Riociguat side effects: what 32,388 FDA adverse event reports show
Drug class
Soluble Guanylate Cyclase Stimulator
Brand names
Adempas
Who reports
32,388 reports · 77% serious · 7,092 with death outcome · 73% female
Used for
Adempas is a soluble guanylate cyclase (sGC) stimulator indicated for the treatment of adults with: • Persistent/recurrent Chronic Thromboembolic Pulmonary Hypertension (CTEPH) (WHO Group 4) after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class.
What it is
Adempas (riociguat) is a soluble guanylate cyclase stimulator tablet for oral administration. Riociguat is methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo [3,4-b]pyridin-3-yl]-5-pyrimidin.
Boxed warning
EMBRYO-FETAL TOXICITY Adempas is contraindicated for use during pregnancy because it may cause fetal harm based on animal data [see Contraindications (4.1) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1) ]. Exclude pregnancy prior to the start of treatment with Adempas.
Causality screen of the 40 strongest signals
What the badges mean
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only (and, for the 300 most-reported drugs, adjusted for age band), and flags pairs whose reports are unusually skewed by sex or come mostly from consumers. Each row also shows the PRR against the other drugs of the same FDA class, which removes most confounding by the condition being treated, and a calibrated p-value: on validation, known non-causes average an ROR of about 2, so significance is judged against that empirical null (✓ = p < 0.05 after calibration). 1,087 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Pulmonary angioplasty | 22 | 2,804.4 1,062.1–7,405.2ROR 2,806.3 · calibrated p 3e-16 ✓ | 357.9 EB05 249.2 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=20 | not reported in cached trials |
| Pulmonary endarterectomy | 90 | 1,024.3 733.9–1,429.7ROR 1,027.2 · calibrated p 1e-16 ✓ | 363.1 EB05 304.4 · IC025 +6.6 3/3 methods agree | Not in label — unassessed | serious n=89 | not reported in cached trials |
| Pulmonary artery therapeutic procedure | 20 | 637.4 343.0–1,184.5ROR 637.8 · calibrated p 6e-13 ✓ | 244.7 EB05 167.3 · IC025 +4.4 3/3 methods agree | Reporting / coding artifact | serious n=20 | not reported in cached trials |
| Endarterectomy | 57 | 218.9 162.0–295.6ROR 219.2 · calibrated p 4e-10 ✓ | 154.8 EB05 123.9 · IC025 +5.6 3/3 methods agree | Not in label — unassessed | serious n=56 | not reported in cached trials |
| Diastolic hypotension | 32 | 156.9 106.6–230.9ROR 157.0 · calibrated p 1e-8 ✓ | 117.4 EB05 87.1 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious n=31 | not reported in cached trials |
| Bendopnoea | 40 | 154.5 109.4–218.2ROR 154.7 · calibrated p 9e-9 ✓ | 117.7 EB05 90.1 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious n=37 · 80% consumer | not reported in cached trials |
| Pulmonary artery occlusion | 16 | 129.1 75.4–220.9ROR 129.2 · calibrated p 1e-7 ✓ | 95.6 EB05 62.4 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=16 | not reported in cached trials |
| Diuretic therapy | 12 | 127.5 68.6–236.9ROR 127.5 · calibrated p 2e-7 ✓ | 91.4 EB05 55.7 · IC025 +3.4 3/3 methods agree | Reporting / coding artifact | serious n=12 | not reported in cached trials |
| Walking distance test abnormal | 53 | 103.0 77.1–137.6ROR 103.2 · calibrated p 2e-7 ✓ | 86.1 EB05 68.4 · IC025 +5.2 3/3 methods agree | Reporting / coding artifact | serious n=37 | not reported in cached trials |
| Pulmonary arterial wedge pressure increased | 23 | 100.4 64.7–155.8ROR 100.5 · calibrated p 4e-7 ✓ | 81.2 EB05 57.0 · IC025 +4.2 3/3 methods agree | Lab value / disease marker | serious n=20 | not reported in cached trials |
