Depo-SubQ Provera 104 Shortage: What Providers and Prescribers Need to Know in 2026

For providers who prescribe Depo-SubQ Provera 104 (medroxyprogesterone acetate 104 mg/0.65 mL subcutaneous), 2026 presents two distinct clinical management challenges: ongoing patient questions about access and a significant regulatory update that has changed the informed consent conversation around this contraceptive. This article consolidates what you need to know.

Availability Status: Not an FDA Shortage, But Stocking Is Inconsistent

As of 2026, Depo-SubQ Provera 104 is not listed on the FDA Drug Shortage Database. Pfizer manufactures the product, and national supply is intact. However, retail pharmacy stocking is inconsistent — particularly in rural and underserved areas where demand-based ordering leaves many pharmacies without routine stock.

The practical implication for prescribers: your patients may arrive for their scheduled injection appointment only to discover their pharmacy doesn't have it. Building a protocol to address this — whether by maintaining in-office stock or providing patients with a pharmacy search strategy — can prevent gaps in coverage.

The December 2025 FDA Meningioma Label Update: Clinical Implications

In December 2025, the FDA approved an update to the prescribing information for both Depo-SubQ Provera 104 and Depo-Provera CI, adding a meningioma warning. The updated label states that cases of meningioma have been reported following repeated administration of medroxyprogesterone acetate, primarily with long-term use.

The evidence base includes a large BMJ population-based case-control study showing an approximately 5.6-fold increase in odds of surgically treated intracranial meningioma (adjusted OR 5.55; 95% CI 2.27–13.56) with prolonged injectable MPA use, and a JAMA Neurology study identifying a roughly 2-fold increased risk. The risk was greatest in women who began use after age 31 or who used it for 4 years or more.

Prescribing Guidance: Who Should and Shouldn't Continue Depo-SubQ Provera 104

Contraindications added with the December 2025 update:

Current meningioma or history of meningioma — Depo-SubQ Provera 104 should be discontinued if a meningioma is diagnosed.

Existing contraindications remain:

Active or history of thromboembolic disorders or cerebrovascular disease

Known, suspected, or past breast malignancy

Significant hepatic disease or jaundice

Undiagnosed vaginal bleeding

Known hypersensitivity to MPA or any ingredient in the formulation

Counseling Patients on the Meningioma Risk

The updated FDA guidance requires that providers counsel patients about the meningioma risk, particularly those with a history of meningioma. Key talking points for informed consent:

The absolute risk of meningioma remains low, particularly for short-term users.

Risk is primarily associated with prolonged use (≥1 year, with highest risk at ≥4 years).

Depo-SubQ Provera 104 is already not recommended for more than 2 years of use due to bone mineral density concerns — a recommendation that pre-dates and aligns with the meningioma risk timeline.

Monitor for signs and symptoms: persistent headaches, vision changes, hearing loss/tinnitus, seizures, or memory changes.

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Bone Mineral Density: The Existing Black Box Warning

The long-standing black box warning on Depo-SubQ Provera 104 concerns bone mineral density (BMD) loss. Women using this product may lose significant BMD; loss is greater with increasing duration of use and may not be completely reversible. The 2-year use limitation reflects this concern. For adolescent patients — a critical period of bone accretion — the risk may be particularly significant.

Drug Interactions to Note

Concomitant use with moderate or strong CYP3A4 inducers (rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) may decrease MPA concentrations, potentially reducing contraceptive efficacy. Aminoglutethimide may also decrease MPA levels. Be alert to these interactions, especially in patients on anticonvulsant therapy.

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Alternatives to Consider for Long-Term Users

For patients approaching the 2-year mark or who have a personal history of meningioma, consider these alternatives:

Depo-Provera CI (150 mg IM): Same active ingredient, same risk profile — but generic available and wider pharmacy access; suitable if the patient prefers injections.

Nexplanon (etonogestrel implant): 3-year progestin implant with no meningioma warning; excellent for patients wanting long-acting, low-maintenance contraception.

Levonorgestrel IUD (Mirena, Kyleena): Localized progestin delivery, minimal systemic exposure, 5–8 year duration, no systemic bone or meningioma concerns.

For endometriosis pain: Leuprolide (Lupron Depot) or Orilissa (elagolix) as GnRH-targeted therapies; continuous combined oral contraceptives as first-line.

Helping Your Patients Find Depo-SubQ Provera 104 When Stocking Is an Issue

For patients who are continuing on Depo-SubQ Provera 104 and struggling to find it at retail pharmacies, medfinder for Providers is a tool that checks real-time pharmacy availability near your practice, helping you direct patients to locations that currently have stock. This is particularly useful for patients in rural or underserved areas where supply is inconsistent.

For a detailed provider workflow, see our guide: How to Help Your Patients Find Depo-SubQ Provera 104 in Stock.