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Tuesday, 13 March 2012

Irinotecan Hydrochloride

Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: (S) - 4,11 - diethyl - 3,4,12,14 - tetrahydro - 4 - hydroxy - 3,14 - dioxo - 1H - pyrano[3′,4′:6,7]indolizino[1,2 - β]quinolin - 9 - yl ester[1,4′-bipiperidine]-1′-carboxylic acid trihydrate monohydrochloride
Molecular Formula: C₃₃H₃₈N₄O₆•HCl•3H₂O
CAS Number: 136572-09-3
Brands: Camptosar

Experience of Supervising Clinician

Administer only under the supervision of qualified clinicians experienced in the use of cytotoxic therapy.¹ Adequate diagnostic and treatment facilities should be readily available to manage complications.¹ ^b

GI Toxicity

Early and late forms of diarrhea may occur; both may be severe.¹ ² ¹⁶ ¹⁷ ¹⁸ ¹⁹ ²⁷ ²⁸ (See Diarrhea under Cautions.)

Early diarrhea (onset within 24 hours of administration) is cholinergic in nature (possibly preceded by diaphoresis, flushing, rhinitis, increased salivation, miosis, lacrimation, and abdominal cramping) and may be prevented or ameliorated by administration of atropine.¹ ²⁸

Late diarrhea (occurring >24 hours after administration) may be prolonged, life-threatening, and lead to dehydration, electrolyte imbalance, or sepsis.¹ Treat late diarrhea promptly with intensive oral loperamide therapy.¹ ² ¹⁶ ¹⁷ ¹⁸ ¹⁹ ²¹ ²² ²⁸ ⁵⁶

Carefully monitor patients with diarrhea; administer fluid and electrolyte replacement for dehydration and anti-infective therapy for ileus, fever, or severe neutropenia.²² ^b Interrupt therapy and reduce subsequent doses if severe diarrhea occurs.¹ (See Dosage Modification for Toxicity sections under Dosage and Administration.)

Myelosuppression

Severe myelosuppression may occur.¹ ¹⁶ ¹⁷ ¹⁸ ¹⁹ ²⁷ ^b (See Hematologic Effects under Cautions.)

Introduction

Antineoplastic agent; a semisynthetic derivative of camptothecin.¹ ² ³ ⁶ ⁷ ⁹ ¹³

Uses for Irinotecan Hydrochloride

Colorectal Cancer

Used as a component of first-line therapy in combination with fluorouracil and leucovorin for the treatment of metastatic carcinoma of the colon or rectum.¹ ²⁷ ³⁶ ³⁷

Also used as a single agent for treatment of metastatic carcinoma of the colon or rectum in patients whose disease has recurred or progressed following initial therapy with fluorouracil-based antineoplastic regimens.¹ ² ³ ⁸ ¹¹ ¹⁷ ¹⁸ ¹⁹ ²⁸ ³² ³³ ³⁶ ³⁷

Small Cell Lung Cancer

Used in combination with cisplatin for the initial treatment of extensive small cell lung cancer†.²⁷ ⁴⁶

Cervical Cancer

Under investigation for the treatment of metastatic or recurrent cervical cancer†.²⁷ ⁴⁷ ⁴⁸ ⁴⁹ ⁵⁰ ⁵¹

Irinotecan Hydrochloride Dosage and Administration

General

Consult specialized references for procedures for proper handling and disposal of antineoplastics.^b

Administer only under the supervision of qualified clinicians experienced in the use of cytotoxic therapy.¹ Adequate diagnostic and treatment facilities should be readily available to manage complications.¹ ^b

Before each irinotecan dose, determine WBC count with differential, hemoglobin, and platelet count.^b Obtain tests no sooner than 48 hours before scheduled treatment.⁵⁶ Consider trends as well as absolute values.⁵⁶

Administer effective antiemetic therapy for management of nausea and vomiting (e.g., dexamethasone 10 mg and a serotonin 5-HT₃ receptor antagonist such as ondansetron or granisetron) IV at least 30 minutes prior to irinotecan therapy.¹ ⁷ ⁸ ²² ²⁸ ⁶⁴ Consider additional oral antiemetic therapy for home use as needed.¹ ²² ⁶⁴

Unless clinically contraindicated, consider prophylactic or therapeutic administration of antimuscarinic therapy (e.g., 0.25–1 mg of atropine sulfate IV or sub-Q) for patients experiencing rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, abdominal cramping, or early diarrhea (i.e., onset within 24 hours of administration).¹ ⁸ ²² ²⁸ ^b

Administration

IV Administration

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

Administer by IV infusion.¹

Avoid extravasation; monitor infusion site for signs of inflammation.¹ ²² (See Local Effects under Cautions.)

Do not admix with other drugs.¹

Handle cautiously; use protective equipment (e.g., protective clothing and gloves); avoid exposure during handling and preparation of IV solution.¹ If skin or mucosal contact occurs, immediately and thoroughly wash skin with soap and water and flush mucosa with water.¹

Inadvertent overdosage has occurred because the manufacturer’s label on the vial was misread.³¹ Take particular care to ensure that the correct dose is administered, including careful attention to the concentration of irinotecan hydrochloride for injection concentrate present in the vial and the appropriate volume needed to provide the prescribed dose.³¹

Dilution

Irinotecan hydrochloride for injection concentrate must be diluted prior to IV administration.¹ ²²

Dilute in 5% dextrose injection (preferred diluent) or 0.9% sodium chloride injection to a final irinotecan hydrochloride concentration of 0.12–2.8 mg/mL; usual diluent volume is 250–500 mL.¹ ³ ¹⁶ ¹⁷ ¹⁸ ¹⁹ ^b

Rate of Administration

Infuse diluted solution over a period of 90 minutes; more rapid infusion rates may increase the likelihood of cholinergic symptoms.¹ ²² (See Diarrhea and also Cholinergic Symptoms under Cautions.)

Dosage

Available as irinotecan hydrochloride as the trihydrate; dosage expressed in terms of the hydrated salt.¹

Adults

Colorectal Cancer (First-line Combination Therapy)

Optimal dosage regimen for irinotecan-based combination therapy has not been established; an unexpectedly high rate of death has been reported in 2 clinical trials using irinotecan with fluorouracil given by rapid IV injection (“bolus”), and some clinicians prefer administration of fluorouracil by IV infusion in this regimen.⁵⁵ ⁵⁶ ⁵⁸

Regimen 1

Initially, irinotecan hydrochloride 125 mg/m² infused over 90 minutes, followed immediately by leucovorin 20 mg/m² given by rapid IV injection (“bolus”), followed immediately by fluorouracil 500 mg/m² given by rapid IV injection (“bolus”).¹ ⁵⁴ Administer weekly for 4 weeks on days 1, 8, 15, and 22 during a 6-week cycle; the next cycle begins on day 43.¹

Modify dosage within a cycle of therapy or when initiating a subsequent cycle of therapy based on individual patient tolerance; monitor patient carefully to obtain optimum therapeutic response with minimum adverse effects.¹ ⁷ ⁸ ¹⁷ ¹⁸ ¹⁹ ²² (See Dosage Modification for Toxicity [Regimen 1 or 2].)

Unless intolerable toxicity develops, additional cycles may be administered every 6 weeks in patients who continue to experience clinical benefit.¹ ^b

Consider reducing the initial dose in patients known to be homozygous for the UGT1A1*28 allele.^b (See Special Populations under Dosage and Administration.)

Regimen 2

Initially, irinotecan hydrochloride 180 mg/m² infused over 90 minutes, followed immediately by leucovorin 200 mg/m² infused IV over 2 hours, followed immediately by fluorouracil 400 mg/m² by rapid IV injection (“bolus”) and then fluorouracil 600 mg/m² infused IV over 22 hours.¹ ⁵³ Administer irinotecan on days 1, 15, and 29 of a 6-week cycle with administration of the leucovorin and fluorouracil (rapid IV injection [“bolus”] and infusional) component of the regimen on days 1, 2, 15, 16, 29, and 30; the next cycle begins on day 43.¹

Unless intolerable toxicity develops, additional cycles may be administered every 6 weeks in patients who continue to experience clinical benefit.¹ ^b

Consider reducing the initial dose in patients known to be homozygous for the UGT1A1*28 allele.^b (See Special Populations under Dosage and Administration.)

