InternPractice — Always a Step Ahead

Overview

Indications And Dose

Multibacillary leprosy in combination with rifampicin and clofazimine (3-drug regimen) | Paucibacillary leprosy in combination with rifampicin (2-drug regimen) ▶BY MOUTH ▶Adult (body-weight up to 35 kg): 50 mg daily, alternatively 1–2 mg/kg daily, may be self- administered ▶Adult (body-weight 35 kg and above): 100 mg daily, may be self-administered Dermatitis herpetiformis ▶BY MOUTH ▶Adult: (consult product literature or local protocols) Treatment of mild to moderate Pneumocystis jirovecii (Pneumocystis carinii) pneumonia (in combination with trimethoprim) ▶BY MOUTH ▶Adult: 100 mg once daily Prophylaxis of Pneumocystis jirovecii (Pneumocystis carinii) pneumonia ▶BY MOUTH ▶Adult: 100 mg daily l UNLICENSED USE Not licensed for treatment of pneumocystis (P. jirovecii) pneumonia.

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Cautions

Anaemia (treat severe anaemia before starting) . avoid in Acute porphyrias p. 1120. cardiac disease. G6PD deﬁciency. pulmonary disease. susceptibility to haemolysis

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Safety

Interactions

→Appendix 1: dapsone

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Side Effects

Agranulocytosis. appetite decreased. haemolysis. haemolytic anaemia. headache. hepatic disorders. hypoalbuminaemia. insomnia. lepra reaction. methaemoglobinaemia. motor loss. nausea. peripheral neuropathy. photosensitivity reaction. psychosis. severe cutaneous adverse reactions (SCARs). skin reactions. tachycardia. vomiting SIDE-EFFECTS, FURTHER INFORMATION Side-effects are dose-related. If dapsone syndrome occurs (rash with fever and eosinophilia)—discontinue immediately (may progress to exfoliative dermatitis, hepatitis, hypoalbuminaemia, psychosis and death).

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Pregnancy

Folic acid p. 1084 (higher dose) should be given to mother throughout pregnancy; neonatal haemolysis and methaemoglobinaemia reported in third trimester.

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Breast Feeding

Haemolytic anaemia; although signiﬁcant amount in milk, risk to infant very small unless infant is G6PD deﬁcient.

