Pravastatin

Evidence Level: L4

Predicted Indications: 9

Pravastatin
1. Pharmacist Assessment Report
Pravastatin: From Hyperlipidemia and Atherosclerosis to Homozygous Familial Hypercholesterolemia

Pharmacist Assessment Report

Pravastatin: From Hyperlipidemia and Atherosclerosis to Homozygous Familial Hypercholesterolemia

One-Sentence Summary

Pravastatin is a statin (HMG-CoA reductase inhibitor) originally used for hyperlipidemia, atherosclerosis and stroke-related conditions. The TxGNN model predicts it may be effective for Homozygous Familial Hypercholesterolemia, but the supporting evidence is indirect: 1 clinical trial (which tests a different drug) and 12 publications (mostly reviews of other lipid-lowering agents).

Quick Overview

Item	Content
Original Indication	Hyperlipidemia, atherosclerosis, stroke and cerebrovascular disorders (the FDA licence records have no indication text, so this comes from the knowledge-graph indication list)
Predicted New Indication	Homozygous familial hypercholesterolemia
TxGNN Prediction Score	99.95%
Evidence Level	L4
US Market Status	Cancelled only (all 5 listed ANDAs are cancelled)
Number of NDAs	5 (all ANDAs, all cancelled)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is not available in the data compiled for this report. Pravastatin is a well-known HMG-CoA reductase inhibitor. It lowers LDL cholesterol by reducing hepatic cholesterol synthesis and upregulating LDL receptors, and it has an established role in hyperlipidemia and atherosclerosis.

Familial hypercholesterolemia is a closely related lipid disorder, so the TxGNN prediction is biologically plausible. There is an important caveat, however. Homozygous FH is characterized by severe LDL receptor deficiency, and statin efficacy depends on residual receptor activity. One review in the data states that statins are not very effective in homozygous FH. The expected benefit is therefore likely limited compared with heterozygous FH.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT03510715	Phase 3	Completed	18	Open-label alirocumab study in children and adolescents (8–17 years) with HoFH. It does not test pravastatin and provides disease context only.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
31696945	2019	Review	Cochrane Database Syst Rev	Statins for children with familial hypercholesterolemia
28685504	2017	Review	Cochrane Database Syst Rev	Earlier version of the review of statins in children with FH
28416195	2017	RCT	Lancet HIV	INTREPID: pitavastatin vs pravastatin in HIV-related dyslipidaemia (not an FH population)
28437620	2017	Review	Endocr Pract	AACE/ACE guidelines for dyslipidemia management
15532136	2004	Commentary	Prescrire Int	Notes pravastatin and simvastatin are reference statins for heterozygous FH, and that statins are not very effective in homozygous FH
15531000	2004	Review	Clin Ther	Rosuvastatin indicated for HoFH (other drug)
12269853	2002	Review	Drugs	Rosuvastatin review, superior to pravastatin in lipid improvement
14727947	2003	Review	Am J Cardiovasc Drugs	Ezetimibe review
14647533	2003	Review	Cardiovasc Drug Rev	Ezetimibe as a cholesterol absorption inhibitor
9129869	1997	Review	Drugs	Atorvastatin review

US Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
ANDA077793	Pravastatin sodium (Aurobindo Pharma)	Tablet	Not recorded (cancelled)
ANDA077987	Pravastatin Sodium (A-S Medication Solutions)	Tablet	Not recorded (cancelled)
ANDA209869	Pravastatin sodium (Golden State Medical Supply)	Tablet	Not recorded (cancelled)
ANDA076341	Pravastatin sodium (RemedyRepack)	Tablet	Not recorded (cancelled)
ANDA076714	Pravastatin sodium (Dr. Reddy’s Laboratories)	Tablet	Not recorded (cancelled)

Safety Considerations

Package insert warnings and contraindications were not available in the data compiled for this report, so please refer to the package insert for authoritative safety information.

Knowledge-graph contraindication signals (not label text): kidney disease, liver disease, gallbladder disease, myopathy and other muscle disease, rhabdomyolysis, thrombocytopenia, peptic ulcer disease, gout, hemophilia, anemia, nephrolithiasis, hypercalcemia, and others. These should be verified against the label.
Drug Interactions: 100 interactions were identified. The moderate-level ones listed include metronidazole, clarithromycin, eluxadoline, naltrexone, pectin, rosuvastatin, simvastatin and tinidazole. Combining pravastatin with other statins (rosuvastatin, simvastatin) deserves particular attention.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction score is high, but the only linked trial tests a different drug (alirocumab), and the literature does not directly evaluate pravastatin in homozygous FH. Statins are also expected to have limited efficacy in this disease because of LDL receptor deficiency. All US licences are cancelled, and the label safety data is missing.

To proceed, the following is needed:

Pravastatin-specific efficacy data in homozygous FH patients (for example, LDL-C response in receptor-negative vs receptor-defective patients)
Comparison with established HoFH therapies
Package insert warnings and contraindications from the FDA label
Mechanism of action data and clarification of the market and licensing situation

Other predictions of note: Two other predictions have more substantial evidence. Familial hypercholesterolemia (heterozygous; L2, with pediatric pravastatin pharmacokinetic and randomized studies) and HIV-associated dyslipidemia (L2, with a Phase 3 fenofibrate-vs-pravastatin trial and several Phase 4 trials) are better candidates for follow-up. Both are about positioning within an established drug class rather than true repurposing.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.