Materiały źródłowe

• #1 Porphyrias in the Age of Targeted Therapies

  https://www.mdpi.com/2075-4418/11/10/1795

  The porphyrias are a group of eight rare genetic disorders, each caused by the deficiency of one of the enzymes in the heme biosynthetic pathway, resulting in the excess accumulation of heme precursors and porphyrins. […] Medical management consists mostly of the avoidance of triggering factors and symptomatic treatment. With an improved understanding of the underlying pathophysiology and disease mechanisms, new treatment approaches have become available, which address the underlying defects at a molecular or cellular level, and promise significant improvement, symptom prevention and more effective treatment of acute and chronic disease manifestations. […] Precipitating factors that can trigger acute porphyria attacks including stress, excess alcohol intake, smoking, fasting, acute illness, steroids, hormonal preparations and other certain medications.

• #1 Porphyria // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/porphyria

  Although there’s no way to prevent porphyria, if you have the condition, avoid triggers to help prevent symptoms. […] Because porphyria is usually an inherited disorder, your siblings and other family members may want to consider genetic testing to determine if they have the condition. Genetic counseling is important to help understand test results and risks.

• #1 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Patients with acute porphyria should avoid the following: Potential precipitating medications (see the Drug Database for Acute Porphyria or the American Porphyria Foundation drug database) […] Heavy alcohol use […] Smoking […] Physical or emotional stress or exhaustion […] Exposure to organic solvents (eg, in herbicides, painting or dry cleaning products) […] Crash diets […] Prolonged periods caloric deprivation or starvation. […] Diets for obesity should provide gradual weight loss and be adopted only during periods of remission. Carriers of variegate porphyria or hereditary coproporphyria should minimize sun exposure; sunscreens that block only ultraviolet B light are ineffective, but opaque zinc oxide or titanium dioxide preparations are beneficial. […] Patients should be identified prominently in the medical record as carriers and should carry a card and wear medical alert jewelry verifying the carrier state and precautions to be observed.

• #1 Porphyria | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/porphyria

  In most cases, a combination of genetic and environmental factors trigger porphyria symptoms. […] by avoiding triggers, development of symptoms of porphyria can be prevented. […] general suggestions for preventing symptoms of porphyria include: […] In all cases avoid known triggers for example, dont smoke or drink alcohol. […] When out in the sun, wear sunglasses, a brimmed hat, a long-sleeved top and long pants. Apply SPF 30+ sunscreen to exposed skin areas. […] Protect your skin every day. For example, wear rubber gloves when handling chemicals or very hot water. Avoid perfumed soaps. Regularly apply barrier cream to the hands. […] Eat regular meals. […] Consider wearing a medical alert bracelet or pendant, as surgery and some medications can provoke symptoms.

• #1 Porphyria Overview: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1389981-overview

  Educate patients about their form of porphyria, its inheritance, precipitating drugs and events, and the importance of seeking treatment in early stages of an attack. […] Encourage patients to wear medical alert bracelets. […] Patients who smoke should be strongly encouraged to quit. Smoking, which increases hepatic cytochrome P450 enzymes and presumably heme synthesis, is associated with more frequent porphyria attacks. […] Perioperative management includes the use of filters on operative lights to prevent skin burns and intestinal perforation. […] A high risk of primary hepatocellular carcinoma has been demonstrated in acute hepatic porphyrias, and periodic surveillance is recommended.

• #1 Acute Hepatic Porphyria: Tips and Treatments

  https://www.webmd.com/brain/acute-hepatic-porphyria-treatments

  Most people with the gene changes that cause AHP dont have symptoms. Certain things have to trigger the disease first. You cant control some of these, like hormone shifts during puberty. But you have a say in many others. Not everyone with AHP has the same triggers, and yours may change over time. […] Doctors suggest that all people with acute porphyria avoid it. […] Regular cigarettes, e-cigs, and marijuana are all potential triggers. […] Many medicines, including barbiturates, sulfa antibiotics, and birth control pills, can bring on an attack. Before you take any meds, check with your doctor. Be sure to tell emergency department staff you have porphyria, so you dont get medicine that makes your symptoms worse. And talk to your doctor about getting a medic alert bracelet or card. […] Low-calorie diets, or going a long time with little or no food can provoke attacks. If you want or need to lose weight, work with your doctor to figure out a way to do it safely.

• #1 How Can I Reduce the Risk of Acute Porphyria Attacks?Envelope icon

  https://porphyrianews.com/health-insights/how-can-i-reduce-the-risk-of-acute-porphyria-attacks/

  Another factor that is can cause acute porphyria attacks is alcohol, especially in excess. Alcohol consumption can lead to acute attacks and, over time, porphyrins can accumulate in the liver and cause liver damage. […] Certain forms of dieting for weight loss also can cause acute porphyria attacks. For example, low-calorie diets and diets low in carbohydrates can be triggers. […] Some studies have suggested that smoking also may be a trigger for acute porphyria attacks. […] Hormones also can play a factor in acute episodes of porphyria. Two major hormones that may trigger acute porphyria attacks are the female hormones progesterone and estrogen. […] Stress has been reported as a possible factor causing acute porphyria attacks although researchers don’t yet know the exact mechanism. Keeping your stress levels low could help reduce your risk of having an acute porphyria attack.

• #1 Porphyria: Types, Symptoms, and Treatment

  https://www.healthline.com/health/porphyria

  Porphyria cannot be prevented. However, symptoms can be reduced by avoiding or eliminating triggers. […] Factors that should be eliminated include: recreational drugs, mental stress, excessive drinking, certain antibiotics. […] Preventing erythropoietic symptoms focuses on reducing light exposure by: staying out of bright sunlight, wearing long sleeves, hats, and other protective clothing while outside, asking for protection during surgery (in rare cases phototoxic injury can occur; this happens when light perforates the organs and leads to infection).

• #1 Acute Hepatic Porphyria: Tips and Treatments

  https://www.webmd.com/brain/acute-hepatic-porphyria-treatments

  Good nutrition is an important part of managing this condition. A dietitian can help you get the right balance of carbs and nutrients. […] These can trigger an attack or make your symptoms worse. Be sure to treat any infection right away with safe antibiotics and get the vaccines your doctor suggests. […] Low iron levels could make it harder for your body to make heme. […] Some women have attacks in the days just before their period. Your doctor may try to prevent this with a hormone that keeps you from ovulating. […] If you have severe attacks every month, your doctor may try weekly doses of hemin to prevent them. This is usually an option only when other measures havent stopped your attacks. […] The FDA approved this med for AHP in 2019. You get it as a shot once a month. In clinical trials, people who got Givlaari had fewer attacks. It isnt for everyone and can cause serious side effects. […] This may be an option if you have severe attacks that other measures havent helped. You and your doctor will discuss the risks and benefits of this serious surgery.