| Dialysis hypotension | 13 | 99.8 55.6–179.1ROR 99.9 · calibrated p 9e-7 ✓ | 77.0 EB05 47.9 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Transplant evaluation | 67 | 97.7 75.6–126.3ROR 97.9 · calibrated p 2e-7 ✓ | 82.9 EB05 67.6 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | serious n=66 | NCT00863681: 1/231 (0.4%) on Riociguat (serious AE) |
| Catheter site vesicles | 24 | 92.7 60.4–142.2ROR 92.8 · calibrated p 6e-7 ✓ | 76.3 EB05 54.0 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=18 | not reported in cached trials |
| Device wireless communication issue | 31 | 91.5 62.8–133.3ROR 91.6 · calibrated p 5e-7 ✓ | 76.5 EB05 56.4 · IC025 +4.6 3/3 methods agree | Reporting / coding artifact | serious n=11 · 100% consumer | not reported in cached trials |
| Device maintenance issue | 62 | 79.8 61.3–103.9ROR 80.0 · calibrated p 9e-7 ✓ | 69.6 EB05 56.2 · IC025 +5.1 3/3 methods agree | Reporting / coding artifact | serious n=14 · 100% consumer | not reported in cached trials |
| Pulmonary arterial pressure increased | 178 | 79.0 67.6–92.3ROR 79.4 · calibrated p 7e-7 ✓ | 69.9 EB05 61.7 · IC025 +5.6 3/3 methods agree | Lab value / disease marker | serious n=158 | not reported in cached trials |
| Catheter management | 98 | 78.8 63.9–97.1ROR 79.0 · calibrated p 8e-7 ✓ | 69.3 EB05 58.5 · IC025 +5.4 3/3 methods agree | Reporting / coding artifact | serious n=92 · 95% clinician | not reported in cached trials |
| Catheter site pruritus | 89 | 73.2 58.8–91.1ROR 73.4 · calibrated p 1e-6 ✓ | 64.9 EB05 54.3 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious n=80 | not reported in cached trials |
| Cardiac failure high output | 21 | 62.5 40.0–97.9ROR 62.6 · calibrated p 9e-6 ✓ | 54.4 EB05 37.5 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=21 | not reported in cached trials |
| Cardiac output increased | 15 | 62.1 36.5–105.5ROR 62.1 · calibrated p 1e-5 ✓ | 53.1 EB05 34.1 · IC025 +3.5 3/3 methods agree | Lab value / disease marker | – | not reported in cached trials |
| Catheter site rash | 37 | 57.8 41.3–80.9ROR 57.9 · calibrated p 9e-6 ✓ | 51.7 EB05 39.2 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=30 | not reported in cached trials |
| Thrombectomy | 26 | 55.8 37.4–83.3ROR 55.8 · calibrated p 1e-5 ✓ | 49.6 EB05 35.6 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=26 · ♀ 50% (drug 73%) | not reported in cached trials |
| Catheter site irritation | 25 | 54.9 36.5–82.7ROR 55.0 · calibrated p 2e-5 ✓ | 48.9 EB05 34.8 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=21 · ♀ 100% (drug 73%) | not reported in cached trials |
| Pulmonary arterial hypertension | 1,126 | 54.2 51.0–57.5ROR 56.1 · calibrated p 7e-6 ✓ | 50.0 EB05 47.6 · IC025 +5.5 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 37.4 | NCT00810693: 1/63 (1.6%) on Riociguat; 2/126 (1.6%) control (serious AE) |
| Vascular device occlusion | 26 | 54.2 36.3–80.8ROR 54.2 · calibrated p 2e-5 ✓ | 48.3 EB05 34.7 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=26 | not reported in cached trials |
| Pulmonary arterial pressure abnormal | 22 | 53.5 34.6–82.7ROR 53.6 · calibrated p 2e-5 ✓ | 47.5 EB05 33.1 · IC025 +3.9 3/3 methods agree | Lab value / disease marker | serious n=15 | not reported in cached trials |
| Oxygen consumption increased | 179 | 53.0 45.6–61.8ROR 53.3 · calibrated p 1e-5 ✓ | 48.8 EB05 43.1 · IC025 +5.2 3/3 methods agree | Lab value / disease marker | serious n=138 | not reported in cached trials |
| Infusion site infection | 169 | 52.1 44.5–60.9ROR 52.4 · calibrated p 1e-5 ✓ | 48.0 EB05 42.2 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious n=98 · 72% consumer | NCT00810693: 1/63 (1.6%) on Riociguat (serious AE) |
| Right ventricular failure | 492 | 48.4 44.2–53.0ROR 49.1 · calibrated p 2e-5 ✓ | 45.0 EB05 41.7 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | serious PRR 33.9 | NCT00810693: 3/63 (4.8%) on Riociguat; 1/126 (0.8%) control (serious AE) |
