Name Search

Metocar

Metocar may be available in the countries listed below.

Ingredient matches for Metocar

Metoprolol

Metoprolol tartrate (a derivative of Metoprolol) is reported as an ingredient of Metocar in the following countries:

• Denmark

International Drug Name Search

Tusso Rhinathiol

Tusso Rhinathiol may be available in the countries listed below.

Ingredient matches for Tusso Rhinathiol

Dextromethorphan

Dextromethorphan hydrobromide (a derivative of Dextromethorphan) is reported as an ingredient of Tusso Rhinathiol in the following countries:

• Belgium


• Luxembourg

International Drug Name Search

Meticorten

In some countries, this medicine may only be approved for veterinary use.

In the US, Meticorten (prednisone systemic) is a member of the drug class glucocorticoids and is used to treat Acute Lymphocytic Leukemia, Adrenocortical Insufficiency, Adrenogenital Syndrome, Allergic Reactions, Ankylosing Spondylitis, Aspiration Pneumonia, Asthma, Atopic Dermatitis, Autoimmune Hemolytic Anemia, Berylliosis, Bullous Pemphigoid, Bursitis, Chorioretinitis, Cluster Headaches, Cogan's Syndrome, Conjunctivitis - Allergic, Corneal Ulcer, Dermatitis Herpetiformis, Dermatomyositis, Eczema, Epicondylitis - Tennis Elbow, Erythroblastopenia, Fibromyalgia, Gouty Arthritis, Graft-versus-host disease, Hay Fever, Herpes Zoster, Herpes Zoster Iridocyclitis, Hypercalcemia of Malignancy, Idiopathic Thrombocytopenic Purpura, Immunosuppression, Inflammatory Conditions, Iridocyclitis, Iritis, Juvenile Rheumatoid Arthritis, Keratitis, Leukemia, Lichen Planus, Lichen Sclerosus, Loeffler's Syndrome, Lymphoma, Multiple Sclerosis, Mycosis Fungoides, Nephrotic Syndrome, Neurosarcoidosis, Osteoarthritis, Pemphigoid, Pemphigus, Pharyngitis, Polymyositis/Dermatomyositis, Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, Sarcoidosis, Seborrheic Dermatitis, Sinusitis, Skin Rash, Synovitis, Systemic Lupus Erythematosus, Systemic Sclerosis, Thrombocytopenia, Toxic Epidermal Necrolysis, Tuberculosis - Extrapulmonary, Tuberculous Meningitis, Ulcerative Colitis and Uveitis - Posterior.

US matches:

• Meticorten

Ingredient matches for Meticorten

Prednisone

Prednisone is reported as an ingredient of Meticorten in the following countries:

• Argentina


• Brazil


• Chile


• Colombia


• Ecuador


• Mexico


• Peru


• Portugal


• South Africa


• United States


• Venezuela

International Drug Name Search

Propanorm

Propanorm may be available in the countries listed below.

Ingredient matches for Propanorm

Propafenone

Propafenone hydrochloride (a derivative of Propafenone) is reported as an ingredient of Propanorm in the following countries:

• Bosnia & Herzegowina


• Czech Republic


• Estonia


• Georgia


• Lithuania


• Russian Federation


• Slovakia

International Drug Name Search

Depakote Pellets

Generic Name: divalproex sodium

Dosage Form: capsule, delayed release pellets
FULL PRESCRIBING INFORMATION

BOXED WARNING

WARNING: LIFE THREATENING ADVERSE REACTIONS

HEPATOTOXICITY

Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid and its derivatives. Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. When Depakote Sprinkle Capsules are used in this patient group, they should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. The incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.

These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months [See Warnings and Precautions (5.1)].

TERATOGENICITY

Valproate can produce teratogenic effects such as neural tube defects (e.g., spina bifida). Accordingly, the use of Depakote Sprinkle Capsules in women of childbearing potential requires that the benefits of its use be weighed against the risk of injury to the fetus. This is especially important when the treatment of a spontaneously reversible condition not ordinarily associated with permanent injury or risk of death (e.g., migraine) is contemplated. [See Warnings and Precautions (5.2)]

An information sheet describing the teratogenic potential of valproate is available for patients [See Patient Counseling Information (17)].

PANCREATITIS

Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with a rapid progression from initial symptoms to death. Cases have been reported shortly after initial use as well as after several years of use. Patients and guardians should be warned that abdominal pain, nausea, vomiting and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, valproate should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated [see Warnings and Precautions (5.3)].