Dosage Modification for Toxicity (Regimen 1 or 2)

Reduce dosage within a cycle of therapy or when initiating a subsequent cycle of therapy as necessary based on toxicity (see Table 1 and Table 2).¹ Further reductions in dosage (i.e., beyond dose level 2) in decrements of 20% may be warranted in patients who continue to experience toxicity.¹ If multiple toxicities occur, adjust dose based on the toxicity requiring the largest dose reduction.¹ ¹⁷ ¹⁸ ¹⁹

Delay subsequent doses of combination therapy until pretreatment bowel function has been restored for ≥24 hours without the need for antidiarrheal agents.¹

Do not initiate a new cycle of therapy until any serious treatment-induced toxicity (as defined by NCI Common Toxicity Criteria) has improved to grade 1 or less.¹ ¹⁵ Do not initiate a new cycle of therapy until treatment-related diarrhea has fully resolved, granulocyte count has recovered to ≥1500/mm³, and platelet count has recovered to ≥100,000/mm³.¹

May delay treatment for 1–2 weeks to allow for recovery from treatment-related toxicities.¹ Consider discontinuing therapy if the treatment-induced toxicity does not resolve after delaying administration for 2 weeks.¹

Treatment on days 1, 8, 15, and 22.

Administration of irinotecan on days 1, 15, and 29, and administration of leucovorin, “bolus” fluorouracil, and infusional fluorouracil on days 1, 2, 15, 16, 29, and 30.

Table 1. Dosage Modifications of Irinotecan-based Combination Therapy for Metastatic Colorectal Cancerb
	Dosage Modifications for Irinotecan-based Combination Therapy (mg/m²)
Regimen/Agent	Reduced Dosage Level 1	Reduced Dosage Level 2
Regimen 1
Irinotecan	100	75
Leucovorin	20	20
Fluorouracil	400	300
Regimen 2
Irinotecan	150	120
Leucovorin	200	200
Fluorouracil “bolus”	320	240
Fluorouracil infusion	480	360

National Cancer Institute Common Toxicity Criteria (version 1.0).

Table 2. Recommended Dosage Modifications for Toxicity for Irinotecan-based Combination Therapy for Metastatic Colorectal Cancerb
Toxicity – NCI Grade (Value)	During a Cycle of Therapy	At the Start of Subsequent Cycles of Therapy (compared with the starting dose in the previous cycle)
No toxicity	Maintain dose level	Maintain dose level
Neutropenia
1 (1500–1999/mm³)	Maintain dose level	Maintain dose level
2 (1000–1499/mm³)	Decrease by 1 dose level	Maintain dose level
3 (500–999/mm³)	Omit dose until resolved to grade 2 or less, then decrease by 1 dose level	Decrease by 1 dose level
4 (<500/mm³)	Omit dose until resolved to grade 2 or less, then decrease by 2 dose levels	Decrease by 2 dose levels
Neutropenic fever	Omit dose until resolved, then decrease by 2 dose levels
Other hematologic toxicities	Dose modifications for leukopenia or thrombocytopenia during a cycle of therapy and at the start of subsequent cycles of therapy are based on NCI toxicity criteria and are the same as those recommended for neutropenia above
Diarrhea
1 (increase of 2–3 stools/day)	Delay dose until resolved to baseline, then resume the same dose	Maintain dose level
2 (increase of 4–6 stools/day)	Omit dose until resolved to baseline, then decrease by 1 dose level	Maintain dose level
3 (increase of 7–9 stools/day)	Omit dose until resolved to baseline, then decrease by 1 dose level	Decrease by 1 dose level
4 (increase of ≥10 stools/day)	Omit dose until resolved to baseline, then decrease by 2 dose levels	Decrease by 2 dose levels
Other nonhematologic toxicities (excluding alopecia, anorexia, asthenia)
1	Maintain dose level	Maintain dose level
2	Omit dose until resolved to grade 1 or less, then decrease by 1 dose level	Maintain dose level
3	Omit dose until resolved to grade 2 or less, then decrease by 1 dose level	Decrease by 1 dose level
4	Omit dose until resolved to grade 2 or less, then decrease by 2 dose levels	Decrease by 2 dose levels
	Note: For mucositis/stomatitis, decrease only fluorouracil, not irinotecan	Note: For mucositis/stomatitis, decrease only fluorouracil, not irinotecan

Colorectal Cancer (Monotherapy for Recurrent or Progressive Disease: Weekly Dosage Schedule)

IV

Initially, 125 mg/m² infused over 90 minutes.¹ ³ ⁷ ⁸ ²⁸ Administer once weekly for 4 weeks followed by a 2-week rest period.¹ ³ ⁷ ⁸ ¹⁷ ¹⁸ ¹⁹ ²²

Modify dosage within a cycle of therapy or for a new cycle of therapy based on individual patient tolerance; monitor patient carefully to obtain optimum therapeutic response with minimum adverse effects.¹ ⁷ ⁸ ¹⁷ ¹⁸ ¹⁹ ²² (See Dosage Modification for Toxicity [Weekly Schedule].)

If no toxicity occurs during an entire 6-week cycle of therapy, increase dose by 25 mg/m² at the start of the next cycle, but dose should not exceed 150 mg/m².¹ ¹⁷ ¹⁸ ¹⁹

Unless intolerable toxicity develops, additional cycles may be administered every 6 weeks in patients who continue to experience clinical benefit.¹ ⁷ ⁸ ^b

Consider reducing the initial dose in patients known to be homozygous for the UGT1A1*28 allele, geriatric patients, patients who have received prior pelvic or abdominal radiation therapy, those with elevated serum bilirubin concentrations, and those with a performance status of 2.^b (See Special Populations under Dosage and Administration.)

Dosage Modification for Toxicity (Weekly Schedule)

Modify dosage within a cycle of therapy or for a new cycle of therapy in increments of 25–50 mg/m² to a dose within the range of 50–150 mg/m² as necessary based on toxicity (see Table 3).¹ ⁷ ¹⁷ ¹⁸ ¹⁹ ²² If multiple toxicities occur, adjust dose based on the toxicity requiring the largest dose reduction.¹ ¹⁷ ¹⁸ ¹⁹

Delay subsequent doses until pretreatment bowel function has been restored for ≥24 hours without the need for antidiarrheal agents.¹

National Cancer Institute Common Toxicity Criteria (version 1.0).

Table 3. Recommended Dosage Modifications for Toxicity for Irinotecan Monotherapy Given on a Weekly Dosage Schedule for Colorectal Cancerb
Toxicity – NCI Grade	During a Cycle of Therapy	At the Start of the Next Cycle of Therapy (after adequate recovery, compared with the starting dose in the previous cycle)
No toxicity	Maintain dose level	Increase dose by 25 mg/m² up to a maximum dose of 150 mg/m²
Neutropenia
1 (1500–1999/mm³)	Maintain dose level	Maintain dose level
2 (1000–499/mm³)	Decrease dose by 25 mg/m²	Maintain dose level
3 (500–999/mm³)	Omit dose until resolved to grade 2 or less, then decrease dose by 25 mg/m²	Decrease dose by 25 mg/m²
4 (<500/mm³)	Omit dose until resolved to grade 2 or less, then decrease dose by 50 mg/m²	Decrease dose by 50 mg/m²
Neutropenic fever	Omit dose until resolved, then decrease dose by 50 mg/m²	Decrease dose by 50 mg/m²
Other hematologic toxicities	Dose modifications for leukopenia, thrombocytopenia, and anemia during a cycle of therapy also are based on NCI toxicity criteria and are the same as those recommended for neutropenia above	Dose modifications for leukopenia, thrombocytopenia, and anemia at the start of subsequent cycles of therapy also are based on NCI toxicity criteria and are the same as those recommended for neutropenia above
Diarrhea
1 (increase of 2–3 stools/day)	Maintain dose level	Maintain dose level
2 (increase of 4–6 stools/day)	Decrease dose by 25 mg/m²	Maintain dose level
3 (increase of 7–9 stools/day)	Omit dose until resolved to grade 2 or less, then decrease dose by 25 mg/m²	Decrease dose by 25 mg/m²
4 (increase of ≥10 stools/day)	Omit dose until resolved to grade 2 or less, then decrease dose by 50 mg/m²	Decrease dose by 50 mg/m²
Other nonhematologic toxicities (excluding alopecia, anorexia, asthenia)
1	Maintain dose level	Maintain dose level
2	Decrease dose by 25 mg/m²	Decrease dose by 25 mg/m²
3	Omit dose until resolved to grade 2 or less, then decrease dose by 25 mg/m²	Decrease dose by 25 mg/m²
4	Omit dose until resolved to grade 2 or less, then decrease dose by 50 mg/m²	Decrease dose by 50 mg/m²

Colorectal Cancer (Monotherapy for Recurrent or Progressive Disease: Once-Every-3-Weeks Dosage Schedule)

IV

Initially, 350 mg/m² infused over 90 minutes.¹

Adjust subsequent doses based on individual patient tolerance; monitor patient carefully to obtain optimum therapeutic response with minimum adverse effects.¹ ⁷ ⁸ ¹⁷ ¹⁸ ¹⁹ ²² (See Dosage Modification for Toxicity [Once-Every-3-Weeks Schedule].)

