The Hospice Clinician Blog

About six months ago, we informed you about the shortage of injectable lorazepam presentations. At the time, most back-ordered products were expected to be available by, at the latest, January 2012. However, it appears that the shortage of injectable lorazepam has gotten worse, not better, since then. According to the American Society of Health-Systems Pharmacists (ASHP) website, there are no injectable lorazepam presentations fully available – all have been discontinued or are in short supply.

Estimated release dates are as follows:

    West-Ward has Ativan injection on back order with an estimated release date of mid-May, 2012. Lorazepam 4 mg/mL 1 mL and 10 mL vials and lorazepam 2 mg/mL 1 mL vials are on back order until mid-to-late May, 2012. All other lorazepam presentations are on back order and the company cannot estimate a release date.
    Hospira has all lorazepam presentations on back order. The 4 mg/mL 1 mL Carpuject syringes have an estimated release date of 2013. Lorazepam 2 mg/mL 1 mL and 10 mL vials and 4 mg/mL 1 mL vials have an estimated release date of June, 2012. Lorazepam 4 mg/mL 10 mL vials have an estimated release date of July, 2012. Lorazepam 2 mg/mL 1 mL Carpuject syringes have an estimated release date of mid-to-late May, 2012.
    Akorn is allocating lorazepam 2 mg/mL 1 mL vials.

During the shortage, ASHP recommends using alternative injectable benzodiazepines, such as diazepam or midazolam.

Diazepam (Valium®)

    Can be given IV into a large peripheral vein, followed by a saline flush to decrease local venous irritation. The maximum IV rate is 5 mg per minute. Can NOT be given IM – absorption is erratic and unreliable.
    Has a more rapid onset than lorazepam and a similar duration of action.
    Normal maintenance dosing is in the range of 2-10 mg IV every 3-4 hours PRN. However, patients with severe anxiety, muscle spasm, or status epilepticus may require a loading dose (such as 10 mg IV x 1), followed by more frequent PRN dosing, to initially get symptoms under control.
    Diazepam is very lipid soluble, so it rapidly distributes into fat tissue, and stays there. So, while its duration of action is not very long, its half-life in the body can range from around 24 hours to more than 2 days. The half-life is prolonged in the elderly and in patients with liver disease. This means that it may take days to even weeks for diazepam to be completely cleared from the system when routine administration is stopped.

Midazolam (Versed®)

    Can be given IV or IM
    Has a more rapid onset but shorter duration of action than lorazepam. The half-life is only about 2 hours, so midazolam is frequently given by continuous infusion since it needs to be dosed so frequently.
    Midazolam dosing is very patient-specific and will need to be carefully titrated based on the patient’s response. A good starting point would be 0.25-0.5 mg IV, given slowly over 2 minutes, followed by slowly titrating to effect by repeating doses every 2-3 minutes if needed. If given intramuscularly, dosing requirements will be higher; if the patient is also taking narcotics, dosing requirements will be lower. Maintenance dosing is usually ~25% of the total dose required to reach the desired sedative effect.

For more information about the shortage, see the ASHP website at http://www.ashp.org/drugshortages/current/bulletin.aspx?id=747.

Let us know… has your hospice been impacted by the injectable lorazepam shortage?

Our hospice partners have been telling us about difficulty in obtaining oxycodone oral solution and dramatically increasing cost when available.  Several of the generic manufacturers for oxycodone solution have discontinued production recently. This is in response to FDA action starting last year to remove “unapproved drugs” from the market-place. For a variety of mostly historical reasons, some drugs, mostly older products, continue to be marketed in the United States without required FDA approval.  The FDA has expressed their concern that the lack of evidence demonstrating that these unapproved drugs are safe and effective is a significant public health concern. Many of these products have been in widespread use in the United States for decades with proven track records of efficacy and safety, however, the FDA considers all of the unapproved products to be marketed illegally and has taken action to force the manufacturers to discontinue them or apply for FDA approval.

FDA sent warning letters to several suppliers of unapproved narcotic medications (including morphine, oxycodone, and hydromorphone) last year.  These companies were given a specified time-frame to stop manufacturing new product, until they went through a formal process for approval of their products with FDA.  Wholesale distributors were instructed to stop shipping “unapproved” product.  The following manufacturers: Mallinckrodt, Lannett, and Glenmark, have stopped production of all oxycodone solutions in accordance with the unapproved drug ruling by FDA.   As far as we can tell that leaves only one manufacturer (Xanodyne Pharmaceuticals) that has an “approved” oxycodone solution product on the market. They market their product as the brand name Roxicodone and it is significantly more expensive than the discontinued “unapproved products”.    

More detailed information can be found on the FDA website at www.fda.gov.

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Best Practices for Dealing with Opioid Shortages in Hospice

Occasionally hospice and palliative care programs have to deal with shortages of medications that are essential to providing quality end-of-life care. We are reminded to remain aware of this issue as it has been a year since the major shortage of opioids affected hospices nationwide. Whether a regional or national shortage, there are some things you can do to help alleviate the problem until resolved.  

• Check with your pharmacies regularly to determine which opioids are available at which pharmacies. Availability may change frequently. This seems to vary not just from one region of the country to another but from one pharmacy to another within the same town. If your hospice has a relationship with a Pharmacy Benefit Manager, utilize their assistance and possible Mail Order options (if shortage is regional.)
• Communicate and share this current supply information among nurses and physicians to reduce problems and delays related to ordering products that are not available.
• Physicians and nurses should be prepared to convert patients from one opioid to another in the event of specific product shortages. Once again, if your hospice has a relationship with a Pharmacy Benefit Manager, utilize their pharmacist consultation services to assist.
• Have equianalgesic conversion references available to help nurses and physicians with opioid conversions.

We have included an abbreviated opioid conversion chart to help. For more information about conversion to methadone, refer to our previous blog article Methadone for Hospice Patients.

Morphine: MS-Contin, MS IR, Roxanol

Oxymorphone: Opana ER, Opana

Hydromorphone: Dilaudid

Oxycodone: Oxycontin, Oxyfast, Oxy IR, Percocet, Percodan

Methadone: Methadose

Hydrocodone: Lortab, Norco, Vicodin

Codeine: Tylenol w/ Codeine

Propoxyphene: Darvocet, Darvon

Meperidine: Demerol

Fentanyl patch: Duragesic

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