Indications and Usage for Depakote Pellets

Epilepsy

Depakote Sprinkle Capsules are indicated as monotherapy and adjunctive therapy in the treatment of adult patients and pediatric patients down to the age of 10 years with complex partial seizures that occur either in isolation or in association with other types of seizures. Depakote Sprinkle Capsules are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures.

Simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. Complex absence is the term used when other signs are also present. [see Warnings and Precautions (5.2), Patient Counseling Information (17.3)].

Depakote Pellets Dosage and Administration

Epilepsy

Depakote Sprinkle Capsules are administered orally. As Depakote dosage is titrated upward, concentrations of clonazepam, diazepam, ethosuximide, lamotrigine, tolbutamide, phenobarbital, carbamazepine, and/or phenytoin may be affected [see Drug Interactions (7.2)].

Complex Partial Seizures

For adults and children 10 years of age or older.

Monotherapy (Initial Therapy)

Depakote has not been systematically studied as initial therapy. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made.

The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males. The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.

Conversion to Monotherapy

Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 - 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made.

Concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks. This reduction may be started at initiation of Depakote therapy, or delayed by 1 to 2 weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable, and patients should be monitored closely during this period for increased seizure frequency.

Adjunctive Therapy

Depakote may be added to the patient's regimen at a dosage of 10 to 15 mg/kg/day. The dosage may be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. If the total daily dose exceeds 250 mg, it should be given in divided doses.

In a study of adjunctive therapy for complex partial seizures in which patients were receiving either carbamazepine or phenytoin in addition to Depakote, no adjustment of carbamazepine or phenytoin dosage was needed [see Clinical studies (14)]. However, since valproate may interact with these or other concurrently administered AEDs as well as other drugs, periodic plasma concentration determinations of concomitant AEDs are recommended during the early course of therapy [see Drug Interactions (7)].

Simple and Complex Absence Seizures

The recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. The maximum recommended dosage is 60 mg/kg/day. If the total daily dose exceeds 250 mg, it should be given in divided doses.

A good correlation has not been established between daily dose, serum concentrations, and therapeutic effect. However, therapeutic valproate serum concentrations for most patients with absence seizures are considered to range from 50 to 100 mcg/mL. Some patients may be controlled with lower or higher serum concentrations [see Clinical Pharmacology (12.2)].

As Depakote dosage is titrated upward, blood concentrations of phenobarbital and/or phenytoin may be affected [see Drug Interactions (7.2)].

Antiepilepsy drugs should not be abruptly discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.

In epileptic patients previously receiving Depakene (valproic acid) therapy, Depakote Sprinkle Capsules should be initiated at the same daily dose and dosing schedule. After the patient is stabilized on Depakote Sprinkle Capsules, a dosing schedule of two or three times a day may be elected in selected patients.

General Dosing Advice

Dosing in Elderly Patients

Due to a decrease in unbound clearance of valproate and possibly a greater sensitivity to somnolence in the elderly, the starting dose should be reduced in these patients. Dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. The ultimate therapeutic dose should be achieved on the basis of both tolerability and clinical response [see Warnings and Precautions (5.12), Use in Specific Populations (8.5) and Clinical Pharmacology (12.3)].

Dose-Related Adverse reactions

The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. The probability of thrombocytopenia appears to increase significantly at total valproate concentrations of ≥ 110 mcg/mL (females) or ≥ 135 mcg/mL (males) [see Warnings and Precautions (5.6)]. The benefit of improved therapeutic effect with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.

G.I. Irritation

Patients who experience G.I. irritation may benefit from administration of the drug with food or by slowly building up the dose from an initial low level.

Administration of Sprinkle Capsules

Depakote Sprinkle Capsules may be swallowed whole or may be administered by carefully opening the capsule and sprinkling the entire contents on a small amount (teaspoonful) of soft food such as applesauce or pudding. The drug/food mixture should be swallowed immediately (avoid chewing) and not stored for future use. Each capsule is oversized to allow ease of opening.

Dosage Forms and Strengths

Depakote Sprinkle Capsules are for oral administration. Depakote Sprinkle Capsules contain specially coated particles of divalproex sodium equivalent to 125 mg of valproic acid in a hard gelatin capsule.

