Dehydroemetine

Paul G. Auwaerter, M.D., Janessa Smith, Pharm.D., BCPS
Pediatric Dosing Author: Alice Jenh Hsu, PharmD, BCPS, AQ-ID

INDICATIONS

FDA

Amoebic dysentery as an alternative to metronidazole IV in patients unable to take oral agents or unresponsive to metronidazole
Amoebic liver abscess unresponsive to metronidazole [no longer available from the CDC]

FORMS

brand name	preparation	manufacturer	route	form	dosage^	cost*
Dehydroemetine	Dehydroemetine	(not available from CDC^#)	IV	ampule	65/ml (1ml)	N/C

*Prices represent the specified cost per unit and the "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

^#Nicholas Piramal India LTD lists injection and tablet forms (2023).

USUAL ADULT DOSING

1 mg/kg/day (up to 60mg/day) IM injection for 4-6 days. Reduce the dose by 50% in elderly and severely ill patients. All patients should also receive diloxanide PO to eliminate surviving organisms in the colon.

Amoebic dysentery: supplementary treatment with tetracycline reduces the risk of bacterial superinfection
Hepatic abscess:
- Supplementary treatment with chloroquine may be given concurrently or immediately afterward.
- A repeat dose may be given 6 weeks later in patients with extensive hepatic abscesses.
Should only be administered in a hospital setting with telemetry monitoring

ADULT RENAL DOSING

DOSING IN HEMODIALYSIS

No data.

DOSING IN PERITONEAL DIALYSIS

No data.

DOSING IN RENAL REPLACEMENT THERAPY

No data.

PEDIATRIC DOSING

USUAL PEDIATRIC DOSING

Children: 1 mg/kg/day IM for no more than 5 days

ADVERSE DRUG REACTIONS

GENERAL

Note: should only be used as a last resort in patients with neuromuscular, renal or cardiac impairments given significant toxicity
Telemetry/ECG cardiac monitoring is recommended with administration; treatment should be stopped immediately if tachycardia, severe hypotension or ECG changes occur.
Weakness and muscular pain often precede more serious toxic effects and should serve as a warning to reduce the dose by 50%.

COMMON

Arrhythmia
Precordial pain
Pain at the injection site
Muscle weakness

OCCASIONAL

GI: diarrhea; vomiting
Neuropathy
Heart failure
Headache
Dyspnea

DRUG INTERACTIONS

Cardiotoxic drugs may potentiate cardiotoxicity, leading to dysrhythmias.

Warfarin, phenytoin, and some antiretrovirals may need dose adjustments.

SPECTRUM

Entamoeba histolytica

PHARMACOLOGY

MECHANISM

The drug is a member of the isoquinolines, similar to emetine, but with fewer side effects. It inhibits polypeptide chain elongation and mammalian cell growth.

PHARMACOKINETIC PARAMETERS

Absorption

Rapid absorption after intramuscular administration.

Metabolism and Excretion

Slow renal excretion.

Protein Binding

No data.

Cmax, Cmin, and AUC

No data.

T1/2

Unchanged emetine may be excreted in the urine for 40-60 days after administration.

Distribution

Well distributed into the liver. Also distributed into the spleen, lungs and kidney.

DOSING FOR DECREASED HEPATIC FUNCTION

No data.

PREGNANCY RISK

X-Contraindicated, animal and human studies show the potential of teratogenicity.

BREASTFEEDING COMPATIBILITY

Contraindicated in breastfeeding.

COMMENTS

Dehydroemetine (a synthetic derivative of emetine) 65mg/ml IV (no longer available from CDC). Emetine was initially derived from the ipecac root.
The drug may still be manufactured ex-US (Nicholas Piramal India LTD lists injection and tablet forms (2023).
- Now rarely used for invasive amebiasis due to severe local and systemic side effects, most famously heart failure and arrhythmia (close ECG monitoring recommended) and availability of less toxic agents (e.g., metronidazole).
It may be an option in treating amebic dysentery and/or extraintestinal amebiasis that fails to respond to metronidazole.
Dehydroemetine is toxic to the fetus and is generally considered contraindicated during pregnancy. However, in cases of fulminant amoebic dysentery in late pregnancy, treatment with dehydroemetine may be life-saving to the mother.
The drug has been used in the past as an antimalarial and antileishmanial agent.

References

Porras-Ramírez G, Hernández-Herrera MH, Porras-Hernández JD. Amebic hepatic abscess in children. J Pediatr Surg. 1995;30(5):662-4. [PMID:7623222]
Comment: The most recent English language report of using the drug in amebic abscess. Patients received dehydroemetine plus metronidazole.
Jain NK, Madan A, Sharma TN, et al. Hepatopulmonary amoebiasis. Efficacy of various treatment regimens containing dehydroemetine and/or metronidazole. J Assoc Physicians India. 1990;38(4):269-71. [PMID:2202709]
Comment: The best therapeutic results were obtained with a combination of dehydroemetine and metronidazole. However, metronidazole was found to be comparable to dehydroemetine.
Yang WC, Dubick M. Mechanism of emetine cardiotoxicity. Pharmacol Ther. 1980;10(1):15-26. [PMID:6996003]
Comment: Addresses major toxicity with this drug.
Scragg JN, Powell SJ. Emetine hydrochloride and dehydroemetine combined with chloroquine in the treatment of children with amoebic liver abscess. Arch Dis Child. 1968;43(227):121-3. [PMID:5642979]
Comment: Dehydroemetine doses as high as 2 mg/kg/day for 10 days have been given in combination with PO chloroquine for the treatment of amoebic liver abscesses in children; however, the WHO recommends a maximum dose of 1 mg/kg/day for a maximum of 5 days in children.
WHO International Pharmacopoeia, Sixth Edition, 2016. https://cdn.who.int/media/docs/default-source/medicines/pharmacopoeia/omitted-monographs/dehydroemetine_dihydrochloride.pdf...(accessed 11/19/2024)
Comment: Chemical composition, manufacturing, storage characteristics.