Is there an incidence of tinnitus with amlodipine or losartan?

Comment by InpharmD Researcher

The prescribing information for both amlodipine and losartan lists tinnitus as an adverse event, with a low prevalence rate (between 0.1% to 1% for amlodipine and <2% for losartan). The available literature, however, provides somewhat conflicting data. Consensus guidance based on European pharmacovigilance reporting categorized both agents as associated with reports of drug-induced tinnitus; losartan is classified as having a more common prevalence rate at 1-10%, while a prevalence rate for amlodipine is not provided. However, primary studies that have reported on antihypertensive agents in patients who develop tinnitus have suggested that calcium channel blockers are more associated with tinnitus and angiotensin receptor blockers are less associated with tinnitus. Given this discrepancy, clinicians should carefully weigh the benefits of treatment with either amlodipine or losartan with the risk of ototoxicity, in the context of other potential ototoxic concomitant medications and other available treatment options.

An extensive literature search identified 1 tertiary and 3 primary studies relevant to this inquiry.

Background

A 2020 clinical guide provided an evidence summary of commercially available drugs associated with audiovestibular side effects, including hearing loss, tinnitus, dizziness, and vertigo, using the British National Formulary reference book and reported pharmacovigilance from pharmaceutical companies and health agencies. This consensus document provided an update of similar guidance published originally in 2005 and then in 2011, including a comprehensive listing of medications associated with ototoxic effects. It is noted that drug-induced tinnitus may be associated with continuous or pulsatile low-/high-pitched ringing in the ear(s) or may be asymptomatic, with pulsatile tinnitus tending to be unilateral and a more indirect sequela of ototoxic medications given its vascular origin. A 4-level classification system is used to stratify drug-induced ototoxicity: (1) ototoxic drugs, (2) drugs inducing tinnitus, (3) drugs inducing vertigo or dizziness, and (4) drugs inducing generic hearing disorders. Amlodipine is classified as group 2 and group 3, indicating explicit reporting of inducing tinnitus. Losartan is classified as group 2 and group 3b, indicating it can induce tinnitus commonly (prevalence ≥1% to <10%). [1]

Relevant Prescribing Information

Adverse Reactions [1]
The following events occurred in <1% but >0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship:
Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus.

Adverse Reactions [2]
Treatment with COZAAR was well-tolerated with an overall incidence of adverse events similar to that of placebo. In controlled clinical trials, discontinuation of therapy for adverse events occurred in 2.3% of patients treated with COZAAR and 3.7% of patients given placebo. In 4 clinical trials involving over 1000 patients on various doses (10-150 mg) of losartan potassium and over 300 patients given placebo, the adverse events that occurred in ≥2% of patients treated with COZAAR and more commonly than placebo were: dizziness (3% vs. 2%), upper respiratory infection (8% vs. 7%), nasal congestion (2% vs. 1%), and back pain (2% vs. 1%).
The following less common adverse reactions have been reported:
Ear and labyrinth disorders: Vertigo, tinnitus.

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question: