Dopamine

C01C - Cardiac stimulants excl. cardiac glycosides ATC C01CA04 Small molecule approved 1974 Parenteral Natural product Black-box warning

JFDA label: Dopamine HCL

⚠ Black-Box Warning

Antidote for peripheral ischemia:

Mechanism of Action

Stimulates both adrenergic and dopaminergic receptors, lower doses are mainly dopaminergic stimulating and produce renal and mesenteric vasodilation, higher doses also are both dopaminergic and beta1-adrenergic stimulating and produce cardiac stimulation and renal vasodilation; large doses stimulate alpha-adrenergic receptors

Indications

Approved

Cardiogenic shock
Hemodynamic support
Inotropic support in advanced heart failure
Sepsis and septic shock

Off-label

Heart block unresponsive to atropine or pacing
Symptomatic bradycardia

Contraindications

Source: Lexicomp

Hypersensitivity to sulfites (commercial preparation contains sodium bisulfite) Absolute
pheochromocytoma Absolute
uncorrected tachyarrhythmias Absolute
ventricular fibrillation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (12)

Not Known Angina pectoris · atrial fibrillation · bradycardia · ectopic beats · hypertension · hypotension · palpitations · tachycardia · vasoconstriction · ventricular arrhythmia · ventricular conduction · widened QRS complex on ECG

Nervous system disorders (2)

Not Known Anxiety · headache

Renal and urinary disorders (2)

Not Known Azotemia · Polyuria

Metabolism and nutrition disorders (1)

Not Known Increased serum glucose (usually not above normal limits)

Gastrointestinal disorders (2)

Not Known Nausea · vomiting

Skin and subcutaneous tissue disorders (2)

Not Known Gangrene (high dose) · piloerection

Eye disorders (2)

Not Known Increased intraocular pressure · mydriasis

General disorders and administration site conditions (1)

Not Known Tissue necrosis

Respiratory, thoracic and mediastinal disorders (1)

Not Known Dyspnea

Dosing

Source: Lexicomp

Hemodynamic support: IV infusion: Manufacturer's labeling: Dosage range: 2 to 20 mcg/kg/minute; titrate to desired response (maximum: 50 mcg/kg/minute; however, doses >20 mcg/kg/minute may not have a beneficial effect on blood pressure and may increase the risk of tachyarrhythmias); infusion may be gradually increased by 5 to 10 mcg/kg/minute increments until optimal response is obtained Cardiogenic shock (off-label dose): IV: 0.5 to 20 mcg/kg/minute (AHA [van Diepen 2017]) Inotropic support in advanced heart failure: IV infusion: 5 to 15 mcg/kg/minute; lower doses are preferred (ACCF/AHA [Yancy 2013]). ACLS guideline recommendations (to treat hypotension especially if associated with symptomatic bradycardia in the immediate post-cardiac arrest care setting) (off-label use): Initial: 5 to 10 mcg/kg/minute; titrate to effect (AHA [Peberdy 2010]) Note: If dosages >20 to 30 mcg/kg/minute are needed, a more direct-acting vasopressor may be more beneficial (ie, epinephrine, norepinephrine). Hemodynamic effects of dopamine are dose dependent (however, this is relative and there is overlap of clinical effects between dosing ranges): Low-dose: 1 to 5 mcg/kg/minute, results in increased renal blood flow and urine output. Note: The use of low-dose dopamine to prevent or treat acute kidney injury is not recommended (KDIGO 2012). Intermediate-dose: 5 to 10 mcg/kg/minute, results in increased renal blood flow, heart rate, cardiac contractility, and cardiac output High-dose: >10 mcg/kg/minute, alpha-adrenergic effects begin to predominate, resulting in vasoconstriction, increased blood pressure, in addition to increased heart rate, cardiac contractility, and cardiac output due to beta-adrenergic effects.