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Dose and formulations

Medicinal Forms

There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: oral suspension, oral solution Tablet CAUTIONARY AND ADVISORY LABELS 8 ▶Dapsone (Non-proprietary) Dapsone 50 mg Dapsone 50mg tablets | 28 tablet P £36.22 DT = £11.56 Dapsone 100 mg Dapsone 100mg tablets | 28 tablet P £97.39 DT = £57.37 2.3 Lyme disease Lyme disease Description of condition Lyme disease, also known as Lyme borreliosis, is an infection caused by bacteria called Borrelia burgdorferi. It is transmitted to humans by the bite of an infected tick. Ticks are mainly found in grassy and wooded areas including urban gardens and parks. Most tick bites do not cause Lyme disease, and the prompt and correct removal of the tick reduces the risk of infection. Lyme disease usually presents with a characteristic erythema migrans rash. This usually becomes visible 1–4 weeks after a tick bite, but can appear from 3 days to 3 months, and last for several weeks. It may be accompanied by non-focal (non-organ related) symptoms, such as fever, swollen glands, malaise, fatigue, neck pain or stiffness, joint or muscle pain, headache, cognitive impairment, or paraesthesia. Other signs and symptoms of Lyme disease may also appear months or years after the initial infection and are typically characterised by focal symptoms (relating to at least 1 organ system). These include neurological (affecting cranial nerves, peripheral and central nervous systems), joint (Lyme arthritis), cardiac (Lyme carditis), or skin (acrodermatitis chronica atrophicans) manifestations. Drug treatment g Patients diagnosed with Lyme disease should be given treatment with an antibacterial drug; the choice of drug should be based on presenting symptoms. In patients who present with focal symptoms, a discussion with, or referral to, a specialist should be considered but should not delay treatment. In patients presenting with erythema migrans rash with or without non-focal symptoms, oral doxycycline p. 597 [unlicensed indication] is recommended as ﬁrst-line treatment. If doxycycline p. 597 cannot be given, oral amoxicillin p. 579 should be used as an alternative. Oral azithromycin p. 566 [unlicensed indication] should be given if both doxycycline p. 597 and amoxicillin p. 579 are unsuitable. In patients presenting with focal symptoms of cranial nerve or peripheral nervous system involvement, oral doxycycline p. 597 [unlicensed indication] is recommended as ﬁrst-line Infection treatment. If doxycycline p. 597 cannot be given, oral amoxicillin p. 579 should be used as an alternative. In patients presenting with symptoms of central nervous system involvement, intravenous ceftriaxone p. 556 is recommended as ﬁrst-line treatment. Oral doxycycline p. 597 [unlicensed indication] should be used as an alternative if ceftriaxone p. 556 cannot be given, or when switching to oral antibacterial treatment. In patients with symptoms of Lyme arthritis or acrodermatitis chronica atrophicans, oral doxycycline p. 597 [unlicensed indication] is recommended as ﬁrst-line treatment. If doxycycline p. 597 cannot be given, oral amoxicillin p. 579 should be used as an alternative. Intravenous ceftriaxone p. 556 should be given if both doxycycline p. 597 and amoxicillin p. 579 are unsuitable. In patients with symptoms of Lyme carditis who are haemodynamically stable, oral doxycycline p. 597 [unlicensed indication] is recommended as ﬁrst-line treatment. If doxycycline p. 597 cannot be given, intravenous ceftriaxone p. 556 should be used as an alternative. In patients with symptoms of Lyme carditis who are haemodynamically unstable, intravenous ceftriaxone p. 556 is recommended. Oral doxycycline p. 597 [unlicensed indication] should be given when switching to oral antibacterial treatment. h Ongoing symptom management g If symptoms continue to persist or worsen after antibacterial treatment, patients should be assessed for possible alternative causes, re-infection with Lyme disease, treatment failure or non-adherence to previous antibacterial treatment, or progression to organ damage caused by Lyme disease (such as nerve palsy). A second course of antibacterial treatment should be given to patients presenting with signs and symptoms of re- infection. In patients presenting with ongoing symptoms due to possible treatment failure, treatment with an alternative antibacterial drug should be considered. A third course of antibacterial treatment is not recommended, and further management should be discussed with a national reference laboratory or suitable specialist depending on symptoms (for example, a rheumatologist or neurologist). h Useful Resources Lyme disease. National Institute for Health and Care Excellence. NICE guideline 95. April 2018. www.nice.org.uk/guidance/ng95 ‘Be tick aware’–Toolkit for raising awareness of the potential risk posed by ticks and tick-borne disease in England. Public Health England. March 2018. www.gov.uk/government/publications/tick-bite-risks-and- prevention-of-lyme-disease 2.4 Methicillin-resistant staphylococcus aureus MRSA Infection Management Infection from Staphylococcus aureus strains resistant to meticillin [now discontinued] (meticillin-resistant Staph. aureus, MRSA) and to ﬂucloxacillin p. 586 can be difﬁcult to manage. Treatment is guided by the sensitivity of the infecting strain. Rifampicin p. 615 or fusidic acid p. 604 should not be used alone because resistance may develop rapidly. A tetracycline alone or a combination of rifampicin and fusidic acid can be used for skin and soft-tissue infections caused by MRSA; clindamycin p. 564 alone is an alternative. A glycopeptide (e.g. vancomycin p. 562) can be used for severe skin and soft-tissue infections associated with MRSA; if a glycopeptide is unsuitable, linezolid p. 605 can be used on expert advice. As linezolid is not active against Gram- negative organisms, it can be used for mixed skin and soft- tissue infections only when other treatments are not available; linezolid must be given with other antibacterials if the infection also involves Gram-negative organisms. A combination of a glycopeptide and fusidic acid or a glycopeptide and rifampicin can be considered for skin and soft-tissue infections that have failed to respond to a single antibacterial. Tigecycline p. 601 and daptomycin p. 602 are licensed for the treatment of complicated skin and soft-tissue infections involving MRSA. A tetracycline or clindamycin can be used for bronchiectasis caused by MRSA. A glycopeptide can be used for pneumonia associated with MRSA; if a glycopeptide is unsuitable, linezolid can be used on expert advice. Linezolid must be given with other antibacterials if the infection also involves Gram-negative organisms. A tetracycline can be used for urinary-tract infections caused by MRSA; trimethoprim p. 607 or nitrofurantoin p. 625 are alternatives. A glycopeptide can be used for urinary-tract infections that are severe or resistant to other antibacterials. A glycopeptide can be used for septicaemia associated with MRSA. See the management of endocarditis, osteomyelitis, or septic arthritis associated with MRSA. Prophylaxis with vancomycin or teicoplanin p. 561 (alone or in combination with another antibacterial active against other pathogens) is appropriate for patients undergoing surgery if: . there is a history of MRSA colonisation or infection without documented eradication; . there is a risk that the patient’s MRSA carriage has recurred; . the patient comes from an area with a high prevalence of MRSA. See eradication of nasal carriage of MRSA in Nose p. 1265. 2.5 Tuberculosis Tuberculosis Overview Tuberculosis is a curable infectious disease caused by bacteria of the Mycobacterium tuberculosis complex (M. tuberculosis, M. africanum, M. bovis or M. microti) and is spread by breathing in infected respiratory droplets from a person with infectious tuberculosis. The most common form of tuberculosis infection is in the lungs (pulmonary) but infection can also spread and develop in other parts of the body (extrapulmonary). The initial infection with tuberculosis clears in the majority of individuals. However, in some cases the bacteria may become dormant and remain in the body with no symptoms (latent tuberculosis) or progress to being symptomatic (active tuberculosis) over the following weeks or months. In individuals with latent tuberculosis only a small proportion will develop active tuberculosis. Many cases of tuberculosis can be prevented by public health measures and when clinical disease does occur most individuals can be cured if treated properly with the correct dose, combination and duration of treatment. Drug-resistant strains of tuberculosis are much harder to treat and signiﬁcantly increase an individual’s risk of long-term complications or death. Treatment phases, overview The standard treatment of active tuberculosis is completed in two phases—an initial phase using four drugs and a continuation phase using two drugs, in fully sensitive cases. g The management of tuberculosis should be under specialist care by clinicians with training in, and experience of, the specialised care of individuals with tuberculosis. This tuberculosis service should include specialised nurses and health visitors. h Within the UK there are two regimens recommended for the treatment of tuberculosis: unsupervised or supervised. The choice of either regimen is dependent on a risk assessment to identify if an individual needs enhanced case management. g In all phases of treatment for tuberculosis, ﬁxed-dose combination tablets should be used, and a daily dosing schedule should be considered in active tuberculosis. h Initial phase g As standard treatment for individuals with active tuberculosis, offer rifampicin p. 615, ethambutol hydrochloride p. 620, pyrazinamide p. 621 and isoniazid p. 621 (with pyridoxine hydrochloride p. 1141) in the initial phase of therapy; modiﬁed according to drug susceptibility testing; and continued for 2 months. Treatment should be started without waiting for culture results if clinical signs and symptoms are consistent with a tuberculosis diagnosis; consider completing the standard treatment even if subsequent culture results are negative. h Continuation phase g After the initial phase, offer standard continuation treatment with rifampicin and isoniazid (with pyridoxine hydrochloride) for a further 4 months in individuals with active tuberculosis without central nervous system involvement. Longer treatment for 10 months should be offered in individuals with active tuberculosis of the central nervous system, with or without spinal involvement. Treatment should be modiﬁed according to drug susceptibility testing. h Unsupervised treatment The unsupervised treatment regimen is for individuals who are likely to take antituberculosis drugs reliably and willingly without supervision. Supervised treatment For individuals requiring supervised treatment (directly observed therapy, DOT), this is offered as part of enhanced case management. g A 3 times weekly dosing schedule can be considered in individuals with tuberculosis if they require enhanced case management and daily directly observed therapy is not available. Antituberculosis treatment dosing regimens of fewer than 3 times a week are not recommended. h g Directly observed therapy should be offered to individuals who: . have a current risk or history of non-adherence; . have previously been treated for tuberculosis; . have a history of homelessness, drug or alcohol misuse; . are in prison or a young offender institution, or have been in the past 5 years; . have a major psychiatric, memory or cognitive disorder; . are in denial of the tuberculosis diagnosis; . have multi-drug resistant tuberculosis; . request directly observed therapy after discussion with the clinical team; . are too ill to self-administer treatment. h Individuals with comorbidities or coexisting conditions, including the immunocompromised g Individuals with comorbidities or coexisting conditions (such as HIV, severe liver disease, chronic kidney disease, diabetes, eye disease or vision impairment, a history of alcohol or substance misuse, or who are pregnant or breastfeeding) should be managed by a specialist multidisciplinary team with experience in managing tuberculosis and the comorbidity or coexisting condition. For individuals who are HIV-positive with active TB, treatment with the standard regimen should not routinely exceed 6 months, unless the tuberculosis has central nervous system involvement, in which case treatment should not routinely extend beyond 12 months. Care should be taken to avoid drug interactions when co- prescribing antiretroviral and antituberculosis drugs. h For further information on the management of tuberculosis in HIV infection, see British HIV Association guideline: Management of tuberculosis in adults living with HIV (available at www.bhiva.org/guidelines). Extrapulmonary tuberculosis Central nervous system tuberculosis g Individuals with central nervous system tuberculosis should be offered standard treatment with initial phase drugs for 2 months (see Initial phase for speciﬁc drugs). After completion of the initial treatment phase, standard treatment with continuation phase drugs should then be offered (see Continuation phase for speciﬁc drugs); and continued for a further 10 months. Treatment for tuberculous meningitis should be offered if clinical signs and other laboratory ﬁndings are consistent with the diagnosis, even if a rapid diagnostic test is negative. An initial high dose of dexamethasone or prednisolone should be offered at the same time as antituberculosis treatment, then slowly withdrawn over 4–8 weeks. h For additional information on corticosteroid use, see NICE clinical guideline: Tuberculosis (see Useful resources). g Referral for surgery should only be considered in individuals who have raised intracranial pressure; or have spinal TB with spinal instability or evidence of spinal cord compression. h Pericardial tuberculosis g An