Contraindications

• Depakote Sprinkle Capsules should not be administered to patients with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions (5.1)].


• Depakote Sprinkle Capsules is contraindicated in patients with known hypersensitivity to the drug [see Warnings and Precautions (5.10)].


• Depakote Sprinkle Capsules is contraindicated in patients with known urea cycle disorders [see Warnings and Precautions (5.4)].

Warnings and Precautions

Hepatotoxicity

Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid. These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months. However, healthcare providers should not rely totally on serum biochemistry since these tests may not be abnormal in all instances, but should also consider the results of careful interim medical history and physical examination.

Caution should be observed when administering Depakote products to patients with a prior history of hepatic disease. Patients on multiple anticonvulsants, children, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease may be at particular risk. Experience has indicated that children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions. When Depakote is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. Above this age group, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.

The drug should be discontinued immediately in the presence of significant hepatic dysfunction, suspected or apparent. In some cases, hepatic dysfunction has progressed in spite of discontinuation of drug [see Boxed Warning and Contraindications (4)].

Teratogenicity/Usage in Pregnancy

Use of Depakote during pregnancy can cause congenital malformations including neural tube defects. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Depakote should be considered for women of childbearing potential only after the risks have been thoroughly discussed with the patient and weighed against the potential benefits of treatment.

Data suggest that there is an increased incidence of congenital malformations associated with the use of valproate by women with seizure disorders during pregnancy when compared to the incidence in women with seizure disorders who do not use antiepileptic drugs during pregnancy, the incidence in women with seizure disorders who use other antiepileptic drugs, and the background incidence for the general population.

There are multiple reports in the clinical literature that indicate the use of antiepileptic drugs during pregnancy results in an increased incidence of congenital malformations in offspring. Antiepileptic drugs, including valproate, should be administered to women of childbearing potential only if they are clearly shown to be essential in the management of their medical condition.

 There have been reports of developmental delay, autism and/or autism spectrum disorder in the offspring of women exposed to valproate during pregnancy.

Antiepileptic drugs should not be discontinued abruptly in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus [see Boxed Warning and Use in Specific Populations (8.1)].

Pancreatitis

Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with rapid progression from initial symptoms to death. Some cases have occurred shortly after initial use as well as after several years of use. The rate based upon the reported cases exceeds that expected in the general population and there have been cases in which pancreatitis recurred after rechallenge with valproate. In clinical trials, there were 2 cases of pancreatitis without alternative etiology in 2416 patients, representing 1044 patient-years experience. Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, Depakote should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated [see Boxed Warning].

Urea Cycle Disorders (UCD)

Depakote is contraindicated in patients with known urea cycle disorders (UCD). Hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with urea cycle disorders, a group of uncommon genetic abnormalities, particularly ornithine transcarbamylase deficiency. Prior to the initiation of Depakote therapy, evaluation for UCD should be considered in the following patients: 1) those with a history of unexplained encephalopathy or coma, encephalopathy associated with a protein load, pregnancy-related or postpartum encephalopathy, unexplained mental retardation, or history of elevated plasma ammonia or glutamine; 2) those with cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low BUN, or protein avoidance; 3) those with a family history of UCD or a family history of unexplained infant deaths (particularly males); 4) those with other signs or symptoms of UCD. Patients who develop symptoms of unexplained hyperammonemic encephalopathy while receiving valproate therapy should receive prompt treatment (including discontinuation of valproate therapy) and be evaluated for underlying urea cycle disorders [see Contraindications (4) and Warnings and Precautions (5.7)].

Suicidal Behavior and Ideation

 Antiepileptic drugs (AEDs), including Depakote increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

 Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

 The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

 The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.

 Table 1 shows absolute and relative risk by indication for all evaluated AEDs.

Table 1. Risk by indication for antiepileptic drugs in the pooled analysis

Indication	Placebo Patients with Events Per 1000 Patients	Drug Patients with Events Per 1000 Patients	Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients	Risk Difference: Additional Drug Patients with Events Per 1000 Patients
Epilepsy	1.0	3.4	3.5	2.4
Psychiatric	5.7	8.5	1.5	2.9
Other	1.0	1.8	1.9	0.9
Total	2.4	4.3	1.8	1.9

 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

 Anyone considering prescribing Depakote or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

 Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.

