Aripiprazole

N-type calcium channel blocker for treatment of severe chronic pain for patients no longer helped by morphine

Ziconotide binding may block N-type calcium channels, which leads to a blockade of excitatory neurotransmitter release.

Dosage. Administer ziconotide intrathecally at 2.4 mcg/d, titrated to pain severity, response to therapy, and adverse events occurrence. Titrate doses up to 2.4 mcg/d at intervals of no more than 2-3 times per week, up to a maximum of 19.2 mcg/d by Day 21. Faster titration should only be used if an urgent need for analgesia outweighs patient safety risk.

Geriatric dosage adjustment. Due to greater frequency of decreased hepatic, renal or cardiac function, and of concomitant drug therapy, start dosage for older patients at the low end of the dosing range.

Pharmacokinetics. The half-life of ziconotide in cerebrospinal fluid is approximately 4.6 hours (range 2.9-6.5 hours). Monitor serum CK.

Safety. A black box warning was issued regarding severe psychiatric symptoms and neurological impairment with ziconotide. Patients with a history of psychosis should not receive ziconotide. Monitor patients frequently for cognitive impairment, hallucinations, or changes in mood or consciousness. Ziconotide can be interrupted or discontinued abruptly without withdrawal effects if serious neurologic or psychiatric signs or symptoms occur. During treatment, caution patients against activity requiring mental alertness or motor coordination and about effects with other CNS-depressant drugs.

Adverse events. In clinical studies, adverse events included psychiatric symptoms, cognitive impairment, and decreased alertness/unresponsiveness, confusion, memory impairment, speech disorder, aphasia, abnormal thinking, and amnesia. Serious adverse events are less frequent when slowly titrated over 21 days, than with a faster titration schedule.

New combinations, formulations

* New combination: Opioid oxycodone and NSAID ibuprofen (Combunox, Forest Laboratories) for the short-term management of moderate to severe pain. Use extra care when treating older adults due to sensitivity to renal and GI effects of NSAIDs and the risk of respiratory depression with opioids.

* New formulation: Aripiprazole (Abilify, Bristol-Myers Squibb, Otsuka) oral solution to provide greater flexibility for patients who have difficulty swallowing pills.

New indications, labeling, method of administration

* Infliximab and methotrexate (Remicade, Centocor) for first-line treatment in patients with rheumatoid arthritis (RA). Expanded indication removes the requirement that patients must fail methotrexate treatment before receiving the infliximab regimen. A labeling revision warns that studies have shown that patients who take infliximab for RA are 3 times more likely to develop lymphoma than those not taking infliximab.

* Etanercept (Enbrel, Amgen, Wyeth) to induce a major clinical response (achieving and maintaining a 70% improvement in signs and symptoms for 6 months) in patients with RA. Revised labeling states that patients with early active RA continue to show inhibition of joint damage 5 years after initiating therapy. A 50 mg/mL pre-filled syringe dose was approved for administration once weekly.

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