Administer once every 3 weeks for as long as intolerable toxicity does not occur and the patient continues to experience clinical benefit.¹

Dosage Modification for Toxicity (Once-Every-3-Weeks Schedule)

Decrease dose in decrements of 50 mg/m² to a dose as low as 200 mg/m² as necessary based on toxicity encountered with the previous dose of irinotecan (see Table 4).¹ If multiple toxicities occur, adjust dose based on the toxicity requiring the largest dose reduction.¹ ¹⁷ ¹⁸ ¹⁹

Delay subsequent doses until pretreatment bowel function has been restored for ≥24 hours without the need for antidiarrheal agents.¹

National Cancer Institute Common Toxicity Criteria (version 1.0).

Table 4. Recommended Dosage Modifications for Toxicity for Irinotecan Monotherapy Given on a Once-Every-3-Weeks Schedule for Colorectal Cancerb
Toxicity – NCI Grade	At the Start of the Next Cycle of Therapy (after adequate recovery, compared with the starting dose in the previous cycle)
No toxicity	Maintain dose level
Neutropenia
1 (1500–1999/mm³)	Maintain dose level
2 (1000–1499/mm³)	Maintain dose level
3 (500–999/mm³)	Decrease dose by 50 mg/m²
4 (<500/mm³)	Decrease dose by 50 mg/m²
Neutropenic fever	Decrease dose by 50 mg/m²
Other hematologic toxicities	Dose modifications for leukopenia, thrombocytopenia, and anemia at the start of subsequent cycles of therapy also are based on NCI toxicity criteria and are the same as those recommended for neutropenia above
Diarrhea
1 (increase of 2–3 stools/day)	Maintain dose level
2 (increase of 4–6 stools/day)	Maintain dose level
3 (increase of 7–9 stools/day)	Decrease dose by 50 mg/m²
4 (≥ 10 increase of stools/day)	Decrease dose by 50 mg/m²
Other nonhematologic toxicities (excluding alopecia, anorexia, asthenia)
1	Maintain dose level
2	Decrease dose by 50 mg/m²
3	Decrease dose by 50 mg/m²
4	Decrease dose by 50 mg/m²

Prescribing Limits

Adults

Colorectal Cancer (Monotherapy for Recurrent or Progressive Disease: Weekly Dosage Schedule)

IV

Maximum dose: 150 mg/m².¹ ¹⁷ ¹⁸ ¹⁹

Special Populations

Hepatic Impairment

In clinical trials for colorectal cancer, irinotecan was not administered to patients with serum bilirubin concentrations >2 mg/dL,¹ ²² patients without hepatic metastases who had serum aminotransferase (transaminase) concentrations >3 times the ULN, or those with hepatic metastases who had serum aminotransferase values >5 times the ULN.¹ ²²

Colorectal Cancer (First-line Combination Therapy)

Specific dosage recommendations not available for patients with bilirubin >2 mg/dL.¹

Colorectal Cancer (Monotherapy for Recurrent or Progressive Disease)

Consider reducing initial dose by one dose level (e.g., to 100 mg/m² for the weekly dosage schedule or to 300 mg/m² for the once-every-3-weeks dosage schedule) in patients with modestly elevated baseline total serum bilirubin concentrations (i.e., 1–2 mg/dL).¹ (See Colorectal Cancer [Monotherapy] sections under Dosage and Administration and also see Hepatic Impairment under Cautions.)

Specific dosage recommendations not available for patients with bilirubin >2 mg/dL;¹ reduction in the initial dose may be considered.³⁸

Renal Impairment

Manufacturer makes no specific dosage recommendations for patients with impaired renal function; use with caution.^b Not recommended in dialysis patients.^b (See Renal Impairment under Cautions.)

Geriatric Patients

Colorectal Cancer (Monotherapy for Recurrent or Progressive Disease)

Consider reducing initial dose by one dose level (e.g., to 100 mg/m² for the weekly dosage schedule or to 300 mg/m² for the once-every-3-weeks dosage schedule) in patients ≥65 years of age.¹ (See Colorectal Cancer [Monotherapy] sections under Dosage and Administration.)

In patients ≥70 years of age receiving the once-every-3-weeks regimen, reduction of initial dose to 300 mg/m² (the dose used in this age group in clinical trials of this regimen) is recommended.^b

Reduced Uridine Diphosphate-glucuronosyltransferase 1A1 (UGT1A1) Activity

Colorectal Cancer (First-line Combination Therapy)

Consider reducing initial dose by at least one dose level (e.g., to 100 mg/m² for regimen 1 or to 150 mg/m² for regimen 2) in patients homozygous for the UGT1A1*28 allele; some heterozygous patients may tolerate usual initial doses.^b Precise dosage reduction is not known; modify subsequent doses based on patient tolerance to treatment.^b (See Reduced UGT1A1 Activity under Cautions and also see Colorectal Cancer [First-line Combination Therapy] under Dosage and Administration.)

Colorectal Cancer (Monotherapy for Recurrent or Progressive Disease)

Consider reducing initial dose by at least one dose level (e.g., to 100 mg/m² for the weekly dosage schedule or to 300 mg/m² for the once-every-3-weeks dosage schedule) in patients homozygous for the UGT1A1*28 allele; heterozygous patients may tolerate usual initial doses.^b Precise dosage reduction is not known; modify subsequent doses based on patient tolerance to treatment.^b (See Colorectal Cancer [Monotherapy] sections under Dosage and Administration.)

Performance Status of 2

Colorectal Cancer (Monotherapy for Recurrent or Progressive Disease)

Consider reducing initial dose by one dose level (e.g., to 100 mg/m² for the weekly dosage schedule or to 300 mg/m² for the once-every-3-weeks dosage schedule).¹ (See Performance Status of Patient under Cautions and also see Colorectal Cancer [Monotherapy] sections under Dosage and Administration.)

Prior Pelvic or Abdominal Radiation Therapy

Colorectal Cancer (Monotherapy for Recurrent or Progressive Disease)

Consider reducing initial dose by one dose level (e.g., to 100 mg/m² for the weekly dosage schedule or to 300 mg/m² for the once-every-3-weeks dosage schedule).¹ (See Radiation Therapy under Cautions and also see Colorectal Cancer [Monotherapy] sections under Dosage and Administration.)

Cautions for Irinotecan Hydrochloride

Contraindications

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

Concurrent use with ketoconazole; discontinue use ≥1 week before beginning irinotecan therapy.^b (See Specific Drugs under Interactions.)

Concurrent use with St. John's wort (Hypericum perforatum); discontinue use ≥2 weeks before beginning irinotecan therapy.^b (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Risks Associated with Combined Regimen of Irinotecan and Rapid-injection (“Bolus”) Fluorouracil

Use in combination with the “Mayo Clinic” regimen of rapid IV injection (“bolus”) fluorouracil/leucovorin (i.e., administration for 4–5 consecutive days every 4 weeks) associated with increased toxicity (GI and vascular syndromes), including deaths.¹ Do not use in combination with this regimen outside of a well-designed clinical trial. ¹

Potentially fatal GI syndrome is manifested by diarrhea, nausea, vomiting, anorexia, and abdominal cramping, and often is associated with severe dehydration, neutropenia, fever, and electrolyte abnormalities.⁵⁶

Vascular syndrome is characterized by acute, fatal MI, pulmonary embolus, or cerebrovascular accident.⁵⁶

GI and vascular syndromes typically occur during or immediately following the first treatment cycle.⁵⁶

Closely monitor patients; institute prompt, aggressive treatment of toxicity; discontinue treatment in patients experiencing unresolved drug-related toxicity.⁵⁶

Performance Status of Patient

Higher rates of hospitalization, neutropenic fever, thromboembolism, treatment discontinuance during the first cycle, and early deaths reported in patients with a baseline performance status of 2 (versus 0 or 1) regardless of treatment regimen (irinotecan in combination with fluorouracil/leucovorin versus fluorouracil/leucovorin alone).¹

Diarrhea

Early and late forms of diarrhea may occur; both may be severe.¹ ² ¹⁶ ¹⁷ ¹⁸ ¹⁹ ²⁷ ²⁸

Early diarrhea (onset within 24 hours of administration) generally is transient and cholinergic in nature (possibly preceded by diaphoresis, flushing, rhinitis, increased salivation, miosis, lacrimation, and abdominal cramping).¹ ²⁷ ²⁸ Higher doses and more rapid infusion rates may increase the likelihood of cholinergic symptoms.¹ ⁸ ²² ²⁸

Late diarrhea (occurring >24 hours after administration) may be prolonged, life-threatening, and lead to dehydration, electrolyte imbalance, or sepsis.¹

Early diarrhea may be prevented or ameliorated by administration of atropine.¹ ²⁷ ²⁸ (See General under Dosage and Administration.)