initial high dose of oral prednisolone should be offered to individuals with active pericardial tuberculosis, at the same time as antituberculosis treatment, then slowly withdrawn over 2–3 weeks. h For additional information on corticosteroid use, see NICE clinical guideline: Tuberculosis (see Useful resources). Latent tuberculosis Some individuals with latent tuberculosis are at increased risk of developing active tuberculosis (such as individuals who are HIV-positive, diabetic, injecting drug users, or receiving treatment with an anti-tumor necrosis factor alpha inhibitor). g If for any reason these individuals do not have treatment for latent tuberculosis, they should be informed of the risks and symptoms of active tuberculosis. h Close contacts g Anyone aged under 65 years who is a close contact (prolonged, frequent or intense contact, for example household contacts or partners) of a person with pulmonary or laryngeal tuberculosis should be tested for latent Infection tuberculosis. Drug treatment should be offered to all individuals aged under 65 years with evidence of latent tuberculosis, if the close contact has suspected infectious or conﬁrmed active pulmonary or laryngeal drug-sensitive tuberculosis. h Immunocompromised g Individuals who are anticipated to be, or who are currently immunocompromised, should have a risk assessment carried out to establish whether tuberculosis testing should be offered. Take into account the severity and duration of their immunocompromise and any risk factors for tuberculosis (such as country of birth or recent contact with an index case with suspected infectious or conﬁrmed pulmonary or laryngeal tuberculosis). Individuals who are severely immunocompromised (such as those with HIV and a CD4 count of less than 200 cells/mm3, or who have had a solid organ or allogeneic stem cell transplant) should be tested for latent tuberculosis using an appropriate method. Individuals who test positive should then be assessed for active disease, and if negative, offered treatment for latent tuberculosis. h For further information on tuberculosis testing methods, see NICE clinical guideline: Tuberculosis (see Useful resources). Healthcare workers g Any new NHS employees who are new entrants from a high incidence country should be offered appropriate testing for latent tuberculosis. Those who are not new entrants from a high incidence country, but who will be in contact with patients or clinical materials should be offered appropriate testing for latent tuberculosis if prior BCG vaccination cannot be veriﬁed. h For further information on tuberculosis testing methods, see NICE clinical guideline: Tuberculosis (see Useful resources) and Bacillus Calmette- Guérin vaccine p. 1365. g Those who test positive should then be assessed for active disease, and if negative, offered treatment for latent tuberculosis. For healthcare workers who are immunocompromised, follow standard advice for testing and treatment (see Immunocompromised above). h Treatment of latent tuberculosis g For individuals aged below 65 years, including those with HIV where treatment for latent tuberculosis is indicated, offer drug treatment with either 3 months of isoniazid (with pyridoxine hydrochloride p. 1141) and rifampicin or 6 months of isoniazid (with pyridoxine hydrochloride). h The choice of regimen is dependent on clinical factors, including age, risk of hepatotoxicity and possible drug interactions. g Testing for HIV, hepatitis B and hepatitis C should be offered before starting antituberculosis treatment as this may affect choice of therapy. Individuals aged 35 to 65 years should only be offered treatment if hepatotoxicity is not a concern. For individuals aged under 35 years offer treatment with 3 months of isoniazid (with pyridoxine hydrochloride) and rifampicin if hepatotoxicity is a concern after an assessment of both liver function (including transaminase levels) and risk factors. For individuals where interactions with rifamycins are a concern (for example, in people with HIV or who those have had a transplant), offer treatment with 6 months of isoniazid (with pyridoxine hydrochloride). Recommended dosage for standard unsupervised 6-month treatment Adult: Rifampicin with isoniazid and ▶body-weight up to 40 kg 3 tablets daily for 2 months (initial phase), use Rifater ® Tablets, pyrazinamide preferably taken before breakfast; ▶body-weight 40–49 kg 4 tablets daily for 2 months (initial phase), use Rifater ® Tablets, preferably taken before breakfast; ▶body-weight 50–64 kg 5 tablets daily for 2 months (initial phase), use Rifater ® Tablets, preferably taken before breakfast; Infection ▶body-weight 65 kg and above 6 tablets