CNS depression potentiated with alcohol, other CNS depressants. Possible neurotoxicity with lithium: monitor, discontinue if occurs. Caution with drugs that prolong the QT interval (eg, ketoconazole, paroxetine). May be potentiated by CYP3A4 inhibitors/substrates or CYP2D6 enzymes (eg, itraconazole, nefazodone, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, sertraline, chlorpromazine, promethazine. May be antagonized by CYP3A4 inducers (eg, rifampin, carbamazepine); monitor and adjust doses. May increase intraocular pressure with anticholinergics. Monitor anticoagulants.
Haloperidol is a typical butyrophenone type antipsychotic that exhibits high affinity dopamine D 2 receptor antagonism and slow receptor dissociation kinetics.  It has effects similar to the phenothiazines .  The drug binds preferentially to D 2 and α 1 receptors at low dose (ED 50 = and mg/kg, respectively), and 5-HT 2 receptors at a higher dose (ED 50 = mg/kg). Given that antagonism of D 2 receptors is more beneficial on the positive symptoms of schizophrenia and antagonism of 5-HT 2 receptors on the negative symptoms, this characteristic underlies haloperidol's greater effect on delusions, hallucinations and other manifestations of psychosis.  Haloperidol's negligible affinity for histamine H 1 receptors and muscarinic M 1 acetylcholine receptors yields an antipsychotic with a lower incidence of sedation, weight gain, and orthostatic hypotension though having higher rates of treatment emergent extrapyramidal symptoms .
Haloperidol use may lead to the development of symptoms that resemble Parkinson's disease, but that are not caused by Parkinson's. These symptoms may include a taut or mask-like expression on the face, drooling, tremors, pill-rolling motions in the hands, cogwheel rigidity (abnormal rigidity in muscles, characterized by jerky movements when the muscle is passively stretched), and a shuffling gait. Taking the anti-Parkinson drugs benztropine mesylate or trihexyphenidyl hydrochloride along with haloperidol help to control these symptoms. Medication to control Parkinsonian-like symptoms may have to be continued after haloperidol is stopped. This is due to different rates of elimination of these drugs from the body.