Bipolar disorder (BD) in adolescents is associated with risky behaviors, including high risk for sexually transmitted infections. When exposed, post exposure prophylaxis (PEP) is recommended within 72 hours for a period of 28 days. The medications used for PEP are known to have common neuropsychiatric side effects, renal toxicity and risk of hepatic injury. The concomitant use of PEP and bipolar medications may have serious additive adverse effects which needs careful assessment and monitoring. PEP medications, in particular raltegravir, are known to have a common side effect of insomnia. The medication options may be more limited during this period and since insomnia is also known to precipitate mania it needs to be addressed. The knowledge of these side effects of PEP medications, understanding its interactions with mood stabilizers like lithium and valproic acid is important when caring for these individuals. The medication options of monotherapy or combination regimen for BD must be discussed with the patient and informed choices would yield better clinical outcomes. Although there is no established standard, but weekly monitoring of complete blood counts and liver functions until PEP is completed would be highly recommended to prevent serious negative events.Copyright © 2021, Gupta et al.