| Dizziness exertional | 51 | 47.6 35.8–63.2ROR 47.7 · calibrated p 3e-5 ✓ | 43.7 EB05 34.5 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=31 | not reported in cached trials |
| Catheter site erythema | 141 | 46.7 39.3–55.3ROR 46.9 · calibrated p 2e-5 ✓ | 43.3 EB05 37.6 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious n=121 | not reported in cached trials |
| Paracentesis | 41 | 45.9 33.5–63.0ROR 46.0 · calibrated p 3e-5 ✓ | 42.1 EB05 32.4 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=38 | not reported in cached trials |
| Catheter site discharge | 72 | 45.3 35.6–57.5ROR 45.4 · calibrated p 3e-5 ✓ | 41.9 EB05 34.4 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=63 | not reported in cached trials |
| Cor pulmonale chronic | 12 | 44.2 24.6–79.4ROR 44.2 · calibrated p 1e-4 ✓ | 39.1 EB05 23.8 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=11 | NCT00863681: 1/231 (0.4%) on Riociguat (serious AE) |
| Infusion site abscess | 30 | 42.9 29.6–62.0ROR 42.9 · calibrated p 6e-5 ✓ | 39.3 EB05 28.9 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=20 | NCT00863681: 1/56 (1.8%) on Riociguat (serious AE) |
| Infusion site warmth | 73 | 41.8 33.0–52.9ROR 41.9 · calibrated p 5e-5 ✓ | 38.9 EB05 32.0 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=28 · 77% consumer | not reported in cached trials |
| Catheterisation cardiac abnormal | 16 | 40.8 24.6–67.6ROR 40.8 · calibrated p 1e-4 ✓ | 36.9 EB05 24.1 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | – | NCT00810693: 1/254 (0.4%) on Riociguat (serious AE) |
| Infusion site induration | 84 | 40.6 32.6–50.6ROR 40.7 · calibrated p 6e-5 ✓ | 37.9 EB05 31.6 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=29 · 80% consumer | not reported in cached trials |
| Infusion site discharge | 101 | 40.6 33.2–49.6ROR 40.7 · calibrated p 6e-5 ✓ | 37.9 EB05 32.1 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=39 · 73% consumer | not reported in cached trials |
| Oxygen therapy | 96 | 40.5 32.9–49.7ROR 40.6 · calibrated p 6e-5 ✓ | 37.8 EB05 31.9 · IC025 +4.7 3/3 methods agree | Reporting / coding artifact | serious n=92 | NCT00863681: 1/109 (0.9%) control (serious AE) |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Riociguat as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (8 of 40 signal terms matched).
- NCT00810693 — A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With Pulmonary Arterial Hypertension (P (N=445, PHASE3; 116 AE terms posted; arms: Riociguat (Adempas, BAY63-2521) up to 2.; Riociguat (Adempas, BAY63-2521) up to 1.; Placebo)
- NCT00863681 — BAY63-2521:Long-term Extension Study in Patients With Pulmonary Arterial Hypertension (N=396, PHASE3; 398 AE terms posted; arms: Former Riociguat 1.0- 2.5 mg; Former Riociguat 1.0 - 1.5 mg; Former Placebo)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Dyspnoea (shortness of breath) | 5,718 | 6.6 6.4–6.8ROR 7.8 · calibrated p 0.072 | 6.5 EB05 6.4 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 5.6 | NCT00810693: 1/126 (0.8%) control (serious AE) |
| Death | 5,399 | 4.1 4.0–4.2ROR 4.7 · calibrated p 0.271 | 4.1 EB05 4.0 · IC025 +2.0 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 3.0 | NCT00863681: 2/231 (0.9%) on Riociguat; 3/109 (2.8%) control (serious AE) |
| Headache | 4,513 | 4.7 4.6–4.8ROR 5.3 · calibrated p 0.206 | 4.7 EB05 4.5 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.7 | NCT00810693: 20/63 (31.7%) on Riociguat; 25/126 (19.8%) control |
| Nausea | 3,769 | 3.1 3.0–3.2ROR 3.4 · calibrated p 0.516 | 3.1 EB05 3.0 · IC025 +1.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.2 | NCT00810693: 10/63 (15.9%) on Riociguat; 16/126 (12.7%) control |
| Diarrhoea (diarrhea) | 3,533 | 3.6 3.5–3.7ROR 3.9 · calibrated p 0.400 | 3.6 EB05 3.5 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.3 | NCT00810693: 1/126 (0.8%) control (serious AE) |
