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Tuesday, 15 May 2012

Metoclopramide Hydrochloride

Class: Prokinetic Agents
VA Class: AU300
Molecular Formula: C₁₄H₂₂ClN₃O₂₂O
CAS Number: 54143-57-6
Brands: Reglan

Tardive Dyskinesia

May result in tardive dyskinesia.⁵ ²⁶⁷ Risk increases with increasing duration of therapy and total cumulative dose.⁵ ²⁶⁷ (See Tardive Dyskinesia under Cautions.)

Discontinue metoclopramide in patients who develop signs or symptoms of tardive dyskinesia.⁵ ²⁶⁷ There is no known treatment for tardive dyskinesia; however, symptoms may lessen or resolve in some patients after discontinuance.⁵ ²⁶⁷

Avoid use for >12 weeks in all but rare cases where therapeutic benefit is thought to outweigh risk of developing tardive dyskinesia.⁵ ²⁶⁷

REMS:

FDA approved a REMS for metoclopramide to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of metoclopramide and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antiemetic; stimulant of upper GI motility (prokinetic agent);¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ²⁶³ ²⁶⁷ potent dopamine-receptor antagonist.² ⁴ ⁵ ⁷ ¹⁹ ²⁸ ³⁴ ⁵² ²⁶⁷

Uses for Metoclopramide Hydrochloride

Diabetic Gastric Stasis

Symptomatic treatment of acute and recurrent diabetic gastric stasis (gastroparesis).⁵ ⁷ ³² ⁴⁴ ⁷⁶ ⁷⁷ ⁷⁸ ⁷⁹ ⁸⁰ ⁸³ ⁸⁴ ⁸⁸ ⁸⁹ ²⁶⁷ Successful therapy often requires long-term, intermittent use, since diabetic gastric stasis is a chronic, recurrent disease.⁵ ⁹

Postsurgical Gastric Stasis

Has been used for the symptomatic treatment of acute and chronic postsurgical gastric stasis† following vagotomy and gastric resection or vagotomy and pyloroplasty.³¹ ³⁷ ⁴⁴ ⁴⁹ ⁸⁴ ¹¹³ ¹¹⁴ ¹¹⁵ ¹⁴⁸ ¹⁴⁹ ¹⁵⁰

Prevention of Postoperative Nausea and Vomiting

Prevention of postoperative nausea and vomiting when nasogastric suction is considered undesirable.⁴ ¹²⁵ ²⁶⁷

Prevention of Cancer Chemotherapy-induced Emesis

Used parenterally in high doses for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy including cisplatin alone or in combination with other antineoplastic agents.⁹⁷ ⁹⁸ ⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³ ²⁶³ ²⁶⁷

Prevention of nausea and vomiting associated with other antineoplastic agents (e.g., cyclophosphamide, dacarbazine, doxorubicin, methotrexate) and with cancer chemotherapy regimens that do not include cisplatin.¹⁰³ ¹⁴⁴ ¹⁴⁵ ¹⁴⁶ ¹⁴⁷ ²¹⁸ ²⁶³ ²⁶⁷

ASCO does not consider metoclopramide an appropriate first-line antiemetic for any group of patients receiving chemotherapy of high emetic risk and states that this drug should be reserved for patients unable to tolerate or refractory to first-line agents (i.e., a type 3 serotonin [5-HT₃] receptor antagonist [e.g., dolasetron, granisetron, ondansetron, palonosetron] with dexamethasone and aprepitant).²⁶³

ASCO states that the combination of a 5-HT₃ receptor antagonist, dexamethasone, and aprepitant is preferred in patients receiving combination chemotherapy with an anthracycline and cyclophosphamide; ASCO recommends combined therapy with a 5-HT₃ receptor antagonist and dexamethasone for other chemotherapy regimens of moderate emetic risk (i.e., 31–90% incidence of emesis without antiemetics) and dexamethasone alone for chemotherapy regimens of low emetic risk (i.e., 11–30% incidence).²⁶³

In patients experiencing nausea and vomiting despite recommended prophylaxis regimens, ASCO recommends that clinicians consider adding a benzodiazepine (e.g., alprazolam, lorazepam), butyrophenone, or phenothiazine to the regimen or substituting high-dose IV metoclopramide for the 5-HT₃ receptor antagonist in the regimen.²⁶³

Antiemetics can be prescribed on an as-needed basis for chemotherapy regimens with minimal emetic risk (<10% incidence of emesis without antiemetics).²⁶³

Metoclopramide has been used orally† for the prevention of chemotherapy-induced nausea and vomiting. ¹⁷⁷ ²¹⁸ ²²¹ ²²⁴ ²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶ ²⁷⁵ Some experts state that patients receiving oral chemotherapy requiring only as-needed (“prn”) antiemetic therapy or receiving an IV chemotherapy regimen with low emetic risk may receive oral† metoclopramide.²⁷⁵

Oral† metoclopramide has been effective when given in combination with dexamethasone for the prevention of delayed emesis in patients receiving chemotherapy.²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶ For prevention of delayed emesis in patients receiving cisplatin or other chemotherapy of high emetic risk, ASCO recommends the combination of dexamethasone and aprepitant.²⁶³

Intubation of the Small Intestine

Used parenterally to facilitate small intestine intubation when the tube (e.g., endoscope, biopsy tube) does not pass through the pylorus during 10 minutes of conventional maneuvers.¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁹ ¹⁷⁶ ²⁶⁷

Radiographic Examination of the Upper GI Tract

Used parenterally to stimulate gastric emptying and intestinal transit of barium when delayed emptying interferes with radiographic examination of the stomach and/or small intestine.⁴ ⁴³ ¹¹⁰ ¹⁸⁴ ²⁶⁷

Gastroesophageal Reflux

Short-term (≤12 weeks) relief of symptomatic, documented gastroesophageal reflux in adults who are unresponsive to conventional therapy (e.g., changes in lifestyle, habits, diet, weight reduction) alone.⁵ ⁹ ³⁰ ³⁹ ⁴⁰ ⁴¹ ⁴² ¹¹¹ ¹¹² ¹¹⁶ ¹¹⁷ ¹²⁵ ¹²⁹ ¹⁸⁵ ¹⁸⁶ ¹⁸⁷ ¹⁸⁸ ¹⁸⁹ ¹⁹⁰

Regular use for this purpose has declined; proton-pump inhibitors provide greater control of acid reflux.²⁵⁸ ²⁷³ ²⁷⁴ Some experts recommend against use of metoclopramide for this purpose based on the drug’s adverse effect profile and lack of high-quality supporting data.²⁷³ ²⁷⁴

Metoclopramide Hydrochloride Dosage and Administration

Administration

Administer orally, by direct IV injection or IV infusion, or IM.⁵ ²⁶³ ²⁶⁷

Metoclopramide therapy should not exceed 12 weeks’ duration.⁵ ²⁶⁷ ²⁶⁸ ²⁶⁹

Oral Administration

Metoclopramide oral solution and tablets are recommended for use in adults only.⁵ ²⁶⁸ ²⁶⁹

IV Administration

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

Dilution

For direct IV injection, use without further dilution.²⁶⁷

If dose is >10 mg, dilute in 50 mL of a compatible IV solution.²⁶⁷

For IV infusion, manufacturer recommends dilution in 50 mL of 5% dextrose, 0.9% sodium chloride, 5% dextrose and 0.45% sodium chloride, Ringer’s, or lactated Ringer’s injection.²⁶⁷

Manufacturer states that 0.9% sodium chloride injection is preferred because metoclopramide hydrochloride is most stable in this solution.²⁶⁷

Rate of Administration

Direct IV injection: Administer each 10 mg slowly over 1–2 minutes.²⁶⁷ Rapid IV injection may cause transient but intense feelings of anxiety and restlessness, followed by drowsiness.²⁶⁷

IV infusion: Administer slowly over ≥15 minutes.²⁶⁷

IM Administration

Inject without further dilution.²⁶⁷

Dosage

Available as metoclopramide hydrochloride; dosage expressed in terms of metoclopramide.⁵ ²⁶⁷

Pediatric Patients

Intubation of the Small Intestine

IV

Children <6 years of age: Usually, one 0.1-mg/kg dose given by direct IV injection.²⁶⁷

Children 6–14 years of age: Usually, one 2.5- to 5-mg dose given by direct IV injection.²⁶⁷

Children >14 years of age: Usually, one 10-mg dose given by direct IV injection.²⁶⁷

Adults

Diabetic Gastric Stasis

Oral

10 mg 4 times daily, given 30 minutes before meals and at bedtime.⁵ Continue for 2–8 weeks, depending on response and likelihood of continued well-being if drug is discontinued.⁵ Reinstitute at earliest symptom recurrence.⁵

IV

If symptoms are severe or oral use is not feasible, 10 mg 4 times daily, given by direct IV injection 30 minutes before meals and at bedtime.⁵ ²⁶⁷ Continued use for up to 10 days may be required until symptoms subside enough to allow oral administration;⁵ ²⁶⁷ however, thoroughly assess the risks and benefits prior to continuing therapy.²⁶⁷

IM

If symptoms are severe or oral use is not feasible, 10 mg 4 times daily, given 30 minutes before meals and at bedtime.⁵ ²⁶⁷ Continued use for up to 10 days may be required until symptoms subside enough to allow oral administration;⁵ ²⁶⁷ however, thoroughly assess the risks and benefits prior to continuing therapy.²⁶⁷

Prevention of Postoperative Nausea and Vomiting

IM

Manufacturer states that usual dose is 10 mg administered near the end of the surgical procedure; 20 mg also may be used.²⁶⁷

