Prialt

PRIALT (ziconotide) solution, intrathecal infusion is indicated for the management of severe chronic pain in adult patients for whom intrathecal therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine.

• Advise patients that psychiatric symptoms (paranoia, hostility, mania, depressive, suicidal) and cognitive symptoms (confusion, memory problems, speech disorder) may occur during treatment with PRIALT.
• Caution patients against engaging in hazardous activity requiring complete mental alertness or motor coordination such as operating machinery or driving a motor vehicle during treatment with PRIALT.
• Caution patients about possible combined effects with other CNS-depressant drugs. Dosage adjustments may be necessary when PRIALT is administered with such agents because of the potentially additive effects.
• Advise patients to contact a physician if the patient experiences new or worsening muscle pain, soreness, weakness with or without darkened urine.
• Instruct patients and their caregivers to contact a physician immediately if the patient has any of the following
  • A change in mental status (e.g., lethargy, confusion, disorientation, decreased alertness)
  • A change in mood, perception (hallucinations, including unusual tactile sensations in the oral cavity)
  • Symptoms of depression or suicidal ideation
  • Nausea, vomiting, seizures, fever, headache, and/or stiff neck, as these may be symptoms of developing meningitis
  • Decreased level of consciousness, unresponsiveness or stupor
  • New muscular symptoms (e.g., muscle cramps, myalgias)
  • Withdrawal symptoms (e.g., nausea, insomnia, flu-like symptoms) as a result of abruptly discontinuing opioid therapy
  • Development of serious skin reaction (e.g., bullous dermatitis, skin ulcers, skin exfoliation)

For use only in the Medtronic SynchroMed® II Infusion System and CADD-Micro Ambulatory Infusion Pump.

Avoid drinking alcohol while you are using ziconotide.

Ziconotide can cause side effects that may impair your thinking or reactions. Avoid driving or doing anything that requires you to be awake and alert.

Your pharmacist can provide more information ziconotide.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Avoid drinking alcohol while you are using ziconotide.

Ziconotide can cause side effects that may impair your thinking or reactions. Avoid driving or doing anything that requires you to be awake and alert.

Before receiving ziconotide, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). Ziconotide can add to sleepiness caused by these other medications.

Also tell your doctor if you are taking a diuretic (water pill).

This list is not complete and there may be other drugs that can interact with ziconotide. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

• It is used to ease pain.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given into the spine.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Prialt (ziconotide) solution, intrathecal infusion is indicated for the management of severe chronic pain in adult patients for whom intrathecal therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine.

Prialt (ziconotide) solution, intrathecal infusion is supplied as a 25 mcg/mL concentration in single-use 20 mL glass vials and as a 100 mcg/mL concentration in single-use glass vials containing 1 mL or 5 mL of solution.

Cognitive and Neuropsychiatric Adverse Reactions

Severe psychiatric symptoms and neurological impairment may occur during treatment with Prialt. Prialt is contraindicated in patients with a pre-existing history of psychosis. Monitor all patients frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness. Prialt therapy can be interrupted or discontinued abruptly without evidence of withdrawal effects in the event of serious neurological or psychiatric signs or symptoms.

Events of acute psychiatric disturbances such as hallucinations (12%), paranoid reactions (3%), hostility (2%), delirium (2%), psychosis (1%), and manic reactions (0.4%) have been reported in patients treated with Prialt. Patients with pretreatment psychiatric disorders may be at an increased risk. Prialt may cause or worsen depression with the risk of suicide in susceptible patients. In placebo-controlled trials, there was a higher incidence of suicide, suicide attempts, and suicide ideations in Prialt-treated patients than in the placebo group (0.27/patient year for Prialt patients and 0.10/patient year for placebo patients).

Management of psychiatric complications may need to include discontinuation of Prialt, treatment with psychotherapeutic agents and/or short-term hospitalization. Before drug is reinitiated, careful evaluation must be performed on an individual basis.

Use of Prialt has been associated with cognitive impairment and decreased alertness/unresponsiveness. The following cognitive adverse reaction rates were reported: confusion (33%), memory impairment (22%), speech disorder (14%), aphasia (12%), thinking abnormal (8%), and amnesia (1%). Cognitive impairment may appear gradually after several weeks of treatment. Reduce the dose of Prialt or discontinue the use of Prialt if signs or symptoms of cognitive impairment develop, but other contributing causes must also be considered. The cognitive effects of Prialt are generally reversible within 2 weeks after drug discontinuation. The median time to reversal of the individual cognitive effects ranged from 3 to 15 days. The elderly (≥ 65 years of age) are at higher risk for confusion. [see Use in Specific Populations (8.5)]

There may be additive effects on cognitive impairment and decreased alertness when Prialt is used in conjunction with other CNS-depressant drugs that may necessitate dosage adjustments.

Meningitis and Other Infections

Meningitis can occur due to inadvertent contamination of the microinfusion device and other means such as CSF seeding due to hematogenous or direct spread from an infected pump pocket or catheter tract. While meningitis is rare with an internal microinfusion device and surgically-implanted catheter, the incidence increases substantially with external devices. In Prialt clinical trials, meningitis occurred in 3% (40) of patients in the Prialt group using either internal or external microinfusion devices and 1% (1 case) of patients in the placebo group.

The risk of meningitis was particularly high in patients with external microinfusion devices and catheters, occurring in 38 out of 41 patients (93%), 37 of whom received Prialt and one who received placebo.

Patients, caregivers, and healthcare providers must be particularly vigilant for the signs and symptoms of meningitis, including but not limited to fever, headache, stiff neck, altered mental status (e.g., lethargy, confusion, disorientation), nausea or vomiting, and occasionally seizures. Serious infection or meningitis can occur within 24 hours of a breach in sterility such as a disconnected catheter, the most common cause of meningitis with external microinfusion devices. The patient and health care provider must be familiar with the handling of the external microinfusion device and care of the catheter skin exit site.

