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Azithromycin side effects

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I was prescribed Azithromycin 500mg * 5 for pneumonia last Sunday. By the fourth pill (Wednesday) I realized that the drug was causing a host of side effects, including massive anxiety, insomnia, loss of appetite, and severe cramping. Thursday was my first day off the pills. Many of the side effects are gone but the anxiety and insomnia remain. I realize that this drug has a long half life and that I still have quite a bit of it in my system. Here's my question: Is it normal for side effects to continue as long as the drug is in your system even though I discontinued it 4 days ago?

Category: Neurologist, Medical

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Category: Pediatric Neurologist
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Thank you for choosing DoctorSpring.

Since the side effects you are experiencing are neuro psychiatric in nature (anxiety and insomnia) it is possible that medication (Azithromycin) triggered these symptoms, which is now persisting (rather than due to continued effect of the drug in the body).

Or in simpler words , Azithromycin initiated it. The drug per se is eliminated from the body. But the anxiety and insomnia is persisting from that trigger.

This should resolve by its own in less than a week. No active interventions are needed now. However do try to stay active with your friends and family. Avoid caffeine and sleep at regular timings.

Azithromycin is a safe drug and very rarely causes these neuro psychiatric symptoms . Still since your symptoms are all corresponding to the drug intake we can assume that these are indeed medication side effects.

Hope this helps
Feel free to ask followups
Thank you

Patient replied :

Thanks for the quick reply, although it reflects a degree of haste that is frustrating given that I paid for the answer. If you research Azithromycin, you quickly realize that it has a half-life of 68 hours; that's obviously why it is such an effective short-run antibiotic - it stays in the system for a long time. Also, if you research for this drug, you learn that neurological side effects are extremely common with this medication, including the very symptoms I describe (indeed, anxiety and insomnia are the most common complaints for low-scoring patients).

Assuming I had 1500 mg in my system when I took the last pill, on a three-day half-life, it will take approximately 15 days for the drug to be eliminated (this is why I do not like your answer). As long as the drug is in me, if follows that it can generate side the point of my question.

Anyway, I knew the answer before I asked but was looking for validation from a knowledgeable source. No reply is necessary.


I understand you do not wish a reply, but still I would like to clarify my part. Kindly refer for reference. This is a world wide trusted database. Wesbites like askpatinet are not trustable in opinion.

Issue 1 : Side effects like Insomnia and Anxiety is indeed very very rare with Azithromycin usage. The reported rate is less that 1% .

Ref : (for both points)

Foulds G, Shepard RM, and Johnson RB, “The Pharmacokinetics of Azithromycin in Human Serum and Tissues,” J Antimicrob Chemother , 1990, 25(Suppl A):73-82.[PubMed 2154441 ]
Centers for Disease Control and Prevention (CDC), "Update to CDC's Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections”, MMWR Morb Mortal Wkly Rep , 2012, 61(31):590-4. [PubMed 22874837 ]
Coates P, Daniel R, Houston AC, et al, “An Open Study to Compare the Pharmacokinetics, Safety, and Tolerability of a Multiple-Dose Regimen of Azithromycin in Young and Elderly Volunteers,” Eur J Clin Microbiol Infect Dis , 1991, 10(10):850-2. [PubMed 1662630 ]
Foulds G, Shepard RM, and Johnson RB, “The Pharmacokinetics of Azithromycin in Human Serum and Tissues,” J Antimicrob Chemother , 1990, 25(Suppl A):73-82.[PubMed 2154441 ]
Ghanem KG and Workowski KA, “Management of Adult Syphilis,” Clin Infect Dis , 2011, 53(Suppl 3):110-28. [PubMed 22080265 ]
Guay DR, “Pharmacokinetics of the New Macrolides,” Infect Med , 1992, 9:9-13.
Heintz BH, Matzke GR, Dager WE, “Antimicrobial Dosing Concepts and Recommendations for Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis,” Pharmacotherapy , 2009, 29(5):562-77. [PubMed 19397464 ]

Adverse Reactions Significant

>10%: Gastrointestinal: Diarrhea (4% to 9%; high single-dose regimens 12% to 14%), nausea (=7%; high single-dose regimens 18%)

2% to 10%:

Dermatologic: Pruritus, rash

Gastrointestinal: Abdominal pain, anorexia, cramping, vomiting (especially with high single-dose regimens)

Genitourinary: Vaginitis

Local: (with I.V. administration): Injection site pain, inflammation

=1% (Limited to important or life-threatening): Acute renal failure, aggressive behavior agitation, allergic reaction, anaphylaxis, anemia, angioedema, anxiety, arrhythmia (including ventricular tachycardia), arthralgia, bronchospasm, candidiasis, chest pain, cholestatic jaundice, conjunctivitis (pediatric patients), constipation, cough increased, deafness, dehydration, dermatitis (fungal), diaphoresis, dizziness, dyspepsia, eczema, edema, enteritis, erythema multiforme (rare), facial edema, fatigue fever, flatulence, fungal infection, gastritis, headache, hearing disturbance, hearing loss, hepatic failure, hepatic necrosis, hepatitis, hyperactivity, hyperkinesia, hypotension, insomnia, interstitial nephritis, jaundice, leukopenia, LFTs increased, loss of smell, loss of taste, malaise, melena, mucositis, nephritis, nervousness, neutropenia (mild), oral candidiasis, oral moniliasis, pain, palpitation, pancreatitis, paresthesia, pharyngitis, photosensitivity, pleural effusion, pseudomembranous colitis, pyloric stenosis, QT c prolongation (rare), rhinitis, seizure, smell perversion, somnolence, somnolence, Stevens-Johnson syndrome (rare), syncope, taste perversion, thrombocytopenia, tinnitus, tongue discoloration (rare), torsade de pointes (rare), toxic epidermal necrolysis (rare), urticaria, vertigo, vesiculobullous rash, weakness

Contraindications Hypersensitivity to azithromycin, other macrolide (eg, azalide or ketolide) antibiotics, or any component of the formulation; history of cholestatic jaundice/hepatic dysfunction associated with prior azithromycin use

Issue 2 : It is well know than Azithromycin has got a longer half life. But by day 4 the levels will come below threshold levels to induce side effects. I would have agreed to your argument had your other side effects stayed same. (loss of appetite , cramping etc). How come they disappeared and few of the side effects remained ? This proves that the drug levels indeed had gone down and the triggered insomnia and anxiety is persisting.

Hope this clarifies.

Patient replied :

Thank you for the informative answer sir, and I certainly apologize if I offended you. This does clarify and is very interesting. I had several of the 1% symptoms (still do including cramping and appetite issues, just not as intense). I fully expect the symptoms to subside as the drug runs its course. Of all the drugs for me to react to, it had to be one with a long half-life! :) Take care and thank you for what you do.

No issues! Glad that your symptoms are coming down.
Wish you a speedy recovery.
Thank you

Dr. Sudhir Kumar
Category: Pediatric Neurologist
Senior Residency, Fellowship: DM, Neurology, CMC, Vellore, 2001
Junior Residency: MD, Internal Medicine, CMC, Vellore, 1998
Medical School: MBBS, Christian Medical College, Vellore, 1995
Dr. Sudhir Kumar and 4 other Medical Specialists are ready to help you

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