Long- and post-Covid patients must have easier access to medications, and the participants of the round table convened in 2023 by then Health Minister Karl Lauterbach agreed on that. They focused on access to medications that are already on the market but are actually approved for other diseases—the so-called off-label use. This is essential for long- and post-Covid affected individuals to at least alleviate some of their symptoms. Because despite various research approaches, there is currently no treatment that can cure those affected.
Long Covid refers to persistent symptoms four weeks after a coronavirus infection, Post Covid after twelve weeks. Many affected people struggle with severe fatigue, experience shortness of breath or cardiovascular problems. A serious consequence is ME/CFS – myalgic encephalomyelitis or Chronic Fatigue Syndrome. With this condition, even small tasks such as brushing teeth can exceed the limit of what they can bear.
From mid-year, four medications will be officially approved for off-label use. They appear on the list released by the Federal Joint Committee (G-BA) at the beginning of April, which had previously been developed over three years by an expert group at the Federal Institute for Drugs and Medical Devices (BfArM). This off-label list is intended to give those affected more security in care and cost questions—will it work? The key questions and answers.
What is actually off-label use and why does it exist?
When a drug is approved, it is approved for specific indications. That can be a particular disease or also a particular age group. Sometimes medications are effective against other conditions as well, then it is called off-label use.
What role do off-label medications play in the treatment of Long Covid?
The treatment of Long and Post-Covid has so far been symptom-oriented: those who develop persistent sleep disturbances after a Covid illness receive a remedy for it—not for Long Covid itself. After the round table, the BfArM published the Therapy Compass in October 2024 to guide doctors. There, listed are active substances that within their approved indications—i.e., “on-label”—can be used for certain Long Covid symptoms and are reimbursable by statutory health insurance.
The problem, however, is that a purely on-label therapy is not enough. This is especially evident in the prescription of antidepressants. Because symptoms such as exhaustion or sleep disturbances can occur in Long Covid without a depressive disorder being present. Nevertheless, some doctors had to establish a psychiatric diagnosis in order to be able to prescribe an effective medication.
What difficulties does off-label use bring with it?
When doctors prescribe medications off-label and thus not “according to the label” as described in the package insert, they themselves are liable—and not, as is usually the case, the pharmaceutical manufacturer. This could be a reason why some medical professionals are more hesitant to make such prescriptions, for example about 13 percent of all prescriptions are off-label. Moreover, the dosing for the medications is not always clear, as it was never tested for other diseases.
In principle, health insurance does not cover costs – in individual cases, however, insured persons can submit an application. Still, an off-label medication can indeed be a covered expense. For this, an expert group must positively assess its usefulness. This is exactly what happened with the medicines on the Off-Label List for Long and Post-Covid. For the four active substances on the list, doctors no longer have to make an incorrect diagnosis and can simply prescribe on the health insurance form. This makes it a more targeted treatment of Long Covid than before. In addition, manufacturers will bear liability, and doctors will receive concrete guidance on application, dosing, and duration of treatment.
What does the Off-Label List actually provide for Long- and Post-Covid-affected individuals concretely?
Ivabradine, Agomelatine, Vortioxetine and Metformin – these four medications are now on the list. The first three are intended to alleviate the most common symptoms, while the latter has preventive benefits.
Ivabradine is actually a drug used to treat angina pectoris, i.e., chest pain and heart failure. Off-label it is prescribed to patients who show an excessive rise in heart rate upon standing—provided that beta-blockers are not an option. The expert group based its recommendation on a study that compared Ivabradine with placebo. Seventy-eight percent of patients reported improvement in the symptoms of their palpitations. Compared with placebo, the drug reduced the standing heart rate.
The second active substance, Agomelatine, is intended off-label to help with exhaustion that frequently occurs in ME/CFS. Normally it is approved for the treatment of severe depression in adults. A randomized study showed that Agomelatine improved fatigue and health-related quality of life after 12 weeks compared with Melatonin. After switching from Melatonin to Agomelatine in group two, fatigue also declined noticeably.
Also an antidepressant is Vortioxetine, approved for adults. Off-label it can be prescribed for cognitive impairments such as reduced attention, memory problems, and depressive symptoms in Long- and Post-Covid. In direct comparison with placebo, Vortioxetine improved depressive symptoms and in parts also cognitive effects. Nevertheless, the question remains whether affected individuals will be able to use this preparation in the future; currently it is not available on the German market.
And last but not least is Metformin. The drug reduces the risk of developing Long Covid in overweight individuals. For this to work, the diabetes medication should be administered within three days after infection. Consequently, this substance, which is normally used to treat diabetes, also landed on the Off-Label List as a prophylaxis for adults and adolescents from 16 years.
The first affected individuals appeared in 2020, and by 2023 the then Health Minister Karl Lauterbach announced the plan for the Off-Label List. Why did it take so long?
The German legislator basically knows a path to make off-label use a covered health-service. They would have applied it here as well, says the BfArM in response to . And it follows bureaucratic principles. For the off-label authorization, an expert group at the BfArM first evaluated the study data on the active substances already used for Long and Post-Covid and discussed them several times over two years. Because the study data are generally sparse and the G-BA needs robust evidence for approval, there were probably only four substances with convincing treatment results in the end. Before the G-BA finally decided on future cost coverage, another five months passed.
Austria moved faster; there, there has been an Off-Label List since the end of 2024. Some affected people criticize the German process as too restrictive. Yet the German process also has its advantages: it ensures that only substances with solid evidence are reimbursed—and that liability lies with the manufacturers. In Austria, on the other hand, only the three largest sickness funds cover the costs, and doctors remain liable for the prescription.
These are not the only medications Long- and Post-Covid-affected people have used off-label so far. What chance is there for additional active substances?
At present, it is not known whether costs for additional active substances will be covered in the future. Astrid Weber, head of the Long-Covid Clinic in Koblenz, told Deutschlandfunk that she regrets that low-dose naltrexone is not on the list. Because this is a medication she has used off-label for the longest time and it is comparatively expensive—patients pay 80 to 90 euros per month themselves. The decision for this drug is still pending. The reason: a Canadian study is currently underway, with results expected in May 2026. If naltrexone performs well there, it could also land on the list.
Moreover, more research is needed to fundamentally cure the disease. In particular, more research funds must flow into the identification of disease mechanisms. After all, Federal Minister of Science Dorothee Bär launched the National Decade Against Post-Infectious Diseases in January, with 500 million euros over ten years provided by the Federal Ministry of Education and Research. It can take 10 to 15 years before new targeted medicines are developed. Therefore, many companies tend to test already available drugs against post-infectious diseases.