Strict aseptic procedures must be used during the preparation of the Prialt solution and refilling of the microinfusion device to decrease the risk of introducing contaminants or other environmental pathogens into the reservoir. In suspected cases (especially in immuno-compromised patients) or in confirmed cases of meningitis, CSF cultures must be obtained and appropriate antibiotic therapy must be promptly instituted. Treatment of meningitis usually requires removal of the microinfusion system, catheter, and any other foreign body materials within the intrathecal space and, therefore, discontinuation of Prialt therapy.

Reduced Level of Consciousness

Patients have become unresponsive or stuporous while receiving Prialt. The incidence of unresponsiveness or stupor in clinical trials was 2% in Prialt-treated patients. During these episodes, patients sometimes appear to be conscious and breathing is not depressed. If reduced levels of consciousness occur, discontinue Prialt until the event resolves, and other etiologies (e.g., meningitis) must be considered. There is no known pharmacologic antagonist for this effect. Patients taking concomitant antiepileptics, neuroleptics, sedatives, or diuretics may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, discontinue other CNS-depressant drugs as clinically appropriate.

Elevation of Serum Creatine Kinase

In clinical studies, 40% of Prialt-treated patients had serum creatine kinase (CK) levels above the upper limit of normal (ULN), and 11% had CK levels that were greater than three times the ULN. In cases where CK was fractionated, only the muscle isoenzyme (MM) was elevated. The time to occurrence was sporadic, but the greatest incidence of CK elevation was during the first two months of treatment. One case of symptomatic myopathy with EMG findings, and two cases of acute renal failure associated with rhabdomyolysis and extreme CK elevations (17,000–27,000 IU/L) have been reported in Prialt-treated patients.

Therefore, monitor serum CK in patients undergoing treatment with Prialt periodically (e.g., every other week for the first month and monthly as appropriate thereafter). Evaluate patients clinically and obtain CK measurements in the setting of new neuromuscular symptoms (e.g., myalgias, myasthenia, muscle cramps, asthenia) or a reduction in physical activity. If these symptoms continue and CK levels remain elevated or continue to rise, reduce the dose or discontinue the use of Prialt.

Withdrawal From Opiates

Prialt is not an opiate and cannot prevent or relieve the symptoms associated with the withdrawal of opiates.

To avoid withdrawal syndrome when opiate withdrawal is necessary, do not abruptly reduce or withdraw opioid medications.

For patients being withdrawn from intrathecal opiates or intrathecal opiate infusion, gradually taper over a few weeks and replace with a pharmacologically equivalent dose of oral opiates.

Driving and Operating Machinery

Use of Prialt has been associated with cognitive impairment and decreased alertness/unresponsiveness. Therefore, caution patients against engaging in hazardous activities that require complete mental alertness or motor coordination such as operating machinery or driving a motor vehicle.

• Advise patients that psychiatric symptoms (paranoia, hostility, mania, depressive, suicidal) and cognitive symptoms (confusion, memory problems, speech disorder) may occur during treatment with Prialt. • Caution patients against engaging in hazardous activity requiring complete mental alertness or motor coordination such as operating machinery or driving a motor vehicle during treatment with Prialt. • Caution patients about possible combined effects with other CNS-depressant drugs. Dosage adjustments may be necessary when Prialt is administered with such agents because of the potentially additive effects. • Advise patients to contact a physician if the patient experiences new or worsening muscle pain, soreness, weakness with or without darkened urine. • Instruct patients and their caregivers to contact a physician immediately if the patient has any of the following ∘ A change in mental status (e.g., lethargy, confusion, disorientation, decreased alertness) ∘ A change in mood, perception (hallucinations, including unusual tactile sensations in the oral cavity) ∘ Symptoms of depression or suicidal ideation ∘ Nausea, vomiting, seizures, fever, headache, and/or stiff neck, as these may be symptoms of developing meningitis ∘ Decreased level of consciousness, unresponsiveness or stupor ∘ New muscular symptoms (e.g., muscle cramps, myalgias) ∘ Withdrawal symptoms (e.g., nausea, insomnia, flu-like symptoms) as a result of abruptly discontinuing opioid therapy ∘ Development of serious skin reaction (e.g., bullous dermatitis, skin ulcers, skin exfoliation)

For use only in the Medtronic SynchroMed® II Infusion System and CADD-Micro Ambulatory Infusion Pump.

Distributed by:

Jazz Pharmaceuticals, Inc.
Palo Alto, CA 94304

© 2013 Jazz Pharmaceuticals

Prialt® is a registered trademark of Jazz Pharmaceuticals plc or its subsidiaries

SynchroMed® is a registered trademark of Medtronic, Inc.

U.S. Patent Nos. 5,364,842; 5,795,864; and 5,891,849

Common side effects of Prialt include: abnormal gait, aphasia, asthenia, dizziness, memory impairment, speech disturbance, ataxia, hypertonia, visual disturbance, and anorexia. Other side effects include: hallucination, nystagmus, urinary retention, vertigo, abnormality in thinking, dysesthesia, fever, and paresthesia. See below for a comprehensive list of adverse effects.

Ziconotide has been assigned to pregnancy category C by the FDA. Animal studies have revealed evidence of embryolethality as evidenced by significant increases in post-implantation loss. Animal maternal toxicity has been reported to have lead to reduced fetal weighs and transient, delayed ossification of the pubic bones. There are no controlled data in human pregnancy. Ziconotide should only be given during pregnancy when benefits outweigh risks.