Segelnickftr2.qxd

Doxycycline-induced Dizziness in Dental Patient Stuart L. Segelnick, D.D.S., M.S.; Mea A. Weinberg, D.M.D., R.Ph., M.S.D. Abstract
The etiology of doxycycline-induced dizziness is complex, sub- Many dentists are unaware of the documented adverse jective and relatively unclear. This adverse drug reaction mayhave a higher incidence than documented in the literature.
drug reaction of doxycycline: induced dizziness. Because Additionally, dentists prescribing tetracyclines, including doxy- doxycycline is frequently prescribed in dentistry, it is cycline and minocycline, should be aware of a condition ofincreased intracranial pressure and pay particular attention to a important for dentists and patients to be aware of this sig- patient who complains of developing a new headache, dizziness nificant adverse reaction to prevent medical complica- tions. A clinical case is reported in which a patient developed Doxycycline hyclate is indicated in the adjunctive treatment of aggressive periodontal infections in which Aggregatibacter actino- dizziness after taking doxycycline that was prescribed fol- mycetemcomitans (formerly known as Actinobacillus actino- lowing periodontal surgery. The dizziness resolved when mycetemcomitans) is often the causative pathogen that invades the the doxycycline was stopped. Patients and dentists epithelium and connective tissue, eluding mechanical debride-ment.1 Doxycycline and minocycline are semisynthetic analogs of should be educated to recognize the signs and symptoms tetracycline HCl. Doxycycline is available in two salt forms.
● Doxycycline monohydrate is used primarily in the treatment of DIZZINESS is a subjective feeling that is often difficult to quantify.
● Doxycycline hyclate is used as an antibiotic and as an anticol- The causes of dizziness are multifactorial and include high blood lagenase, nonantimicrobial agent for the treatment of chronic pressure, multiple medications (e.g., antihypertensives and nar- cotics). Different medical conditions are associated with dizziness, Dentists should be aware of a particular adverse drug reaction, including vertigo, low glycemic level and ear problems. Because whereby doxycycline can induce dizziness when it is taken system- dizziness can be a serious problem, we propose through this article ically in the adjunctive treatment of periodontal infections. We to help dentists understand how patients could develop dizziness highlight the clinical presentation of a patient with doxycycline- induced dizziness and discuss the etiology, signs and symptoms.
Case Report
A 58-year-old Caucasian male presented for regenerative periodon-
tal therapy in November 2008. The patient was not taking any over-
the-counter drugs, prescription drugs or neutraceuticals. The sur-
gical area encompassed teeth #13 through #15. Full thickness flaps
were elevated after 2% lidocaine with 1:100,000 epinephrine was
utilized for local anesthesia.
After scaling and root planing and osseous resection, bone grafts were placed into the remaining two wall osseous defects by#14 and #15. Four 4-0 silk sutures and Coe-Pak were placed.
Hemostasis was achieved. Postoperatively, the patient was given aprescription for doxycycline hyclate 100mg capsules for 10 days:200 mg loading dose (taken in the evening) followed by 100 mgevery morning and ibuprofen 600 mg (one tablet every four to sixhours when needed for pain).3 The patient was given both verbaland written instructions on the proper use of doxycycline. This reg-imen for doxycycline is indicated for both dental and medical infec-tions.4-8 The patient called the office four days later to report that he had arrived home the night of the surgery and took his doxycyclineas directed. However, he didn’t take any of the ibuprofen because hefelt it wasn’t necessary.At 4 a.m. the next day, he got up from his bedto use the bathroom. He felt dizzy and passed out. He bumped hishead and was taken to the hospital with no memory of everfalling—there is only one other case report documenting amnesia,which occurred after a sudden onset of a headache following theingestion of 200 mg of doxycycline.9 The computed tomography (CT) scan was negative and the patient was sent home. He was instructed by the physician to con-tinue taking his medications. The following morning when he gotup from bed, he felt dizzy again, but he got up carefully and slowly.
The patient returned to the office eight days after surgery for postoperative suture and pack removal. Healing was uneventful.
