Medication Guide App

Racemethionine (Systemic)



INN:

Methionine {02}


JAN:

DL-Methionine {02}

VA CLASSIFICATION
Primary: GU900
Secondary: AD900

Commonly used brand name(s): M-Caps; Pedameth; Uracid.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Acidifier (urinary)—

antidote (to acetaminophen overdose)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Dermatitis, contact (treatment) and
Urine odor—Racemethionine is indicated for the treatment of dermatitis and ulcerations, and for the control of urine odor, caused by ammoniacal urine in incontinent adults. Racemethionine is also indicated in infants for the treatment of diaper rash. {02} {03} {04} {13} {14}

[Toxicity, acetaminophen (treatment)]—Racemethionine may be used in the treatment of acetaminophen overdose {06} {09} {10} to protect against hepatotoxicity. {03} {08} {15} {18} {19} {21} {22} However, oral N-acetylcysteine is considered the treatment of choice for acetaminophe overdose. {16} {21} {23} {24} (See Acetylcysteine [Systemic] monograph.) Use of racemethionine should be limited to emergency situations in which N-acetylcysteine is not available. {25}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    149.21 {02} {03}

Mechanism of action/Effect:

Acidifier, urinary—Racemethionine produces ammonia-free urine by lowering the urinary pH. {04} {13} {14}

Antidote, to acetaminophen overdose—Racemethionine may protect against acetaminophen overdose–induced hepatotoxicity by maintaining or restoring hepatic concentrations of glutathione. {05} {06} {08} {09} {10} {15} {18} {20} {21} Glutathione is required to inactivate an intermediate metabolite of acetaminophen, which is hepatotoxic. {08} {18} {21} In acetaminophen overdose, excessive quantities of this metabolite are formed because the primary metabolic pathways (glucuronide and sulfate conjugation) {09} {16} become saturated. The excess metabolite binds irreversibly to essential hepatic proteins and enzymes, causing cell damage and death. {08} {15} {16} {21} Racemethionine serves as a precursor for the synthesis of glutathione and sulfate. {20}


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Problems in humans have not been documented.

Breast-feeding

It is not known whether racemethionine is distributed into breast milk.

Pediatrics

Appropriate studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of racemethionine in children.


Geriatrics


Appropriate studies on the relationship of age to the effects of racemethionine have not been performed in the geriatric population. However, geriatrics-specific problems that would limit the usefulness of this medication in the elderly are not expected.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Levodopa{05}{11}    (concurrent use with racemethionine may decrease the therapeutic effects of levodopa)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Acetone, urine{12}    (test may show false positive results)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Acidosis, metabolic{03}{28}    (may be exacerbated)


Hepatic function impairment, history of{04}{13}{14}{18} or
Hepatic function impairment, severe{03}    (use of racemethionine for other than emergency uses may worsen hepatic toxemia)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):


For treatment of acetaminophen toxicity
» Acetaminophen concentration, plasma{05}{09}{10}{21}    (should be determined not less than 4 hours following ingestion of acetaminophen overdose to determine the need for antidotal therapy)


Alanine aminotransferase (ALT [SGPT]) and
Aspartate aminotransferase (AST [SGOT]) and
Bilirubin and
Prothrombin time    (serum determinations should be assessed daily for 3 or 4 consecutive days if plasma acetaminophen concentrations indicate potential hepatotoxicity {05} {16} {21} {26})


Blood urea nitrogen (BUN){15} and
Creatinine, serum{15}    (recommended because of the potential for development of renal failure; however, BUN may not be elevated if the liver is unable to produce urea by-products {21})


Complete blood counts    (recommended daily for 3 or 4 days to detect thrombocytopenia {05} {26})


Glucose, blood    (recommended daily for 3 or 4 days to detect hypoglycemia {05} {26})


Toxicology screen, urine{16}    (acetaminophen is commercially available in combination with other drugs; therefore, ingestion of other potentially toxic medications should be ruled out in overdose situations)




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Drowsiness {03}
    
nausea and vomiting {03}{05}{07}{08}{19}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Racemethionine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Other medical problems, especially history of, or severe hepatic function impairment, or metabolic acidosis

Proper use of this medication

For treatment of contact dermatitis
» Importance of not taking more medication than the amount prescribed, and getting enough protein in the diet in order to avoid abnormally low weight gain in infants

Taking medicine with, or just after meals

Adding contents of capsule to juice, water, or warm milk or infant formula, if necessary

Proper administration technique for oral solution

For all uses

» Proper dosing

» Proper storage

Precautions while using this medication
Checking with physician if no improvement after 10 days