Prevention of Cancer Chemotherapy-induced Emesis

Oral†

Some experts state that patients receiving IV chemotherapy regimens with low emetic risk may receive 10–40 mg of metoclopramide before the chemotherapy dose and then every 4 or 6 hours as needed.²⁷⁵

Some experts state that patients receiving oral chemotherapy requiring only as-needed (“prn”) antiemetic therapy may receive 10–40 mg of metoclopramide before the chemotherapy dose and then every 4 or 6 hours as needed.²⁷⁵

When given in combination with dexamethasone in clinical trials for the prevention of delayed emesis (i.e., vomiting occurring ≥24 hours after chemotherapy), 20–40 mg (or 0.5 mg/kg) of metoclopramide has been given 2–4 times daily for 3 or 4 days.²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶

IV

Manufacturer states that metoclopramide usually is given by IV infusion 30 minutes before administration of chemotherapy, and then repeated every 2 hours for 2 additional doses followed by every 3 hours for 3 additional doses.²⁶⁷ Manufacturer states that initial 2 doses should be 2 mg/kg if highly emetogenic chemotherapy used;²⁶⁷ for less emetogenic drugs or regimens, initial 1-mg/kg dose may be sufficient.²⁶⁷ However, combinations of other antiemetic agents generally are preferred as first-line regimens in patients receiving chemotherapy of moderate or high emetic risk (see Prevention of Cancer Chemotherapy-induced Emesis under Uses). ²⁶³ ²⁷⁵

Intubation of the Small Intestine

IV

Usually, one 10-mg dose given by direct IV injection.²⁶⁷

Radiographic Examination of the Upper GI Tract

IV

Usually, one 10-mg dose given by direct IV injection.²⁶⁷

Gastroesophageal Reflux

Oral

Usually, 10–15 mg up to 4 times daily (30 minutes before each meal and at bedtime) for 4–12 weeks, depending on symptoms and response.⁵ Patients sensitive to therapeutic and/or adverse effects of metoclopramide may require initial dose of 5 mg.⁵

For intermittent symptoms or symptoms at specific times of the day, one 20-mg dose before the provoking situation may be preferred to daily administration of multiple doses.⁵

In patients with esophageal erosion and ulceration, 15 mg 4 times daily for 12 weeks has provided healing; monitor endoscopically because of the poor correlation between symptoms and healing.⁵

Prescribing Limits

Adults

Avoid use of metoclopramide for >12 weeks in all but rare cases where therapeutic benefit is thought to outweigh risk of developing tardive dyskinesia.⁵ ²⁶⁷ (See Boxed Warning and see Tardive Dyskinesia under Cautions.)

Gastroesophageal Reflux

Oral

Safety and efficacy beyond 12 weeks not established; use beyond 12 weeks not recommended.⁵

Special Populations

Hepatic Impairment

Dosage modification does not appear to be necessary.⁵ ²⁶⁷

Renal Impairment

Modify dosage according to degree of renal impairment.⁵ ⁵⁴ ⁵⁸ ⁵⁹ ¹³⁵ ¹⁴² ²⁶⁷

In patients with Cl_cr <40 mL/minute, manufacturers recommend an initial dosage of approximately 50% of the usual dosage.⁵ ²⁶⁷ Subsequently, increase or decrease dosage according to response and tolerance.⁵ ²⁶⁷

Geriatric Patients

Select dosage with caution, usually initiating therapy at the low end of the dosage range.⁵ ²⁶⁷

Administer lowest effective dosage.⁵ ²⁶⁷ In geriatric patients with gastroesophageal reflux, initial 5-mg dose may be required due to possible sensitivity to therapeutic and/or adverse effects of metoclopramide.⁵

Cautions for Metoclopramide Hydrochloride

Contraindications

Mechanical obstruction or perforation or other situations in which stimulation of GI motility might be dangerous.⁵ ²⁶⁷

GI hemorrhage⁵ ²⁶⁷ (however, has been used to empty the stomach of blood prior to endoscopy in patients with acute upper GI hemorrhage).⁴ ¹²⁵

Pheochromocytoma (due to potential for hypertensive crisis).⁵ ²⁶⁷

History of seizure disorders.⁴ ⁵ ²⁶⁷

Concomitant therapy with drugs likely to cause extrapyramidal reactions (e.g., phenothiazines, butyrophenones).⁴ ⁵ ²⁶⁷

Known intolerance to metoclopramide.⁵ ²⁶⁷

Known hypersensitivity to metoclopramide or any ingredient in the formulation.⁵ ²⁶⁷

Warnings/Precautions

Warnings

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements involving the tongue, face, mouth, or jaw, and sometimes the trunk and/or extremities, may occur; movements may be choreoathetotic in appearance.⁵ ⁹³ ⁹⁴ ¹³⁰ ¹⁵⁷ ¹⁵⁸ ¹⁵⁹ ²⁶⁷ ²⁷⁰ ²⁷¹ ²⁷² (See Boxed Warning.)

Reported in about 20% of patients receiving the drug for ≥12 weeks.⁵ ²⁶⁷ ²⁷⁰ ²⁷¹ Avoid use of metoclopramide for >12 weeks in all but rare cases where therapeutic benefit is thought to outweigh risk of developing tardive dyskinesia.⁵ ²⁶⁷ ²⁷²

Although risk of developing tardive dyskinesia may be increased in geriatric patients, women, and patients with diabetes mellitus, it is not possible to predict which patients will develop metoclopramide-induced tardive dyskinesia.⁵ ²⁶⁷ ²⁷⁰ ²⁷¹ ²⁷² Risk of occurrence and irreversibility increases with increasing duration of therapy and total cumulative dose.⁵ ²⁶⁷ ²⁷¹ ²⁷²

Discontinue metoclopramide in patients who develop signs or symptoms of tardive dyskinesia.⁵ ²⁶⁷ ²⁷⁰ ²⁷¹ There is no known effective treatment for tardive dyskinesia; however, tardive dyskinesia may remit, either partially or completely, in some patients within several weeks to months after discontinuance.⁵ ²⁶⁷ ²⁷¹

Metoclopramide may suppress or partially suppress signs of tardive dyskinesia, thereby masking the underlying disease process; effect of this suppression on the long-term course of tardive dyskinesia is unknown.⁵ ²⁶⁷ Do not use metoclopramide for symptomatic control of tardive dyskinesia.⁵ ²⁶⁷

Extrapyramidal Symptoms

Potential for extrapyramidal reactions,⁴ ⁵ ⁹⁰ ⁹¹ ¹²⁵ ¹⁶⁹ ²⁰⁵ ²⁰⁶ ²⁰⁷ ²⁶⁷ especially in pediatric patients and adults <30 years of age or when high doses (e.g., IV doses for prophylaxis of cancer chemotherapy-induced nausea and vomiting) are administered.⁵ ⁹¹ ¹⁶⁹ ²⁶⁷

Commonly manifested as acute dystonic reactions or akathisia; stridor and dyspnea (possibly due to laryngospasm) reported rarely.⁵ ²⁶⁷

Generally occur within 24–48 hours after starting therapy⁵ ²⁰⁵ ²⁰⁶ ²⁰⁷ ²⁶⁷ and usually subside within 24 hours following drug discontinuance.⁴ ⁹⁰ ²⁰⁵

Most patients respond rapidly to treatment with diazepam⁴ or an agent with central anticholinergic activity (e.g., diphenhydramine hydrochloride 20–50 mg orally, IM, or IV;⁵ ²⁶⁷ ²⁷⁵ ²⁷⁶ benztropine 1–2 mg IM⁵ ²⁶⁷ ).⁴ ⁵ ¹⁷⁰ ²⁰⁶ ²⁰⁷ ²⁶⁷

Parkinsonian Symptoms

Parkinsonian symptoms (e.g., tremor, rigidity, bradykinesia, akinesia) occur rarely; may be associated with usual¹⁶⁰ or excessive metoclopramide doses⁶² or decreased renal function.⁹ ⁵⁴

Possible exacerbation of parkinsonian symptoms;⁵ ⁹ ⁵⁴ ⁶² ¹⁶⁰ ²⁶⁷ use with caution, if at all, in patients with parkinsonian syndrome.⁵ ²⁶⁷

More common during first 6 months of therapy but occur occasionally after longer periods.⁵ ²⁶⁷

Symptoms generally subside within 2–3 months following drug discontinuance.⁵ ²⁶⁷

Neuroleptic Malignant Syndrome (NMS)

NMS (characterized by hyperthermia, varying levels of consciousness, muscular rigidity, and autonomic dysfunction) reported rarely.⁵ ²⁰⁸ ²⁶⁷

Important to determine whether untreated or inadequately treated extrapyramidal reactions and serious medical illness (e.g., pneumonia, systemic infection) may coexist.⁵ ²⁶⁷ Also consider the possibility of central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, and primary CNS pathology.⁵ ²⁶⁷

Immediately discontinue metoclopramide and other drugs not considered essential, provide intensive symptomatic treatment, monitor patient, and treat any concomitant serious medical condition for which specific therapies are available.⁵ ²⁶⁷ Dantrolene and bromocriptine have been used in the treatment of NMS, but their efficacy has not been established and there currently is no specific drug therapy.⁵ ²⁶⁷

Depression

Mild to severe depression (including suicidal ideation and suicide) has occurred in patients with or without prior history of depression.⁵ ²¹⁰ ²¹¹ ²¹⁵ ²⁶⁷

Use with extreme caution and only when anticipated benefits outweigh possible risks in patients with a history of mental depression, especially those with suicidal tendencies.⁵ ²⁶⁷

Sensitivity Reactions

Procainamide Cross-sensitivity

Theoretical potential for patients who are allergic to procainamide to exhibit cross-sensitivity to metoclopramide (since the drugs are structurally similar).¹¹ ¹²

General Precautions

GI Anastomosis or Closure

When deciding whether to use metoclopramide or NG suction to prevent postoperative nausea and vomiting, consider the possibility that metoclopramide theoretically could produce increased pressure on suture lines following GI anastomosis or closure.²⁶⁷

Fluid and Electrolyte Effects

Possible transient increases in plasma aldosterone concentrations and sodium retention; closely monitor patients (e.g., those with CHF or cirrhosis) at risk of developing fluid retention and volume overload or hypokalemia.³ ⁵ ⁶⁹ ²⁶⁷

Discontinue metoclopramide if fluid retention or volume overload occurs at any time during therapy.⁵ ²⁶⁷

Hypertension

Possible increase in circulating catecholamines in hypertensive patients; use with caution in these patients.⁵ ²⁶⁷

CNS Depression

Drowsiness may occur, particularly at higher dosages.⁵ ²⁶⁷ Performance of activities requiring mental alertness and physical coordination (operating machinery, driving a motor vehicle) may be impaired.⁵ ²⁶⁷

Withdrawal Effects

Adverse reactions, particularly CNS reactions, may occur following discontinuance of drug.⁵ Some patients may experience withdrawal symptoms including dizziness, nervousness, and/or headaches following discontinuance.⁵

Patients with Cytochrome-b₅ Reductase Deficiency

Patients with cytochrome-b₅ reductase deficiency have an increased risk of methemoglobinemia and/or sulfhemoglobinemia when metoclopramide is administered.⁵ ²⁶⁷

Patients with Glucose-6-phosphate Dehydrogenase Deficiency

Methylene blue is not recommended for treatment of metoclopramide-induced methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.⁵ ²⁶⁷

Specific Populations

Pregnancy

Category B.⁵ ²⁶⁷

Lactation

Distributed into milk.⁵ ¹³⁹ ¹⁴⁰ ²⁶⁷ Use caution in nursing women.⁵ ²⁶⁷

Pediatric Use

Manufacturers currently recommend use in children only to facilitate intubation of the small intestine;²⁶⁷ however, has been effective for the management of gastric stasis†¹⁷⁸ ¹⁸⁰ ¹⁸¹ and gastroesophageal reflux†¹⁷⁹ ¹⁸² in infants and children.

Use with caution; incidence of extrapyramidal reactions is increased in children.⁵ ⁹¹ ¹²⁵ ¹⁵⁶ ²⁶⁷

Use with caution in neonates.⁵ ²⁶⁷ Neonatal susceptibility to methemoglobinemia is increased due to prolonged clearance (may cause excessive serum concentrations) in combination with decreased neonatal levels of cytochrome-b₅ reductase.⁵ ²⁶⁷

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients repond differently than younger adults.⁵ ²⁶⁷

Possible increased risk of tardive dyskinesia.⁵ ²⁶⁷

Risk of adverse parkinsonian effects increases with increasing dosage; administer lowest effective dosage in geriatric patients.⁵ ²⁶⁷ If parkinsonian symptoms develop, generally should discontinue metoclopramide before initiating specific antiparkinsonian therapy.⁵ ²⁶⁷

Confusion and oversedation may occur.⁵ ²⁶⁷

Substantially eliminated by kidneys; risk of adverse reactions may be greater in patients with impaired renal function.⁵ ²⁶⁷ (See Renal Impairment under Dosage and Administration.)

Select dosage with caution because of age-related decreases in renal function and concomitant disease and drug therapy.⁵ ²⁶⁷ (See Geriatric Patients under Dosage and Administration).

Hepatic Impairment

Possible increased risk of fluid retention and hypokalemia in patients with cirrhosis.³ ⁵ ⁶⁹ ²⁶⁷ (See Fluid and Electrolyte Effects under Cautions.)

Discontinue if fluid retention or volume overload occurs at any time during therapy.⁵ ²⁶⁷

Renal Impairment

Clearance may be reduced.⁵ ⁵⁴ ⁵⁹ ¹⁴² ¹⁹² ²⁶⁷ Possible increased risk of adverse effects.⁵ ²⁶⁷ Use with caution; reduce dosage during prolonged therapy in patients with renal impairment.⁵ ⁵⁴ ⁵⁸ ⁵⁹ ⁶⁹ ¹³⁵ ¹⁴² ²⁶⁷ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Restlessness, drowsiness, fatigue, lassitude, nausea, bowel disturbances (principally diarrhea).⁴ ⁵ ⁹⁰ ¹²⁵ ²⁶⁷

Interactions for Metoclopramide Hydrochloride

Orally Administered Drugs

Possible decreased absorption of certain drugs that disintegrate, dissolve, and/or are absorbed mainly in the stomach.⁴ ⁵ ¹¹⁹ ¹²⁵ ²⁶⁷ Clinical importance not determined.^c

Possible enhanced rate and extent of absorption of drugs mainly absorbed in the small intestine.⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷ Clinical importance not determined.^c

Specific Drugs

Drug	Interaction	Comments
Acetaminophen	Possible enhanced rate and extent of acetaminophen absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷	Clinical importance not determined^c
Anesthetic agents	Acute hypotension reported with concomitant IV metoclopramide and hypotensive anesthetic agents (with or without ganglionic blocking agents) during neurosurgical procedures¹⁶² ¹⁶³	Clinical importance not known¹²⁵ ¹⁶² ¹⁶³
Anticholinergic agents (e.g., atropine)	Antagonism of GI motility effects of metoclopramide ⁵ ²⁶⁷
Aspirin	Possible enhanced rate and extent of aspirin absorption⁴ ¹²⁰ ¹²⁵	Clinical importance not determined^c
Butyrophenones	Potential for extrapyramidal reactions⁴ ⁵ ²⁶⁷ and worsening of symptoms in patients with parkinsonian syndrome¹³⁰ ¹⁵⁸ ¹⁶⁰	Concomitant use contraindicated⁴ ⁵ ²⁶⁷
Cholinergic agents	Potentiation of GI motility effects of metoclopramide⁵
CNS depressants (alcohol, opiates or other analgesics, barbiturates or other sedatives, anesthetics)	Increased CNS depressant effects;⁵ ²⁶⁷ possible enhanced rate and extent of alcohol absorption⁴ ⁵ ¹²⁵ ²⁶⁷	Use caution to avoid excessive sedation;^c clinical importance of enhanced alcohol absorption not determined^c
Cyclosporine	Possible enhanced rate and extent of cyclosporine absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷	Clinical importance not determined^c
Diazepam	Possible enhanced rate and extent of diazepam absorption⁴ ¹²⁰ ¹²⁵	Clinical importance not determined^c
Digoxin	Possible decreased digoxin absorption; Lanoxin tablets apparently not affected because of small drug-particle size and rapid absorption⁴ ⁵ ¹¹⁹ ¹²⁵ ²⁶⁷
Insulin	Possible alteration of glycemic control secondary to metoclopramide-related changes in the delivery of food to and the rate of absorption in the intestine⁵ ²⁶⁷	Adjustment of insulin dose or timing may be necessary⁵ ²⁶⁷
Levodopa	Possible enhanced rate and extent of levodopa absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷	Clinical importance not determined^c
Lithium	Possible enhanced rate and extent of lithium absorption⁴ ¹²⁰ ¹²⁵	Clinical importance not determined^c
MAO inhibitors	Possible hypertensive reaction due to metoclopramide-induced release of catcholamines⁵ ²⁶⁷	Use with caution, if at all⁵ ²⁶⁷
Opiate analgesics	Antagonism of GI motility effects of metoclopramide⁵ ¹⁵ ³³ ²⁶⁷
Phenothiazines	Potential for extrapyramidal reactions⁴ ⁵ ²⁶⁷ and worsening of symptoms in patients with parkinsonian syndrome¹³⁰ ¹⁵⁸ ¹⁶⁰	Concomitant use contraindicated⁴ ⁵ ²⁶⁷
Tetracycline	Possible enhanced rate and extent of tetracycline absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷	Clinical importance not determined^c

Metoclopramide Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Following oral administration, rapidly and almost completely absorbed;⁴ ⁵ ⁷ ⁵³ ⁵⁴ ⁵⁵ ⁵⁶ ¹³³ ¹³⁴ ¹³⁵ ²⁶⁷ limited data indicate that 30–100% of an oral dose reaches systemic circulation as unchanged metoclopramide.⁵ ⁵⁴ ⁵⁶ ¹³³ ¹³⁴ ¹³⁵ ²⁶⁷ Peak plasma concentration usually attained at 1–2 hours.⁵ ⁵⁵ ²⁶⁷

Following IM administration, absolute bioavailability is 74–96%.⁷

Onset

Following oral administration, 30–60 minutes for effects on GI tract.⁵ ⁷ ²⁶⁷

Following IM administration, 10–15 minutes for effects on GI tract.⁵ ⁷ ²⁶⁷

Following IV administration, 1–3 minutes for effects on GI tract.⁵ ⁷ ²⁶⁷

Duration

1–2 hours.⁵ ²⁶⁷

Special Populations

In patients with gastric stasis, absorption may be delayed or diminished.¹⁴

In infants, metoclopramide may accumulate in plasma after multiple doses; mean peak plasma concentration was 2-fold higher after 10th dose compared with that after first dose in infants (3.5 weeks–5.4 months of age) with gastroesophageal reflux receiving metoclopramide oral solution.⁵ ²⁶⁷

Distribution

Extent

In mice, distributed into most body tissues and fluids; high concentrations in GI mucosa, liver, biliary tract, and salivary glands, with lower concentrations in brain, heart, thymus, adrenals, adipose tissue, and bone marrow.⁴ ⁷