• #1 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  A high-carbohydrate diet may decrease the risk of acute attacks. Some patients can sometimes treat mild acute attacks by increasing their intake of dextrose or glucose. Prolonged use should be avoided in order to decrease risk of obesity, diabetes mellitus, metabolic syndrome, and dental caries. […] To prevent renal damage, chronic systemic arterial hypertension should be treated aggressively (using safe medications). Patients with evidence of impaired renal function are referred to a nephrologist. […] The incidence of hepatocellular cancer is high among carriers of acute porphyria, especially in patients with active disease. Patients who are 49 years should undergo yearly or twice yearly surveillance, including liver screening with ultrasound. Early intervention can be curative and increases life expectancy.

• #1 Acute Porphyria – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/acute-porphyria/

  Its important for patients to understand what can make their condition worse and what signs to look out for. Eating a diet high in carbohydrates can help manage the illness. Doctors should talk with patients about the importance of drinking enough fluids, which can help get rid of porphyrins, a type of harmful compound, in the body. […] In situations where patients start experiencing high blood pressure, a diet low in salt, fat, and cholesterol is recommended. […] Patients should also be warned to avoid activities that could cause dehydration, deplete their body of carbohydrates, and tire them out excessively.

• #1 Porphyrias in the Age of Targeted Therapies

  https://www.mdpi.com/2075-4418/11/10/1795

  The phase III clinical trial, in which a significant reduction in the annualized acute porphyria attack rate (74% reduction in the treatment versus the placebo group) decreased the need for hemin use, and improved daily pain scores were observed with the monthly administration of givosiran at a dose of 2.5 mg/kg. […] Individuals with PCT experience bullous lesions and fluid-filled vesicles, which easily rupture and heal with crusting and scarring. […] Protection from exposure to sunlight, ultraviolet light and light emitted by fluorescent sources is the most important aspect of the prevention of cutaneous manifestations.

• #1 The porphyrias – British Porphyria Association

  http://porphyria.org.uk/the-eight-porphyrias/

  Although porphyria cant be cured, in some of the porphyrias, a number of lifestyle changes can help to minimise the chance of triggering symptoms. […] it is vital to take a few simple precautions to reduce the risk of attacks. […] everyone with VP should avoid triggers for acute attacks. […] Avoid direct sunlight as much as possible, even sunlight that passes through window glass in your home or car. […] Protect your skin by wearing dark-coloured densely woven clothing with long sleeves, light cotton gloves and a wide-brimmed hat. […] Ordinary sunscreens are not very effective. […] Your GP needs to prescribe it for you. […] Until an approved treatment is made available in the UK, it is mostly it is a matter of: avoiding being out in the sun, under bright artificial light or close to a window.

• #1 The porphyrias – British Porphyria Association

  http://porphyria.org.uk/the-eight-porphyrias/

  However, as Dundee Cream is highly visible when applied, and its formulation is frequently garment unfriendly, many patients find it rather impractical and that any benefit in terms of slowing inevitable EPP reactions is outweighed by its negatives. […] Vitamin D supplementation is required to prevent Vitamin D deficiency and bone density problems such as osteoporosis. […] The most important aspect of day-to-day management of CEP for most patients is the avoidance of sun/light exposure, as well as ultraviolet light and light emitted by fluorescent sources. […] If trauma occurs, antiseptic treatments should be used to prevent bacterial superinfections that can make skin blisters worse and result in scarring and mutilation. […] The procedure is associated with numerous risks and is usually only performed in severe transfusion-dependent patients.

• #1 Long-term management and treatment of acute intermittent porphyria with recurring attacks using pharmacological prophylaxis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10697622/

  There is no definitive guidance on whether patients with acute intermittent porphyria (AIP) with recurrent attacks need pharmacological prophylactic treatment. […] Prophylaxis could be considered for patients with AIP with 4 biochemically confirmed attacks/year after routine treatment of 12 years, during which the severity and frequency of attacks should be closely monitored to determine the necessity of pharmacologic prophylaxis. […] Prophylactic treatment was recommended to patients with 4 clinically and/or biochemically confirmed severe AAR in the previous year after the routine treatment of 12 years. […] A total of 9 patients with frequent attacks received pharmacologic prophylactic treatment, 7 received HA, 1 received givosiran, and 1 received HA and switched to givosiran due to participation in a phase 3 clinical trial.

• #1 Long-term management and treatment of acute intermittent porphyria with recurring attacks using pharmacological prophylaxis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10697622/

  The findings from this retrospective review of long-term management and treatment of AIP could be used to guide our AIP management practice and provide clues as to whether a patient with recurrent attacks requires pharmacologic prophylaxis and when to initiate it. […] Provision of prophylactic treatment should be limited to patients with frequent recurrent attacks after a thorough clinical investigation or observation period of at least 1 year, and the clinical presentations including the frequency and severity of attacks in the first 2 years after diagnosis should be examined. […] We recommend that pharmacologic prophylaxis be considered for patients with AIP with 4 clinically and biochemically confirmed annualized attacks in the previous year after the standard treatment of 12 years.

• #1 Porphyria, Acute Intermittent – Hematology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.7.7.

  1. Recommend avoidance of known factors causing porphyria attacks, including drugs. Detailed lists of safe and unsafe drugs can be found on European websites (porphyria.eu, www.drugs-porphyria.org) and North American websites (drug database at porphyriafoundation.com, porphyriadrugs.com) discussing porphyria. Patients should avoid tobacco smoking, marijuana smoking, and heavy alcohol intake. […] 7) For patients who have multiple attacks per year despite avoiding triggers, prophylactic hemin, gonadotropin-releasing hormone analogues (for women with recurrent luteal phase attacks), or givosiran (a small interfering RNA therapeutic directed against the gene that is induced in AIP, given as a once-monthly subcutaneous injection) may be indicated. Evidence supporting the use of givosiran in AIP comes from a small randomized controlled trial.

• #1 Benefits of prophylactic heme therapy in severe acute intermittent porphyria

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6358544/

  Acute intermittent porphyria (AIP), an autosomal dominant inborn error of metabolism, is the most common and severe form of the acute porphyrias. […] We report two patients with such frequent attacks of AIP, who have been managed with prophylactic heme therapy on a weekly basis. […] During 11-month duration of weekly prophylactic heme infusions, we observed a 100% decrease in acute attacks and inpatient admissions in one subject and a 75% decrease in the other. […] Thus, prophylactic heme therapy, through a multi-disciplinary approach, decreases the incidence of acute attacks, decreases health care costs and leads to better patient satisfaction and quality of life. […] Subjects were educated and counseled about weekly Panhematin infusions as prophylaxis to try to prevent frequent recurrent attacks.

• #1 Benefits of prophylactic heme therapy in severe acute intermittent porphyria

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6358544/

  After the young woman had returned monthly for 6months, each time with recurrent acute attacks that required hospitalizations, we convinced her to have a central venous port placed and by this means to receive a trial of weekly prophylactic IV heme in the form of Panhematin. […] After he had returned monthly for 12months, requiring hospital admissions of 57days out of every 30days, we convinced the patient to again have a central venous port inserted and thereby to undertake a trial of weekly prophylactic IV Panhematin. […] In a total of 11months’ follow-up for both the subjects after they had instituted weekly prophylactic Panhematin, we observed markedly decreased numbers of emergency room visits and inpatient admissions for acute porphyric attacks. […] Weekly regimens also significantly reduced both direct and total costs for the health care systems and led to better reimbursements to our healthcare system.