General Dosing Information

For treatment of contact dermatitis
If there is no improvement after 10 days of therapy, it is recommended that racemethionine be discontinued because the probable cause of the rash is something other than ammoniacal urine. {04}

For treatment of acetaminophen toxicity
Oral N-acetylcysteine is considered the treatment of choice for acetaminophen overdose. {16} {21} {23} {24} (See Acetylcysteine [Systemic] monograph). Use of racemethionine should be limited to emergency situations in which N-acetylcysteine is not available. {25}

Patients with suspected acetaminophen overdose should receive supportive therapy. This may include establishing and maintaining adequate airway, respiratory, and circulatory function; {16} maintaining fluid and electrolyte balance; {21} correcting hypoglycemia; and administering vitamin K 1 (if prothrombin time ratio exceeds 1.5) and fresh frozen plasma {05} or prothrombin complex concentrate (if prothrombin time ratio exceeds 3). {21}

Gastric decontamination, by means of lavage or ipecac-induced emesis may be beneficial if carried out within 4 hours after ingestion of potentially toxic doses of acetaminophen. {16}

Administration of activated charcoal following acetaminophen overdose is controversial. {16} Activated charcoal effectively adsorbs acetaminophen, {16} {22} but also adsorbs racemethionine, thereby diminishing the antidotal effectiveness of both agents. {22} {24}

Additional therapy to treat mixed overdose with other agents (i.e., naloxone for an opioid analgesic) may be needed, {16} especially if symptoms of central nervous system (CNS) depression occur within a few hours after ingestion of potentially toxic doses of acetaminophen.

Racemethionine therapy must be instituted within 8 to 12 hours after acetaminophen ingestion. {03} {05} {06} {07} {09} {15} {21} {22} If given more than 15 hours postingestion, racemethionine may precipitate hepatic encephalopathy. {05} {06} {07} {09} {15} {18} {21} It is recommended that racemethionine be administered as soon as possible after ingestion of an overdose is suspected, without waiting for the results of plasma acetaminophen concentrations or other laboratory tests. {09} {21}

Plasma acetaminophen concentration should be determined not less than 4 hours following ingestion of the overdose. Concentrations determined prior to this time are not reliable for assessing potential hepatotoxicity. {05} {09} {21} The following chart, derived from the Rumack-Matthew nomogram, {05} {09} {10} {21} may be used to predict which patients may develop hepatotoxicity when the time of ingestion is known:

Acetaminophen plasma
concentration
(mcg/mL)
Time after
ingestion
(hours)
> 150
4
> 100
6
> 70
8
> 50
10
> 20
16
> 8
20
> 4
24


If the initial determination indicates a plasma concentration below those listed at the times indicated, cessation of antidotal therapy can be considered. {09}

Diet/Nutrition


For treatment of contact dermatitis:
It is essential that adequate protein intake be maintained during therapy with racemethionine and that the recommended dosage of medication not be exceeded. Excessive dosages of racemethionine added alone to the diet over an extended period of time may result in lower than normal weight gain in infants, whe protein intake is insufficient. {04} {13} {14}



Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

RACEMETHIONINE CAPSULES USP

Usual adult and adolescent dose
Acidifier, urinary
Oral, 200 mg three or four times a day. {04} {13} {14} {17} Each dose should be taken with a meal. {04} {13} {14}

[Antidote, to acetaminophen overdose]
Oral, 2.5 grams every four hours, up to a total dose of 10 grams. {03} {05} {09} {18} {19} {21} The first dose must be given within eight to twelve hours after the toxic ingestion. {03} {05} {06} {07} {09} {15} {18} {21}


Usual pediatric dose
Acidifier, urinary
Oral, contents of 1 capsule (200 mg) added to the evening bottle, preferably while it is still warm, or added to a glass of juice or water. {04} {13} {14}

[Antidote, to acetaminophen overdose]
Children 12 years of age or older: See Usual adult and adolescent dose.

Children 3 to 11 years of age: Oral, 1 gram every four hours, up to a total dose of 4 grams. {26} {27} The first dose must be given within eight to twelve hours after the toxic ingestion. {03} {05} {06} {07} {09} {15} {18} {21}

Children up to 3 years of age: Dosage has not been established.


Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


200 mg (Rx) [M-Caps] [Pedameth] [Uracid]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), {04} unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container. {01} {04} {13}

Preparation of dosage form:
For patients who cannot take oral solids—Contents of capsules may be added to juice, water, or warm milk or infant formula.


RACEMETHIONINE ORAL SOLUTION

Usual adult and adolescent dose
See Racemethionine Capsules USP.

Usual pediatric dose
Acidifier, urinary
Children over 14 months of age: See Usual adult and adolescent dose.