(For additional information see "Dopamine: Pediatric drug information") Hemodynamic support: Infants, Children, and Adolescents: IV infusion: Refer to adult dosing. Pediatric Advanced Life Support (PALS) guideline recommendation (to maintain cardiac output and for postresuscitation stabilization) (off-label use): IV or Intraosseous infusion: Dose range: 2 to 20 mcg/kg/minute; titrate gradually by 5- to 10-mcg/kg/minute increments until optimal response is obtained (AHA [Kleinman 2010]) Hemodynamic effects of dopamine are dose dependent (however, this is relative and there is overlap of clinical effects between dosing ranges): Low-dose: 1 to 5 mcg/kg/minute, results in increased renal blood flow and urine output. Note: The use of low-dose dopamine to prevent or treat acute kidney injury is not recommended (KDIGO 2012). Intermediate-dose: 5 to 10 mcg/kg/minute, results in increased renal blood flow, heart rate, cardiac contractility, and cardiac output High-dose: >10 mcg/kg/minute, alpha-adrenergic effects begin to predominate, resulting in vasoconstriction, increased blood pressure in addition to increased heart rate, cardiac contractility, and cardiac output due to beta-adrenergic effects.

Refer to adult dosing.

Warnings & Precautions

Source: Lexicomp

Arrhythmias

May cause increases in heart rate, increasing the risk of tachycardia and other tachyarrhythmias including ventricular arrhythmias (Tisdale 1995). In heart transplant candidates, institute appropriate measures to protect patient against risks of sudden cardiac death (Young 2000).

Extravasation

Vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation; infuse into a large vein if possible. Avoid infusion into leg veins. Watch IV site closely. [US Boxed Warning]: If extravasation occurs, infiltrate the area with diluted phentolamine (5 to 10 mg in 10 to 15 mL of saline) with a fine hypodermic needle. Phentolamine should be administered as soon as possible after extravasation is noted to prevent sloughing/necrosis. Disease-related concerns:

Cardiovascular disease

Use with caution in patients with cardiovascular disease, cardiac arrhythmias and/or occlusive vascular disease.

Active myocardial ischemia/post-myocardial infarction

Use with caution in patients with active myocardial ischemia or recent myocardial infarction; may increase myocardial oxygen consumption.

Electrolyte imbalance

Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy to minimize the risk of arrhythmias (ACC/AHA/ESC [Zipes 2006]; Tisdale 1995).

Shock

The use of dopamine in adult patients with shock (majority of patients had septic shock) demonstrated a higher incidence of adverse events (eg, tachyarrhythmias) (De Backer 2010). Higher 28-day mortality was also seen in patients with septic shock with the use of dopamine as compared to norepinephrine (De Backer 2012; Vasu 2012). Concurrent drug therapy issues:

Monoamine oxidase inhibitors (MAO-I)

Use with extreme caution in patients taking MAO inhibitors; prolong hypertension may result from concurrent use. Dosage form specific issues:

Sodium metabisulfite

Product may contain sodium metabisulfite. Other warnings/precautions:

Appropriate use

Assure adequate circulatory volume to minimize need for vasoconstrictors when used in hemodynamic support. Avoid hypertension; monitor blood pressure closely and adjust infusion rate.

Long-term therapy

According to the ACCF/AHA 2013 heart failure guidelines, long-term use of intravenous inotropic therapy without a specific indication or for reasons other than palliation is potentially harmful (ACCF/AHA [Yancy 2013]).

Pregnancy & Lactation

Pregnancy

FDA category C Teratogenic

Adverse events have been observed in some animal reproduction studies. It is not known if dopamine crosses the placenta. Medications used for the treatment of cardiac arrest in pregnancy are the same as in the non-pregnant woman. Appropriate medications should not be withheld due to concerns of fetal teratogenicity. Dopamine use during the post-resuscitation phase may be considered; however, the effects of vasoactive medications on the fetus should also be considered. Doses and indications should follow current Advanced Cardiovascular Life Support guidelines (Jeejeebhoy [AHA] 2015).

Lactation

It is not known if dopamine is present in breast milk. The manufacturer recommends that caution be exercised when administering dopamine to breastfeeding women.

Monitoring

Clinical pearl	Blood pressure, ECG, heart rate, CVP, RAP, MAP; serum glucose, renal function; urine output; if pulmonary artery catheter is in place, monitor CI, PCWP, SVR, and PVR Consult individual institutional policies and procedures.