Treat late diarrhea promptly with intensive oral loperamide hydrochloride therapy (e.g., 4 mg at the onset of diarrhea, then 2 mg every 2 hours [or 4 mg every 4 hours at night¹ ⁵⁶ ] until patient is diarrhea-free for 12 hours).¹ ² ¹⁶ ¹⁷ ¹⁸ ¹⁹ ²¹ ²² ²⁸ ⁵⁶ Do not use loperamide at these dosages for >48 consecutive hours; risk of paralytic ileus.⁶³ ^b Premedication with loperamide is not recommended.^b

Consider a 7-day course of oral fluoroquinolone therapy if diarrhea persists for >24 hours despite loperamide therapy, or if diarrhea occurs with fever.¹ ⁵⁶ If diarrhea persists for >48 hours, some clinicians advise discontinuance of loperamide and hospitalization for parenteral hydration.⁵⁶

Monitor patients with diarrhea carefully; give fluid and electrolyte replacement if patient becomes dehydrated or anti-infective therapy if ileus, fever, or severe neutropenia develops.¹ ²² Some clinicians recommend appropriate anti-infective therapy in any patient with prolonged diarrhea, regardless of neutrophil count (continued until resolution).⁵⁶

Interruption of therapy and subsequent dosage reduction may be required.^b (See Dosage Modification for Toxicity sections under Dosage and Administration.)

Hematologic Effects

Severe myelosuppression, particularly neutropenia,¹ ¹⁶ ¹⁷ ¹⁸ ¹⁹ ²⁷ and deaths caused by sepsis have been reported.¹ ¹⁸ ¹⁹ ²⁸

Increased risk of grade 3 or 4 neutropenia observed in patients with even modestly elevated (i.e., 1–2 mg/dL) total serum bilirubin concentrations.¹ Possible increased risk of myelosuppression in patients with abnormal glucuronidation of bilirubin (e.g., Gilbert’s syndrome).¹

Prompt anti-infective therapy recommended for complications of neutropenia.¹ Initiate prophylactic treatment with an oral fluoroquinolone in patients with ANC <500/ mm³, even in the absence of fever or diarrhea.¹ ⁵⁶

Interrupt therapy if neutropenic fever occurs or if ANC <1000/mm³.¹ ¹⁸ ¹⁹ Reduced dosage recommended following recovery to an ANC ≥1000/mm³ (see Tables 2, 3, and 4 under Dosage and Administration.)¹ Interrupt therapy in patients with a rapidly falling ANC, even if the current ANC is considered adequate to permit treatment.⁵⁶

Manufacturer states that routine administration of a hematopoietic agent (e.g., filgrastim, sargramostim) is not necessary; however, such use may be considered in individual patients experiencing severe neutropenia.¹

Obtain blood tests no sooner than 48 hours before scheduled treatment; consider trends in the ANC as well as absolute values.⁵⁶

Do not use in patients with severe bone marrow failure; causes neutropenia, leukopenia, and anemia, any of which may be severe.⁶³ ^b

Reduced UGT1A1 Activity

Patients homozygous for UGT1A1*28 allele have reduced UGT1A1 activity; these patients have increased exposure to the active metabolite SN-38 and are at an increased risk for neutropenia during irinotecan treatment; consider decreasing initial dose.^b (See Reduced Uridine Diphosphate-glucuronosyltransferase 1A1 [UGT1A1] Activity under Dosage and Administration.)

Heterozygous patients may be at increased risk, but clinical results are variable; most tolerate usual initial doses.^b

Colitis and Ileus

Possible colitis complicated by ulceration, bleeding, ileus, and infection; initiate anti-infective therapy promptly if ileus develops.¹

Renal Effects

Renal impairment and acute renal failure have occurred rarely, usually in patients who became volume depleted from severe vomiting and/or diarrhea.¹

Cardiovascular Effects

A vascular syndrome characterized by acute, fatal MI, pulmonary embolus, or cerebrovascular accident has been reported in patients receiving irinotecan in combination with rapid IV (“bolus”) fluorouracil/leucovorin.⁵⁶ (See Risks Associated with Combined Regimen of Irinotecan and Rapid-injection [“Bolus”] Fluorouracil under Cautions.)

Cardiovascular and thromboembolic events also reported in patients receiving irinotecan with fluorouracil as IV infusion.⁶⁰

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm;¹ embryotoxic and teratogenic in animals.¹ Avoid pregnancy during therapy.¹ If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.¹

Sensitivity Reactions

Hypersensitivity reactions, including severe anaphylactic or anaphylactoid reactions, have been reported.¹

General Precautions

Adequate Patient Evaluation and Monitoring

Monitor patients receiving irinotecan in combination with fluorouracil/leucovorin closely (e.g., weekly assessment), particularly during the first cycle of treatment; most of the treatment-related toxicities leading to early death have occurred within the first 3–4 weeks.⁵⁶

Local Effects

Avoid extravasation; monitor infusion site for signs of inflammation.¹ ²² If manifestations of extravasation appear, immediately stop infusion and restart in another vein;²² flush infusion site promptly with sterile water and apply an ice pack.¹

Nausea and Vomiting

Nausea and/or vomiting occur frequently and may be severe.¹

Administer effective antiemetic therapy (e.g., dexamethasone 10 mg and a serotonin 5-HT₃ receptor antagoni

Monday, 12 March 2012

Nexa Select with DHA

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

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

What are Nexa Select with DHA (prenatal multivitamins)?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

How should I take prenatal vitamins?

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

Never take more than the recommended dose of prenatal vitamins.

Take your prenatal vitamin with a full glass of water.

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

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

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

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

What happens if I miss a dose?

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

What happens if I overdose?

What should I avoid while taking prenatal vitamins?

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

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

Prenatal vitamins side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

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

upset stomach;

headache; or

unusual or unpleasant taste in your mouth.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect prenatal vitamins?

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

diuretics (water pills);

heart or blood pressure medications;

tretinoin (Vesanoid);

isotretinoin (Accutane, Amnesteen, Clavaris, Sotret);

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

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

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

More Nexa Select with DHA resources

Nexa Select with DHA Use in Pregnancy & Breastfeeding
Nexa Select with DHA Drug Interactions
0 Reviews for Nexa Select with DHA - Add your own review/rating

Cal-Nate MedFacts Consumer Leaflet (Wolters Kluwer)

CareNatal DHA MedFacts Consumer Leaflet (Wolters Kluwer)

CitraNatal 90 DHA MedFacts Consumer Leaflet (Wolters Kluwer)

CitraNatal Assure Prescribing Information (FDA)

CitraNatal Harmony Prescribing Information (FDA)

Concept DHA Prescribing Information (FDA)

Docosavit Prescribing Information (FDA)

Duet DHA with Ferrazone MedFacts Consumer Leaflet (Wolters Kluwer)

Folbecal MedFacts Consumer Leaflet (Wolters Kluwer)

Folcal DHA Prescribing Information (FDA)

Folcaps Care One Prescribing Information (FDA)

Gesticare DHA Prescribing Information (FDA)

Gesticare DHA MedFacts Consumer Leaflet (Wolters Kluwer)

Inatal Advance Prescribing Information (FDA)

Inatal Ultra Prescribing Information (FDA)

Multi-Nate DHA Prescribing Information (FDA)

Multi-Nate DHA Extra Prescribing Information (FDA)

MultiNatal Plus MedFacts Consumer Leaflet (Wolters Kluwer)

Natelle One Prescribing Information (FDA)

Neevo Caplets MedFacts Consumer Leaflet (Wolters Kluwer)

Neevo DHA MedFacts Consumer Leaflet (Wolters Kluwer)

OB Complete 400 MedFacts Consumer Leaflet (Wolters Kluwer)

Paire OB Plus DHA Prescribing Information (FDA)

PreNexa MedFacts Consumer Leaflet (Wolters Kluwer)

PreNexa Prescribing Information (FDA)

PreferaOB Prescribing Information (FDA)

Prenatal Plus Prescribing Information (FDA)

Prenatal Plus Iron Prescribing Information (FDA)

Prenate Elite Prescribing Information (FDA)

Prenate Elite MedFacts Consumer Leaflet (Wolters Kluwer)

Prenate Elite tablets

Prenate Essential Prescribing Information (FDA)

PrimaCare Advantage MedFacts Consumer Leaflet (Wolters Kluwer)

PrimaCare ONE capsules

PrimaCare One MedFacts Consumer Leaflet (Wolters Kluwer)

Renate DHA Prescribing Information (FDA)

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

Se-Natal 19 Prescribing Information (FDA)

Tandem DHA Prescribing Information (FDA)

Tandem OB Prescribing Information (FDA)

TriAdvance Prescribing Information (FDA)

Triveen-One MedFacts Consumer Leaflet (Wolters Kluwer)

Triveen-PRx RNF Prescribing Information (FDA)

UltimateCare ONE NF Prescribing Information (FDA)

Ultra NatalCare MedFacts Consumer Leaflet (Wolters Kluwer)

Vinate AZ Prescribing Information (FDA)

Vitafol-One MedFacts Consumer Leaflet (Wolters Kluwer)

Zatean-CH Prescribing Information (FDA)

Compare Nexa Select with DHA with other medications

Vitamin/Mineral Supplementation during Pregnancy/Lactation

Where can I get more information?