The patient’s blood pressure was taken and was 128/78 with a pulseof 71. He reported getting dizzy spells when he awoke, but the dizzi-ness quickly passed when he rose. It was recommended that thepatient stop taking the antibiotic, and he was referred to his physi-cian for evaluation. The patient reported in a subsequent interviewand again when he returned for his three-month periodontal main-tenance appointment that the dizziness disappeared after hestopped taking the doxycycline.
Discussion
Antibiotic-induced adverse drug reactions play a pivotal role in the
overall health care of the patient, including increased office and
hospital costs for treatment.10 Reducing the incidence of adverse
reactions starts with clinician and patient education.
Table 1 lists adverse reactions to doxycycline according to body systems. Sometimes the patient may experience an adverse reactionand neither the patient nor the dentist attributes it to the drug itselfbut rather to a medical condition. For example, doxycycline pre-scribed by the dentist has been documented to cause esophageal ulcers. The symptoms of a sore throat and odynophagia (difficulty in swallowing) experienced by the patient may not be thought to be caused by the drug itself. The patient, however, believes he or she isexperiencing a possible cold and usually reports the symptoms CNS: dizziness, headache, intracranial hypertension, visual changes.
directly to the physician rather than to the treating dentist.3 CV: pericarditis.
One central nervous system adverse reaction that has been DERM: photosensitivity reactions (exaggerated sunburn), skin rash,
reported occasionally in the medical literature but not in the dental literature is doxycycline-induced dizziness.11-13 Thus, it should be ENDOCRINE: brown/black discoloration of thyroid gland (no dysfunction),
noted that the dosing of doxycycline in some medical studies may not be the same as what is required for dental infections. The usual GI: nausea, vomiting, diarrhea, abdominal pain, esophageal ulcers, dys-
dosage of oral doxycycline is 100 mg every 12 hours on the first day, pepsia, psuedomembranous colitis (due to Clostridium difficle), anorexia.
then 100 mg a day as a single dose (maximum is 100 mg every 12 HEMATOLOGIC: hemolytic anemia, neutrophenia, thrombocytopenia,
A clinical medical study compared adverse reactions following HEPATIC: hepatotoxicity.
administration of either minocycline (100 mg at bedtime for 7 HYPERSENSITIVITY REACTIONS: urticaria, anaphylaxis.
days) or doxycycline (100 mg twice daily for 7 days) to patients. It ORAL: tooth discoloration, black hairy tongue (candidiasis), taste
must be noted that only medical references are included in this alterations, increased thirst, sore throat, odynophagia (painful article, because there are no documented dental studies. Results indicated that the most significant adverse effect was gastrointesti- RENAL: rise in BUN (blood urea nitrogen) levels.
nal upset, dizziness, nausea, vomiting, abdominal pain or cramps,diarrhea, dyspepsia, increased flatulence and taste alteration.13Vomiting alone (P = 0.004) or any gastrointestinal upset, includingvomiting (P < 0.001), occurred significantly more often in thedoxycycline group.
The occurrence of dizziness (P > 0.1) or other adverse effects did not differ between the two groups. However, when adverseeffects were examined by drug regimen and gender, significance Stop taking medication if dizziness, sudden onset of new headache or was again shown. Men and women who were administered doxycy- disturbance in vision occurs. Notify dentist and physician immediately.
cline reported side effects more frequently than those in the Slowly get up from sitting position to avoid dizziness.
minocycline group. Dizziness was reported in 9% of the patients: Doxycycline should be taken on empty stomach, one hour before and two hours after eating; however, if there is GI upset, take it Patient instructions on taking doxycycline should be both verbal and written. Table 2 lists important points that must be discussed Do not take concurrently with any antacid product that contains alu- with the patient, including how and when to take the medication minum, bismuth salts, calcium and magnesium or any other product and what signs and symptoms could be expected.
containing zinc or iron. Wait two hours before or after when con- The dizziness experienced in our patient may be related to a medical condition referred to as pseudotumor cerebri (PTC), also It is recommended to avoid intake of dairy products, due to a 20%- known as intracranial hypertension,which is a self-limiting condition 30% decrease in doxycycline absorption.
