Dolasetron

Mechanism of effect

Dolasetron is a selective serotonin receptor (5-HT₃) antagonist which blocks serotonin both peripherally (primary site of action) and centrally at the chemoreceptor trigger zone

Pharmacokinetics

Absorption

Oral: Rapid and complete

Distribution

Hydrodolasetron: Children: 5.9 to 7.4 L/kg; Adults: 5.8 L/kg

Metabolism

Hepatic; rapid reduction by carbonyl reductase to hydrodolasetron (active metabolite); further metabolized by CYP2D6, CYP3A, and flavin monooxygenase

Excretion

Urine ~67% (dolasetron: <1% excreted unchanged in urine; hydrodolasetron: 53% to 61% of the total dose); Feces ~33%

Time to Peak

Hydrodolasetron: IV: 0.6 hours; Oral: ~1 hour

Half-Life Elimination

Dolasetron: IV: ≤10 minutes

Hydrodolasetron:

Oral: Children: 5.5 hours; Adolescents: 6.4 hours; Adults: 8.1 hours

IV: Children: 4.8 hours; Adults: 7.3 hours

Severe renal impairment: 11 hours

Severe hepatic impairment: 11 hours

Protein Binding

Hydrodolasetron: 69% to 77% (~50% bound to alpha₁-acid glycoprotein)

Drug indications

: Labeled Indications

Chemotherapy-associated nausea and vomiting (oral): Prevention of nausea and vomiting associated with initial and repeat course of moderately emetogenic cancer chemotherapy in adults and children ≥2 years

Postoperative nausea and vomiting (injection): Prevention and treatment of postoperative nausea and vomiting (PONV) in adults and children ≥2 years

Dosage

Usual Adult Dose for Nausea/Vomiting - Postoperative

Recommended dose: 12.5 mg IV approximately 15 minutes before the cessation of anesthesia or as soon as nausea and vomiting presents

Comments:
-The recommended dose should not be exceeded. If a prophylactic dose fails, avoid initiating another dose as rescue therapy.
-This drug should be given as a single dose, and may be given as an IV infusion over at least 30 seconds or diluted and infused over 15 minutes.

Uses:
-For the prevention of postoperative nausea and vomiting
-For the treatment of postoperative nausea and/or vomiting

Usual Pediatric Dose for Nausea/Vomiting - Postoperative

2 to 16 years:
-Recommended dose: 0.35 mg/kg IV approximately 15 minutes before the cessation of anesthesia or as soon as nausea and vomiting presents
-Maximum dose: 12.5 mg
-Alternative dose: 1.2 mg/kg (of the IV injection solution) given orally within 2 hours before surgery, up to a maximum dose of 100 mg

Comments:
-The injection solution may be mixed with apple or apple-grape juice and administered orally; the mixed product may be kept up to 2 hours at room temperature before use.
-This drug should be given as a single dose, and may be given as an IV infusion over at least 30 seconds or diluted and infused over 15 minutes.

Uses:
-For the prevention of postoperative nausea and vomiting
-For the treatment of postoperative nausea and/or vomiting

Usual Pediatric Dose for Nausea/Vomiting - Chemotherapy Induced

2 to 16 years:
-Recommended dose: 1.8 mg/kg orally within 1 hour before chemotherapy
-Maximum dose: 100 mg

Comment:
-The recommended dose should not be exceeded.

Use:
-For the prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy

Drug contraindications

Side effects

Side effects requiring immediate medical attention

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

Check with your doctor immediately if any of the following side effects occur while taking dolasetron:

More common

Chest pain or discomfort
lightheadedness, dizziness, or fainting
slow or irregular heartbeat
unusual tiredness or weakness

Less common

Chills
decrease in the amount of urine
fast, pounding, or irregular heartbeat or pulse
fever