Thrombocytopenia

The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. In a clinical trial of Depakote as monotherapy in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day on average, had at least one value of platelets ≤ 75 x 109/L. Approximately half of these patients had treatment discontinued, with return of platelet counts to normal. In the remaining patients, platelet counts normalized with continued treatment. In this study, the probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of ≥ 110 mcg/mL (females) or ≥ 135 mcg/mL (males). The therapeutic benefit which may accompany the higher doses should therefore be weighed against the possibility of a greater incidence of adverse effects.

Because of reports of thrombocytopenia, inhibition of the secondary phase of platelet aggregation, and abnormal coagulation parameters, (e.g., low fibrinogen), platelet counts and coagulation tests are recommended before initiating therapy and at periodic intervals. It is recommended that patients receiving Depakote be monitored for platelet count and coagulation parameters prior to planned surgery. Evidence of hemorrhage, bruising, or a disorder of hemostasis/coagulation is an indication for reduction of the dosage or withdrawal of therapy.

Hyperammonemia

Hyperammonemia has been reported in association with valproate therapy and may be present despite normal liver function tests. In patients who develop unexplained lethargy and vomiting or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured [see Contraindications (4) and Warnings and Precautions (5.4)].

Hyperammonemia should also be considered in patients who present with hypothermia [see Warnings and Precautions (5.9)]. If ammonia is increased, valproate therapy should be discontinued. Appropriate interventions for treatment of hyperammonemia should be initiated, and such patients should undergo investigation for underlying urea cycle disorders [see Contraindications (4) and Warnings and Precautions (5.4, 5.8)]. Asymptomatic elevations of ammonia are more common and when present, require close monitoring of plasma ammonia levels. If the elevation persists, discontinuation of valproate therapy should be considered.

Hyperammonemia and Encephalopathy associated with Concomitant Topiramate Use

Concomitant administration of topiramate and valproic acid has been associated with hyperammonemia with or without encephalopathy in patients who have tolerated either drug alone. Clinical symptoms of hyperammonemic encephalopathy often include acute alterations in level of consciousness and/or cognitive function with lethargy or vomiting. Hypothermia can also be a manifestation of hyperammonemia [see Warnings and Precautions (5.9)]. In most cases, symptoms and signs abated with discontinuation of either drug. This adverse event is not due to a pharmacokinetic interaction. It is not known if topiramate monotherapy is associated with hyperammonemia. Patients with inborn errors of metabolism or reduced hepatic mitochondrial activity may be at an increased risk for hyperammonemia with or without encephalopathy. Although not studied, an interaction of topiramate and valproic acid may exacerbate existing defects or unmask deficiencies in susceptible persons. In patients who develop unexplained lethargy, vomiting, or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured [see Contraindications (4) and Warnings and Precautions (5.4, 5.7)].

Hypothermia

Hypothermia, defined as an unintentional drop in body core temperature to < 35°C (95°F), has been reported in association with valproate therapy both in conjunction with and in the absence of hyperammonemia. This adverse reaction can also occur in patients using concomitant topiramate with valproate after starting topiramate treatment or after increasing the daily dose of topiramate [see Drug Interactions (7.3)]. Consideration should be given to stopping valproate in patients who develop hypothermia, which may be manifested by a variety of clinical abnormalities including lethargy, confusion, coma, and significant alterations in other major organ systems such as the cardiovascular and respiratory systems. Clinical management and assessment should include examination of blood ammonia levels.

Multi-Organ Hypersensitivity Reactions

Multi-organ hypersensitivity reactions have been rarely reported in close temporal association to the initiation of valproate therapy in adult and pediatric patients (median time to detection 21 days: range 1 to 40 days). Although there have been a limited number of reports, many of these cases resulted in hospitalization and at least one death has been reported. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. Other associated manifestations may include lymphadenopathy, hepatitis, liver function test abnormalities, hematological abnormalities (e.g., eosinophilia, thrombocytopenia, neutropenia), pruritus, nephritis, oliguria, hepato-renal syndrome, arthralgia, and asthenia. Because the disorder is variable in its expression, other organ system symptoms and signs, not noted here, may occur. If this reaction is suspected, valproate should be discontinued and an alternative treatment started. Although the existence of cross sensitivity with other drugs that produce this syndrome is unclear, the experience amongst drugs associated with multi-organ hypersensitivity would indicate this to be a possibility.