Crosses the placenta¹³⁸

Distributed into milk in humans;⁵ ¹³⁹ ¹⁴⁰ ²⁶⁷ milk concentrations are higher than plasma concentrations 2 hours after oral administration.¹³⁹ ¹⁴⁰

Plasma Protein Binding

13–30% (principally albumin).⁵ ⁷ ²⁶⁷

Elimination

Metabolism

Minimally metabolized; not known whether major metabolite found in urine is active.⁵ ⁵³ ²⁶⁷

Elimination Route

Excreted in urine (85%) as unchanged drug and metabolites⁵ ⁷ ⁵³ ⁵⁴ ¹³³ ²⁶⁷ and also in feces (about 5%).⁷ ⁵³

Minimally removed by hemodialysis⁵ ¹²⁹ ¹⁹²

Saturday, 12 May 2012

Tusana-D

Generic Name: chlorpheniramine, hydrocodone, and phenylephrine (KLOR fe NEER a meen, HYE droe KOE done, FEN il EFF rin)

Brand Names: B-Tuss, Coughtuss, Cytuss HC, De-Chlor HC, DroTuss-CP, Ed-TLC, Ed-Tuss HC, Endal-HD Plus, H-C Tussive, Histussin-HC, Hydro-PC II, Hydro-PC II Plus, Hydron CP, Liquicough HC, Maxi-Tuss HCX, Mintuss MS, Neo HC, Poly-Tussin, Poly-Tussin HD, Relacon-HC, Relacon-HC NR, Relasin-HC, Rindal HD Plus, Rindal-HD, Triant-HC, Tusana-D, Z-Cof HC

What is Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

Chlorpheniramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Hydrocodone is a narcotic cough medicine.

Phenylephrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of chlorpheniramine, hydrocodone, and phenylephrine is used to treat runny or stuffy nose, sinus congestion, and cough caused by the common cold or flu.

Chlorpheniramine, hydrocodone, and phenylephrine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

Do not take this medication if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. Serious, life threatening side effects can occur if you use chlorpheniramine, hydrocodone, and phenylephrine before the MAO inhibitor has cleared from your body. Chlorpheniramine, hydrocodone, and phenylephrine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine, hydrocodone, and phenylephrine. Before using this medication, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by chlorpheniramine, hydrocodone, and phenylephrine. Hydrocodone may be habit-forming and should be used only by the person it was prescribed for. Never share hydrocodone with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

What should I discuss with my healthcare provider before taking Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

To make sure you can safely take this medication, tell your doctor if you have any of these other conditions:

asthma, COPD, sleep apnea, or other breathing disorder;

liver or kidney disease;

heart disease or high blood pressure;

diabetes;

a thyroid disorder;

curvature of the spine;

a history of head injury or brain tumor;

epilepsy or other seizure disorder;

low blood pressure;

glaucoma;

gallbladder disease;

Addison's disease or other adrenal gland disorders;

enlarged prostate, urination problems;

mental illness; or

a history of drug or alcohol addiction.

Hydrocodone may be habit-forming and should be used only by the person it was prescribed for. Never share hydrocodone with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it. FDA pregnancy category C. It is not known whether chlorpheniramine, hydrocodone, and phenylephrine will harm an unborn baby. Hydrocodone may cause addiction or withdrawal symptoms in a newborn if the mother takes the medication during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant while using chlorpheniramine, hydrocodone, and phenylephrine. It is not known whether chlorpheniramine, hydrocodone, and phenylephrine 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.

How should I take Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

You may take this medication with or without food.

Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Store at room temperature away from moisture and heat. Keep track of the amount of medicine used from each new bottle. Hydrocodone is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

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?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of hydrocodone can be fatal.

Overdose symptoms may include extreme drowsiness, feeling restless or nervous, vomiting, stomach pain, warmth or tingly feeling, seizure (convulsions), pinpoint pupils, confusion, cold and clammy skin, weak pulse, shallow breathing, fainting, or breathing that stops.

What should I avoid while taking Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

Chlorpheniramine, hydrocodone, and phenylephrine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine, hydrocodone, and phenylephrine.

Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have a serious side effect such as:

severe dizziness, anxiety, restless feeling, or nervousness;

fast, pounding, or uneven heartbeats;

shallow breathing, slow heartbeat;

confusion, hallucinations, unusual thoughts or behavior;

feeling like you might pass out;

urinating less than usual or not at all;

easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms;

dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, chest pain, shortness of breath, seizure); or

upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

nausea, vomiting, upset stomach, constipation;

dry mouth;

blurred vision;

dizziness, drowsiness;

problems with memory or concentration;

sleep problems (insomnia);

ringing in your ears;

warmth, tingling, or redness under your skin; or

skin rash or itching.

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 Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

Before using this medication, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by chlorpheniramine, hydrocodone, and phenylephrine.

Tell your doctor about all other medications you use, especially:

blood pressure medication;

cimetidine (Tagamet);

rifampin (Rifadin, Rifater, Rifamate, Rimactane);

zidovudine (Retrovir, AZT);

an antidepressant;

a diuretic (water pill);

medication to treat irritable bowel syndrome;

bladder or urinary medications such as oxybutynin (Ditropan, Oxytrol) or tolterodine (Detrol);

aspirin or salicylates (such as Disalcid, Doan's Pills, Dolobid, Salflex, Tricosal, and others);

seizure medication such as phenytoin (Dilantin) or phenobarbital (Luminal, Solfoton);

a beta-blocker such as atenolol (Tenormin), carteolol (Cartrol), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal), sotalol (Betapace), timolol (Blocadren), and others; or

medicines to treat psychiatric disorders, such as chlorpromazine (Thorazine), haloperidol (Haldol), mesoridazine (Serentil), pimozide (Orap), or thioridazine (Mellaril).

This list is not complete and other drugs may interact with chlorpheniramine, hydrocodone, and phenylephrine. 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 Tusana-D resources

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

Chlorpheniramine/Hydrocodone/Phenylephrine Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Tusana-D with other medications

Cough and Nasal Congestion

Where can I get more information?

Your pharmacist can provide more information about chlorpheniramine, hydrocodone, and phenylephrine.

See also: Tusana-D side effects (in more detail)

Thursday, 10 May 2012

Questran Powder for Oral Suspension 4g

1. Name Of The Medicinal Product

Questran Powder for Oral Suspension 4g

2. Qualitative And Quantitative Composition

Each sachet contains 4g anhydrous colestyramine (a basic anion-exchange resin).

3. Pharmaceutical Form

Powder for Oral Suspension.

4. Clinical Particulars

4.1 Therapeutic Indications

Questran is used for:

1.	Primary prevention of coronary heart disease in men between 35 and 59 years of age and with primary hypercholesterolaemia who have not responded to diet and other appropriate measures.
2.	Reduction of plasma cholesterol in hypercholesterolaemia, particularly in those patients who have been diagnosed as Fredrickson's Type II (high plasma cholesterol with normal or slightly elevated triglycerides).
3.	Relief of pruritus associated with partial biliary obstruction and primary biliary cirrhosis.
4.	Relief of diarrhoea associated with ileal resection, Crohn's disease, vagotomy and diabetic vagal neuropathy.
5.	Management of radiation-induced diarrhoea.

4.2 Posology And Method Of Administration

Adults:

As a precautionary measure, where concurrent drug therapy exists then such drugs should be administered at least one hour before or 4-6 hours after Questran.

Questran should not be taken in its dry form.

Questran should be administered mixed with water or a suitable liquid, such as fruit juice, and stirred to a uniform consistency.

Questran may also be mixed with skimmed milk, thin soups, pulpy fruits with high moisture content, e.g. apple sauce, etc..

1. For primary prevention of coronary heart disease and to reduce cholesterol: After initial introduction over a three to four week period, 3 to 6 Questran sachets per day, administered either as a single daily dose or in divided doses up to four times daily, according to dosage requirements and patient acceptability. Dosage may be modified according to response and can be increased to 9 sachets per day if necessary.

Occasional slight gastro-intestinal upsets, e.g. constipation, may occur when starting Questran. These usually pass with continued usage of Questran and are minimised by starting therapy gradually.

Final dose required	Week 1	Week 2	Week 3	Week 4
	Sachets per day
3	1	2	3	3
4	1	2	3	4
6	1	2	3	6

2. To relieve pruritus: One or two sachets daily are usually sufficient.

3. To relieve diarrhoea: As for reduction of cholesterol but it may be possible to reduce this dosage. In all patients presenting with diarrhoea induced by bile acid malabsorption, if a response is not seen within 3 days, then alternative therapy should be initiated.

Children 6 - 12 years:

The initial dose is determined by the following formula:

Subsequent dosage adjustment may be necessary where clinically indicated.

Children under 6 years: The dose has not been established in infants and children under 6 years.

Elderly:

No dosage adjustment is necessary.

4.3 Contraindications

Questran is contra-indicated in patients who have shown hypersensitivity to any of the product ingredients.

In patients with complete biliary obstruction, since Questran cannot be effective where bile is not secreted into the intestine.

4.4 Special Warnings And Precautions For Use

Reduction of serum folate concentrations has been reported in children with familial hypercholesterolaemia. Supplementation with folic acid should be considered in these cases.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Questran may delay or reduce the absorption of certain drugs (such as digitalis, tetracycline, chlorothiazide, warfarin and thyroxine). The response to concomitant medication should be closely monitored and appropriate adjustments made if necessary.

Questran may interfere with the pharmacokinetics of drugs that undergo enterohepatic recirculation.

Patients should take other drugs at least one hour before or 4-6 hours after Questran to minimise possible interference with their absorption.

4.6 Pregnancy And Lactation

The safety of colestyramine in pregnancy and lactation has not been established and the possibility of interference with absorption of fat soluble vitamins should be considered.