• #1 Porphyric Neuropathy

  https://practicalneurology.com/diseases-diagnoses/neuromuscular/porphyric-neuropathy/31689/

  Timely diagnosis and treatment and new medications to prevent attacks provide more options for treating acute hepatic porphyrias. […] Early diagnosis of AHP and avoidance or elimination of potential precipitants can prevent neurologic complications. […] Preventive therapy of frequent attacks includes prophylactic intravenous (IV) heme (once weekly), ALAS-1 mRNA antagonists, and identification and elimination of precipitants. […] Within 3 to 4 days of administration, IV heme normalizes ALA and PBG levels by suppressing hepatic ALAS1 induction. […] A single prophylactic treatment 1 to 4 times / month of 3 to 4 mg / kg of IV heme can prevent recurrent attacks. […] Givosiran was approved by the Food and Drug Administration (FDA) for treatment of AHPs in late 2019. […] The approved dosage of subcutaneous givosiran is 2.5 mg / kg once monthly.

• #1 Acute Intermittent Porphyria (AIP) – American Porphyria Foundation

  https://porphyriafoundation.org/for-patients/types-of-porphyria/aip/

  Dietary counseling is very important. Affected individuals who are prone to attacks should eat a normal balanced diet and should not greatly restrict their intake of carbohydrates or calories, even for short periods of time. […] Hormone manipulation may be effective in preventing such attacks and some affected women have been treated with gonadotropin-releasing hormone analogues (GnRH or LHRH treatments such as Lupron) to suppress ovulation and prevent frequent, cyclic attacks. Some individuals who experience recurrent attacks may benefit from regular, prophylactic hematin infusion. This is sometimes recommended for women with severe symptoms before or during the time of their menses. […] The prognosis of AIP is usually good if the disorder is recognized before severe nerve damage has occurred and if treatment and preventive measures are begun.

• #1 The acute hepatic porphyrias – Wang – Translational Gastroenterology and Hepatology

  https://tgh.amegroups.org/article/view/6239/html

  The mainstays of management during an acute attack are elimination of triggering factors, treatment of the acute symptoms, and therapy with intravenous heme. […] A number of conditions are known to induce heme synthesis and the expression of ALAS1 in the liver, which can lead to acute attacks. A mainstay in management of acute attacks is identifying and eliminating inducers of acute attacks. […] Patients who experience more than 3-4 attacks per year should consider prophylactic hematin therapy. […] A novel therapy is in development for prevention of acute attacks based on RNA-interference against ALAS1. […] Regular, long-term administration of hematin typically requires the placement of an indwelling venous catheter for access. […] The data indicate a high degree of efficacy with acceptable side-effects.

• #1 Acute Intermittent Porphyria Treatment & Management: Approach Considerations, Diet

  https://emedicine.medscape.com/article/205220-treatment

  The treatment goal for acute attacks of acute intermittent porphyria (AIP) is to decrease heme synthesis and reduce the production of porphyrin precursors. […] A minority of patients with AIP experience recurrent attacks. In addition to avoidance of precipitating factors, treatment options that may be considered in those cases include gonadotrophin-releasing hormone analogues (for women with attacks related to their menstrual cycles) and prophylactic hematin infusions. […] Givosiran (Givlaari) is approved by the US Food and Drug Administration (FDA) for adults with acute hepatic porphyrias, in which attacks are caused by induction of the enzyme 5-aminolevulinic acid synthase 1 (ALAS1). […] Rarely, liver transplantation may be indicated for patients with intractable recurrent attacks that are life-threatening or severely affect quality of life. Liver transplantation cures AIP. […] A comprehensive rehabilitation program, overseen by a physiatrist, can help patients regain functional independence after attacks of AIP. […] Gene therapy for AIP is currently under investigation.

• #1 Spotlight on givosiran for treating porphyria | DDDT

  https://www.dovepress.com/spotlight-on-givosiran-as-a-treatment-option-for-adults-with-acute-hep-peer-reviewed-fulltext-article-DDDT

  Givosiran is indicated for the treatment of AHP in general, caution in generalizability is warranted given the small number of subjects with VP or HCP. […] Givosiran was developed by Alnylam Pharmaceuticals (Cambridge, MA), is a siRNA that decreases hepatic delta-aminolevulinic acid synthase 1 (ALAS1) expression to prevent recurrent acute attacks of AIP or other acute porphyrias. […] Givosiran selectively targets hepatocytes due to its linkage to N-acetylgalactosamine (GalNac) leading to its selective uptake via asialoglycoprotein receptors (ASGPR). […] Givosiran exhibits linear plasma pharmacokinetics over a dose range of 0.35 to 2.5 mg/kg. […] Givosiran was found in multiple organs, including the heart, lungs, and adrenal glands, at significantly lower concentrations, ranging from 1/100 to 1/800 than of the concentrations found in the liver.

• #1 Spotlight on givosiran for treating porphyria | DDDT

  https://www.dovepress.com/spotlight-on-givosiran-as-a-treatment-option-for-adults-with-acute-hep-peer-reviewed-fulltext-article-DDDT

  Givosiran is a novel therapy that has shown to have significant efficacy in prevention of frequent recurrent attacks of AIP in recent clinical trials. […] Givosiran was studied in a similar patient population with a high disease burden; at least 2 attacks in the 6 months prior to study enrollment. Importantly, prophylactic hemin use was not permitted in the study population. […] Givosiran treatment led to sustained lowering of median ALA levels to near normal and PBG levels by 75% through month 24 as seen in Figure 6. […] Givosiran is very expensive. For patients weighing 75.6 kg or less, the average annual cost of givosiran, 2.5 mg/kg =189 mg/1 mL dose 12 months, is $575,000 per year, or $442,000 per year after expected discounts. […] Givosiran has potential adverse effects, especially risk of hepatic and renal adverse effects and of hyperhomocysteinemia, the latter a risk especially in patients with defects in MTHFR activity.

• #1

  https://www.healio.com/news/hematology-oncology/20181114/treatment-of-terribly-disabling-porphyria-complicated-by-disease-rarity-misdiagnosis

  These people dont have a lot of good therapeutic options and need a therapeutic that will both help prevent attacks as well as help alleviate the disease manifestations most commonly pain, nausea and fatigue in between attacks. […] It is important to develop new treatments to make porphyria attacks less frequent. […] Although there is no cure for porphyria, there are treatment options for each category of disease. […] Phase 1/phase 2 open-label extension studies of givosiran also presented at this years Annual International Liver Congress showed that the safety profile supports continued clinical development, given a greater than 90% decrease in the mean annualized porphyria attack rate and hemin use compared with baseline. […] The bottom line for the future is to determine whether givosiran can be effective to prevent acute attacks.