Interaction with Carbapenem Antibiotics

Carbapenem antibiotics (ertapenem, imipenem, meropenem) may reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations drop significantly or seizure control deteriorates [see Drug Interactions (7.1)].

Somnolence in the Elderly

In a double-blind, multicenter trial of valproate in elderly patients with dementia (mean age = 83 years), doses were increased by 125 mg/day to a target dose of 20 mg/kg/day. A significantly higher proportion of valproate patients had somnolence compared to placebo, and although not statistically significant, there was a higher proportion of patients with dehydration. Discontinuations for somnolence were also significantly higher than with placebo. In some patients with somnolence (approximately one-half), there was associated reduced nutritional intake and weight loss. There was a trend for the patients who experienced these events to have a lower baseline albumin concentration, lower valproate clearance, and a higher BUN. In elderly patients, dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence [see Dosage and Administration (2.4)].

Monitoring: Drug Plasma Concentration

Since Depakote may interact with concurrently administered drugs which are capable of enzyme induction, periodic plasma concentration determinations of valproate and concomitant drugs are recommended during the early course of therapy [see Drug Interactions (7)].

Effect on Ketone and Thyroid function Tests

Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test.

There have been reports of altered thyroid function tests associated with valproate. The clinical significance of these is unknown [see Adverse Events (6.2)].

Effect on HIV and CMV Viruses Replication

There are in vitro studies that suggest valproate stimulates the replication of the HIV and CMV viruses under certain experimental conditions. The clinical consequence, if any, is not known. Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. Nevertheless, these data should be borne in mind when interpreting the results from regular monitoring of the viral load in HIV infected patients receiving valproate or when following CMV infected patients clinically.

Adverse Reactions

The following adverse reactions are discussed in greater detail in other sections of the labeling:

Hepatic failure (5.1)

Teratogenicity (5.2)

Pancreatitis (5.3)

Hyperammonemic encephalopathy (5.4, 5.7)

Somnolence in the elderly (5.12)

Thrombocytopenia (5.6)

Multi-organ hypersensitivity reactions (5.10)

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

Epilepsy

Based on a placebo-controlled trial of adjunctive therapy for treatment of partial seizures, Depakote was generally well tolerated with most adverse reactions rated as mild to moderate in severity. Intolerance was the primary reason for discontinuation in the Depakote -treated patients (6%), compared to 1% of placebo-treated patients.

In a long term (12-month) safety study in pediatric patients (N=169) between the ages of 3 and 10 years old, no clinically meaningful differences in the adverse event profile were observed when compared to adults.

Table 2 lists treatment-emergent adverse reactions which were reported by ≥ 5% of Depakote -treated patients and for which the incidence was greater than in the placebo group, in the placebo-controlled trial of adjunctive therapy for treatment of complex partial seizures. Since patients were also treated with other antiepilepsy drugs, it is not possible, in most cases, to determine whether the following adverse reactions can be ascribed to Depakote alone, or the combination of Depakote and other antiepilepsy drugs.

Table 2. Adverse reactions Reported by ≥ 5% of Patients Treated with Depakote During Placebo-Controlled Trial of Adjunctive Therapy for Complex Partial Seizures

Body System/Event	Depakote (%) (n = 77)	Placebo (%) (n = 70)
Body as a Whole
Headache	31	21
Asthenia	27	7
Fever	6	4
Gastrointestinal System
Nausea	48	14
Vomiting	27	7
Abdominal Pain	23	6
Diarrhea	13	6
Anorexia	12	0
Dyspepsia	8	4
Constipation	5	1
Nervous System
Somnolence	27	11
Tremor	25	6
Dizziness	25	13
Diplopia	16	9
Amblyopia/Blurred Vision	12	9
Ataxia	8	1
Nystagmus	8	1
Emotional Lability	6	4
Thinking Abnormal	6	0
Amnesia	5	1
Respiratory System
Flu Syndrome	12	9
Infection	12	6
Bronchitis	5	1
Rhinitis	5	4
Other
Alopecia	6	1
Weight Loss	6	0

Table 3 lists treatment-emergent adverse reactions which were reported by ≥ 5% of patients in the high dose Depakote group, and for which the incidence was greater than in the low dose group, in a controlled trial of Depakote monotherapy treatment of complex partial seizures. Since patients were being titrated off another antiepilepsy drug during the first portion of the trial, it is not possible, in many cases, to determine whether the following adverse reactions can be ascribed to Depakote alone, or the combination of Depakote and other antiepilepsy drugs.

