Neonatal Hemochromatosis Medication

Updated: Oct 20, 2017
  • Author: Ann M Simonin, MD, FAAP; Chief Editor: Carmen Cuffari, MD  more...
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Medication

Medication Summary

Few drugs are available for treating neonatal hemochromatosis. Infants with neonatal hemochromatosis have been treated with a combination of antioxidants, cryoprotective agents, and chelation.

Three antioxidants are used throughout the course of therapy: N -acetylcysteine, alpha-tocopherol polyethylene glycol succinate (TPGS), and selenium. These are used in combination with prostaglandin E and deferoxamine, which have a cryoprotective effect and which chelate iron, respectively.

A suggested cocktail is the following: N -acetylcysteine 200 mg/kg/d PO divided tid for 17-21 doses, alpha-TPGS 25 IU/kg/d PO divided bid for 6 weeks, deferoxamine 30 mg/kg/d IV infused over 8 hours until the serum ferritin level is less than 500 mcg/L, selenium 3 mcg/kg/d IV continuous infusion for the length of hospitalization, and prostaglandin E1 0.4 mcg/kg/h IV increased to 0.6 mcg/kg/h over 3-4 hours. The infusion is maintained for 10 days. [13]

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Chelating agents

Class Summary

These agents inhibit toxin by reacting with it to form less active or inactive complex. The complex is then excreted from the body.

Deferoxamine (Desferal)

Deferoxamine is freely soluble in water. Approximately 8 mg of iron is bound by 100 mg. It is excreted in urine and bile and produces red discoloration of urine. This agent readily chelates iron from ferritin and hemosiderin but not transferrin. It is most effective with continuous infusion. It may be administered IM, SC, or slow IV infusion. Deferoxamine does not effectively chelate other trace metals of nutritional importance.

Vials contain 500 mg of lyophilized sterile drug; add 2 mL sterile water for injection to each vial, bringing concentration to 250 mg/mL. For IV use, may be diluted in 0.9% sterile saline, dextrose 5% in water (D5W), or Ringer solution. IM administration is preferred except in patients with hypotension and cardiovascular collapse, in whom IV should be considered.

The use of deferoxamine in treatment of neonatal hemochromatosis is controversial. Experience is limited; therefore, use with caution.

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Antioxidants

Class Summary

These agents protect sensitive tissues throughout the body from oxidizing substances known as free radicals. Although antioxidants protect most cell membranes, vitamin E is particularly important in preventing damage to the linings of blood vessels and maintaining good circulation.

N-Acetylcysteine (Acetadote)

This agent is a derivative of amino acid cysteine and scavenger of oxygen free radicals. It is also a glutathione precursor and is used to replenish depleted intracellular glutathione. Therefore, it theoretically augments antioxidant defenses.

Alpha-tocopherol (Aquasol-E, E-Gems, Ester-E)

Vitamin E is particularly important in preventing damage to linings of blood vessels and maintaining good circulation. It acts as an antioxidant in cell membranes to prevent propagated oxidation of unsaturated fatty acids. It is also known to impair hematologic response to iron.

Selenium (Selenicaps, Selenimin)

Selenium is an essential trace element, part of the enzyme glutathione peroxidase. It protects cell components from oxidative damage due to peroxides produced in cellular metabolism.

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Prostaglandins

Class Summary

These agents elicit cryoprotective effect.

Alprostadil (Prostin VR Pediatric)

Alprostadil (prostaglandin E1) is used primarily to keep patency of ductus arteriosus but also has a mild pulmonary vasodilatory effect. It is reported to inhibit macrophage activation, neutrophil chemotaxis, and release of oxygen radicals and lysosomal enzymes. It affects coagulation by inhibiting platelet aggregation and possibly by inhibiting activation of factor X. It may promote fibrinolysis by stimulating production of tissue plasminogen activator.

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Surfactants

Class Summary

Exogenous surfactant can be helpful in treatment of airspace disease (eg, respiratory distress syndrome [RDS]). After inhaled administration, surface tension is reduced and alveoli are stabilized, decreasing the work of breathing and increasing lung compliance.

Beractant (Survanta)

This agent mimics the surface tension–lowering properties of natural lung surfactant. It contains colfosceril palmitate, cetyl alcohol, and tyloxapol. It is used for prophylaxis of RDS in premature infants with birthweight < 1350 g or RDS in premature infants with birthweight >1350 g who have evidence of pulmonary immaturity. It is also used for rescue treatment of infants who develop RDS.

Calfactant (Infasurf)

This is a natural bovine calf lung extract containing phospholipids, fatty acids, and surfactant-associated proteins B (260 mcg/mL) and C (390 mcg/mL). Surfactant is an endogenous complex of lipids and proteins that lines alveolar walls and promotes alveolar stability by reducing surface tension. Relative surfactant deficiency is variably present in many lung diseases.

Poractant alfa (Curosurf)

This agent lines alveolar walls and promotes alveolar stability against collapse by reducing surface tension at the air-liquid interface of the alveoli.

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Inotropic agents

Class Summary

Positive inotropic agents increase the force of contraction of the myocardium and are used to treat acute and chronic congestive heart failure (CHF). Some may also increase or decrease the heart rate (ie, positive or negative chronotropic agents), provide vasodilatation, or improve myocardial relaxation. These additional properties influence the choice of drug for specific circumstances.

Dopamine

Dopamine is used to treat hypotension that is not secondary to hypovolemia. It has a preferential sparing effect on the renal circulation. It is often used with dobutamine.

Dopamine stimulates adrenergic and dopaminergic receptors. Its hemodynamic effect depends on dose. Low doses predominantly stimulate dopaminergic receptors that in turn produce renal and mesenteric vasodilation. High doses produce cardiac stimulation and renal vasodilation.

The mechanism of action of dopamine in neonates is controversial because of variations in endogenous norepinephrine stores, receptor function, and ability to increase stroke volume.

Low doses (< 2 mcg/kg/min) provide dopaminergic stimulation and increases urine output, fractional excretion of sodium, and creatinine clearance.

Intermediate doses (2-10 mcg/kg/min) increase cardiac contractility and blood pressure at low doses and increases heart rate at high doses. Inotropic response varies with gestational age and baseline stroke volume.

High doses (>20 mcg/kg/min) predominantly increase systemic and pulmonary vascular resistance. Use with caution in patients with persistent pulmonary hypertension of the newborn.

Dobutamine

Dobutamine provides inotropic support in patients with shock and hypotension. It is not a pressor. This agent is used for demonstrated or suspected decreased cardiac contractility. It is often used in concert with dopamine. Echocardiography is useful in evaluating need (eg, contractility, ventricular dilation, ejection fraction).

Dobutamine produces vasodilation and increases the inotropic state. At high dosages, it may increase heart rate. Onset of action is 1-2 min, peak effect in 10 min. Administer as continuous IV infusion because half-life is several minutes. It is metabolized in the liver.

Dobutamine acts as a synthetic catecholamine with primarily beta1-adrenergic activity. It increases myocardial contractility, cardiac index, oxygen delivery, and oxygen consumption. It decreases systemic and pulmonary vascular resistance in adults.

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