that causes elevated intracranial pressure.14,15 It has been reported to Doxycycline should be taken with full glass of water and in upright be caused by medications used to treat skin disorders, including position to reduce risk of esophageal ulcers and irritation.
tetracyclines (minocycline, doxycycline), retinoids and corticos- teroids.16-18 This condition commonly causes throbbing headache, Do not lie down for at least two hours after taking dose of doxycycline.
blurred vision, vision loss, nausea, vomiting and dizziness. In most If experiencing swallowing difficulties or chest pain, patient should cases, the symptoms improve when doxycycline is stopped.
notify dentist or physician immediately.
Although all tetracyclines (tetracycline HCl, doxycycline and Avoid exposure to direct sunlight and ultraviolet light during and for minocycline) are implicated in PTC, doxycycline is the least report- four to five days after discontinuing therapy. Sunscreens provide lit- ed probably because the “older” documented literature is on tle protection against phototoxicity.
patients with acne, in which doxycycline is usually not prescribed.17 Use of doxycycline may make oral contraceptives less effective; Additionally, there is a 27.3% incidence of headache after locally advise using alternative birth control methods.
applied doxycycline (Atridox) and a 9% incidence after minocy- Use of doxycycline might increase incidence of vaginal candidiasis.
cline and scaling (Arestin).19,20 There are no published studies that Notify physician and dentist immediately if diarrhea occurs.
show these headaches have any association with PTC.
Figure1. Pseudotumor
cerebri finding of disc
Diagnosis of intracranial hypertension is based on physical examina- tion, neuroimaging and lumbar puncture. The only neurologic sign is ophthalmologist viewingback of eye.34 Optic disc is raised intracranial pressure. Otherwise, the computed tomography (CT scan) and magnetic resonance imaging (MRI) are normal, which is a leave eye to form opticnerve. Swelling of disc finding in patients with PTC.17,18 This may lead to permanent damage of the optic nerve and associated decrease in vision.There are ophthalmo- logic changes with the development of papilloedema, which is swellingof the optic disc caused by increased intracranial pressure18,21 (Figure 1).
It is not well known how soon after starting the drug doxycy- cline-induced PTC develops, but it can show up within two weeks18,22and may be related to dosage.23 However, because the exact etiology The cause of doxycycline-induced PTC is relatively unknown; how- of doxycycline-induced PTC is relatively unclear, it cannot be ruled ever, one proposed mechanism by which doxycycline causes out even at lower dosages; therefore, the patient should still be mon- intracranial hypertension may include interference with the ener- itored for it.23 Thus, even at subantimicrobial doses of 20 mg, there gy-dependent absorption mechanism by affecting cyclic adenosine could be an increased incidence of this adverse effect, although it monophosphate (cAMP, a messenger important in many biological has never been documented. Additionally, since the locally applied processes that is synthesized from ATP) at the arachnoid granula- minocycyline and doxycycline products may be absorbed systemi- tions,18,20 which are small projections of the arachnoid (membrane cally, dizziness is also plausible. The dentist should not dismiss a covering the brain) into the venous sinuses of the brain, which per- patient’s complaint of a newly developed headache, dizziness or mit cerebrospinal spinal fluid to exit the brain.
visual disturbance, such as blurred vision. If PTC is suspected, the Idiopathic, non-medication-induced pseudotumor cerebri patient should be referred to a neurologist and ophthalmologist.
most frequently occur in obese women in their 30s and 40s.
Treatment involves terminating the tetracycline with resolution of However, tetracycline usage should be considered as the etiologic the intracranial hypertension over two to four weeks.24 Early diag- agent in patients with signs and symptoms of PTC who are not nosis by the dentist is important. The outcome of treatment is good obese and can be male or female and any age group.16,17 if PTC is recognized early to prevent permanent visual loss.17 The patient should be questioned as to when the symptoms appeared in relation to taking the tetracycline. It must be deter- 1. Renvert S, Wikström M, Dahlén G, Slots J, Egelberg J. On the inability of root debride- ment and periodontal surgery to eliminate Actinobacillus actinomycetemcomitans from mined if the dizziness is originating from the disease or infection periodontal pockets. J Clin Periodontol 1990;17(6):351–355.
