ziprasidone

ROUTE	ONSET	PEAK	DURATION
PO	within hrs	1–3 days†	unknown
IM	rapid	60 min	unknown

Contraindicated in:

Hypersensitivity
History of QT interval prolongation (persistent QTc interval >500 msec), arrhythmias, recent MI or uncompensated HF
Concurrent use of other drugs known to prolong the QT interval including quinidine, dofetilide, sotalol, other class Ia and III antiarrhythmics, pimozide, sotalol, thioridazine, chlorpromazine, pentamidine, arsenic trioxide, mefloquine, tacrolimus, droperidol, and moxifloxacin
Hypokalemia or hypomagnesemia.

Use Cautiously in:

Concurrent diuretic therapy or diarrhea (may ↑ the risk of hypotension, hypokalemia, or hypomagnesemia)
Hepatic impairment
History of cardiovascular or cerebrovascular disease
Hypotension, concurrent antihypertensive therapy, dehydration, or hypovolemia (may ↑ risk of orthostatic hypotension)
At risk for aspiration pneumonia or falls
History of suicide attempt
OB: Neonates at ↑ risk for extrapyramidal symptoms and withdrawal after delivery when exposed during the 3rd trimester; use during pregnancy only if potential maternal benefit justifies potential fetal risk
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
Pedi: Safety and effectiveness not established in children
Geri: Appears on Beers list. ↑ risk of stroke, cognitive decline, and mortality in older adults with dementia. Avoid use in older adults, except for schizophrenia or bipolar disorder.

Adv. Reactions/Side Effects ⬆ ⬇

CV: orthostatic hypotension, QT interval prolongation.

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash, STEVENS-JOHNSON SYNDROME (SJS), urticaria.

EENT: rhinorrhea.

Endo: galactorrhea, hyperglycemia.

GI: constipation, diarrhea, nausea, dysphagia.

GU: amenorrhea, impotence.

Hemat: AGRANULOCYTOSIS, leukopenia, neutropenia.

Metab: hyperlipidemia, weight gain.

Neuro: dizziness, drowsiness, restlessness, extrapyramidal reactions, NEUROLEPTIC MALIGNANT SYNDROME, seizures, syncope, tardive dyskinesia.

Resp: cough.

Interactions ⬆ ⬇

Drug-Drug:

Concurrent use of quinidine, dofetilide, other class Ia and III antiarrhythmics, pimozide, sotalol, thioridazine, chlorpromazine, pentamidine, arsenic trioxide, mefloquine, tacrolimus, droperidol, moxifloxacin, or other agents that prolong the QT interval may result in potentially life-threatening adverse drug reactions; concurrent use contraindicated.
Additive CNS depression may occur with alcohol, antidepressants, antihistamines, opioid analgesics, or sedative/hypnotics.
Levels and effectiveness may be ↓ by carbamazepine.
Levels and effects may be ↑ by ketoconazole.

Route/Dosage ⬆ ⬇

Schizophrenia

PO (Adults): 20 mg twice daily initially; dose increments may be made at 2-day intervals up to 80 mg twice daily.
IM (Adults): 10–20 mg as needed up to 40 mg/day; may be given as 10 mg every 2 hr or 20 mg every 4 hr.

Acute Manic or Mixed Episodes Associated with Bipolar I Disorder

PO (Adults): 40 mg twice on first day, then 60 or 80 mg twice daily on 2nd day, then 40–80 mg twice daily.

Maintenance Treatment of Bipolar I Disorder (as adjunct to lithium or valproate)

PO (Adults): Continue same dose on which patient was initially stabilized (range: 40–80 mg twice daily).