| Dizziness | 3,522 | 4.6 4.5–4.7ROR 5.0 · calibrated p 0.230 | 4.6 EB05 4.4 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.5 | NCT00810693: 1/254 (0.4%) on Riociguat (serious AE) |
| Hypotension (low blood pressure) | 3,401 | 11.2 10.8–11.5ROR 12.4 · calibrated p 0.015 ✓ | 11.0 EB05 10.7 · IC025 +3.4 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 8.0 | NCT00810693: 1/254 (0.4%) on Riociguat (serious AE) |
| Fatigue (tiredness) | 2,967 | 2.5 2.4–2.6ROR 2.6 · calibrated p 0.761 | 2.5 EB05 2.4 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 2.6 | NCT00810693: 7/254 (2.8%) on Riociguat; 8/126 (6.3%) control |
| Hospitalisation | 2,311 | 9.9 9.6–10.4ROR 10.6 · calibrated p 0.026 ✓ | 9.8 EB05 9.5 · IC025 +3.2 3/3 methods agree | Reporting / coding artifact | serious PRR 7.5 | not reported in cached trials |
| Vomiting | 2,120 | 2.9 2.8–3.1ROR 3.1 · calibrated p 0.604 | 2.9 EB05 2.8 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.5 | NCT00810693: 7/63 (11.1%) on Riociguat; 11/126 (8.7%) control |
| Cough | 1,797 | 4.2 4.0–4.4ROR 4.4 · calibrated p 0.317 | 4.2 EB05 4.0 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 4.0 | NCT00810693: 3/63 (4.8%) on Riociguat; 13/126 (10.3%) control |
| Oedema peripheral (swelling of legs/feet) | 1,790 | 9.6 9.2–10.0ROR 10.1 · calibrated p 0.031 ✓ | 9.5 EB05 9.1 · IC025 +3.2 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 7.8 | NCT00810693: 14/63 (22.2%) on Riociguat; 14/126 (11.1%) control |
| Pneumonia (lung infection) | 1,766 | 3.5 3.4–3.7ROR 3.7 · calibrated p 0.439 | 3.5 EB05 3.4 · IC025 +1.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.7 | NCT00810693: 1/254 (0.4%) on Riociguat (serious AE) |
| Fluid retention | 1,756 | 23.1 22.1–24.2ROR 24.4 · calibrated p 8e-4 ✓ | 22.3 EB05 21.5 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious PRR 20.7 | NCT00863681: 2/231 (0.9%) on Riociguat (serious AE) |
| Malaise (feeling unwell) | 1,670 | 2.5 2.4–2.6ROR 2.5 · calibrated p 0.795 | 2.5 EB05 2.4 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 2.4 | NCT00863681: 1/56 (1.8%) on Riociguat (serious AE) |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Pulmonary angioplasty — n=22, PRR 2,804.4
- Pulmonary endarterectomy — n=90, PRR 1,024.3
- Endarterectomy — n=57, PRR 218.9
- Diastolic hypotension — n=32, PRR 156.9
- Bendopnoea — n=40, PRR 154.5
- Transplant evaluation — n=67, PRR 97.7 (also seen in trial arm)
- Catheter site vesicles — n=24, PRR 92.7
- Catheter site pruritus — n=89, PRR 73.2
- Cardiac failure high output — n=21, PRR 62.5
- Catheter site rash — n=37, PRR 57.8
✓ A hand-written Bradford Hill causality assessment exists for this drug: Riociguat ↔ Hypotension.
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Riociguat?
In FDA FAERS, the most frequently co-reported reaction terms for Riociguat are dyspnoea, headache, nausea, diarrhoea, dizziness, hypotension. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Riociguat have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: EMBRYO-FETAL TOXICITY Adempas is contraindicated for use during pregnancy because it may cause fetal harm based on animal data [see Contraindications (4.1) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1) ]. Exclude pregnancy prior to the start of treatment with Adempas.
Do FAERS signals prove that Riociguat causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 7b57509a-3d5d-41d4-8fed-1471e26372a3, effective 20260813; matched on
openfda.generic_name.exact:"RIOCIGUAT") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 1,127 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath - ClinicalTrials.gov API v2 (query
RIOCIGUAT, results-bearing studies sorted by enrollment)
Page generated 2026-10-14. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.