that patient has or from the doxycycline that is being used to treat 2. Suomalainen K, Sorsa T, Golub LM, Ramamurthy N, Lee HM, Uitto VJ, Saari H, Konttinen YT. Specificity of the anticollagenase action of tetracyclines: relevance to their the condition. For example, one of the symptoms of Lyme disease anti-inflammatory potential. Antimicrob Agents and Chemother 1992;36(1):227-229.
from a tick bite is dizziness and doxycycline is also used to treat the 3. Segelnick SL,Weinberg MA. Recognizing doxycycline-induced esophageal ulcers in den- tal practice. J Am Dent Assoc 2008;139(5):581-585.
disease.12 Dentists prescribing tetracyclines, including doxycycline 4. Summary of antibiotic treatments in adults http://www.mims.co.uk/news/882429/ and minocycline, should be aware of the condition of increased Summary-Antibiotic-Treatments-Adults/ Accessed July 13, 2009.
intracranial hypertension (pseudotumor cerebri) and pay particu- 5. Kulkarni GV, Lee WK, Aitken S, Birek P, McCulloch CA. A randomized, placebo-con- trolled trial of doxycycline: effect on the microflora of recurrent periodontitis lesions in lar attention to a patient who complains of a new headache, dizzi- high risk patients. J Periodontol 1991;62(3):197-202.
ness or blurred vision. Increased intracranial pressure can lead to 6. Ng VW, Bissada NF. Clinical evaluation of systemic doxycycline and ibuprofen administra- tion as an adjunctive treatment for adult periodontitis. J Periodontol 1998;69(7):772-776.
progressive visual impairment and blindness in 4% to 12% of 7. NI antimicrobial guidelines for primary care http://www.dhsspsni.gov.uk/antimicro- patients.21Thus, once the diagnosis of PTC is suspected, immediate bial_guidelines_for_primary_care_november_2008.pdf Accessed July 13, 2009.
8. Walker C, Karpinia K. Rationale for antibiotic use in periodontics. J Periodontol therapy should be started to prevent visual damage.21 Additionally, doxycycline should be prescribed with caution to 9. Heveling T, Kubalek R. Doxycycline-induced amnesia. A case report. Eur J Clin women of childbearing age who are overweight or have a history of 10. Gleckman RA,Czachor JS.Antibiotic side effects.Semin Respir Crit Care Med 2000;21(1):53-60.
11. Dotevall L, Hagberg L. Adverse effects of minocycline versus doxycycline in the treat- Furthermore, dizziness or lightheadedness can be a symptom ment of Lyme Neuroborreliosis. Clin Infect Dis 2000;30:410-411.
12. Phimda K, Hoontrakul S, Suttinont C, Chareonwat S, Osuwanaluk K, Suwancharoen D, of orthostatic hypotension. In our case, physicians ruled out ortho- Silpasakorn S, Saisongkorh W, Peacock SJ, Day NP, Suputtamongkol Y. Doxycycline ver- static hypotension (also referred to as postural hypotension), which sus azithromycin for the treatment of leptospirosis and scrub typhus.Antimicrob AgentsChemother 2007;51(9):3259-3263.
occurs when there is a rapid lowering in blood pressure upon 13. Romanowski B, Talbot H, Stadnyk M, Kowalchuk P, Bowie WR. Minocycline compared assuming an upright position. It is characterized by a decrease in with doxycycline in the treatment of nongonoccal urethritis and mucopurulent cervici-tis. Ann Intern Med 1993;119(1):16-22.
systolic blood pressure of 20/10 mmHG and a decrease in diastolic 14. Ang ER, Zimmerman TC, Malkin E. Pseudotumor cerebri secondary to minocycline blood pressure of 10 mmHG within three minutes of standing.25 intake. J Am Board Fam Pract 2002;15(3):229-233.
