P&T News: March 1996, Vol. 16, No. 9
Jane C. Blayney, Pharm.D.
Peer Review Status: Internally Peer Reviewed by Sue A.
Barcellos, M.D., Assistant Professor, Director of the Headache
Clinic, Department of Neurology
Safety: Prescribing Cautions
The development of sumatriptan was based upon the concept that a
selective serotonin receptor agonist may provide a clinically
effective means of treating patients with migraine headache. Studies
have clearly demonstrated that key therapies in the acute attack of
migraine (i.e., dihydroergotamine, ergotamine, and sumatriptan) share
the common pharmacologic activity of serotonin receptor agonism.
There is evidence to suggest that the site of action of sumatriptan
is at the level of the blood vessel wall, as sumatriptan is a potent
constrictor of certain cranial blood vessels in vitro. Sumatriptan
may also alleviate migraine pain by blocking the release of
proinflammatory neurotransmitters at the level of the nerve terminal
in the perivascular space.6,9
Because of sumatriptan's ability to constrict blood vessels, sumatriptan may also precipitate coronary vasospasm.10 Serious coronary events, including some that have been fatal, have occurred.6 In extensive worldwide postmarketing experience, deaths have been reported following the use of both injectable and oral sumatriptan.4,5 In most cases, these have occurred several hours (i.e., 3 or more hours) after sumatriptan use, and probably reflect underlying disease and spontaneous events. However, there have been several fatalities that occurred within a few hours after sumatriptan use.4 The specific contribution of sumatriptan to most of these deaths cannot be determined. In one case, a 41-year-old woman with a six-day history of unilateral headache, uncertain history of cardiovascular disease with known risk factors (positive family history, postmenopausal, and smoking), and a history of asthma and codeine allergy, experienced nausea, vomiting, a sense of warmth, chest pressure, and sweating within seven minutes of dosing with sumatriptan injection.4 These symptoms were followed by hypotension after one-half hour, and then ventricular tachycardia/fibrillation leading to death. Another patient who injected herself with sumatriptan subcutaneously for cluster headache had chest pain after the first and second injections (one day apart). With a third injection one week later, she developed an acute myocardial infarction.6
In a study by Brown et al, patients were given a 10-minute intravenous infusion of sumatriptan during a planned coronary angiography.10 Intravenous sumatriptan appeared to cause a modest constriction of coronary arteries in patients with preexisting coronary artery disease or coronary artery spasm.
Because of the risks associated with sumatriptan use, it should only be used where a clear diagnosis of migraine has been established. The risks and benefits should thoroughly be assessed before sumatriptan is prescribed for patients in whom unrecognized coronary artery disease is likely without a prior evaluation for underlying cardiovascular disease.4,5 Table 1 1ists contraindications and precautions to sumatriptan use. It is recommended that the first dose of sumatriptan be given in a physician's office for patients with underlying coronary artery disease (CAD) risk factors.
Deaths attributed to strokes, cerebral hemorrhage, and other cerebrovascular events have also been reported in patients treated with sumatriptan.4,5 In many cases it appears possible that the cerebrovascular events were primary in origin, with sumatriptan administered in the incorrect belief that the symptoms experienced were migrainous. Accordingly, it is important to advise patients not to administer sumatriptan if the headache being experienced is atypical.
|
Table 1. Contraindications/Precautions for the Use of Sumatriptan4,5 |
|
Absolute Contraindications
Relative Contraindications
|
Other Adverse Reactions
The most common adverse reaction is pain at the injection site. Other
common adverse events include atypical sensations (such as tingling,
pressure sensations), flushing, chest discomfort, weakness,
dizziness, and vertigo. There have been rare reports of seizure
following administration of sumatriptan. Table 2 provides a
comparison of adverse events for sumatriptan given by the
subcutaneous versus the ora1 route. Of note, the incidence of
tingling, feeling of warmth, heaviness, flushing, and pressure
sensations appear to be higher following subcutaneous treatment
versus therapy with the oral formulation.10
The adverse effects of the oral formulation of sumatriptan are dose-related. In one double-blind, parallel-group study of 1130 migraineurs, headache relief occurred within two hours in 67%, 73%, and 67% of patients treated with sumatriptan 100 ma, 200 ma, and 300 mg respectively, compared with 27 % of patients treated with placebo. Although efficacy did not improve with increasing dose, the incidence of adverse events did. Adverse events were experienced by 36%, 47%, and 53% of patients treated with sumatriptan 100 ma, 200 ma, and 300 ma, respectively, compared with 17 % of patients treated with placebo. 11
