Table 2. Comparison of Aprepitant and Standard Regimens continued...
Lorazepam may be administered orally, IM, IV, and sublingually. Dosages range from 0.5 to 3 mg (alternatively, 0.025-0.05 mg/kg, or 1.5 mg/m2, but ≤4 mg per dose) in adults and 0.03 to 0.05 mg/kg in children every 6 to 12 hours.[Level of evidence: I][105,110,111] Midazolam produces mild-to-marked sedation for 1 to 4.5 hours at doses equal to 0.04 mg/kg given IV over 3 to 5 minutes.[112,113] Alprazolam has been shown to be effective when given in combination with metoclopramide and methylprednisolone.
The adverse effects of lorazepam include the following:
- Perceptual disturbances.
- Disorders of micturition and/or defecation.
- Visual disturbances.
- Anterograde amnesia.
- Psychological dependence.
- Depressed mental acuity with intoxication.
Olanzapine is an antipsychotic in the thienobenzodiazepine drug class that blocks multiple neurotransmitters: dopamine at D1, D2, D3, and D4brain receptors; serotonin at 5-HT2a, 5-HT2c, 5-HT3, and 5-HT6 receptors; catecholamines at alpha-1 adrenergic receptors; acetylcholine at muscarinic receptors; and histamine at H1 receptors. Common side effects include the following:[117,118,119]
Olanzapine has also been associated with increased risk of hyperlipidemia, hyperglycemia, new-onset diabetes and, in rare cases, diabetic ketoacidosis.[117,119,120] Olanzapine is used with caution in elderly patients; it has been associated with increased risk of death and increased incidence of cerebrovascular adverse events in patients with dementia-related psychosis and carries a boxed warning to that effect. Olanzapine's activity at multiple receptors, particularly at the D2 and 5-HT3 receptors that appear to be involved in N&V, suggests that it may have significant antiemetic properties.
There have been case reports on the use of olanzapine as an antiemetic.[Level of evidence: II];[122,123,124,125] These case reports prompted a phase I study in which olanzapine was used for the prevention of delayed emesis in cancer patients receiving their first cycle of chemotherapy consisting of cyclophosphamide, doxorubicin, cisplatin, and/or irinotecan. The protocol was completed by 15 patients, and no grade 4 toxicities were seen. The maximum tolerated dose was 5 mg/day for 2 days prior to chemotherapy and 10 mg/day for 7 days postchemotherapy. On the basis of these data, olanzapine appeared to be a safe and effective agent for the prevention of delayed emesis in chemotherapy-naive cancer patients receiving cyclophosphamide, doxorubicin, cisplatin, and/or irinotecan.