Your pharmacist can provide more information about prenatal vitamins.

Valproic Acid Capsules

Dosage Form: capsule, liquid filled
Valproic Acid Capsules, USP

250 mg softgels (soft-gelatin capsules)

Rx only

BOXED WARNING

HEPATOTOXICITY

HEPATIC FAILURE RESULTING IN FATALITIES HAS OCCURRED IN PATIENTS RECEIVING VALPROIC ACID. EXPERIENCE HAS INDICATED THAT 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 VALPROIC ACID 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.

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.

TERATOGENICITY

VALPROATE CAN PRODUCE TERATOGENIC EFFECTS SUCH AS NEURAL TUBE DEFECTS (E.G., SPINA BIFIDA). ACCORDINGLY, THE USE OF VALPROATE 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, INFORMATION FOR PATIENTS.

A PATIENT INFORMATION LEAFLET DESCRIBING THE TERATOGENIC POTENTIAL OF VALPROATE IS AVAILABLE FOR PATIENTS.

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.)

Valproic Acid Capsules Description

Valproic acid is a carboxylic acid designated as 2-propylpentanoic acid. It is also known as dipropylacetic acid. Valproic acid has the following structure:

Valproic acid (pKa 4.8) has a molecular weight of 144 and occurs as a colorless liquid with a characteristic odor. It is slightly soluble in water (1.3 mg/mL) and very soluble in organic solvents.

Valproic acid is supplied as soft-gelatin capsules for oral administration. Each capsule contains 250 mg valproic acid.

Inactive Ingredients

Corn oil, FD&C Blue No. 1, gelatin, glycerin, purified water and titanium dioxide.

Valproic Acid Capsules - Clinical Pharmacology

Pharmacodynamics

Valproic acid dissociates to the valproate ion in the gastrointestinal tract. The mechanisms by which valproate exerts its antiepileptic effects have not been established. It has been suggested that its activity in epilepsy is related to increased brain concentrations of gamma-aminobutyric acid (GABA).

Pharmacokinetics

Absorption/Bioavailability

Equivalent oral doses of divalproex sodium products and Valproic Acid Capsules deliver equivalent quantities of valproate ion systemically.

Although the rate of valproate ion absorption may vary with the conditions of use (e.g., fasting or postprandial) these differences should be of minor clinical importance under the steady state conditions achieved in chronic use in the treatment of epilepsy.

However, it is possible that differences among the various valproate products in Tmax and Cmax could be important upon initiation of treatment. For example, in single dose studies, the effect of feeding had a greater influence on the rate of absorption of the divalproex sodium tablet (increase in Tmax from 4 to 8 hours) than on the absorption of the divalproex sodium sprinkle capsules (increase in Tmax from 3.3 to 4.8 hours).

While the absorption rate from the G.I. tract and fluctuation in valproate plasma concentrations vary with dosing regimen and formulation, the efficacy of valproate as an anticonvulsant in chronic use is unlikely to be affected. Experience employing dosing regimens from once-a-day to four-times-a-day, as well as studies in primate epilepsy models involving constant rate infusion, indicate that total daily systemic bioavailability (extent of absorption) is the primary determinant of seizure control and that differences in the ratios of plasma peak to trough concentrations are inconsequential from a practical clinical standpoint.

Co-administration of oral valproate with food should cause no clinical problems in the management of patients with epilepsy (see DOSAGE AND ADMINISTRATION). Nonetheless, any changes in dosage administration, or the addition or discontinuance of concomitant drugs should ordinarily be accompanied by close monitoring of clinical status and valproate plasma concentrations.

Distribution

Protein Binding

The plasma protein binding of valproate is concentration dependent and the free fraction increases from approximately 10% at 40 mcg/mL to 18.5% at 130 mcg/mL. Protein binding of valproate is reduced in the elderly, in patients with chronic hepatic diseases, in patients with renal impairment, and in the presence of other drugs (e.g., aspirin). Conversely, valproate may displace certain protein-bound drugs (e.g., phenytoin, carbamazepine, warfarin, and tolbutamide). (See PRECAUTIONS - Drug Interactions for more detailed information on the pharmacokinetic interactions of valproate with other drugs.)

CNS Distribution

Valproate concentrations in cerebrospinal fluid (CSF) approximate unbound concentrations in plasma (about 10% of total concentration).

Metabolism

Valproate is metabolized almost entirely by the liver. In adult patients on monotherapy, 30-50% of an administered dose appears in urine as a glucuronide conjugate. Mitochondrial β-oxidation is the other major metabolic pathway, typically accounting for over 40% of the dose. Usually, less than 15-20% of the dose is eliminated by other oxidative mechanisms. Less than 3% of an administered dose is excreted unchanged in urine.

The relationship between dose and total valproate concentration is nonlinear; concentration does not increase proportionally with the dose, but rather, increases to a lesser extent due to saturable plasma protein binding. The kinetics of unbound drug are linear.

Elimination

Mean plasma clearance and volume of distribution for total valproate are 0.56 L/hr/1.73 m2 and 11 L/1.73 m2, respectively. Mean plasma clearance and volume of distribution for free valproate are 4.6 L/hr/1.73 m2 and 92 L/1.73 m2. Mean terminal half-life for valproate monotherapy ranged from 9 to 16 hours following oral dosing regimens of 250 to 1000 mg.

The estimates cited apply primarily to patients who are not taking drugs that affect hepatic metabolizing enzyme systems. For example, patients taking enzyme-inducing antiepileptic drugs (carbamazepine, phenytoin, and phenobarbital) will clear valproate more rapidly. Because of these changes in valproate clearance, monitoring of antiepileptic concentrations should be intensified whenever concomitant antiepileptics are introduced or withdrawn.

Special Populations

Effect of Age

Neonates

Children within the first two months of life have a markedly decreased ability to eliminate valproate compared to older children and adults. This is a result of reduced clearance (perhaps due to delay in development of glucuronosyltransferase and other enzyme systems involved in valproate elimination) as well as increased volume of distribution (in part due to decreased plasma protein binding). For example, in one study, the half-life in children under 10 days ranged from 10 to 67 hours compared to a range of 7 to 13 hours in children greater than 2 months.

Children

Pediatric patients (i.e., between 3 months and 10 years) have 50% higher clearances expressed on weight (i.e., mL/min/kg) than do adults. Over the age of 10 years, children have pharmacokinetic parameters that approximate those of adults.

Elderly

The capacity of elderly patients (age range: 68 to 89 years) to eliminate valproate has been shown to be reduced compared to younger adults (age range: 22 to 26). Intrinsic clearance is reduced by 39%; the free fraction is increased by 44%. Accordingly, the initial dosage should be reduced in the elderly. (See DOSAGE AND ADMINISTRATION).

Effect of Gender

There are no differences in the body surface area adjusted unbound clearance between males and females (4.8 ± 0.17 and 4.7 ± 0.07 L/hr per 1.73 m2, respectively).

Effect of Race

The effects of race on the kinetics of valproate have not been studied.

Effect of Disease

Liver Disease

(See BOXED WARNING, CONTRAINDICATIONS, and WARNINGS). Liver disease impairs the capacity to eliminate valproate. In one study, the clearance of free valproate was decreased by 50% in 7 patients with cirrhosis and by 16% in 4 patients with acute hepatitis, compared with 6 healthy subjects. In that study, the half-life of valproate was increased from 12 to 18 hours. Liver disease is also associated with decreased albumin concentrations and larger unbound fractions (2 to 2.6 fold increase) of valproate. Accordingly, monitoring of total concentrations may be misleading since free concentrations may be substantially elevated in patients with hepatic disease whereas total concentrations may appear to be normal.