4.7 Effects On Ability To Drive And Use Machines

None.

4.8 Undesirable Effects

Since Questran may interfere with the absorption of fat soluble vitamins, the diet may require supplementation with Vitamins A, D and K during prolonged high dose administration.

Chronic use of Questran may be associated with increased bleeding tendency due to hyperprothrombinaemia associated with Vitamin K deficiency. This will usually respond promptly to parenteral Vitamin K administration; recurrences can be prevented by oral administration of Vitamin K.

Hyperchloraemic acidosis has occasionally been reported following the prolonged use of anion exchange resins.

Gastro-intestinal side effects are those most frequently reported. The principal complaint is constipation which may be controlled with the usual remedies, and frequently disappears on continued usage of Questran. Large doses of Questran can cause diarrhoea.

Taste disturbance and skin irritation have been reported rarely but causal relationship to colestyramine remains undetermined. Rare reports of intestinal obstruction have been received.

4.9 Overdose

One case of medication error experienced heartburn and nausea after taking colestyramine 27g t.i.d. for a week. The potential problem in overdosage would be obstruction of the gastrointestinal tract.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Colestyramine resin absorbs and combines with the bile acids in the intestine to form an insoluble complex which is excreted in the faeces. This results in a continuous, though partial, removal of bile acids from the enterohepatic circulation by preventing their reabsorption. The increased faecal loss of bile acids leads to an increased oxidation of cholesterol to bile acids and a decrease in serum cholesterol levels and low density lipoprotein serum levels. Colestyramine is hydrophilic but it is not soluble in water, nor is it hydrolysed by digestive enzymes.

In patients with partial biliary obstruction, the reduction of serum bile acid levels reduces excess bile acids deposited in the dermal tissue with resultant decrease in pruritus.

5.2 Pharmacokinetic Properties

Colestyramine is not absorbed from the digestive tract.

5.3 Preclinical Safety Data

No further significant information.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Acacia

Citric acid anhydrous

Orange juice flavour

Polysorbate 80

Propylene glycol

Alginate

Sucrose

6.2 Incompatibilities

None known.

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

Do not store above 30°C. .

6.5 Nature And Contents Of Container

Original packs containing 50 or 60 laminate sachets composed of paper, polyethylene and aluminium.

6.6 Special Precautions For Disposal And Other Handling

No special instructions.

7. Marketing Authorisation Holder

Bristol-Myers Squibb Holdings Limited

t/a Bristol-Myers Pharmaceuticals

Uxbridge Business Park

Sanderson Road

Uxbridge

Middlesex UB8 1DH

8. Marketing Authorisation Number(S)

PL 0125/5009R

9. Date Of First Authorisation/Renewal Of The Authorisation

22 January 1987/23 April 1997

10. Date Of Revision Of The Text

8^th September 2010

Friday, 4 May 2012

Idamycin

Generic Name: idarubicin (EYE da ROO bi sin)

Brand Names: Idamycin PFS

What is Idamycin (idarubicin)?

Idarubicin is a cancer (antineoplastic) medication. Idarubicin interferes with the growth of cancer cells and slows their growth and spread in the body.

Idarubicin is used to treat a type of blood cancer (acute myeloid leukemia -AML) in adults .

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

What is the most important information I should know about Idamycin (idarubicin)?

Idarubicin should only be administered under the supervision of a qualified healthcare provider experienced in the use of cancer chemotherapeutic agents.

Serious side effects have been reported with the use of idarubicin including: allergic reactions (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives); severe heart damage with prolonged use; decreased bone marrow function and blood problems (extreme fatigue; easy bruising or bleeding; black, bloody or tarry stools; fever or chills; or signs of infection); severe nausea, vomiting, diarrhea, and loss of appetite; and others.Talk to your doctor about the possible side effects from treatment with idarubicin.

What should I discuss with my healthcare provider before using Idamycin (idarubicin)?

Do not use idarubicin without first talking to your doctor if you have

kidney disease;

liver disease;

heart disease;

poor bone marrow function;

received radiation therapy that encompassed the heart; or

previously received treatment with doxorubicin (Adriamycin, Rubex), doxorubicin liposomal (Doxil), daunorubicin (Cerubidine), daunorubicin liposomal (Daunoxome), idarubicin (Idamycin), or mitoxantrone (Novantrone).

The use of idarubicin may be dangerous if you have any of the conditions listed above.

Idarubicin is in the FDA pregnancy category D. This means that idarubicin is known to be harmful to an unborn baby. Do not use idarubicin without first talking to your doctor if you are pregnant or could become pregnant during treatment. Discuss with your doctor the appropriate use of birth control during treatment with idarubicin if necessary. Because of the potential for serious side effects in a nursing infant, breast-feeding should be avoided during treatment with idarubicin. The safety and effectiveness of idarubicin in children has not been established.

How should I use Idamycin (idarubicin)?

Idarubicin should only be administered under the supervision of a qualified healthcare provider experienced in the use of cancer chemotherapeutic agents.

Your doctor will determine the correct amount and frequency of treatment with idarubicin depending upon the type of cancer being treated and other factors. Talk to your doctor if you have any questions or concerns regarding the treatment schedule.

Your doctor will probably want you to have regularly scheduled blood tests and other medical evaluations during treatment with idarubicin to monitor progress and side effects.

Skin accidentally exposed to idarubicin should be rinsed thoroughly with soap and warm water.

Your healthcare provider will store idarubicin as directed by the manufacturer. If you are storing idarubicin at home, follow the directions provided by your healthcare provider.

What happens if I miss a dose?

Contact your doctor if you miss a dose of idarubicin.

What happens if I overdose?

If for any reason an overdose of idarubicin is suspected, seek emergency medical attention or contact your healthcare provider immediately.

Symptoms of a idarubicin overdose tend to be similar to side effects caused by the medication, although often more severe.

What should I avoid while using Idamycin (idarubicin)?

Skin accidentally exposed to idarubicin should be rinsed thoroughly with soap and warm water.

Do not receive "live" vaccines during treatment with idarubicin. Administration of a live vaccine may be dangerous during treatment with idarubicin.

Idamycin (idarubicin) side effects

If you experience any of the following serious side effects from idarubicin, contact your doctor immediately:

an allergic reaction (including difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);

decreased bone marrow function and blood problems (extreme fatigue; easy bruising or bleeding; black, bloody or tarry stools; or fever, chills, or signs of infection);

congestive heart failure (difficulty breathing, fluid retention, chest pain);

irregular heartbeats;

tissue or vein reactions near the site of administration;

liver damage (abdominal pain, yellowing of the skin or eyes);

severe nausea, vomiting, diarrhea, and loss of appetite;

inflamation and sores inside the mouth, throat, or intestines;

fever, chills, or other signs of infection;

numbness, tingling, or difficult movement of a body part;

seizures; or

increased levels of uric acid in the body (joint pain and stiffness).

Other, less serious side effects may be more likely to occur. Continue taking idarubicin and talk to your doctor if you experience:

facial flushing during administration;

eye irritation or tearing;

darkening of the nail beds and skin folds;

temporary hair loss; or

red colored urine for 1 or 2 days following a dose.

Some breast cancer patients developed a second cancer (leukemia) after treatment with idarubicin. Idarubicin may cause premature menopause.

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 Idamycin (idarubicin)?

Do not use idarubicin without first talking to your doctor if you have had previous treatment with doxorubicin (Adriamycin, Rubex), doxorubicin liposomal (Doxil), daunorubicin (Cerubidine), daunorubicin liposomal (Daunoxome), idarubicin (Idamycin), or mitoxantrone (Novantrone). Because there is a maximum amount of these medications that should be administered to an individual, you may not be able to use idarubicin.

Before using idarubicin, tell your doctor if you are taking any of the following medicines.

paclitaxel (Taxol);

cimetidine (Tagamet, Tagamet HB, others);

progesterone (Prometrium);

verapamil (Calan, Calan SR, Covera-HS, Isoptin, Isoptin SR, Verelan, Verelan PM, others)

cyclosporine (Gengraf, Neoral, Sandimmune);

cyclophosphamide (Cytoxan, Cytoxan Lyophilized, Neosar);

phenobarbital;

phenytoin (Dilantin); or

streptozocin (Zanosar).

You may not be able to take idarubicin, or you may require a dosage adjustment or special monitoring during treatment if you are taking any of the medicines listed above.

Do not receive "live" vaccines during treatment with idarubicin. Administration of a live vaccine may be dangerous during treatment with idarubicin.

Drugs other than those listed here may also interact with idarubicin. Talk to your doctor and pharmacist before taking any other prescription or over-the-counter medicines, including vitamins, minerals, and herbal products, during treatment with idarubicin.

More Idamycin resources

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

Idamycin Prescribing Information (FDA)

Idamycin PFS Prescribing Information (FDA)

Idamycin PFS MedFacts Consumer Leaflet (Wolters Kluwer)

Idamycin PFS Monograph (AHFS DI)

Idamycin PFS Advanced Consumer (Micromedex) - Includes Dosage Information

Idarubicin Prescribing Information (FDA)

Idarubicin Professional Patient Advice (Wolters Kluwer)

Compare Idamycin with other medications

Leukemia
Leukocytoclastic Vasculitis
Solid Tumors

Where can I get more information?

Your pharmacist can provide more information about idarubicin.

See also: Idamycin side effects (in more detail)

Wednesday, 2 May 2012

Excedrin Tension Headache Express Gels

Generic Name: acetaminophen and caffeine (a SEET a MIN oh fen and KAF een)

Brand Names: Excedrin Quick Tab Peppermint, Excedrin Quick Tab Spearmint, Excedrin Tension Headache, Excedrin Tension Headache Caplet, Excedrin Tension Headache Express Gels, Excedrin Tension Headache Geltab, Valorin Extra

What is Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

Acetaminophen is a pain reliever and a fever reducer.