Availability ⬆ ⬇

(Generic available)

Capsules: 20 mg; 40 mg; 60 mg; 80 mg;
Lyophilized powder for injection: 20 mg/vial;

Assessment ⬆ ⬇

Monitor patient’s mental status (orientation, mood, behavior) prior to and periodically during therapy.
Assess weight and BMI initially and periodically during therapy.
Monitor BP (sitting, standing, lying) and pulse rate prior to and frequently during initial dose titration. Patients found to have persistent QTc interval measurements of >500 msec should have ziprasidone discontinued. Patients who experience dizziness, palpitations, or syncope may require further evaluation (i.e., Holter monitoring).
Assess for rash during therapy. May be treated with antihistamines or corticosteroids. Usually resolves upon discontinuation of ziprasidone. Medication should be discontinued if no alternative etiology for rash is found. May cause SJS or DRESS. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
Observe carefully when administering medication to ensure medication is actually taken and not hoarded or cheeked.
Monitor for onset of akathisia (restlessness or desire to keep moving) and extrapyramidal side effects (parkinsonian: difficulty speaking or swallowing, loss of balance control, pill rolling of hands, mask-like face, shuffling gait, rigidity, tremors and dystonic muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) every 2 mo during therapy and 8–12 wk after therapy has been discontinued. Notify health care professional if these symptoms occur, as reduction in dose or discontinuation of medication may be necessary. Trihexyphenidyl or benztropine may be used to control these symptoms.
Although not yet reported for ziprasidone, monitor for possible tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities, lip smacking or puckering, puffing of cheeks, uncontrolled chewing, rapid or worm-like movements of tongue). Report these symptoms immediately; may be irreversible.
Monitor frequency and consistency of bowel movements. Increasing bulk and fluids in the diet may help to minimize constipation.
Ziprasidone lowers the seizure threshold. Institute seizure precautions for patients with history of seizure disorder.
Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). Notify health care professional immediately if these symptoms occur.
Monitor for symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).
Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability increase risk. Institute prevention if indicated.

Lab Test Considerations:

Monitor serum potassium and magnesium prior to and periodically during therapy. Patients with low potassium or magnesium should have levels treated and checked prior to resuming therapy. Obtain fasting blood glucose and cholesterol levels initially and periodically during therapy.
- Monitor CBC frequently during initial mo of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue therapy if this occurs.
- Monitor serum prolactin prior to and periodically during therapy. May cause ↑ serum prolactin levels.

Implementation ⬆ ⬇

Dose adjustments should be made at intervals of no less than 2 days. Usually patients should be observed for several wk before dose titration.
- Patients on parenteral therapy should be converted to oral doses as soon as possible.
PO: Administer capsules with food or milk to decrease gastric irritation. DNC: Swallow capsules whole; do not open, crush, or chew.
IM: Reconstitution: Add 1.2 mL of sterile water for injection to the vial; shake vigorously until all drug is dissolved for a concentration of 20 mg/mL. Discard unused portion. Do not mix with other products or solutions. Do not administer solutions that are discolored or contain particulate matter.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed, at the same time each day. Do not discontinue medication without discussing with health care professional, even if feeling well. Patients on long-term therapy may need to discontinue gradually.
Inform patient of possibility of extrapyramidal symptoms. Instruct patient to report these symptoms immediately.
Advise patient to change positions slowly to minimize orthostatic hypotension. Protect from falls.
May cause seizures and drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications. Caution patient to avoid concurrent use of alcohol and other CNS depressants, including opioids.
Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
Instruct patient to notify health care professional promptly if dizziness, loss of consciousness, palpitations, menstrual abnormalities, galactorrhea, or sexual dysfunction occur.
Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding during therapy. Monitor neonates exposed to ziprasidone during third trimester for extrapyramidal and/or withdrawal symptoms. Some neonates recovered within hrs or days without specific treatment; others required prolonged hospitalization. Monitor infants exposed through breast milk for excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements). May impair fertility in females. Inform patient of pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics. Register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at womensmentalhealth.org/research/pregnancyregistry/.
Advise patient of need for continued medical follow-up for psychotherapy, eye exams, and laboratory tests.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