• #1 Porphyric Neuropathy

  https://practicalneurology.com/diseases-diagnoses/neuromuscular/porphyric-neuropathy/31689/

  Givosiran treatment resulted in a 73% reduction in mean annualized attack rate compared with placebo treatment. […] Timely diagnosis, prompt treatment, and elimination of potential precipitants can prevent neurologic complications of AHP. […] Givosiran, a small interfering mRNA therapy, represents a novel and targeted treatment approach and is the only FDA-approved treatment for the prevention of recurrent disabling attacks.

• #1 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Patients who experience recurrent and predictable attacks (typically women with attacks related to the menstrual cycle) can be given monthly givosiran at a dose of 2.5 mg/kg body weight by subcutaneous injection. Alternatively, patients may benefit from prophylactic heme therapy given shortly before the expected onset of an acute attack or weekly as prophylaxis. […] Frequent premenstrual attacks in some women are aborted by administration of a gonadotropin-releasing hormone agonist plus low-dose estrogen. Low-dose oral contraceptives are sometimes used successfully, but the progestin component is likely to exacerbate the porphyria.

• #1 Hormonal Contraception | International Porphyria Network

  https://new.porphyrianet.org/en/content/hormonal-contraception

  All lists of drugs that should be avoided in the acute porphyrias (AIP, VP, HCP) include the contraceptive pill. […] The only safe policy, therefore, is to use barrier methods of contraception and avoid the pill and other hormonal methods. […] Women who have had an attack of acute porphyria, even those who have been on the pill well before the attack started, should avoid all hormonal methods of contraception. […] Women who have never had symptoms but come from a family with one of the acute porphyrias should be tested to see whether they are affected. […] If, after receiving full information about acute porphyria and discussion of the likely consequences with their doctor, they do decide to start on the contraceptive pill, they should have a urine test for PBG. […] Women who have never had symptoms and have already been taking the pill for some time before they are found to be affected often wish to continue. […] The above advice applies only to the combined oral contraceptive pill that contains an oestrogen and a progestogen and to oral and depot progestogen-only preparations. […] All these remarks apply only to the acute porphyrias.

• #1 Porphyrias in the Age of Targeted Therapies

  https://www.mdpi.com/2075-4418/11/10/1795

  The treatment of acute porphyria attacks consists of symptomatic therapy, including medication for pain control and nausea, seizure control, correction of electrolyte disturbances, hemodynamic stabilization and mechanical ventilation if indicated. […] The only curative treatment approach for AHP is orthotopic liver transplantation (OLT), which has been shown to lead to rapid normalization of ALA and PBG levels and effectively prevent further acute porphyria attacks. […] Individuals who experience frequently recurrent acute attacks may benefit from off-label, regular prophylactic hematin infusions on a weekly or monthly basis in an attempt to regularly suppress increasing porphyrin precursor concentrations. […] In 2019, the Food and Drug Administration (FDA) and, in 2020, the European Medicines Agency (EMA) approved givosiran (Givlaari™, Alnylam Pharmaceuticals, Cambridge, MA, USA), a synthetic small interfering RNA (siRNA) molecule that targets and downregulates ALAS1 mRNA.

• #1 Porphyrias: Anesthetic Considerations – OpenAnesthesia

  https://www.openanesthesia.org/keywords/porphyrias-anesthetic-considerations/

  Both general and regional/neuraxial anesthesia have been safely administered. […] Anesthetic drugs that should be avoided include barbiturates, diazepam, etomidate, ketamine, phenytoin, and phenobarbital. […] For patients with acute porphyrias: […] Prolonged fasting should be avoided. Clear carbohydrate liquids up until two hours of surgery should be encouraged and dextrose-containing fluids should be used. […] Treatment of an acute crisis includes cardiorespiratory monitoring, treatment of abdominal pain/nausea/vomiting, hydration, monitoring of electrolytes, and administration of heme arginate, if necessary.

• #1 Malaria Prophylaxis for Patients With Porphyria Travelling in Southern Africa | Porphyria for Professionals

  https://porphyria.uct.ac.za/porphyria-professionals/porphyria-professionals/prescribing-porphyria-treatment-specific-disorders-poprhyria/malaria-prophylaxis-patients-porphyria-travelling-southern-africa

  Malaria Prophylaxis for Patients With Porphyria Travelling in Southern Africa […] In addition to the sensible precautions, appropriate prophylactic use of antimalarial drugs is important. […] The following recommendations are intended for patients with acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HCP). Patients with porphyria cutanea tarda (PCT) and erythropoietic protoporphyria (EPP) are not drug-sensitive, and may use antimalarial drugs freely. […] Note that the safety of the drugs recommended here cannot be guaranteed. These are newer drugs and there is still little actual clinical experience of their use in porphyria. However, on current information, they would not be expected to result in an exacerbation of porphyria. […] The following are the drugs recommended for use in porphyria. […] Atovaquone plus proguanil […] Mefloquine (Lariam) […] Drugs which should not be used […] Dapsone-pyrimethamine (Maloprim) […] Chloroquine […] Proguanil, (Paludrine) and proguanil/chloroquine combination (Daramol) […] Drugs which should be used with extreme caution only […] Doxycycline […] Halofantrine […] Artemisinin-lumefantrine (Coartem) […] Treatment of Malaria […] Drugs recommended for use […] Quinine sulphate […] Mefloquine […] Drugs to be avoided […] Chloroquine […] Doxycycline, tetracycline and clindamycin […] Fansidar (Sulfadoxine and pyrimethamine combination) […] Non-Falciparum Malaria […] Further Information […] Travelling to Areas Other than Southern Africa.

• #1 Diagnosis and management of acute hepatic porphyrias (AHP)AGA Logo_Horizontal

  https://gastro.org/clinical-guidance/diagnosis-and-management-of-acute-hepatic-porphyrias-ahp/

  Experts share 12 pieces of best practice advice for diagnosing and managing acute hepatic porphyrias. […] 6. Patients should be counseled to avoid identifiable triggers that may precipitate acute attacks, such as alcohol and porphyrinogenic medications. […] 7. Prophylactic heme therapy or givosiran, administered in an outpatient setting, should be considered in patients with recurrent attacks (4 or more per year). […] 12. Patients should be counseled on the chronic and long-term complications of AHP, including neuropathy, chronic kidney disease, hypertension, hepatocellular carcinoma and the need for long-term monitoring.

• #1 Acute Intermittent Porphyria (AIP) – American Porphyria Foundation

  https://porphyriafoundation.org/for-patients/types-of-porphyria/aip/

  Most people who inherit the gene for AIP never develop symptoms. However, experts recommend that all relatives of someone with AIP obtain testing, to determine who has the genetic trait and who does not. Those who test positive for the trait should be educated as to measures that will help avoid attacks. Prevention and avoidance of unsafe medications is essential to good management. […] Patients and family members who have inherited AIP should be counseled on how to limit their risk of any future acute attacks. This should include information about AIP and what causes attacks, how to check if a prescribed medication is safe or unsafe and details of relevant patient support groups. […] The objective of treatment is to manage symptoms, prevent complications and to suppress heme creation (synthesis) in the liver with Panhematin, which reduces the production of porphyrin precursors. Initial treatment steps also include stopping any medications that can potentially worsen AIP or cause an attack and ensuring proper caloric intake, which can include intravenous infusion of sufficient nutrients (glucose and salt).