Renal Disease

A slight reduction (27%) in the unbound clearance of valproate has been reported in patients with renal failure (creatinine clearance < 10 mL/minute); however, hemodialysis typically reduces valproate concentrations by about 20%. Therefore, no dosage adjustment appears to be necessary in patients with renal failure. Protein binding in these patients is substantially reduced; thus, monitoring total concentrations may be misleading.

Plasma Levels and Clinical Effect

The relationship between plasma concentration and clinical response is not well documented. One contributing factor is the nonlinear, concentration dependent protein binding of valproate which affects the clearance of the drug. Thus, monitoring of total serum valproate cannot provide a reliable index of the bioactive valproate species.

For example, because the plasma protein binding of valproate is concentration dependent, the free fraction increases from approximately 10% at 40 mcg/mL to 18.5% at 130 mcg/mL. Higher than expected free fractions occur in the elderly, in hyperlipidemic patients, and in patients with hepatic and renal diseases.

Epilepsy

The therapeutic range is commonly considered to be 50 to 100 mcg/mL of total valproate, although some patients may be controlled with lower or higher plasma concentrations.

Clinical Trials

The studies described in the following section were conducted using divalproex sodium tablets.

Epilepsy

The efficacy of divalproex sodium in reducing the incidence of complex partial seizures (CPS) that occur in isolation or in association with other seizure types was established in two controlled trials.

In one, multiclinic, placebo controlled study employing an add-on design (adjunctive therapy), 144 patients who continued to suffer eight or more CPS per 8 weeks during an 8 week period of monotherapy with doses of either carbamazepine or phenytoin sufficient to assure plasma concentrations within the "therapeutic range" were randomized to receive, in addition to their original antiepilepsy drug (AED), either divalproex sodium or placebo. Randomized patients were to be followed for a total of 16 weeks. The following table presents the findings.

Adjunctive Therapy Study Median Incidence of CPS per 8 Weeks
Add-on Treatment	Number of Patients	Baseline Incidence	Experimental Incidence
*Reduction from baseline statistically significantly greater for divalproex sodium than placebo at p ≤ 0.05 level.
divalproex sodium	75	16.0	8.9*
Placebo	69	14.5	11.5

Figure 1 presents the proportion of patients (X axis) whose percentage reduction from baseline in complex partial seizure rates was at least as great as that indicated on the Y axis in the adjunctive therapy study. A positive percent reduction indicates an improvement (i.e., a decrease in seizure frequency), while a negative percent reduction indicates worsening. Thus, in a display of this type, the curve for an effective treatment is shifted to the left of the curve for placebo. This figure shows that the proportion of patients achieving any particular level of improvement was consistently higher for divalproex sodium than for placebo. For example, 45% of patients treated with divalproex sodium had a ≥50% reduction in complex partial seizure rate compared to 23% of patients treated with placebo.

Figure 1.

The second study assessed the capacity of divalproex sodium to reduce the incidence of CPS when administered as the sole AED. The study compared the incidence of CPS among patients randomized to either a high or low dose treatment arm. Patients qualified for entry into the randomized comparison phase of this study only if 1) they continued to experience 2 or more CPS per 4 weeks during an 8 to 12 week long period of monotherapy with adequate doses of an AED (i.e., phenytoin, carbamazepine, phenobarbital, or primidone) and 2) they made a successful transition over a two week interval to divalproex sodium. Patients entering the randomized phase were then brought to their assigned target dose, gradually tapered off their concomitant AED and followed for an interval as long as 22 weeks. Less than 50% of the patients randomized, however, completed the study. In patients converted to divalproex sodium monotherapy, the mean total valproate concentrations during monotherapy were 71 and 123 mcg/mL in the low dose and high dose groups, respectively.

The following table presents the findings for all patients randomized who had at least one post-randomization assessment.

Monotherapy Study Median Incidence of CPS per 8 Weeks
Treatment	Number of Patients	Baseline Incidence	Randomized Phase Incidence
*Reduction from baseline statistically significantly greater for high dose than low dose at p ≤ 0.05 level.
High dose divalproex sodium	131	13.2	10.7*
Low dose divalproex sodium	134	14.2	13.8

Figure 2 presents the proportion of patients (X axis) whose percentage reduction from baseline in complex partial seizure rates was at least as great as that indicated on the Y axis in the monotherapy study. A positive percent reduction indicates an improvement (i.e., a decrease in seizure frequency), while a negative percent reduction indicates worsening. Thus, in a display of this type, the curve for a more effective treatment is shifted to the left of the curve for a less effective treatment. This figure shows that the proportion of patients achieving any particular level of reduction was consistently higher for high dose divalproex sodium than for low dose divalproex sodium. For example, when switching from carbamazepine, phenytoin, phenobarbital or primidone monotherapy to high dose divalproex sodium monotherapy, 63% of patients experienced no change or a reduction in complex partial seizure rates compared to 54% of patients receiving low dose divalproex sodium.

Figure 2.

Indications and Usage for Valproic Acid Capsules

Valproic acid is indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures. Valproic acid is 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 which 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 FOR STATEMENT REGARDING FATAL HEPATIC DYSFUNCTION.

Contraindications

VALPROIC ACID SHOULD NOT BE ADMINISTERED TO PATIENTS WITH HEPATIC DISEASE OR SIGNIFICANT HEPATIC DYSFUNCTION.

Valproic acid is contraindicated in patients with known hypersensitivity to the drug.

Valproic acid is contraindicated in patients with known urea cycle disorders (see WARNINGS).

Warnings

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, physicians 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 valproic acid 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 valproic acid 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 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.

Usage in Pregnancy

VALPROATE CAN PRODUCE TERATOGENIC EFFECTS. 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. THEREFORE, VALPROATE 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.

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.

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.

Human Data

Congenital Malformations

The North American Antiepileptic Drug Pregnancy Registry reported 16 cases of congenital malformations among the offspring of 149 women with epilepsy who were exposed to valproic acid monotherapy during the first trimester of pregnancy at doses of approximately 1,000 mg per day, for a prevalence rate of 10.7% (95% CI 6.3%-16.9%). Three of the 149 offspring (2%) had neural tube defects and 6 of the 149 (4%) had less severe malformations. Among epileptic women who were exposed to other antiepileptic drug monotherapies during pregnancy (1,048 patients) the malformation rate was 2.9% (95% CI 2.0% to 4.1%). There was a 4-fold increase in congenital malformations among infants with valproic acid-exposed mothers compared with those treated with other antiepileptic monotherapies as a group (Odds Ratio 4.0; 95% CI 2.1 to 7.4). This increased risk does not reflect a comparison versus any specific antiepileptic drug, but the risk versus the heterogeneous group of all other antiepileptic drug monotherapies combined. The increased teratogenic risk from valproic acid in women with epilepsy is expected to be reflected in an increased risk in other indications (e.g., migraine or bipolar disorder).

THE STRONGEST ASSOCIATION OF MATERNAL VALPROATE USAGE WITH CONGENITAL MALFORMATIONS IS WITH NEURAL TUBE DEFECTS (AS DISCUSSED UNDER THE NEXT SUBHEADING). HOWEVER, OTHER CONGENITAL ANOMALIES (E.G. CRANIOFACIAL DEFECTS, CARDIOVASCULAR MALFORMATIONS AND ANOMALIES INVOLVING VARIOUS BODY SYSTEMS), COMPATIBLE AND INCOMPATIBLE WITH LIFE, HAVE BEEN REPORTED. SUFFICIENT DATA TO DETERMINE THE INCIDENCE OF THESE CONGENITAL ANOMALIES IS NOT AVAILABLE.

Neural Tube Defects

THE INCIDENCE OF NEURAL TUBE DEFECTS IN THE FETUS IS INCREASED IN MOTHERS RECEIVING VALPROATE DURING THE FIRST TRIMESTER OF PREGNANCY. THE CENTERS FOR DISEASE CONTROL (CDC) HAS ESTIMATED THE RISK OF VALPROIC ACID EXPOSED WOMEN HAVING CHILDREN WITH SPINA BIFIDA TO BE APPROXIMATELY 1 TO 2%. THE AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS (ACOG) ESTIMATES THE GENERAL POPULATION RISK FOR CONGENITAL NEURAL TUBE DEFECTS AS 0.14% TO 0.2%.

Tests to detect neural tube and other defects using current accepted procedures should be considered a part of routine prenatal care in pregnant women receiving valproate.