Chemistry & Properties

Formula	C8H11NO2
Molecular weight	153.18 g/mol
IUPAC name	4-(2-aminoethyl)benzene-1,2-diol
CAS	51-61-6
PubChem CID	681
InChIKey	`VYFYYTLLBUKUHU-UHFFFAOYSA-N`
logP	0.6 (XLogP -1.0)
Polar surface area	66.48 Å²
H-bond acceptors / donors	3 / 3
Drug-likeness (QED)	0.54
Lipinski violations	0

SMILES

NCCc1ccc(O)c(O)c1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	2.121 h
Volume of distribution	0.755 L/kg
Protein binding	4.7%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2C19	Substrate	—
CYP2C9	Substrate	—
CYP2D6	Substrate	—

Receptor binding (top 19)

Target	Action	Affinity
DOPAMINE D4 (DRD4)	Binding	pKi 8.2
D4 receptor (DRD4)	Agonist	pKi 7.6
DOPAMINE D3 (DRD3)	Binding	pKi 7.5
D3	Binding	pKi 7.2
DOPAMINE D4.4	Binding	pKi 7.2
DOPAMINE D5 (DRD5)	Binding	pKi 6.6
DOPAMINE D2 (DRD2)	Binding	pKi 6.6
D5 receptor (DRD5)	Agonist	pKi 6.6
DOPAMINE D4.2	Binding	pKi 6.6
Norepinephrine transporter	Binding	pKi 6.5
TA1 (TRAR1)	Binding	pKi 6.4
D4	Binding	pKi 6.2
Dopamine2-like	Binding	pKi 6.1
DOPAMINE D1 (DRD1)	Binding	pKi 6.0
DOPAMINE D2 Long (DRD2)	Binding	pKi 5.8

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)OCT2 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)OCT1 (Substrate)OCT2 (Substrate)OCT3 (Substrate)P-gp (Substrate)

Drug–drug interactions (81, DDInter)

Interacting drug	Severity	Management
Cocaine (nasal)	major
Cocaine (topical)	major
Doxepin	major
Iobenguane (I-131)	major
Methylene blue	major
Ozanimod	major
Procarbazine	major
Acarbose	moderate
Acetohexamide	moderate
Albiglutide	moderate
Alimemazine	moderate
Alogliptin	moderate
Canagliflozin	moderate
Chlorpropamide	moderate
Dapagliflozin	moderate
Desmopressin	moderate
Diatrizoate	moderate
Diethylpropion	moderate
Doxapram	moderate
Dulaglutide	moderate
Empagliflozin	moderate
Ertugliflozin	moderate
Exenatide	moderate
Fludeoxyglucose (18F)	moderate
Formoterol	moderate
Glimepiride	moderate
Glipizide	moderate
Glyburide	moderate
Indacaterol	moderate
Insulin aspart (aspart protamine)	moderate
Insulin aspart (aspart)	moderate
Insulin degludec	moderate
Insulin detemir	moderate
Insulin glargine	moderate
Insulin glulisine	moderate
Insulin human	moderate
Insulin human (inhalation, rapid acting)	moderate
Insulin human (isophane)	moderate
Insulin human (regular)	moderate
Insulin human (zinc extended)	moderate

Showing 40 of 81.

Registered Products (7)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Domine 40 mg / ml Amp	Ampoule 40 mg/ml	5 amp	Hikma Pharmaceuticals Co.Ltd/Jordan	—
Dopamine Fresenius	Ampoule 200 mg/5 ml	1 amp pack varies	Sun Set Drug Store	—
Dopamine Fresenius	Suspension 200 mg/5 ml	5 ml pack varies	Sun Set Drug Store	—
Dopamine HCL	Ampoule 50 mg/5 ml	5 amp pack varies	Al Hilal Drug Store	—
Dopamine HCL	Ampoule 50 mg/5 ml	30 amp pack varies	Al Hilal Drug Store	—
Dopamine HCL	Ampoule 50 mg/5 ml	10 amp pack varies	Al Hilal Drug Store	—
Dopamine HCL	Ampoule 50 mg/5 ml	50 amp pack varies	Al Hilal Drug Store	—