• #1 Porphyria and genetics | EBSCO Research Starters

  https://www.ebsco.com/research-starters/health-and-medicine/porphyria-and-genetics

  Genetic testing may identify individuals at risk for porphyria. An individual who has a family member with the diagnosis of porphyria may be eligible for testing. An individual whose family member has had a test that showed DNA changes can also be tested for these changes. […] Genetic mutation cannot be corrected. However, attacks can be anticipated, prevented, or controlled. Steps to avoid porphyria attacks and complications include protecting skin from injury or infection and avoiding drugs and other triggers. […] Triggers for acute intermittent porphyria include drugs, such as barbiturates; sulfa drugs; seizure drugs; and steroid hormones, such as estrogen and progesterone. Other triggers include hormonal changes related to the menstrual cycle, weight-loss diets or fasting, infections, alcohol, stress, surgery, and cigarette smoke. […] Triggers for porphyria cutanea tarda include alcohol, estrogens, hydrocarbons, and certain pesticides or chemicals. Sunlight and weight-loss diets or fasting can trigger erythropoietic protoporphyria. Sunlight can trigger congenital erythropoietic protoporphyria.

• #1 Porphyria – UF Health

  https://ufhealth.org/conditions-and-treatments/porphyria

  Genetic counseling may benefit people who want to have children and who have a family history of any type of porphyria.

• #1 Alnylam Act® Acute Hepatic Porphyrias Sponsored Testing Program – PreventionGenetics

  https://www.preventiongenetics.com/sponsoredTesting/ahp

  Alnylam Pharmaceuticals and PreventionGenetics have partnered to offer genetic testing and counseling for patients pubescent and older who may carry a gene mutation known to be associated with the acute hepatic porphyrias. […] The Alnylam Act program was created to provide access to genetic testing and counseling to patients as a way to help people make more informed decisions about their health. […] Random (spot) urine for aminolevulinic acid (ALA), porphobilinogen (PBG), porphyrins is the primary test used to diagnosis AHP. A genetic test can be used to determine which AHP type a patient has and can be useful for at-risk family screening. […] Individuals in the US and Canada tested through the Alnylam Act program are eligible for optional pre- and post-test genetic counseling to help them understand their test results. This service is provided through GenomeMedical, a third-party genetic counseling service, and is made available by Alnylam at no charge as part of the program.

• #1 Importance of a Treatment Plan for Porphyria and What to IncludeEnvelope icon

  https://porphyrianews.com/health-insights/treatment-plan-for-porphyria/

  Porphyria is a rare disease that affects fewer than 200,000 people in the U.S. Many physicians are, therefore, unfamiliar with it and its treatment. This could be a major problem, particularly in a medical emergency. If you have the disease, working with your primary doctor to develop and maintain a treatment plan can help ensure that you get the best care possible. […] The treatment for porphyria depends on the severity of symptoms and the specific type of disease. Doctors usually treat acute porphyrias with heme infusions to slow the body’s production of porphyrins. In severe cases, patients may require a liver transplant. […] If you have cutaneous porphyrias, you should take care to avoid sunlight as much as possible. Doctors may treat you by taking blood draws to reduce your iron levels.

• #1 Importance of a Treatment Plan for Porphyria and What to IncludeEnvelope icon

  https://porphyrianews.com/health-insights/treatment-plan-for-porphyria/

  Your treatment plan should also contain the contact information of your primary care physician. Other emergency contacts, such as your healthcare proxy and a relative, should also be included. […] Acute porphyria can be life-threatening, especially if the disease affects the muscles that control breathing. Some patients may also experience seizures, hallucinations, and other symptoms, which may make it difficult or impossible for them to explain their condition when they’re experiencing a medical emergency, underscoring the importance of having a treatment plan readily available. […] If you provide emergency room personnel with your plan, they can contact your physician for any questions about your treatment. Another copy should go to your healthcare proxy, a legally designated individual who can, if necessary, make medical decisions on your behalf. Make sure you discuss the plan with your medical proxy.

• #1 Importance of a Treatment Plan for Porphyria and What to IncludeEnvelope icon

  https://porphyrianews.com/health-insights/treatment-plan-for-porphyria/

  Review your treatment plan and update all necessary sections after each doctor’s visit. Were you prescribed new medications? Does your doctor have new recommendations? Are you trying a new treatment? Has your doctor changed the dosages of your current medications? Include all this information in your treatment plan.

• #1 What is Porphyria? Causes, Prevention & Treatment

  https://www.drkarunhematology.com/blog/what-is-porphyria-causes-prevention-and-treatment/

  There is no cure for porphyria, but there are ways to prevent and treat the symptoms and complications. The prevention and treatment of porphyria depend on the type and severity of the condition, as well as the individuals medical history and lifestyle. […] Some general measures to prevent and treat porphyria include: […] Avoiding or minimizing the exposure to the triggers, such as alcohol, smoking, certain medications, fasting, stress, or sunlight […] Taking supplements or medications to replenish or reduce the levels of heme, porphyrins, or other substances in the body […] Using protective clothing, sunscreen, or artificial light sources to prevent or reduce skin damage from sunlight […] Seeking medical attention promptly if symptoms occur or worsen, especially during an acute attack

• #2 Porphyria: Symptoms, Diagnosis and Treatment

  https://www.webmd.com/a-to-z-guides/porphyria-symptoms-causes-treatment

  Most cases of prophyria are caused by genetic mutations, so you can’t prevent it. But if you know you have it, you can help prevent attacks by figuring out and avoiding your triggers. […] Most cases (about 75%-80%) of PCT are caused by exposure to things in your environment or an infection. To help avoid developing this form of PCT, avoid: Alcohol, Smoking, Medicines that have estrogen or iron, Get treatment for chronic hepatitis C and HIV, if you have these conditions, Get treatment for hemochromatosis, if you have this condition.

• #2 Porphyria | MedLink Neurology

  https://www.medlink.com/articles/porphyria

  Patients should avoid the risk factors known to precipitate acute attacks. Most important among these are certain drugs, steroid hormones, and anesthetic agents, as well as severe fasting, stress, infections, smoking, and alcohol. […] Screening of families to identify presymptomatic carriers is crucial to decrease the risk of overt disease of acute porphyrias through counseling about avoidance of potential precipitants. […] Levels of gonadal hormones are associated with a worsening of porphyria and explain the rarity of the expression of the disease before puberty and its frequency in adult women in the luteal phase of the menstrual cycle. In women where such an association is recognized, attacks can be prevented with a luteinizing hormone-releasing hormone analogue. […] Information, counseling, and education for asymptomatic and symptomatic patients are crucial; this helps avoid triggering factors of acute intermittent porphyria. Dietary precautions can help in preventing the next attack. A high intake of energy, sugar, and candies and a low alcohol intake keep biochemical disease activity at a lower level.

