By Matt Martin, PharmD, PCCA Clinical Services Manager, and Melissa Merrell Rhoads, PharmD, PCCA Director of Formulation Development

Midrin^™ was a commercially available product indicated for relief of tension and vascular headaches. The product contained a combination of acetaminophen 325 mg, which “reduces the perception of pain impulses originating from dilated cerebral vessels”; dichloralphenazone 100 mg, a mild sedative; and isometheptene mucate 65 mg, which “acts by constricting dilated cranial and cerebral arterioles, thus reducing the stimuli that lead to vascular headaches,” according to the package insert. ¹ Neither the brand-name Midrin nor any generic equivalents are currently manufactured.

In 2017, the Food and Drug Administration (FDA) notified manufacturers and labelers to stop distributing drug products that contain isometheptene mucate, one of the active ingredients found in Midrin. As of January 1, 2018, all companies manufacturing isometheptene-containing drugs had agreed to cease distribution.² Isometheptene mucate was originally approved for safety in 1948, before the current FDA drug-approval process was put in place. For this reason, the FDA considers isometheptene-containing manufactured products unapproved new drugs, requiring pharmaceutical companies to submit a new drug application and perform clinical trials proving effectiveness before these products can be manufactured again. For more information about this, read our blog article, “ Compounding Opportunity with Isometheptene Mucate USP .”

Compounding pharmacists had been able to fulfill patient needs for these therapies until recently, when dichloralphenazone became unavailable. Prescribers and patients have therefore begun looking for alternatives. Chloral hydrate and hydroxyzine HCl have been used as alternatives to dichloralphenazone for some patients.

Chloral Hydrate

Chloral Hydrate is a sedative and hypnotic agent.³ Dichloralphenazone 100 mg contains approximately 65 mg of chloral hydrate. This mathematical relationship is illustrated below:

Dichloralphenazone’s molecular weight is 519.03, and chloral hydrate’s molecular weight is 165.4.

There are two moles of chloral hydrate in each mole of dichloralphenazone.

Two moles of chloral hydrate = 2 x 165.4 = 330.8

519.03/330.8 = 100 mg dichloralphenazone/X mg chloral hydrate

X = 63.73 mg chloral hydrate, or approximately 65 mg of chloral hydrate

Hydroxyzine HCl

Hydroxyzine HCl has been considered as an option when prescribers or patients would like to avoid the use of chloral hydrate. Hydroxyzine HCl could provide a sedative effect and may help with anxiety.⁴

To assist compounding pharmacies in meeting the needs of prescribers and patients, PCCA offers isometheptene mucate , acetaminophen , chloral hydrate and hydroxyzine HCl that are USP grade, and that meet The PCCA Standard^™ above and beyond industry requirements. PCCA members with Clinical Services support can see our related capsule formulas in our formula database.

Matt Martin, PharmD, is the Clinical Services Manager at PCCA. He joined the PCCA Clinical Services department in September 2014. Matt graduated from Morehead State University with a BS in Chemistry in 2002, and received his PharmD from the University of Kentucky College of Pharmacy in 2006. Prior to joining the PCCA team, Matt worked in pharmacy compounding for more than eight years, and has experience with both sterile and nonsterile preparations.

Melissa Merrell Rhoads, PharmD, PCCA Director of Formulation Development, received her pharmacy degree from Mercer University in Atlanta, Georgia, in 1995. She currently is involved with and oversees the development and implementation of new formulas at PCCA. She had more than six years of compounding experience with pharmacies in Georgia and Florida prior to joining the PCCA staff in 2004. Her areas of interest include women’s health, veterinary and pain management compounding.

References

1. Midrin. (n.d.). RxList. Retrieved May 17, 2021, from https://www.rxlist.com/midrin-drug.htm

2. U.S. Food and Drug Administration. (2018, June 13). FDA notification regarding isometheptene-containing drug products. https://www.fda.gov/drugs/unapproved-drugs/fda-notification-regarding-isometheptene-containing-drug-products

3. Noctec. (n.d.). RxList. Retrieved May 20, 2021, from https://www.rxlist.com/noctec-drug.htm

4. Vistaril^®. (2014, May). U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/011459s048%2C011795s025lbl.pdf

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care, or encourage its abandonment.