Caffeine is used in this product to increase the pain relieving effects of acetaminophen.

The combination of acetaminophen and caffeine is used to treat pain from conditions such as headache, muscle aches, menstrual cramps, arthritis, backache, toothaches, colds and fevers.

Acetaminophen and caffeine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen. Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen.

What should I discuss with my healthcare provider before taking Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

Do not take this medication if you are allergic to acetaminophen (Tylenol) or caffeine. Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have kidney or liver disease, or a history of alcoholism.

It is not known whether this medicine will harm an unborn baby. Do not take acetaminophen and caffeine without medical advice if you are pregnant. Acetaminophen and caffeine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

Use this medication exactly as directed on the label, or as prescribed by your doctor.

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death.

One acetaminophen and caffeine pill contains 500 mg of acetaminophen. Know the amount of acetaminophen in the specific product you are taking.

The orally disintegrating tablet (Excedrin QuickTabs) should be placed directly on the tongue. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing. Swallow several times as the tablet dissolves. If desired, you may drink liquid to help swallow the dissolved tablet.

Call your doctor if your symptoms do not improve, especially if you still have a fever after 3 days of using this medication, or pain after 10 days of use. Stop taking acetaminophen and caffeine and call your doctor at any time if your symptoms get worse.

Acetaminophen may cause false urine glucose test results. Talk to your doctor if you have diabetes and you notice changes in glucose test results while taking acetaminophen and caffeine.

Store at room temperature away from heat and moisture.

What happens if I miss a dose?

Since acetaminophen and caffeine is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, 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?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include loss of appetite, confusion, nausea, vomiting, diarrhea, sweating, fast or uneven heart rate, seizure (convulsions), pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

What should I avoid while taking Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen. Avoid coffee, tea, cola, energy drinks or other sources of caffeine while taking this medication. They can add to the side effects of the caffeine in the medication.

Excedrin Tension Headache Express Gels (acetaminophen and caffeine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using acetaminophen and caffeine and call your doctor at once if you have a serious side effect such as:

low fever with nausea, stomach pain, and loss of appetite;

dark urine, clay-colored stools; or

jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

sleep problems (insomnia); or

feeling nervous, irritable, or jittery.

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 Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

There may be other drugs that can interact with acetaminophen and caffeine. 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 Excedrin Tension Headache Express Gels resources

Excedrin Tension Headache Express Gels Side Effects (in more detail)
Excedrin Tension Headache Express Gels Use in Pregnancy & Breastfeeding
Excedrin Tension Headache Express Gels Drug Interactions
Excedrin Tension Headache Express Gels Support Group
2 Reviews for Excedrin Tension Headache Expresss - Add your own review/rating

Compare Excedrin Tension Headache Express Gels with other medications

Cold Symptoms
Headache
Osteoarthritis
Pain
Period Pain
Sinusitis

Where can I get more information?

Your pharmacist can provide more information about acetaminophen and caffeine.

See also: Excedrin Tension Headache Expresss side effects (in more detail)

Sunday, 29 April 2012

Phenobarbital

Class: Barbiturates
VA Class: CN301
CAS Number: 50-06-6
Brands: Luminal

Introduction

Barbiturate;^a ^b ^c ^d anxiolytic, sedative, hypnotic, and anticonvulsant.^a ^b ^f

Uses for Phenobarbital

Insomnia and Anxiety

Relief of anxiety, tension, and apprehension.^c ^d However, barbiturates used infrequently for routine sedation, since there are few clinical situations in which oral barbiturates provide a safety or efficacy advantage over nonbarbiturate sedatives/hypnotics.^f

Short-term treatment of insomnia.^c ^d However, generally not used orally as a hypnotic because several hours are required to achieve maximal effects^a and barbiturates have decreased effectiveness for sleep induction and maintenance after 2 weeks.^d

Drug Withdrawal

Withdrawal of barbiturate or nonbarbiturate hypnotics in patients who are physically dependent on these drugs.^a

Surgery

Preoperatively, to produce sedation and relieve anxiety.^a ^c

Seizure Disorders

Management of tonic-clonic seizures and partial seizures; used alone (particularly in infants and young children) or, more commonly, in combination with phenytoin or other anticonvulsants.^b

Prevention of febrile seizures in infants and young children.^b

Second-line agent in the termination of status epilepticus; may be useful to prevent seizure recurrence after seizures are initially terminated with other anticonvulsants (e.g., diazepam, phenytoin) or for termination of status epilepticus that does not respond to initial therapy with other anticonvulsants.^b ^c Usefulness of parenteral phenobarbital in terminating acute seizure episodes is limited by its slow onset of action.^a ^b ^d

Prophylactic management of epilepsy.^c ^d

Hyperbilirubinemia in Neonates

Prevention and treatment of hyperbilirubinemia in neonates†.^a

Cholestasis

Has been used to reduce bilirubin concentrations in patients with congenital nonhemolytic unconjugated hyperbilirubinemia† or chronic intrahepatic cholestasis†.^a

Has been used in the management of hyperlipemia associated with intrahepatic and extrahepatic cholestasis†.^a

Phenobarbital Dosage and Administration

General

Adjust dosage carefully and slowly according to individual requirements and response.^a ^b

Following chronic administration, withdraw phenobarbital slowly to avoid the possibility of precipitating withdrawal symptoms if the patient is physically dependent on the drug.^a ^d

To prevent rebound in rapid eye movement (REM) sleep, withdrawal of a single therapeutic dose over 5 or 6 days (e.g., reducing dosage from 3 to 2 doses daily for 1 week) has been recommended when barbiturates are discontinued following prolonged use.^a

Seizures

2–3 weeks of therapy may be required to achieve full anticonvulsant effects.^b

When transferring a patient to another anticonvulsant drug, reduce phenobarbital dosage gradually over 1 week while, at the same time, instituting therapy with a low dose of the replacement drug.^b

Withdraw phenobarbital or reduce dosage slowly to avoid precipitating seizures or status epilepticus.^b

Insomnia

Do not administer for periods >2 weeks.^a

Administration

Administer orally or by IM or slow IV injection.^a ^b ^c ^d Sub-Q injection not recommended.^a ^d

Oral Administration

Frequently administered in 2 or 3 divided doses;^a however, there is no advantage in dividing the daily dosage (because of the long half-life).^a ^b

IV Administration

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

Reserve IV administration for emergency treatment of acute seizure states; however, usefulness in these conditions is limited.^a ^b (See Seizure Disorders under Uses.)

Patient should be hospitalized and under close supervision.^a

To minimize the risk of irritation and thrombosis, do not use small veins (e.g., those on the dorsum of the hands or wrist).^d

Avoid intra-arterial injection.^b (See Intra-arterial Injection under Cautions.)

Rate of Administration

≤60 mg/minute.^a ^b ^d

IM Administration

Maximum volume of single injections is 5 mL; administer deeply into a large muscle to avoid tissue irritation.^d

Dosage

Available as phenobarbital sodium; dosage expressed in terms of the salt.^d

Pediatric Patients

Anxiety

Oral

6 mg/kg daily or 180 mg/m² daily, in 3 equally divided doses.^a ^c

Surgery

Oral

1–3 mg/kg preoperatively.^a ^d

IM

16–100 mg administered 60–90 minutes before surgery;^a alternatively, 1–3 mg/kg preoperatively.^a ^d

Drug Withdrawal

Oral

Infants: 3–10 mg/kg daily.^a After symptoms are relieved, decrease dosage gradually and withdraw drug completely over a 2-week period.^a

Seizure Disorders

Oral

15–50 mg 2 or 3 times daily.^c Alternatively, 3–5 mg/kg or 125 mg/m² daily.^b

IV or IM

4–6 mg/kg daily for 7–10 days to reach therapeutic blood concentrations; alternatively, 10–15 mg/kg daily.^d

Prevention of Febrile Seizures

Oral

3–4 mg/kg daily.^b

Status Epilepticus

IV or IM

15–20 mg/kg IV over 10–15 minutes.^d Alternatively 100–400 mg IM or IV; allow up to 30 minutes for maximum anticonvulsant effect before administering additional doses (to prevent overdosage).^b

Hyperbilirubinemia in Neonates†

Oral

7 mg/kg per day from the first to fifth day of life.^a

IM, then Oral

5 mg/kg IM on the first day of life, followed by 5 mg/kg orally on the second to seventh day.^a

Cholestasis†

Oral

Children <12 years of age: Dosages of 3–12 mg/kg daily in 2 or 3 divided doses have been used.^a

Adults

Insomnia and Anxiety

Anxiety

Oral

30–120 mg daily.^c

Insomnia

Oral

100–320 mg.^c

100–320 mg.^c ^d

Drug Withdrawal

Oral

30-mg dose for each 100- to 200-mg dose of the barbiturate or nonbarbiturate hypnotic that the patient has been taking daily, administered in 3 or 4 divided doses.^a If the patient shows signs of withdrawal on the first day, a loading dose of 100–200 mg of phenobarbital sodium may be administered IM in addition to the oral dose.^a

After stabilization on phenobarbital sodium, decrease the total daily dose of phenobarbital sodium by 30 mg per day.^a After withdrawal symptoms are relieved, gradually decrease dosage and withdraw completely over a 2-week period.^a

Surgery

IM

100–200 mg given 60–90 minutes before surgery.^a ^d

Seizure Disorders

Oral

100–300 mg daily,^b ^c usually at bedtime.^b

Status Epilepticus

IV or IM

20–320 mg; repeat in 6 hours, if necessary.^d Alternatively, 200–600 mg; allow up to 30 minutes for maximum anticonvulsant effect before administering additional doses (to prevent overdosage).^b