• #2 Acute Intermittent Porphyria Treatment & Management: Approach Considerations, Diet

  https://emedicine.medscape.com/article/205220-treatment

  The treatment goal for acute attacks of acute intermittent porphyria (AIP) is to decrease heme synthesis and reduce the production of porphyrin precursors. […] A minority of patients with AIP experience recurrent attacks. In addition to avoidance of precipitating factors, treatment options that may be considered in those cases include gonadotrophin-releasing hormone analogues (for women with attacks related to their menstrual cycles) and prophylactic hematin infusions. […] Givosiran (Givlaari) is approved by the US Food and Drug Administration (FDA) for adults with acute hepatic porphyrias, in which attacks are caused by induction of the enzyme 5-aminolevulinic acid synthase 1 (ALAS1). […] Rarely, liver transplantation may be indicated for patients with intractable recurrent attacks that are life-threatening or severely affect quality of life. Liver transplantation cures AIP. […] A comprehensive rehabilitation program, overseen by a physiatrist, can help patients regain functional independence after attacks of AIP. […] Gene therapy for AIP is currently under investigation.

• #2 How Can I Reduce the Risk of Acute Porphyria Attacks?Envelope icon

  https://porphyrianews.com/health-insights/how-can-i-reduce-the-risk-of-acute-porphyria-attacks/

  Another factor that is can cause acute porphyria attacks is alcohol, especially in excess. Alcohol consumption can lead to acute attacks and, over time, porphyrins can accumulate in the liver and cause liver damage. […] Certain forms of dieting for weight loss also can cause acute porphyria attacks. For example, low-calorie diets and diets low in carbohydrates can be triggers. […] Some studies have suggested that smoking also may be a trigger for acute porphyria attacks. […] Hormones also can play a factor in acute episodes of porphyria. Two major hormones that may trigger acute porphyria attacks are the female hormones progesterone and estrogen. […] Stress has been reported as a possible factor causing acute porphyria attacks although researchers don’t yet know the exact mechanism. Keeping your stress levels low could help reduce your risk of having an acute porphyria attack.

• #2 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Patients with acute porphyria should avoid the following: Potential precipitating medications (see the Drug Database for Acute Porphyria or the American Porphyria Foundation drug database) […] Heavy alcohol use […] Smoking […] Physical or emotional stress or exhaustion […] Exposure to organic solvents (eg, in herbicides, painting or dry cleaning products) […] Crash diets […] Prolonged periods caloric deprivation or starvation. […] Diets for obesity should provide gradual weight loss and be adopted only during periods of remission. Carriers of variegate porphyria or hereditary coproporphyria should minimize sun exposure; sunscreens that block only ultraviolet B light are ineffective, but opaque zinc oxide or titanium dioxide preparations are beneficial. […] Patients should be identified prominently in the medical record as carriers and should carry a card and wear medical alert jewelry verifying the carrier state and precautions to be observed.

• #2 Acute Intermittent Porphyria – Hormonal and Metabolic Disorders – MSD Manual Consumer Version

  https://www.msdmanuals.com/home/hormonal-and-metabolic-disorders/the-porphyrias/acute-intermittent-porphyria

  Attacks of acute intermittent porphyria can be prevented by […] Maintaining good nutrition, including eating sufficient carbohydrates […] Avoiding alcohol […] Avoiding medications that can cause an attack […] Avoiding smoking […] Avoiding physical and emotional stress and exhaustion […] Avoiding fasting or crash diets to lose weight rapidly. […] People who have attacks at predictable times, such as women whose attacks are related to the menstrual cycle, can be given heme by vein to prevent attacks. […] Givosiran is sometimes given once per month by injection under the skin to prevent acute attacks.

• #2 Porphyria Cutanea Tarda – Endocrine and Metabolic Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/porphyria-cutanea-tarda

  Patients should avoid sun exposure, using hats and clothing and zinc or titanium oxide sunscreens. Typical sunscreens that block UV light are ineffective, but UVA-absorbing sunscreens, such as those containing dibenzylmethanes, may help somewhat. […] Alcohol ingestion should be avoided permanently, and smoking should be stopped. If needed, estrogen supplementation, especially administered transdermally in low doses, can usually be resumed safely after a disease remission.

• #2 Acute Intermittent Porphyria (AIP) – American Porphyria Foundation

  https://porphyriafoundation.org/for-patients/types-of-porphyria/aip/

  Dietary counseling is very important. Affected individuals who are prone to attacks should eat a normal balanced diet and should not greatly restrict their intake of carbohydrates or calories, even for short periods of time. […] Hormone manipulation may be effective in preventing such attacks and some affected women have been treated with gonadotropin-releasing hormone analogues (GnRH or LHRH treatments such as Lupron) to suppress ovulation and prevent frequent, cyclic attacks. Some individuals who experience recurrent attacks may benefit from regular, prophylactic hematin infusion. This is sometimes recommended for women with severe symptoms before or during the time of their menses. […] The prognosis of AIP is usually good if the disorder is recognized before severe nerve damage has occurred and if treatment and preventive measures are begun.

• #2 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  A high-carbohydrate diet may decrease the risk of acute attacks. Some patients can sometimes treat mild acute attacks by increasing their intake of dextrose or glucose. Prolonged use should be avoided in order to decrease risk of obesity, diabetes mellitus, metabolic syndrome, and dental caries. […] To prevent renal damage, chronic systemic arterial hypertension should be treated aggressively (using safe medications). Patients with evidence of impaired renal function are referred to a nephrologist. […] The incidence of hepatocellular cancer is high among carriers of acute porphyria, especially in patients with active disease. Patients who are 49 years should undergo yearly or twice yearly surveillance, including liver screening with ultrasound. Early intervention can be curative and increases life expectancy.

• #2 Porphyria: Types, Symptoms, and Treatment

  https://www.healthline.com/health/porphyria

  Porphyria cannot be prevented. However, symptoms can be reduced by avoiding or eliminating triggers. […] Factors that should be eliminated include: recreational drugs, mental stress, excessive drinking, certain antibiotics. […] Preventing erythropoietic symptoms focuses on reducing light exposure by: staying out of bright sunlight, wearing long sleeves, hats, and other protective clothing while outside, asking for protection during surgery (in rare cases phototoxic injury can occur; this happens when light perforates the organs and leads to infection).

• #2 The porphyrias – British Porphyria Association

  http://porphyria.org.uk/the-eight-porphyrias/

  However, as Dundee Cream is highly visible when applied, and its formulation is frequently garment unfriendly, many patients find it rather impractical and that any benefit in terms of slowing inevitable EPP reactions is outweighed by its negatives. […] Vitamin D supplementation is required to prevent Vitamin D deficiency and bone density problems such as osteoporosis. […] The most important aspect of day-to-day management of CEP for most patients is the avoidance of sun/light exposure, as well as ultraviolet light and light emitted by fluorescent sources. […] If trauma occurs, antiseptic treatments should be used to prevent bacterial superinfections that can make skin blisters worse and result in scarring and mutilation. […] The procedure is associated with numerous risks and is usually only performed in severe transfusion-dependent patients.

