Acute, transitional and long-term cluster headache treatment: pharmacokinetic issues

ABSTRACT

Introduction: The cornerstones of cluster headache therapy are based on the tripod of acute, transitional and preventative treatments that respectively aim to the control of the bouts, the transitional suppression of the relapse and the prevention of the entire cluster period. Particularly in chronic cluster headache, where a long-term preventative therapy is necessary, multiple drug regimens increase the risk of drug-drug interactions leading to variability in the clinical efficacy and to potentially harmful adverse effects.

Areas covered: We focused on how clinically significant pharmacokinetic drug-drug and food-drug interactions can be carefully managed both in cluster headache patients with a progressive frequency of bouts and in chronic cluster headache sufferers. In fact, in these cases a long-term preventive therapy is indicated, increasing the possibility of interactions both with other transitional and acute cluster headache medications and with other foods or xenobiotics.

Expert opinion: Pharmacokinetic interactions for both preventive, transitional and acute drugs are significant with a number of xenobiotics and other medications. Therefore, the pharmacokinetic issues knowledge is advisable for a safe and effective cluster headache management.

KEYWORDS:

• Pharmacokinetics
• acute treatment
• drug-food interactions
• transitional therapy
• cluster headache
• drug-drug interactions
• long-term treatment

Article highlights

• Therapeutic options for CH include preventive, transitional and acute medications for the pain management.

• Long-term verapamil administration represents the first line option and is associated with pharmacokinetic drug interactions due to its affinity for P-glycoprotein and its inhibition of CYP3A4. Atorvastatin and lithium co-administration should be avoided because of the associated risk of fatal myocardial infarction or neurotoxicity. Certain citrus (especially grapefruit), excess of coffee/tea, liquorice and ethanol all have important interactions. See Table 2 for drug interactions and clinical effects.

• Lithium represents the second line option for preventive treatment because of its narrow therapeutic window. Renal pharmacokinetic interactions are significant with non-steroidal antinflammatory drugs, diuretics, angiotensin-converting enzyme inhibitors and COX inhibitors.

• Topiramate is not considered as a first line long-term therapy, likely should not exceed 100–150 mg/day, and prescribed with caution in those patients with kidney stones. Controlled clinical trials are needed to provide proof of efficacy of this drug.

• Transitional steroids allow augmentation of preventatives while inducing headache-free or near headache-free states in 70–80% of patients, and reducing potential triptans overuse. While taking steroids, avoid furanocoumarins containing foods – particularly grapefruit.

• Subcutaneous (SC) sumatriptan shows the most favourable pharmacokinetic profile compared to all the other triptans. SC sumatriptan may be effective at doses less than 4–6 mg warranting dividing single-dose vials into portions as determined to be effective.

This box summarizes key points contained in the article.

Declaration of interest

F de Andrés was supported by Instituto de Salud Carlos III-Sara Borrell program (CD13/00348). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.