Managing Acute Porphyrias: International Guidelines
Summing UP features the latest porphyria research in easy-to-understand summaries that have been reviewed and approved by the UPA's Scientific Advisory Board of porphyria experts.
Guidelines for the management of acute porphyria: recommendations from the International Porphyria Network
Published in The Lancet Hematology
May 2026
These guidelines are the result of an international effort by porphyria experts to evaluate the existing research and evidence about the management of acute porphyrias (specifically AIP, HCP and VP), and develop recommendations to support safe and consistent care across the world. However, clinical practice may vary based on access to medication and the country of residence.
These guidelines do not substitute clinical judgement for each individual patient.
Who created the guidelines?
The guidelines were developed by an international panel of porphyria experts, including doctors from multiple specialties, scientists and patient advocates who were brought together by the International Porphyria Network (IPNET).
How were the guidelines created?
The panel used a process that is well established in the medical field for creating guidelines.
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Defining and coming to consensus on key terms that would be relevant for recommendations. For example, determining when acute porphyria is considered active vs. in remission.
Identifying a list of questions that the guidelines should answer.
Reviewing the scientific literature to identify what research existed for each of the questions and to evaluate the quality of the evidence.
Quality of evidence is determined by factors like how many people were included, how were they selected and how was information collected.
For questions where there was little published evidence, expert panel members completed a survey, and their responses were compiled.
The summary of the available research and the expert responses were compiled and presented to the whole panel, then smaller working groups of 2-3 people worked on each individual recommendation.
The draft recommendations were then discussed and voted on by the entire panel. In order to be included in the guidelines a majority of the panel members needed to agree. Strong recommendations had more than 80% agreement . Conditional recommendation had more than 50% agreement.
Recommendations: Preventing attacks and managing triggers
Avoiding known triggers is an important part of managing acute porphyria.
Acute porphyria attacks can be triggered when processes in the liver turn up the first step of making heme. This leads to a build up of the molecules PBG and ALA because later steps in the heme-making process can’t keep up with the increased production.
Things that are known to increase production include some medications, alcohol and fasting/dieting.
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Some drugs can trigger acute porphyria attacks; however the risk varies depending on the individual and how active their porphyria is. When possible, drugs that are known to be safe for porphyria should be prescribed but this should be balanced with other considerations like whether safe alternatives are available and the potential risks of not treating another condition.
The panel had three recommendations:
Everyone with acute porphyria- regardless of whether they’ve ever had a porphyria attack- should be informed of the risk that some drugs may cause an attack and be shown how to check drug safety. *
In a life-threatening emergency, a needed drug should not be withheld because of porphyria-related concerns.
In a non-urgent situation, use of drugs considered safe in porphyria are preferred unless the benefits of a porphyrinogenic drug (drugs that can induce an attack) outweigh the risks.
*Drug Safety Resources:
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The panel recommends that all individuals with porphyria avoid smoking.
There is some evidence that smoking may induce more frequent and severe attacks, and some of the compounds found in cigarette smoke could induce attacks.
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The recommendations for alcohol consumption vary depending on how active your porphyria is:
Those with active porphyria (have had an attack in the last two years) are advised to avoid alcohol completely.
Binge drinking is discouraged for everyone, however if the porphyria is not active, patients may be able to consume limited alcohol in accordance with WHO guidelines.
The panel also cautioned that alcohol may also increase the risk of liver cancer, even among people who do not have active porphyria.
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Rapid weight loss, particularly when carbohydrates are restricted (such as with low-carb or keto diets), increases the risk on a porphyria attack. This risk must be balanced with the importance of maintaining a healthy weight to overall health.
In general, planned weight loss should be discussed with your doctor to minimise the risk of attacks and monitoring (such as regularly monitoring urine ALA/PBG levels) should be put in place. Some approaches to losing weight are safer than others: methods that can be reversed/stopped like dieting or medications are safer that something irreversible like bariatric surgery.
Recommendations for, if, and how to approach weight loss vary based on how active your porphyria is:
For individuals with active porphyria (have had an attack in the last two years) all planned weight loss including by diet, weight loss mediations, and bariatric surgery should be avoided.
For individuals with high ALA/PBG who have not had an attack within the last two years, bariatric surgery should be avoided. Other types of planned weight loss such as through diet or medications can be attempted with consultation with your doctor.
For individuals with normal ALA/PBG who have not have an attack in at least two years, planned weight loss via diet, medication, or bariatric surgery can be allowed.
Individuals who had active porphyria and are now stabilised with givosiran should work with their health care provider to assess their individual risk.
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Hormonal birth control and other drugs containing female sex hormones (particularly progestogens) can potentially trigger attacks and should be approached with caution.
Recommendations vary depending on the type of contraceptive:
Hormonal IUDs: preferred form of contraception for acute porphyria patients. Experts reported it has been well-tolerated by many patients, including those with active porphyria. The dose of hormone in these devices is low and localized to the uterus, but there is a chance it could contribute to an attack in some.