• #2 Porphyria Los Angeles | Porphyria Treatment | Porphyria Specialist

  https://www.tabibmd.com/symptoms-conditions/porphyria/

  Porphyria treatments are about controlling symptoms and vary depending on whether your condition is acute or cutaneous. However, minimizing exposure to potential triggers is recommended in both cases. […] That may include stopping medications that trigger symptoms or avoiding exposure to sunlight. In patients with cutaneous porphyria who need to avoid the sun, vitamin D supplements may be recommended to compensate. […] Other treatments for cutaneous porphyria include the drawing of blood to reduce excess hemoglobin, the use of malaria drugs to absorb porphyrins, and prescription beta carotene, which can boost your skins tolerance to sunlight. […] Patients with acute porphyria often benefit from medications that control pain, nausea, and vomiting. Intravenous sugar may be essential to maintain adequate carbohydrate levels, as well as intravenous fluids to maintain hydration. Some patients also benefit from injections of hemin, a substance that limits the bodys production of porphyrin.

• #2 Long-term management and treatment of acute intermittent porphyria with recurring attacks using pharmacological prophylaxis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10697622/

  The findings from this retrospective review of long-term management and treatment of AIP could be used to guide our AIP management practice and provide clues as to whether a patient with recurrent attacks requires pharmacologic prophylaxis and when to initiate it. […] Provision of prophylactic treatment should be limited to patients with frequent recurrent attacks after a thorough clinical investigation or observation period of at least 1 year, and the clinical presentations including the frequency and severity of attacks in the first 2 years after diagnosis should be examined. […] We recommend that pharmacologic prophylaxis be considered for patients with AIP with 4 clinically and biochemically confirmed annualized attacks in the previous year after the standard treatment of 12 years.

• #2 Diagnosis and management of acute hepatic porphyrias (AHP)AGA Logo_Horizontal

  https://gastro.org/clinical-guidance/diagnosis-and-management-of-acute-hepatic-porphyrias-ahp/

  Experts share 12 pieces of best practice advice for diagnosing and managing acute hepatic porphyrias. […] 6. Patients should be counseled to avoid identifiable triggers that may precipitate acute attacks, such as alcohol and porphyrinogenic medications. […] 7. Prophylactic heme therapy or givosiran, administered in an outpatient setting, should be considered in patients with recurrent attacks (4 or more per year). […] 12. Patients should be counseled on the chronic and long-term complications of AHP, including neuropathy, chronic kidney disease, hypertension, hepatocellular carcinoma and the need for long-term monitoring.

• #2 Benefits of prophylactic heme therapy in severe acute intermittent porphyria

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6358544/

  After the young woman had returned monthly for 6months, each time with recurrent acute attacks that required hospitalizations, we convinced her to have a central venous port placed and by this means to receive a trial of weekly prophylactic IV heme in the form of Panhematin. […] After he had returned monthly for 12months, requiring hospital admissions of 57days out of every 30days, we convinced the patient to again have a central venous port inserted and thereby to undertake a trial of weekly prophylactic IV Panhematin. […] In a total of 11months’ follow-up for both the subjects after they had instituted weekly prophylactic Panhematin, we observed markedly decreased numbers of emergency room visits and inpatient admissions for acute porphyric attacks. […] Weekly regimens also significantly reduced both direct and total costs for the health care systems and led to better reimbursements to our healthcare system.

• #2 Panhematin for Prevention of Acute Attacks of Porphyria | Clinical Trial | medthority.com

  https://www.medthority.com/clinical-trials/acute-hepatic-porphyria/panhematin-for-prevention-of-acute-attacks-of-porphyria/

  The purpose of this study is to determine if Panhematin is safe and effective for prevention of acute attacks of porphyria. […] The study aims to provide high quality evidence for the use on hemin for prevention of acute attacks of porphyria. […] High quality studies have not been done previously for treating or preventing acute attacks with hemin. […] The lack of strong evidence for efficacy of hemin for treatment and prevention of attacks limits its availability for patients with acute porphyrias. […] This is a double-blind, randomized, placebo-controlled, parallel group trial investigating the efficacy and safety of Panhematin for preventing acute attacks in at least 20 subjects with well-documented acute porphyria. […] It is expected that they will have had 6 or more attacks in one year before starting hemin prophylaxis.

• #2 Porphyrias in the Age of Targeted Therapies

  https://www.mdpi.com/2075-4418/11/10/1795

  The treatment of acute porphyria attacks consists of symptomatic therapy, including medication for pain control and nausea, seizure control, correction of electrolyte disturbances, hemodynamic stabilization and mechanical ventilation if indicated. […] The only curative treatment approach for AHP is orthotopic liver transplantation (OLT), which has been shown to lead to rapid normalization of ALA and PBG levels and effectively prevent further acute porphyria attacks. […] Individuals who experience frequently recurrent acute attacks may benefit from off-label, regular prophylactic hematin infusions on a weekly or monthly basis in an attempt to regularly suppress increasing porphyrin precursor concentrations. […] In 2019, the Food and Drug Administration (FDA) and, in 2020, the European Medicines Agency (EMA) approved givosiran (Givlaari™, Alnylam Pharmaceuticals, Cambridge, MA, USA), a synthetic small interfering RNA (siRNA) molecule that targets and downregulates ALAS1 mRNA.

• #2 04156 Recurrent acute intermittent porphyria attacks after normalization of porphobilinogen on givosiran prophylaxis | BMJ Open Gastroenterology

  https://bmjopengastro.bmj.com/content/11/Suppl_1/A22.2

  Givosiran is an interfering RNA therapeutic targeting hepatic ALAS1 mRNA, and the first-in-its-class drug approved for treatment of acute hepatic porphyrias (AHP). It reduces ALAS1 expression, thus reducing delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) over-production and accumulation. […] The goal of givosiran prophylaxis is normalization of urine PBG and prevention of attacks. […] In clinical trials of givosiran, attack rates were substantially reduced in AHP patients, but levels of ALA and PBG that occurred during infrequent attacks were not described. […] This suggests that mechanisms additional to elevation in levels of ALA and PBG, which are potentially neurotoxic, may contribute to symptoms during attacks of AHP.

• #2 Porphyric Neuropathy

  https://practicalneurology.com/diseases-diagnoses/neuromuscular/porphyric-neuropathy/31689/

  Timely diagnosis and treatment and new medications to prevent attacks provide more options for treating acute hepatic porphyrias. […] Early diagnosis of AHP and avoidance or elimination of potential precipitants can prevent neurologic complications. […] Preventive therapy of frequent attacks includes prophylactic intravenous (IV) heme (once weekly), ALAS-1 mRNA antagonists, and identification and elimination of precipitants. […] Within 3 to 4 days of administration, IV heme normalizes ALA and PBG levels by suppressing hepatic ALAS1 induction. […] A single prophylactic treatment 1 to 4 times / month of 3 to 4 mg / kg of IV heme can prevent recurrent attacks. […] Givosiran was approved by the Food and Drug Administration (FDA) for treatment of AHPs in late 2019. […] The approved dosage of subcutaneous givosiran is 2.5 mg / kg once monthly.