daily for 2 months (initial phase), use Rifater ® Tablets, preferably taken before breakfast Adult: 15 mg/kg once daily for 2 months (initial phase) Ethambutol hydrochloride Adult: Rifampicin with isoniazid ▶body-weight up to 50 kg 450/300 mg daily for 4 months (continuation phase after 2-month initial phase), use Rifinah ®150/100 Tablets, preferably taken before breakfast; ▶body-weight 50 kg and above 600/300 mg daily for 4 months (continuation phase after 2-month initial phase), use Rifinah ®300/150 Tablets, preferably taken before breakfast or (if combination preparations not appropriate): Child: 10 mg/kg once daily (max. per dose 300 mg) for 6 months (initial and continuation Isoniazid phases) Adult: 300 mg daily for 6 months (initial and continuation phases) Child: Rifampicin ▶body-weight up to 50 kg 15 mg/kg once daily for 6 months (initial and continuation phases); maximum 450 mg per day; ▶body-weight 50 kg and above 15 mg/kg once daily for 6 months (initial and continuation phases); maximum 600 mg per day Adult: ▶body-weight up to 50 kg 450 mg once daily for 6 months (initial and continuation phases); ▶body-weight 50 kg and above 600 mg once daily for 6 months (initial and continuation phases) Child: Pyrazinamide ▶body-weight up to 50 kg 35 mg/kg once daily for 2 months (initial phase); maximum 1.5 g per day; ▶body-weight 50 kg and above 35 mg/kg once daily for 2 months (initial phase); maximum 2 g per day Adult: ▶body-weight up to 50 kg 1.5 g once daily for 2 months (initial phase); ▶body-weight 50 kg and above 2 g once daily for 2 months (initial phase) Child: 20 mg/kg once daily for 2 months (initial phase) Ethambutol hydrochloride Adult: 15 mg/kg once daily for 2 months (initial phase) In general, doses should be rounded up to facilitate administration of suitable volumes of liquid or an appropriate strength of tablet.The exception is ethambutol hydrochloride p. 620 due to the risk of toxicity. Doses may also need to be recalculated to allow for weight gain in younger children. The fixed-dose combination preparations ( Rifater ®, Rifinah ®) are unlicensed for use in children. Consideration may be given to use of these preparations in older children, provided the respective dose of each drug is appropriate for the weight of the child. Recommended dosage for intermittent supervised 6-month treatment Child: 15 mg/kg 3 times a week (max. per dose 900 mg) for 6 months (initial and continuation phases) Isoniazid Adult: 15 mg/kg 3 times a week (max. per dose 900 mg) for 6 months (initial and continuation phases) Child: 15 mg/kg 3 times a week (max. per dose 900 mg) for 6 months (initial and continuation phases) Rifampicin Adult: 600–900 mg 3 times a week for 6 months (initial and continuation phases) Child: Pyrazinamide ▶body-weight up to 50 kg 50 mg/kg 3 times a week (max. per dose 2 g 3 times a week) for 2 months (initial phase); ▶body-weight 50 kg and above 50 mg/kg 3 times a week (max. per dose 2.5 g 3 times a week) for 2 months (initial phase) Adult: ▶body-weight up to 50 kg 2 g 3 times a week for 2 months (initial phase); ▶body-weight 50 kg and above 2.5 g 3 times a week for 2 months (initial phase) Child: 30 mg/kg 3 times a week for 2 months (initial phase) Ethambutol hydrochloride Adult: 30 mg/kg 3 times a week for 2 months (initial phase) In general, doses should be rounded up to facilitate administration of suitable volumes of liquid or an appropriate strength of tablet.The exception is ethambutol hydrochloride due to the risk of toxicity. Doses may also need to be recalculated to allow for weight gain in younger children. The fixed-dose combination preparations ( Rifater ®, Rifinah ®) are unlicensed for use in children. Consideration may be given to use of these preparations in older children, provided the respective dose of each drug is appropriate for the weight of the child. Individuals with severe liver disease should be treated under the care of a specialist team. Careful monitoring of liver function is necessary in individuals with non-severe liver disease, abnormal liver function, or who misuse alcohol or drugs. h For advice on immunisation against tuberculosis, see Bacillus Calmette-Guérin vaccine p. 1365. Treatment failure Major causes of treatment failure include incorrect prescribing by the clinician and inadequate compliance by the infected individual. g All individuals diagnosed with tuberculosis should have an allocated case manager to help with the development of a health and social care plan, supervision of treatment, and support with the completion of treatment. Multidisciplinary tuberculosis teams should implement strategies (such as random urine tests, pill counts, home visits, health education