Evidence suggests that pregnant women who receive folic acid supplementation may be at decreased risk for congenital neural tube defects in their offspring compared to pregnant women not receiving folic acid. Whether the risk of neural tube defects in the offspring of women receiving valproate specifically is reduced by folic acid supplementation is unknown. DIETARY FOLIC ACID SUPPLEMENTATION BOTH PRIOR TO AND DURING PREGNANCY SHOULD BE ROUTINELY RECOMMENDED TO PATIENTS CONTEMPLATING PREGNANCY.

Other Adverse Pregnancy Effects

PATIENTS TAKING VALPROATE MAY DEVELOP CLOTTING ABNORMALITIES (SEE PRECAUTIONS - GENERAL AND WARNINGS). A PATIENT WHO HAD LOW FIBRINOGEN WHEN TAKING MULTIPLE ANTICONVULSANTS INCLUDING VALPROATE GAVE BIRTH TO AN INFANT WITH AFIBRINOGENEMIA WHO SUBSEQUENTLY DIED OF HEMORRHAGE. IF VALPROATE IS USED IN PREGNANCY, THE CLOTTING PARAMETERS SHOULD BE MONITORED CAREFULLY. PATIENTS TAKING VALPROATE MAY DEVELOP HEPATIC FAILURE (SEE WARNINGS - HEPATOTOXICITY AND BOX WARNING). FATAL HEPATIC FAILURES, IN A NEWBORN AND IN AN INFANT, HAVE BEEN REPORTED FOLLOWING THE MATERNAL USE OF VALPROATE DURING PREGNANCY.

Animal Data

Animal studies have demonstrated valproate-induced teratogenicity. Increased frequencies of malformations, as well as intrauterine growth retardation and death, have been observed in mice, rats, rabbits, and monkeys following prenatal exposure to valproate. Malformations of the skeletal system are the most common structural abnormalities produced in experimental animals, but neural tube closure defects have been seen in mice exposed to maternal plasma valproate concentrations exceeding 230 mcg/mL (2.3 times the upper limit of the human therapeutic range) during susceptible periods of embryonic development. Administration of an oral dose of 200 mg/kg/day or greater (50% of the maximum human daily dose or greater on a mg/m2 basis) to pregnant rats during organogenesis produced malformations (skeletal, cardiac, and urogenital) and growth retardation in the offspring. These doses resulted in peak maternal plasma valproate levels of approximately 340 mcg/mL or greater (3.4 times the upper limit of the human therapeutic range or greater). Behavioral deficits have been reported in the offspring of rats given a dose of 200 mg/kg/day throughout most of pregnancy. An oral dose of 350 mg/kg/day (approximately 2 times the maximum human daily dose on a mg/m2 basis) produced skeletal and visceral malformations in rabbits exposed during organogenesis. Skeletal malformations, growth retardation, and death were observed in rhesus monkeys following administration of an oral dose of 200 mg/kg/day (equal to the maximum human daily dose on a mg/m2 basis) during organogenesis. This dose resulted in peak maternal plasma valproate levels of approximately 280 mcg/mL (2.8 times the upper limit of the human therapeutic range).

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, valproate should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated (see BOXED WARNING).

Urea Cycle Disorders (UCD)

Valproic acid is contraindicated in patients with known urea cycle disorders. 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 valproate 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 and PRECAUTIONS).

Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including Valproic acid, 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
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 Valproic acid 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.

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 PRECAUTIONS - Drug Interactions).

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 events. 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).

Thrombocytopenia

The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia [see PRECAUTIONS]) may be dose-related. In a clinical trial of divalproex sodium 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 × 10 9 /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.

Precautions

Hepatic Dysfunction

See BOXED WARNING, CONTRAINDICATIONS, and WARNINGS.

Pancreatitis

See BOXED WARNING and WARNINGS.

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 - Topiramate). 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.

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. Hyperammonemia should also be considered in patients who present with hypothermia (see PRECAUTIONS - Hypothermia). 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 and WARNINGS - Urea Cycle Disorders and PRECAUTIONS - Hyperammonemia and Encephalopathy Associated with Concomitant Topiramate Use).

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 PRECAUTIONS - Hypothermia). 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 and WARNINGS - Urea Cycle Disorders and PRECAUTIONS - Hyperammonemia).

General

Because of reports of thrombocytopenia (see WARNINGS), 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 valproic acid be monitored for platelet count and coagulation parameters prior to planned surgery. In a clinical trial of divalproex sodium 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 ×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). Evidence of hemorrhage, bruising, or a disorder of hemostasis/coagulation is an indication for reduction of the dosage or withdrawal of therapy.

Since valproate 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 PRECAUTIONS - Drug Interactions).

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.

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.

Multi-organ Hypersensitivity Reaction

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), pruritis, 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.

Information for Patients

Since valproic acid has been associated with certain types of birth defects, female patients of child-bearing age considering the use of valproic acid should be advised of the risk and of alternative therapeutic options and to read the Patient Information Leaflet, which appears as the last section of the labeling. 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 considered.

Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see PRECAUTIONS – Pregnancy).

Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis and, therefore, require further medical evaluation promptly.

Suicidal Thinking and Behavior - Patients, their caregivers, and families should be counseled that AEDs, including Valproic Acid, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of 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 the healthcare providers (see WARNINGS).

Patients should be informed of the signs and symptoms associated with hyperammonemic encephalopathy (see PRECAUTIONS - Hyperammonemia) and be told to inform the prescriber if any of these symptoms occur.

Since valproic acid may produce CNS depression, especially when combined with another CNS depressant (e.g., alcohol), patients should be advised not to engage in hazardous activities, such as driving an automobile or operating dangerous machinery, until it is known that they do not become drowsy from the drug.

Patients should be instructed that a fever associated with other organ system involvement (rash, lymphadenopathy, etc.) may be drug-relat

Sunday, 11 March 2012

Ipol

Pronunciation: poe-LEE-oh-VYE-russ
Generic Name: Poliovirus Vaccine
Brand Name: Ipol

Ipol is used for:

Preventing polio.

Ipol is a vaccine. It works by stimulating the body to create antibodies, which provides protection against the polio virus.

Do NOT use Ipol if:

you are allergic to any ingredient in Ipol, including 2-phenoxyethanol, formaldehyde, streptomycin, polymyxin B, or neomycin

you have had a severe reaction to a previous dose of this vaccine

you have a fever

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

Before using Ipol:

Some medical conditions may interact with Ipol. 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, including latex

if you have an infection, diarrhea, or a weakened immune system, are debilitated, or are undergoing chemotherapy or radiation therapy

Some MEDICINES MAY INTERACT with Ipol. However, no specific interactions with Ipol are known at this time.

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

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

Ipol is usually administered as an injection at your doctor's office, hospital, or clinic. If you are using Ipol at home, carefully follow the injection procedures taught to you by your health care provider.

If Ipol contains particles or is discolored, or if the vial is cracked or damaged in any way, do not use it.

Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Dispose of properly after use. Ask your doctor or pharmacist to explain local regulations for proper disposal.

It is very important to complete your vaccination schedule. If you miss a dose of Ipol, contact your doctor immediately.

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

Important safety information:

Keep all doctor and lab appointments while using Ipol.

If you have a fever, illness, or infection, your doctor may delay giving the vaccine. Discuss this with your doctor.

Ipol is not recommended for use in INFANTS younger than 6 weeks of age. Safety and effectiveness in this age group have not been confirmed.

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

Possible side effects of Ipol:

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:

Crying; decreased appetite; drowsiness; fever, pain, redness, tenderness, or a raised area at the injection site; fussiness; spitting up feedings; tiredness; vomiting.

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

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

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: Ipol 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.

Proper storage of Ipol:

Store Ipol in the refrigerator, between 35 and 46 degrees F (2 and 8 degrees C). Do not freeze. Keep Ipol out of the reach of children and away from pets.

General information:

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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Ipol resources

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

Ipol Concise Consumer Information (Cerner Multum)

Ipol Advanced Consumer (Micromedex) - Includes Dosage Information

IPOL Prescribing Information (FDA)

Poliovirus Vaccine Inactivated Monograph (AHFS DI)

Compare Ipol with other medications

Poliomyelitis Prophylaxis

Saturday, 10 March 2012

Ivy Block Topical

Generic Name: bentoquatam (Topical route)

BEN-toe-kwa-tam

Commonly used brand name(s)

In the U.S.

