Brand Name: Pulmiprove 125mg Tablet
Pulmiprove 62.5mg Tablet.
Active Ingredient: Bosentan Monohydrate
When is Pulmiprove Tablet prescribed for?
Treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and symptoms in patients with WHO functional class III. Efficacy has been shown in:
• Primary (idiopathic and heritable) PAH
• PAH secondary to scleroderma without significant interstitial pulmonary disease
• PAH associated with congenital systemic-to-pulmonary shunts and Eisenmenger's physiology
Some improvements have also been shown in patients with PAH WHO functional class II.
Pulmiprove is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease
How should you take Pulmiprove Tablet?
Tablets are to be taken orally morning and evening, with or without food. The film-coated tablets are to be swallowed with water.
Pulmonary arterial hypertension
Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension.
In adult patients, Pulmiprove treatment should be initiated at a dose of 62.5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily.
For pediatric patients aged 2 years or older, the optimal maintenance dose has not been defined in well-controlled studies.
Pulmiprove may slightly improve their exercise capacity when the dose is increased to 250 mg twice daily. A careful benefit/risk assessment should be made, taking into consideration that the liver toxicity is dose dependent.
When you should not take Pulmiprove Tablet?
- Hypersensitivity to the active substance or to any of the excipients
- Moderate to severe hepatic impairment, i.e., Child-Pugh class B or C
- Baseline values of liver aminotransferases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT), greater than 3 times the upper limit of normal.
- Concomitant use of cyclosporine A
- Pregnancy
- Women of child-bearing potential who are not using reliable methods of contraception
Possible Drug interaction with Pulmiprove Tablet:
Bosentan is metabolised by CYP2C9 and CYP3A4. Inhibition of these isoenzymes may increase the plasma concentration of bosentan.
- Fluconazole: combination is not recommended.
- Ketoconazole, Itraconazole or Ritonavir: For the same reason, concomitant administration with bosentan is not recommended.
- Cyclosporine A: co-administration with bosentan is contraindicated.
- Tacrolimus, Sirolimus: co-administration with bosentan is not advisable.
- Glibenclamide: this combination should not be used. No drug-drug interaction data are available with the other sulfonylureas.
- Hormonal contraceptives: hormone-based contraceptives alone, regardless of the route of administration (i.e., oral, injectable, transdermal or implantable forms), are not considered as reliable methods of contraception.
- Warfarin: No dose adjustment is needed for warfarin and similar oral anticoagulant agents when bosentan is initiated, but intensified monitoring of INR is recommended.
- Simvastatin: Monitoring of cholesterol levels and subsequent dosage adjustment should be considered.
- Ketoconazole: No dose adjustment of Pulmiprove is considered necessary.
- Rifampicin: co-administration of bosentan with rifampicin decreased the plasma concentrations of bosentan.
- Epoprostenol: the Cmax and AUC values of bosentan were similar in patients with or without continuous infusion of epoprostenol.
- Sildenafil: Caution is recommended in the case of co-administration.
- Digoxin: interaction is unlikely to be of clinical relevance.
- Lopinavir + ritonavir (and other ritonavir-boosted protease inhibitors): Appropriate monitoring of the HIV therapy is recommended.
- Other antiretroviral agents: no specific recommendation can be made with regard to other available antiretroviral agents due to the lack of data. It is emphasised that due to the marked hepatotoxicity of nevirapine, which could accumulate with bosentan liver toxicity, this combination is not recommended.
Special Warning and Precaution when using Pulmiprove Tablet:
Pulmiprove should only be initiated if the systemic systolic blood pressure is higher than 85 mmHg.
Liver function:
Elevations in liver aminotransferases, i.e., aspartate and alanine aminotransferases (AST and/or ALT), associated with bosentan are dose dependent. Liver enzyme changes typically occur within the first 26 weeks of treatment. Liver aminotransferase levels must be measured prior to initiation of treatment and subsequently at monthly intervals for the duration of treatment with Pulmiprove. In addition, liver aminotransferase levels must be measured 2 weeks after any dose increase.
Haemoglobin concentration:
Treatment with bosentan has been associated with dose-related decreases in haemoglobin concentration. It is recommended that haemoglobin concentrations be checked prior to initiation of treatment, every month during the first 4 months, and quarterly thereafter.
Women of child-bearing potential:
Pulmiprove treatment must not be initiated in women of child-bearing potential unless they practise reliable contraception and the result of the pre-treatment pregnancy test is negative.
Pulmonary veno-occlusive disease:
Should signs of pulmonary oedema occur when Pulmiprove is administered in patients with PAH, the possibility of associated veno-occlusive disease should be considered.
Pulmonary arterial hypertension patients with concomitant left ventricular failure:
Treatment with diuretics should be considered in patients with evidence of fluid retention before the start of treatment with Pulmiprove.
Pulmonary arterial hypertension associated with HIV infection:
When treatment with Pulmiprove is initiated in patients who require ritonavir-boosted protease inhibitors, the patient's tolerability of Pulmiprove should be closely monitored. These patients should also be monitored carefully regarding their HIV infection.
Special information if you are pregnant or breastfeeding.
Pregnancy
Studies in animals have shown reproductive toxicity. There are no reliable data on the use of Pulmiprove in pregnant women. The potential risk for humans is still unknown. Pulmiprove is contraindicated in pregnancy.
Use in women of child-bearing potential
Before the initiation of Pulmiprove treatment in women of child-bearing potential, the absence of pregnancy should be checked, appropriate advice on reliable methods of contraception provided, and reliable contraception initiated. Patients and prescribers must be aware that due to potential pharmacokinetic interactions, Pulmiprove may render hormonal contraceptives ineffective. Therefore, women of child-bearing potential must not use hormonal contraceptives (including oral, injectable, transdermal or implantable forms) as the sole method of contraception but must use an additional or an alternative reliable method of contraception. If there is any doubt about what contraceptive advice should be given to the individual patient, consultation with a gynaecologist is recommended. Because of possible hormonal contraception failure during Pulmiprove treatment, and also bearing in mind the risk that pulmonary hypertension severely deteriorates with pregnancy, monthly pregnancy tests during treatment with Pulmiprove are recommended to allow early detection of pregnancy.
Breast-feeding
It is not known whether bosentan is excreted into human breast milk. Breast-feeding is not recommended during treatment with Pulmiprove.
Possible Side Effects of Pulmiprove Tablet
Very common: Headache
Common: Anaemia, Haemoglobin decrease, Palpitations, Syncope, Hypersensitivity reactions (including dermatitis, pruritus and rash)
Uncommon: Thrombocytopenia, Neutropenia, Leukopenia
Rare: Anaphylaxis and/or Angioedema