Table 3. Adverse reactions Reported by ≥ 5% of Patients in the High Dose Group in the Controlled Trial of Depakote Monotherapy for Complex Partial Seizuresa

Body System/Event	High Dose (%) (n = 131)	Low Dose (%) (n = 134)
Body as a Whole
Asthenia	21	10
Digestive System
Nausea	34	26
Diarrhea	23	19
Vomiting	23	15
Abdominal Pain	12	9
Anorexia	11	4
Dyspepsia	11	10
Hemic/Lymphatic System
Thrombocytopenia	24	1
Ecchymosis	5	4
Metabolic/Nutritional
Weight Gain	9	4
Peripheral Edema	8	3
Nervous System
Tremor	57	19
Somnolence	30	18
Dizziness	18	13
Insomnia	15	9
Nervousness	11	7
Amnesia	7	4
Nystagmus	7	1
Depression	5	4
Respiratory System
Infection	20	13
Pharyngitis	8	2
Dyspnea	5	1
Skin and Appendages
Alopecia	24	13
Special Senses
Amblyopia/Blurred Vision	8	4
Tinnitus	7	1
a. Headache was the only adverse event that occurred in ≥ 5% of patients in the high dose group and at an equal or greater incidence in the low dose group.

The following additional adverse reactions were reported by greater than 1% but less than 5% of the 358 patients treated with Depakote in the controlled trials of complex partial seizures:

Body as a Whole: Back pain, chest pain, malaise.

Cardiovascular System: Tachycardia, hypertension, palpitation.

Digestive System: Increased appetite, flatulence, hematemesis, eructation, pancreatitis, periodontal abscess.

Hemic and Lymphatic System: Petechia.

Metabolic and Nutritional Disorders: SGOT increased, SGPT increased.

Musculoskeletal System: Myalgia, twitching, arthralgia, leg cramps, myasthenia.

Nervous System: Anxiety, confusion, abnormal gait, paresthesia, hypertonia, incoordination, abnormal dreams, personality disorder.

Respiratory System: Sinusitis, cough increased, pneumonia, epistaxis.

Skin and Appendages: Rash, pruritus, dry skin.

Special Senses: Taste perversion, abnormal vision, deafness, otitis media.

Urogenital System: Urinary incontinence, vaginitis, dysmenorrhea, amenorrhea, urinary frequency.

Other Patient Populations

Adverse reactions that have been reported with all dosage forms of valproate from epilepsy trials, spontaneous reports, and other sources are listed below by body system.

Gastrointestinal

The most commonly reported side effects at the initiation of therapy are nausea, vomiting, and indigestion. These effects are usually transient and rarely require discontinuation of therapy. Diarrhea, abdominal cramps, and constipation have been reported. Both anorexia with some weight loss and increased appetite with weight gain have also been reported. The administration of delayed-release divalproex sodium may result in reduction of gastrointestinal side effects in some patients.

CNS Effects

Sedative effects have occurred in patients receiving valproate alone but occur most often in patients receiving combination therapy. Sedation usually abates upon reduction of other antiepileptic medication. Tremor (may be dose-related), hallucinations, ataxia, headache, nystagmus, diplopia, asterixis, "spots before eyes", dysarthria, dizziness, confusion, hypesthesia, vertigo, incoordination, and parkinsonism have been reported with the use of valproate. Rare cases of coma have occurred in patients receiving valproate alone or in conjunction with phenobarbital. In rare instances encephalopathy with or without fever has developed shortly after the introduction of valproate monotherapy without evidence of hepatic dysfunction or inappropriately high plasma valproate levels. Although recovery has been described following drug withdrawal, there have been fatalities in patients with hyperammonemic encephalopathy, particularly in patients with underlying urea cycle disorders [see Warnings and Precautions (5.4)].

Several reports have noted reversible cerebral atrophy and dementia in association with valproate therapy.

Dermatologic

Transient hair loss, skin rash, photosensitivity, generalized pruritus, erythema multiforme, and Stevens-Johnson syndrome. Rare cases of toxic epidermal necrolysis have been reported including a fatal case in a 6 month old infant taking valproate and several other concomitant medications. An additional case of toxic epidermal necrosis resulting in death was reported in a 35 year old patient with AIDS taking several concomitant medications and with a history of multiple cut