15. Starling J III, Koo J. Evidence based or theoretical concern? Pseudotumor cerebri and Generally, the use of systemic antibiotics should not be consid- depression and as acitretin side effects. J Drug Dermatol 2005;4:690-696.
ered as the sole therapy in clinical dentistry and should be used 16. Friedman DI. Medication-induced intracranial hypertension in Dermatology. Am J Clin adjunctively. The authors agree with many clinical studies26-29 that 17. Friedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial hypertension.
showed that improved clinical outcomes often do not result from the use of antibiotics. Thus, antibiotics may not be necessary for 18. Diegre KB. Not so benign intracranial hypertension. Br Med J 2003;22;326:613-614.
19. Atridox package insert http://atridox.com/wrap/files/AtridoxPackageInsert/data routine periodontal and oral surgical procedures. However, antibi- otics can be considered as part of pre- or postsurgical therapy when 20. Arestin is safe and well tolerated in clinical trials.http://www.myarestin.com/why- arestin—safety-profile.html. Accessed July 13, 2009.
periodontal osseous or soft-tissue grafts are placed because these 21. Pierog SH, Al-Salihi FL, Cinotti D. Pseudotumor cerebri-A complication of tetracycline newly placed grafts have not yet established a blood supply (revas- treatment of acne. J Adolesc Health Care 1986;7;139-140.
22. Chiu AM, Chuenkongkaew WL, Cornblath WT, et al. Minocycline treatment and pseudo- cularization) with the host bone or tissue.30 Until a blood supply is tumor cerebri syndrome. Am J Ophthalmol 1998;126:116-121.
established with inflammatory cells that may reduce the incidence 23. Tabibian JH, Gutierrez MA. Doxycycline-induced pseudotumor cerebri. J S Med Assoc for infection, an antibiotic regimen may be enforced.
24. Lochhead J,Elston SK.Doxycycline induced intracranial hypertension.Br Med J 2003;326:641-642.
The dizziness experienced by the patient in this report may 25. Fessel J, Robertson D. Orthostatic hypertension: when pressor reflexes overcompensate.
have been due to the stress of the surgery. Stress has been shown to 26. Pendrill K, Reddy J. The use of prophylactic penicillin in periodontal surgery. J cause and exacerbate dizziness.31 However, there is very little litera- ture on the subject and none that we could find pertaining to peri- 27. Powell CA, Mealy BL, Deas DE, McDonnell HT, Moritz AJ. Postsurgical infections: preva- lence associated with various periodontal surgical procedures. J Periodontol 28. Happonen RP, Bäckström AC,Ylipaavalniemi P. Prophylactic use of phenoxymethylpeni- cillin and tinidazole in mandibular third molar surgery, a comparative placebo con- Conclusion
trolled clinical trial. Br J Oral Maxillofac Surg 1990;28(3):12-15.
The dentist and patient must be aware that dizziness may be a rel- 29. Poeschl P. Postoperative prophylactic antibiotic treatment in third molar surgery: neces- atively common but, possibly, not properly reported complication sity? J Oral Maxillofac Surg 1990; 62(1):3-8.
30. Guiha R, El Khodeiry S, Mota L, Caffesse R. Histological evaluation of healing and revas- of doxycycline. Besides discontinuing the offending tetracycline, cularization of the subepithelial connective tissue graft. J Periodontol 2001;72(4);470-478.
another tetracycline should not be prescribed, including suban- 31. Andersson G, Yardley L. Time-series analysis of the relationship between dizziness and stress. Scand J Psychol 2000;41:49-54.
timicrobial doses of 20 mg doxycycline. If PTC is suspected, the 32. Wynn RL, Meiller TF, Crossley HL. Drug Information Handbook for Dentistry. 13th ed.
patient should be taken off the doxycycline and referral to a neu- 2007-2008. Hudson (Cleveland): Lexi-Comp. 2008:542.
33. Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clin rologist or ophthalmologist may be necessary. ■ 34. The North American Neuro-Ophthalmology Society (NANOS): Pseudotumor Cerebri.
http://www.nanosweb.org/patien_info/brochures/PseudotumorCerebri.asp. Accessed Queries about this article can be sent to Dr. Segelnick at EperioDr@aol.com.

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