Rare

Agitation
black, tarry stools
bleeding gums
bloating or swelling of the face, arms, hands, lower legs, or feet
blood in the urine or stools
blurred vision
burning while urinating
changes in skin color
confusion
cough
delirium
depression
diarrhea
difficult or labored breathing
difficult or painful urination
difficulty with swallowing
dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
feeling of warmth
feeling uncoordinated
frequent urination
hallucinations
headache
hives or welts, itching, or skin rash
increased volume of pale, dilute urine
irritability
lethargy
muscle twitching
nausea
noisy breathing
numbness and tingling of the face, fingers, or toes
pain in the arms, legs, or lower back, especially pain in the calves or heels upon exertion
pain, tenderness, or swelling of the foot or leg
pale skin
pale, bluish-colored, or cold hands or feet
pinpoint red or purple spots on the skin
puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
rapid weight gain
red skin
rigid muscles
seizures
sweating
swelling of the face, ankles, or hands
tightness in the chest
tingling of the hands or feet
tremor
troubled breathing with exertion
unusual bleeding or bruising
unusual weight gain or loss
vomiting
weak or absent pulses in the legs

Side effects not requiring immediate medical attention

Some side effects of dolasetron may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

Belching
heartburn
indigestion
pain
stomach discomfort, upset, or pain

Rare

Abnormal dreams
bad, unusual, or unpleasant (after) taste
bloating
bloody nose
change in taste
changes in vision
continuing ringing or buzzing or other unexplained noise in the ears
darkened urine
difficulty having a bowel movement (stool)
difficulty seeing at night
difficulty with moving
feeling of constant movement of self or surroundings
feeling of unreality
hearing loss
increased sensitivity of the eyes to sunlight
increased sweating
joint pain
loss of appetite
muscle aching or cramping
muscle pain or stiffness
pain or burning sensation at the injection site
pains in the stomach, side, or abdomen, possibly radiating to the back
redness of the face, neck, arms, and occasionally, upper chest
sensation of spinning
sense of detachment from self or body
shakiness and unsteady walk
shakiness in the legs, arms, hands, or feet
swollen joints
unsteadiness, trembling, or other problems with muscle control or coordination
weight loss
yellow eyes or skin

