Haloperidol Decanoate

Haloperidol decanoate is the decanoate ester of the butyrophenone, HALDOL (haloperidol). It has a markedly extended duration of effect. It is available in sesame oil in sterile form for intramuscular (IM) injection. The structural formula of haloperidol decanoate, 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-4 piperidinyl decanoate, is:

Haloperidol decanoate is almost insoluble in water (0.01 mg/mL), but is soluble in most organic solvents.

Each mL of HALDOL Decanoate (haloperidol decanoate) 50 for IM injection contains 50 mg haloperidol (present as haloperidol decanoate 70.52 mg) in a sesame oil vehicle, with 1.2% (w/v) benzyl alcohol as a preservative.

Each mL of HALDOL Decanoate (haloperidol decanoate) 100 for IM injection contains 100 mg haloperidol (present as haloperidol decanoate 141.04 mg) in a sesame oil vehicle, with 1.2% (w/v) benzyl alcohol as a preservative.

HALDOL Decanoate (haloperidol decanoate) 50 and HALDOL Decanoate (haloperidol decanoate) 100 are indicated for the treatment of schizophrenic patients who require prolonged parenteral antipsychotic therapy.

HALDOL Decanoate (haloperidol decanoate) 50 and HALDOL Decanoate (haloperidol decanoate) 100 are the long-acting forms of HALDOL (haloperidol). The basic effects of haloperidol decanoate are no different from those of HALDOL with the exception of duration of action. Haloperidol blocks the effects of dopamine and increases its turnover rate; however, the precise mechanism of action is unknown.

Administration of haloperidol decanoate in sesame oil results in slow and sustained release of haloperidol. The plasma concentrations of haloperidol gradually rise, reaching a peak at about 6 days after the injection, and falling thereafter, with an apparent half-life of about 3 weeks. Steady state plasma concentrations are achieved after the third or fourth dose. The relationship between dose of haloperidol decanoate and plasma haloperidol concentration is roughly linear for doses below 450 mg. It should be noted, however, that the pharmacokinetics of haloperidol decanoate following intramuscular injections can be quite variable between subjects.

Schizophrenia

Treatment of schizophrenia.a b d 185

Antipsychotic agents are used for all phases of schizophrenia, including acute psychotic episodes as well for long-term stabilization and to minimize risk of relapse.185

Patients who do not respond to or tolerate one drug may be successfully treated with an agent from a different class or with a different adverse effect profile.136 137 138 185

APA considers certain atypical (second-generation) antipsychotic agents first-line for the acute phase of schizophrenia, principally because of the decreased risk of adverse extrapyramidal effects and tardive dyskinesia, with the understanding that the relative advantages, disadvantages, and cost-effectiveness of atypical antipsychotic agents compared with first-generation antipsychotic agents remain controversial.185

Conventional antipsychotic agents may be considered first-line in patients with acute psychotic episodes who have been treated successfully in the past with, or who prefer, conventional agents.185

Long-acting haloperidol decanoate ester used principally for prolonged antipsychotic therapy (e.g., chronic schizophrenic disorder).100 101 105 106 108 110 111 112 185 Parenteral antipsychotic therapy with a long-acting preparation may be particularly useful in patients with a history of poor compliance.105 106 108 110 111 112 185 However, should not be used in the acute management of severely agitated patients.100 101

Tourette’s Syndrome

Control of tics and vocal utterances of Tourette’s syndrome (Gilles de la Tourette’s syndrome).b d e

May be used concomitantly with a stimulant for tic disorders (e.g., Tourette’s syndrome) and comorbid attention deficit hyperactivity disorder† (ADHD) in children in whom stimulants alone cannot control tics.147 148

Disruptive Behavior Disorder and ADHD

Treatment of severe behavioral problems in children marked by combativeness and/or explosive hyperexcitable behavior (out of proportion to immediate provocations).b d e

Short-term treatment in children with hyperactivity associated with excessive motor activity and accompanying conduct disorders that are manifested as impulsive behavior, difficulty sustaining attention, aggression, mood lability, and/or poor frustration tolerance.b d e

Manufacturers recommend reserving for severe behavioral problems or ADHD, only after failure of psychotherapy or drug therapy other than antipsychotics.d e Some experts recommend use only for comorbid tics in children with ADHD.148

Delirium

Management of delirium†.121 130 172

Antipsychotic agents often considered drugs of choice for delirium†.121 172 Haloperidol generally is considered the antipsychotic of choice for most patients with delirium† because of its relatively low risk of anticholinergic activity and of sedative and hypotensive effects.121 130 132 170

Various antipsychotic agents may be given orally, IM, or IV, but IV† administration is considered most effective in emergency situations or where oral access is limited.121 IV administration also may be associated with less severe extrapyramidal effects.121 123 130

Consider risk of QT-interval prolongation, possibly leading to atypical ventricular tachycardia (torsades de pointes), ventricular fibrillation, and sudden death, if haloperidol is used IV† for delirium.121 124 125 126 130 131 132 133 134 169 Institute appropriate monitoring (e.g., ECG).121 124 125 126 130 131 132 133 134 162 163 164 (See Delirium under Dosage and Administration and see QT-interval Prolongation and Sudden Death under Cautions.)

Nausea and Vomiting

Has been used in the prevention and control of severe nausea and vomiting† (e.g., cancer chemotherapy-induced emesis).a Appears to be as effective as phenothiazines in preventing cancer chemotherapy-induced emesis; additional studies required.a

Storage

Oral

Tight, light-resistant containers100 101 102 103 104 at 15–30°C.a Avoid freezing.100 101 103

Tight, light-resistant containers100 101 102 103 104 at 20–25°C.a

Parenteral

Haloperidol decanoate: 15–30°C.c Do not refrigerate or freeze.c Protect from light.c

Haloperidol lactate: 15–30°C.b Do not freeze.b Protect from light.b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Incompatible with sterile water for injection or sodium chloride injection and with other aqueous injections.101

May be compatible with some drugs for a short period of time after mixing, but at least one manufacturer recommends that the lactate not be mixed with other drugs.102

• Principal pharmacologic effects are similar to those of piperazine-derivative phenothiazines.a

• Precise mechanism of antipsychotic action is unclear, but appears to depress the CNS at the subcortical level of the brain, midbrain, and brain stem reticular formation; appears to inhibit the ascending reticular activating system of the brain stem (possibly through the caudate nucleus), thereby interrupting the impulse between the diencephalon and the cortex.a

• May antagonize actions of glutamic acid within the extrapyramidal system.a Inhibition of catecholamine receptors may also be important in the mode of action; may also inhibit the reuptake of various neurotransmitters in the midbrain.a

• Appears to have strong central antidopaminergic and weak central anticholinergic activity.a

• Precise mechanism of antiemetic action is unclear, but has been shown to directly affect the chemoreceptor trigger zone (CTZ), apparently by blocking dopamine receptors in the CTZ.a

• Like other dopamine receptor antagonists (e.g., phenothiazines), may cause extrapyramidal reactions, and there appears to be a very narrow range between effective therapeutic dosage for management of acute psychotic disorders and that causing extrapyramidal symptoms.a

• Produces less sedation, hypotension, and hypothermia than chlorpromazine.a