Some clinicians administer phenobarbital sodium IV until seizures stop or a total dose of 20 mg/kg has been given.^a ^b Discontinue IV injections as soon as the desired effect is obtained.^b

Cholestasis†

Oral

Dosages of 90–180 mg daily in 2 or 3 divided doses have been used.^a

Special Populations

Hepatic Impairment

Dosage reduction recommended in patients with hepatic impairment;^c ^d ^e avoid use in patients with marked hepatic impairment.^c ^d

Renal Impairment

Dosage reduction recommended.^d ^e

Geriatric Patients

Dosage reduction recommended.^d ^e ^f

Cautions for Phenobarbital

Contraindications

Known hypersensitivity to any barbiturates.^c ^d

Respiratory disease in which dyspnea or obstruction is evident.^c ^d

Marked impairment of hepatic function.^c ^d

History of manifest or latent porphyria^c ^d (due to potential for exacerbation of acute intermittent porphyria or porphyria variegata).^f

Previous addiction to sedative and/or hypnotic drugs.^c ^d

Warnings/Precautions

Warnings

Pain Reaction

Potential for paradoxical excitement and/or euphoria, restlessness, or delirium in patients with severe pain.^f Barbiturates could mask important symptoms in patients with acute or chronic pain.^d ^f Use with caution in such patients.^d ^f Should not be used to relieve pain or to produce sedation or sleep in the presence of uncontrolled pain.^c ^f

Abuse Potential

Possible tolerance, psychologic dependence, and physical dependence.^c ^d (See Contraindications under Cautions.)

WIthdrawal Effects

Abrupt cessation after prolonged use in dependent individuals may result in withdrawal symptoms (e.g., delirium, convulsions) and potentially be fatal.^c ^d Drug must be withdrawn gradually in patients receiving excessive dosages over extended periods of time.^d

CNS Depression

Performance of activities requiring mental alertness and physical coordination may be impaired.^c ^d

Concurrent use of other CNS depressants may potentiate CNS depression.^c ^d (See Specific Drugs under Interactions.)

Respiratory and Cardiovascular Effects

Possible respiratory depression, apnea, laryngospasm, hypertension, or vasodilation and hypotension, particularly if phenobarbital is administered IV too rapidly.^d ^f Administer slowly; personnel and equipment should be readily available for administration of artificial respiration.^d ^f

Sensitivity Reactions

Dermatologic Effects and Hypersensitivity Reactions

Exfolative dermatitis (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), sometimes fatal, reported rarely.^b ^c ^d Because skin eruptions can precede potentially fatal reactions, discontinue phenobarbital whenever dermatologic reactions occur.^d ^f

Hypersensitivity reactions (e.g., localized swelling, particularly of the eyelids, cheeks, or lips; erythematous dermatitis) may occur, particularly in patients with a history of asthma, urticaria, or angioedema.^c

General Precautions

Intra-arterial Injection

Inadvertent intra-arterial administration can cause spasm and severe pain along the affected artery, resulting in local reactions varying in severity from transient pain to gangrene.^d

Discontinue injection if the patient complains of pain or if signs of inadvertent intra-arterial injection (e.g., patches of discolored skin, a white hand with cyanosed skin, delayed onset of action) occur.^b ^d Appropriate therapy for such inadvertent injection has not been fully established; consult manufacturers’ labeling for current recommendations.^b ^d

Suicide

Use with caution, if at all, in depressed patients; potential for suicidal tendencies.^c ^d ^f Prescribe drug in the smallest feasible quantity.^c

Concomitant Diseases

Use parenterally with extreme caution in debilitated patients or patients with severe hepatic impairment, pulmonary or cardiac disease, status asthmaticus, uremia, or shock.^d ^f

Specific Populations

Pregnancy

Tablets: Category B.^c Injection: Category D.^d

Barbiturates have caused postpartum hemorrhage and hemorrhagic disease in neonates; readily reversible with vitamin K therapy.^f ⁱ

Possible withdrawal symptoms in neonates born to women who received barbiturates throughout the last trimester of pregnancy.^f Premature neonates are particularly susceptible to the depressant effects of barbiturates.^f

Lactation

Distributed into milk; use with caution.^c ^d

Pediatric Use

May produce paradoxical excitement and hyperactivity or exacerbate existing hyperactivity; if severe, substitute another barbiturate or therapeutic agent.^b

Possible behavioral (e.g., hyperactivity, fussiness, lethargy, disturbed sleep, irritability, disobedience, stubbornness, depressive symptoms) or cognitive effects (e.g., deficits on neuropsychiatric tests, impaired short-term memory and memory concentration tasks) associated with anticonvulsant use.^d ⁱ If such changes occur and alternative causes are not readily evident, consider the possibility that anticonvulsant therapy may be responsible and the need for dosage reduction or substitution of alternative anticonvulsant(s).ⁱ

Phenobarbital sodium injection contains benzyl alcohol.^d Manufacturer does not recommend use in neonates;^d AAP states that the presence of small amounts of this preservative in a commercially available injection should not proscribe its use when indicated in neonates.^h

Geriatric Use

Possible increased sensitivity to barbiturates.^d Geriatric patients may frequently react to barbiturates with excitement, confusion, or depression.^c ^f

Hepatic Impairment

Use with caution; should not be used in patients with marked hepatic impairment.^c ^d (See Contraindications under Cautions.)

Renal Impairment

Use with extreme caution in patients with nephritis.^b ^d Use parenterally with extreme caution in patients with uremia.^d ^f

Common Adverse Effects

Residual sedation, drowsiness, lethargy, vertigo, nausea, vomiting, headache.^c ^d ^f

Interactions for Phenobarbital

Metabolized by hepatic microsomal enzymes.^d Induces hepatic microsomal enzymes.^c ^d

Specific Drugs

Drug	Interaction	Comments
Anticoagulants, oral (e.g., warfarin)	Possible decreased plasma warfarin concentrations^c ^d	Monitor PT; adjust anticoagulant dosage as necessary, especially with initiation or discontinuance of phenobarbital^c ^f
Antidepressants, tricyclics	Antidepressant may precipitate seizures, resulting in decreased seizure controlⁱ Potentiation of respiratory depression following toxic doses of tricyclic antidepressantsⁱ	Monitor epileptic patients for decreased seizure control following initiation of antidepressant therapy; adjust phenobarbital dosage, if necessaryⁱ
CNS depressants (e.g., sedatives, hynotics, antihistamines, tranquilizers, alcohol)	Possible additive depressant effects^c ^d
Contraceptives, oral	Possible enhanced metabolism of estrogenic and progestinic components; potential for decreased oral contraceptive effectiveness and increased risk of pregnancy with phenobarbital pretreatment or concurrent therapy^d	Consider alternate methods of contraception^d
Corticosteroids	Possible increased corticosteroid metabolism^d	Dosage adjustment of corticosteriod may be required;^d closely monitor asthmatics receiving corticosteroids when phenobarbital is initiatedⁱ
Doxycycline	Possible decreased half-life of doxycycline; effect may persist up to 2 weeks after discontinuance of phenobarbital^d	If possible, avoid concomitant administration;^f if administered concomitantly, monitor clinical response to doxycycline^d
Griseofulvin	Possible decreased griseofulvin absorption, resulting in decreased blood concentrations^d	Avoid concomitant administration;^d if concomitant therapy is necessary, administration of griseofulvin in 3 divided daily doses may improve absorption.^f Monitor blood griseofulvin concentrations and increase dosage, if necessary^f
MAO inhibitors	Possible prolongation of phenobarbital effects^d	Dosage adjustment of phenobarbital may be required^f
Phenytoin	Increased, decreased, or no change in plasma phenytoin concentrations reported^d ⁱ	Monitor plasma concentrations of phentoin and phenobarbital; adjust dosages as necessary^d ⁱ
Valproic acid	Possible increased plasma phenobarbital concentrations^d	Monitor plasma phenobarbital concentrations and adjust dosage as needed^d

Phenobarbital Pharmacokinetics

Absorption

Bioavailability

Slowly absorbed from GI tract following oral administration,^b with peak plasma concentrations usually attained within 8–12 hours and peak brain concentrations in 10–15 hours.^b

Following IV administration, ≥15 minutes may be required to reach peak brain concentrations.^d

Onset

Following oral administration, onset occurs within 30 minutes.^c

Following IV administration, onset occurs within 5 minutes, with maximum CNS depression occurring ≥15 minutes after administration.^b ^d Onset is slower following IM administration.^b ^d

Duration

About 5–6 hours^c or 4–6 hours^d following oral or parenteral administration, respectively.