Ivy Block

Available Dosage Forms:

Lotion

Suspension

Therapeutic Class: Protectant, Dermatological

Uses For Ivy Block

Bentoquatam protects the skin like a shield against poison ivy, poison oak, and poison sumac by physically blocking skin contact with their resin. The best protection against getting these conditions is to avoid contact with these plants. This medicine does not dry oozing and weeping caused by the rash of poison ivy, poison oak, or poison sumac.

Bentoquatam is available without prescription.

Before Using Ivy Block

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

Allergies

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

Pediatric

Although there is no specific information comparing use of bentoquatam in children 6 years of age or older with use in other age groups, this medicine is not expected to cause different side effects or problems in these children than it does in adults. Use is not recommended for children up to 6 years of age.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of bentoquatam in the elderly with use in other age groups, this medicine is not expected to cause different side effects or problems in older people than it does in younger adults.

Interactions with Medicines

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

Interactions with Food/Tobacco/Alcohol

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

Proper Use of Ivy Block

Although this medicine provides some protection, avoiding contact with poison ivy, poison oak, or poison sumac is best.

Do not use this medicine in or near the eyes. If this medicine does get into your eyes, wash them out immediately for 20 minutes with large amounts of cool tap water. If your eyes still burn or are painful, check with your doctor.

To use bentoquatam lotion:

Shake the lotion well before using.

Rub on enough lotion to leave a smooth wet film on skin.

Allow the medicine to dry on the skin at least 15 minutes before being exposed to poison ivy, poison oak, or poison sumac.

Maximum protection lasts for 4 hours but lotion must be reapplied whenever the dried film on the skin cannot be seen.

Remove medicine with soap and water when it is no longer needed.

Dosing

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

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

For prevention of skin irritation from poison ivy, poison oak, or poison sumac (allergic contact dermatitis):
- For topical dosage form (lotion):
  - Adults and children six years of age and older—Apply to the area(s) of skin that may be affected at least fifteen minutes before exposure. Reapply whenever dry film is not seen or every four hours as needed.
  - Children up to six years of age—Use must be determined by the doctor.

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Ivy Block

If a rash or irritation occurs, stop using bentoquatam and check with your health care professional.

Ivy Block Side Effects

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

Check with your doctor as soon as possible if any of the following side effects occur:

Rare

Mild redness of skin

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

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

See also: Ivy Block Topical side effects (in more detail)

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

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

Compare Ivy Block Topical with other medications

Allergic Urticaria

Sunday, 4 March 2012

Iopamidol-370

Generic Name: iopamidol (eye oh PAM ih dol)

Brand Names: Iopamidol-370, Isovue-300, Isovue-370

What is Iopamidol-370 (iopamidol)?

Iopamidol is in a group of drugs called radiopaque (RAY dee oh payk) contrast agents. Iopamidol contains iodine, a substance that absorbs x-rays. Radiopaque contrast agents are used to allow blood vessels, organs, and other non-bony tissues to be seen more clearly on a CT scan or other radiologic (x-ray) examination.

Iopamidol is used to help diagnose certain disorders of the heart, brain, blood vessels, and nervous system.

Iopamidol may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Iopamidol-370 (iopamidol)?

You should not receive iopamidol if you have any type of active infection.

Tell your doctor if you have asthma, hay fever, or history of food or drug allergies, especially if you have had any type of reaction to another contrast agent.

Drink extra fluids before and after you receive iopamidol. This medication can cause you to get dehydrated, which can lead to dangerous effects on your kidneys. Follow your doctor's instructions about the types and amount of fluids you should drink before and after your test. After receiving iopamidol you will be required to lie as still as possible and keep your head raised above the level of your spine during the test. Avoid abrupt movement or physical straining during your test and for several hours afterward. Too much movement can cause iopamidol to mix with your spinal fluid and increase your risk of serious side effects.

What should I discuss with my health care provider before receiving Iopamidol-370 (iopamidol)?

Tell your doctor if you have ever had any type of reaction to another contrast agent.

You should not receive iopamidol if you have any type of active infection.

Before receiving iopamidol, tell your doctor if you have:

a brain tumor or hematoma;

a recent head or brain injury;

epilepsy or other seizure disorder;

kidney disease;

liver disease;

sickle cell anemia;

multiple sclerosis;

alcoholism;

a history of stroke, blood clots, or circulation problems;

asthma, hay fever, or a history of food or drug allergies;

diabetes;

multiple myeloma (bone cancer);

pheochromocytoma; or

a thyroid disorder.

If you have any of these conditions, you may not be able to receive iopamidol, or you may need a dosage adjustment or special tests during treatment.

FDA pregnancy category B. This medication is not expected to 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 iopamidol 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.

Older adults may need special care in avoiding dehydration by drinking extra fluids before and after the radiologic test. Your kidney function may also need to be watched closely after you have received iopamidol.

How is iopamidol used?

Iopamidol is given as an injection through a needle placed into the space around your spinal cord. You will receive this injection in a clinic or hospital setting during your radiologic test. The medicine must be injected slowly, so the needle will stay in place for 1 to 2 minutes before it is removed.

Drink extra fluids before and after you receive iopamidol. This medication can cause you to get dehydrated, which can lead to dangerous effects on your kidneys. Follow your doctor's instructions about the types and amount of fluids you should drink before and after your test. After receiving iopamidol you will be required to lie as still as possible and keep your head raised above the level of your spine during the test. Some people receiving this medication have had reactions to iopamidol that did not start until 30 to 60 minutes after the medicine was first given. Your doctor or other healthcare provider may want to watch you during this period of time after your injection. This is to make sure you do not have any unwanted side effects or delayed reactions.

This medication can cause you to have unusual results with certain thyroid tests. If you have such tests within 16 days after receiving iopamidol, tell the doctor in charge that you have recently received iopamidol.

What happens if I miss a dose?

Since iopamidol is used only during your radiologic test, you will not be on a dosing schedule.

What happens if I overdose?

Seek emergency medical attention if you think you have received too much of this medicine. Symptoms of an iopamidol overdose may include seizure (convulsions).

What should I avoid while receiving Iopamidol-370 (iopamidol)?

Do not allow yourself to become dehydrated during the first few days after receiving iopamidol. Call your doctor if you have any vomiting or diarrhea during this time. Follow your doctor's instructions about the types and amount of fluids you should drink.

Avoid abrupt movement or physical straining during your test and for several hours afterward. Too much movement can cause iopamidol to mix with your spinal fluid and increase your risk of serious side effects.

Iopamidol-370 (iopamidol) side effects

Some of the side effects of iopamidol can occur up to 24 hours after you have received the medication.

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. Call your doctor at once if you have any of these serious side effects:

urinating less than usual or not at all;

severe headache lasting several days, especially if you also have nausea and vomiting;

seizure (convulsions);

feeling light-headed, fainting;

uneven heartbeat;

wheezing or trouble breathing;

fever, chills, body aches, flu symptoms;

severe swelling of the glands in your neck or jaw; or

pain, tenderness, redness, or skin changes where the medicine was injected.

Other less serious side effects are more likely to occur, such as:

headache;

nausea, vomiting;

joint or muscle pain;

back ache, stiff neck;

numbness, warmth, or tingly feeling;

burning or tingling pain in your lower back, buttocks, or the back of your leg;

ringing in your ears;

increased sweating, itchy skin;

chills, stuffy nose, sneezing;

problems with your vision or hearing; or

confusion, slurred speech.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Iopamidol-370 (iopamidol)?

Do not use a phenothiazine medicine to treat nausea or vomiting for at least 48 hours after receiving iopamidol. Phenothiazines include chlopromazine (Thorazine), perphenazine (Trilafon), prochlorperazine (Compazine), promazine (Sparine), promethazine (Phenergan), thiethylperazine (Torecan), and triflupromazine (Stelazine).

Before receiving iopamidol, tell your doctor if you are using any of the following drugs:

seizure medicines (Dilantin, Tegretol, and others);

cold medicine, diet pills;

a stimulant such as Ritalin, Adderall, Cafergot, Dexedrine;

medicine to treat a mental illness such as schizophrenia;

an MAO inhibitor such as isocarboxazid (Marplan), tranylcypromine (Parnate), phenelzine (Nardil), or selegiline (Eldepryl, Emsam); or

antidepressants such as amitriptyline (Elavil), clomipramine (Anafranil), desipramine (Norpramin), imipramine (Tofranil), or nortriptyline (Pamelor).

If you are using any of these drugs, you may need to stop using them for a short time before receiving iopamidol.

There may be other drugs not listed that can affect iopamidol. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Iopamidol-370 resources

Iopamidol-370 Drug Interactions
Iopamidol-370 Support Group
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Where can I get more information?

Your doctor or pharmacist has more information about iopamidol written for health professionals that you may read.