Interactions

Amlodipine/Atorvastatine , Busulfan , Sibutramine , Tapentadol , Almotriptan , Apomorphine , Atenolol , Atomoxetine , Amlodipine , Amitriptyline , Amiodarone , Epirubicin , lacosamide , Benzthiazide , hydroflumethiazide , levamlodipine , osilodrostat , selpercatinib , ozogamicin , st. john's wort , vortioxetine , digitoxin , levomethadyl acetate , ozanimod , lefamulin , lofexidine , macimorelin , methotrimeprazine , 5-hydroxytryptophan , rilpivirine , Romidepsin , bosutinib , Methyclothiazide , Pasireotide , Siponimod , Rucaparib , Lomefloxacin , Ceritinib , Nilutamide , norfloxacin , Crizotinib , Telavancin , Deutetrabenazine , Entrectinib , Cabozantinib , Levomilnacipran , Foscarnet , lenvatinib , encorafenib , midostaurin , Triclabendazole , ivosidenib , ezogabine , Nadolol , Isradipine , Iloperidone , Pimavanserin , Degarelix , Trimeprazine , Triflupromazine , Amisulpride , Paliperidone , Pazopanib , Bendroflumethiazide , Esmolol , Gatifloxacin , Carteolol , Nebivolol , Nicardipine , Nisoldipine , Torsemide , probucol , Abiraterone , Felodipine , Penbutolol , Efavirenz , Eribulin , Inotuzumab‎ , Idarubicin , Goserelin , Anagrelide , Bumetanide , Procainamide , Polyethylene glycol , Mefloquine , Panobinostat , Ribociclib , Ibutilide , Halothane , vemurafenib , Osimertinib , Quinine , Chloroquine , Mesoridazine , Mifepristone , Pindolol , Telithromycin , Sufentanil , Alfentanil , Droperidol , primaquine , valbenazine , Arsenic , Tryptophan , Vilazodone , Ivabradine , Frovatriptan , Fenfluramine , dronedarone , saquinavir , eletriptan , Mirtazapine , protriptyline , meperidine , Nefazodone , ISOPROTERENOL , Pentazocine , Naratriptan , isocarboxazid , Remifentanil , methylene blue , Ziprasidone , Histrelin , propoxyphene , Tamoxifen , Metaproterenol , Prochlorperazine , Quinidine , Acebutolol , Amoxapine , Quetiapine , lithium , Buprenorphine , Chlorothiazide , Phenelzine , Toremifene , Atazanavir , Ranolazine , Linezolid , astemizole , ethacrynic acid , Pentamidine , Zolmitriptan , ritodrine , Leuprolide acetate , escitalopram , Clofazimine , fentanyl , Clomipramine , Solifenacin , Enzalutamide , Flecainide , Bicalutamide , Bisoprolol , Voriconazole , Carvedilol , Ketoconazole , Clarithromycin , Chlorpromazine , Clozapine , Haloperidol , Hydroxychloroquine , Hydrochlorothiazide , Vardenafil , Verapamil , Venlafaxine , Moxifloxacin , Mitoxantrone , Nortriptyline , Nifedipine , Nilotinib , Nimodipine , Lapatinib , Levofloxacin , Maprotiline , Methadone , Metoprolol , Metolazone , Fluconazole , Furazolidone , Furosemide , Fingolimod , Granisetron , Labetalol , Citalopram , Cisapride , Flutamide , Fluphenazine , Fluvoxamine , Fluoxetine , Sunitinib , Sertraline , Sotalol , Sorafenib , Sevoflurane , Ciprofloxacin , Doxorubicin , Disopyramide , Digoxin , Diltiazem , Rizatriptan , Risperidone , Thioridazine , Gemifloxacin , Daunorubicin , Desipramine , Duloxetine , Doxepin , Terbutaline , Trifluoperazine , Triptorelin , Trimipramine , Tizanidine , Timolol , Pimozide , Tacrolimus , Tetrabenazine , Trazodone , Tramadol , Tranylcypromine , perphenazine , Propafenone , Propranolol , Promethazine , Procarbazine , Posaconazole , Imipramine , Betaxolol , Bupropion , Buspirone , Papaverine , Paroxetine , Adenosine , Erythromycin , Ofloxacin , Oxaliplatin , Ondansetron , Oxytocin , Palonosetron , vandetanib , sparfloxacin , Indapamide , Dofetilide , Promazine , Vasopressin , Chlorthalidone , Arsenic trioxide , Desvenlafaxine , Milnacipran , Halofantrine , Grepafloxacin , Mibefradil , Dexfenfluramine , Terfenadine , Abarelix , Asenapine , Alfuzosin , Perflutren , Apalutamide , Pitolisant , Clevidipine , gilteritinib , glasdegib , Bepridil , bedaquiline , Dasatinib , Gemtuzumab , lasmiditan , vemurafenib , Halaven

fostemsavir , polyethylene glycol 3350 with electrolytes ,trichlormethiazide

Alerts

You should not take dolasetron if you are allergic to it.

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

kidney disease;
a serious heart condition such as "sick sinus syndrome";
a heart rhythm disorder such as slow heartbeats, or atrial fibrillation (fast, irregular heart rhythm);
personal or family history of long QT syndrome;
congestive heart failure; or
an electrolyte imbalance (such as low levels of potassium or magnesium in your blood).

Points of recommendation

It is not known whether dolasetron will harm an unborn baby. Tell your doctor if you are pregnant.

It is not known whether dolasetron passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Dolasetron should not be given to a child younger than 2 years old.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Dolasetron is usually taken 1 hour before chemotherapy. Follow your doctor's instructions.

Store at room temperature away from moisture, heat, and light.

Tell your doctor if you forget to take your dose within 1 hour before chemotherapy. Do not take extra medicine to make up the missed dose.

Pregnancy level

B

Animal studies have failed to reveal evidence of teratogenicity or impaired fertility. There are no controlled data in human pregnancy.

Use is recommended only if clearly needed and the benefit outweighs the risk.

AU TGA pregnancy category: B1
US FDA pregnancy category: B

Breast feeding warning

AU: Use is not recommended.
US: Caution is recommended.

Excreted into human milk: Unknown
Excreted into animal milk: Unknown

Comments: The effects in the nursing infant are unknown.

When animal models were given the oral formulation of this drug, survival, growth, and development of pups were not affected.

Drug information of Dolasetron