Oral contraception:
For individuals who have had an attack in the last two years, the panel recommends avoiding oral contraception.
For those who have not had an attack in the last two years and who cannot tolerate an IUD, oral contraception, particularly low-dose estrogen-progestogen combinations can be tried.
Injectable or implantable progestogens: not recommended for anyone with porphyria, regardless of how active the porphyria is.
Recommendations: Treating Acute Attacks
The panel made the following recommendations about treating acute attacks:
The preferred treatment for acute attacks is hemin.
Carbohydrate infusions (glucose or dextrose) may be used if hemin is not available or delayed, if the symptoms don’t meet the threshold of an acute attack and/or to ensure adequate caloric intake.
Givosiran is not recommended to treat acute attacks.
Hyponatremia (low sodium) can pose a serious risk and should be investigated and treated appropriately during an attack.
For the purposes of these guidelines, acute attacks are defined as:
Symptoms last for at least 24 hours, with;
Significantly increased urine PBG (at least 10x the upper limit of normal), and;
At least two of the following:
Intense pain
Nausea, vomiting, and/or constipation
High blood pressure or rapid heart rate (tachycardia)
Low sodium (hyponatremia)
Muscle weakness, paralysis or reduced reflexes (peripheral neuropathy)
Urinary retention or incontinence
Central nervous system involvement (seizures, confusion, reduced consciousness, psychosis or PRES on an MRI scan).
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Carbohydrates can either be taken orally or injected intravenously. Carbohydrate loading isn’t well researched, however can be useful in some instances.
Recommendations:
Hemin is the preferred and recommended treatment. Intravenous carbohydrate should not be used as the sole treatment if hemin is available.
Intravenous carbohydrate loading can be used when:
Hemin is not available or while waiting for hemin to arrive.
As an interim measure while waiting for confirmation of an attack.
For mild attack symptoms.
Intravenous carbohydrates should not be used when the patient has significant hyponatremia (low sodium).
Maintain adequate caloric intake of carbohydrates during an attack because fasting can worsen attacks. This can either be done through eating or drinking (oral intake) or intravenously if oral intake is difficult because of nausea, vomiting or low appetite.
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Hemin is believed to shorten attacks, reduce attack severity and reduce the risk of long-term complications.
The panel recommends treating acute porphyria attacks with hemin.
If the patient has symptoms but does not meet the threshold of an acute attack, the panel does not recommend administering hemin.*
In the short term, the main side-effect of of hemin infusion is vein inflammation (phlebitis). This risk can be reduced by:
Reconstituting hemin in albumin instead of saline
Flushing the vein with 0.9% sodium chloride after the hemin is administered
Administering the hemin through a central line or large peripheral vein.
Hemin is safe to use in pregnancy.
*Note: In the US, hemin can be started based on clinical symptoms before lab results are available if the patient has a confirmed porphyria diagnosis and has previously had attacks.
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Hyponatremia (low sodium) is common during acute attacks and can be dangerous. There are multiple underlying factors that may contribute to hyponatremia and identifying those factors are important to correct hyponatremia.
The panel recommends treating hyponatremia promptly to prevent progression and investigating the underlying cause of the hyponatremia. The treatment of hyponatremia should follow your country’s guidelines.
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The panel does not recommend using givosiran to treat acute attacks.
Managing Recurrent Attacks
Some acute porphyria patients will develop recurrent attacks.
Recurrent attacks are defined in these guidelines as four or more attacks in a 12-month period within the last two years.
Before beginning any preventative (prophylactic) treatments for recurrent attacks, the panel recommends an assessment to ensure all modifiable attack triggers like unsafe medications, alcohol and dieting have been eliminated.
The panel had the following recommendations for managing recurrent attacks:
Givosiran is the preferred treatment for recurrent attacks.
If givosiran is not available, prophylactic hemin or GnRH-analogues (for women with cyclic attacks) should be considered.
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The panel recommends givosiran as the preferred treatment for patients who continue to have recurrent acute attacks.
Givosiran helps to reduce and prevent recurrent acute attacks but reducing the activity of the first enzyme in the heme pathway in the liver, which reduces the overall amount of ALA and PBG the liver can make.
There are side effects from givosiran such as nausea, fatigue and impacts on liver and kidney function:
Patients should be closely monitored on givosiran, particularly during the first 6 months as their body adjusts to the medication.
Elevated homocysteine is common in givosiran and is treated with vitamin B6 (pyridoxine).
Safety of givosiran in pregnancy has not been established.
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The panel suggests considering givosiran for some patients who have sporadic attacks (have had an attack in the last 2 years) if they are at high risk of harm. For example, if they have neuropathy from an earlier attack and additional attacks could impede their recovery. This decision should be made in consultation with a porphyria specialist.