counselling, and language appropriate reminder services) to help with adherence to, and successful completion of treatment. h Treatment interruptions A break in antituberculosis treatment of at least 2 weeks (during the initial phase) or missing more than 20% of prescribed doses is classiﬁed as treatment interruption. Re- establishing treatment appropriately following interruptions is key to ensuring treatment success without relapse, drug resistance or further adverse events. g If an adverse reaction recurs upon re-introducing a particular drug, do not give that drug in future regimens and consider extending the total regimen accordingly. h Treatment interruptions due to drug-induced hepatotoxicity g Following treatment interruption due to drug-induced hepatotoxicty, all potential causes of hepatotoxicity should be investigated. Once aspartate or alanine transaminase levels fall below twice the upper limit of normal, bilirubin levels have returned to the normal range, and hepatotoxic symptoms have resolved, antituberculosis therapy should be sequentially re-introduced at previous full doses over a period of no more than 10 days. Start with ethambutol hydrochloride p. 620 and either isoniazid p. 621 (with pyridoxine hydrochloride) or rifampicin below. In individuals with severe or highly infectious tuberculosis who need to interrupt the standard regimen, consider continuing treatment with at least 2 drugs with low risk of hepatotoxicity, such as ethambutol hydrochloride and streptomycin p. 546 (with or without a ﬂuoroquinolone antibiotic, such as levoﬂoxacin p. 592 or moxiﬂoxacin p. 593), with ongoing monitoring by a liver specialist. h Treatment interruptions due to cutaneous reactions g If an individual with severe or highly infectious tuberculosis has a cutaneous reaction, consider continuing treatment with a combination of at least 2 drugs with low risk for causing cutaneous reactions, such as ethambutol hydrochloride and streptomycin, with monitoring by a dermatologist. h Drug-resistant tuberculosis g Treatment of drug-resistant tuberculosis should be managed by a multidisciplinary team with experience in such cases, and where appropriate facilities for infection-control exist. h The risk of resistance is minimised by ensuring therapy is administered in the correct dose and combination for the prescribed duration. Single drug-resistant tuberculosis g For single drug-resistance in individuals with tuberculosis with central nervous system involvement, refer to a specialist with experience in managing drug-resistant tuberculosis. h For those without central nervous system involvement, the following treatment regimens are recommended: Resistance to isoniazid: . g First 2 months (initial phase): rifampicin, pyrazinamide p. 621 and ethambutol hydrochloride; . Continue with (continuation phase): rifampicin and ethambutol hydrochloride for 7 months (up to 10 months for extensive disease). h Resistance to pyrazinamide: . g First 2 months (initial phase): rifampicin, ethambutol Infection hydrochloride and isoniazid (with pyridoxine hydrochloride); . Continue with (continuation phase): rifampicin and isoniazid (with pyridoxine hydrochloride) for 7 months. h Resistance to ethambutol hydrochloride: . g First 2 months (initial phase): rifampicin, pyrazinamide and isoniazid (with pyridoxine hydrochloride); . Continue with (continuation phase): rifampicin and isoniazid p. 621 (with pyridoxine hydrochloride p. 1141) for 4 months. h Resistance to rifampicin below: . g Offer treatment with at least 6 antituberculosis drugs to which the mycobacterium is likely to be sensitive. h Multi-drug resistant tuberculosis g In multidrug-resistant tuberculosis (resistance to isoniazid and rifampicin, with or without any other resistance), positive cases of rifampicin resistance require treatment with at least 6 antituberculosis drugs to which the mycobacterium is likely to be sensitive. Testing for resistance to second-line drugs is recommended and treatment should be modiﬁed according to susceptibility. h Useful Resources Tuberculosis. National Institute for Health and Care Excellence. NICE guideline 33. September 2019. www.nice.org.uk/guidance/ng33 Other drugs used for Tuberculosis Rifabutin, p. 608 ANTIMYCOBACTERIALS › RIFAMYCINS

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Clinical care

Patient And Carer Advice

Blood disorders On long-term treatment, patients and their carers should be told how to recognise signs of blood disorders and advised to seek immediate medical attention if symptoms such as fever, sore throat, rash, mouth ulcers, purpura, bruising or bleeding develop.

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