• #2 Porphyric Neuropathy

  https://practicalneurology.com/diseases-diagnoses/neuromuscular/porphyric-neuropathy/31689/

  Givosiran treatment resulted in a 73% reduction in mean annualized attack rate compared with placebo treatment. […] Timely diagnosis, prompt treatment, and elimination of potential precipitants can prevent neurologic complications of AHP. […] Givosiran, a small interfering mRNA therapy, represents a novel and targeted treatment approach and is the only FDA-approved treatment for the prevention of recurrent disabling attacks.

• #2 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Patients who experience recurrent and predictable attacks (typically women with attacks related to the menstrual cycle) can be given monthly givosiran at a dose of 2.5 mg/kg body weight by subcutaneous injection. Alternatively, patients may benefit from prophylactic heme therapy given shortly before the expected onset of an acute attack or weekly as prophylaxis. […] Frequent premenstrual attacks in some women are aborted by administration of a gonadotropin-releasing hormone agonist plus low-dose estrogen. Low-dose oral contraceptives are sometimes used successfully, but the progestin component is likely to exacerbate the porphyria.

• #2 Porphyrias: Anesthetic Considerations – OpenAnesthesia

  https://www.openanesthesia.org/keywords/porphyrias-anesthetic-considerations/

  Both general and regional/neuraxial anesthesia have been safely administered. […] Anesthetic drugs that should be avoided include barbiturates, diazepam, etomidate, ketamine, phenytoin, and phenobarbital. […] For patients with acute porphyrias: […] Prolonged fasting should be avoided. Clear carbohydrate liquids up until two hours of surgery should be encouraged and dextrose-containing fluids should be used. […] Treatment of an acute crisis includes cardiorespiratory monitoring, treatment of abdominal pain/nausea/vomiting, hydration, monitoring of electrolytes, and administration of heme arginate, if necessary.

• #2 Porphyria – UF Health

  https://ufhealth.org/conditions-and-treatments/porphyria

  Genetic counseling may benefit people who want to have children and who have a family history of any type of porphyria.

• #2 Treatment of the Acute Attack | Porphyria for Patients

  https://porphyria.uct.ac.za/porphyria-patients/treatment/treatment-acute-attack

  An essential first step is to in ensure that a full diagnosis of the porphyrias has been made including: […] Your first responsibility is to take all necessary drug precautions to avoid developing an acute attack. In families who are well educated about the dangers of the acute attack and its relationship to drug induction, the acute attack is now a very rare phenomenon. All family members should be screened so that carriers can take the same precautions. […] The first step is to confirm the presence of an acute attack. Consult a doctor as soon as possible and insist that your urine is tested for the presence of elevated PBG. […] Patients require in most instances to be admitted to hospital. They usually need powerful analgesics such as pethidine for control of the pain of the acute attack.

• #2 Porphyria | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/porphyria

  In most cases, a combination of genetic and environmental factors trigger porphyria symptoms. […] by avoiding triggers, development of symptoms of porphyria can be prevented. […] general suggestions for preventing symptoms of porphyria include: […] In all cases avoid known triggers for example, dont smoke or drink alcohol. […] When out in the sun, wear sunglasses, a brimmed hat, a long-sleeved top and long pants. Apply SPF 30+ sunscreen to exposed skin areas. […] Protect your skin every day. For example, wear rubber gloves when handling chemicals or very hot water. Avoid perfumed soaps. Regularly apply barrier cream to the hands. […] Eat regular meals. […] Consider wearing a medical alert bracelet or pendant, as surgery and some medications can provoke symptoms.

• #2 Importance of a Treatment Plan for Porphyria and What to IncludeEnvelope icon

  https://porphyrianews.com/health-insights/treatment-plan-for-porphyria/

  Your treatment plan should also contain the contact information of your primary care physician. Other emergency contacts, such as your healthcare proxy and a relative, should also be included. […] Acute porphyria can be life-threatening, especially if the disease affects the muscles that control breathing. Some patients may also experience seizures, hallucinations, and other symptoms, which may make it difficult or impossible for them to explain their condition when they’re experiencing a medical emergency, underscoring the importance of having a treatment plan readily available. […] If you provide emergency room personnel with your plan, they can contact your physician for any questions about your treatment. Another copy should go to your healthcare proxy, a legally designated individual who can, if necessary, make medical decisions on your behalf. Make sure you discuss the plan with your medical proxy.

• #2 Porphyria – British Liver Trust

  https://britishlivertrust.org.uk/information-and-support/liver-conditions/porphyria/

  Following diagnosis, most people with porphyria are able to lead relatively normal lives by following simple measures to prevent symptoms occurring. […] To prevent acute attacks, it is sensible to avoid: taking or accepting medication without first checking that it is safe for you. A list of drugs that are considered safe in the treatment of porphyrias can be obtained from the organisations listed below. […] People with cutaneous porphyrias should stay out of the sun as much as possible. Even exposure to bright light through the windows of a building or car should be avoided. When outside it is advisable to wear sun-protective clothing and heavy sun block containing zinc or titanium. […] PCT, the most common skin porphyria, is linked with iron-overload and may cause serious liver damage if not regulated. You may be asked to avoid food rich in iron, vitamin C supplements and high dose oestrogen via contraception. […] As is the case in anyone who has a liver condition, alcohol should be avoided.

• #2 How Can I Reduce the Risk of Acute Porphyria Attacks?Envelope icon

  https://porphyrianews.com/health-insights/how-can-i-reduce-the-risk-of-acute-porphyria-attacks/

  If you have one of the acute types of porphyria you may have experienced acute porphyria attacks. These attacks usually consist of pain in the abdomen, which may spread into the back and thighs. They also may involve nausea, vomiting, constipation, confusion, and disorientation. Severe attacks may require hospitalization. […] Many of these periods are provoked by certain circumstances that may be preventable. Here is more information about the factors that can trigger attacks and how you can avoid them. […] Being proactive can help you to reduce your risk of acute attacks. […] There are a large number of medications that can trigger attacks. These medications are known as porphyrinogens and include some anesthetics, antihistamines — allergy medicines — antiepileptics, antihyperglycemics, antibiotics, and heart medicines.

• #2 Treatment of the acute attack | International Porphyria Network

  https://new.porphyrianet.org/en/content/treatment-acute-attack

  Mild attacks may resolve with supportive treatment. Severe attacks should be treated with intravenous hemin. […] Most patients are managed with prophylactic human hemin, Long term treatment with hemin usually provides some benefit, but is only partially effective with many patients continuing to have attacks and hospital admissions, as well as debilitating symptoms such as pain, nausea, and fatigue, which have a profound negative impact on all aspects of their lives. […] Givlaari (givosiran) is a new treatment to prevent recurrent attacks which has shown high efficacy and an acceptable safety profile in clinical trials.

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