|
Table 2. Sumatriptan Adverse Events[12] | ||||
|
Adverse Event |
Percent of Patients Reporting | |||
|
Subcutaneous |
Oral | |||
|
6 mg |
25 mg |
50 mg |
100 mg | |
|
Atypical Sensations* |
42.0% |
|
|
|
|
Feeling of heaviness |
7.3 % |
less than 1 % |
less than 1 % |
2 % |
|
Feeling of tightness |
5.1 % |
less than 1 % |
2 % |
2 % |
|
Pressure sensation |
7.1 % |
less than 1 % |
2 % |
2 % |
|
Tingling |
13.5 % |
0 |
4 % |
5 % |
|
Warm/Hot sensations |
10.8 % |
2 % |
3 % |
3 % |
|
Cardiovascular |
|
|
|
|
|
Flushing |
6.6 % |
0 % |
4 % |
2 % |
|
Palpitations |
--- |
0 % |
less than 1 % |
2 % |
|
Chest discomfort |
4.5 % |
--- |
--- |
--- |
|
Musculoskeletal |
|
|
|
|
|
Weakness |
4.9 % |
2 % |
less than 1 % |
2 % |
|
Neurological |
|
|
|
|
|
Dizzienss/vertigo |
11.9 % |
less than 0.1 % |
less than 0.1 % |
less than 0.1 % |
|
Drowsiness/sedation |
2.7 % |
less than 0.1 % |
less than 0.1 % |
less than 0.1 % |
|
Miscellaneous |
|
|
|
|
|
Injection site reaction |
58.6 % |
NA |
NA |
NA |
|
NA = Not Applicable | ||||
Dosing
Oral sumatriptan is marketed in 25 mg and 50 mg tablets. The initial
dose is a single 25 mg tablet taken with fluids. If a satisfactory
response has not been obtained within two hours, a second dose of up
to 100 mg may be given.l3 If headache returns, additional doses may
be taken at intervals of at least two hours, up to a maximum daily
dose of 300 ma. It is important during repeated dosing to use the
lowest effective dose in order to reduce the incidence of adverse
reactions. Patients with liver dysfunction should receive a maximum
single dose not exceeding 50 ma. Table 3 lists the dosing for both
the oral and injectable forms of sumatriptan. Unlike other
antimigraine drugs, such as ergotamine, that are considered to be
effective only if given early in an attack, sumatriptan is also
effective when given late.2
|
Table 3. Dosing Guidelines for Sumatriptan4,5,13 |
|
Subcutaneous:
Oral:
|
Conclusion
Sumatriptan represents a unique therapeutic option for the acute
treatment of migraine attacks with or without aura. Administered
subcutaneously, sumatriptan alleviates headache in approximately 80%
of patients within 2 hours of dosing. About 70% (range 56% to 78%) of
patients treated with oral sumatriptan 100 mg experienced relief of
headache and associated symptoms within 2 to 4 hours. With the
release of oral sumatriptan this year, it is likely that more
patients will be prescribed sumatriptan therapy due to the increased
ease of oral administration over the injectable form. However, the
risks and benefits must also be thoroughly assessed before oral
sumatriptan is prescribed, particularly for patients in whom
unrecognized CAD is likely without a prior evaluation for underlying
cardiovascular disease. Chest pain and atypical sensations occur less
frequently with the oral formulation; however, the incidence of
coronary events are similar. Also, the dosing of oral sumatriptan is
complex and it is important to counsel patients to use the lowest
effective dose and minimize the number of repeat doses in order to
reduce the incidence of adverse reactions.
References
Pharmacokinetic data show that at 24 hours the serum blood level of ceftriaxone still exceeds the MIC90 of susceptible organisms. Ceftriaxone should be utilized in adult dosing at 1 gram "once daily" until culture and sensitivity results allow the clinician to switch to a less expensive antibiotic with a narrower spectrum of activity. Higher doses, 2 grams q24 hours, should be reserved for:
1) Sites of infection which would exhibit poor penetration (e.g., gram-negative meningitis, gram-negative endocarditis, deep abscesses).
2) Patients weighing more than 250 lbs.
Pharmacokinetic Features
References
Drugs Added to Stock
ALENDRONATE Tablets: 10mg and 40 mg Alendronate (Fosamax[R] - Merck) is an aminobiphosphonate that inhibits osteoclast-mediated bone resorption. It is indicated for the treatment of osteoporosis in post-menopausal women (10 mg per day) and the treatment of Paget's disease of bone (40 mg per day).
TRETINOIN Capsules: 10 mg Tretinoin (all-trans-retinoic acid, Vesanoid[R] - Roche) is indicated
for the induction of remission in patients with acute promyelocytic leukemia.
Additional Actions
The following additional strengths of products already stocked have been added:
Goserelin Acetate (Zoladex[R] - Zeneca) 10.8 mg injection Note: This three-month depot injection is indicated for the management of prostatic cancer.
Oxycodone 5 mg Immediate-Release Capsules
Oxycodone (OxyContin[R] - Purdue) 10 ma, 20 ma, and 40 mg
Sustained-Release Tablets
Drugs Deleted From Stock
ETHYL CHLORIDE SKIN REFRIGERANT SPRAY Deleted due to safety concerns. Fluori-Methane[R] skin refrigerant spray is available.