Plasma Concentrations

Plasma concentrations of 10–25 mcg/mL associated with anticonvulsant activity in most patients.^d Concentrations >50 mcg/mL may produce coma; concentrations >80 mcg/mL are potentially lethal.^b

Distribution

Extent

Rapidly distributed to all tissues and fluids, with high concentrations in the brain, liver, and kidneys.^d

Crosses the placenta and is distributed into milk.^d

Plasma Protein Binding

20–45%.^b

Elimination

Metabolism

Metabolized primarily by hepatic microsomal enzymes.^d

Elimination Route

Excreted prinicipally in urine (25–50% as unchanged drug).^d

Half-life

Adults: 53–118 hours.^d

Children and neonates: 60–180 hours.^d

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 15–30°C.^c Protect from moisture.^c

Elixir

Tight containers at 20–25°C.^e

Parenteral

Injection

15–30°C.^d

Compatibility

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

Parenteral

Solution Compatibility^HID

Compatible
Dextran 6% in dextrose 5%
Dextran 6% in sodium chloride 0.9%
Dextrose–Ringer’s injection combinations
Dextrose–Ringer’s injection, lactated, combinations
Dextrose–saline combinations
Dextrose 2.5, 5, or 10% in water
Fructose 10% in sodium chloride 0.9%
Fructose 10% in water
Invert sugar 5 and 10% in sodium chloride 0.9%
Invert sugar 5 and 10% in water
Ionosol products
Ringer’s injection
Ringer’s injection, lactated
Sodium chloride 0.45 or 0.9%
Sodium lactate (1/6) M
Incompatible
Alcohol 5%, dextrose 5%

Drug Compatibility

Admixture CompatibilityHID
Compatible
Amikacin sulfate
Aminophylline
Calcium chloride
Calcium gluconate
Colistimethate sodium
Dimenhydrinate
Meropenem
Polymyxin B sulfate
Thiopental sodium
Verapamil HCl
Incompatible
Chlorpromazine HCl
Ephedrine sulfate
Hydralazine HCl
Hydrocortisone sodium succinate
Hydroxyzine HCl
Meperidine HCl
Morphine sulfate
Norepinephrine bitartrate
Pentazocine lactate
Procaine HCl
Prochlorperazine mesylate
Promethazine HCl
Streptomycin sulfate
Vancomycin HCl

Y-site CompatibilityHID
Compatible
Doxapram HCl
Enalaprilat
Fentanyl citrate
Fosphenytoin sodium
Levofloxacin
Linezolid
Meropenem
Methadone HCl
Morphine sulfate
Propofol
Sufentanil citrate
Incompatible
Amphotericin B cholesteryl sulfate complex
Lansoprazole
Variable
Hydromorphone HCl

ActionsActions

CNS effects appear to be related, at least partially, to the drug’s ability to enhance activity of GABA, the principal inhibitory neurotransmitter in the CNS,¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ by altering inhibitory synaptic transmissions that are mediated by GABA_A receptors.¹⁰⁵ ¹⁰⁶ ¹⁰⁸

Capable of producing all levels of CNS depression—from mild sedation to hypnosis to deep coma to death.^c ^d

Anticonvulsant effects of barbiturates are multiple and rather nonselective.ⁱ Principal mechanism of action appears to be reduction of monosynaptic and polysynaptic transmission resulting in decreased excitability of the entire nerve cell; barbiturates also increase the threshold for electrical stimulation of the motor cortex.ⁱ

Barbiturates lower serum bilirubin concentrations in neonates and patients with congenital nonhemolytic unconjugated hyperbilirubinemia, presumably by induction of glucuronyl transferase, the enzyme that conjugates bilirubin.^f

Advice to Patients

Potential for phenobarbital to impair mental alertness or physical coordination; do not drive or operate machinery until effects on individual are known.^c ^d

Importance of taking exactly as prescribed; do not exceed the recommended dosage.^c ^d

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and alcohol consumption.^c ^d Importance of avoiding alcohol while taking the drug.^c ^d

Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^c ^d

Importance of advising patients of other important precautionary information.^c ^d (See Cautions.)

Preparations

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

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

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

Phenobarbital
Routes	Dosage Forms	Strengths
Oral	Elixir	20 mg/5 mL C-IV*
	Tablets	15 mg*
		16 mg C-IV*
		30 mg C-IV*
		32 mg C-IV*
		60 mg C-IV*
		65 mg C-IV*
		100 mg C-IV*

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

Phenobarbital Sodium
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection	30 mg/mL*	Phenobarbital Sodium Injection ( C-IV; with alcohol 10% and propylene glycol 75%)	Wyeth
		60 mg/mL*	Phenobarbital Sodium Injection ( C-IV; with alcohol 10% and propylene glycol 75%)	Wyeth
		65 mg/mL*	Phenobarbital Sodium Injection ( C-IV; with alcohol 10% benzyl alcohol 1.5% and propylene glycol 67.8%)	Baxter
		130 mg/mL*	Luminal Sodium ( C-IV; with alcohol 10% and propylene glycol 67.8%)	Sanofi-Aventis
			Phenobarbital Sodium Injection ( C-IV; with alcohol 10% and propylene glycol 75%)	Wyeth
			Phenobarbital Sodium Injection ( C-IV; with alcohol 10% benzyl alcohol 1.5% and propylene glycol 67.8%)	Baxter

Comparative Pricing

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

PHENobarbital 16.2MG Tablets (QUALITEST): 100/$12.99 or 300/$16.98

PHENobarbital 20MG/5ML Elixir (QUALITEST): 473/$26.96 or 1419/$79.29

PHENobarbital 32.4MG Tablets (QUALITEST): 100/$11.99 or 200/$14.98

PHENobarbital 64.8MG Tablets (QUALITEST): 100/$12.99 or 200/$15.98

PHENobarbital 97.2MG Tablets (QUALITEST): 100/$12.99 or 200/$19.96

Disclaimer

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

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

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

References

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

100. Jones-Pharma. Brevital sodium (methohexital sodium) for injection prescribing information (dated 2001 Mar 28). In: Physicians’ desk reference. 56th ed. Montvale, NJ: Medical Economics Company Inc; 2002:1815-17.

103. Abbott. Pentothal thiopental sodium for injection prescribing information. North Chicago, IL; 1993 Nov.

104. Carmichael FJ, Haas DA. General Anesthetics. In: Kalant H and Roschlau WHE, eds. Principles of Medical Pharmacology. 6th edition. New York: Oxford University Press; 1998:278-92.

105. Evers AS, Crowder CM. General Anesthetics. In: Hardman JG, Gilman AG, Limbird LE, eds Goodman and Gilman’s The pharmacological basis of therapeutics. 10th ed. McGraw-Hill; 2001: 337-44.

106. Donnelly AJ, Shafer AL. Perioperative care. In: Young LL, Koda-Kimble MA, eds. Applied Therapeutics: The clinical use of drugs. 6th ed. Vancouver WA: Applied Therapeutics, Inc.; 1995:8-1-8-24.

107. Tanelian DL, Kosek P, Mody I et al. The role of the GABA_A receptor/chloride channel complex in anesthesia. Anesthesiology. 1993; 78:757-76. [IDIS 316350] [PubMed 8385426]

108. Hales TG, Olsen RW. Basic pharmacology of intravenous induction agents. In: Bowdle TA, Horita A, Kharasch ED, eds. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone; 1994:295-306.

a. AHFS Drug Information 2004. McEvoy GK, ed. Phenobarbital . Bethesda, MD: American Society of Health-System Pharmacists; 2004:2370-1.

b. AHFS Drug Information 2004. McEvoy GK, ed. Phenobarbital. Bethesda, MD: American Society of Health-System Pharmacists; 2004:2108-9.

c. West-ward Pharmaceutical Corp. Phenobarbital tablets prescribing information. Eatontown, NJ; 2001 Jan.

d. Elkins-Sinn, Inc. Phenobarbital Sodium injection prescribing information. Cherry Hill, NJ; 2002 Apr.

e. Pharmaceutical Associates, Inc. Phenobarb elixir prescribing information. Greenville, NC; 2000 Apr.

f. AHFS Drug Information 2004. McEvoy GK, ed. Barbiturate general statement . Bethesda, MD: American Society of Health-System Pharmacists; 2004:2363-6.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1331-5.

h. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356 8.

i. AHFS Drug Information 2004. McEvoy GK, ed. Anticonvulsants general statement . Bethesda, MD: American Society of Health-System Pharmacists; 2004:2102-7.

More Phenobarbital resources

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Phenobarbital Prescribing Information (FDA)

phenobarbital Concise Consumer Information (Cerner Multum)

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Hyperbilirubinemia
Insomnia
Sedation
Seizures

Tuesday, 15 May 2012

Metoclopramide Hydrochloride

Introduction

Uses for Metoclopramide Hydrochloride

Diabetic Gastric Stasis

Postsurgical Gastric Stasis

Prevention of Postoperative Nausea and Vomiting

Prevention of Cancer Chemotherapy-induced Emesis

Intubation of the Small Intestine

Radiographic Examination of the Upper GI Tract

Gastroesophageal Reflux

Metoclopramide Hydrochloride Dosage and Administration

Administration

Oral Administration

IV Administration

Dilution

Rate of Administration

IM Administration

Dosage

Pediatric Patients

Intubation of the Small Intestine

IV

Adults

Diabetic Gastric Stasis

Oral

IV

IM

Prevention of Postoperative Nausea and Vomiting

IM

Prevention of Cancer Chemotherapy-induced Emesis

Oral†

IV

Intubation of the Small Intestine

IV

Radiographic Examination of the Upper GI Tract

IV

Gastroesophageal Reflux

Oral

Prescribing Limits

Adults

Gastroesophageal Reflux

Oral

Special Populations

Hepatic Impairment

Renal Impairment

Geriatric Patients

Cautions for Metoclopramide Hydrochloride

Contraindications

Warnings/Precautions

Warnings

Tardive Dyskinesia

Extrapyramidal Symptoms

Parkinsonian Symptoms

Neuroleptic Malignant Syndrome (NMS)

Depression

Sensitivity Reactions

Procainamide Cross-sensitivity

General Precautions

GI Anastomosis or Closure

Fluid and Electrolyte Effects

Hypertension

CNS Depression

Withdrawal Effects

Patients with Cytochrome-b5 Reductase Deficiency

Patients with Glucose-6-phosphate Dehydrogenase Deficiency

Specific Populations

Pregnancy

Lactation

Pediatric Use

Geriatric Use

Hepatic Impairment

Renal Impairment

Common Adverse Effects

Interactions for Metoclopramide Hydrochloride

Orally Administered Drugs

Specific Drugs

Metoclopramide Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Onset

Patients with Cytochrome-b₅ Reductase Deficiency