Children 6 to 14 months of age: Oral, 75 mg four times a day for three to five days. {04}

Children 2 to 6 months of age: Oral, 75 mg three times a day for three to five days. {04}

Children up to 2 months of age—Dosage has not been established.

Note: In severe cases, or when the infant is older than 1 year of age, the dosage may be doubled for the first two days of treatment. {04}


[Antidote, to acetaminophen overdose]
See Racemethionine Capsules USP.


Usual geriatric dose
See Racemethionine Capsules USP.

Strength(s) usually available
U.S.—


75 mg per 5 mL (Rx) [Pedameth]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container. {04}


RACEMETHIONINE TABLETS USP

Usual adult and adolescent dose
Acidifier, urinary
Oral, 500 mg three or four times a day. {17} Each dose should be taken with a meal. {04} {13} {14}

[Antidote, to acetaminophen overdose]
See Racemethionine Capsules USP.


Usual pediatric dose
The capsule or oral solution dosage form is recommended in pediatric patients.

Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


500 mg (Rx)[Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container. {01}



Developed: 12/05/1994



References
  1. The United States pharmacopeia. The national formulary. USP 21st revision (January 1, 1985). NF 16th ed (January 1, 1985). Rockville, MD: The United States Pharmacopeial Convention, Inc., 1985: 932.
  1. Fleeger CA, editor. USAN 1994. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1993: 568.
  1. Reynolds JEF, editor. Martindale, the extra pharmacopoeia. 30th ed. London: The Pharmaceutical Press, 1993: 683-4.
  1. Pedameth package insert (Forest—US), Rev 10/89, Rec 3/8/94.
  1. Ellenhorn MJ, Barceloux DG. Medical toxicology. Diagnosis and treatment of human poisoning. New York: Elsevier, 1988: 80, 124, 160-4.
  1. Prescott LF. New approaches in managing drug overdosage and poisoning. Br Med J 1983; 287: 274-6.
  1. Monteagudo FSE, Straughan JL, van der Merwe LP. The choice between intravenous N-acetylcysteine and oral methionine in paracetamol poisoning. S Afr J Med 1986; 69: 279.
  1. Vale JA, Meredith TJ, Goulding R. Treatment of acetaminophen poisoning. The use of oral methionine. Arch Intern Med 1981; 141: 394-6.
  1. Davis M. Protective agents for acetaminophen overdose. Semin Liver Dis 1986; 6: 138-47.
  1. Meredith TJ, Prescott LF, Vale JA. Why do patients still die from paracetamol poisoning? Br Med J 1986; 293: 345-6.
  1. Hansten PD, Horn JR. Drug interactions. 6th ed. Philadelphia: Lea & Febiger, 1989: 405-6.
  1. Wallach J. Interpretation of diagnostic tests. A synopsis of laboratory medicine. 4th ed. Boston: Little, Brown and Company, 1986: 662.
  1. M-Caps package insert (Pal-Pak—US), Rec 5/23/94.
  1. Uracid package insert (Wesley—US), Rec 5/24/94.
  1. Prescott LF, Critchley JAJH. The treatment of acetaminophen poisoning. Ann Rev Pharmacol Toxicol 1983; 23: 87-101.
  1. Lewis RK, Paloucek FP. Assessment and treatment of acetaminophen overdose. Clin Pharm 1991; 10: 765-74.
  1. Olin BR, editor. Drug facts and comparisons. St. Louis: Facts and Comparisons Inc, 1992: 563.
  1. Crome P, Vale JA, Volans GN, et al. Oral methionine in the treatment of severe paracetamol (acetaminophen) overdose. Lancet 1976; 2: 829-30.
  1. Hamlyn AN, Lesna M, Record CO, et al. Methionine and cysteamine in paracetamol (acetaminophen) overdose, prospective controlled trial of early therapy. J Int Med Res 1981; 9: 226-31.
  1. Buckpitt AR, Rollins DE, Mitchell JR. Varying effects of sulfhydryl nucleophiles on acetaminophen oxidation and sulfhydryl adduct formation. Biochem Pharmacol 1979; 28: 2941-6.
  1. Prescott LF. Paracetamol overdosage. Pharmacological considerations and clinical management. Drugs 1983; 25: 290-314.
  1. Klein-Schwartz W, Oderda GM. Adsorption of oral antidotes for acetaminophen poisoning (methionine and N-acetylcysteine) by activated charcoal. Clin Toxicol 1981; 18: 283-90.
  1. Panel comment, 8/94.
  1. Panel comment, 8/94.
  1. Panel comment, 8/94.
  1. Panel comment, 8/94.
  1. Meredith TJ, Newman B, Goulding R. Paracetamol poisoning in children. Br Med J 1978; 12: 478-9.
  1. Panel comment, 8/94.
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