The panel also considered using givosiran for other individuals, but did not recommend givosiran use for:
Those who do not meet the threshold for recurrent attacks and not at high risk, or who have high urine PBG with chronic symptoms. The panel did not feel like it had enough information or data to make a recommendation, though it noted that research is being done in this area.
For those who have high urine PBG but no symptoms. The panel did not believe using givosiran to be justified on the available information.
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Prophylactic or preventative hemin is administered with the intention to prevent attacks from happening rather than to treat attacks that are in progress.
The panel recommendation is that hemin be used preventively for those experiencing recurrent attacks if givosiran is not available or unsuitable in a particular case (for example with pregnancy). In these cases of recurrent attacks, preventative hemin is preferred to only administering hemin during an attack.
There are drawbacks to using hemin prophylactically over the long term, including risk of iron overload, blood clots, loss of access to veins, and hemin becoming less effective over the long term.
Because of the potential drawbacks to long term hemin use, the decision to start prophylactic hemin should ideally be made with a porphyria specialist and hemin should be administered with the lowest frequency that is effective for the patient, usually one infusion every 1-4 weeks. Monitoring should be put in place for possible side effects.
Hemin use may also be given “on demand”, meaning it is not a regularly scheduled infusion like when given prophylactically, but rather it is given when a person first starts developing their symptoms and has not yet progressed to severe pain or vomiting (which requires hospitalization). This should also be discussed with a porphyra specialist.
Both prophylactic and on-demand hemin are administered in an outpatient setting in an infusion center.
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If givosiran is not available or tolerated, the panel suggests patients who experience cyclic attacks related to their period can consider GnRH analogues.
GnRH analogues induce menopause while the patient is taking them and may reduce cyclic porphyria attacks.
Use of GnRH analogues should be limited to one year because these medications are known to cause bone density loss. Add-back estrogen can help mitigate this risk, but may also come with a risk of causing attacks.
Regular monitoring for bone density loss and other complications related to these medications should be implemented.
Follow Up and Testing
The experience of patients with acute porphyria varies widely. Some people will have only one or a few attacks in their lifetime, some find out they have acute porphyria through genetic testing and never have symptoms, and some will develop recurring attacks.
The last set of questions the panel considered were about the type of follow up and testing patients should have based on how active their porphyria was.
The panel’s recommendations are:
All patients with acute porphyria regardless of symptoms or elevated urine ALA and PBG should have at least one appointment with a porphyria specialist
Patients with active porphyria (have had an attack in the last 2 years) or high levels of urine PBG should be followed by a porphyria specialist.
Patients over 50 who have had an attack at anytime in their life, or who have high levels of urine PBG should have regular (every 6 months) screenings for liver cancer
Genetic testing for asymptomatic family members is recommended if someone in the family has had a porphyria attack or has high levels of urine PBG.
Patients who have never had an attack and have normal urine PBG levels do not require special screening for liver health or ongoing follow ups with a porphyria specialist.
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Initial Visit
The panel recommends that everyone diagnosed with acute porphyria be offered at least one appointment with a porphyria specialist.
An initial visit should include:
Education about porphyria and attack triggers
Estimating attack risk
Measurement of baseline urine ALA and PBG normalized to creatinine. Determining baseline levels is useful to monitor the condition and determine if anything is changing.
Discussion of family testing.
Follow Up
The panel recognizes that health care resources are often limited and determining who should receive ongoing follow-up with a porphyria specialist should be done based on risk.
Ongoing follow up with a porphyria specialist is recommended for patients with high urine PBG and/or who have had an attack within the last two years.
Follow up should include:
Review of recent symptoms and attacks
Changes in medical history and medication
Discussion of lifestyle modifications to reduce attack risk
Measurement of baseline urine ALA and PBG normalized to creatinine.
Monitoring kidney function and blood pressure
Liver screening for patients over 50
Other testing to monitor medications or porphyria-related complications
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There is an increased risk of liver cancer in some patients with acute porphyria, and regular screening is recommended for higher-risk patients to catch and treat cancer early.
The panel recommends screening for patients over 50 who:
Have had at least one attack at any time in their life and/or,
Have a urine PBG that is at least 4x higher than the upper limit of normal
Screening is generally by ultrasound and should follow your country’s guidelines.
The panel does not recommend screening for those under 50 and those who have never had an attack or testing showing elevated urine PBG.
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The panel recommends genetic testing for family members of all patients who have symptomatic acute porphyria or high urine PBG. This testing should be supported with genetic counseling.
The value in testing is that it can help with earlier diagnosis and preventing attacks by identifying family members who have an acute porphyria gene variant.
What Next?
The panel identified the need for more research into the acute porphyrias and additional topics that require more guidance such as diagnosis, supportive care during attacks, managing skin symptoms for VP and HCP, and managing pregnancy.
IPNET plans to review these guidelines in 3-5 years as more research is done and our understanding of porphyria improves.
CONTENT REVIEWED BY UNITED PORPHYRIAS ASSOCIATION SCIENTIFIC ADVISORY BOARD
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