Does Penicillin V (Pen VK) cause increased intracranial pressure?

Penicillin V (Pen VK) and Intracranial Pressure

Penicillin V (Pen VK) does not typically cause increased intracranial pressure as a common side effect, though rare cases of antibiotic-induced intracranial hypertension have been reported with tetracyclines and other antibiotics, but not specifically with penicillin V.

Evidence on Antibiotics and Intracranial Pressure

Antibiotics Associated with Intracranial Hypertension

The most recent and comprehensive evidence on drug-induced intracranial hypertension (DIIH) indicates that tetracycline-class antibiotics are strongly associated with increased intracranial pressure 1. However, penicillin V is not listed among the antibiotics with strong or even moderate associations with intracranial hypertension.

According to a 2020 systematic review, the antibiotics most strongly associated with drug-induced intracranial hypertension are:

• Tetracycline-class antibiotics (strongly associated - Category IV/V)
• Nalidixic acid (weakly associated - Category I/II)
• Second and third-generation fluoroquinolones (weakly associated - Category I/II) 1

Penicillin V was not identified as a significant risk factor for intracranial hypertension in this comprehensive review.

Case Reports and Specific Evidence

There is a single case report from 2024 mentioning intracranial hypertension occurring after administration of penicillin and gentamicin together 2. However, this is an isolated case report with multiple confounding factors, and causality cannot be definitively established.

In contrast, a 1992 study specifically examined vancomycin (another antibiotic, but not a penicillin) and found it could increase intracranial pressure, likely due to histamine release 3. This effect has not been documented with penicillin V.

Management of Intracranial Pressure if it Occurs

If increased intracranial pressure were to develop during antibiotic therapy (regardless of cause), guidelines recommend:

1. Identifying and discontinuing any potential causative agent 4
2. Measuring CSF pressure via lumbar puncture to confirm diagnosis 4
3. Managing elevated pressure through:
   • Lumbar drainage to reduce opening pressure by 50% 4
   • Considering acetazolamide or other medications to reduce ICP 4
   • In severe cases, considering ventriculoperitoneal shunting 4

Clinical Implications

When prescribing penicillin V:

• Routine monitoring for increased intracranial pressure is not necessary
• Be aware of symptoms that might indicate increased intracranial pressure (persistent headache, visual disturbances, papilledema)
• If symptoms of increased intracranial pressure develop, consider other causes before attributing to penicillin V

Conclusion

Based on the available evidence, penicillin V (Pen VK) is not known to cause increased intracranial pressure as a common or recognized side effect. While rare cases of antibiotic-induced intracranial hypertension exist, penicillin V has not been identified as a high-risk medication for this adverse effect in systematic reviews or clinical guidelines.